2022年02月, 北海道, 北海道科学技術賞　　　　　　　　　　　　　　　

2018年, 北海道大学大学院医学研究院・大学院医学院・医学部医学科, 優秀研究賞　　　　　　　　　　　　　　　

2006年, 日本手外科学会, Traveling Fellow　　　　　　　　　　　　　　　

2003年, 北海道整形災害外科学会, 学術奨励賞　　　　　　　　　　　　　　　

Chondroprotective functions of neutrophil-derived extracellular vesicles by promoting the production of secreted frizzled-related protein 5 in cartilage.
Keita Kitahara, Taku Ebata, Chen Liyile, Yoshio Nishida, Yuki Ogawa, Taiki Tokuhiro, Junki Shiota, Tatsuya Nagano, Taichi E Takasuka, Tsutomu Endo, Tomohiro Shimizu, Hend Alhasan, Tsuyoshi Asano, Daisuke Takahashi, Kentaro Homan, Tomohiro Onodera, Ken Kadoya, M Alaa Terkawi, Norimasa Iwasaki
Cell communication and signaling : CCS, 22, 1, 569, 569, 2024年11月27日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Osteoarthritis (OA) is the most common degenerative joint disease characterized by cartilage degradation and various degrees of inflammation in the synovium. Growing evidence highlights that neutrophil extracellular vesicles (EVs) play a protective role in arthritic joints by promoting the resolution of inflammation and the synthesis of proteoglycans in cartilage. However, this homeostatic function is dependent on the activation state of neutrophils and the surrounding environment/tissues. Hence, we explored the chondroprotective functions of neutrophil-derived EVs under different stimulation conditions and the underlying molecular mechanism. METHODS: Human blood-derived neutrophils, murine bone marrow-derived neutrophils, C-28I2 cells and primary chondrocytes were used. Neutrophils were stimulated with different cytokines, and their EVs were isolated for chondrocyte stimulation and further subjected to RNA-sequencing analysis. Two experimental murine OA models were used, and the treatment was performed by intraarticular injections. RESULTS: Conditioned medium from neutrophils stimulated with TGF-β (N-β) had the greatest inhibitory effect on the expression of catabolic factors in stimulated chondrocytes. These protective effects were not impaired when conditioned medium of N-β from AnxA1-deficient mice was used. Consistent with these results, EVs isolated from N-β significantly reduced the expression of catabolic factors in stimulated chondrocytes. Bulk RNA-seq analysis revealed that secreted frizzled-related protein 5 (SFRP5) is upregulated in N-β-EV-stimulated chondrocytes. Furthermore, recombinant SFRP5 treatment significantly reduced the expression of catabolic factors in vitro and catabolic process in experimental murine OA models. CONCLUSIONS: The current study emphasizes the potential therapeutic application of neutrophils in OA and provides new knowledge on the molecular mechanisms underlying their function.

Dynamic transcriptome analysis of osteal macrophages identifies distinct subset with senescence features in experimental osteoporosis.
Yoshio Nishida, M Alaa Terkawi, Gen Matsumae, Shunichi Yokota, Taiki Tokuhiro, Yuki Ogawa, Hotaka Ishizu, Junki Shiota, Tsutomu Endo, Hend Alhasan, Taku Ebata, Keita Kitahara, Tomohiro Shimizu, Daisuke Takahashi, Masahiko Takahata, Ken Kadoya, Norimasa Iwasaki
JCI insight, 2024年10月31日, ［国際誌］
英語, 研究論文（学術雑誌）, Given the potential fundamental function of osteal macrophages in bone pathophysiology, we study here their precise function in experimental osteoporosis. Gene profiling of osteal macrophages from ovariectomized mice demonstrated the upregulation of genes that were involved in oxidative stress, cell senescence and apoptotic process. A scRNA-seq analysis revealed that osteal macrophages were heterogenously clustered into 6 subsets that expressed proliferative, inflammatory, anti-inflammatory and efferocytosis gene signatures. Importantly, postmenopausal mice exhibited a 20-fold increase in subset-3 that showed a typical gene signature of cell senescence and inflammation. These findings suggest that the decreased production of estrogen due to postmenopause altered the osteal macrophages subsets, resulting in a shift toward cell senescence and inflammatory conditions in the bone microenvironment. Furthermore, adoptive macrophage transfer onto calvarial bone was performed and mice that received oxidative-stressed macrophages exhibited greater osteolytic lesions than control macrophages, suggesting the role of these cells in development of inflammaging in bone microenvironment. Consistently, depletion of senescent cells and oxidative-stressed macrophages subset alleviated the excessive bone loss in postmenopausal mice. Our data provided a new insight into the pathogenesis of osteoporosis and sheds light on a new therapeutic approach for the treatment/prevention of postmenopausal osteoporosis.

Intervention for impending pathological fractures at proximal femur is associated with lower mortality rates in patients with intermediate-to-high risk according to the Katagiri-New score.
Toshiyuki Nishimoto, Hirokazu Shimizu, Masatake Matsuoka, Daisuke Takahashi, Tomohiro Shimizu, Norimasa Iwasaki, Ken Kuwahara, Tamotsu Soma, Hiroaki Hiraga, Akira Iwata
BMC musculoskeletal disorders, 25, 1, 836, 836, 2024年10月22日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Prophylactic intervention for impending pathological fractures (IF) is associated with improved survival in patients with long-bone metastasis. However, information regarding whether the tumor burden and/or physical status are associated with survival benefits of intervention for IF is lacking. METHODS: This multicenter retrospective study investigated 121 patients who underwent surgery for 63 impending and 58 complete metastatic fractures of the proximal femur between 2008 and 2023. After matching for age, sex, body mass index, and Katagiri-New score, 42 patients with IF were compared with 42 patients with complete pathological fractures. The 1-year mortality rate was considered the primary outcome, and was compared and stratified by risk based on the Katagiri-New score. The 1-year mortality rate was evaluated according to the surgical method in the subgroup analysis of patients with IF. RESULTS: The 1-year mortality rate was significantly lower in patients with IF with intermediate-to-high risk(p = 0.04), whereas no difference was observed in patients with low-to-high risk. IF was associated with a significantly higher rate of home discharge (p < 0.01) and improved post-operative ambulatory function (p = 0.07). The subgroup analysis of patients with IF revealed no difference in the survival rate between nailing and hemiarthroplasty. CONCLUSION: Patients with intermediate-to-high risk IF based on the Katagiri-New score had a lower mortality rate than those who underwent surgery for pathological fractures. A higher rate of home discharge was observed in patients with IF. Based on the Katagiri-New score, survival benefits can be obtained from prophylactic intervention for IF of the proximal femur in patients with intermediate-to high-risk.

CCR7 depletion alleviates bony growth imbalance following physeal injury in mice.
WooYoung Kim, Yuko Sakai, Masatake Matsuoka, Yoshiaki Hosokawa, Ryuichi Fukuda, Kentaro Homan, Tomohiro Onodera, Norimasa Iwasaki
Scientific reports, 14, 1, 24891, 24891, 2024年10月22日, ［国際誌］
英語, 研究論文（学術雑誌）, Growth plates are the frequent sites of skeletal injury in children, leading to skeletal growth imbalances. Chemokines, including the receptor CCR7, play a crucial role in stem cell recruitment and cartilage homeostasis, with previous studies linking CCR7 to osteoarthritis progression. However, its role in growth plate cartilage remains unclear. We analyzed the role of CCR7 in the physeal cartilage repair process in mice model. Physeal injury was created in the proximal tibia in 3-week-old C57BL/6 mice (WT) and CCR7-knockout mice (CCR7-/-). Tibial length was measured macroscopically and sections of the physeal injury were analyzed histologically and immunohistochemically. Height and bone volume of the tibial growth plate and bone mineral density (BMD) of the subchondral area were measured by micro-CT. Mesenchymal stem cells (MSCs) were harvested and gene expression after osteogenic differentiation was analyzed using qRT-PCR. At 1, 3 and 5 weeks postoperatively, injured tibiae of CCR7-/- mice were less shortened than those of WT mice. Bone volume of the physeal bridge was significantly lower in CCR7-/- mice than in WT mice. In contrast, BMD of the subchondral area was comparable between CCR-/- and WT mice, and between sham and operated tibiae. In osteogenic differentiation, CCR7-/- mice showed significantly lowered expression of osteogenic markers such as Osterix, Runx2 and Type X collagen. We demonstrated CCR7 depletion in mice inhibited physeal bridge formation and ameliorated growth imbalances after physeal injury.

Natural Recovery of Very Limited Elbow Flexion After Rare Lateral Humeral Condylar Fracture in a 4-Year-Old Boy: A Case Report.
Koki Ohta, Yuichiro Matsui, Hiroyuki Kato, Daisuke Kawamura, Takeshi Endo, Daisuke Momma, Tamotsu Kamishima, Tatsunori Horie, Hirofumi Miyaji, Norimasa Iwasaki
JBJS case connector, 14, 4, 2024年10月01日, ［国際誌］
英語, 研究論文（学術雑誌）, CASE: A 4-year-old boy developed malunion after open reduction and internal fixation (ORIF) of a rare lateral condylar humeral fracture running from the lateral humerus, through the trochlear cartilage, to the medial trochlea. Five months after ORIF, the active elbow flexion was limited to 50°. Magnetic resonance imaging (MRI) showed a step-off of the anterior trochlear cartilage, causing the limited flexion. After conservative observation for 5 years, the flexion improved to 135° and MRI showed that the step-off had disappeared. CONCLUSION: This case indicates that it is possible for pediatric patients to recover their range of motion following malunion of an elbow fracture.

Cervical motion analysis using wearable inertial sensors to patients with cervical ossification of posterior longitudinal ligament.
Satoshi Osuka, Masahiko Takahata, Ryo Takeda, Takeshi Chiba, Hiroaki Hori, Yoshiaki Kataoka, Norimasa Iwasaki, Masahiko Mukaino, Harukazu Tohyama
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2024年09月29日, ［国際誌］
英語, 研究論文（学術雑誌）, This study aimed to clarify cervical kinematics during daily activities, including level walking and stair ascending, in patients with cervical ossification of the posterior longitudinal ligament (C-OPLL). Eighteen patients with myelopathy caused by C-OPLL and 18 healthy controls were recruited to participate in the study. The sagittal cervical kinematics during level walking and stair ascent were quantitatively assessed using a motion analysis system based on wearable inertial sensors. The Japanese Orthopaedic Association score, Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, Neck Disability Index, and deep sensation in the lower extremities were assessed in all participants. Nine of 18 patients with C-OPLL presented with deep sensory disturbances. Patients with C-OPLL with deep sensory disturbances exhibited different sagittal plane cervical motion patterns than healthy controls during level walking and stair ascent. During the first phase of stair ascent, both patients with C-OPLL and healthy controls flexed their necks to the same degree; however, during the middle and final phases of stair ascent and all phases of level walking, the mean cervical flexion angle of patients with C-OPLL with deep sensory disturbances was significantly higher than that of patients with C-OPLL without deep sensory disturbance and healthy controls. Our data suggest that patients with C-OPLL presenting with deep sensory disturbances are likely to walk with their necks flexed and gaze downward to observe their steps throughout their daily lives. This habitual neck posture may lead to a vicious cycle of cervical kyphosis and worsening of compressive myelopathy.

Evaluating the Alignment of Artificial Intelligence-Generated Recommendations With Clinical Guidelines Focused on Soft Tissue Tumors.
Masatake Matsuoka, Tomohiro Onodera, Ryuichi Fukuda, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Eiji Kondo, Norimasa Iwasaki
Journal of surgical oncology, 2024年09月05日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The integration of artificial intelligence (AI), particularly, in oncology, has significantly shifted the paradigms of medical diagnostics and treatment planning. However, the utility of AI, specifically OpenAI's ChatGPT, in soft tissue sarcoma treatment, remains unclear. METHODS: We evaluated ChatGPT's alignment with the Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of soft tissue tumors 2020. Twenty-two clinical questions (CQs) were formulated to encompass various aspects of sarcoma diagnosis, treatment, and management. ChatGPT's responses were classified into "Complete Alignment," "Partial Alignment," or "Nonalignment" based on the recommendation and strength of evidence. RESULTS: ChatGPT demonstrated an 86% alignment rate with the JOA guidelines. The AI provided two instances of complete alignment and 17 instances of partial alignment, indicating a strong capability to match guideline criteria for most questions. However, three discrepancies were identified in areas concerning the treatment of atypical lipomatous tumors, perioperative chemotherapy for synovial sarcoma, and treatment strategies for elderly patients with malignant soft tissue tumors. Reassessment with guideline input led to some adjustments, revealing both the potential and limitations of AI in complex sarcoma care. CONCLUSION: Our study demonstrates that AI, specifically ChatGPT, can align with clinical guidelines for soft tissue sarcoma treatment. It also underscores the need for continuous refinement and cautious integration of AI in medical decision-making, particularly in the context of treatment for soft tissue sarcoma.

Midterm Results of Severe Hip Dysplasia after Using a Cementless Acetabular Component with Bulk Bone Graft in Total Hip Arthroplasty: A Minimum Five-Year Follow-Up Study.
Takuya Konno, Tomohiro Shimizu, Masahiro Inoue, Takeshi Masuda, Mohamad Alaa Terkawi, Norimasa Iwasaki, Daisuke Takahashi
Bioengineering (Basel, Switzerland), 11, 8, 2024年08月19日, ［国際誌］
英語, 研究論文（学術雑誌）, In patients with severe hip dysplasia, total hip arthroplasty (THA) using bulk bone graft (BBG) enhances anatomic cup positioning and provides early structural support. This study assesses the mid-term outcomes of THA with BBG in patients with over 50% graft bone coverage. Among 1951 patients who underwent THA between 2003 and 2007, 183 had BBG. After excluding early dropouts and infections, 151 patients remained. They were classified into uncovered (<50% coverage, 79 patients) and covered (>50% coverage, 72 patients) groups. The efficacy of cup fixation was compared between these groups. After ten years, the survival rate for not needing THA revision was 98% in the uncovered group and 100% in the covered group, while the rate for radiographic stability was 93% versus 99%, respectively. Although the cutoff value for the uncovered portion could not be clarified in this study, the mid-term results for 50% to approximately 70% uncovered were comparable to those for 50% or lesser, which have previously been expected to perform well. Recently, biomechanically advantageous bone grafting techniques have been identified, and based on the results of this study, it may be possible to expand the indications for THA with bone grafting for developmental dysplasia of the hip.

Higher association of articular surface destruction with rheumatoid forefoot deformity arising from dislocation of the metatarsophalangeal joints in the lateral column.
Yuki Suzuki, Tomohiro Onodera, Koji Iwasaki, Masatake Matsuoka, Masanari Hamasaki, Eiji Kondo, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2024年08月14日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: To evaluate the relationship between the pattern and severity of metatarsophalangeal (MTP) joint dislocation in the lesser toes and severity of joint destruction in rheumatoid forefoot deformities. METHODS: Participants comprised of 13 patients (16 feet) who underwent resection arthroplasty of the metatarsal head of the lesser toes for rheumatoid arthritis of the MTP joints. Correlations between preoperative radiographic findings and histological grades second to fifth metatarsal heads taken intraoperatively were analyzed. RESULTS: In 62 metatarsal heads, complete dislocation of the MTP joint in the lesser toes significantly resulted in severe joint destruction compared to mild or moderate dislocation (P < 0.05). The proportion of severe cartilage damage in MTP joints with complete dislocation was 100 % in the 5th MTP joint, 83.3 % in the 4th MTP joint, and 58.3 % in the 2nd and 3rd MTP joints. Moreover, complete dislocation of the MTP joints in the lateral column showed the most severe joint destruction compared to that in the medial column (P = 0.03). CONCLUSION: Complete dislocation of the MTP joint in the lateral column is related to joint destruction in rheumatoid forefoot deformities.

Bimodal machine learning model for unstable hips in infants: integration of radiographic images with automatically-generated clinical measurements.
Hirokazu Shimizu, Ken Enda, Hidenori Koyano, Tomohiro Shimizu, Shun Shimodan, Komei Sato, Takuya Ogawa, Shinya Tanaka, Norimasa Iwasaki, Daisuke Takahashi
Scientific reports, 14, 1, 17826, 17826, 2024年08月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Bimodal convolutional neural networks (CNNs) are frequently combined with patient information or several medical images to enhance the diagnostic performance. However, the technologies that integrate automatically generated clinical measurements within the images are scarce. Hence, we developed a bimodal model that produced automatic algorithm for clinical measurement (aaCM) from radiographic images and integrated the model with CNNs. In this multicenter research project, the diagnostic performance of the model was investigated with 813 radiographic hip images of infants at risk of developmental dysplasia of the hips (232 and 581 images of unstable and stable hips, respectively), with the ground truth defined by provocative examinations. The results indicated that the accuracy of aaCM was equal or higher than that of specialists, and the bimodal model showed better diagnostic performance than LightGBM, XGBoost, SVM, and single CNN models. aaCM can provide expert's knowledge in a high level, and our proposed bimodal model has better performance than the state-of-art models.

Amputation surgery associated with shortened survival in patients with localized extremity bone sarcoma.
Nayuhito Yanagisawa, Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Eiji Kondo, Norimasa Iwasaki
Journal of orthopaedics, 54, 124, 130, 2024年08月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: This study assesses survival rates among patients with localized extremity bone sarcoma who have undergone amputation, pinpointing subpopulations that are disproportionately affected by amputation-related survival disparities. METHODS: Examination of data was conducted using the Surveillance, Epidemiology, and End Results (SEER) program, analyzing records of 3765 patients diagnosed with localized extremity bone sarcoma between 2000 and 2019. Of these, 857 received amputations (Amputation cohort), and 2908 underwent limb-sparing surgeries. Propensity score matching, considering demographic and clinical features, was utilized to ensure a fair comparison. RESULTS: Following propensity score matching, the study focused on 1714 cases. The Amputation cohort was observed to have significantly poorer survival rates (Cancer-Specific Survival [CSS]: Hazard Ratio [HR] = 1.28, 95% Confidence Interval [CI]: 1.05-1.55; Overall Survival [OS]: HR = 1.37, 95% CI: 1.15-1.63). Subsequent subgroup analysis indicated that individuals with tumors exceeding 8 cm in size or those located in the lower limbs were notably at a higher risk of shortened survival (for tumors >8 cm - CSS: HR = 1.32, 95% CI: 1.02-1.71; OS: HR = 1.39, 95% CI: 1.09-1.76; for lower limb tumors - CSS: HR = 1.25, 95% CI: 1.01-1.54; OS: HR = 1.33, 95% CI: 1.11-1.61). CONCLUSIONS: Our findings demonstrate that patients diagnosed with localized extremity bone sarcoma undergoing amputation exhibit lower survival rates, especially in cases involving tumors of greater size or those situated in the lower limbs. In patient groups where amputation is inevitable, careful follow-up is required after surgical intervention.

Depletion of b-series ganglioside prevents limb length discrepancy after growth plate injury.
Yoshiaki Hosokawa, Masatake Matsuoka, Yuko Sakai, Ryuichi Fukuda, Keizumi Matsugasaki, Kentaro Homan, Jun-Ichi Furukawa, Tomohiro Onodera, Norimasa Iwasaki
BMC musculoskeletal disorders, 25, 1, 565, 565, 2024年07月20日, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Growth plate damage in long bones often results in progressive skeletal growth imbalance and deformity, leading to significant physical problems. Gangliosides, key glycosphingolipids in cartilage, are notably abundant in articular cartilage and regulate chondrocyte homeostasis. This suggests their significant roles in regulating growth plate cartilage repair. METHODS: Chondrocytes from 3 to 5 day-old C57BL/6 mice underwent glycoblotting and mass spectrometry. Based on the results of the glycoblotting analysis, we employed GD3 synthase knockout mice (GD3-/-), which lack b-series gangliosides. In 3-week-old mice, physeal injuries were induced in the left tibiae, with right tibiae sham operated. Tibiae were analyzed at 5 weeks postoperatively for length and micro-CT for growth plate height and bone volume at injury sites. Tibial shortening ratio and bone mineral density were measured by micro-CT. RESULTS: Glycoblotting analysis indicated that b-series gangliosides were the most prevalent in physeal chondrocytes among ganglioside series. At 3 weeks, GD3-/- exhibited reduced tibial shortening (14.7 ± 0.2 mm) compared to WT (15.0 ± 0.1 mm, P = 0.03). By 5 weeks, the tibial lengths in GD3-/- (16.0 ± 0.4 mm) closely aligned with sham-operated lengths (P = 0.70). Micro-CT showed delayed physeal bridge formation in GD3-/-, with bone volume measuring 168.9 ± 5.8 HU at 3 weeks (WT: 180.2 ± 3.2 HU, P = 0.09), but normalizing by 5 weeks. CONCLUSION: This study highlights that GD3 synthase knockout mice inhibit physeal bridge formation after growth plate injury, proposing a new non-invasive approach for treating skeletal growth disorders.

Radiation therapy improves survival in elderly patients with localized extremity soft tissue sarcoma.
Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Ryuichi Fukuda, Eiji Kondo, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2024年07月15日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: This study aims to evaluate the efficacy of radiation therapy in enhancing survival outcomes among elderly patients diagnosed with localized extremity soft tissue sarcomas (STSs). Furthermore, it seeks to explore whether the survival benefits conferred by radiation therapy differ according to tumor characteristics and treatment modalities. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database to identify patients aged 80 years and older diagnosed with localized extremity STSs. The study assessed 1498 eligible patients, analyzing cancer-specific survival (CSS) and overall survival (OS) through Kaplan-Meier survival analysis and Cox proportional hazards modeling. Propensity score matching was employed to adjust for potential confounders. RESULTS: Among the analyzed patients, 773 patients underwent radiation therapy (Radiation group), while 725 patients either did not receive radiation therapy or it was unknown if they had (No-Radiation group). The 5-year OS rate was 40% in the radiation group compared to 38% in the no-radiation group. After propensity score matching, radiation therapy was associated with a significant improvement in OS (P = 0.005, HR = 0.8, 95% CI 0.7-0.9). Subgroup analyses indicated that patients undergoing primary tumor resection benefited most from radiation therapy in terms of OS. CONCLUSION: Radiation therapy is associated with improved overall survival in elderly patients with localized extremity STSs. These findings suggest that radiation therapy should be considered as a key component of the treatment strategy for this patient population, taking into account individual patient characteristics and comorbidities.

Effect of the Sauvé–Kapandji method on the wrist contact surface for distal radial ulnar joint disorders
Tomoaki Suzuki, Daisuke Momma, Nozomu Inoue, Eiji Kondo, Yuichiro Matsui, Norimasa Iwasaki
BMC Musculoskeletal Disorders, 25, 1, Springer Science and Business Media LLC, 2024年07月11日
研究論文（学術雑誌）, Abstract

Background

The Sauvé–Kapandji (S-K) method is a surgical procedure performed for chronic deformities of the distal radial ulnar joint (DRUJ). Changes to the joint contact surface from pre- to postoperatively under physiological in vivo conditions have not yet been determined for this useful treatment. The aim of the present study was therefore to compare the articular contact area of the wrist joint between before and after the S-K method for DRUJ disorders.

Methods

The SK method was performed for 15 patients with DRUJ osteoarthritis and ulnar impaction syndrome. We calculated the Mayo Wrist Score as the patient’s clinical findings and created 3-dimensional bone models of cases in which the S-K method was performed and calculated the contact area and shift in the center of the contact area using customized software.

Results

The Mean modified Mayo Wrist Score improved significantly from 60.3 preoperatively to 80.3 postoperatively (P < 0.01). Scaphoid contact area to the radius increased significantly from 112.6 ± 37.0 mm² preoperatively to 127.5 ± 27.8 mm² postoperatively (P = 0.03). Lunate contact area to radius-ulna was 121.3 ± 43.3 mm² preoperatively and 112.5 ± 37.6 mm² postoperatively, but this decrease was not significant (P = 0.38). Contact area ratio of scaphoid to lunate increased significantly from 1.01 ± 0.4 preoperatively to 1.20 ± 0.3 postoperatively (P = 0.02). Postoperative translations of the center of the scaphoid and lunate contact areas were decomposed into ulnar and proximal directions. Ulnar and proximal translation distances of the scaphoid contact area were 0.8 ± 1.7 mm and 0.4 ± 0.6 mm, respectively, and those of the lunate contact area were 1.1 ± 1.7 mm and 0.4 ± 1.1 mm, respectively. This study revealed changes in wrist contact area and center of the contact area before and after the S-K method.

Conclusion

These results may accurately indicate changes in wrist joint contact area from pre- to postoperatively using the S-K method for patients with DRUJ disorder. Evaluation of changes in contact area due to bone surface modeling of the wrist joint using 3DCT images may be useful in considering surgical methods.

Deep learning-based detection of lumbar spinal canal stenosis using convolutional neural networks.
Hisataka Suzuki, Terufumi Kokabu, Katsuhisa Yamada, Yoko Ishikawa, Akito Yabu, Yasushi Yanagihashi, Takahiko Hyakumachi, Hiroyuki Tachi, Tomohiro Shimizu, Tsutomu Endo, Takashi Ohnishi, Daisuke Ukeba, Ken Nagahama, Masahiko Takahata, Hideki Sudo, Norimasa Iwasaki
The spine journal : official journal of the North American Spine Society, 2024年06月22日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND CONTEXT: Lumbar spinal canal stenosis (LSCS) is the most common spinal degenerative disorder in elderly people and usually first seen by primary care physicians or orthopedic surgeons who are not spine surgery specialists. Magnetic resonance imaging (MRI) is useful in the diagnosis of LSCS, but the equipment is often not available or difficult to read. LSCS patients with progressive neurologic deficits have difficulty with recovery if surgical treatment is delayed. So, early diagnosis and determination of appropriate surgical indications are crucial in the treatment of LSCS. Convolutional neural networks (CNNs), a type of deep learning, offers significant advantages for image recognition and classification, and work well with radiographs, which can be easily taken at any facility. PURPOSE: Our purpose was to develop an algorithm to diagnose the presence or absence of LSCS requiring surgery from plain radiographs using CNNs. STUDY DESIGN: Retrospective analysis of consecutive, nonrandomized series of patients at a single institution. PATIENT SAMPLE: Data of 150 patients who underwent surgery for LSCS, including degenerative spondylolisthesis, at a single institution from January 2022 to August 2022, were collected. Additionally, 25 patients who underwent surgery at 2 other hospitals were included for extra external validation. OUTCOME MEASURES: In annotation 1, the area under the curve (AUC) computed from the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. In annotation 2, correlation coefficients were used. METHODS: Four intervertebral levels from L1/2 to L4/5 were extracted as region of interest from lateral plain lumbar spine radiographs totaling 600 images were obtained. Based on the date of surgery, 500 images derived from the first 125 cases were used for internal validation, and 100 images from the subsequent 25 cases used for external validation. Additionally, 100 images from other hospitals were used for extra external validation. In annotation 1, binary classification of operative and nonoperative levels was used, and in annotation 2, the spinal canal area measured on axial MRI was labeled as the output layer. For internal validation, the 500 images were divided into each 5 dataset on per-patient basis and 5-fold cross-validation was performed. Five trained models were registered in the external validation prediction performance. Grad-CAM was used to visualize area with the high features extracted by CNNs. RESULTS: In internal validation, the AUC and accuracy for annotation 1 ranged between 0.85-0.89 and 79-83%, respectively, and the correlation coefficients for annotation 2 ranged between 0.53 and 0.64 (all p<.01). In external validation, the AUC and accuracy for annotation 1 were 0.90 and 82%, respectively, and the correlation coefficient for annotation 2 was 0.69, using 5 trained CNN models. In the extra external validation, the AUC and accuracy for annotation 1 were 0.89 and 84%, respectively, and the correlation coefficient for annotation 2 was 0.56. Grad-CAM showed high feature density in the intervertebral joints and posterior intervertebral discs. CONCLUSIONS: This technology automatically detects LSCS from plain lumbar spine radiographs, making it possible for medical facilities without MRI or nonspecialists to diagnose LSCS, suggesting the possibility of eliminating delays in the diagnosis and treatment of LSCS that require early treatment.

Paradoxical Change in Subchondral Bone Density in the Medial Compartment of the Proximal Tibial Articular Surface After High Tibial Osteotomy: A Detailed Subchondral Bone Density Analysis.
Yuki Fujie, Koji Iwasaki, Masanari Hamasaki, Yuki Suzuki, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
The American journal of sports medicine, 3635465241256100, 3635465241256100, 2024年06月20日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: High tibial osteotomy (HTO) aims to realign the varus knee to alleviate stress in the medial compartment. However, detailed information on the impact of HTO on stress distribution across the tibiofemoral joint surface still needs to be completely elucidated. PURPOSE/HYPOTHESIS: The present study aimed to analyze the subchondral bone density distribution to validate the alignment threshold causing paradoxical changes. We hypothesized that there would be a paradoxical stress change in the medial compartment beyond a specific threshold for lower limb realignment after HTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective clinical study of 32 knees from 30 patients who underwent medial opening-wedge HTO between 2015 and 2019 was conducted at Hokkaido University Hospital. The subchondral bone density across the tibiofemoral joint was analyzed using computed tomography-osteoabsorptiometry before and after HTO. The high-density area (HDA) within the medial and lateral compartments and their subregions, which were quartered in the coronal plane, was specifically examined. RESULTS: The hip-knee-ankle angle, medial proximal tibial angle (MPTA), joint line obliquity (JLO), and joint line convergence angle significantly changed after HTO (P < .01). The HDA of the medial compartment to the total HDA ratio decreased from 83% to 77%. Paradoxically, the HDA in the most central subregion of the medial compartment increased from 24% to 30%. There were significant differences between MPTA and JLO in patients with and without paradoxical changes in the HDA. MPTA and JLO cutoff values causing paradoxical changes in the HDA were 94° and 4°, respectively. CONCLUSION: There was a paradoxical stress increase in the M4 region at the medial compartment associated with the MPTA and JLO beyond specific thresholds. Therefore, surgical planning should be cautiously performed to prevent overcorrection, which can lead to adverse stress distribution changes.

Ossification of the posterior longitudinal ligament is linked to heterotopic ossification of the ankle/foot tendons.
Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Ryo Fujita, Daisuke Yoneoka, Masahiro Kanayama, Ken Kadoya, Tomoka Hasegawa, Mohamad Alaa Terkawi, Katsuhisa Yamada, Hideki Sudo, Taku Ebata, Misaki Ishii, Norimasa Iwasaki
Journal of bone and mineral metabolism, 2024年06月08日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification. MATERIALS AND METHODS: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0-4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis. RESULTS: The prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0-5.5 times higher in patients with OPLL (40-56%) than in the controls (10-11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34-2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament. CONCLUSIONS: The strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.

Involvement of Siglec-15 in regulating RAP1/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor.
Hideyuki Kobayashi, M Alaa Terkawi, Masahiro Ota, Tomoka Hasegawa, Tomomaya Yamamoto, Tomohiro Shimizu, Dai Sato, Ryo Fujita, Toshifumi Murakami, Norio Amizuka, Norimasa Iwasaki, Masahiko Takahata
Bone research, 12, 1, 35, 35, 2024年06月07日, ［国際誌］
英語, 研究論文（学術雑誌）, DNAX-associated protein 12 kD size (DAP12) is a dominant immunoreceptor tyrosine-based activation motif (ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis. Although several DAP12-associated receptors (DARs) have been identified in osteoclasts, including triggering receptor expressed on myeloid cells 2 (TREM-2), C-type lectin member 5 A (CLEC5A), and sialic acid-binding Ig-like lectin (Siglec)-15, their precise role in the development of osteoclasts and bone remodeling remain poorly understood. In this study, mice deficient in Trem-2, Clec5a, Siglec-15 were generated. In addition, mice double deficient in these DAR genes and FcεRI gamma chain (FcR)γ, an alternative ITAM adaptor to DAP12, were generated. Bone mass analysis was conducted on all mice. Notably, Siglec-15 deficient mice and Siglec-15/FcRγ double deficient mice exhibited mild and severe osteopetrosis respectively. In contrast, other DAR deficient mice showed normal bone phenotype. Likewise, osteoclasts from Siglec-15 deficient mice failed to form an actin ring, suggesting that Siglec-15 promotes bone resorption principally by modulating the cytoskeletal organization of osteoclasts. Furthermore, biochemical analysis revealed that Sigelc-15 activates macrophage colony-stimulating factor (M-CSF)-induced Ras-associated protein-1 (RAP1)/Ras-related C3 botulinum toxin substrate 1 (Rac1) pathway through formation of a complex with p130CAS and CrkII, leading to cytoskeletal remodeling of osteoclasts. Our data provide genetic and biochemical evidence that Siglec-15 facilitates M-CSF-induced cytoskeletal remodeling of the osteoclasts.

Improvement of absorbability, osteoconductivity, and strength of a β-tricalcium phosphate spacer for opening wedge high tibial osteotomy: clinical evaluations with 106 patients.
Jun Yamaguchi, Eiji Kondo, Kazunori Yasuda, Jun Onodera, Koji Yabuuchi, Takuma Kaibara, Kimiaki Takami, Norimasa Iwasaki, Tomonori Yagi
BMC musculoskeletal disorders, 25, 1, 441, 441, 2024年06月05日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: An ideal synthetic spacer for medial opening wedge high tibial osteotomy (MOWHTO) has not yet been developed. The authors have developed a new β-tricalcium phosphate (β-TCP) spacer with 60% porosity (N-CP60) by modifying the micro- and macro-pore structures of a conventional β-TCP spacer (CP60) that is widely used in clinical practice. The purpose of this study was to compare the absorbability, osteoconductivity, and in vivo strength of the N-CP60 spacer with those of the CP60 spacer, when used in MOWHTO. METHODS: First, the porosity, diameter distribution of macro- and micropores, and compressive strength of each β-TCP block were examined using methodology of biomaterial science. Secondly, a clinical study was performed using a total of 106 patients (106 knees) with MOWHTO, who were followed up for 18 months after surgery. In these knees, the N-CP60 and CP-60 spacers were implanted into 49 tibias and 57 tibias, respectively. The absorbability and osteoconductivity were radiologically evaluated by measuring the area of the implanted spacer remaining unabsorbed and assessing with the Hemert's score, respectively. The incidence of cracking in the implanted spacers was determined using computed radiography. Statistical comparisons were made with non-parametric tests. The significance level was set at p = 0.05. RESULTS: The N-CP60 and CP60 blocks had almost the same porosity (mean, 61.0% and 58.7%, respectively). The diameter of macropores was significantly larger (p < 0.0001) in the N-CP60 block than in the CP60 block, while the diameter of micropores was significantly smaller (p = 0.019) in the N-CP60 block. The ultimate strength of the N-CP60 block (median, 36.8 MPa) was significantly greater (p < 0.01) than that of the CP60 block (31.6 MPa). As for the clinical evaluations, the absorption rate of the N-CP60 spacer at 18 months after implantation (mean, 48.0%) was significantly greater (p < 0.001) than that of the CP60 spacer (29.0%). The osteoconductivity of the N-CP60 spacer was slightly but significantly higher (p = 0.0408) than that of the CP60 spacer only in zone 1. The incidence of in vivo cracking of the posteriorly located N-CP60 spacer at one month (mean, 75.5%) was significantly lower (p = 0.0035) than that of the CP60 spacer (91.2%). CONCLUSIONS: The absorbability, osteoconductivity, and compressive strength of the new N-CP60 spacer were significantly improved by modifying the macro- and micro-pore structures, compared with the conventional CP60 spacer. The N-CP60 spacer is more clinically useful than the CP60 spacer. TRIAL REGISTRATION NUMBER: H29-0002.

Bone Marrow Aspirate Concentrate Combined with Ultra-Purified Alginate Bioresorbable Gel Enhances Intervertebral Disc Repair in a Canine Model: A Preclinical Proof-of-Concept Study.
Daisuke Ukeba, Yoko Ishikawa, Katsuhisa Yamada, Takashi Ohnishi, Hiroyuki Tachi, Khin Khin Tha, Norimasa Iwasaki, Hideki Sudo
Cells, 13, 11, 2024年06月05日, ［国際誌］
英語, 研究論文（学術雑誌）, Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.

Elucidation of the association between additional distal femoral resection and extension angle improvement following the actual surgical steps with the Robot-TKA system.
Ryosuke Hishimura, Koji Iwasaki, Yuki Suzuki, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
The Knee, 49, 36, 44, 2024年06月04日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: This study investigates the association between additional distal femoral resection and improved flexion contracture in total knee arthroplasty (TKA) with a robot-assisted system. Flexion contracture is a common issue in patients with knee osteoarthritis, which causes postoperative complications and functional limitations. This study aims to evaluate the effectiveness of additional bone resection in flexion contracture correction and knee extension angle improvement after the actual surgical steps. METHODS: The study included 11 patients who underwent posterior-stabilized (PS)-type TKA with a robot-assisted system. The surgical technique consisted of precise bone resection and range of motion evaluation using a navigation system. A precut technique was used to facilitate posterior access and remove osteophytes that cause the contracture. The amount of additional distal femoral resection was determined based on the thickness of the insert trial required for achieving full extension. RESULTS: The flexion contracture correction angle and the amount of additional distal femoral resection demonstrated a linear relationship. An average of 2.0° with the standard error (SE) of 0.6° improvement in flexion contracture was observed per 1.0 mm of additional bone resection. The postoperative evaluation demonstrated a significant improvement in knee extension angle, thereby reducing the contracture degree. CONCLUSION: This study was the first to perform the additional distal femoral resection on the living knee, which closely replicates the actual surgical steps. The current study revealed that an additional 1.0 mm of distal femoral resection in PS-type TKA improves knee extension angle by 2.0° (SE 0.6°) within an additional resection range of 1.0 mm to 3.3 mm.

Analysis of foot-originating malignant bone tumors: Epidemiology, characteristics, and survival outcomes.
Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Ryuichi Fukuda, Eiji Kondo, Norimasa Iwasaki
Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons, 2024年05月29日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The study examines the characteristics and outcomes of foot-originating malignant bone tumors via Surveillance Epidemiology and End Results (SEER) database analysis. METHODS: A retrospective review of 14,695 malignant bone tumor cases from 2000 to 2019 was conducted. RESULTS: Of the eligible cases, 147 (2.3 %) were foot-origin tumors, typically smaller and more commonly treated with surgery than those in other locations. These tumors were more frequently treated with surgical resection, with a higher proportion undergoing amputation. In contrast, foot-origin tumors were less often managed with chemotherapy and radiation. Foot-origin tumors exhibited higher survival rates compared to non-foot-origin tumors as shown in univariate analysis, although multivariate analysis did not reflect significant differences. CONCLUSION: Foot-originating malignant bone tumors tend to be smaller and are frequently surgically treated, correlating with favorable survival outcomes. These findings point to early detection as a potential factor in the improved survival rates, not necessarily the tumor's origin.

A patient and public involvement study to explore patient perspectives on the efficacy of treatments for pain and numbness derived from ossification of posterior longitudinal ligament of the spine.
Masahiko Takahata, Yasuko Masuda, Tsutomu Endo, Yoshinao Koike, Masashi Yamazaki, Hiroshi Taneichi, Masayuki Miyagi, Hiroshi Takahashi, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2024年05月28日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Chronic pain and numbness are common complaints in patients with ossification of the posterior longitudinal ligament of the spine (OPLL). However, it is unclear whether the current treatments are effective in patients with OPLL in terms of improving pain and numbness. METHODS: A cross-sectional survey of patients with OPLL was conducted to determine patient satisfaction with surgery and drug therapy for pain and numbness, and its association with health-related quality of life. The survey was conducted by a patient association and its members, and anonymized data were analyzed by physicians. Comparisons between groups were made using T-tests or Kruskal-Wallis and Steel-Dwass tests, chi-square tests, and Fisher's exact tests. RESULTS: Data from 121 patients with OPLL (age 69 ± 11 years, 69 males; 43 females; and 7 unknown) who completed a mailed questionnaire were analyzed. Of the 93 patients with a history of surgery for OPLL, 24% and 18% reported much improvement in pain and numbness, respectively. After surgery, 42% and 48% reported some improvement, and 34% and 34% reported no improvement, respectively. Patients whose numbness did not improve with surgery had a significantly poorer health-related quality of life than those who did. Of the 78 patients who received medication, only 2% reported "much improvement," 64% reported "some improvement," and 31% reported "no improvement at all." Compared to patients with OPLL only in the cervical spine, those with diffuse-type OPLL showed poorer improvement in numbness after surgery and poorer quality of life. CONCLUSIONS: The majority of patients with OPLL belonging to the association were unsatisfied with surgery and pharmacotherapy in terms of pain and numbness improvement, indicating that there is an unmet medical need for more effective treatment for chronic pain and numbness in patients with OPLL.

Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models.
Maria Tada, Yuki Kudo, Michihito Kono, Masatoshi Kanda, Shuhei Takeyama, Kodai Sakiyama, Hotaka Ishizu, Tomohiro Shimizu, Tsutomu Endo, Ryo Hisada, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Norimasa Iwasaki, Tatsuya Atsumi
Clinical immunology (Orlando, Fla.), 264, 110255, 110255, 2024年05月18日, ［国際誌］
英語, 研究論文（学術雑誌）, Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.

Effect of urgent surgery within 8 hours compared to surgery between 8 and 24 hours on perioperative complications and neurological prognosis in patients older than 70 years with cervical spinal cord injury: a propensity score-matched analysis.
Tomoaki Shimizu, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Hiroki Ushirozako, Kento Inomata, Akio Minami, Katsuhisa Yamada, Tsutomu Endo, Masahiko Takahata, Norimasa Iwasaki, Hiroshi Takahashi, Masao Koda, Masashi Yamazaki
Journal of neurosurgery. Spine, 40, 5, 642, 652, 2024年05月01日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: This study aimed to investigate the effect of surgery within 8 hours on perioperative complications and neurological prognosis in older patients with cervical spinal cord injury by using a propensity score-matched analysis. METHODS: The authors included 87 consecutive patients older than 70 years who had cervical spinal cord injury and who had undergone posterior decompression and fusion surgery within 24 hours of injury. The patients were divided into two groups based on the time from injury to surgery: surgery within 8 hours (group 8 hours) and between 8 and 24 hours (group 8-24 hours). Following the preliminary study, the authors established a 1:1 matched model using propensity scores to adjust for baseline characteristics and neurological status on admission. Perioperative complication rates and neurological outcomes at discharge were compared between the two groups. RESULTS: Preliminary analysis of 87 prematched patients (39 in group 8 hours and 48 in group 8-24 hours) revealed that the motor index score (MIS) on admission was lower for lower extremities (12.3 ± 15.5 vs 20.0 ± 18.6, respectively; p = 0.048), and total extremities (26.7 ± 27.1 vs 40.2 ± 30.6, respectively; p = 0.035) in group 8 hours. In terms of perioperative complications, group 8 hours had significantly higher rates of cardiopulmonary dysfunction (46.2% vs 25.0%, respectively; p = 0.039). MIS improvement (the difference in scores between admission and discharge) was greater in group 8 hours for lower extremities (15.8 ± 12.6 vs 9.0 ± 10.5, respectively; p = 0.009) and total extremities (29.4 ± 21.7 vs 18.7 ± 17.7, respectively; p = 0.016). Using a 1:1 propensity score-matched analysis, 29 patient pairs from group 8 hours and group 8-24 hours were selected. There were no significant differences in baseline characteristics, neurological status on admission, and perioperative complications between the two groups, including cardiopulmonary dysfunction. Even after matching, MIS improvement was significantly greater in group 8 hours for upper extremities (13.0 ± 10.9 vs 7.8 ± 8.3, respectively; p = 0.045), lower extremities (14.8 ± 12.7 vs 8.3 ± 11.0, respectively; p = 0.044) and total extremities (27.8 ± 21.0 vs 16.0 ± 17.5, respectively; p = 0.026). CONCLUSIONS: Results of the comparison after matching demonstrated that urgent surgery within 8 hours did not increase the perioperative complication rate and significantly improved the MIS, suggesting that surgery within 8 hours may be efficient, even in older patients.

Glycosphingolipids in Osteoarthritis and Cartilage-Regeneration Therapy: Mechanisms and Therapeutic Prospects Based on a Narrative Review of the Literature.
Kentaro Homan, Tomohiro Onodera, Masatake Matsuoka, Norimasa Iwasaki
International journal of molecular sciences, 25, 9, 2024年04月30日, ［国際誌］
英語, 研究論文（学術雑誌）, Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell-surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolisms and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

The alterations in nerve growth factor concentration in plasma and synovial fluid before and after total knee arthroplasty.
Tomohiro Onodera, Koji Iwasaki, Masatake Matsuoka, Yasuhide Morioka, Shinji Matsubara, Eiji Kondo, Norimasa Iwasaki
Scientific reports, 14, 1, 8943, 8943, 2024年04月18日, ［国際誌］
英語, 研究論文（学術雑誌）, Total knee arthroplasty (TKA) is an effective procedure for pain relief; however, the emergence of postsurgical pain remains a concern. In this study, we investigated the production of nerve growth factor (NGF) and mediators that affect NGF production and their function in the synovial fluid and plasma after TKA. This study included 19 patients (20 knees) who had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and knee osteoarthritis (OA) who underwent TKA, categorized into OA and non-OA groups. The levels of NGF, inflammatory cytokines, and lipid mediators were analyzed before and after surgery. The intraoperative synovial fluid NGF concentration was more than seven times higher in the non-OA group than in the OA group. The intra-articular NGF levels increased significantly by more than threefold postoperatively in the OA group but not in the non-OA group. Moreover, the levels of inflammatory cytokines and lipid mediators were increased in the synovial fluid of both groups. The intra-articular cytokines or NGF concentrations positively correlated with postoperative pain. Targeted NGF control has the potential to alleviate postsurgical pain in TKA, especially in patients with OA, emphasizing the importance of understanding NGF dynamics under different knee conditions.

Clinical outcomes of perforator-based propeller flaps versus free flaps in soft tissue reconstruction for lower leg and foot trauma: a retrospective single-centre comparative study.
Mitsutoshi Ota, Makoto Motomiya, Naoya Watanabe, Kohei Shimoda, Norimasa Iwasaki
BMC musculoskeletal disorders, 25, 1, 297, 297, 2024年04月16日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The efficacy and safety of perforator-based propeller flaps (PPF) versus free flaps (FF) in traumatic lower leg and foot reconstructions are debated. PPFs are perceived as simpler due to advantages like avoiding microsurgery, but concerns about complications, such as flap congestion and necrosis, persist. This study aimed to compare outcomes of PPF and FF in trauma-related distal lower extremity soft tissue reconstruction. METHODS: We retrospectively studied 38 flaps in 33 patients who underwent lower leg and foot soft tissue reconstruction due to trauma at our hospital from 2015 until 2022. Flap-related outcomes and complications were compared between the PPF group (18 flaps in 15 patients) and the FF group (20 flaps in 18 patients). These included complete and partial flap necrosis, venous congestion, delayed osteomyelitis, and the coverage failure rate, defined as the need for secondary flaps due to flap necrosis. RESULTS: The coverage failure rate was 22% in the PPF group and 5% in the FF group, with complete necrosis observed in 11% of the PPF group and 5% of the FF group, and partial necrosis in 39% of the PPF group and 10% of the FF group, indicating no significant difference between the two groups. However, venous congestion was significantly higher in 72% of the PPF group compared to 10% of the FF group. Four PPFs and one FF required FF reconstruction due to implant/fracture exposure from necrosis. Additionally, four PPFs developed delayed osteomyelitis post-healing, requiring reconstruction using free vascularized bone graft in three out of four cases. CONCLUSIONS: Flap necrosis in traumatic lower-leg defects can lead to reconstructive failure, exposing implants or fractures and potentially causing catastrophic outcomes like osteomyelitis, jeopardizing limb salvage. Surgeons should be cautious about deeming PPFs as straightforward and microsurgery-free procedures, given the increased complication rates compared to FFs in traumatic reconstruction. DATA ACCESS STATEMENT: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author Correction: Effect of longer femoral head on leg length, offset, and range of motion in total hip arthroplasty: a simulation study.
Tomohiro Shimizu, Takuji Miyazaki, Shunichi Yokota, Hotaka Ishizu, Daisuke Takahashi, Norimasa Iwasaki
Scientific reports, 14, 1, 8481, 8481, 2024年04月11日, ［国際誌］
英語

Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights.
Shunichi Yokota, Hotaka Ishizu, Takuji Miyazaki, Daisuke Takahashi, Norimasa Iwasaki, Tomohiro Shimizu
Biomedicines, 12, 4, 2024年04月11日, ［国際誌］
英語, 研究論文（学術雑誌）, The increased incidence of osteoarthritis (OA), particularly knee and hip OA, and osteoporosis (OP), owing to population aging, have escalated the medical expense burden. Osteoarthritis is more prevalent in older women, and the involvement of subchondral bone fragility spotlights its association with OP. Notably, subchondral insufficiency fracture (SIF) may represent a more pronounced condition of OA pathophysiology. This review summarizes the relationship between OA and OP, incorporating recent insights into SIF. Progressive SIF leads to joint collapse and secondary OA and is associated with OP. Furthermore, the thinning and fragility of subchondral bone in early-stage OA suggest that SIF may be a subtype of OA (osteoporosis-related OA, OPOA) characterized by significant subchondral bone damage. The high bone mineral density observed in OA may be overestimated due to osteophytes and sclerosis and can potentially contribute to OPOA. The incidence of OPOA is expected to increase along with population aging. Therefore, prioritizing OP screening, early interventions for patients with early-stage OA, and fracture prevention measures such as rehabilitation, fracture liaison services, nutritional management, and medication guidance are essential.

Clinical Outcomes of Total Wrist Arthroplasty in Patients With Rheumatoid Arthritis: Minimum 10-Year Follow-Up Study.
Yuichiro Matsui, Akio Minami, Makoto Kondo, Jyunichi Ishikawa, Makoto Motomiya, Daisuke Kawamura, Norimasa Iwasaki
The Journal of hand surgery, 2024年04月09日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: We developed a semiconstrained total wrist prosthesis that was used in a series of patients with rheumatoid arthritis. We previously reported favorable clinical outcomes for up to 5 years after surgery; however, the longer-term outcomes remain unclear. The objective of this study was to evaluate the clinical outcomes of this wrist prosthesis for the treatment of severe wrist rheumatoid arthritis during a minimum 10 years of follow-up. METHODS: From 2010 through 2012, total wrist arthroplasty using the semiconstrained total wrist arthroplasty device was performed in 20 wrists in 20 patients with rheumatoid arthritis (five men and 15 women). The mean patient age was 64 years (range, 50-84 years). Preoperative radiographs showed Larsen grade IV changes in 16 wrists and grade V changes in four wrists. Patients were evaluated clinically and radiologically before surgery, 5 years after surgery, and 10 years or more after surgery. Evaluated parameters were the visual analog scale for pain, range of motion, Figgie score, and Disabilities of the Arm, Shoulder, and Hand score. RESULTS: The minimum 10-year follow-up clinical results (mean, 11.3 years) were available for all 14 surviving patients (three men and 11 women). Significant improvements in the mean visual analog scale for pain, Figgie score, and Disabilities of the Arm, Shoulder, and Hand score, compared with those before surgery, were maintained from 5 years after surgery to the final follow-up. The mean wrist flexion angle tended to slightly decrease at 5 years after surgery compared with that before surgery but remained similar from 5 years after surgery to the final follow-up. The increase in the mean wrist extension angle, compared with that before surgery, was maintained from 5 years after surgery to the final follow-up. Radiographic evaluation had already revealed implant loosening in five of the 19 wrists at 5 years after surgery, but there were no new cases of component loosening identified at the final follow-up. CONCLUSIONS: Total wrist arthroplasty using the semiconstrained arthroplasty system achieves favorable clinical outcomes with no serious complications requiring revision for 10 years after surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Surgical Resection of Primary Tumor for Bone Metastatic Breast Cancer Patients at Initial Presentation.
Nayu Kitsuya, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Yuki Suzuki, Masanari Hamasaki, Eiji Kondo, Norimasa Iwasaki
Anticancer research, 44, 4, 1591, 1601, 2024年04月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND/AIM: The purpose of this study was to investigate whether primary tumor resection in patients with bone metastatic breast cancer has an impact on survival using the Surveillance, Epidemiology, and End Results database, considering subtype classification. PATIENTS AND METHODS: We included all female patients with bone metastatic breast cancer at initial presentation between 2010 and 2016 with known hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses. Cases showing unknown cause of death or unknown HR/HER2 status were excluded. Survival analysis was performed using Cox proportional hazards modeling to calculate hazard ratios (HZR). RESULTS: Of the 13,450 patients included in this study, 2,073 patients were HR+/HER2+, 8,597 patients were HR+/HER2-, 797 patients were HR-/HER2+, and 1,182 patients were HR-/HER2- (triple-negative). Five-year overall survival (OS) rate was 34.5% in HR+/HER2+, 26.0% in HR+/HER2-, 29.2% in HR-/HER2+ and 8.0% in triple-negative. Triple-negative patients showed the worsen OS [HR+/HER2+: HZR=2.1, 95% confidence interval (CI)=1.9-2.3; HR+/HER2-: HZR= 2.4, 95%CI=2.2-2.6; HR-/HER2+: HZR=1.5, 95%CI=1.3-1.6]. After excluding patients who died within six months, primary tumor resection prolonged survival in each subtype classification except HR-/HER2+. CONCLUSION: Patients with triple-negative bone metastatic breast cancer showed unfavorable survival. Primary tumor resection prolonged survival in each subtype except for HR-/HER2+.

Bone Density Distribution Pattern in the Lateral Wall of the Femoral Intercondylar Notch: Implications for the Direct Insertion of the Femoral ACL Attachment.
Yutaro Sugawara, Koji Iwasaki, Yuki Suzuki, Ryosuke Hishimura, Shinji Matsubara, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
Orthopaedic journal of sports medicine, 12, 4, 23259671241236807, 23259671241236807, 2024年04月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The ideal position of the femoral bone tunnel in the anterior cruciate ligament (ACL) is controversial. The functional importance of the ACL fiber varies depending on where it is attached to the femur. Functionally important fibers can cause high mechanical stress on the bone, and the Wolff law predicts that bone mineral density will increase at high mechanical stress sites. PURPOSE/HYPOTHESIS: The purpose of this study was to use computed tomography imaging to determine the distribution pattern of bone density in the lateral intercondylar wall. It was hypothesized that the high-density area (HDA) of the lateral intercondylar wall would reflect the functional insertion of the ACL as reported in previous anatomic studies. STUDY DESIGN: Descriptive epidemiology study. METHODS: Data from 39 knees without ACL injuries were retrospectively collected. The HDA of the lateral intercondylar wall was defined as the region containing the top 10% of the radiodensity values. The shape of the HDA was approximated as an ellipse, and the quadrant method was used to determine the center of the ellipse. The association between the ratio of the minor axis to the major axis of the ellipse and background characteristics was investigated. RESULTS: According to the quadrant method, the center of the HDA ellipse was 33.6% in the deep-shallow direction and 23.4% in the high-low direction. The center of the ellipse was comparable to the anatomic center of the ACL footprint, as previously reported. The ratio of the minor axis to the major axis of the ellipse was 0.58 (95% CI, 0.54-0.62). There was a significant negative correlation between the ratio of the minor axis to the major axis of the HDA ellipse and the posterior tibial slope (r = -0.38, P = .02). CONCLUSION: The center of the HDA ellipse was found to be similar to the anatomic center of the ACL footprint. Considering the mechanical stress responses in bone, the HDA of the lateral intercondylar wall has the potential to represent the ACL insertion, especially functional insertion.

Articular cartilage corefucosylation regulates tissue resilience in osteoarthritis.
Kentaro Homan, Tomohiro Onodera, Hisatoshi Hanamatsu, Jun-Ichi Furukawa, Daisuke Momma, Masatake Matsuoka, Norimasa Iwasaki
eLife, 12, 2024年03月11日, ［国際誌］
英語, 研究論文（学術雑誌）, This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation in mice resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.

The Influence of Patello-Femoral Overstuffing After Modular Unlinked Bicompartmental Knee Arthroplasty (BiKA) for Medial Tibio-Femoral and Patello-Femoral Osteoarthritis of the Knee.
Rikiya Baba, Yasumitsu Ohkoshi, Tatsunori Maeda, Ko Suzuki, Akane Iwadate, Koji Iwasaki, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
The Journal of arthroplasty, 39, 3, 638, 644, 2024年03月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The factors affecting results after bicompartmental knee arthroplasty (BiKA) have not been fully elucidated. This major ligament-preserving procedure may be more susceptible to overstuffing of the patello-femoral (PF) joint than the major ligament-sacrificing total knee arthroplasty. Currently, we investigated the effect of PF overstuffing after BiKA on its clinical outcome. METHODS: There were 71 patients (74 knees) who underwent modular unlinked BiKA at our clinic who had a follow-up of 5 to 9 years. Final follow-up results were assessed by evaluating knee range of motion, the 2011 Knee Society Score (2011KSS), Japanese Knee Osteoarthritis Measure, and radiological findings. The degree of postoperative PF overstuffing was evaluated by computed tomography and magnetic resonance images for 55 knees, and the correlation between the degree of overstuffing and postoperative clinical results were examined. RESULTS: Overall clinical results improved significantly after surgery without any revision cases. The X-ray measurements showed the improved coronal alignments and the appropriate implant installation angles. Higher degree of postoperative PF overstuffing caused by insufficient amount of osteotomy on the anterior surface of the femur correlated with worse postoperative total 2011KSS at 2 years after surgery (Spearman's rank correlation coefficient (rs) = -0.387, P = .004), as opposed to no correlation at the time of the final follow-up (Spearman's rank correlation coefficient = 0.068, P = .623). CONCLUSION: Modular unlinked BiKA provided patients with a high level of satisfaction and functional improvement over 5 to 9 years postoperatively. However, because PF overstuffing affects initial patient satisfaction, the amount of osteotomy should be determined carefully during the surgery.

Simultaneous medial closing wedge distal femoral varus osteotomy and double-bundle anterior cruciate ligament reconstruction in the symptomatic femoral valgus deformity: A case report.
Masatake Matsuoka, Eiji Kondo, Koji Iwasaki, Tomohiro Onodera, Ryuichi Nakamura, Hiroshi Nakayama, Takenori Akiyama, Daisuke Momma, Norimasa Iwasaki
Joint diseases and related surgery, 35, 2, 422, 432, 2024年02月13日, ［国際誌］
英語, 研究論文（学術雑誌）, Distal femoral varus osteotomy (DFVO) is a widely recognized surgical procedure used to address valgus malalignment in patients with knee joint disorders. However, it still remains unclear whether anterior cruciate ligament (ACL) reconstruction can be performed in a single procedure along with DFVO. Herein, we present a 73-year-old female patient who developed lateral osteoarthritis of the knee with valgus alignment due to chronic ACL deficiency following a twisting injury during skiing. She was physiologically very active, and strongly demanded to return to sports. We performed a combined procedure involving a medial closing wedge DFVO using an anatomical locking plate, along with double-bundle ACL reconstruction. The postoperative radiograph confirmed successful correction of knee alignment, specifically achieving varus alignment with precise conformance of the anatomical plate to the medial contour of the distal femur following the osteotomy. The patient resumed her previous sports activities without experiencing knee pain. The operated knee demonstrated restored anterior stability, as indicated by negative Lachman test results, and regained full range of motion. Both the Knee Injury and Osteoarthritis Outcome Score and the 2011 Knee Society score demonstrated continuous postoperative improvements over the three-year follow-up period, indicating positive functional outcomes and joint preservation. To the best of our knowledge, this is the first case of medial closing wedge DFVO with anatomic double-bundle ACL reconstruction in the symptomatic femoral valgus deformity with chronic ACL deficiency in the literature.

Zinc improves Denosumab and eldecalcitol efficacy for bone mineral density in patients with hypozincemia.
Hotaka Ishizu, Tomohiro Shimizu, Yusuke Ohashi, Kenichi Kusunoki, Masahiro Kanayama, Norimasa Iwasaki, Fumihiro Oha
Journal of bone and mineral metabolism, 42, 2, 233, 241, 2024年02月07日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: We aimed to investigate the effects of zinc deficiency and zinc medication in osteoporosis patients undergoing denosumab (DMAb). MATERIALS AND METHODS: This retrospective study was conducted at a single hospital. The participants were female osteoporosis patients visiting between April 2019 and April 2020. All patients were treated with DMAb and eldecalcitol and recommended zinc-rich food. Based on zinc medication and serum zinc levels at the 12th month of dietary guidance, patients were categorized into the following four groups: hypozincemia with zinc medication, latent zinc deficiency with zinc medication, without zinc medication, and control without zinc medication. Longitudinal serum zinc concentrations, bone mineral density (BMD), and occurrence of fractures were measured. We investigated the factors influencing no response to DMAb and eldecalcitol treatment. RESULTS: Among the 145 patients followed up for 24 months, dietary guidance did not change the serum zinc concentration; however, zinc medication significantly increased these levels. The hypozincemia group did not show a significant BMD increase in the lumbar spine and femoral neck after DMAb and eldecalcitol treatment during dietary guidance; however, zinc medication increased these to the same levels as the other groups. In multivariate analyses, hypozincemia and thyroid disease were identified as the factors affecting no response. While 28.2% of patients with latent zinc deficiency without zinc medication suffered fractures, no fractures occurred in hypozincemia patients with zinc medication. CONCLUSION: Hypozincemia may reduce the efficacy of DMAb and eldecalcitol in increasing BMD and fracture prevention.

Secondary fracture and mortality risk with very high fracture risk osteoporosis and proximal femoral fracture.
Hotaka Ishizu, Tomohiro Shimizu, Kosuke Arita, Komei Sato, Renya Takahashi, Kenichi Kusunoki, Shun Shimodan, Tsuyoshi Asano, Norimasa Iwasaki
Journal of bone and mineral metabolism, 42, 2, 196, 206, 2024年02月03日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: We aimed to investigate secondary fracture and mortality rates, and risk factors in patients with proximal femoral fractures. MATERIALS AND METHODS: We conducted a multicenter prospective cohort study on female patients with proximal femoral fractures who underwent surgical treatment between April 2020 and March 2021. Postoperative follow-ups were performed at 6-, 12-, 18-, and 24-month intervals to determine the secondary fracture and mortality rates, and the risk factors and its influence were examined. RESULTS: Of the 279 registered patients, 144 patients (51.6%) were diagnosed with very high fracture risk osteoporosis. The postoperative osteoporosis rate exceeded 96%; however, osteoanabolic agents were used sparingly. The risk factor of both secondary fracture and mortality was very high fracture risk osteoporosis, and secondary fractures within 12 months were markedly occurred. Secondary fracture rates increased as the number of matched very high fracture risk osteoporosis criteria increased. Notably, secondary fractures and mortality were recorded in 21.4% and 23.5% of the patients who met all criteria, respectively. CONCLUSION: Over half of the female patients with proximal femoral fractures had very high fracture risk osteoporosis. Although, very high fracture risk osteoporosis demonstrated a notably increased risk of secondary fractures, particularly at 12 months post-surgery, the use of osteoanabolic agents was substantially low. Collectively, our findings highlight the need to consider the risk of very high fracture risk osteoporosis, expand the use of medications to include osteoanabolic agents, and reconsider the current healthcare approach for proximal femoral fractures.

Effect of longer femoral head on leg length, offset, and range of motion in total hip arthroplasty: a simulation study.
Tomohiro Shimizu, Takuji Miyazaki, Shunichi Yokota, Hotaka Ishizu, Daisuke Takahashi, Norimasa Iwasaki
Scientific reports, 14, 1, 1829, 1829, 2024年01月21日, ［国際誌］
英語, 研究論文（学術雑誌）, In this study, we investigated the relationship between head length, leg length, offset, and dislocation resistance using range of motion (ROM) simulations based on computed tomography data to examine if a longer femoral head reduces the risk of dislocation. The femoral components were set to eliminate leg length differences with a + 0 mm head, and variations for + 4-, + 7-, and + 8-mm heads were analyzed. Offset and ROM were assessed when longer heads were used, with the leg length adjusted to be similar to that of the contralateral side. While internal rotation at flexion and external rotation at extension increased with + 4-mm longer heads, the + 7- and + 8-mm heads did not increase dislocation resistance. When adjusting for leg length, the longer heads showed no significant differences in offset and ROM. Enhancing dislocation resistance by solely increasing the offset with a longer head, while simultaneously adjusting the depth of stem insertion, may be a beneficial intraoperative technique. Although a + 4-mm longer head possibly increases ROM without impingement, heads extended by + 7 or + 8 mm may not exhibit the same advantage. Therefore, surgeons should consider this technique based on the implant design.

Methylprednisolone pulse-enhanced neutrophil extracellular trap formation in mice with imiquimod-induced lupus-like disease, resulting in ischaemia of the femoral head cartilage.
Hodaka Ogawa, Shunichi Yokota, Yumeka Hosoi, Ayano Shindo, Naho Ogawa, Ryodai Yamamura, Tomohiro Shimizu, Issei Nakade, Suishin Arai, Mai Taniguchi, Yuka Nishibata, Sakiko Masuda, Daigo Nakazawa, Utano Tomaru, Norimasa Iwasaki, Akihiro Ishizu
Lupus science & medicine, 10, 2, 2023年12月28日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Methylprednisolone (mPSL) pulse therapy is an essential option for patients with active systemic lupus erythematosus, but there is a risk of adverse events related to microcirculation disorders, including idiopathic osteonecrosis of the femoral head (ONFH). Recent studies have revealed that excessive neutrophil extracellular traps (NETs) are involved in microcirculation disorders. This study aimed to demonstrate that mPSL pulse could induce NETs in lupus mice and identify the factors contributing to this induction. METHODS: Six mice with imiquimod (IMQ)-induced lupus-like disease and six normal mice were intraperitoneally injected with mPSL on days 39 to 41, and five mice with IMQ-induced lupus-like disease and six normal mice were injected with phosphate-buffered saline. Pathological examinations were conducted to evaluate the ischaemic state of the femoral head and tissue infiltration of NET-forming neutrophils. Proteome analysis was performed to extract plasma proteins specifically elevated in mPSL-administered mice with IMQ-induced lupus-like disease, and their effects on NET formation were assessed in vitro. RESULTS: Mice with IMQ-induced lupus-like disease that received mPSL pulse demonstrated ischaemia of the femoral head cartilage with tissue infiltration of NET-forming neutrophils. Proteome analysis suggested that prenylcysteine oxidase 1 (PCYOX1) played a role in this phenomenon. The reaction of PCYOX1-containing very low-density lipoproteins (VLDL) with its substrate farnesylcysteine (FC) induced NETs in vitro. The combined addition of IMQ and mPSL synergistically enhanced VLDL-plus-FC-induced NET formation. CONCLUSION: PCYOX1 and related factors are worthy of attention to understand the underlying mechanisms and create novel therapeutic strategies for mPSL-mediated microcirculation disorders, including ONFH.

Radiofrequency Echographic Multispectrometry (REMS) can Overcome the Effects of Structural Internal Artifacts and Evaluate Bone Fragility Accurately.
Hotaka Ishizu, Tomohiro Shimizu, Yuki Sakamoto, Fumi Toyama, Keita Kitahara, Hiroki Takayama, Moritaka Miyamoto, Norimasa Iwasaki
Calcified tissue international, 114, 3, 246, 254, 2023年12月21日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: This study measured bone mineral density (BMD) in a Japanese population using the novel non-ionizing system using radiofrequency echographic multispectrometry (REMS) and compared the results with those obtained using traditional dual-energy X-ray absorptiometry (DXA). We aimed to identify any discrepancies between measurements obtained using these instruments and identify the influencing factors. METHODS: This cross-sectional study examined patients with osteoporosis treated at a single center from April to August 2023. We examined BMD assessment by DXA and REMS in lumbar spine and proximal femur. Patients were categorized into two groups: those with discrepancies between lumbar spine BMD measured by DXA and REMS, and those without. Semiquantitative evaluation of vertebral fractures and abdominal aortic calcification scoring were also performed and compared between the two groups, along with various patient characteristics. RESULTS: A total of 70 patients (88.6% female; mean age 78.39 ± 9.50 years) undergoing osteoporosis treatment were included in the study. A significant difference was noted between DXA and REMS measurement of BMD and T-scores, with REMS recording consistently lower values. The discrepancy group exhibited a higher incidence of multiple vertebral fractures and increased vascular calcification than the non-discrepancy group. Multivariate analysis indicated that diabetes mellitus, severe vertebral fractures, and increased abdominal aortic calcification scores were significantly associated with discrepancies in lumbar spine T-scores. CONCLUSION: This study suggests that REMS may offer a more accurate measurement of BMD, overcoming the overestimation of BMD by DXA owing to factors such as vertebral deformities, abdominal aortic calcification, and diabetes mellitus.

A simple free flap strategy using end-to-side anastomosis to the main vessels in injured extremity.
Makoto Motomiya, Naoya Watanabe, Mitsutoshi Ota, Kohei Shimoda, Daisuke Kawamura, Norimasa Iwasaki
JPRAS open, 38, 48, 59, 2023年12月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: During free flap surgery, the surgeon sometimes encounters problems with anastomosis such as intractable arterial spasms or vessel size discrepancy in venous anastomoses. End-to-side (ETS) anastomosis has the advantages of limited chance of vessel spasm and easy handling by adjusting for vessel size discrepancy. We introduced the arterial and venous end-to-side anastomosis (AV-ETS) strategy, which is based on the ETS anastomosis to the main artery and accompanying veins, to avoid intraoperative anastomotic problems when creating a free flap. The aim of this study was to compare flap outcomes and intraoperative anastomotic problems before and after introduction of the AV-ETS strategy in extremity free flap surgery. MATERIALS AND METHODS: We retrospectively examined 72 consecutive extremity free flaps. Before introducing the AV-ETS strategy, we used the conventional strategy in which the recipient artery was selected according to the number of the remaining main artery and the anastomosis technique was flexibly changed, although the end-to-end (ETE) technique was used in most cases. RESULTS: The conventional group had 18 flaps and the AV-ETS group had 54 flaps. The rate of flap survival did not differ between these groups, and there were no cases of flap failure after the introduction of the AV-ETS strategy. The AV-ETS group had significantly fewer flaps that required a change in preoperative planning for the recipient artery or anastomotic site of the artery. CONCLUSIONS: The AV-ETS strategy may facilitate reliable preoperative planning and the performance of stable free flap surgery without requiring a flexible response during surgery.

Epidemic Preventive Management during the Coronavirus Disease 2019 Pandemic Is a Risk Factor for Delirium after Spinal Cord Injury Surgery.
Hiroki Ushirozako, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Tomoaki Shimizu, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Yukihiro Matsuyama
Spine surgery and related research, 7, 6, 474, 481, 2023年11月27日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Epidemic preventive management during the coronavirus disease 2019 (COVID-19) pandemic may have negatively impacted perioperative outcomes in patients with traumatic spinal cord injury (SCI). However, little is known about the relationship between epidemic preventive management and delirium after traumatic SCI. Here, we clarified the predictors of delirium after SCI surgery. METHODS: We retrospectively analyzed 231 patients (mean age, 66 years) who underwent SCI surgery between 2017 and 2021. Patients were categorized into the delirium and non-delirium groups. Preoperative characteristics and laboratory data related to the occurrence of delirium were assessed. During the study period, we continued early surgical intervention. However, early rehabilitation intervention was not performed in the hospital rehabilitation room from May 2020 due to epidemic preventive management, which involved performing rehabilitation on the bed for 8 days postoperatively. RESULTS: Postoperatively, 33 (14.3%) patients experienced delirium. Univariate analysis showed that age (p<0.01), presence of a psychiatric disorder (p<0.05), dementia (p<0.05), serum albumin (p<0.05) and hemoglobin (p<0.01) levels, American Society of Anesthesiologists classification score (p<0.05), and treatment during the COVID-19 pandemic (p<0.01) differed significantly in the delirium and non-delirium groups. Multivariate logistic regression analysis showed that an age ≥73 years (odds ratio [OR], 15.78; 95% confidence interval [CI], 4.54-54.80; p<0.01), treatment during the COVID-19 pandemic (OR, 3.85; 95% CI, 1.61-9.22; p<0.01), and psychiatric disorder (OR, 29.38; 95% CI, 5.63-153.43; p<0.01) were associated with delirium. CONCLUSIONS: Our comprehensive preventive management during the COVID-19 pandemic was identified as one of the risk factors for delirium after SCI surgery. Patients with preventive management should be cautioned regarding the risk of delirium.

Valgus instability and related factors beyond 2 years following unlinked total elbow arthroplasty.
Yuki Matsui, Makoto Kondo, Yasuhiko Nishio, Sadatoshi Kato, Norimasa Iwasaki
Journal of shoulder and elbow surgery, 33, 3, 544, 549, 2023年11月26日, ［国際誌］
英語, 研究論文（学術雑誌）, HYPOTHESIS AND BACKGROUND: Total elbow arthroplasty (TEA), categorized into linked and unlinked types, is commonly reported treatment for rheumatoid arthritis of the elbow. Although unlinked TEA preserves bone, it may result in instability. This study aimed to assess the outcomes of unlinked TEA in rheumatoid arthritis of the elbow beyond two years and to identify factors correlating with postoperative valgus instability of unlinked TEA. METHODS: This study included patients who underwent TEA for rheumatoid arthritis of the elbow at our department between August 2009 and January 2017, with a follow-up period exceeding two years. Elbow joint range of motion (ROM) and clinical scores were evaluated preoperatively and at the final follow-up. Factors contributing to valgus instability, such as the Larsen grade, sex, age, side, preoperative ROM, postoperative ROM, implant placement, preoperative carrying angle, and the use of biological disease-modifying antirheumatic drugs (bDMARDs), were also assessed. RESULTS: This study encompassed 26 elbows from 23 patients, with a mean patient age at surgery of 64.8 years and a mean follow-up duration of 92.4 months. Significant improvements were observed in the ROM (extension: from -31° preoperatively to -21° postoperatively [p = 0.02], flexion: from 116°-137° [p < 0.001]), Japanese Orthopaedic Association-Japan Elbow Society Elbow Function Score (from 45.9-86.3 points [p < 0.001]), and Mayo Elbow Performance Score (from 43.6-91.7 points [p < 0.001]). At the last follow-up, two elbows exhibited radiolucent lines around the humeral stem, whereas seven had valgus instability. Factors correlated with valgus instability included total arc at the final follow-up, preoperative carrying angle, and the use of bDMARDs. DISCUSSION AND CONCLUSION: Unlinked TEA demonstrated favorable midterm outcomes for rheumatoid arthritis of the elbow, albeit with occasional valgus instability. Surgeons should consider preoperative carrying angle and bDMARD use, and exercise caution regarding intraoperative extensions.

Assessing knee joint biomechanics and trunk posture according to medial osteoarthritis severity.
Yuki Suzuki, Yasumitsu Ohkoshi, Kensaku Kawakami, Kenta Shimizu, Shuya Chida, Kengo Ukishiro, Tomohiro Onodera, Koji Iwasaki, Tatsunori Maeda, Sho'ji Suzuki, Eiji Kondo, Norimasa Iwasaki
Scientific reports, 13, 1, 19186, 19186, 2023年11月06日, ［国際誌］
英語, 研究論文（学術雑誌）, During progression of knee osteoarthritis (OA), gait biomechanics changes three-dimensionally; however, its characteristics and trunk posture according to OA severity remain unknown. The present study investigated three-dimensional knee joint biomechanics and trunk posture according to knee OA severity. Overall, 75 patients (93 knees) with medial knee OA [Kellgren-Lawrence grade ≥ 2, grade 2: 20 patients with 24 knees (mean 60.0 years old); grade 3: 25 with 28 knees (mean 62.0 years old); grade 4: 30 with 41 knees (mean 67.9 years old)] and 14 healthy controls (23 knees, mean 63.6 years old) underwent gait analysis using an optical motion capture system and point cluster technique. In grade 2 knee OA, the relative contribution of the knee adduction moment (KAM) increased significantly (P < 0.05), and that of the knee flexion moment decreased (P < 0.05) prior to significant progression of varus knee deformity. Grade 3 knee OA showed significant exacerbation of varus knee deformity (P < 0.01) and KAM increase (P < 0.001). The maximum knee extension angle decreased (P < 0.05) and trunk flexion increased during gait in grade 4 knee OA (P < 0.001). Our study clarified the kinematics and kinetics of medial knee OA with trunk flexion according to severity. Kinetic conversion occurred in grade 2 knees prior to progression of varus deformities, knee flexion contractures, and sagittal imbalance during gait in patients with severe knee OA.

Unique skin findings in a case of the A3 pulley trigger finger due to an osteochondroma
Takuya Yabumoto, Takeshi Endo, Ryo Itoga, Daisuke Kawamura, Yuichiro Matsui, Norimasa Iwasaki
Joint Diseases and Related Surgery, 35, 1, 249, 253, Joint Diseases and Related Surgery, 2023年10月31日, ［国際誌］
英語, 研究論文（学術雑誌）, Trigger finger is usually caused by stenosing tenosynovitis and hypertrophy of the retinacular sheath, and the most common site of tendon triggering is the A1 pulley. Although the A3 pulley trigger finger has been described in a few cases caused by hypertrophy of the retinacular sheath and ganglion, associated skin findings have not been reported to date. Herein, we report a rare case of the A3 pulley trigger finger due to osteochondroma with unique skin findings in a 50-year-old woman. In this case, we observed a V-shaped skin depression on the palmar side of the proximal interphalangeal joint of the right middle finger during finger locking. Additionally, we observed bilateral linear skin depressions on the sides of the proximal phalange. These findings might be caused by the traction force on the A3 pulley, connected to the skin via the Grayson and Cleland ligaments, which are fibrous tissues that connect the skin and tendon sheath.

Joint instability in patients with borderline developmental dysplasia of the hip.
Fumiya Kizawa, Daisuke Suzuki, Satoshi Nagoya, Arata Kanaizumi, Tomohiro Shimizu, Tohru Irie, Daisuke Takahashi, Norimasa Iwasaki
Clinical biomechanics (Bristol, Avon), 111, 106136, 106136, 2023年10月30日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The treatment strategy for developmental dysplasia of the hip is determined based on the lateral center-edge angle. Nonetheless, an evaluation of joint instability may be important in determining the treatment strategy. This study classified the displacement patterns of the femoral head center during hip abduction. METHODS: Ten patients with borderline developmental dysplasia of the hip, 10 patients with developmental dysplasia of the hip, and 10 patients with normal hips were analyzed. Image matching was performed using X-ray images of hip abduction with a three-dimensional hip model. The displacement of the femoral head center and its trajectory length were measured. A cluster analysis was conducted to classify the displacement pattern of the femoral head center, and trajectory lengths were compared. FINDINGS: Displacement was classified into three patterns: medialization, hinge abduction, and centering. Patients with borderline developmental hip dysplasia exhibited all three patterns. Almost all patients with developmental dysplasia of the hip showed medialization and hinge abduction, whereas all normal patients had the centering type. The mean trajectory length indices for the medialization and hinge abduction types were significantly longer than those for the centering type (P = 0.01 and P = 0.016, respectively). INTERPRETATION: Borderline developmental dysplasia of the hip is a heterogeneous condition characterized by varying hip instability levels. Our findings suggest that uniform evaluation based on the lateral center-edge angle is inappropriate and that joint instability must be evaluated in each patient with borderline developmental dysplasia of the hip.

Arthrodesis of the interphalangeal joints of the hand by two-dimensional intraosseous wiring.
Tomoaki Suzuki, Daisuke Kawamura, Yuichiro Matsui, Norimasa Iwasaki
BMC musculoskeletal disorders, 24, 1, 843, 843, 2023年10月25日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Numerous techniques for arthrodesis have been described to fix interphalangeal (IP) joints, and the fixation method should be considered on a case-by-case basis. This study aimed to investigate the availability of IP joint arthrodesis of the hand, using a two-dimensional intraosseous wiring (two-DIOW) method. METHODS: A total of 43 joints (19 thumb IP joints, 9 proximal finger interphalangeal (PIP) joints and 15 distal interphalangeal (DIP) joints in 29 patients with a mean age of 66 years (range, 24-85 y) were retrospectively analyzed. All operations were performed with two-DIOW method. We evaluated the bone union rate, correction loss, presence of any surgical complications, and oral steroid use in cases of joint fixation using the two-DIOW method. RESULTS: Of these 43 digits, 42 achieved bone union (97.7%). Non-union was seen in a thumb IP joint of mutilans rheumatoid arthritis. Mean correction loss of deviation was 1.0°, and flexion or extension angulation was 1.6° in the direction of extension. Surgical complications included mild nail deformity in 2 digits and wire irritation necessitating wire removal in 2 digits. Oral steroids were used for 18 of the 43 digits, including 2 digits complicated by nail deformities. There was no infection and skin necrosis in all digits with or without steroid use. CONCLUSIONS: The two-DIOW method appears to offer an effective method of IP joint fixation, but caution should be exercised in digits of severe joint destruction and in the treatment of wire knot.

Arthrodesis of the interphalangeal joints of the hand by two-dimensional intraosseous wiring
Tomoaki Suzuki, Daisuke Kawamura, Yuichiro Matsui, Norimasa Iwasaki
BMC Musculoskeletal Disorders, 24, 1, 385, 385, Springer Science and Business Media LLC, 2023年10月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Abstract

Background

Numerous techniques for arthrodesis have been described to fix interphalangeal (IP) joints, and the fixation method should be considered on a case-by-case basis. This study aimed to investigate the availability of IP joint arthrodesis of the hand, using a two-dimensional intraosseous wiring (two-DIOW) method.

Methods

A total of 43 joints (19 thumb IP joints, 9 proximal finger interphalangeal (PIP) joints and 15 distal interphalangeal (DIP) joints in 29 patients with a mean age of 66 years (range, 24–85 y) were retrospectively analyzed. All operations were performed with two-DIOW method. We evaluated the bone union rate, correction loss, presence of any surgical complications, and oral steroid use in cases of joint fixation using the two-DIOW method.

Results

Of these 43 digits, 42 achieved bone union (97.7%). Non-union was seen in a thumb IP joint of mutilans rheumatoid arthritis. Mean correction loss of deviation was 1.0°, and flexion or extension angulation was 1.6° in the direction of extension. Surgical complications included mild nail deformity in 2 digits and wire irritation necessitating wire removal in 2 digits. Oral steroids were used for 18 of the 43 digits, including 2 digits complicated by nail deformities. There was no infection and skin necrosis in all digits with or without steroid use.

Conclusions

The two-DIOW method appears to offer an effective method of IP joint fixation, but caution should be exercised in digits of severe joint destruction and in the treatment of wire knot.

Chronic shoulder injury related to vaccine administration following coronavirus disease 2019 vaccination: a case report.
Masahiro Miyano, Yukinori Tsukuda, Shigeto Hiratsuka, Masanari Hamasaki, Norimasa Iwasaki
Journal of medical case reports, 17, 1, 456, 456, 2023年10月17日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Shoulder injury related to vaccine administration, defined as shoulder pain and limited range of motion occurring after administration in the upper arm, has been previously reported. The symptom resolved completely after treatment with oral nonsteroidal anti-inflammatory drugs or an intraarticular steroid injection, however there have been few reports of long-term symptoms following coronavirus disease 2019 vaccination. This case report describes a healthy, middle-aged, healthcare worker who developed post-vaccination subacromial-subdeltoid bursitis that lasted for more than 6 months after Pfizer-BioNTech coronavirus disease 2019 vaccination. CASE PRESENTATION: A 55-year-old Japanese woman with no significant medical history was vaccinated in the standard site, with the needle direction perpendicular to the skin. Within a few hours after the second vaccination, severe shoulder pain and limited range of motion appeared. Although shoulder range of motion improved, her shoulder pain did not improved for several months, and she consulted an orthopedic doctor 5 months later. Radiographs of her left shoulder did not provide helpful diagnostic information. High intensity in the subacromial-subdeltoid space was seen on short TI inversion recovery of magnetic resonance imaging, showing subacromial-subdeltoid bursitis. She was diagnosed with a shoulder injury related to vaccine administration. The patient was started on an oral anti-inflammatory drug, and the left subacromial space was injected with 2.5 mg of betamethasone with 3 ml of 1% lidocaine without epinephrine every 2 weeks. One month after starting this treatment, since her shoulder pain had not improved, the oral anti-inflammatory drug was switched to tramadol hydrochloride acetaminophen. However, 3 months after switching medication, the shoulder pain continued, and she worked so as to have minimal impact on her shoulder. CONCLUSION: A case of subacromial-subdeltoid bursitis following a second dose of the Pfizer-BioNTech coronavirus disease 2019 vaccine that lasted many months is reported. Injection technique is a modifiable risk factor, the adverse effects of which could potentially be mitigated with appropriate and relevant training of healthcare providers. To prevent this type of case, the appropriate landmark, needle length, and direction should be confirmed.

An international study to explore the feasibility of collecting standardised outcome data for Complex Regional Pain Syndrome: recommendations for an international clinical research registry.
Sharon Grieve, Florian Brunner, Danylo F Cabral, Robyn Connett, Hitoshi Hirata, Norimasa Iwasaki, Yasunobu Nakagawa, Afrin Sagir, Gudson Sousa, Jean-Jacques Vatine, Nicole Vaughan-Spickers, Jijun Xu, Lisa Buckle, Candida McCabe
British journal of pain, 17, 5, 468, 478, 2023年10月, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Complex Regional Pain Syndrome (CRPS) is a persistent pain condition with low prevalence. Multi-centre collaborative research is needed to attain sufficient sample sizes for meaningful studies. This international observational study: (1) tested the feasibility and acceptability of collecting outcome data using an agreed core measurement set (2) tested and refined an electronic data management system to collect and manage the data. METHODS: Adults with CRPS, meeting the Budapest diagnostic clinical criteria, were recruited to the study from 7 international research centres. After informed consent, a questionnaire comprising the core set outcome measures was completed: on paper at baseline (T1), and at 3 or 6 months (T2) using a paper or e-version. Participants and clinicians provided feedback on the data collection process. Clinicians completed the CRPS severity score at T1 and optionally, at T2. Ethical approval was obtained at each international centre. RESULTS: Ninety-eight adults were recruited (female n=66; mean age 46.6 years, range 19-89), of whom 32% chose to receive the T2 questionnaire in an electronic format. Fifty-five participants completed both T1 and T2. Eighteen participants and nine clinicians provided feedback on their data collection experience. CONCLUSION: This study confirmed the questionnaire core outcome data are feasible and practicable to collect in clinical practice. The electronic data management system provided a robust means of collecting and managing the data across an international population. The findings have informed the final data collection tools and processes which will comprise the first international, clinical research registry and data bank for CRPS.

Effect of Patient Age on Clinical and Radiological Outcomes After Medial Open-Wedge High Tibial Osteotomy: A Comparative Study With 344 Knees.
Koji Yabuuchi, Eiji Kondo, Takuma Kaibara, Jun Onodera, Koji Iwasaki, Masatake Matsuoka, Tomohiro Onodera, Norimasa Iwasaki, Tomonori Yagi, Kazunori Yasuda
Orthopaedic journal of sports medicine, 11, 10, 23259671231200227, 23259671231200227, 2023年10月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: There exists some controversy regarding whether patient age is a predictive factor for outcomes after high tibial osteotomy (HTO). PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate whether patient age affects clinical and radiological outcomes after medial open-wedge HTO (OWHTO) in a large population with a wider age range than previous studies. It was hypothesized that there would be no differences in outcomes when compared across age-groups. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective comparative study was conducted using 344 patients (303 knees) who underwent OWHTO from 2009 to 2018. These patients were divided into 3 groups based on age at the time of surgery: ≥55 years (group Y: 76 knees in 57 patients), 56 to 64 years (group M: 129 knees in 120 patients), and ≤65 years (group O: 139 knees in 126 patients). Clinical and radiological evaluations were performed immediately before surgery and at the final follow-up period, at a mean of 5.1 years (range, 3-11 years). Comparisons among the 3 groups were conducted with 1-way analysis of variance for continuous variables. When a significant result was obtained, a post hoc test with Bonferroni correction was conducted for multiple comparisons. RESULTS: In clinical evaluations, there were no significant differences among the 3 groups either preoperatively or postoperatively concerning the Japanese Orthopaedic Association score, the Lysholm score, or the Knee injury and Osteoarthritis Outcome Score (KOOS), with the exception of the preoperative KOOS Symptoms subscale, which was significantly higher in group Y versus group O (48.9 ± 18.7 vs 58.7 ± 15.4, respectively; P = .011). The Tegner activity score was significantly different among the groups, both preoperatively and postoperatively (P < .001 for both). There was no significant difference in the occurrence of complications or the survival rate at final follow-up among the 3 groups. CONCLUSION: The study findings suggest that patient age does not affect clinical and radiological outcomes after OWHTO.

Initial patient demographics affecting return to original work after traumatic hand injury in a rural area in Japan: A retrospective single-center study
Kazuhiro Yamamoto, Makoto Motomiya, Kota Ono, Yuichiro Matsui, Keigo Yasui, Norimasa Iwasaki
Journal of Orthopaedic Science, Elsevier BV, 2023年10月, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Time off work after traumatic hand injury not only affects individuals but also has socioeconomic repercussions, becoming a serious problem from the viewpoint of labor shortages. In depopulated rural areas, the impact of labor shortages due to time off work is more serious than in urban areas; however, few studies have examined return to original work in rural areas. The purpose of this study was to investigate the patient demographics at the time of hand injury that affect return to original work in a rural area of Japan. METHODS: We retrospectively examined 246 patients with traumatic hand and/or forearm injuries who were working at the time of injury, and who underwent surgical operations and postoperative rehabilitation in a level II hospital in a rural agricultural area. We examined patients' initial demographic data, including gender, age, occupation (white or blue collar), employment status (self-employed, full-time, or part-time workers), complications other than hand injury, workers' compensation, dominant hand injury, and injury severity as determined using the modified Hand Injury Severity Score. Multivariate logistic regression analysis examined the association between initial patient demographics and return to original work within 150 days after injury. RESULTS: In total, 186 patients (76 %) were able to return to original work within 150 days. A multivariate logistic regression analysis showed that three explanatory variables (i.e., severity of injury, complications other than hand injury, and female gender) significantly compromised return to original work. CONCLUSIONS: In the treatment of traumatic hand injury, intensive support should be provided for return to original work for patients who are expected to have difficulty returning to work quickly. In addition, labor shortages can be mitigated by sharing information with the workplace about patients' prospects of return to original work.

Median neuropathy after multiple punctures of the forearm for catheterization: A case report.
Tomoaki Suzuki, Yuichiro Matsui, Daisuke Momma, Takeshi Endo, Norimasa Iwasaki
World journal of clinical cases, 11, 25, 5941, 5946, 2023年09月06日, ［国際誌］
英語, BACKGROUND: Neuropathy may occur at some sites after catheterization for close examination of cardiac disease. Although the radial artery is considered a relatively uncom-plicated site for catheterization, the radial artery and median nerve are in relatively close proximity, with the risk of median nerve injury depending on the angle of puncture. The purpose of this study was to report the outcomes of surgery performed for conservative therapy-resistant median neuropathy following forearm catheterization. CASE SUMMARY: A 50-year-old woman experienced palsy from the right thumb to the radial side of the ring finger after catheterization from the radial artery of the right forearm. Paresthesia developed at the same site and a positive tinel-like sign was seen for the median nerve area at the high level of the puncture site. Nerve conduction study showed reduced compound muscle action potentials and loss of sensory nerve action potentials. Symptoms did not improve despite pharmacotherapy and the patient gradually developed flexion restrictions of the index and middle fingers. Median nerve injury and associated flexor tendon adhesion was diagnosed, and the patient was referred for surgery at 3 mo after injury. When the same area was opened, no injury to the median nerve epithelium was obvious, but the area of the positive tinel-like sign was highly adherent to surrounding tissue and to the flexor digitorum superficialis of the index and middle fingers. The surgery was terminated with adequate adhesion release. Rehabilitation was initiated postoperatively, improving neurological symptoms and range of motion of the fingers. Six months after surgery, the patient returned to daily activities without discomfort. CONCLUSION: This case provides the appropriate diagnosis and treatment for a suspected peripheral nerve injury.

Development of Notch-Free, Pre-Bent Rod Applicable for Posterior Corrective Surgery of Thoracolumbar/Lumbar Adolescent Idiopathic Scoliosis.
Yoko Ishikawa, Satoshi Kanai, Katsuro Ura, Terufumi Kokabu, Katsuhisa Yamada, Yuichiro Abe, Hiroyuki Tachi, Hisataka Suzuki, Takashi Ohnishi, Tsutomu Endo, Daisuke Ukeba, Masahiko Takahata, Norimasa Iwasaki, Hideki Sudo
Journal of clinical medicine, 12, 17, 2023年09月04日, ［国際誌］
英語, 研究論文（学術雑誌）, Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional spine deformity. Lenke type 5 AIS is defined as a structural thoracolumbar/lumbar curve with nonstructural thoracic curves. Although a rod curvature will affect clinical outcomes, intraoperative contouring of the straight rod depends on the surgeon's knowledge and experience. This study aimed to determine the optimum rod geometries to provide a pre-bent rod system for posterior spinal surgery in patients with Lenke type 5 AIS. These pre-bent rods will be beneficial for achieving proper postoperative outcomes without rod contouring based on surgeon experience. We investigated 20 rod geometries traced in posterior spinal reconstruction in patients with Lenke type 5 AIS. The differences between the center point clouds in each cluster were evaluated using the iterative closest point (ICP) method with modification. Before the evaluation using the ICP method, the point clouds were divided into four clusters based on the rod length using a hierarchical cluster analysis. Because the differences in the values derived from the ICP method were <5 mm for each length-based cluster, four representative rod shapes were generated from the length-based clusters. We identified four optimized rod shapes that will reduce operation time, leading to a decreased patient and surgeon burden.

The Impact of Diffuse Idiopathic Skeletal Hyperostosis on Nutritional Status, Neurological Outcome, and Perioperative Complications in Patients with Cervical Spinal Cord Injury.
Tomoaki Shimizu, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Hiroki Ushirozako, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Hiroshi Takahashi, Masashi Yamazaki
Journal of clinical medicine, 12, 17, 2023年09月01日, ［国際誌］
英語, 研究論文（学術雑誌）, This retrospective study aimed to investigate the characteristics of patients with cervical spinal cord injuries (CSCI) with diffuse idiopathic skeletal hyperostosis (DISH). We included 153 consecutive patients with CSCI who underwent posterior decompression and fusion surgery. The patients were divided into two groups based on the presence of DISH. Patient characteristics, neurological status on admission, nutritional status, perioperative laboratory variables, complications, neurological outcomes at discharge, and medical costs were compared between the groups. The DISH group (n = 24) had significantly older patients (72.1 vs. 65.9, p = 0.036), more patients with low-impact trauma (62.5% vs. 34.1%, p = 0.009), and a lower preoperative prognostic nutritional index on admission (39.8 vs. 42.5, p = 0.014) than the non-DISH group (n =129). Patients with DISH had significantly higher rates of ventilator management (16.7% vs. 3.1%, p = 0.022) and pneumonia (29.2% vs. 8.5%, p = 0.010). There was no significant difference in medical costs and neurological outcomes on discharge. Patients with CSCI and DISH were older, had poor nutritional status, and were prone to postoperative respiratory complications, while no differences were found between the neurological outcomes of patients with CSCI with and without DISH.

A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration.
Takashi Ohnishi, Kentaro Homan, Akira Fukushima, Daisuke Ukeba, Norimasa Iwasaki, Hideki Sudo
Cells, 12, 17, 2023年08月28日, ［国際誌］
英語, 研究論文（学術雑誌）, Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.

ラット坐骨神経を使用した慢性絞扼性神経障害の新規モデル開発
山本 康弘, 角家 健, 内藤 聖人, 石島 旨章, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1757, S1757, (公社)日本整形外科学会, 2023年08月
日本語

四肢原発悪性骨腫瘍症例における患肢温存術と切断術の比較 米国SEERデータベースを用いた研究
柳澤 那由他, 松岡 正剛, 小野寺 智洋, 岩崎 浩司, 鈴木 裕貴, 濱崎 雅成, 近藤 英司, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1887, S1887, (公社)日本整形外科学会, 2023年08月
日本語

診断時遠隔転移を有する四肢発生原発性悪性骨腫瘍の原発巣切除が生存に与える影響 米国SEERデータベースを用いた研究
福田 龍一, 松岡 正剛, 小野寺 智洋, 岩崎 浩司, 鈴木 裕貴, 濱崎 雅成, 近藤 英司, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1888, S1888, (公社)日本整形外科学会, 2023年08月
日本語

腰椎後方除圧術における棘上棘間靱帯・棘突起温存は,術後の二次性椎間板変性の進行を抑制する
大西 貴士, 中下 並人, 山田 勝久, 須藤 英毅, 岩崎 倫政
東日本整形災害外科学会雑誌, 35, 3, 292, 292, 東日本整形災害外科学会, 2023年08月
日本語

AI技術により作成した3D腰神経MRI像を用いたL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術シミュレーションの有用性
山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 須藤 英毅, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1698, S1698, (公社)日本整形外科学会, 2023年08月
日本語

三次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証
石川 蓉子, 小甲 晃史, 山田 勝久, 安倍 雄一郎, 舘 弘之, 鈴木 久崇, 大西 貴士, 遠藤 努, 岩崎 倫政, 須藤 英毅
日本整形外科学会雑誌, 97, 8, S1914, S1914, (公社)日本整形外科学会, 2023年08月
日本語

アテロコラーゲンを用いた自家培養軟骨移植後に軟骨下骨嚢胞を生じた1例
甲斐原 拓真, 近藤 英司, 濱崎 雅成, 鈴木 裕貴, 岩崎 浩司, 松岡 正剛, 小野寺 智洋, 種井 善一, 田中 伸哉, 岩崎 倫政
東日本整形災害外科学会雑誌, 35, 3, 361, 361, 東日本整形災害外科学会, 2023年08月
日本語

薬剤誘発性FGF23関連低リン血症性骨軟化症に伴う両側大腿骨頭軟骨下脆弱性骨折の1例
奥村 眞子, 清水 智弘, 石津 帆高, 横田 隼一, 宮崎 拓自, 高橋 大介, 岩崎 倫政
東日本整形災害外科学会雑誌, 35, 3, 254, 254, 東日本整形災害外科学会, 2023年08月
日本語

骨折リスクの高い骨粗鬆症の脊柱矢状断アライメント異常の検証
有田 皓介, 清水 智弘, 石津 帆高, 岩崎 倫政, 浅野 毅
東日本整形災害外科学会雑誌, 35, 3, 282, 282, 東日本整形災害外科学会, 2023年08月
日本語

炎症性軟骨細胞は骨細胞のパイロトーシスを誘導する
小川 裕生, 徳廣 泰貴, 江畑 拓, 北原 圭太, 塩田 惇喜, 西田 善郎, 清水 智弘, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1573, S1573, (公社)日本整形外科学会, 2023年08月
日本語

炎症収束型好中球由来細胞外小胞による軟骨細胞抗異化作用についての検討
北原 圭太, 江畑 拓, 照川 アラー, 清水 智弘, 遠藤 努, 浅野 毅, 高橋 大介, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1667, S1667, (公社)日本整形外科学会, 2023年08月
日本語

RANKL中和抗体中止後の骨吸収過剰亢進におけるメカニズム解明アプローチ
石津 帆高, 清水 智弘, 長谷川 智香, 網塚 憲生, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1739, S1739, (公社)日本整形外科学会, 2023年08月
日本語

Ferroptosisを標的としたポリエチレン摩耗粉による炎症性骨吸収抑制効果
小川 拓也, 横田 隼一, 徳廣 泰貴, 照川 アラー, 照川 ヘンド, 西田 善郎, 塩田 惇喜, 北原 圭太, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1831, S1831, (公社)日本整形外科学会, 2023年08月
日本語

閉経後骨粗鬆症モデルマウスを用いた新規骨マクロファージ由来分子タンパクの生体内治療効果
塩田 惇喜, 照川 アラー, 高橋 大介, 清水 智弘, 横田 隼一, 北原 圭太, 西田 善郎, 徳廣 泰貴, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1872, S1872, (公社)日本整形外科学会, 2023年08月
日本語

細胞老化に着目した骨マクロファージの骨代謝調節機能の検討
西田 善郎, 松前 元, 横田 隼一, 照川 ヘンド, 清水 智弘, 高橋 大介, 遠藤 努, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1873, S1873, (公社)日本整形外科学会, 2023年08月
日本語

破骨細胞分化阻害剤としての骨マクロファージ由来神経ペプチド様タンパク質の同定
徳廣 泰貴, 塩田 惇喜, 西田 善郎, 北原 圭太, 清水 智弘, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1878, S1878, (公社)日本整形外科学会, 2023年08月
日本語

Metastatic acetabular classification Type 4の寛骨臼周囲転移性骨腫瘍に対し再建術を行った1例　　　　　　　　　　　　　　　
楠 兼一, 浅野 毅, 清水 智弘, 大橋 佑介, 高橋 大介, 岩崎 倫政
Hip Joint, 49, 1, 134, 139, 日本股関節学会, 2023年08月
日本語, 71歳男。術前のCT検査で左寛骨臼の「ドーム」「内壁」「前柱」「後柱」すべてに病変(転移)を認め、Metastatic acetabular classification Type 4に分類されたが、後柱は骨接合可能であったため、Type 3相当にグレードダウンした状態で寛骨臼の再建とTHAを行うことができた。手術方法は、Kocher-Langenbeck approachで展開し、先ず骨頭の脱臼・骨切りを行い、後柱の骨折部を確認し、後柱後方と臼蓋縁をクランプで圧迫把持し整復した状態でストレートプレートを用いて後柱を固定し、不安定性は消失した。次に臼蓋上方を鋭匙で新鮮化し、臼蓋内上方の骨欠損部に同種骨頭1/6を塊状骨として充填し、KTプレートで補強を行った後にセメントカップを固定した。大腿骨側にはExeterセミロングステムを使用した。術後1週から1/2荷重を開始、2週から全荷重を開始し、術後1ヵ月で独歩可能となったが、その後、全身状態の悪化から離床時間が短くなり、術後7ヵ月で死亡した。

セメントレス人工股関節の中心性脱臼に至ったadverse reactions to metal debrisによる偽腫瘍の1例　　　　　　　　　　　　　　　
横山 慎, 清水 智弘, 高橋 大介, 浅野 毅, 石津 帆高, 宮崎 拓自, 岩崎 倫政
Hip Joint, 49, 2, 599, 603, 日本股関節学会, 2023年08月
日本語, 症例は84歳で、左股関節痛を主訴とした。30年前に両側人工股関節全置換術、10年前に右側人工股関節再置換術の既往があった。単純CTで中心性脱臼とオステオライシスによる嚢胞を認め、造影CTでは股関節腹側にリング状に造影された腫瘤性病変を認め、MRI Gd造影のT1強調画像では低～等信号であった。血液検査ではチタン濃度が1332ng/mLであった。インプラント破損による中心性脱臼、偽腫瘍、寛骨臼骨欠損と診断し、impaction grafting法による再置換術を施行した。術中所見としてメタルヘッドが筋膜直下にあり、大腿骨前方に偽腫瘍を認め、メタルヘッドはメタルカップを貫通し、メタルカップとポリエチレンライナーに大きな摩耗を認めた。偽腫瘍はメタローシスと診断され、病理組織学的所見では密なリンパ球の凝集と黒色の金属粒子を認めた。再置換術後1年経過してHarris hip scoreは手術時の16点から93点に改善し、血清チタン濃度は690ng/mLまで低下した。

人工股関節全置換術後に生じた腸恥滑液包炎による大腿動静脈圧迫を呈した1例　　　　　　　　　　　　　　　
村上 相登, 浅野 毅, 菅原 悠太郎, 高橋 大介, 清水 智弘, 岩崎 倫政
Hip Joint, 49, 2, 772, 776, 日本股関節学会, 2023年08月
日本語, 症例は84歳女性で、右変形性股関節症に対する人工股関節全置換術後2年より右下肢腫脹・疼痛が出現し、前医で腸恥滑液包炎と診断され、手術目的に当科紹介となった。術前MRIでは腸恥滑液包炎・血腫による大腿動静脈圧迫を呈し、単純X線よりカップ突出によるインピンジメントが原因と考え、カップ再置換術を施行した。術後6ヵ月の時点で腸恥滑液包は消失し、その後は症状の出現なく、良好に経過している。

Single-step ultra-purified alginate gel implantation in patients with knee chondral defects.
Tomohiro Onodera, Daisuke Momma, Masatake Matsuoka, Eiji Kondo, Koji Suzuki, Masayuki Inoue, Masaki Higano, Norimasa Iwasaki
The bone & joint journal, 105-B, 8, 880, 887, 2023年08月01日, ［国際誌］
英語, 研究論文（学術雑誌）, AIMS: Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. METHODS: A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. RESULTS: No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). CONCLUSION: This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells.

AI技術により作成した3D腰神経MRI像を用いたL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術シミュレーションの有用性
山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 須藤 英毅, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1698, S1698, (公社)日本整形外科学会, 2023年08月
日本語

骨髄由来間葉系細胞移植による再生医療を背景とした椎間板再生に有効な核酸ターゲットの探索
大西 貴士, 宝満 健太郎, 須藤 英毅, 山田 勝久, 岩崎 倫政
日本整形外科学会雑誌, 97, 8, S1858, S1858, (公社)日本整形外科学会, 2023年08月
日本語

三次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証
石川 蓉子, 小甲 晃史, 山田 勝久, 安倍 雄一郎, 舘 弘之, 鈴木 久崇, 大西 貴士, 遠藤 努, 岩崎 倫政, 須藤 英毅
日本整形外科学会雑誌, 97, 8, S1914, S1914, (公社)日本整形外科学会, 2023年08月
日本語

腰椎後方除圧術における棘上棘間靱帯・棘突起温存は,術後の二次性椎間板変性の進行を抑制する　　　　　　　　　　　　　　　
大西 貴士, 中下 並人, 山田 勝久, 須藤 英毅, 岩崎 倫政
東日本整形災害外科学会雑誌, 35, 3, 292, 292, 東日本整形災害外科学会, 2023年08月
日本語

アテロコラーゲンを用いた自家培養軟骨移植後に軟骨下骨嚢胞を生じた1例　　　　　　　　　　　　　　　
甲斐原 拓真, 近藤 英司, 濱崎 雅成, 鈴木 裕貴, 岩崎 浩司, 松岡 正剛, 小野寺 智洋, 種井 善一, 田中 伸哉, 岩崎 倫政
東日本整形災害外科学会雑誌, 35, 3, 361, 361, 東日本整形災害外科学会, 2023年08月
日本語

Incidence and Risk Factors for Pneumonia in the Chronic Phase of Cervical Spinal Cord Injury with Complete Motor Paralysis.
Chikara Ushiku, Kota Suda, Takehiro Michikawa, Satoko Matsumoto Harmon, Miki Komatsu, Osahiko Tsuji, Masahiko Takahata, Mitsuru Saito, Norimasa Iwasaki, Akio Minami
Spine surgery and related research, 7, 4, 333, 340, 2023年07月27日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Pneumonia is one of the leading causes of acute- and chronic-phase mortality in patients with cervical spinal cord injury (CSCI) with quadriplegia. The risk factors for chronic-phase pneumonia recurrence in CSCI are still unknown. This study aimed to investigate the incidence of pneumonia in the chronic phase after injury and to identify its risk factors. METHODS: This retrospective clinical observational study included patients with CSCI with American Spinal Injury Association Impairment Scale grades of A or B admitted to our center within 72 h of CSCI injury who started treatment and were available for follow-up for at least 90 days. The patients were assessed for incidences of pneumonia and its associations with clinical characteristics, including risk factors at the time of injury. Patients in whom pneumonia developed within 30 days postadmission and those after 30 days of hospitalization were comparatively examined using univariate and multivariate analyses. RESULTS: Pneumonia occurred in 36% of the 69 enrolled patients throughout the study period and in 20% of all patients after 30 days of hospitalization. Multivariate analysis of risk factors for pneumonia showed that atelectasis (adjusted OR [aOR], 95% confidence interval [CI]: 4.9, 1.2-20.0), enteral feeding (aOR [95% CI]: 13.3 [3.0-58.9]), mechanical ventilation (aOR [95% CI]: 4.0 [1.0-15.0]), and tracheotomy (aOR [95% CI]: 14.6 [2.3-94.6]) within 30 days of admission were significantly associated with the occurrence of pneumonia even after 30 days of hospitalization. CONCLUSIONS: The risk factors for developing pneumonia in the chronic phase were atelectasis, enteral feeding, mechanical ventilation, and tracheotomy within 30 days of hospitalization. This study suggests that treatment of atelectasis, long-term respiratory muscle rehabilitation, and training to improve swallowing function are essential to prevent the recurrence of pneumonia after 30 days of hospitalization.

Validation of parameters recommended for secondary screening for developmental dysplasia of the hip in Japan.
Tomohiro Shimizu, Daisuke Takahashi, Hisataka Suzuki, Hirokazu Shimizu, Takuya Ogawa, Shunichi Yokota, Hotaka Ishizu, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2023年07月12日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Based on the Japanese Pediatric Orthopaedic Association's guidelines, secondary screening and imaging including ultrasonography and radiography, are recommended in infants with limited hip abduction (<70°) or in those with multiple risk factors including the following: asymmetrical skin creases, a family history of developmental dysplasia of the hip, female sex, and pelvic position at delivery. However, there is still little information regarding the usefulness of this guideline. The objective of this study was to investigate the association between the risk factors and developmental dysplasia of the hip diagnosed using ultrasound and radiography. METHODS: A total of 356 infants (67 boys and 289 girls) underwent secondary ultrasonographic and radiological screening for developmental dysplasia of the hip in our hospital. Risk factors were documented from their medical records. The recommended item score, which we defined as an integrated value of the recommended item, was calculated for each patient. The limitation of hip abduction alone was a criterion for secondary screening; therefore, we defined the scores as follows: the limitation of hip abduction scored 2 points and other recommended scores were assigned 1 point. If the recommended item score was 2 points or more, we classified the infants as high-risk. RESULTS: A total of 280 of 356 infants were included in the high-risk group, which showed a higher ratio of cases with abnormal imaging findings than the low-risk group. According to the multivariate logistic regression analyses among the recommended items, being female, skin asymmetry, and limb limitation were identified as independent risk factors for imaging abnormality and the need for Pavlik harness treatment. CONCLUSIONS: The recommended items for secondary screening based on the Japanese Pediatric Orthopaedic Association's guidelines could be useful for screening infants in need of treatment.

High whole-body bone mineral density in ossification of the posterior longitudinal ligament.
Ryo Fujita, Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Daisuke Yoneoka, Ryota Suzuki, Masaru Tanaka, Katsuhisa Yamada, Hideki Sudo, Tomoka Hasegawa, Mohamad Alaa Terkawi, Ken Kadoya, Norimasa Iwasaki
The spine journal : official journal of the North American Spine Society, 23, 10, 1461, 1470, 2023年07月10日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND CONTEXT: Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail. PURPOSE: We investigated whether patients with OPLL develop increased whole-body BMD. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with symptomatic OPLL (OPLL [+]; n=99). Control data (OPLL [-]; n=226) without spinal ligament ossification were collected from patients who underwent spinal decompression, spinal fusion, or hip replacement surgery. OUTCOME MEASURES: Demographic data, including age, body mass index (BMI), comorbidities, history of treatment for osteoporosis, and history of vertebral and nonvertebral fractures, was obtained from all participants. In addition, whole-body BMD, including the lumbar spine, thoracic spine, femoral neck, skull, ribs, entire upper extremity, entire lower extremity, and pelvis, were measured in all participants using whole-body dual-energy X-ray absorptiometry. METHODS: Patient data were collected from 2018 to 2022. All participants were categorized based on sex, age (middle-aged [<70 years] and older adults [≥70 years]), and OPLL type (localized OPLL [OPLL only in the cervical spine], diffuse OPLL [OPLL in regions including the thoracic spine]), and OPLL [-]) and each parameter was compared. The factors associated with whole-body BMD were evaluated via multivariable linear regression analysis. RESULTS: Compared with the OPLL (-) group, the OPLL (+) group of older women had significantly higher BMD in all body parts (p<.01), and the OPLL (+) group of older men had significantly higher BMD in all body parts except the ribs, forearm, and skull (p<.01). The factors associated with increased BMD of both the femoral neck (load-bearing bone) and skull (nonload-bearing bone) were age, BMI, and coexisting diffuse OPLL in women and BMI and coexisting localized OPLL in men. CONCLUSIONS: Patients with OPLL have increased whole-body BMD regardless of sex, indicating that it is not simply due to load-bearing from obesity. These findings suggested that OPLL is associated with a systemic pathology.

Complications Associated with Preventive Management to Reduce the Risk of COVID-19 Spread After Surgery for Spinal Cord Injury.
Hiroki Ushirozako, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Tomoaki Shimizu, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Yukihiro Matsuyama
The Journal of bone and joint surgery. American volume, 105, 13, 1001, 1011, 2023年07月05日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Preventive management to reduce the risk of coronavirus disease-2019 (COVID-19) spread led to delays in active rehabilitation, which may have negatively impacted the outcomes of patients with traumatic spinal cord injury (SCI). Therefore, the aim of this study was to clarify the influence of preventive management on the rate of perioperative complications after surgical treatment for SCI. METHODS: This single-center retrospective study examined the cases of 175 patients who had SCI surgery between 2017 and 2021. We could not continue early rehabilitation interventions starting on April 30, 2020, because of our preventive management to reduce the risk of COVID-19 spread. Using a propensity score-matched model, we adjusted for age, sex, American Spinal Injury Association impairment scale score at admission, and risk factors for perioperative complications described in previous studies. Perioperative complication rates were compared between the COVID-19 pandemic and prepandemic groups. RESULTS: Of the 175 patients, 48 (the pandemic group) received preventive management. The preliminary analysis revealed significant differences between the unmatched pandemic and prepandemic groups with respect to age (75.0 versus 71.2 years, respectively; p = 0.024) and intraoperative estimated blood loss (152 versus 227 mL; p = 0.013). The pandemic group showed significant delays in visiting the rehabilitation room compared with the prepandemic group (10 versus 4 days from hospital admission; p < 0.001). There were significant differences between the pandemic and prepandemic groups with respect to the rates of pneumonia (31% versus 16%; p = 0.022), cardiopulmonary dysfunction (38% versus 18%; p = 0.007), and delirium (33% versus 13%; p = 0.003). With a propensity score-matched analysis (C-statistic = 0.90), 30 patients in the pandemic group and 60 patients in the prepandemic group were automatically selected. There were significant differences between the matched pandemic and prepandemic groups with respect to the rates of cardiopulmonary dysfunction (47% versus 23%; p = 0.024) and deep venous thrombosis (60% versus 35%; p = 0.028). CONCLUSIONS: Even with early surgical intervention, late mobilization and delays in active rehabilitation during the COVID-19 pandemic increased perioperative complications after SCI surgery. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Bone metastatic cancer of unknown primary at initial presentation.
Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Yuki Suzuki, Hamasaki Masanari, Eiji Kondo, Norimasa Iwasaki
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 26, 2, 461, 467, 2023年07月03日, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. RESULTS: Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2 months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. DISCUSSION: Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results.

【リハビリテーション診療に必要な動作解析】手・手指の機能解剖 リハビリテーションに必要な手・手指の機能解剖について
遠藤 健, 岩崎 倫政
MEDICAL REHABILITATION, 289, 125, 131, (株)全日本病院出版会, 2023年07月
日本語, 手・手指は,多様な肢位を取ることで,つまむ(pinch),握る(grip)などの動作を可能とし,種々の日常生活動作に関与する.手指の運動には,前腕部に起始を持つ外在筋と,手部に起始を持つ内在筋が複合的に作用する.また,手指の中でも,母指と他の指では大きく機能が異なり,母指に特徴的な運動が対立運動である.対立運動は母指の屈曲,外転,回内による複合的な動作である.手指と手関節は共同的に運動し,一方が伸展する際はもう一方は屈曲するのが自然な動作である.手関節は大きく橈骨手根関節と手根中央関節に分けられ,おおよそ半分ずつ手関節の運動に寄与する.本稿では,それぞれの運動の理解に必要となる機能解剖に関して述べる.また,手指の動きを網羅する運動法であるsix-pack exercise,拘縮を防ぐための安全な肢位(safe position)も紹介する.(著者抄録)

RANKL中和抗体中止後の骨吸収過剰亢進におけるメカニズム解明アプローチ　　　　　　　　　　　　　　　
石津 帆高, 清水 智弘, 長谷川 智香, 網塚 憲生, 岩崎 倫政
日本骨代謝学会学術集会プログラム抄録集, 41回, 141, 141, (一社)日本骨代謝学会, 2023年07月
日本語

【形態解剖→機能解剖→画像→疾患・治療→ケアへと結びつく!整形外科ならではの解剖】4章 手・手指 機能解剖
遠藤 健, 岩崎 倫政
整形外科看護, 2023夏季増刊, 126, 129, (株)メディカ出版, 2023年06月
日本語

腰椎後方除圧術における棘上棘間靱帯・棘突起温存は、術後の二次性椎間板変性の進行を抑制する
大西 貴士, 中下 並人, 楫野 知道, 久田 雄一郎, 山田 勝久, 須藤 英毅, 岩崎 倫政
日本関節病学会誌, 42, 3, 189, 189, (一社)日本関節病学会, 2023年06月
日本語

薬剤誘発性FGF23関連低リン血症性骨軟化症に伴う両側大腿骨頭軟骨下脆弱性骨折の1例
奥村 眞子, 清水 智弘, 石津 帆高, 横田 隼一, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 42, 3, 129, 129, (一社)日本関節病学会, 2023年06月
日本語

臼蓋骨欠損に対してKerboull-type plateとMetal meshを用いた人工股関節再置換術の術後成績の比較検討
石津 帆高, 清水 智弘, 笹沢 史生, 高橋 大介, 金山 雅弘, 岩崎 倫政
日本関節病学会誌, 42, 3, 183, 183, (一社)日本関節病学会, 2023年06月
日本語

人工股関節全置換術におけるヘッド延長の脚長、オフセット、可動域に与える影響
宮崎 拓自, 清水 智弘, 小川 拓也, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 42, 3, 187, 187, (一社)日本関節病学会, 2023年06月
日本語

大腿骨寛骨臼インピンジメントと発育性股関節形成不全の股関節応力分布に与える影響の比較
小川 裕生, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 42, 3, 187, 187, (一社)日本関節病学会, 2023年06月
日本語

SLEモデルマウスに対するステロイドパルス治療の大腿骨頭血流に与える影響の検証
横田 隼一, 清水 智弘, 高橋 大介, 岩崎 倫政, 石津 明洋
日本関節病学会誌, 42, 3, 256, 256, (一社)日本関節病学会, 2023年06月
日本語

腰椎後方除圧術における棘上棘間靱帯・棘突起温存は、術後の二次性椎間板変性の進行を抑制する　　　　　　　　　　　　　　　
大西 貴士, 中下 並人, 楫野 知道, 久田 雄一郎, 山田 勝久, 須藤 英毅, 岩崎 倫政
日本関節病学会誌, 42, 3, 189, 189, (一社)日本関節病学会, 2023年06月
日本語

コロナ禍で始まった大腿骨近位部骨折リエゾンサービス1年後の骨粗鬆症加療状況　　　　　　　　　　　　　　　
下段 俊, 清水 智弘, 梅本 貴央, 百貫 亮太, 高橋 大介, 岩崎 倫政
骨折, 45, Suppl., S283, S283, (一社)日本骨折治療学会, 2023年06月
日本語

Computer model of IL-6-dependent rheumatoid arthritis in F759 mice
Reiji Yamamoto, Satoshi Yamada, Toru Atsumi, Kaoru Murakami, Ari Hashimoto, Seiichiro Naito, Yuki Tanaka, Izuru Ohki, Yuta Shinohara, Norimasa Iwasaki, Akihiko Yoshimura, Jing-Jing Jiang, Daisuke Kamimura, Shintaro Hojyo, Shimpei I Kubota, Shigeru Hashimoto, Masaaki Murakami
International Immunology, 35, 9, 403, 421, Oxford University Press (OUP), 2023年05月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Abstract

The interleukin-6 (IL-6) amplifier, which describes the simultaneous activation of signal transducer and activator of transcription 3 (STAT3) and NF-κb nuclear factor kappa B (NF-κB), in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-κB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NF-κB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 (interleukin 17) signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-κB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and C-C motif chemokine ligand 2 (CCL2), phenotypes consistent with in vitro experiments. The binding also promoted cell growth in the synovium and the recruitment of T helper 17 (Th17) cells and macrophages in the joints. Anti-IL-6 blocking antibody treatment inhibited inflammatory responses even at the late phase, but anti-IL-17 and anti-TNFα antibodies did not. However, anti-IL-17 antibody at the early phase showed inhibitory effects, suggesting that the IL-6 amplifier is dependent on IL-6 and IL-17 stimulation at the early phase, but only on IL-6 at the late phase. These findings demonstrate the molecular mechanism of F759 arthritis can be recapitulated in silico and identify a possible therapeutic strategy for IL-6 amplifier-dependent chronic inflammatory diseases.

Dyslipidemia as a novel risk for the development of symptomatic ossification of the posterior longitudinal ligament.
Shotaro Fukada, Tsutomu Endo, Masahiko Takahata, Masahiro Kanayama, Yoshinao Koike, Ryo Fujita, Ryota Suzuki, Toshifumi Murakami, Tomoka Hasegawa, Mohamad Alaa Terkawi, Tomoyuki Hashimoto, Kastuhisa Yamada, Hideki Sudo, Ken Kadoya, Norimasa Iwasaki
The spine journal : official journal of the North American Spine Society, 23, 9, 1287, 1295, 2023年05月07日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND CONTEXT: Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear. PURPOSE: We aimed to determine the association between dyslipidemia and symptomatic OPLL. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination. OUTCOME MEASURES: Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia. METHODS: Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis. RESULTS: The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m2 and 23.0 kg/m2). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus. CONCLUSIONS: We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight.

Bilateral Humeral Retrotorsion Angle Measured Using an Ultrasound-Assisted Technique in Asian Baseball Players.
Shota Ike, Daisuke Momma, Kyosuke Numaguchi, Yuki Matsui, Masashi Yokota, Jun Oohinata, Eiji Kondo, Norimasa Iwasaki
Orthopaedic journal of sports medicine, 11, 5, 23259671231166927, 23259671231166927, 2023年05月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Repetitive pitching is thought to restrict the physiological derotation process of the humeral head. Some studies have reported that side-to-side differences in the humeral retrotorsion angle (ΔHRA) occur between the ages of 9 and 11 years in baseball players. However, it remains unclear whether the ΔHRA in Asian baseball players depends on pitching skill or competitive level. PURPOSE: To evaluate the ΔHRA in Asian collegiate and professional baseball players and to determine the effects of pitching activity on the physiological derotation process of the humeral head. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: We evaluated 128 shoulders in 64 Asian baseball players who were stratified into 4 groups as follows: 13 professional pitchers; 9 professional fielders; 8 collegiate pitchers; and 34 collegiate fielders. The throwing and nonthrowing side HRA was assessed using an ultrasound-assisted technique, and the ΔHRA was compared among the 4 groups. In addition, Pearson correlation analysis was used to assess the relationship between ΔHRA and glenohumeral range of motion, baseball starting age, and fastball velocity in pitchers. RESULTS: The HRA was significantly greater in the throwing arm than in the nonthrowing arm in each group, with no significant differences among the groups. There was no correlation between ΔHRA and range of motion or fastball velocity. There was a significant negative correlation between baseball starting age and ΔHRA in professional fielders (r = -0.633; P = .036). CONCLUSION: The findings of the present study provide evidence that in Asian baseball players, the HRA was significantly greater in the throwing arm than in the nonthrowing arm. There were no clear associations between HRA and pitching ability or competitive level.

Evaluation of Surgical Indications for Full Endoscopic Discectomy at Lumbosacral Disc Levels Using Three-Dimensional Magnetic Resonance/Computed Tomography Fusion Images Created with Artificial Intelligence.
Katsuhisa Yamada, Ken Nagahama, Yuichiro Abe, Yoshinori Hyugaji, Daisuke Ukeba, Tsutomu Endo, Takashi Ohnishi, Katsuro Ura, Hideki Sudo, Norimasa Iwasaki, Masahiko Takahata
Medicina (Kaunas, Lithuania), 59, 5, 2023年04月28日, ［国際誌］
英語, 研究論文（学術雑誌）, Background and Objectives: Although full endoscopic lumbar discectomy with the transforaminal approach (FED-TF) is a minimally invasive spinal surgery for lumbar disc herniation, the lumbosacral levels present anatomical challenges when performing FED-TF surgery due to the presence of the iliac bone. Materials and Methods: In this study, we simulated whether FED-TF surgery could be safely performed on a total of 52 consecutive cases with L5-S1 or L5-L6 disc herniation using fused three-dimensional (3D) images of the lumbar nerve root on magnetic resonance imaging (MRI) created with artificial intelligence and of the lumbosacral spine and iliac on computed tomography (CT) images. Results: Thirteen of the fifty-two cases were deemed operable according to simulated FED-TF surgery without foraminoplasty using the 3D MRI/CT fusion images. All 13 cases underwent FED-TF surgery without neurological complications, and their clinical symptoms significantly improved. Conclusions: Three-dimensional simulation may allow for the assessment from multiple angles of the endoscope entry and path, as well as the insertion angle. FED-TF surgery simulation using 3D MRI/CT fusion images could be useful in determining the indications for full endoscopic surgery for lumbosacral disc herniation.

Symptomatic bilateral complete discoid medial menisci of the knee in a child: A case report.
Yuki Suzuki, Eiji Kondo, Takuma Kaibara, Masatake Matsuoka, Ryosuke Hishimura, Koji Iwasaki, Tomohiro Onodera, Daisuke Momma, Shinya Tanaka, Norimasa Iwasaki
Joint diseases and related surgery, 34, 2, 455, 462, 2023年04月26日, ［国際誌］
英語, 研究論文（学術雑誌）, Bilateral complete discoid medial menisci are extremely rare congenital anatomic variants of the knee. Currently, arthroscopic partial meniscectomy with or without peripheral suture repair is performed for symptomatic discoid meniscus. However, most of the outcomes are short-term. In this article, we present a pediatric case of symptomatic bilateral complete discoid medial menisci and highlight the effectiveness of arthroscopic partial meniscectomy with or without peripheral suture on symptomatic complete discoid medial menisci based on 60-month excellent clinical and functional results.

Anatomical and Simulation Studies Based on Three-Dimensional-Computed Tomography Image Reconstruction of Femoral Offset.
Tomohiro Shimizu, Daisuke Takahashi, Hotaka Ishizu, Shunichi Yokota, Yoshihiro Hasebe, Keita Uetsuki, Norimasa Iwasaki
Diagnostics (Basel, Switzerland), 13, 8, 2023年04月16日, ［国際誌］
英語, 研究論文（学術雑誌）, Although the hip joint morphology varies by race, few studies have investigated the associations between two-dimensional (2D) and three-dimensional (3D) morphologies. This study aimed to use computed tomography simulation data and radiographic (2D) data to clarify the 3D length of offset, 3D changes in the hip center of rotation, and femoral offset as well as investigate the anatomical parameters associated with the 3D length and changes. Sixty-six Japanese patients with a normal femoral head shape on the contralateral side were selected. In addition to radiographic femoral, acetabular, and global offsets, 3D femoral and cup offsets were investigated using commercial software. Our findings revealed that the mean 3D femoral and cup offsets were 40.0 mm and 45.5 mm, respectively; both were distributed around the mean values. The difference between the 3D femoral and cup offsets (i.e., 5 mm) was associated with the 2D acetabular offset. The 3D femoral offset was associated with the body length. In conclusion, these findings can be applied to the design of better ethnic-specific stem designs and can help physicians achieve more accurate preoperative diagnoses.

Secondary fracture rates and risk factors 1 year after a proximal femoral fracture under FLS.
Hotaka Ishizu, Tomohiro Shimizu, Shu Yamazaki, Yusuke Ohashi, Komei Sato, Shun Shimodan, Norimasa Iwasaki
Journal of bone and mineral metabolism, 41, 4, 1, 8, 2023年04月10日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: We aimed to investigate the secondary fracture rates and risk factors in patients with proximal femoral fractures using fracture liaison service (FLS) during the coronavirus disease (COVID)-19 pandemic. MATERIALS AND METHODS: In this multi-center prospective cohort study, patients with proximal femoral fractures who were treated surgically at three hospitals from April 2020 to March 2021 were included. Follow-up examinations at 6 and 12 months postoperatively were conducted to investigate the clinical data and ascertain whether osteoporosis treatment could be continued. RESULTS: A total of 316 patients with proximal femoral fractures were registered. During the follow-up period, 17 patients died and 67 patients could not visit the hospitals owing to the COVID-19 pandemic. In total, 172 patients who could be followed-up 12 months postoperatively were examined using dual-energy X-ray absorptiometry during hospitalization; underwent postoperative osteoporosis treatment, mainly with bisphosphonates (89.5%); and were administered medications continuously. Secondary fractures occurred within 1 year in 14 patients (8.1%). Multivariate analysis showed that patients who used sleeping pills and had a lower functional independence measure had an increased risk for developing secondary fractures. CONCLUSION: During the COVID-19 pandemic, secondary fractures can be prevented if the patients can be followed and osteoporosis treatment can be continued. Conversely, despite adequate osteoporosis drug examination and treatment, a certain number of secondary fractures still occurred. The finding that postoperative osteoporosis therapy using routine medications and rehabilitation is associated with secondary fractures may support the importance of establishing clinical standards consisting of a multidisciplinary collaboration for FLS.

Comparison of the Efficacy of Zoledronate Acid or Denosumab After Switching from Romosozumab in Japanese Postmenopausal Patients.
Tetsuro Oue, Tomohiro Shimizu, Tsuyoshi Asano, Shun Shimodan, Hotaka Ishizu, Kosuke Arita, Norimasa Iwasaki
Calcified tissue international, 112, 6, 683, 690, 2023年04月10日, ［国際誌］
英語, 研究論文（学術雑誌）, We aimed to compare the efficacy of switching from romosozumab (RMAb) to denosumab (DMAb) or zoledronic acid (Zol) with respect to changes in bone mineral density (BMD) and bone metabolism. We also aimed to determine predictors of changes in BMD among patients who received sequential therapy from RMAb. One hundred patients who received RMAb therapy were recruited for this study. A total 49 patients received bisphosphonate (BP) pre-treatment and 51 received active vitamin D3 analog pre-treatment or no treatment. Forty-two patients were switched to Zol (BP-RMAb-Zol; 20 and RMAb-Zol; 22), and 58 patients were switched to DMAb (BP-RMAb-DMAb; 29 and RMAb-DMAb; 29). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were also evaluated. In the BP-RMAb-Zol group, TRACP-5b increased after administration of Zol, and the mean BMD of the lumbar spine (LS) was significantly lower than those in the BP-RMAb-DMAb, RMAb-Zol and RMAb-DMAb groups at 24 months. The % changes in BMD of the LS after 24 months were associated with TRACP-5b values at baseline and at 12 months in patients who received Zol therapy, and with TRACP-5b value at baseline in patients who received DMAb therapy. The DMAb follow-on regimen could be considered more effective than Zol as a sequential agent for the enhancement of BMD after RMAb in patients with BP pretreatment. TRACP-5b, especially the baseline value, may predict the efficacy of sequential therapy from RMAb, as well as previous treatments.

ボタンホール変形に対するOhshio法の治療経験　　　　　　　　　　　　　　　
遠藤 健, 河村 太介, 松井 雄一郎, 門間 太輔, 松居 祐樹, 小林 英之, 鈴木 智亮, 岩崎 倫政
日本手外科学会雑誌, 40, 1, OD40, 1, (一社)日本手外科学会, 2023年04月
日本語

全人工手関節手根骨ステムの至適なエントリーポイントの同定　　　　　　　　　　　　　　　
遠藤 健, 河村 太介, 松井 雄一郎, 門間 太輔, 芝山 浩樹, 松居 祐樹, 岩崎 倫政
日本手外科学会雑誌, 39, 6, 1037, 1037, (一社)日本手外科学会, 2023年04月
日本語

3次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証
石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 安倍 雄一郎, 岩崎 倫政, 須藤 英毅
Journal of Spine Research, 14, 3, 136, 136, (一社)日本脊椎脊髄病学会, 2023年04月
日本語

AIにて自動作成した3D腰椎神経根画像を用いた全内視鏡下経椎間孔アプローチ手術における安全域の形態解析 進入角度・腰椎高位別解析
山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 須藤 英毅, 岩崎 倫政
Journal of Spine Research, 14, 3, 205, 205, (一社)日本脊椎脊髄病学会, 2023年04月
日本語

AI技術を用いて作成した3次元腰神経画像によるL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術(FED)の手術適応可否の評価
山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 須藤 英毅, 岩崎 倫政
Journal of Spine Research, 14, 3, 308, 308, (一社)日本脊椎脊髄病学会, 2023年04月
日本語

Lenke 5特発性側彎症における最下位固定椎の側方変位がL4傾斜と冠状面バランスに与える影響 術式別解析
山田 勝久, 須藤 英毅, 安倍 雄一郎, 小甲 晃史, 舘 弘之, 遠藤 努, 大西 貴士, 高畑 雅彦, 岩崎 倫政
Journal of Spine Research, 14, 3, 401, 401, (一社)日本脊椎脊髄病学会, 2023年04月
日本語

腰椎後方除圧術における棘上棘間靱帯・棘突起温存は,術後の二次性椎間板変性の進行を抑制する
大西 貴士, 中下 並人, 楫野 知道, 久田 雄一郎, 山田 勝久, 須藤 英毅, 岩崎 倫政
Journal of Spine Research, 14, 3, 442, 442, (一社)日本脊椎脊髄病学会, 2023年04月
日本語

Peripheral nerve-derived fibroblasts promote neurite outgrowth in adult dorsal root ganglion neurons more effectively than skin-derived fibroblasts.
Masato Hara, Ken Kadoya, Takeshi Endo, Norimasa Iwasaki
Experimental physiology, 108, 4, 621, 635, 2023年04月, ［国際誌］
英語, 研究論文（学術雑誌）, NEW FINDINGS: What is the central question of this study? Although fibroblasts are involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. What is the main finding and its importance? Nerve-derived fibroblasts have a greater neurite-promoting effect than skin-derived fibroblasts, and epineurium-derived fibroblasts can promote neurite outgrowth more effectively than parenchyma-derived fibroblasts. The epineurium-derived fibroblasts and parenchyma-derived fibroblasts have distinctly different molecular profiles, including genes of soluble factors to promote axonal growth. Fibroblasts are molecularly and functionally different depending on their localization in nerve tissue, and epineurium-derived fibroblasts might be involved in axon regeneration after peripheral nerve injury more than previously thought. ABSTRACT: Although fibroblasts (Fb) are components of a peripheral nerve involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. The objective of the present study was to investigate the capacity of Fb derived from peripheral nerves to stimulate the outgrowth of neurites from adult dorsal root ganglion neurons and to clarify their molecular characteristics. Fibroblasts were prepared from the epineurium and parenchyma of rat sciatic nerves and skin. The Fb derived from epineurium showed the greatest effect on neurite outgrowth, followed by the Fb derived from parenchyma, indicating that Fb derived from nerves promote neurite outgrowth more effectively than skin-derived Fb. Although both soluble and cell-surface factors contributed evenly to the neurite-promoting effect of nerve-derived Fb, in crush and transection injury models, Fb were not closely associated with regenerating axons, indicating that only soluble factors from Fb are available to regenerating axons. A transcriptome analysis revealed that the molecular profiles of these Fb were distinctly different and that the gene expression profiles of soluble factors that promote axonal growth are unique to each Fb. These findings indicate that Fb are molecularly and functionally different depending on their localization in nerve tissue and that Fb derived from epineurium might be involved more than was previously thought in axon regeneration after peripheral nerve injury.

Effects of Preserving Anatomically Positioned and Adequate Remnant ACL Tissue in Double-Bundle ACL Reconstruction.
Dai Sato, Masayuki Inoue, Yasuhiko Kasahara, Hiroki Hamano, Ryota Suzuki, Eiji Kondo, Norimasa Iwasaki
Orthopaedic journal of sports medicine, 11, 4, 23259671231162389, 23259671231162389, 2023年04月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The advantages of remnant tissue preservation in anterior cruciate ligament (ACL) reconstruction (ACLR) remain controversial. HYPOTHESIS: It was hypothesized that a large amount of remnant tissue, especially if anatomically positioned, would improve patient-reported outcomes and second-look graft appearance after preserved double-bundle ACLR (DB-ACLR). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective study included 89 consecutive patients who underwent unilateral remnant-preserving DB-ACLR using 2 hamstring tendon autografts. The authors categorized the arthroscopic findings into 3 groups according to the location and volume of the ACL remnant tissue in the femoral notch: (1) anatomical attachment (group AA; n = 34); (2) nonanatomical attachment (group NA; n = 33); and (3) no remnant (group NR; n = 22). Based on second-look arthroscopy, the reconstructed graft was graded as excellent, fair, or poor. Patient-reported outcomes were evaluated at 2 years after surgery using the Knee injury and Osteoarthritis Outcome Score (KOOS) and the Japanese Anterior Cruciate Ligament Questionnaire-25 (JACL-25). RESULTS: The AA and NA groups had a significantly shorter time from injury to surgery compared with the NR group (P = .0165). Considering the second-look arthroscopic findings, the authors found a significant difference in synovial coverage of the grafts between the 3 groups (P = .0018). There were no significant differences in the overall KOOS and JACL-25 score among the 3 groups; however, the KOOS-Sport and Recreation and KOOS-Quality of Life subscale scores were significantly higher in the AA group compared with the NA and NR groups (P = .0014 and .0039, respectively). The JACL-25 score for middle- to high-speed flexion and extension was significantly better in the AA group versus the NR group (P = .0261). CONCLUSION: This study showed that preserving anatomically positioned and adequate remnant tissue during DB-ACLR improved second-look graft appearance and KOOS-Sport and Recreation and KOOS-Quality of Life scores.

Simultaneous and sialic acid linkage-specific N- and O-linked glycan analysis by ester-to-amide derivatization.
Hisatoshi Hanamatsu, Yoshiaki Miura, Takashi Nishikaze, Ikuko Yokota, Kentaro Homan, Tomohiro Onodera, Yoshihiro Hayakawa, Norimasa Iwasaki, Jun-Ichi Furukawa
Glycoconjugate journal, 40, 2, 259, 267, 2023年04月, ［国際誌］
英語, 研究論文（学術雑誌）, Characterization of O-glycans linked to serine or threonine residues in glycoproteins has mostly been achieved using chemical reaction approaches because there are no known O-glycan-specific endoglycosidases. Most O-glycans are modified with sialic acid residues at the non-reducing termini through various linkages. In this study, we developed a novel approach for sialic acid linkage-specific O-linked glycan analysis through lactone-driven ester-to-amide derivatization combined with non-reductive β-elimination in the presence of hydroxylamine. O-glycans released by non-reductive β-elimination were efficiently purified using glycoblotting via chemoselective ligation between carbohydrates and a hydrazide-functionalized polymer, followed by modification of methyl or ethyl ester groups of sialic acid residues on solid-phase. In-solution lactone-driven ester-to-amide derivatization of ethyl-esterified O-glycans was performed, and the resulting sialylated glycan isomers were discriminated by mass spectrometry. In combination with PNGase F digestion, we carried out simultaneous, quantitative, and sialic acid linkage-specific N- and O-linked glycan analyses of a model glycoprotein and human cartilage tissue. This novel glycomic approach will facilitate detailed characterization of biologically relevant sialylated N- and O-glycans on glycoproteins.

Clinical outcomes of short-segment lumbar fusion in patients older than 85 years with a minimum 2-year follow-up.
Takeru Tsujimoto, Ryo Itoga, Masahiro Kanayama, Fumihiro Oha, Yukitoshi Shimamura, Masaru Tanaka, Yuichi Hasegawa, Syotaro Fukada, Tomoyuki Hashimoto, Masahiko Takahata, Norimasa Iwasaki
Journal of neurosurgery. Spine, 39, 1, 1, 7, 2023年03月24日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Although the number of elderly patients requiring lumbar fusion for lumbar degenerative disorders has increased over time, the postoperative outcomes of lumbar fusion in very elderly patients (> 85 years) remains unknown. This study aimed to evaluate the comprehensive outcomes of lumbar fusion in elderly patients older than 85 years with mid-term follow-up. METHODS: The authors retrospectively researched patients older than 85 years who underwent single- or double-level posterior lumbar interbody fusion or transforaminal lumbar interbody fusion from 2012 to 2019. Twenty-nine patients who had at least 2 years of follow-up were included in this study. The average age was 86.4 years, and the average follow-up period was 42.2 months. Each patient was matched with 60- to 75-year-old controls. The Oswestry Disability Index (ODI) score; Roland-Morris Disability Questionnaire (RMDQ) score; Japanese Orthopaedic Association (JOA) score; JOA recovery rate; and low-back pain (LBP), leg pain, and leg numbness visual analog scale (VAS) scores were obtained. The spinopelvic parameters were measured using lateral standing radiographs of the whole spine. RESULTS: Although there were no significant differences in the ODI, RMDQ, JOA recovery rate, and leg pain and leg numbness VAS scores at 2 years postoperatively between the very elderly and control groups, the VAS LBP score was significantly lower in the very elderly group than in the control group. Preoperative and postoperative sagittal vertical axes were significantly higher and sacral slopes were significantly lower in the very elderly group than in the control group. The incidences of postoperative delirium and new lumbar vertebral fracture were significantly higher in the very elderly group (17.2%) than in the control group (4.6%). CONCLUSIONS: This study showed that lumbar fusion could be performed in patients older than 85 years with satisfactory postoperative outcomes at the 2-year follow-up. In contrast, progressive spinopelvic sagittal imbalance, the incidence of lumbar vertebral fracture up to the final follow-up, and postoperative delirium were greater in the very elderly group than in the control group.

Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report.
Hiroshi Ikeda, Shigeru Yamaguchi, Yukitomo Ishi, Kento Wakabayashi, Ai Shimizu, Hiromi Kanno-Okada, Takeshi Endo, Mitsutoshi Ota, Michinari Okamoto, Hiroaki Motegi, Norimasa Iwasaki, Miki Fujimura
Neuropathology : official journal of the Japanese Society of Neuropathology, 43, 5, 413, 420, 2023年03月20日, ［国際誌］
英語, Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.

Macrophage‐derived extracellular vesicles trigger non‐canonical pyroptosis in chondrocytes leading to cartilage catabolism in osteoarthritis
Taku Ebata, Mohamad Alaa Terkawi, Keita Kitahara, Syunichi Yokota, Junki Shiota, Yoshio Nishida, Gen Matsumae, Hend Alhasan, Masanari Hamasaki, Kazutoshi Hontani, Tomohiro Shimizu, Daisuke Takahashi, Tsutomu Endo, Tomohiro Onodera, Ken Kadoya, Norimasa Iwasaki
Arthritis & Rheumatology, 75, 8, 1358, 1369, 2023年03月16日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The severity of osteoarthritis and cartilage degeneration are highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. Here, we explored the pathological role of inflammatory macrophage extracellular vesicles in cartilage degeneration. METHODS: Macrophages were stimulated by treatment with bacterial lipopolysaccharides to mimic the state of inflammatory macrophages and the resulting extracellular vesicles were harvested for chondrocyte stimulation in vitro and intraarticular injection in a mouse model. The stimulated chondrocytes were further subjected to RNA-seq analysis and other functional assays. The action of caspase-11 was disrupted in vitro using a specific siRNA or wedelolactone, and in experimental OA-murine models by the intraarticular injection of wedelolactone. RESULTS: Stimulated chondrocytes exhibited a significant elevation in the expression of chondrocyte catabolic factors. Consistent with these results, RNA-seq analyses of stimulated chondrocytes indicated that upregulated genes are mainly categorized into apoptotic process and TNF-signaling pathway which suggests the induction of apoptotic process. Moreover, these chondrocytes exhibited a significant elevation in the expression of pyroptosis-related molecules that were correlated with the expression of chondrocyte catabolic factors. The disruption of caspase-11 significantly alleviated pyroptotic and catabolic processes in stimulated chondrocytes and the pathological changes in collagenase-and joint instability-induced OA models. CONCLUSIONS: Our results provide a new insight into the pathological mechanisms of OA and suggest that non-canonical pyroptosis in chondrocytes represents an attractive therapeutic target for future treatment.

Amputation surgery associated with shortened survival in patients with localized soft tissue sarcoma.
Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Masanari Hamasaki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 29, 2, 637, 645, 2023年03月15日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The objectives of this study were to clarify whether localized extremity soft tissue sarcoma (STS) patients who underwent amputation surgery experienced worsened survival and to identify those patients for whom amputation surgery worsened survival. METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified 8897 patients with localized extremity STS between 1983 and 2016. Of these 6431 patients, 733 patients underwent amputation surgery (Amputation group), and 5698 underwent limb-sparing surgery (Limb-sparing group). RESULTS: After adjusting for patient background by propensity score matching, a total of 1346 patients were included. Patients in the Amputation group showed worsened survival (cancer-specific survival (CSS): hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.15-1.75, overall survival (OS): HR = 1.41, 95%CI 1.20-1.65). In subclass analysis, patients with high-grade STS, spindle cell sarcoma and liposarcoma in the Amputation group showed shortened survival (high-grade-CSS: HR = 1.44, 95%CI 1.16-1.77, OS: HR = 1.38, 95%CI 1.18-1.62; spindle cell sarcoma-CSS: HR = 4.75, 95%CI 1.56-14.4, OS: HR = 2.32, 95%CI 1.45-3.70; liposarcoma-CSS: HR = 2.91, 95%CI 1.54-5.50, OS: HR = 2.32, 95%CI 1.45-3.70). CONCLUSIONS: Survival was shortened in localized extremity STS patients who received amputation surgery.

アネキシンA1(AnxA1)の炎症性骨吸収抑制効果の検討 人工関節術後無菌性緩みの治療薬開発にむけて
西田 善郎, 照川 ヘンド, 江畑 拓, 清水 智弘, 横田 隼一, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 97, 3, S953, S953, (公社)日本整形外科学会, 2023年03月
日本語

人工関節置換術後無菌性緩みの局所骨溶解におけるチミジンホスホリラーゼの機能解析
松前 元, 清水 智弘, 田 園, 高橋 大介, 江畑 拓, 照川 ヘンド, 横田 隼一, 角家 健, 照川 アラー, 岩崎 倫政
北海道整形災害外科学会雑誌, 64, 2, 59, 72, 北海道整形災害外科学会, 2023年03月
日本語, マクロファージは,炎症と病的骨吸収を惹起することで人工関節後の無菌性緩みに関与する.本研究の目的は,無菌性緩み発症におけるマクロファージ由来因子の同定とその機能解析である.まず,ポリエチレン摩耗粉とマクロファージを共培養し,RNAシークエンス解析を行った.この結果,破骨細胞分化に関与する12個の因子を同定した.この中で,チミジンホスホリラーゼ(TYMP)が最も破骨細胞を誘導した.無菌性緩み症例の血清と滑膜からTYMPが同定できた.動物実験では,TYMPは炎症細胞,破骨細胞の誘導に加え,骨吸収域を増加させた.TYMPの破骨細胞誘導機序を検証するためRNAシークエンス解析を行ったところ,Srcチロシンキナーゼの一種であるFYNが有意に上昇した.そこでFYNの抑制剤であるサラカチニブをモデルマウスに投与したところ,摩耗粉による骨吸収域が有意に低下した.以上の結果から,TYMPは人工関節無菌性緩みにおける有用な治療ターゲットとなり得ることが示唆された.(著者抄録)

末梢神経再生治療の最前線-基礎から臨床へ- シュワン細胞の軸索再生メカニズムから考える末梢神経再生治療戦略
遠藤 健, 角家 健, 鈴木 智亮, 鈴木 裕貴, 照川 アラー, 河村 太介, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S154, S154, (公社)日本整形外科学会, 2023年03月
日本語

大腿骨顆間外側壁における骨密度分布 前十字靱帯の大腿骨付着部に関する考察
菅原 悠太郎, 岩崎 浩司, 遠藤 香織, 菱村 亮介, 松原 新史, 松岡 正剛, 門間 太輔, 小野寺 智洋, 近藤 英司, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S193, S193, (公社)日本整形外科学会, 2023年03月
日本語

慢性絞扼性神経障害の新規動物モデル開発と病態解明
山本 康弘, 角家 健, 内藤 聖人, 石島 旨章, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S316, S316, (公社)日本整形外科学会, 2023年03月
日本語

遠隔転移を有する軟部肉腫症例において原発巣切除は生存を延長する SEERデータベースを用いた研究
松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 松原 新史, 菱村 亮介, 近藤 英司, 岩崎 倫政
北海道整形災害外科学会雑誌, 64, 2, 49, 58, 北海道整形災害外科学会, 2023年03月
日本語, 【目的】本研究の目的は,遠隔転移を有する四肢発生軟部肉腫(Soft tissue sarcoma:STS)症例について,原発巣切除が生存を延長するか否かを明らかにし,さらに原発巣切除を考慮すべき患者群を明らかにすることである.【方法】SEERデータベースを用いて,1983年から2016年の間に初診時に遠隔転移を有する四肢発生STS1453例を抽出した.そのうち原発巣切除を施行された患者は898名,されなかった症例は555名であった.傾向スコアマッチングにより患者背景を調整後,804名を解析対象とし切除群では生存が延長した(Cancer specific survival(CSS):Hazard ratio[HR]=0.59,95% confidence interval[CI]0.50-0.71;Overall survival[OS]:HR=0.60,95% CI 0.60-0.71).サブクラス解析では,病理学的高悪性度腫瘍や未分化多形肉腫,平滑筋肉腫,滑膜肉腫症例において,原発巣切除は生存を改善した(高悪性度;CSS:HR=0.57,95% CI 0.45-0.72,OS:HR=0.58,95% CI 0.48-0.71,未分化多形肉腫;CSS:HR=0.60,95% CI 0.42-0.84,OS:HR=0.61,95% CI 0.46-0.82,平滑筋肉腫;CSS:HR=0.50,95% CI 0.33-0.75,OS HR=0.50,95% CI 0.35-0.72,滑膜肉腫;CSS:HR=0.46,95% CI 0.31-0.68,OS:HR=0.43,95% CI 0.30-0.62).【結語】本研究は,遠隔転移を有する四肢発生STS症例において原発巣切除術が生存を延長することを示した.今後,本研究結果を追試するための前向き臨床試験が必要である.(著者抄録)

三次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証
石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 安倍 雄一郎, 岩崎 倫政, 須藤 英毅
日本整形外科学会雑誌, 97, 3, S905, S905, (公社)日本整形外科学会, 2023年03月
日本語

ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子
菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 42, 1, 30, 33, (一社)日本関節病学会, 2023年03月
日本語, 目的:特発性大腿骨頭壊死症患者(ONFH)が股関節以外に骨壊死を引き起こす多発骨壊死は,3関節以上と定義した際には約3%とこれまで報告されてきた。一方で,無症候性壊死を検出感度の高い全身MRIを用いた先行研究では,ONFH患者の約25%に多発骨壊死が発生し全例ステロイド関連ONFHであった。そこで本研究は,ステロイド関連ONFH症例を対象として,多発骨壊死の関連性を調査することを目的とした。方法:対象は当院における定点モニタリング対象となったONFH症例328名のうち,特発性ONFH 9名,アルコール関連ONFH 75名およびデータ詳細不明の16名を除外したステロイド関連ONFH 228名(男性108名,女性120名)である。基礎疾患,ステロイド投与最大量,ステロイドパルス療法,アルコール,喫煙,股関節以外の関節の骨壊死発生を調査した。結果:多発骨壊死は228名中59名(男性24名,女性35名)に生じていた。多発骨壊死症を生じたONFH症例は,若年,両側ONFH症例,ステロイド高用量,ステロイドパルス症例,喫煙,全身性エリテマトーデス症例の傾向があった。多変量解析を行ったところ,ステロイドパルス(オッズ比3.0倍,P=0.008)が多発骨壊死の独立した関連因子であった。考察・結論:ONFH発生に関してステロイド投与量やステロイドパルスが関連することと同様に,多発骨壊死とステロイドパルスは関連したことから多発骨壊死発生もステロイド感受性が関連することが示唆された。多発性骨壊死発生のメカニズムはわかっていないが,ステロイド関連ONFHが発生した際には,多発骨壊死のスクリーニングを行うことを考慮する必要があると考えられた。(著者抄録)

抗RANKL抗体とゾレドロン酸がマウス化膿性骨髄炎モデルに与える効果の違い
小林 英之, 藤田 諒, 平塚 重人, 清水 智弘, 佐藤 大, 濱野 博基, 岩崎 倫政, 高畑 雅彦
北海道整形災害外科学会雑誌, 64, 2, 39, 48, 北海道整形災害外科学会, 2023年03月
日本語, 骨髄炎は強い疼痛と機能障害を伴う進行性の炎症性骨破壊を特徴とする.骨粗鬆症治療薬であるZoledronic acid(ZA)と抗Receptor activator of nuclear factor-kB ligand(RANKL)抗体は強力な破骨細胞抑制効果により,炎症性骨破壊の抑制が期待できるが,骨髄炎に対する効果と安全性は確立されていない.本研究では,遺伝子組み換え発光黄色ブドウ球菌をマウス大腿骨に植菌した骨髄炎モデルマウスを作成し,ZAと抗RANKL抗体を投与した.縦断的に感染の指標となる黄色ブドウ球菌の発光量とマイクロCTによる骨破壊を観察した結果,ZA投与群では感染の自然治癒が遅延していた.一方骨破壊はZAと抗RANKL抗体は有意に骨破壊を抑制した.組織学的評価では,ZA投与で破骨細胞数が著明に減少し,骨壊死範囲が有意に大きくなっているのに対し,抗RANKL抗体投与では壊死骨周囲でRANKL非依存的に誘導されたと考えられる破骨細胞が多く見られ,壊死骨増加を来さなかった.抗RANKL抗体は感染巣となる壊死骨の除去を妨げず,骨保護効果を発揮することが期待できると考えられた.(著者抄録)

人工関節置換術後無菌性緩みの局所骨溶解におけるチミジンホスホリラーゼの機能解析
松前 元, 清水 智弘, 田 園, 高橋 大介, 江畑 拓, 照川 ヘンド, 横田 隼一, 角家 健, 照川 アラー, 岩崎 倫政
北海道整形災害外科学会雑誌, 64, 2, 59, 72, 北海道整形災害外科学会, 2023年03月
日本語, マクロファージは,炎症と病的骨吸収を惹起することで人工関節後の無菌性緩みに関与する.本研究の目的は,無菌性緩み発症におけるマクロファージ由来因子の同定とその機能解析である.まず,ポリエチレン摩耗粉とマクロファージを共培養し,RNAシークエンス解析を行った.この結果,破骨細胞分化に関与する12個の因子を同定した.この中で,チミジンホスホリラーゼ(TYMP)が最も破骨細胞を誘導した.無菌性緩み症例の血清と滑膜からTYMPが同定できた.動物実験では,TYMPは炎症細胞,破骨細胞の誘導に加え,骨吸収域を増加させた.TYMPの破骨細胞誘導機序を検証するためRNAシークエンス解析を行ったところ,Srcチロシンキナーゼの一種であるFYNが有意に上昇した.そこでFYNの抑制剤であるサラカチニブをモデルマウスに投与したところ,摩耗粉による骨吸収域が有意に低下した.以上の結果から,TYMPは人工関節無菌性緩みにおける有用な治療ターゲットとなり得ることが示唆された.(著者抄録)

北海道における女性整形外科医の働き方 女性整形外科医の経験と北海道大学における女性整形外科医師の働き方
後藤 佳子, 大泉 尚美, 清水 智弘, 門間 太輔, 近藤 英司, 岩崎 倫政
北海道整形災害外科学会雑誌, 64, 2, 74, 81, 北海道整形災害外科学会, 2023年03月
日本語

RA,RA周辺疾患の骨代謝動態および微細構造とインプラント手術 ステロイド長期使用患者における脊椎固定術のインプラントフェイラーとその対策
高畑 雅彦, 山田 勝久, 遠藤 努, 大西 貴士, 筌場 大介, 須藤 英毅, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S140, S140, (公社)日本整形外科学会, 2023年03月
日本語

成育基本法の拡充に則した側彎症検診のあり方 3Dスキャナーと人工知能による側彎症検診 検診の確実な実施に向けた課題への取り組み
須藤 英毅, 石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 安倍 雄一郎, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S349, S349, (公社)日本整形外科学会, 2023年03月
日本語

AI技術を用いて作成した三次元腰神経画像によるL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術(FED)の手術適応可否の評価
山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 須藤 英毅, 高畑 雅彦, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S427, S427, (公社)日本整形外科学会, 2023年03月
日本語

SLEモデルマウスへのステロイドパルスは好中球細胞外トラップを誘導する　　　　　　　　　　　　　　　
小川 帆貴, 横田 隼一, 清水 智弘, 西端 友香, 益田 紗季子, 外丸 詩野, 岩崎 倫政, 石津 明洋
日本リウマチ学会総会・学術集会プログラム・抄録集, 67回, 886, 886, (一社)日本リウマチ学会, 2023年03月
日本語

リーメンビューゲル治療前に水平牽引を行うことで脱臼整復率は改善する　　　　　　　　　　　　　　　
小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S52, S52, (公社)日本整形外科学会, 2023年03月
日本語

Angulated innominate osteotomyにおける術中三次元矯正と術後1年単純X線との関連　　　　　　　　　　　　　　　
小川 拓也, 高橋 大介, 清水 智弘, 宮崎 拓自, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S52, S52, (公社)日本整形外科学会, 2023年03月
日本語

大腿骨近位部骨折後のリエゾンサービスにおける二次骨折発生とリスク因子 COVID-19状況下の前向き研究
佐藤 恒明, 清水 智弘, 石津 帆高, 山崎 秀, 大橋 佑介, 下段 俊, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S126, S126, (公社)日本整形外科学会, 2023年03月
日本語

ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子
菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S158, S158, (公社)日本整形外科学会, 2023年03月
日本語

ロモソズマブの逐次療法におけるゾレドロン酸とデノスマブの比較
大上 哲郎, 清水 智弘, 浅野 毅, 下段 俊, 石津 帆高, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S202, S202, (公社)日本整形外科学会, 2023年03月
日本語

発育性股関節形成不全の二次検診受診時期による装具治療の有無の検討
小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S224, S224, (公社)日本整形外科学会, 2023年03月
日本語

コロナ禍で始まった大腿骨近位部骨折リエゾンサービス1年後の骨粗鬆症加療状況
下段 俊, 清水 智弘, 梅本 貴央, 百貫 亮太, 竹内 博紀, 小川 裕生, 池 翔太, 福島 瑛, 佐藤 知哉, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S238, S238, (公社)日本整形外科学会, 2023年03月
日本語

人工股関節全置換術後1年における筋量および筋力の変化 筋量DXAを用いた筋量測定
七條 俊希, 千田 伸一, 樋口 陽子, 相馬 栄大, 武田 恵李, 大井 雅人, 高橋 要, 大羽 文博, 田中 将, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 97, 2, S406, S406, (公社)日本整形外科学会, 2023年03月
日本語

日本人におけるTHAの適切なオフセットの検証
高橋 大介, 清水 智弘, 宮崎 拓自, 小川 拓也, 岩崎 倫政
日本整形外科学会雑誌, 97, 3, S735, S735, (公社)日本整形外科学会, 2023年03月
日本語

人工股関節全置換術におけるヘッド延長の脚長,オフセット,可動域に与える影響 A computer simulation study
宮崎 拓自, 清水 智弘, 小川 拓也, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 97, 3, S735, S735, (公社)日本整形外科学会, 2023年03月
日本語

アネキシンA1(AnxA1)の炎症性骨吸収抑制効果の検討 人工関節術後無菌性緩みの治療薬開発にむけて
西田 善郎, 照川 ヘンド, 江畑 拓, 清水 智弘, 横田 隼一, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 97, 3, S953, S953, (公社)日本整形外科学会, 2023年03月
日本語

Covid-19流行下における大腿骨近位部骨折治療 full-PPE装備での手術治療の特徴
浅野 毅, 菅原 悠太郎, 佐藤 恒明, 松岡 知樹, 芝山 浩樹, 山賀 慎太郎, 高橋 大介, 清水 智弘, 岩崎 倫政
日本整形外科学会雑誌, 97, 3, S1052, S1052, (公社)日本整形外科学会, 2023年03月
日本語

VLIANステムでTHA術後ステム周囲骨折は予防できるか 多施設共同研究の結果から
高橋 大介, 清水 智弘, 宮崎 拓自, 浅野 毅, 下段 俊, 高橋 要, 福井 隆史, 大浦 久典, 片山 直行, 岩崎 倫政
日本整形外科学会雑誌, 97, 3, S1075, S1075, (公社)日本整形外科学会, 2023年03月
日本語

大腿骨近位部骨折における重症骨粗鬆症患者の割合
山崎 秀, 下段 俊, 楠 兼一, 中條 誠也, 鈴木 瞭太, 百貫 亮太, 梅本 貴央, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 97, 3, S1170, S1170, (公社)日本整形外科学会, 2023年03月
日本語

骨折リスクの高い重症骨粗鬆症患者の脊柱矢状面アライメント異常の検証
有田 皓介, 清水 智弘, 石津 帆高, 岩崎 倫政
日本整形外科学会雑誌, 97, 3, S1179, S1179, (公社)日本整形外科学会, 2023年03月
日本語

ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子
菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 42, 1, 30, 33, (一社)日本関節病学会, 2023年03月
日本語, 目的:特発性大腿骨頭壊死症患者(ONFH)が股関節以外に骨壊死を引き起こす多発骨壊死は,3関節以上と定義した際には約3%とこれまで報告されてきた。一方で,無症候性壊死を検出感度の高い全身MRIを用いた先行研究では,ONFH患者の約25%に多発骨壊死が発生し全例ステロイド関連ONFHであった。そこで本研究は,ステロイド関連ONFH症例を対象として,多発骨壊死の関連性を調査することを目的とした。方法:対象は当院における定点モニタリング対象となったONFH症例328名のうち,特発性ONFH 9名,アルコール関連ONFH 75名およびデータ詳細不明の16名を除外したステロイド関連ONFH 228名(男性108名,女性120名)である。基礎疾患,ステロイド投与最大量,ステロイドパルス療法,アルコール,喫煙,股関節以外の関節の骨壊死発生を調査した。結果:多発骨壊死は228名中59名(男性24名,女性35名)に生じていた。多発骨壊死症を生じたONFH症例は,若年,両側ONFH症例,ステロイド高用量,ステロイドパルス症例,喫煙,全身性エリテマトーデス症例の傾向があった。多変量解析を行ったところ,ステロイドパルス(オッズ比3.0倍,P=0.008)が多発骨壊死の独立した関連因子であった。考察・結論:ONFH発生に関してステロイド投与量やステロイドパルスが関連することと同様に,多発骨壊死とステロイドパルスは関連したことから多発骨壊死発生もステロイド感受性が関連することが示唆された。多発性骨壊死発生のメカニズムはわかっていないが,ステロイド関連ONFHが発生した際には,多発骨壊死のスクリーニングを行うことを考慮する必要があると考えられた。(著者抄録)

変形性膝関節症患者における下腿加速度と膝関節の荷重分布との関係 ウェアラブルセンサーを用いて
佐橋 健人, 岩崎 浩司, 安倍 雄一郎, 渡邊 謙太郎, 千徳 風真, 千葉 健, 小野寺 智洋, 近藤 英司, 岩崎 倫政, 遠山 晴一
日本整形外科学会雑誌, 97, 3, S864, S864, (公社)日本整形外科学会, 2023年03月
日本語

Usefulness of Intraoperative Arthrography for Postaxial Polysyndactyly of the Foot.
Yuko Sakai, Daisuke Kawamura, Takeshi Endo, Norimasa Iwasaki
Journal of pediatric orthopedics, 43, 3, e244-e248, 2023年03月01日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Surgery for polydactyly of the foot aims to achieve good cosmesis and improve shoe fitting. An accurate understanding of toe morphology will help to minimize the skin incision or optimize the surgical plan before incision. However, it is difficult to determine the shape of the articular surface using radiographs of children with immature bone. We performed arthrography during surgery for postaxial polydactyly of the foot to assess the cartilaginous structures. The purpose of this study was to investigate the usefulness of arthrography in postaxial polydactyly of the foot. METHODS: We included 36 digits of 31 patients (16 males and 15 females), including 5 bilateral cases. The age at surgery ranged from 9 to 75 months (mean, 20 mo). Intraoperative arthrography was performed and all radiographs and arthrograms were reviewed and classified by 3 observers using the Watanabe classification. The absolute percentage agreement between the observers was calculated. The senior author assigned the arthrograms as the reference. The types determined by the other 2 observers using radiographs and arthrograms were compared with the reference. RESULTS: Full agreement occurred in 66.7% of the radiographs and in 75% of arthrograms. The mean kappa coefficient was 0.58, indicating fair agreement, between the reference and the radiologic assessment, while it was 0.81, indicating excellent or almost perfect agreement, in the evaluation using arthrograms. CONCLUSIONS: Intraoperative arthrography is an easy and reliable diagnostic method that can be used to determine the detailed articular shape. LEVEL OF EVIDENCE: Level III.

Higher Association of Pelvis-Knee-Ankle Angle Compared With Hip-Knee-Ankle Angle With Knee Adduction Moment and Patient-Reported Outcomes After High Tibial Osteotomy.
Koji Iwasaki, Yasumitsu Ohkoshi, Yoshiaki Hosokawa, Shuya Chida, Kengo Ukishiro, Kensaku Kawakami, Sho'ji Suzuki, Tatsunori Maeda, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
The American journal of sports medicine, 51, 4, 977, 984, 2023年03月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: High tibial osteotomy (HTO) reduces the load distribution of the medial compartment by modifying leg alignment. Knee adduction moment (KAM), a surrogate measure of dynamic loading in the knee joint, decreases after HTO. However, leg alignment does not fully account for KAM. PURPOSE: To assess the association between the pelvis-knee-ankle angle (PKA), a novel radiographic parameter reflecting leg alignment and pelvic width, and KAM and patient-reported outcomes after HTO. STUDY DESIGN: Cross sectional study; Level of evidence, 3. METHODS: PKA is the angle between the line from the midpoint of the anterior superior iliac spine to the center of the knee joint and the mechanical axis of the tibia. In this study, 54 patients with medial compartment knee osteoarthritis and varus alignment who underwent 3-dimensional gait analysis preoperatively and 2 years after medial open-wedge HTO were evaluated. The primary outcomes were hip-knee-ankle angle (HKA), PKA, KAM peaks, and Knee Society Score (KSS). Single and multivariate regression analysis including PKA and KAM peaks as well as other demographic and radiologic factors was performed. RESULTS: HKA was weakly correlated with the first peak KAM (r = -0.33; P < .01) and second peak KAM (r = -0.27; P = .01) before HTO, but not significantly correlated after HTO. PKA was moderately correlated with the first peak KAM (r = 0.45; P < .01) and second peak KAM (r = 0.45; P < .01) before HTO and with the first peak KAM (r = 0.51; P < .01) and second peak KAM (r = 0.56; P < .01) after HTO. Multivariate linear regression revealed that postoperative PKA was still associated with the KAM peaks after HTO. Only postoperative PKA was correlated with the KSS satisfaction subscale (r = -0.30; P = .03). CONCLUSION: Although HKA was not correlated with KAM peaks after HTO, PKA was significantly correlated with KAM peaks in patients with varus knee osteoarthritis after HTO.

Patterns of Vertebral Bone Marrow Edema in the Normal Healing Process of Lumbar Interbody Fusion: Baseline Data for Diagnosis of Pathological Events.
Yuichi Hasegawa, Masahiro Kanayama, Fumihiro Oha, Yukitoshi Shimamura, Takeru Tsujimoto, Tomoyuki Hashimoto, Norimasa Iwasaki
Spine, 48, 5, 358, 363, 2023年03月01日, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Retrospective investigation using a prospectively collected database. OBJECTIVE: To examine the appearance and characteristics of vertebral bone marrow edema (BME) in the normal healing of lumbar interbody fusion. SUMMARY OF BACKGROUND DATA: Although BME in pathological spinal conditions has been well-documented, the patterns and characteristics of BME in the normal healing process of spinal fusion remains unexplored. MATERIALS AND METHODS: We reviewed imaging from 225 patients with normal healing following posterior lumbar interbody fusion or transforaminal lumbar interbody fusion. BME was identified on magnetic resonance imaging at the third postoperative week and categorized with respect to its appearance, including assessment of area and extension within the relevant vertebrae. RESULTS: Three hundred eighty-nine of the 450 instrumented vertebrae (86.4%) displayed evidence BME. All instances of BME were associated with the area of contact with the endplate. The average extent of BME was 32.7±1.0%. BME within normal healing following interbody fusion could be categorized into four types: no edema (13.6%), anterior corner (36.6%), around-the-cage focal (48.0%), and diffuse (1.8%). Anterior corner BME was significantly associated with instances of single cage placement than in dual cages (42.6% vs. 24.7%, P =0.0002). Single cages had a significantly higher rate of BME than dual cages (92.0% vs. 75.3%, P <0.0001). The extent of BME was significantly greater in the single cage cohort (36.9% vs. 24.2% in dual cages, P <0.0001). CONCLUSIONS: This serves as the first study demonstrating the patterns of BME associated with normal healing following lumbar interbody fusion procedures. Anterior corner BME and around-the-cage focal BME were the most common patterns encountered, with diffuse BME a relatively rare pattern. These findings might contribute to the better differentiation of postoperative pathological events from normal healing following lumbar interbody fusion. LEVEL OF EVIDENCE: 4.

Comparison of re-revision rate and radiological outcomes between Kerboull-type plate and metal mesh with impaction bone grafting for revision total hip arthroplasty.
Hotaka Ishizu, Tomohiro Shimizu, Fumio Sasazawa, Daisuke Takahashi, Mohamad Alaa Terkawi, Kaname Takahashi, Yusuke Ohashi, Masahiro Kanayama, Norimasa Iwasaki
BMC musculoskeletal disorders, 24, 1, 134, 134, 2023年02月20日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: This study compared the re-revision rate and radiographic outcomes of revision total hip arthroplasty (THA) using a Kerboull-type acetabular reinforcement device (KT plate) with bulk structural allograft and metal mesh with impaction bone grafting (IBG). METHODS: Ninety-one hips of 81 patients underwent revision THA for American Academy of Orthopedic Surgeons (AAOS) classification type III defects from 2008 to 2018. Of these, seven hips of five patients and 15 hips of 13 patients were excluded due to insufficient follow-up information (< 24 months) and large bone defects with a vertical defect height ≥ 60 mm, respectively. The current study compared the survival and radiographic parameters of 45 hips of 41 patients using a KT plate (KT group) and 24 hips of 24 patients using a metal mesh with IBG (mesh group). RESULTS: Eleven hips (24.4%) in the KT group and 1 hip (4.2%) in the mesh group exhibited radiological failure. Moreover, 8 hips in the KT group (17.0%) required a re-revision THA, while none of the patients in the mesh group required a re-revision. The survival rate with radiographic failure as the endpoint in the mesh group was significantly higher than that in the KT group (100% vs 86.7% at 1-year and 95.8% vs 80.0% at 5-years, respectively; p = 0.032). On multivariable analysis evaluating factors associated with radiographic failure, there were no significant associations with any radiographic measurement. Of the 11 hips with radiographic failure, 1 (11.1%), 3 (12.5%), and 7 (58.3%) hips were of Kawanabe classification stages 2, 3, and 4, respectively. CONCLUSIONS: The findings of this study suggest that revision THA using KT plates with bulk structure allografts could provide poorer clinical outcomes than revision THA using a metal mesh with IBG. Although revision THA using KT plates with bulk structural allografts could set the true hip center, there is no association between a high hip center and clinical outcomes. The relationship between the position of the KT plate and the host bone might be considered more carefully.

Influence of Lateral Translation of Lowest Instrumented Vertebra on L4 Tilt and Coronal Balance for Thoracolumbar and Lumbar Curves in Adolescent Idiopathic Scoliosis
Katsuhisa Yamada, Hideki Sudo, Yuichiro Abe, Terufumi Kokabu, Hiroyuki Tachi, Tsutomu Endo, Takashi Ohnishi, Daisuke Ukeba, Katsuro Ura, Masahiko Takahata, Norimasa Iwasaki
Journal of Clinical Medicine, 12, 4, 1389, 1389, MDPI AG, 2023年02月09日, ［国際誌］
英語, 研究論文（学術雑誌）, This study aimed to evaluate the lowest instrumented vertebra translation (LIV-T) in the surgical treatment of thoracolumbar/lumbar adolescent idiopathic scoliosis and to analyze the radiographic parameters in relation to LIV-T and L4 tilt and global coronal balance. A total of 62 patients underwent posterior spinal fusion (PSF, n = 32) or anterior spinal fusion (ASF, n = 30) and were followed up for a minimum of 2 years. The mean preoperative LIV-T was significantly larger in the ASF group than the PSF (p < 0.01), while the final LIV-T was equivalent. LIV-T at the final follow-up was significantly correlated with L4 tilt and the global coronal balance (r = 0.69, p < 0.01, r = 0.38, p < 0.01, respectively). Receiver-operating characteristic analysis for good outcomes, with L4 tilt <8° and coronal balance <15 mm at the final follow-up, calculated the cutoff value of the final LIV-T as 12 mm. The cutoff value of preoperative LIV-T that would result in the LIV-T of ≤12 mm at the final follow-up was 32 mm in PSF, although no significant cutoff value was calculated in ASF. ASF can centralize the LIV better than PSF with a shorter segment fusion, and could be useful in obtaining a good curve correction and global balance without fixation to L4 in cases with large preoperative LIV-T.

Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model
Hisataka Suzuki, Katsuro Ura, Daisuke Ukeba, Takashi Suyama, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Katsuhisa Yamada, Hideki Sudo
Cells, 12, 3, 505, 505, MDPI AG, 2023年02月03日, ［国際誌］
英語, 研究論文（学術雑誌）, Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA (p < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (p < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (p < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.

Protocol for treating lumbar spinal canal stenosis with a combination of ultrapurified, allogenic bone marrow-derived mesenchymal stem cells and in situ-forming gel: a multicentre, prospective, double-blind randomised controlled trial.
Hideki Sudo, Takashi Miyakoshi, Yudai Watanabe, Yoichi M Ito, Kaoru Kahata, Khin Khin Tha, Nozomi Yokota, Hiroe Kato, Tomoko Terada, Norimasa Iwasaki, Teruyo Arato, Norihiro Sato, Toshiyuki Isoe
BMJ open, 13, 2, e065476, 2023年02月02日, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: In patients with combined lumbar spinal canal stenosis (LSCS), a herniated intervertebral disc (IVD) that compresses the dura mater and nerve roots is surgically treated with discectomy after laminoplasty. However, defects in the IVD after discectomy may lead to inadequate tissue healing and predispose patients to the development of IVD degeneration. Ultrapurified stem cells (rapidly expanding clones (RECs)), combined with an in situ-forming bioresorbable gel (dMD-001), have been developed to fill IVD defects and prevent IVD degeneration after discectomy. We aim to investigate the safety and efficacy of a new treatment method in which a combination of REC and dMD-001 is implanted into the IVD of patients with combined LSCS. METHODS AND ANALYSIS: This is a multicentre, prospective, double-blind randomised controlled trial. Forty-five participants aged 20-75 years diagnosed with combined LSCS will be assessed for eligibility. After performing laminoplasty and discectomy, participants will be randomised 1:1:1 into the combination of REC and dMD-001 (REC-dMD-001) group, the dMD-001 group or the laminoplasty and discectomy alone (control) group. The primary outcomes of the trial will be the safety and effectiveness of the procedure. The effectiveness will be assessed using visual analogue scale scores of back pain and leg pain as well as MRI-based estimations of morphological and compositional quality of the IVD tissue. Secondary outcomes will include self-assessed clinical scores and other MRI-based estimations of compositional quality of the IVD tissue. All evaluations will be performed at baseline and at 1, 4, 12, 24 and 48 weeks after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees of the institutions involved. We plan to conduct dissemination of the outcome data by presenting our data at national and international conferences, as well as through formal publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCT2013210076.

Arthroscopic superior capsular reconstruction combined with pectoralis minor transfer for irreparable anterosuperior rotator cuff tear: a case report.
Yukinori Tsukuda, Atsushi Urita, Masahiro Miyano, Hiroshi Taneichi, Norimasa Iwasaki
JSES reviews, reports, and techniques, 3, 1, 101, 106, 2023年02月, ［国際誌］
英語

Dupuytren's contracture-associated SNPs increase SFRP4 expression in nonimmune cells including fibroblasts to enhance inflammation development.
Hiroaki Kida, Jing-Jing Jiang, Yuichiro Matsui, Ikuko Takahashi, Rie Hasebe, Daisuke Kawamura, Takeshi Endo, Hiroki Shibayama, Makoto Kondoh, Yasuhiko Nishio, Kinya Nishida, Yoshihiro Matsuno, Tsukasa Oikawa, Shimpei Kubota, Shintaro Hojyo, Norimasa Iwasaki, Shigeru Hashimoto, Yuki Tanaka, Masaaki Murakami
International immunology, 35, 7, 303, 312, 2023年01月31日, ［国際誌］
英語, 研究論文（学術雑誌）, Dupuytren's contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two SNPs associated with DC, rs16879765 and rs17171229, in secreted frizzled related protein 4 (SFRP4). We investigated the association of SRFP4 with the IL-6 amplifier, which amplifies the production of IL-6, growth factors, and chemokines in non-immune cells and aggravates inflammatory diseases via NF-κB enhancement. Knockdown of SFRP4 suppressed activation of the IL-6 amplifier in vitro and in vivo, whereas the overexpression of SFRP4 induced the activation of NF-κB-mediated transcription activity. Mechanistically, SFRP4 induced NF-κB activation by directly binding to molecules of the ubiquitination SFC complex, such as IkBα and βTrCP, followed by IkBα degradation. Furthermore, SFRP4 expression was significantly increased in fibroblasts derived from DC patients bearing the risk alleles. Consistently, fibroblasts with the risk alleles enhanced activation of the IL-6 amplifier. These findings indicate that the IL-6 amplifier is involved in the pathogenesis of DC, particularly in patients harboring the SFRP4 risk alleles. Therefore, SFRP4 is a potential therapeutic target for various inflammatory diseases and disorders, including DC.

Characteristics of the Patients with Poor Clinical Outcomes After Symptomatic Postoperative Lumbar Epidural Hematoma.
Takeru Tsujimoto, Masahiro Kanayama, Fumihiro Oha, Yukitoshi Shimamura, Masaru Tanaka, Yuichi Hasegawa, Syotaro Fukada, Tomoyuki Hashimoto, Masahiko Takahata, Norimasa Iwasaki
World neurosurgery, 172, e364-e371, 2023年01月12日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Symptomatic postoperative lumbar epidural hematoma (PLEH) may lead to poor outcomes even after evacuation. This study aimed to verify the short-term clinical outcomes after the evacuation of PLEH and to clarify the characteristics of the patients with poor postoperative outcomes. METHODS: Twenty-five patients (average age; 70.4 years) underwent PLEH evacuation after lumbar spine surgery. The mean follow-up period was 12.0 (range 3-37) months. Pre and postoperative Japanese Orthopedic Association scores and visual analog scale (VAS) of low back pain (LBP), leg pain, and leg numbness were retrospectively collected. The dural sac cross-sectional area at the most compressed level was measured on magnetic resonance imaging. The patients were classified into 2 groups: poor outcome group (P group) had less than 50% of Japanese Orthopedic Associationrecovery rate and good group (G group) with 50% or more recovery rate. RESULTS: The rate of delayed evacuation (over 24 hours of onset) was significantly higher in P group than in G group (P = 0.027). There was no significant difference in dural sac cross-sectional areabetween the 2 groups (P = 0.438). VAS of LBP, leg pain, and leg numbness in G group significantly improved postoperatively. Although VAS of LBP and leg pain in P group significantly improved postoperatively, there was no significant difference between the pre and postoperative VAS of leg numbness. CONCLUSIONS: Delayed evacuation of PLEH can lead to poor postoperative outcomes after lumbar spine surgery. Moreover, patients with poor outcomes remained with postoperative leg numbness. Early evacuation of symptomatic PLEH is key to avoid poor outcomes and persistent leg numbness.

Lumbar ossification of the ligamentum flavum reflects a strong ossification tendency of the entire spinal ligament.
Kazuha Nakabachi, Tsutomu Endo, Masahiko Takahata, Ryo Fujita, Yoshinao Koike, Ryota Suzuki, Yuichi Hasegawa, Toshifumi Murakami, Katsuhisa Yamada, Hideki Sudo, Mohamad Alaa Terkawi, Ken Kadoya, Norimasa Iwasaki
Scientific reports, 13, 1, 638, 638, 2023年01月12日, ［国際誌］
英語, 研究論文（学術雑誌）, Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index. Subjects with OLF were grouped according to this index: localized OLF (n = 138), intermediate OLF (n = 70), and extensive OLF (n = 31). The proportion of subjects with lumbar OLF increased with increasing OLF index (localized 13.7%, intermediate 41.4%, and extensive 70.9%). Multiple regression analysis found that lumbar OLF index was associated with thoracic OLF index, and co-existence of ossification of the posterior longitudinal ligament (OPLL) of the thoracic and lumbar spine. This study showed that subjects with more multilevel lumbar OLF were more likely to develop multilevel thoracic OLF and to have coexisting OPLL. Patients with lumbar OLF may be a distinctive subgroup with a strong tendency to ossification of the entire spinal ligament.

Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years.
Takuma Kaibara, Eiji Kondo, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Keita Sakamoto, Yoshitaka Oda, Zen-Ichi Tanei, Daisuke Momma, Shinya Tanaka, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 29, 1, 207, 216, 2023年01月09日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Recently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PURPOSE: To evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. METHODS: Thirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. RESULTS: The mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36-84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8-41 months) after A-ACI. CONCLUSION: The present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36-84 months).

Prediction of Cobb Angle Using Deep Learning Algorithm with Three-Dimensional Depth Sensor Considering the Influence of Garment in Idiopathic Scoliosis
Yoko Ishikawa, Terufumi Kokabu, Katsuhisa Yamada, Yuichiro Abe, Hiroyuki Tachi, Hisataka Suzuki, Takashi Ohnishi, Tsutomu Endo, Daisuke Ukeba, Katsuro Ura, Masahiko Takahata, Norimasa Iwasaki, Hideki Sudo
Journal of Clinical Medicine, 12, 2, 499, 499, MDPI AG, 2023年01月07日, ［国際誌］
英語, 研究論文（学術雑誌）, Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Early detection of deformity and timely intervention, such as brace treatment, can help inhibit progressive changes. A three-dimensional (3D) depth-sensor imaging system with a convolutional neural network was previously developed to predict the Cobb angle. The purpose of the present study was to (1) evaluate the performance of the deep learning algorithm (DLA) in predicting the Cobb angle and (2) assess the predictive ability depending on the presence or absence of clothing in a prospective analysis. We included 100 subjects with suspected AIS. The correlation coefficient between the actual and predicted Cobb angles was 0.87, and the mean absolute error and root mean square error were 4.7° and 6.0°, respectively, for Adam’s forward bending without underwear. There were no significant differences in the correlation coefficients between the groups with and without underwear in the forward-bending posture. The performance of the DLA with a 3D depth sensor was validated using an independent external validation dataset. Because the psychological burden of children and adolescents on naked body imaging is an unignorable problem, scoliosis examination with underwear is a valuable alternative in clinics or schools.

手指ボタンホール変形に対するOhshio法の治療経験
遠藤 健, 河村 太介, 松井 雄一郎, 松居 祐樹, 鈴木 智亮, 小林 英之, 岩崎 倫政, 門間 太輔
北海道整形災害外科学会雑誌, 65, 142nd suppl, 56, 56, 北海道整形災害外科学会, 2023年
日本語

The Novel Ulnar Nerve Coverage Method Which Has the Potential to Prevent the Postoperative Ulnar Neuropathy after Plate Fixation of Distal Humerus Fractures: Three Case Reports.
Hiroki Shibayama, Shintaro Yamaga, Yutaro Sugawara, Tsuyoshi Asano, Norimasa Iwasaki
Case reports in orthopedics, 2023, 5008141, 5008141, 2023年, ［国際誌］
英語, INTRODUCTION: Postoperative ulnar neuropathy is still an unresolved complication in patients undergoing plate fixation of distal humerus fractures. We hypothesized that decreased blood flow to the ulnar nerve due to intraoperative procedures is an important factor in the development of postoperative ulnar neuropathy. We herein report three cases of distal humerus fractures in which the soft tissues surrounding the ulnar nerve were preserved as much as possible and finally not transferred anteriorly. Case Presentation. A 76-year-old woman, 82-year-old woman, and 34-year-old woman underwent plate fixation for distal humerus fractures. None of the patients developed postoperative ulnar neuropathy, and there were no complaints of numbness after postoperative day 1. Nerve conduction studies were performed after 3 months postoperatively and revealed that the motor nerve conduction velocities and compound motor nerve action potentials of the ulnar nerve in two of the three patients were higher than those of the noninjured side. In one of the three patients, these values were slightly lower than those of the noninjured side. All three patients achieved bony union after several months postoperatively. CONCLUSIONS: We obtained good outcomes with the ulnar nerve coverage method for preventing postoperative ulnar neuropathy in patients with distal humerus fractures. Preservation of blood flow to the ulnar nerve was considered important, and anatomical repositioning of the ulnar nerve after plate fixation has the potential to prevent adhesion between the ulnar nerve and the plate.

後縦靱帯骨化症患者は全身的な骨形成の亢進が示唆される アキレス腱と足底腱の骨化解析
遠藤 努, 小池 良直, 山田 勝久, 大西 貴士, 筌場 大介, 岩崎 倫政, 高畑 雅彦, 金山 雅弘
北海道整形災害外科学会雑誌, 65, 142nd suppl, 14, 14, 北海道整形災害外科学会, 2023年
日本語

AI技術により作成した3D腰神経MRI像を用いたL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術シミュレーションの有用性
山田 勝久, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 岩崎 倫政, 長濱 賢, 安倍 雄一郎, 須藤 英毅
北海道整形災害外科学会雑誌, 65, 142nd suppl, 15, 15, 北海道整形災害外科学会, 2023年
日本語

腰椎後方除圧術における棘上棘間靱帯・棘突起温存は、術後の二次性椎間板変性の進行を抑制する
大西 貴士, 山田 勝久, 岩崎 倫政, 中下 並人, 楫野 知道, 久田 雄一郎, 須藤 英毅
北海道整形災害外科学会雑誌, 65, 142nd suppl, 15, 15, 北海道整形災害外科学会, 2023年
日本語

3次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証
石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 岩崎 倫政, 須藤 英毅, 安倍 雄一郎
北海道整形災害外科学会雑誌, 65, 142nd suppl, 16, 16, 北海道整形災害外科学会, 2023年
日本語

治療に苦慮した慢性再発性多発性骨髄炎(CRMO)を背景とした環軸椎回旋位固定の一例
石田 健太, 遠藤 努, 高畑 雅彦, 須藤 英毅, 山田 勝久, 大西 貴士, 筌場 大介, 浦 勝郎, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 18, 18, 北海道整形災害外科学会, 2023年
日本語

遅発性麻痺を生じた高齢者の頸椎脱臼骨折の一例
白井 良樹, 浦 勝郎, 山田 勝久, 筌場 大介, 大西 貴士, 遠藤 努, 高畑 雅彦, 岩崎 倫政, 須藤 英毅
北海道整形災害外科学会雑誌, 65, 142nd suppl, 21, 21, 北海道整形災害外科学会, 2023年
日本語

炎症性軟骨細胞は骨細胞のパイロトーシスを誘導する
小川 裕生, 徳廣 泰貴, 江畑 拓, 北原 圭太, 塩田 惇喜, 西田 善郎, 清水 智弘, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 3, 3, 北海道整形災害外科学会, 2023年
日本語

細胞老化に着目した骨マクロファージの骨代謝調節機能の検討
西田 善郎, 松前 元, 横田 隼一, 照川 ヘンド, 清水 智弘, 高橋 大介, 遠藤 努, 照川 アラー, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 5, 5, 北海道整形災害外科学会, 2023年
日本語

大腿骨近位部骨折後のリエゾンサービスにおける二次骨折発生とリスク因子 Covid 19状況下の前向き研究
石津 帆高, 清水 智弘, 佐藤 恒明, 大橋 佑介, 山崎 秀, 岩崎 倫政, 下段 俊
北海道整形災害外科学会雑誌, 65, 142nd suppl, 42, 42, 北海道整形災害外科学会, 2023年
日本語

大腿骨近位部骨折患者における重症骨粗鬆症の割合
山崎 秀, 下段 俊, 梅本 貴央, 山崎 秀, 清水 智弘, 岩崎 倫政, 高橋 大介
北海道整形災害外科学会雑誌, 65, 142nd suppl, 42, 42, 北海道整形災害外科学会, 2023年
日本語

骨マクロファージ由来神経ペプチド様タンパク質は破骨細胞分化を阻害する
徳廣 泰貴, 塩田 惇喜, 北原 圭太, 西田 善郎, 清水 智弘, 遠藤 努, 高橋 大介, 照川 アラー, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 43, 43, 北海道整形災害外科学会, 2023年
日本語

RANKL中和抗体中止後の骨吸収過剰亢進におけるメカニズム解明アプローチ
石津 帆高, 清水 智弘, 岩崎 倫政, 長谷川 智香, 網塚 憲生
北海道整形災害外科学会雑誌, 65, 142nd suppl, 44, 44, 北海道整形災害外科学会, 2023年
日本語

ロモソズマブの逐次療法におけるゾレドロン酸とデノスマブの比較
大上 哲郎, 清水 智弘, 石津 穂高, 岩崎 倫政, 浅野 毅, 下段 俊
北海道整形災害外科学会雑誌, 65, 142nd suppl, 44, 44, 北海道整形災害外科学会, 2023年
日本語

新規骨マクロファージ由来分子タンパクの生体内治療効果
塩田 惇喜, 照川 アラー, 高橋 大介, 清水 智弘, 横田 隼一, 北原 圭太, 西田 善郎, 徳廣 泰貴, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 65, 65, 北海道整形災害外科学会, 2023年
日本語

炎症収束型好中球由来細胞外小胞による軟骨細胞における抗異化作用の検討
北原 圭太, 江畑 拓, 横田 隼一, 塩田 惇喜, 西田 善郎, 徳廣 泰貴, 清水 智弘, 浅野 毅, 高橋 大介, 角家 健, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 66, 66, 北海道整形災害外科学会, 2023年
日本語

骨折リスクの高い骨粗鬆症の脊柱矢状断アライメント異常の検証
有田 皓介, 清水 智弘, 石津 帆高, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 72, 72, 北海道整形災害外科学会, 2023年
日本語

Polished cement stemにおけるhead延長が脚長、オフセット、可動域に与える影響A computer simulation study
宮崎 拓自, 清水 智弘, 小川 拓也, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 87, 87, 北海道整形災害外科学会, 2023年
日本語

不安定型大腿骨転子部骨折に対し前方アプローチで一期的人工骨頭置換を行った症例の検討
加藤 琢磨, 放生 憲博, 清水 智弘, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 90, 90, 北海道整形災害外科学会, 2023年
日本語

コロナ禍で始めた大腿骨近位部骨折リエゾンサービスにおける骨粗鬆症治療継続状況と中断例の検討
下段 俊, 梅本 貴央, 久田 雄一郎, 沼口 京介, 高橋 錬也, 石田 健太, 佐藤 知哉, 清水 智弘, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 92, 92, 北海道整形災害外科学会, 2023年
日本語

Ferroptosisを標的としたポリエチレン摩耗粉による炎症性骨吸収抑制効果
小川 拓也, 横田 隼一, 徳廣 泰貴, 照川 アラー, 照川, 西田 善郎, 塩田 惇喜, 北原 圭太, 清水 智弘, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 93, 93, 北海道整形災害外科学会, 2023年
日本語

ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子
菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 94, 94, 北海道整形災害外科学会, 2023年
日本語

Angulated Innominate Osteotomyにおける術中三次元矯正と術後1年単純X線との関連
小川 拓也, 高橋 大介, 清水 智弘, 宮崎 拓自, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 95, 95, 北海道整形災害外科学会, 2023年
日本語

乳児股関節健診推奨項目は発育性股関節形成不全の予測因子となりうるか?
大橋 佑介, 清水 智弘, 清水 寛和, 小川 拓也, 宮崎 拓自, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 95, 95, 北海道整形災害外科学会, 2023年
日本語

発育性股関節形成不全の二次検診受診時期による装具治療の有無の検討　　　　　　　　　　　　　　　
小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 96, 96, 北海道整形災害外科学会, 2023年
日本語

リーメンビューゲル治療前に水平牽引を行うことで脱臼整復率は改善する　　　　　　　　　　　　　　　
小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 96, 96, 北海道整形災害外科学会, 2023年
日本語

北海道における先端的医療技術としてのAIと遠隔医療の取り組み 股関節周囲外傷・疾患診療におけるAIの活用
清水 智弘, 山田 勝久, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 1, 18, 20, 北海道整形災害外科学会, 2023年
日本語

後縦靱帯骨化症患者は全身的な骨形成の亢進が示唆される アキレス腱と足底腱の骨化解析
遠藤 努, 小池 良直, 山田 勝久, 大西 貴士, 筌場 大介, 岩崎 倫政, 高畑 雅彦, 金山 雅弘
北海道整形災害外科学会雑誌, 65, 142nd suppl, 14, 14, 北海道整形災害外科学会, 2023年
日本語

AI技術により作成した3D腰神経MRI像を用いたL5/Sレベルの全内視鏡下椎間板ヘルニア摘出術シミュレーションの有用性
山田 勝久, 筌場 大介, 遠藤 努, 大西 貴士, 浦 勝郎, 高畑 雅彦, 岩崎 倫政, 長濱 賢, 安倍 雄一郎, 須藤 英毅
北海道整形災害外科学会雑誌, 65, 142nd suppl, 15, 15, 北海道整形災害外科学会, 2023年
日本語

腰椎後方除圧術における棘上棘間靱帯・棘突起温存は、術後の二次性椎間板変性の進行を抑制する
大西 貴士, 山田 勝久, 岩崎 倫政, 中下 並人, 楫野 知道, 久田 雄一郎, 須藤 英毅
北海道整形災害外科学会雑誌, 65, 142nd suppl, 15, 15, 北海道整形災害外科学会, 2023年
日本語

3次元デプスセンサーと人工知能を用いた側彎角の自動予測 着衣の有無による精度検証
石川 蓉子, 小甲 晃史, 山田 勝久, 舘 弘之, 鈴木 久崇, 大西 貴士, 岩崎 倫政, 須藤 英毅, 安倍 雄一郎
北海道整形災害外科学会雑誌, 65, 142nd suppl, 16, 16, 北海道整形災害外科学会, 2023年
日本語

治療に苦慮した慢性再発性多発性骨髄炎(CRMO)を背景とした環軸椎回旋位固定の一例
石田 健太, 遠藤 努, 高畑 雅彦, 須藤 英毅, 山田 勝久, 大西 貴士, 筌場 大介, 浦 勝郎, 岩崎 倫政
北海道整形災害外科学会雑誌, 65, 142nd suppl, 18, 18, 北海道整形災害外科学会, 2023年
日本語

Efficacy of a machine learning-based approach in predicting neurological prognosis of cervical spinal cord injury patients following urgent surgery within 24 h after injury.
Tomoaki Shimizu, Kota Suda, Satoshi Maki, Masao Koda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiro Ota, Hiroki Ushirozako, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Hiroshi Takahashi, Masashi Yamazaki
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 107, 150, 156, 2023年01月, ［国際誌］
英語, 研究論文（学術雑誌）, We aimed to develop a machine learning (ML) model for predicting the neurological outcomes of cervical spinal cord injury (CSCI). We retrospectively analyzed 135 patients with CSCI who underwent surgery within 24 h after injury. Patients were assessed with the American Spinal Injury Association Impairment Scale (AIS; grades A to E) 6 months after injury. A total of 34 features extracted from demographic variables, surgical factors, laboratory variables, neurological status, and radiological findings were analyzed. The ML model was created using Light GBM, XGBoost, and CatBoost. We evaluated Shapley Additive Explanations (SHAP) values to determine the variables that contributed most to the prediction models. We constructed multiclass prediction models for the five AIS grades and binary classification models to predict more than one-grade improvement in AIS 6 months after injury. Of the ML models used, CatBoost showed the highest accuracy (0.800) for the prediction of AIS grade and the highest AUC (0.90) for predicting improvement in AIS. AIS grade at admission, intramedullary hemorrhage, longitudinal extent of intramedullary T2 hyperintensity, and HbA1c were identified as important features for these prediction models. The ML models successfully predicted neurological outcomes 6 months after injury following urgent surgery in patients with CSCI.

Deep fibrous histiocytoma of the index finger: a case report.
Hiroki Shibayama, Yuichiro Matsui, Daisuke Kawamura, Daisuke Momma, Takeshi Endo, Yuki Matsui, Yasutaka Yawaka, Kanako C Hatanaka, Emi Takakuwa, Hirokazu Sugino, Yutaka Hatanaka, Tadashi Hasegawa, Norimasa Iwasaki
Case reports in plastic surgery & hand surgery, 10, 1, 2207637, 2207637, 2023年, ［国際誌］
英語, Our patient presented with an elastic soft mass of his left index finger. Hematoxylin and eosin staining showed a high cellular density with spindle-shaped cells in a storiform pattern. Immunohistochemical staining was positive for CD68, factor XIIIa and α-smooth muscle actin, and negative for CD34, STAT6, S100 protein, and desmin.

Three-stage total knee arthroplasty combined with deformity correction and leg lengthening using Taylor spatial frames and conversion to internal fixation for severe intra- and extra-articular deformities and hypoplasia in a patient with hemophilic knee arthropathy: A case report.
Akira Fukushima, Koji Iwasaki, Ryousuke Hishimura, Shinji Matsubara, Zenta Joutoku, Masatake Matsuoka, Tomoyuki Endo, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
The Knee, 40, 90, 96, 2023年01月, ［国際誌］
英語, BACKGROUND: Hemophilic arthropathy is a cause of severe knee deformity, because chronic synovitis due to repeated hemarthrosis affects the area of the epiphyseal plates in juvenile cases. Total knee arthroplasty (TKA) is the standard treatment for end-stage knee arthropathy. However, it is difficult to perform one-stage TKA in patients with severe intra- and extra-articular deformities. CASE PRESENTATION: We reported a case of hemophilic arthropathy in a 55-year-old male with leg length discrepancy of 4 cm, limited range of knee motion (-40° extension and 85° flexion), intra-articular deformity (medial proximal tibial angle: 69°; mechanical lateral distal femoral angle: 79°), extra-articular deformity at the distal femoral metaphyseal (30° valgus and 45° flexion deformity), and varus malalignment (% mechanical axis: 33%). We planned a three-stage TKA. Firstly, we performed gradual correction and lengthening of the distal femur using Taylor spatial flame. Six months after surgery, we performed conversion surgery from external fixation to internal fixation. Finally, we performed TKA with rotating hinged type implant. Two years after surgery, physical examination showed a normal gait, leg length discrepancy of 2 cm (the right leg was shorter), improvement in the range of knee motion (0° extension and 100° flexion). CONCLUSION: To the best of our knowledge, this presents the first combination of three-stage TKA with correction of femoral deformity and leg lengthening using a Taylor spatial frame and conversion to internal fixation in a patient with hemophilic knee arthropathy and severe intra- and extra-articular deformities.

Early Changes in Postural Balance Following Inverted V-Shaped High Tibial Osteotomy in Patients With Knee Osteoarthritis.
Kento Sabashi, Takeshi Chiba, Koji Iwasaki, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki, Harukazu Tohyama
Journal of applied biomechanics, 39, 2, 1, 6, 2023年01月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Patients with knee osteoarthritis and varus knee deformity have impaired postural balance, resulting in decreased walking performance and an increased risk of falls. This study aimed to investigate the early changes in the postural balance following inverted V-shaped high tibial osteotomy (HTO). Fifteen patients with medial knee osteoarthritis were recruited. Postural balance was assessed using the center-of-pressure (COP) data during single-leg standing before and 6 weeks after inverted V-shaped HTO. The maximum range, mean velocity, and area of COP movements in the anteroposterior and mediolateral directions were analyzed. Preoperative and postoperative visual analog scale for knee pain was assessed. The maximum range of COP in the mediolateral direction decreased (P = .017), whereas the mean velocity of COP in the anteroposterior direction increased 6 weeks postoperatively (P = .011). The visual analog scale score for knee pain significantly improved at 6 weeks postoperatively (P = .006). Valgus correction with inverted V-shaped HTO resulted in improved postural balance in the mediolateral direction and good short-term clinical outcomes early following surgery. Early rehabilitation after inverted V-shaped HTO should focus on postural balance in the anteroposterior direction.

Radiolunate Arthrodesis in the Rheumatoid Wrist: A Retrospective Clinical and Radiologic Long-Term Follow-up
Hiroki Hamano, Daisuke Kawamura, Makoto Motomiya, Yuichiro Matsui, Atsushi Urita, Norimasa Iwasaki
The Journal of Hand Surgery, Elsevier BV, 2023年01月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: This study aimed to determine the results of radiolunate arthrodesis for rheumatoid arthritis (RA) after a long-term follow-up period of up to 20 years under tight postoperative medical control of RA. We also compared the results between patients with and without degenerative changes in the midcarpal joints at follow-up. We determined the radiologic factors predictive of secondary degenerative changes in the midcarpal joint. METHODS: This was a long-term retrospective analysis of 16 wrists of 14 patients with RA treated with radiolunate arthrodesis first reported in 2013. The mean follow-up period was 14 years (range, 8-23 years; SD, 4.6 years). Ten wrists had a Larsen classification of grade III, whereas 6 wrists had grade IV. The range of motion was assessed, and clinical outcomes were graded using the Mayo Wrist Score and Stanley classification system. The Carpal Height Index, Ulnar Translation Index, and changes in the midcarpal joint contour were determined from radiographs. We categorized the changes in the midcarpal joint as unchanged or degenerative. RESULTS: At final follow-up, the clinical scores improved; however, the extension and flexion range of motion was significantly reduced compared with that before surgery. The Carpal Height Index and Ulnar Translation Index improved immediately after surgery and remained stable at final follow-up. The changes in the midcarpal joint were categorized as unchanged in 6 wrists and degenerative in 10 wrists. The clinical outcomes were similar between the groups. The mean preoperative Ulnar Translation Index was significantly higher in the degenerative group than in the unchanged group. CONCLUSIONS: Radiolunate arthrodesis in patients with RA maintained good clinical results and corrected alignment, even during long-term follow-up. Preoperative severe ulnar translation deformity was a risk factor for postoperative degeneration of the midcarpal joint, and pre-existing degenerative changes at the midcarpal joint might lead to loss of wrist range of motion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments.
Tsutomu Endo, Masahiko Takahata, Ryo Fujita, Yoshinao Koike, Ryota Suzuki, Yuichi Hasegawa, Toshifumi Murakami, Misaki Ishii, Katsuhisa Yamada, Hideki Sudo, Norimasa Iwasaki
Scientific reports, 12, 1, 22617, 22617, 2022年12月30日, ［国際誌］
英語, 研究論文（学術雑誌）, Obesity and metabolic disturbances are prevalent in ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF); however, the involvement of dyslipidemia (DL) in OPLL/OLF remains uncertain. We investigated the association between dyslipidemia and OPLL/OLF using a dataset of 458 individuals receiving health screening tests, including computed tomography. Subjects were grouped according to the presence or location of OPLL/OLF: controls (no OPLL/OLF, n = 230), OLF (n = 167), cervical OPLL (n = 28), and thoracic OPLL (n = 33). They were also grouped according to the presence of dyslipidemia (DL[+], n = 215; DL[-], n = 243). The proportion of dyslipidemia in the OLF and OPLL groups was 1.6-2.2 times higher than that in the control group. The proportion of OLF and OPLL in the DL(+) group was significantly higher than that in the DL(-) group (OLF, 43% vs. 29%; cervical OPLL, 14.4% vs. 3.2%; thoracic OPLL, 11.1% vs. 3.7%). Multivariate logistic regression analysis showed an association between all ossification types and dyslipidemia. This study demonstrated an association of dyslipidemia with OPLL/OLF; further investigation on the causal relationship between dyslipidemia and ectopic spinal ligament ossification is warranted to develop a therapeutic intervention for OPLL/OLF.

Effects of Posterior Spinal Correction and Fusion on Postural Stability in Patients with Adolescent Idiopathic Scoliosis.
Satoshi Osuka, Hideki Sudo, Katsuhisa Yamada, Hiroyuki Tachi, Kentaro Watanabe, Fuma Sentoku, Takeshi Chiba, Norimasa Iwasaki, Masahiko Mukaino, Harukazu Tohyama
Journal of clinical medicine, 12, 1, 2022年12月29日, ［国際誌］
英語, 研究論文（学術雑誌）, The present study aimed to assess the effects of posterior spinal correction and fusion on postural stability in patients with adolescent idiopathic scoliosis (AIS). The study included 41 female patients with AIS at our institution. All patients performed three 10 s single-leg standing trials on a force plate. The center of pressure (COP) was measured preoperatively, and at 1 week and 6 months postoperatively. The postural stability parameters were absolute minimum time-to-boundary (TTB), mean of the minimum TTB, mean COP velocity, standard deviation, range, and 95% confidence ellipse area. One-way repeated analysis of variance or Friedman test was applied to the postural stability parameters. Multiple comparisons were performed using the Bonferroni correction. The absolute minimum TTB and the mean minimum TTB showed a significant increase 6 months post-operation as compared to preoperatively and 1 week postoperatively. The COP velocity significantly decreased at 6 months post-operation compared to preoperatively and 1 week postoperatively. These changes in postural stability indicate that spinal correction and fusion can be considered to improve postural stability during single-leg standing tests in the postoperative period.

Spinal Canal and Spinal Cord in Rat Continue to Grow Even after Sexual Maturation: Anatomical Study and Molecular Proposition.
Akihito Sotome, Ken Kadoya, Yuki Suzuki, Norimasa Iwasaki
International journal of molecular sciences, 23, 24, 2022年12月16日, ［国際誌］
英語, 研究論文（学術雑誌）, Although rodents have been widely used for experimental models of spinal cord diseases, the details of the growth curves of their spinal canal and spinal cord, as well as the molecular mechanism of the growth of adult rat spinal cords remain unavailable. They are particularly important when conducting the experiments of cervical spondylotic myelopathy (CSM), since the disease condition depends on the size of the spinal canal and the spinal cord. Thus, the purposes of the present study were to obtain accurate growth curves for the spinal canal and spinal cord in rats; to define the appropriate age in weeks for their use as a CSM model; and to propose a molecular mechanism of the growth of the adult spinal cord in rats. CT myelography was performed on Lewis rats from 4 weeks to 40 weeks of age. The vertical growth of the spinal canal at C5 reached a plateau after 20 and 12 weeks, and at T8 after 20 and 16 weeks, in males and females, respectively. The vertical growth of the C5 and T8 spinal cord reached a plateau after 24 weeks in both sexes. The vertical space available for the cord (SAC) of C5 and T8 did not significantly change after 8 weeks in either sex. Western blot analyses showed that VEGFA, FGF2, and BDNF were highly expressed in the cervical spinal cords of 4-week-old rats, and that the expression of these growth factors declined as rats grew. These findings indicate that the spinal canal and the spinal cord in rats continue to grow even after sexual maturation and that rats need to be at least 8 weeks of age for use in experimental models of CSM. The present study, in conjunction with recent evidence, proposes the hypothetical model that the growth of rat spinal cord after the postnatal period is mediated at least in part by differentiation of neural progenitor cells and that their differentiation potency is maintained by VEGFA, FGF2, and BDNF.

Implications of navigation system use for glenoid component placement in reverse shoulder arthroplasty.
Hiroaki Kida, Atsushi Urita, Daisuke Momma, Yuki Matsui, Takeshi Endo, Daisuke Kawamura, Hiroshi Taneichi, Norimasa Iwasaki
Scientific reports, 12, 1, 21190, 21190, 2022年12月07日, ［国際誌］
英語, 研究論文（学術雑誌）, Recently, three-dimensional (3D) planning, patient-specific instruments, and navigation system have been developed to improve the accuracy of baseplate placement in reverse shoulder arthroplasty (RSA). The purpose of this study was to evaluate baseplate placement using the navigation system. Sixty-four shoulders in 63 patients who underwent RSA for rotator cuff tear arthropathy or irreparable rotator cuff tears were enrolled. Conventional RSA was performed in 31 shoulders and navigated RSA using pre-operative planning software was performed in 33 shoulders. The use of augmented baseplates, the version and inclination of the baseplate, and screw length were compared between conventional RSA and navigated RSA. Augmented baseplates were used more frequently in navigated RSA than in conventional RSA (20 vs 9 shoulders, p = 0.014). Baseplate alignment was 1.0° (SD 5.1) of retroversion and 2.4° (SD 6.8) of superior inclination in conventional RSA and 0.2° (SD 1.9) of anteversion and 0.3° (SD 1.7) of superior inclination in navigated RSA. Compared with conventional RSA, precision of baseplate version and inclination were higher in navigated RSA (both p < 0.001). Superior, inferior, and posteroinferior screws were significantly longer in navigated RSA than in conventional RSA (p = 0.021, 0.001 and < 0.001, respectively). Precision of superior and inferior screw lengths was significantly higher in navigated RSA than in conventional RSA (both p = 0.001). Our results suggest that adoption of pre-operative planning software increased augmented baseplate use to minimize the glenoid reaming. The navigation system allows placement of the baseplate accurately, according to the pre-operative plan. Furthermore, the navigation system enables monitoring of screw length and direction in real time.

Superb Microvascular Imaging法を用いた手根管症候群での正中神経内血流評価 健康成人との比較
遠藤 健, 松井 雄一郎, 河村 太介, 松居 祐樹, 鈴木 智亮, 小林 英之, 岩崎 倫政
末梢神経, 33, 2, 268, 268, 日本末梢神経学会, 2022年12月
日本語

Safety of early posterior fusion surgery without endovascular embolization for asymptomatic vertebral artery occlusion associated with cervical spine trauma.
Mitsuru Asukai, Hiroki Ushirozako, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Yukihiro Matsuyama
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 31, 12, 3392, 3401, 2022年12月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Vertebral artery occlusion (VAO) is an increasingly recognized complication of cervical spine trauma. However, the management strategy of VAO remains heavily debated. Therefore, the aim of this retrospective study was to investigate the safety of early fusion surgery for traumatic VAO. METHODS: This study included a total of 241 patients (average age 64.7 years; 201 men) who underwent early surgical treatment for acute cervical spine injury between 2012 and 2019. The incidence of VAO, cerebral infarction rates, the recanalization rates, and cerebral thromboembolism after recanalization were retrospectively analyzed. RESULTS: VAO occurred in 22 patients (9.1%). Of the 22 patients with VAO, radiographic cerebral infarction was detected in 4 patients (21.1%) at initial evaluation, including 1 symptomatic medullar infarction (4.5%) and 3 asymptomatic cerebrum infarctions. A patient who experienced right medullar infarction showed no progression of the neurologic damage. Follow-up imaging revealed that the VAOs of 9 patients (40.9%) were recanalized, and the recanalization did not correlate with clinical adverse outcomes. The arteries of the remaining 13 (59.1%) patients remained occluded and clinically silent until the final follow-up (mean final follow-up 33.0 months). CONCLUSION: Despite the lack of a concurrent control group with preoperative antiplatelet therapy or endovascular embolization for VAO, our results showed low symptomatic stroke rate (4.5%), high recanalization rate (40.9%), and low mortality rate (0%). Therefore, we believe that the indication for early stabilization surgery as management strategy of asymptomatic VAO might be one of the safe and effective treatment options for prevention of symptomatic cerebral infarction.

Efficacy of the microscopic parachute end-to-side technique for creating large-to-small venous anastomoses in free flaps in the extremities.
Makoto Motomiya, Naoya Watanabe, Mitsutoshi Ota, Kohei Shimoda, Daisuke Kawamura, Norimasa Iwasaki
JPRAS open, 34, 189, 198, 2022年12月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The availability of reliable and suitably sized veins is limited for creating free flaps to treat severe trauma and infection, and it is important to manage vessel size discrepancy between the recipient and flap veins. We evaluated the clinical outcomes of free flaps with large-to-small venous end-to-side (ETS) anastomoses using the microscopic parachute end-to-side (MPETS) anastomosis in soft tissue defects in the extremities. This procedure comprises mainly a wide-slit venotomy and parachute procedure at the heel. METHODS: We examined 24 free flaps in 23 patients given a large-to-small venous anastomosis using the MPETS technique. Patient demographics, details of vessel anastomoses, and flap outcomes and complications were obtained from medical records. RESULTS: Two veins were anastomosed in six flaps. Thirty anastomosed veins were assessed, and 24 deep veins, all of which accompanied main arteries, were chosen as recipient veins. The mean diameters were 1.5 mm in the recipient veins and 2.7 mm in the flap veins, and the mean vessel size discrepancy was 1.8-fold (range 1.3-3.3 fold). Because of the presence of venous valves at the anastomotic site, trimming of venous cusps was performed in six veins. All flaps survived, though one venous thrombosis occurred because of pedicle kinking in a case with a short pedicle. CONCLUSIONS: The MPETS technique is simple, reliable, and useful for performing various types of venous anastomoses regardless of a vessel size discrepancy and the presence of a venous valve. This may be a good option for large-to-small venous anastomosis in free flaps.

The Impact of Carpal Tunnel Release on Two-Point Discrimination, Quick Disabilities of Arm, Shoulder and Hand Score and Distal Motor Latency - A Multi-centre Prospective Study.
Yukinobu Kamiya, Akio Minami, Yasuaki Tojo, Yoji Mikami, Norimasa Iwasaki, Akinori Sakai
The journal of hand surgery Asian-Pacific volume, 27, 6, 991, 999, 2022年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The authors conducted a prospective, multi-centre study to assess the impact of carpal tunnel release (CTR) on Two-Point Discrimination (2-PD), Quick Disabilities of Arm, Shoulder and Hand Score (Q-DASH), and Distal Motor Latency (DL). The primary aim was to determine the change in outcome measurements (2-PD, Q-DASH and DL) preoperatively and postoperatively at 6 months and 1 year. The secondary aims of the study were to determine whether the postoperative outcomes were different at the 6-month and 1-year follow-up and if there was difference in outcomes based on the preoperative severity of carpal tunnel syndrome (CTS). Methods: A total of 205 hands in 171 patients underwent CTR at five hospitals over a 2-year period. A total of 110 hands in 94 patients were followed-up and analysed. The 2-PD, Q-DASH and DL were measured for all patients preoperatively and at 6 months and 1 year postoperatively. Patients were divided into two groups 'mild' and 'severe' based on pre-operative DL score (mild ≤ 8.1 msec). The change in preoperative and postoperative 2-PD, Q-DASH and DL values were compared. The change in pre-operative and post-operative 2-PD and Q-DASH values were also compared between the 'mild' and 'severe' groups. Results: The 2-PD, Q-DASH and DL showed significant improvement at 6-month and 1-year follow-ups compared to pre-operative values. However, there were no significant differences in all three parameters between the 6-month and 1-year measurements. There was significant improvement in preoperative and postoperative 2-PD and Q-DASH scores between the mild and severe groups. Conclusions: CTR is an effective treatment for patients with CTS with significant improvement in all three outcome parameters (2-PD, Q-DASH and DL). The improvement in outcome plateaus at 6 months and additional follow-up may not be useful. Level of Evidence: Level II (Therapeutic).

Changes in wrist joint contact area following radial shortening osteotomy for Kienböck’s disease
Junki Shiota, Daisuke Momma, Yuichiro Matsui, Nozomu Inoue, Eiji Kondo, Norimasa Iwasaki
Scientific Reports, 12, 1, 4001, 4001, Springer Science and Business Media LLC, 2022年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Abstract

We hypothesized that the contact area of the articular surface of the wrist joint could be evaluated using a custom-designed analytical program. The aim of the study was to compare the articular contact area of the wrist joint before and after radial shortening osteotomy for Kienböck’s disease. Nine wrists of 9 patients underwent radial shortening osteotomy for Kienböck’s disease. Computed tomography (CT) images of the wrist joint were reconstructed using a 3D reconstruction software package. Radioscaphoid and radiolunate joint contact areas and translation of the joint contact area from preoperative to postoperative were calculated using customized software. The mean Modified Mayo Wrist Score was significantly improved from 50.6 preoperatively to 83.3 at final follow-up (p < .001). Preoperatively, the pain was reported as severe in five wrists and moderate in four wrists, while at final follow-up, five patients were free from pain and four patients had mild pain with vigorous activity. The preoperative radioscaphoid joint contact area was 133.4 ± 49.5 mm² and the postoperative radioscaphoid joint contact area was 156.4 ± 73.1 mm². The preoperative radiolunate joint contact area was 194.8 ± 92.1 mm² and the postoperative radiolunate joint contact area was 148.3 ± 97.9 mm². The radial translation distance was 0.4 ± 1.2 mm, the dorsal translation distance was 0.6 ± 1.2 mm, and the proximal translation distance was 0.2 ± 0.4 mm. CT-based analysis revealed that the center of the contact area translated radially following radial shortening.

Perioperative Complications of Open Spine Surgery in Older Adults over 90 Years of Age.
Takeru Tsujimoto, Masahiro Kanayama, Kota Suda, Fumihiro Oha, Miki Komatsu, Yukitoshi Shimamura, Masaru Tanaka, Daisuke Ukeba, Yuichi Hasegawa, Tomoyuki Hashimoto, Masahiko Takahata, Norimasa Iwasaki
Spine surgery and related research, 6, 6, 664, 670, 2022年11月27日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Despite perioperative risks in nonagenarian patients who undergo open spine surgery for degeneration disorder or spinal trauma being of great interest, the prevalence of complications in this group remains unclear. This study aims to examine the perioperative complications of open spine surgery in the elderly over 90 years of age. METHODS: Preoperative and intraoperative characteristics including the American Society of Anesthesiologists Physical Status (ASA-PS) class, type of surgery, and complications within 30 postoperative days were retrospectively collected from the medical records of nonagenarians who underwent open spine surgery between April 2004 and July 2019 at our spine centers. RESULTS: A total of 48 patients met the inclusion criteria of this study. All belong to ASA-PS class 2 (69%) or 3. Preoperative American Spinal Injury Association Impairment Scale grades in trauma group were grade A in 4 cases, B in 1 case, C in 5 cases, D in 11 cases, and E in 1 case. Major complications (deep surgical site infection, cardiac event, respiratory disorder, gastrointestinal hemorrhage, and renal failure) occurred in 13 cases, and the rate of overall perioperative complications was 45.8%. One patient who underwent cervical stabilization for cervical fracture dislocation died at postoperative 13 days due to respiratory disorder. The rates of major complications and overall perioperative complications were 3.6% and 14.3% in the degenerative group and 45.5% and 81.8% in the trauma group, respectively. Especially in the trauma group, respiratory disorder occurred in 7 cases, delirium in 11 cases, and urinary tract infection in 5 cases. CONCLUSIONS: Although the perioperative complication rate reached 81.8% in spinal trauma cases, the complication rate in degenerative disorders was relatively low as 14.3%. Open spine surgery for degenerative disorders can be relatively safe even in nonagenarians, whereas the risks of perioperative complications, including respiratory disorder and delirium, were high in spinal trauma cases.

Posterolateral full-endoscopic debridement and irrigation is effective in treating thoraco-lumbar pyogenic spondylodiscitis, except in cases with large abscess cavities
Katsuhisa Yamada, Masahiko Takahata, Ken Nagahama, Akira Iwata, Tsutomu Endo, Ryo Fujita, Hiroyuki Hasebe, Takashi Ohnishi, Hideki Sudo, Manabu Ito, Norimasa Iwasaki
European Spine Journal, 32, 3, 859, 866, Springer Science and Business Media LLC, 2022年11月24日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To determine the efficacy and poor prognostic factors of posterolateral full-endoscopic debridement and irrigation (PEDI) surgery for thoraco-lumbar pyogenic spondylodiscitis. METHODS: We included 64 patients (46 men, 18 women; average age: 63.7 years) with thoracic/lumbar pyogenic spondylodiscitis who had undergone PEDI treatment and were followed up for more than 2 years. Clinical outcomes after PEDI surgery were retrospectively investigated to analyze the incidence and risk factors for prolonged and recurrent infection. RESULTS: Of 64 patients, 53 (82.8%) were cured of infection after PEDI surgery, and nine (17.2%) had prolonged or recurrent infection. Multivariate analysis demonstrated that significant risk factors for poor prognosis included a large intervertebral abscess cavity (P = 0.02) and multilevel intervertebral infections (P < 0.05). CONCLUSION: PEDI treatment is an effective, minimally invasive procedure for pyogenic spondylodiscitis. However, a large intervertebral abscess space could cause instability at the infected spinal column, leading to prolonged or recurrent infection after PEDI. In cases with a large abscess cavity with or without vertebral bone destruction, endoscopic drainage alone may have a poor prognosis, and spinal fixation surgery could be considered.

Risk factors of AIS C incomplete cervical spinal cord injury for poor prognosis-The significance of anorectal evaluation.
Osahiko Tsuji, Kota Suda, Takehiro Michikawa, Masahiko Takahata, Masahiro Ozaki, Tsunehiko Konomi, Satoko Harmon-Matsumoto, Miki Komatsu, Chikara Ushiku, Yusuke Menjo, Seiji Iimoto, Kota Watanabe, Masaya Nakamura, Morio Matsumoto, Akio Minami, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 28, 6, 1227, 1233, 2022年11月02日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Although the prognosis of incomplete cervical spinal cord injury (SCI) diagnosed as American Spinal Injury Association Impairment Scale grade C (AIS C) is generally favorable, some patients remain non-ambulatory. The present study explored the clinical factors associated with the non-ambulatory state of AIS C patients. METHODS: This study was a single-center retrospective observational study. Seventy-three participants with AIS C on admission were enrolled and divided into two groups according to ambulatory ability after one year. Prognostic factors of SCI were compared in ambulatory (A-group) and non-ambulatory participants (NA-group). Univariable and multivariable logistic regression analyses were performed on demographic information, medical history, mechanism of injury, presence of fracture, ASIA motor scores (MS) of the extremities, neurological findings, including an anorectal examination on admission, and imaging findings. RESULTS: Forty-one patients were included in the A-group and 32 in the NA-group. Univariable analysis revealed that the following factors were related to poor outcomes (p < 0.05): older age, history of cerebrovascular disorder, impairment/absence of S4-5 sensory score, deep anal pressure (DAP) (-), voluntary anal contraction (VAC) (-), anorectal tone (-), anal wink reflex (-), and low MS of the upper and lower extremities. In the multivariable analysis using age, presence or absence of sacral abnormality, and history of cerebrovascular disorders (adjusted for these three factors), older age and presence of sacral abnormality on admission were independent risk factors for a non-ambulatory state at the 1-year follow-up. CONCLUSIONS: Incomplete AIS C SCI individuals with older age and/or impairment of anorectal examination could remain non-ambulatory at 1-year follow-up.

乳児股関節健診推奨項目は発育性股関節形成不全の予測因子となりうるか　　　　　　　　　　　　　　　
大橋 佑介, 清水 智弘, 清水 寛和, 小川 拓也, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本小児整形外科学会雑誌, 31, 3, S54, S54, (一社)日本小児整形外科学会, 2022年11月
日本語

発育性股関節形成不全の二次検診受診時期による装具治療の有無の検討　　　　　　　　　　　　　　　
小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本小児整形外科学会雑誌, 31, 3, S54, S54, (一社)日本小児整形外科学会, 2022年11月
日本語

リーメンビューゲル治療前に水平牽引を行うことで脱臼整復率は改善する　　　　　　　　　　　　　　　
小川 拓也, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本小児整形外科学会雑誌, 31, 3, S66, S66, (一社)日本小児整形外科学会, 2022年11月
日本語

Angulated Innominate Osteotomyにおける術中三次元矯正と術後1年単純X線との関連　　　　　　　　　　　　　　　
小川 拓也, 高橋 大介, 清水 智弘, 宮崎 拓自, 岩崎 倫政
日本小児整形外科学会雑誌, 31, 3, S71, S71, (一社)日本小児整形外科学会, 2022年11月
日本語

最先端医療の今 免疫細胞由来因子Cardiotrophin-Like Cytokine Factor 1(CLCF1)の骨粗鬆症モデルマウスにおける検討　　　　　　　　　　　　　　　
横田 隼一, 高橋 大介, 照川 アラー, 清水 智弘, 岩崎 倫政
Medical Science Digest, 48, 12, 604, 608, (株)ニュー・サイエンス社, 2022年11月
日本語, 免疫細胞由来分子であるCLCF1の発現が,閉経後の骨粗鬆症患者で減少していることが報告されており,CLCF1が骨代謝制御に関与すると考えられる。そこで本研究では,骨粗鬆症におけるCLCF1の機能を検証した。CLCF1投与により,卵巣摘出骨粗鬆症モデルマウスの骨量減少が抑制された。同様に,in vitroでCLCF1は破骨細胞数と象牙質スライスでの骨吸収領域が有意に減少させ,骨芽細胞の分化には抑制効果を示さなかった。RNA-seqによる網羅的解析により,CLCF1の作用にはインターフェロンシグナル(IFN)活性化とNF-κBシグナル抑制が関与していた。これらの結果から,CLCF1はIFN活性化とNF-κB抑制を介して,骨芽細胞の骨形成に影響を与えずに,破骨細胞分化と骨吸収を抑制する。CLCF1は骨粗鬆症の新規治療薬として有用である可能性が示唆された。(著者抄録)

人工関節置換術後無菌性緩みに対するポリエチレンライナー放射線架橋線量の検討　　　　　　　　　　　　　　　
塩田 惇喜, アラー照川, 高橋 大介, 清水 智弘, 松前 元, 江畑 拓, 横田 隼一, 西田 善郎, 北原 圭介, 徳廣 泰貴, 岩崎 倫政
日本バイオマテリアル学会大会予稿集, 44回, 145, 145, 日本バイオマテリアル学会, 2022年11月
日本語

Ferroptosisを標的としたポリエチレン摩耗粉による炎症性骨吸収抑制効果　　　　　　　　　　　　　　　
横田 隼一, 照川 アラー, 照川 ヘンド, 西田 善郎, 塩田 惇喜, 北原 圭太, 徳廣 泰貴, 清水 智弘, 高橋 大介, 岩崎 倫政
日本バイオマテリアル学会大会予稿集, 44回, 410, 410, 日本バイオマテリアル学会, 2022年11月
日本語

Utility of thermal image scanning in screening for febrile patients in cold climates.
Takuya Ogawa, Yukinori Tsukuda, Yuki Suzuki, Shigeto Hiratsuka, Ryo Inoue, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 27, 6, 1333, 1337, 2022年11月, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Infrared thermography (IRT) for fever screening systems was introduced in not only general hospitals, but also orthopedic hospitals as a countermeasure against the spread of coronavirus disease 2019 (COVID-19). Despite the widespread use of IRT, various results have shown low and high efficacies, so the utility of IRT is controversial, especially in cold climates. The aims of this study were to investigate the utility of IRT in screening for fever in a cold climate and to devise suitable fever screening in orthopedic surgery for COVID-19. METHODS: A total of 390 orthopedic surgery patients were enrolled to the outdoor group and 210 hospital staff members were enrolled to the indoor group. Thermographic temperature at the front of the face in the outdoor group was immediately measured after entering our hospital from a cold outdoor environment. Measurements for the indoor group were made after staying in the hospital (environmental temperature, 28 °C) for at least 5 h. Body temperature was then measured using an axillary thermometer >15 min later in both groups. RESULTS: In the outdoor group, mean thermographic temperature was significantly lower than axillary temperature and IRT could not detect febrile patients with axillary temperatures >37.0 °C. Mean thermographic temperature was significantly lower in the outdoor group than in the indoor group. Sensitivity was 11.5% for the outdoor group, lower than that for the indoor group. CONCLUSIONS: We verified that IRT was not accurate in a cold climate. IRT is inadequate as a screening method to accurately detect febrile individuals, so we believe that stricter countermeasures for second screening need to be employed to prevent nosocomial infections and disease clusters of COVID-19, even in orthopedic hospitals.

Long-Term Clinical Course of Patients After Decompression and Posterior Instrumented Fusion Surgery for Thoracic Ossification of the Posterior Longitudinal Ligament: An Average Follow-Up of 18 years
Masahiko Takahata, Tsutomu Endo, Yoshinao Koike, Kuniyoshi Abumi, Kota Suda, Ryo Fujita, Toshifumi Murakami, Hideki Sudo, Katsuhisa Yamada, Takashi Ohnishi, Katsuro Ura, Daisuke Ukeba, Norimasa Iwasaki
Global Spine Journal, 14, 4, 219256822211355, 219256822211355, SAGE Publications, 2022年10月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Study Design

Retrospective observational study.

Objectives

To evaluate the long-term recurrence rates and functional status of patients with thoracic ossification of the posterior longitudinal ligament (OPLL) after decompression and posterior fusion surgery.

Methods

Thirty-seven consecutive patients who underwent posterior thoracic spine surgery at a single institution were retrospectively reviewed. The long-term neurological and functional outcomes of 25 patients who were followed up for ≥10 years after surgery were assessed. Factors associated with the recurrence of myelopathy were also analyzed.

Results

The mean preoperative Japanese Orthopaedic Association score was 3.7, which improved to 6.5 at postoperative year 2 and declined to 6.0 at a mean follow-up of 18 years. No patient experienced a relapse of myelopathy due to OPLL within the instrumented spinal segments. However, 15 (60%) patients experienced late neurological deterioration, 10 of whom had a relapse of myelopathy due to OPLL or ossification of the ligamentum flavum (OLF) in the region outside the primary operative lesion, while 4 developed myelopathy due to traumatic vertebral fracture of the ankylosed spine. Young age, a high body mass index, and lumbar OPLL are likely associated with late neurological deterioration.

Conclusions

Decompression and posterior instrumented fusion surgery is a reliable surgical procedure with stable long-term clinical outcomes for thoracic OPLL. However, as OPLL may progress through the spine, attention should be paid to the recurrence of paralysis due to OPLL or OLF in regions other than the primary operative lesion and vertebral fractures of the ankylosed spine after surgery for thoracic OPLL.

Molecular and Regenerative Characterization of Repair and Non-repair Schwann Cells.
Tomoaki Suzuki, Ken Kadoya, Takeshi Endo, Norimasa Iwasaki
Cellular and molecular neurobiology, 43, 5, 2165, 2178, 2022年10月12日, ［国際誌］
英語, 研究論文（学術雑誌）, Although evidence has accumulated to indicate that Schwann cells (SCs) differentiate into repair SCs (RSCs) upon injury and that the unique phenotype of these cells allow them to provide support for peripheral nerve regeneration, the details of the RSCs are not fully understood. The findings of the current study indicate that the RSCs have enhanced adherent properties and a greater capability to promote neurite outgrowth and axon regeneration after peripheral nerve injury, compared to the non-RSCs. Further, transcriptome analyses have demonstrated that the molecular signature of the RSCs is distinctly different from that of the non-RSCs. The RSCs upregulate a group of genes that are related to inflammation, repair, and regeneration, whereas non-RSCs upregulate genes related to myelin maintenance, Notch, and aging. These findings indicate that the RSCs have markedly different cellular, regenerative, and molecular characteristics compared to the non-RSCs, even though the RSCs were just derived from non-RSCs upon injury, thus providing the basis for understanding the mechanisms related to SC mediated repair after peripheral nerve injury.

Histochemical assessment of accelerated bone remodeling and reduced mineralization in Il-6 deficient mice.
Yasuhito Moritani, Tomoka Hasegawa, Tomomaya Yamamoto, Hiromi Hongo, Yimin, Miki Abe, Hirona Yoshino, Ko Nakanishi, Haruhi Maruoka, Hotaka Ishizu, Tomohiro Shimizu, Masahiko Takahata, Norimasa Iwasaki, Minqi Li, Kanchu Tei, Yoichi Ohiro, Norio Amizuka
Journal of oral biosciences, 64, 4, 410, 421, 2022年10月11日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Interleukin-6 (IL-6) contributes to the regulation of functions in various tissues and organs. Even though IL-6 has been reported to modulate bone metabolism in previous studies, this finding is controversial. This study aims to evaluate the possible involvement of IL-6 in bone metabolism by examining the histological activity of osteoblasts and osteoclasts in the femora of Il-6 deficient (Il-6-/-) mice. METHODS: Eight-week-old male Il-6-/- mice and their wild-type littermates were fixed with a paraformaldehyde solution, and their femora were extracted for micro-CT analysis, immunohistochemistry, and real-time PCR analysis. RESULTS: Il-6-/- femora showed an increased bone volume/tissue volume (TV) but a reduced bone mineral density compared with the wild-type. Furthermore, the tissue-nonspecific alkaline phosphatase positive area/TV ratio, the expression of Runx2, Osterix, and Rankl, and the number of tartrate-resistant acid phosphatase-positive osteoclasts were all increased in the Il-6-/- mice. A considerable number of unmineralized areas within the bone matrix and abundant sclerostin-reactive osteocytes were observed in Il-6-/- femoral metaphyses but not in the wild-type. Interestingly, the gene expression of Cd206 was elevated in Il-6-/- femora, and many F4/80-positive macrophages/monocytes and CD206-immunoreactive macrophages in the primary trabeculae had migrated closer to the growth plate, where intense RANKL immunoreactivity was detected. These results suggest that, in an IL-6-deficient state, CD206-positive macrophages may differentiate into osteoclasts when in contact with RANKL-reactive osteoblastic cells. CONCLUSION: In a state of IL-6 deficiency, the population and cell activities of osteoblast, osteoclasts, and macrophages seemed to be facilitated, except for the reduced mineralization in bone.

Giant Geode at the Humeral Head in the Rheumatoid Shoulder Treated With Allograft Bone Grafting and Shoulder Arthroplasty.
Atsushi Urita, Takeshi Endo, Norimasa Iwasaki, Hiroshi Taneichi
The Journal of rheumatology, 49, 10, 1174, 1175, 2022年10月, ［国際誌］
英語, 研究論文（学術雑誌）

Occurrence Rate of Cyclops Lesion After Anatomic Double-Bundle ACL Reconstruction: Comparison Between Remnant Tissue Preservation and Resection Methods.
Ryosuke Hishimura, Eiji Kondo, Yuki Suzuki, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Daisuke Momma, Tomonori Yagi, Kazunori Yasuda, Norimasa Iwasaki
Orthopaedic journal of sports medicine, 10, 10, 23259671221130688, 23259671221130688, 2022年10月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The occurrence rate of cyclops lesion after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction with remnant tissue preservation remains unclear. HYPOTHESIS: The study hypotheses were as follows: (1) the occurrence rate of cyclops lesion will be comparable between the remnant-preserving and remnant-resecting ACL reconstruction methods, and (2) there will be no significant differences in clinical outcomes between the remnant-preserving and remnant-resecting procedures. METHODS: This retrospective comparative study involved 177 patients who underwent unilateral anatomic double-bundle ACL reconstruction using hamstring tendon autografts from 2014 to 2018 at our hospital. According to the Crain classification of ACL remnant tissue, 98 patients with remnant types I, II, or III underwent the remnant-preserving procedure (group A), and the remaining 79 patients with remnant type IV underwent the remnant-resecting procedure (group B). All patients underwent second-look arthroscopy. Patients were evaluated according to arthroscopic and clinical results at postoperative 15.2 ± 8.4 months (mean ± SD). Statistical comparisons between groups were made using the paired Student t test, chi-square test, and Fisher exact test. STUDY DESIGN: Cohort study; Level of evidence, 3. RESULTS: At second-look arthroscopy, the incidence of cyclops lesions was significantly higher in group B than in group A (29.1% vs 13.3%; P = .0139). Cyclops lesions were divided into 4 locations: femoral side (type 1), midsubstance (type 2), tibial side (type 3), and anterior (type 4) of the ACL graft. The ratio of the tibial-side cyclops lesion (type 3) was significantly higher in group B than in group A (P = .0354). There were no significant differences in the clinical evaluation scores between the procedures. Side-to-side anterior laxity was significantly less in group A than in group B (0.7 vs 1.6 mm; P = .0035). Concerning postoperative laceration and synovium coverage of the grafts, group A was significantly better than group B (P < .0001). CONCLUSION: In this cohort of patients undergoing double-bundle ACL reconstruction, resection of the ACL remnant was associated with a significantly higher rate of cyclops lesion formation when compared with preservation of the remnant.

High-Throughput Screening Assay Identifies Berberine and Mubritinib as Neuroprotection Drugs for Spinal Cord Injury via Blood-Spinal Cord Barrier Protection.
Yuki Suzuki, Shinsuke Nakagawa, Takeshi Endo, Akihito Sotome, Rufei Yuan, Tsuyoshi Asano, Satoko Otsuguro, Katsumi Maenaka, Norimasa Iwasaki, Ken Kadoya
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 19, 6, 1976, 1991, 2022年10月, ［国際誌］
英語, 研究論文（学術雑誌）, Because the breakdown of the blood-brain spinal cord barrier (BBSCB) worsens many central nervous system (CNS) diseases, prevention of BBSCB breakdown has been a major therapeutic target, especially for spinal cord injury (SCI). However, effective drugs that protect BBSCB function have yet to be developed. The purpose of the current study was 1) to develop a high-throughput screening assay (HTSA) to identify candidate drugs to protect BBSCB function, 2) to identify candidate drugs from existing drugs with newly developed HTSA, and 3) to examine the therapeutic effects of candidate drugs on SCI. Our HTSA included a culture of immortalized human brain endothelial cells primed with candidate drugs, stress with H2O2, and evaluation of their viability. A combination of the resazurin-based assay with 0.45 mM H2O2 qualified as a reliable HTSA. Screening of 1,570 existing drugs identified 90 drugs as hit drugs. Through a combination of reproducibility tests, exclusion of drugs inappropriate for clinical translation, and dose dependency tests, berberine, mubritinib, and pioglitazone were identified as a candidate. An in vitro BBSCB functional test revealed that berberine and mubritinib, but not pioglitazone, protected BBSCB from oxygen-glucose deprivation and reoxygenation stress. Additionally, these two drugs minimized BBSCB breakdown 1 day after cervical SCI in mice. Furthermore, berberine and mubritinib reduced neuronal loss and improved gait performance 8 weeks after SCI. Collectively, the current study established a useful HTSA to identify potential neuroprotective drugs by maintaining BBSCB function and demonstrated the neuroprotective effect of berberine and mubritinib after SCI.

Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma.
Yasuhiro Yamamoto, Ken Kadoya, Mohamad Alaa Terkawi, Takeshi Endo, Kohtarou Konno, Masahiko Watanabe, Satoshi Ichihara, Akira Hara, Kazuo Kaneko, Norimasa Iwasaki, Muneaki Ishijima
Life science alliance, 5, 10, 2022年10月, ［国際誌］
英語, 研究論文（学術雑誌）, Although inflammation is indispensable for the repair process in Wallerian degeneration (WD), the role of neutrophils in the WD repair process remains unclear. After peripheral nerve injury, neutrophils accumulate at the epineurium but not the parenchyma in the WD region because of the blood-nerve barrier. An increase or decrease in the number of neutrophils delayed or promoted macrophage infiltration from the epineurium into the parenchyma and the repair process in WD. Abundant neutrophil extracellular traps (NETs) were formed around neutrophils, and its inhibition dramatically increased macrophage infiltration into the parenchyma. Furthermore, inhibition of either MIF or its receptor, CXCR4, in neutrophils decreased NET formation, resulting in enhanced macrophage infiltration into the parenchyma. Moreover, inhibiting MIF for just 2 h after peripheral nerve injury promoted the repair process. These findings indicate that neutrophils delay the repair process in WD from outside the parenchyma by inhibiting macrophage infiltration via NET formation and that neutrophils, NETs, MIF, and CXCR4 are therapeutic targets for peripheral nerve regeneration.

Establishment of the removal method of undifferentiated induced pluripotent stem cells coexisting with chondrocytes using R-17F antibody.
Takuji Miyazaki, Hisatoshi Hanamatsu, Tomohiro Onodera, Jun-Ichi Furukawa, Liang Xu, Kentaro Homan, Rikiya Baba, Toshisuke Kawasaki, Norimasa Iwasaki
Regenerative medicine, 17, 11, 793, 803, 2022年09月26日, ［国際誌］
英語, 研究論文（学術雑誌）, Aim: Tumorigenicity of residual undifferentiated induced pluripotent stem cells (iPSCs) is a major concern. The purpose of this study was to investigate the optimal conditions for removal of iPSCs using R-17F antibody, which recognizes specific glycosphingolipids glycans on undifferentiated iPSCs and exhibits selective cytotoxicity to iPSCs. Materials & methods: After adding of R-17F and secondary antibody to co-cultured iPSCs and chondrocytes, residual iPSCs were quantitatively evaluated by iPS specific glycome analysis. Results: Undifferentiated iPSCs were sufficiently removed using R-17F in combination with an equal amount of a secondary antibody. Furthermore, teratomas were not observed upon transplantation of co-cultured cells pretreated under the same conditions into testes of immunodeficient mice. Conclusion: This removal method incorporating R-17F may be useful for regenerative medicine using iPSCs.

Glycosphingolipid GM3 prevents albuminuria and podocytopathy induced by anti-nephrin antibody.
Nagako Kawashima, Shokichi Naito, Hisatoshi Hanamatsu, Masaki Nagane, Yasuo Takeuchi, Jun-Ichi Furukawa, Norimasa Iwasaki, Tadashi Yamashita, Ken-Ichi Nakayama
Scientific reports, 12, 1, 16058, 16058, 2022年09月26日, ［国際誌］
英語, 研究論文（学術雑誌）, Podocytopathy, which is characterized by injury to podocytes, frequently causes proteinuria or nephrotic syndrome. There is currently a paucity of effective therapeutic drugs to treat proteinuric kidney disease. Recent research suggests the possibility that glycosphingolipid GM3 maintains podocyte function by acting on various molecules including nephrin, but its mechanism of action remains unknown. Here, various analyses were performed to examine the potential relationship between GM3 and nephrin, and the function of GM3 in podocytes using podocytopathy mice, GM3 synthase gene knockout mice, and nephrin injury cells. Reduced amounts of GM3 and nephrin were observed in podocytopathy mice. Intriguingly, this reduction of GM3 and nephrin, as well as albuminuria, were inhibited by administration of valproic acid. However, when the same experiment was performed using GM3 synthase gene knockout mice, valproic acid administration did not inhibit albuminuria. Equivalent results were obtained in model cells. These findings indicate that GM3 acts with nephrin in a collaborative manner in the cell membrane. Taken together, elevated levels of GM3 stabilize nephrin, which is a key molecule of the slit diaphragm, by enhancing the environment of the cell membrane and preventing albuminuria. This study provides novel insight into new drug discovery, which may offer a new therapy for kidney disease with albuminuria.

骨粗鬆症における骨マクロファージのサブタイプ変化とその機能解析
松前 元, 照川 アラー, 横田 隼一, 江畑 拓, 高橋 大介, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1536, S1536, (公社)日本整形外科学会, 2022年09月
日本語

ウェアラブルデバイスの有用性 足部ウェアラブルデバイスによる歩行解析の妥当性と臨床研究の実際
角家 健, 宝満 健太郎, 岩崎 倫政
日本関節病学会誌, 41, 3, 209, 209, (一社)日本関節病学会, 2022年09月
日本語

AIと診断・治療 経椎間孔アプローチ進入角度に基づいたKambin's triangleの三次元的形態解析 AIにて自動作成した3D腰椎神経根画像を用いて
山田 勝久, 長濱 賢, 安倍 雄一郎, 日向寺 義則, 須藤 英毅, 遠藤 努, 大西 貴士, 長谷部 弘之, 藤田 諒, 高畑 雅彦, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1740, S1740, (公社)日本整形外科学会, 2022年09月
日本語

ステロイド関連特発性大腿骨頭壊死症における多発骨壊死の関連因子　　　　　　　　　　　　　　　
菅原 悠太郎, 清水 智弘, 横田 隼一, 石津 帆高, 宮崎 拓自, 小川 拓也, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 41, 3, 148, 148, (一社)日本関節病学会, 2022年09月
日本語

整形外科領域におけるAIの応用 ハイブリット人工知能を用いた寛骨臼形成不全の自動解析システムの開発　　　　　　　　　　　　　　　
清水 智弘, 高橋 大介, 清水 寛和, 岩崎 倫政
日本関節病学会誌, 41, 3, 206, 206, (一社)日本関節病学会, 2022年09月
日本語

急速破壊型股関節症におけるNLRP3インフラマソーム経路を介した高度滑膜炎関与の検証　　　　　　　　　　　　　　　
横田 隼一, 清水 智弘, 小川 拓也, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 41, 3, 229, 229, (一社)日本関節病学会, 2022年09月
日本語

CLCF1投与によるインターフェロンシグナルの活性化を介した骨粗鬆症モデルマウスの骨量減少抑制効果について
横田 隼一, 松前 元, 江畑 拓, 照川 ヘンド, 清水 智弘, 高橋 大介, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1537, S1537, (公社)日本整形外科学会, 2022年09月
日本語

アネキシンA1(AnxA1)の炎症性骨吸収抑制効果の検討 人工関節術後無菌性緩みの治療薬開発にむけて
照川 ヘンド, 西田 善郎, 松前 元, 江畑 拓, 横田 隼一, 高橋 大介, 清水 智弘, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1543, S1543, (公社)日本整形外科学会, 2022年09月
日本語

骨リモデリング調節におけるアネキシンA1の機能解析
西田 善郎, 松前 元, 江畑 拓, 横田 隼一, 照川 ヘンド, 塩田 惇喜, 北原 圭太, 清水 智弘, 高橋 大介, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1549, S1549, (公社)日本整形外科学会, 2022年09月
日本語

炎症収束型好中球由来細胞外小胞による軟骨細胞抗異化作用の検討
北原 圭太, 江畑 拓, 清水 智弘, 浅野 毅, 照川 アラー, 高橋 大介, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1559, S1559, (公社)日本整形外科学会, 2022年09月
日本語

変性軟骨細胞が骨細胞機能に及ぼす影響 変形性関節症における軟骨-軟骨下骨連関機序の解明
徳廣 泰貴, 江畑 拓, 濱崎 雅成, 松前 元, 高橋 大介, 清水 智弘, 照川 アラー, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1573, S1573, (公社)日本整形外科学会, 2022年09月
日本語

軟骨細胞パイロトーシス制御による軟骨変性抑制効果
江畑 拓, 照川 アラー, 横田 隼一, 照川 ヘンド, 松前 元, 清水 智弘, 高橋 大介, 小野寺 智洋, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1580, S1580, (公社)日本整形外科学会, 2022年09月
日本語

人工股関節全置換術におけるヘッド延長の脚長、オフセット、可動域に与える影響 A computer simulation study
宮崎 拓自, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1710, S1710, (公社)日本整形外科学会, 2022年09月
日本語

機械学習予測モデルを介した脆弱性骨折術後患者の再骨折予測因子抽出の検討　　　　　　　　　　　　　　　
清水 寛和, 清水 智弘, 遠田 健, 石田 雄介, 石津 帆高, 伊勢 昂生, 田中 伸哉, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1797, S1797, (公社)日本整形外科学会, 2022年09月
日本語

乳児股関節超音波画像に対する人工知能解析システムの開発　　　　　　　　　　　　　　　
清水 寛和, 清水 智弘, 遠田 健, 児矢野 英典, 高橋 大介, 石田 雄介, 小川 拓也, 田中 伸哉, 岩崎 倫政
日本整形外科学会雑誌, 96, 8, S1797, S1797, (公社)日本整形外科学会, 2022年09月
日本語

In Reply to the Letter to the Editor Regarding "Does Primary Tumor Resection in Patients with Metastatic Primary Mobile Vertebral Column Sarcoma Improve the Survivals?".
Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Norimasa Iwasaki
World neurosurgery, 165, 210, 210, 2022年09月, ［国際誌］
英語

Matrix Vesicle-Mediated Mineralization and Osteocytic Regulation of Bone Mineralization.
Tomoka Hasegawa, Hiromi Hongo, Tomomaya Yamamoto, Miki Abe, Hirona Yoshino, Mai Haraguchi-Kitakamae, Hotaka Ishizu, Tomohiro Shimizu, Norimasa Iwasaki, Norio Amizuka
International journal of molecular sciences, 23, 17, 2022年09月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO43-) flow into the vesicles via membrane transporters and enzymes located on the vesicles' membranes, while calcium ions (Ca2+), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca2+ and PO43- in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle's membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process. The mechanisms of this phenomenon remain unclear, but osteocytes may play a key role; it is assumed that osteocytes enable the transport of Ca2+ and PO43- through the canaliculi of the osteocyte network, as well as regulate the mineralization of the surrounding bone matrix via the Phex/SIBLINGs axis. Thus, bone mineralization is biologically regulated by osteoblasts and osteocytes.

Correlation between carpal rotational alignment and postoperative wrist range of motion following total wrist arthroplasty
Mitsutoshi Ota, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Takeshi Endo, Norimasa Iwasaki
BMC Musculoskeletal Disorders, 23, 1, 821, 821, Springer Science and Business Media LLC, 2022年08月30日, ［国際誌］
英語, 研究論文（学術雑誌）, Abstract

Background

Although total wrist arthroplasty (TWA) has become a common treatment option for wrists with damage due to rheumatoid arthritis (RA), the optimal implant axial alignment for TWA has been inadequately studied. This study was performed to investigate the relationships between implant alignment and carpal rotational alignment and the wrist range of motion (ROM) following TWA.

Methods

This study included 18 patients who underwent TWA using a DARTS® Total Wrist System (Teijin Nakashima Medical, Okayama, Japan) for wrist RA. Pre- and 6-month postoperative computed tomography scans were performed, including the radial volar line (Rv), capitohamate axis (CH), and Rv-CH angle in axial scans. The wrist ROM was also measured. The relationship between the Rv-CH angle and ROM was examined.

Results

The mean Rv-CH angle showed significant wrist pronation from 73.0° to 83.4° postoperatively. We observed a significant positive correlation (0.58) between the postoperative Rv-CH angle and extension and a significant negative correlation (− 0.56) between the postoperative Rv-CH angle and flexion.

Conclusions

Implantation of the DARTS® TWA prosthesis resulted in pronation of the carpal axial alignment, which was correlated with postoperative wrist extension. The volar cortex of the distal radius can be a novel reference axis for adequate implant placement.

Comparison of clinical features between patients with bone and soft tissue fibrosarcomas.
Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki
Journal of surgical oncology, 126, 7, 1299, 1305, 2022年08月08日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND AND OBJECTIVES: Fibrosarcomas predominantly arise in soft tissues, but can also develop in bone. Because of their rarity, whether bone development has an impact on clinical features has not been addressed. METHODS: We included fibrosarcoma patients diagnosed between 1983 and 2016 in the Surveillance, Epidemiology, and End Results database. Differences in clinical features between fibrosarcoma of bone (FS-B) and fibrosarcoma of soft tissue (FS-ST) were investigated. RESULTS: After excluding patients without information regarding cause of death, site of origin, distant tumor or survival, 1443 patients were included. Of those, 98 patients had FS-B. Patients with FS-B were younger, more frequently male, with fibrosarcomas that more often developed in an extremity and were histologically high-grade. In contrast, no difference in potential to metastasize was observed. Survival was almost equal between FS-B and FS-ST (FS-B/FS-ST: cancer-specific survival, hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.8-1.7; overall survival, HR: 1.3, 95% CI: 0.9-1.7). CONCLUSIONS: Our results clearly indicated that patient backgrounds differed, such as younger age and greater tendencies to affect males, develop in an extremity and show high-grade tumor in patients with FS-B. In contrast, no differences were observed in distant metastatic potential or survival.

人工知能を用いた乳児股関節超音波健診システムの開発
清水 寛和, 清水 智弘, 高橋 大介, 小川 拓也, 岩崎 倫政
東日本整形災害外科学会雑誌, 34, 3, 236, 236, 東日本整形災害外科学会, 2022年08月
日本語

臼蓋骨欠損に対してKT plateとMetal meshを用いた人工股関節再置換術の術後成績,X線学的指標の比較検討
石津 帆高, 清水 智弘, 笹沢 史生, 金山 雅弘, 高橋 大介, 岩崎 倫政
東日本整形災害外科学会雑誌, 34, 3, 254, 254, 東日本整形災害外科学会, 2022年08月
日本語

機械学習予測モデルを介した脆弱性骨折術後患者の再骨折予測因子抽出の検討
清水 寛和, 清水 智弘, 石津 帆高, 岩崎 倫政
東日本整形災害外科学会雑誌, 34, 3, 368, 368, 東日本整形災害外科学会, 2022年08月
日本語

骨粗鬆症の逐次療法 ビスホスホネートからの逐次療法　　　　　　　　　　　　　　　
清水 智弘, 石津 帆高, 有田 皓介, 岩崎 倫政
日本骨粗鬆症学会雑誌, 8, Suppl.1, 10, 10, (一社)日本骨粗鬆症学会, 2022年08月
日本語

大腿骨近位部骨折術後の骨粗鬆症治療状況と治療率改善への取り組み 骨折リエゾンサービス導入前後の比較　　　　　　　　　　　　　　　
小川 裕生, 下段 俊, 福島 瑛, 池 翔太, 竹内 博紀, 百貫 亮太, 梅本 貴央, 清水 智弘, 高橋 大介, 岩崎 倫政
日本骨粗鬆症学会雑誌, 8, Suppl.1, 112, 112, (一社)日本骨粗鬆症学会, 2022年08月
日本語

閉経後女性ランナーと非女性ランナーにおける骨密度および骨代謝マーカーの検討　　　　　　　　　　　　　　　
後藤 佳子, 清水 智弘, 門間 太輔, 清水 幸衣, 小林 範子, 笠原 靖彦, 吉本 尚, 近藤 英司, 岩崎 倫政
日本骨粗鬆症学会雑誌, 8, Suppl.1, 119, 119, (一社)日本骨粗鬆症学会, 2022年08月
日本語

コロナ禍で始まった大腿骨近位部骨折リエゾンサービス1年後の骨粗鬆症加療状況　　　　　　　　　　　　　　　
下段 俊, 清水 智弘, 梅本 貴央, 百貫 亮太, 竹内 博紀, 小川 裕生, 池 翔太, 福島 瑛, 佐藤 知哉, 高橋 大介, 岩崎 倫政
日本骨粗鬆症学会雑誌, 8, Suppl.1, 174, 174, (一社)日本骨粗鬆症学会, 2022年08月
日本語

脆弱性骨折をきたした関節リウマチ患者の再骨折リスク　　　　　　　　　　　　　　　
石津 帆高, 清水 寛和, 清水 智弘, 江畑 拓, 小川 裕生, 宮野 真博, 有田 皓介, 大橋 佑介, 岩崎 倫政
日本骨粗鬆症学会雑誌, 8, Suppl.1, 178, 178, (一社)日本骨粗鬆症学会, 2022年08月
日本語

脆弱性骨盤骨折患者の骨粗鬆症加療状況　　　　　　　　　　　　　　　
大上 哲郎, 下段 俊, 清水 智弘, 高橋 大介, 岩崎 倫政
Hip Joint, 48, 401, 403, 日本股関節学会, 2022年08月
日本語, 当院で2018～2020年に骨盤骨折の病名登録をされた患者のうち、交通事故などによる高エネルギー外傷、転移性骨腫瘍による病的骨折を除外した38例を対象とし、「脆弱性骨折既往の有無」「骨盤骨折受傷前後の骨粗鬆症治療の有無」「二次骨折の有無」などについて調査した。脆弱性骨折の既往は9例(24%)にあり、内訳は大腿骨近位部骨折6例、椎体骨折3例であった。骨盤骨折受傷前に骨粗鬆症治療を受けていたのは9例(24%)、受傷後に骨粗鬆症治療を受けたのは22例(58%)であった。二次骨折は6例(16%)に発生しており、内訳は大腿骨近位部骨折3例、椎体骨折3例であった。当院では大腿骨近位部骨折に骨粗鬆症治療介入のクリニカルパスがあり、受傷後の骨粗鬆症治療率は81%と骨盤骨折に比べて高い。今後、骨盤骨折に対してもクリニカルパス導入や骨折リエゾンサービス介入を行い、二次骨折を防止することが望まれる。

脱臼整復時にインプラント分解を生じた大腿骨頸部骨折後バイポーラー型人工骨頭の1例　　　　　　　　　　　　　　　
北原 圭太, 浅野 毅, 佐藤 恒明, 清水 智弘, 高橋 大介, 岩崎 倫政
Hip Joint, 48, 585, 588, 日本股関節学会, 2022年08月
日本語, 症例は82歳男性で、左股関節痛を主訴とした。胸部大動脈瘤に対するステント留置術後入院中に転倒して受傷した。左大腿骨頸部骨折の診断で、受傷9日目に後方アプローチでバイポーラー型人工骨頭挿入術を施行した。術後は順調に離床が進んでいたが、11日目にベッド上で患肢屈曲および内旋位となって下肢自動運動困難となっているところを発見され、透視下で後方脱臼を確認した。整復操作中にdisassemblyを生じたため、2日後に観血的再手術を施行しアウターヘッドおよびインナーヘッドのインプラントを交換した。再手術後はhip spicaを装着していたが、再びベッド上で人工骨頭のdisassemblyをきたした。再々手術では人工骨頭再置換術を行い、前捻角を増捻するとともにオフセットも増加させ、術後はdisassemblyを生じることなく経過した。脱臼肢位の理解が乏しい認知症などの症例に対しては人工股関節全置換術やモノポーラー型の使用も考慮され得る。

側臥位でtraction tableを使用した、大腿骨転子下骨折の治療成績　　　　　　　　　　　　　　　
紺野 拓也, 高橋 大介, 清水 智弘, 岩崎 倫政
Hip Joint, 48, 594, 597, 日本股関節学会, 2022年08月
日本語, 対象は2015年5月～2018年8月の22例(男性6例、女性16例、受傷時平均年齢76.3歳)で、経過観察期間は平均11.2ヵ月であった。使用固定器具はCM long 3例、CM short 2例、multifix long 2例、γ-long 15例であり、観血的整復は9例に必要とした。骨折型はSeinsheimer分類でType IIA 5例、IIB 1例、IIC 7例、IIIA 4例、V 5例であった。手術時間は平均105分、体位を取るのに要した時間は平均40分、出血量は平均154.2mLであった。術後直後の整復度はgood 13例、fair 7例、poor 2例であり、合併症は偽関節1例、遠位screw折損1例であった。仰臥位で通常通りトラクションテーブルで手術を行った転子下骨折4例と比較すると、体位を取るのに要した時間に違いはなかったが、手術時間と出血量は側臥位トラクションの方が多い傾向であった。

高齢者に対するpolished taperセメントステムを用いた人工股関節全置換術の成績　　　　　　　　　　　　　　　
山崎 秀, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
Hip Joint, 48, 193, 196, 日本股関節学会, 2022年08月
日本語, 当院でpolished taperセメントステムによる人工股関節全置換術を行った高齢者62例65関節を対象に、これらを70歳代群49例と80歳代群13例に分け、術後成績を比較検討した。その結果、術後平均観察期間は70歳代群が53.9ヵ月、80歳代群が52.7ヵ月と有意差はみられなかった。また、HHS、JHEQは両群とも術後有意に改善し、術前後のHHS、JHEQの変化量も有意差は認められなかった。尚、いずれの群も術後骨折や脱臼を生じた例はなかった。

生物学的製剤による加療を行った特発性股関節軟骨融解症の一例　　　　　　　　　　　　　　　
松岡 知樹, 清水 智弘, 有田 皓介, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
Hip Joint, 48, 474, 477, 日本股関節学会, 2022年08月
日本語, 12歳女児。誘因なく右鼠径部痛が生じたため近医を受診後、精査加療目的で当科へ紹介となった。所見ではX線で明らかな異常はみられなかったが、股関節MRIで関節液の貯留と大腿骨の骨髄浮腫がみられた。大腿骨頭軟骨下脆弱性骨折の診断のもと保存的に加療されるも、股関節は外転位となり、側彎が出現した。そこで再度、MRIを行ったところ、骨髄内の信号変化の場所が移動しており、関節穿刺では感染は否定的であった。だが、臨床経過と関節内のTNFαの上昇が認められたことから、本症例は特発性股関節軟骨融解症と診断された。治療としてNSAIDsを投与するも効果がなく、アダリムマブを投与した結果、3ヵ月後には疼痛や外転位・骨髄浮腫は改善し、関節内のTNFαも著明に減少した。

Superior capsular reconstruction for recurrent anterior shoulder dislocation with irreparable rotator cuff tear: a case report.
Keizumi Matsugasaki, Atsushi Urita, Yukinori Tsukuda, Hiroshi Taneichi, Norimasa Iwasaki
JSES reviews, reports, and techniques, 2, 3, 406, 411, 2022年08月, ［国際誌］
英語

High Rate of Radiographic Union at the Fibular Osteotomy Site With No Complications After an Acute Oblique Osteotomy and Ligation Procedure to Shorten the Fibula in High Tibial Osteotomy.
Daisuke Ueda, Kazunori Yasuda, Takuma Kaibara, Koji Yabuuchi, Jun Yamaguchi, Jun Onodera, Norimasa Iwasaki, Tomonori Yagi, Eiji Kondo
Orthopaedic journal of sports medicine, 10, 8, 23259671221117480, 23259671221117480, 2022年08月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: A fibular shortening osteotomy is needed to perform lateral closing-wedge high tibial osteotomy (LCW-HTO). To achieve this shortening, we have recently developed an acute oblique osteotomy and ligation (AO/L) procedure for the center of the fibular shaft, based on the AO procedure. PURPOSE: To compare the 2-year follow-up outcomes between the AO/L procedure and the AO procedure. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A prospective comparative cohort study was conducted involving 83 patients (83 knees) who underwent shortening osteotomy of the fibula in LCW-HTO between April 2017 and March 2019. The first consecutive 41 knees (AO group) underwent fibular osteotomy with the AO procedure. The remaining 42 knees (AO/L group) underwent fibular osteotomy with the AO/L procedure. All of the patients were evaluated for at least 2 years postoperatively via clinical and radiological assessments. To determine the time needed for complete union at the osteotomy site, we evaluated the radiographs using a radiographic union score for tibial fractures, which was modified for fibular osteotomy. Comparison of outcomes between the 2 groups was performed using the Student t test for continuous variables and the Mann-Whitney U test or Fisher exact test for discrete variables. RESULTS: Around the fibular osteotomy site, no perioperative complications were found in either group. The radiographic union score was significantly higher in the AO/L group than in the AO group (P < .0001 at 2, 3, and 6 months; P = .0290 at 12 and 24 months). The union rate at the fibular osteotomy site was significantly higher in the AO/L group (97.6%) than in the AO group (82.9%) at 12 months (P = .0290). CONCLUSION: The AO/L procedure significantly accelerated the formation of bridging callus at the fibular osteotomy site and provided a significantly higher union rate compared with the AO procedure. Both AO/L and AO procedures were free from perioperative complications. These results suggest that the AO/L procedure is clinically useful as an osteotomy procedure to shorten the fibula in LCW-HTO.

Extra-Articular Corrective Osteotomy for Malunion of Intra-Articular Fracture of the Elbow in a Child: A Case Report.
Hiroki Shibayama, Daisuke Kawamura, Norimasa Iwasaki
Journal of orthopaedic case reports, 12, 8, 27, 32, 2022年08月, ［国際誌］
英語, INTRODUCTION: Malunion of intra-articular fracture of the elbow in children is uncommon and may be difficult to treat. Intra-articular corrective osteotomies are still not commonly performed in children, and the main reason is the concern regarding the risk of osteonecrosis. We present a case of extra-articular corrective osteotomy for malunion after open reduction and internal fixation for fracture dislocation of the elbow. CASE REPORT: An 8-year-old boy was injured by a fall and he underwent an operation the day after the injury with diagnosis of lateral condyle fracture of the right humerus. He was referred to our department 4 months after the operation due to restricted range of motion. His elbow exhibited cubitus varus, and range of motion was 80° of flexion, -30° of extension, 55° of pronation, and 85° of supination. Plain radiographs showed malunion, a Baumann angle of 3°, and a tilting angle of 5°. We diagnosed this injury not as lateral condyle fracture but as posterolateral dislocation with Milch type 1 lateral condyle fracture associated with osteochondral flap fracture of the coronoid process with computed tomography images at the time of injury. Because the patient was only 8 years old, we decided to perform an extra-articular corrective osteotomy to encourage bone remodeling and improve the flexion range of motion. After the operation, the range of motion improved as 130° of flexion, -30o of extension, 85o of pronation, and 90° of supination 4 years after the operation. Plain radiographs showed that the epiphysis of the capitellum was closed, and the trochlea presented a fishtail deformity. CONCLUSION: We obtained relatively good outcomes with extra-articular corrective osteotomy, and long-term follow-up is necessary. Especially in the elbow, the injury itself may cause fishtail deformity due to avascular necrosis of the trochlea, and if an additional osteotomy is performed, the risk increases. Although there is concern about the occurrence of secondary osteoarthritis, we expect that the intra-articular deformity would be remodeled due to the patient's young age if normal elbow movement could be obtained.

Total hip arthroplasty with femoral shortening osteotomy using polished cemented stem vs. modular cementless stem in patients with Crowe type IV developmental dysplasia of the hip.
Takuji Miyazaki, Tomohiro Shimizu, Hisanori Ohura, Naoyuki Katayama, Norimasa Iwasaki, Daisuke Takahashi
Archives of orthopaedic and trauma surgery, 143, 6, 3487, 3493, 2022年08月01日, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: There is still little information regarding the advantages of a using a polished tapered stem for Crowe Type IV developmental dysplasia of the hip (DDH). This study aimed to investigate the mid-term clinical and radiological outcomes of primary total hip arthroplasty (THA) with femoral shortening osteotomy using modular and polished tapered stems and to compare the results between the modular and polished tapered stems. MATERIALS AND METHODS: This retrospective review included 32 patients (37 hips) with Crowe type IV DDH who underwent primary THA with femoral shortening osteotomy using a modular stem (cementless group, 14 hips) or a polished tapered stem (cement group, 23 hips) between 1996 and 2018. Clinical data and radiographic assessments were reviewed to analyze the differences between the two groups. RESULTS: The mean duration of patient follow-up of the cementless group (134.4 months) was longer than that of the cement group (75.5 months). There were no differences in clinical results, time of bone union, and survival rate between the two groups. However, the cementless group exhibited a higher ratio of intraoperative fracture and thinning of cortical bone including stress shielding, medullary changes, stem alignment changes, and osteolysis, compared to the cement group. CONCLUSIONS: The findings of this study suggest that THA with femoral shortening osteotomy using both cemented and modular stems can provide satisfactory results. However, considering the occurrence of intraoperative fracture and radiographic analysis in the current study, the cement stem may have an advantage for patients with bone fragility and deterioration in bone quality.

Influence of differences in bone morphology on the distribution patterns of subchondral bone density across the trapeziometacarpal joint.
Yukinori Tsukuda, Yuichiro Matsui, Kaori Endo, Yuki Matsui, Daisuke Kawamura, Norimasa Iwasaki
Scientific reports, 12, 1, 12368, 12368, 2022年07月20日, ［国際誌］
英語, 研究論文（学術雑誌）, We aimed to clarify the effects of morphological patterns of the trapezium and first metacarpal on the distribution of subchondral bone density across the articular surface of the trapeziometacarpal (TMC) joint using computed tomography osteoabsorptiometry. Thirty-three patients with normal TMC joints were evaluated. The percentages of the high-density areas in the radial-dorsal and ulnar-volar regions of the trapezium were significantly higher than that in the ulnar-dorsal region, and that of the ulnar-dorsal region of the first metacarpal was significantly lower than in the other three regions. The percentage of the high-density area of the radial-dorsal region of the trapezium and trapezial inclination (TI) showed a significant positive correlation, and the percentages of the high-density areas in the ulnar-dorsal and ulnar-volar regions had significant negative correlations with TI at the articular surface of the first metacarpal. These results indicate that bony morphologic differences in the trapezium affect the distribution pattern of subchondral bone density through the TMC joint.

Inhibitory role of Annexin A1 in pathological bone resorption and therapeutic implications in periprosthetic osteolysis.
Hend Alhasan, Mohamad Alaa Terkawi, Gen Matsumae, Taku Ebata, Yuan Tian, Tomohiro Shimizu, Yoshio Nishida, Shunichi Yokota, Fayna Garcia-Martin, Mahmoud M Abd Elwakil, Daisuke Takahashi, Mahmoud A Younis, Hideyoshi Harashima, Ken Kadoya, Norimasa Iwasaki
Nature communications, 13, 1, 3919, 3919, 2022年07月07日, ［国際誌］
英語, 研究論文（学術雑誌）, There is currently no therapy available for periprosthetic osteolysis, the most common cause of arthroplasty failure. Here, the role of AnxA1 in periprosthetic osteolysis and potential therapeutics were investigated. Reducing the expression of AnxA1 in calvarial tissue was found to be associated with increased osteolytic lesions and the osteolytic lesions induced by debris implantation were more severe in AnxA1-defecient mice than in wild-type mice. AnxA1 inhibits the differentiation of osteoclasts through suppressing NFκB signaling and promoting the PPAR-γ pathway. Administration of N-terminal-AnxA1 (Ac2-26 peptide) onto calvariae significantly reduced osteolytic lesions triggered by wear debris. These therapeutic effects were abrogated in mice that had received the PPAR-γ antagonist, suggesting that the AnxA1/PPAR-γ axis has an inhibitory role in osteolysis. The administration of Ac2-26 suppressed osteolysis induced by TNF-α and RANKL injections in mice. These findings indicate that AnxA1 is a potential therapeutic agent for the treatment of periprosthetic osteolysis.

Liver metastasis in soft tissue sarcoma at initial presentation.
Yuta Kawae, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki
Journal of surgical oncology, 126, 6, 1074, 1079, 2022年07月06日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND AND OBJECTIVES: Noncontrast computed tomography of the chest is the standard imaging modality for cancer staging in patients with soft tissue sarcoma (STS), but appropriate candidates for liver screening have not been clarified. METHODS: We reviewed all patients with STS diagnosed between 2010 and 2018 in the Surveillance, Epidemiology, and End Results database. Incidence of liver metastasis at initial presentation and high incidence of liver metastasis by histological subtype were investigated. In addition, risk factors for liver metastasis were investigated by multiple logistic regression analysis. RESULTS: After excluding patients without information about liver metastasis, cause of death or primary liver tumor, 47 260 patients were included in this study. Of those, 1471 patients (3.2%) showed liver metastasis at initial presentation. The histological subtype showing the highest incidence of liver metastasis was desmoplastic small round cell tumor (30.3%), followed by malignant hemangioendothelioma (11.5%) and angiomyoliposarcoma (10.5%). Deep-rooted tumor, location in the body wall, retroperitoneum, or thorax/peritoneum, high histological grade, and higher T stage were associated with higher incidences of liver metastasis at initial presentation. CONCLUSION: Risk factors for liver metastasis were deep location, trunk development, larger tumor size, high histological grade, and specific histological subtypes.

CLCF 1の骨代謝へ与える影響と、新規骨粗鬆症治療薬としての可能性　　　　　　　　　　　　　　　
横田 隼一, 松前 元, 照川 ヘンド, 西田 善郎, 清水 智弘, 照川 アラー, 岩崎 倫政
日本骨代謝学会学術集会プログラム抄録集, 40回, 125, 125, (一社)日本骨代謝学会, 2022年07月
日本語

骨リモデリング調節におけるアネキシンA1の機能解析　　　　　　　　　　　　　　　
西田 善郎, 松前 元, 江畑 拓, 横田 隼一, 照川 ヘンド, 塩田 惇喜, 北原 圭太, 清水 智弘, 高橋 大介, 照川 アラー, 岩崎 倫政
日本骨代謝学会学術集会プログラム抄録集, 40回, 132, 132, (一社)日本骨代謝学会, 2022年07月
日本語

Establishment of a New Qualitative Evaluation Method for Articular Cartilage by Dynamic T2w MRI Using a Novel Contrast Medium as a Water Tracer
Yoshiaki Hosokawa, Tomohiro Onodera, Kentaro Homan, Jun Yamaguchi, Kohsuke Kudo, Hiroyuki Kameda, Hiroyuki Sugimori, Norimasa Iwasaki
CARTILAGE, 13, 3, 19476035221111503, 19476035221111503, SAGE PUBLICATIONS INC, 2022年07月, ［国際誌］
英語, 研究論文（学術雑誌）, Objective In the early stages of cartilage damage, diagnostic methods focusing on the mechanism of maintaining the hydrostatic pressure of cartilage are thought to be useful. O-17-labeled water, which is a stable isotope of oxygen, has the advantage of no radiation exposure or allergic reactions and can be detected by magnetic resonance imaging (MRI). This study aimed to evaluate MRI images using O-17-labeled water in a rabbit model. Design Contrast MRI with O-17-labeled water and macroscopic and histological evaluations were performed 4 and 8 weeks after anterior cruciate ligament transection surgery in rabbits. A total of 18 T2-weighted images were acquired, and O-17-labeled water was manually administered on the third scan. The O-17 concentration in each phase was calculated from the signal intensity at the articular cartilage. Macroscopic and histological grades were evaluated and compared with the O-17 concentration. Results An increase in O-17 concentration in the macroscopic and histologically injured areas was observed by MRI. Macroscopic evaluation showed that the O-17 concentration significantly increased in the damaged site group. Histological evaluations also showed that O-17 concentrations significantly increased at 36 minutes 30 seconds after initiating MRI scanning in the Osteoarthritis Research Society International (OARSI) grade 3 (0.493 in grade 0, 0.659 in grade 1, 0.4651 in grade 2, and 0.9964 in grade 3, P < 0.05). Conclusion O-17-labeled water could visualize earlier articular cartilage damage, which is difficult to detect by conventional methods.

Effect of the Inverted V-Shaped Osteotomy on Patellofemoral Joint and Tibial Morphometry as Compared With the Medial Opening Wedge High Tibial Osteotomy.
Eiji Kondo, Koji Yabuuchi, Zenta Joutoku, Shinji Matsubara, Koji Iwasaki, Masatake Matsuoka, Tomohiro Onodera, Daisuke Momma, Masayuki Inoue, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda
The American journal of sports medicine, 50, 9, 2439, 2452, 2022年07月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Recent studies have reported that medial opening wedge (OW) high tibial osteotomy (HTO) induces patella baja, resulting in degenerative changes in the patellofemoral joint. We have developed an inverted V-shaped (iV) HTO, which is classified as a neutral wedge osteotomy. HYPOTHESES: The study hypotheses were as follows: (1) patellar height, posterior tibial slope, and tibial length will not change between pre- and postoperative evaluations after iV-HTO; (2) the lateral shift ratio of the patella and the distance between the tibial tubercle and the trochlear groove may be significantly decreased after iV-HTO. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 191 patients (220 knees) who underwent HTO for medial osteoarthritis were enrolled retrospectively in this study: 107 knees underwent OW-HTO and 113 knees underwent iV-HTO. Clinical and radiological evaluations were performed before and at least 3 years after surgery. RESULTS: Postoperatively, the mean Caton-Deschamps ratio was significantly decreased (P < .0001) from 0.95 to 0.79 in the OW group, while there were no significant changes in the iV group. The mean posterior tibial slope was significantly increased (P < .0001) from 8.5° to 10.5° in the OW group, while there were no significant differences in the iV group. Although the entire leg length was significantly increased (P < .0003) in both groups after HTO, there were no significant differences in tibial length between the pre- and postoperative periods in the iV group. Regarding the congruity of the patellofemoral joint, the mean lateral shift ratio did not significantly change in the OW group, whereas it was significantly decreased (P = .0012) from 11.5% to 8.8% in the iV group. The mean tibial tubercle-trochlear groove distance was significantly decreased (P < .0001) from 12.8 to 9.7 mm in the iV group, while it was significantly increased in the OW group (P < .0001). Concerning the clinical outcome, the Japanese Orthopaedic Association (JOA) and Lysholm knee scores at final follow-up (OW vs iV: JOA, 91.2 vs 90.1; Lysholm, 92.5 vs 89.0) were significantly increased (P < .0001) as compared with the preoperative values (OW vs iV: JOA, 68.3 vs 66.8; Lysholm, 67.9 vs 61.0). CONCLUSION: Patellar height, posterior tibial slope, and tibial length did not change after the iV-HTO, while they were significantly changed after the OW-HTO. Although the preoperative degrees of varus knee and patellofemoral osteoarthritis were more severe in the iV group than the OW group, the iV-HTO led to altered patellofemoral joint congruity.

Real-world persistence of twice-weekly teriparatide and factors associated with the discontinuation in patients with osteoporosis.
Ryo Fujita, Tsutomu Endo, Masahiko Takahata, Kentaro Haraya, Hisataka Suzuki, Itaru Oda, Masahiro Kanayama, Tsuyoshi Asano, Keiichi Shigenobu, Akira Iwata, Katsuhisa Yamada, Hirohito Takeuchi, Hisanori Ohura, Daisuke Yoneoka, Norimasa Iwasaki
Journal of bone and mineral metabolism, 40, 5, 782, 789, 2022年06月27日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: A 28.2 μg twice-weekly formulation of teriparatide (2/W-TPD) was developed to provide comparably high efficacy for osteoporosis to a 56.5 μg once-weekly formulation while improving the safety and persistence rate. In the current study, we aimed to elucidate the real-world persistence of 2/W-TPD and to identify the factors associated with the discontinuation of 2/W-TPD in patients with severe osteoporosis. MATERIALS AND METHODS: This retrospective study included 90 patients who were treated with 2/W-TPD at three hospitals in Japan. Patient information was collected, including age, sex, distance to the hospital, family structure, comorbidities, previous treatment for osteoporosis, timing of the injection, side effects and duration of 2/W-TPD treatment, barthel index (BI), and bone mineral density (BMD) of the lumbar spine and femoral neck. We examined the factors influencing 2/W-TPD discontinuation using the Cox proportional hazards model. RESULTS: The 12 month completion rate of 2/W-TPD therapy was 47.5%. The Cox hazard analysis identified side effects [Hazard Ratio (HR) = 14.59, P < 0.001], low BMD of the femoral neck (HR = 0.04, P = 0.002), and morning injection (HR = 3.29, P = 0.006) as risk factors influencing the discontinuation of 2/W-TPD. Other variables, including age, did not contribute to the continuation of 2/W-TPD. CONCLUSION: One year continuation rate of 2/W-TPD was higher than the previously reported value of the once-weekly formulation in real-world setting, probably due to the lower incidence of side effects. Introducing injection of 2/W-TPD may further improve the persistence of TPD therapy for osteoporosis.

Genetic insights into ossification of the posterior longitudinal ligament of the spine
Yoshinao Koike, Masahiko Takahata, Masahiro Nakajima, Nao Otomo, Hiroyuki Suetsugu, Xiaoxi Liu, Tsutomu Endo, Shiro Imagama, Kazuyoshi Kobayashi, Takashi Kaito, Satoshi Kato, Yoshiharu Kawaguchi, Masahiro Kanayama, Hiroaki Sakai, Takashi Tsuji, Takeshi Miyamoto, Hiroyuki Inose, Toshitaka Yoshii, Masafumi Kashii, Hiroaki Nakashima, Kei Ando, Yuki Taniguchi, Kazuhiro Takeuchi, Shuji Ito, Kohei Tomizuka, Keiko Hikino, Yusuke Iwasaki, Yoichiro Kamatani, Shingo Maeda, Hideaki Nakajima, Kanji Mori, Atsushi Seichi, Shunsuke Fujibayashi, Tsukasa Kanchiku, Kei Watanabe, Toshihiro Tanaka, Kazunobu Kida, Sho Kobayashi, Masahito Takahashi, Kei Yamada, Hiroshi Takuwa, Hsing-Fang Lu, Shumpei Niida, Kouichi Ozaki, Yukihide Momozawa, Masashi Yamazaki, Atsushi Okawa, Morio Matsumoto, Norimasa Iwasaki, Chikashi Terao, Shiro Ikegawa
medRxiv, 12, Cold Spring Harbor Laboratory, 2022年06月17日, ［国際誌］
英語, 研究論文（学術雑誌）, Abstract

Background

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease, leading to severe neurological deficits. Its etiology and pathogenesis are mostly unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship.

Methods

To clarify the etiology and pathogenesis of OPLL, we conducted a meta-analysis of genome-wide association studies (GAWSs) using 22,016 Japanese individuals. We classified OPLL into cervical, thoracic and the other types, and conducted GWAS sub-analyses. We conducted a gene- based association analysis and a transcriptome-wide Mendelian randomization approach to identify other potential causal genes. To investigate cell groups related to OPLL, we conducted cell type group enrichment analysis. To identify traits with a causal effect on OPLL, we evaluated the genetic correlation with 99 complex traits and then performed mendelian randomization (MR) analyses. Finally, we generated polygenic risk score (PRS) to investigate the genetic impact of the causal trait on OPLL subtypes.

Results

A GWAS meta-analysis identified 14 significant loci, including eight novel loci. GWAS sub-analyses identified subtype-specific signals. A Gene-based association analysis and a transcriptome-wide Mendelian randomization approach identified five and three potential causal genes, respectively. These loci/genes contained bone metabolism-related genes. Cell type group enrichment analysis observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells. Genetic correlations showed positive correlation with T2D and BMI and negative correlation with cerebral aneurysm and osteoporosis. MR analyses demonstrated a significant causal effect of increased BMI and high bone mineral density (BMD) on OPLL, but not of T2D, indicating that high BMI confounded the T2D correlation. A PRS for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL.

Conclusion

We identified multiple causative genes involved in bone metabolism that are candidates for future therapeutic targets. By MR analyses, we showed for the first time a causal relationship between the common metabolic conditions (high BMI and BMD) and OPLL. We successfully linked intervenable traits to OPLL.

Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification.
Takafumi Fukui, Hironao Tateno, Takashi Nakamura, Yuma Yamada, Yusuke Sato, Norimasa Iwasaki, Hideyoshi Harashima, Ken Kadoya
International journal of molecular sciences, 23, 12, 2022年06月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats. Liposomes in cell bodies were detected with infrared fluorescence of DiD conjugated to liposomes. Three days later, all nerve-administered liposomes were retrogradely transported to the spinal cord and DRGs, whereas only muscle-administered liposomes consisting of DSPC reached the spinal cord and DRGs. Modification with Cholera toxin B subunit improved the transport efficiency of liposomes to the spinal cord and DRGs from 4.5% to 17.3% and from 3.9% to 14.3% via nerve administration, and from 2.6% to 4.8% and from 2.3% to 4.1% via muscle administration, respectively. Modification with octa-arginine (R8) improved the transport efficiency via nerve administration but abolished the transport capability via muscle administration. These findings provide the initial data for the development of a novel DDS targeting the spinal cord and DRGs via peripheral administration.

Scrotal pain of a patient with ankylosing spondylitis successfully treated with TNF-alpha inhibitor: a case report.
Hisataka Suzuki, Takeru Tsujimoto, Masahiro Ota, Yuichi Hasegawa, Fumihiro Oha, Yukitoshi Shimamura, Masaru Tanaka, Tomoyuki Hashimoto, Norimasa Iwasaki, Masahiro Kanayama
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 29, 1, 402, 404, 2022年06月08日, ［国内誌］
英語

Histochemical examination of blood vessels in murine femora with intermittent PTH administration.
Haruhi Maruoka, Shen Zhao, Hirona Yoshino, Miki Abe, Tomomaya Yamamoto, Hiromi Hongo, Mai Haraguchi-Kitakamae, Alireza Nasoori, Hotaka Ishizu, Yuhi Nakajima, Masayuki Omaki, Tomohiro Shimizu, Norimasa Iwasaki, Paulo Henrique Luiz de Freitas, Minqi Li, Tomoka Hasegawa
Journal of oral biosciences, 64, 3, 329, 336, 2022年05月15日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To verify the biological effects of parathyroid hormone (PTH) on the blood vessels in the bone, this study aimed to investigate histological alterations in endomucin-positive blood vessels and perivascular cells in murine femora after intermittent PTH administration. For comparison with blood vessels in the bone, we examined the distribution of endomucin-positive blood vessels and surrounding αSMA-immunoreactive perivascular cells in the liver, kidney, and aorta with or without PTH administration. METHODS: Six-week-old male C57BL/6J mice received hPTH [1-34] or vehicle for two weeks. All mice were fixed with a paraformaldehyde solution after euthanasia, and the right femora, kidney, liver, and aorta were extracted for immunohistochemical analysis of endomucin, αSMA, ephrinB2, EphB4, and HIF1α. Light microscopic observations of semi-thin sections and transmission electron microscopic (TEM) observations of ultra-thin sections were performed on the left femora. RESULTS: After intermittent PTH administration, αSMA-reactive/ephrinB2-positive stromal cells appeared around endomucin-positive/EphB4-immunoreactive blood vessels in the bone. In addition, intense immunoreactivities of EphB4 and HIF1α were seen in vascular endothelial cells after the PTH treatment. Several stromal cells surrounding PTH-treated blood vessels exhibited well-developed rough endoplasmic reticulum under TEM observations. In contrast to bone tissues, αSMA-positive stromal cells did not increase around the endomucin-positive blood vessels in the kidney, liver, or aorta, even after PTH administration. CONCLUSION: These findings show that intermittent PTH administration increases αSMA-reactive/ephrinB2-positive perivascular stromal cells in bone tissue but not in the kidney, liver, or aorta, suggesting that PTH preferentially affects blood vessels in the bone.

IL4 stimulated macrophages promote axon regeneration after peripheral nerve injury by secreting uPA to stimulate uPAR upregulated in injured axons.
Yuki Matsui, Ken Kadoya, Yusuke Nagano, Takeshi Endo, Masato Hara, Gen Matsumae, Tomoaki Suzuki, Yasuhiro Yamamoto, Mohamad Alaa Terkawi, Norimasa Iwasaki
Cellular and molecular life sciences : CMLS, 79, 6, 289, 289, 2022年05月10日, ［国際誌］
英語, 研究論文（学術雑誌）, Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.

Low-Grade Inflammation in the Pathogenesis of Osteoarthritis: Cellular and Molecular Mechanisms and Strategies for Future Therapeutic Intervention.
M Alaa Terkawi, Taku Ebata, Shunichi Yokota, Daisuke Takahashi, Tsutomu Endo, Gen Matsumae, Tomohiro Shimizu, Ken Kadoya, Norimasa Iwasaki
Biomedicines, 10, 5, 2022年05月10日, ［国際誌］
英語, 研究論文（学術雑誌）, Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA.

Rare case of real-time observation of paralytic deterioration after cervical dislocation in the hyperacute phase.
Tsutomu Endo, Kota Suda, Takafumi Fukui, Satoko Matsumoto, Miki Komatsu, Masahiro Ota, Chikara Ushiku, Junichi Yamane, Akio Minami, Masahiko Takahata, Norimasa Iwasaki
BMC musculoskeletal disorders, 23, 1, 412, 412, 2022年05月02日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: There have been no prior reports of real-time detailed records leading to complete quadriplegia immediately after fracture dislocation in high-energy trauma. Here, we report a case of cervical dislocation in which the deterioration to complete motor paralysis (modified Frankel B1) and complete recovery (Frankel E) could be monitored in real time after reduction in the hyperacute phase. CASE PRESENTATION: A 65-year-old man was involved in a car accident and sustained a dislocation at the C5/6 level (Allen-Ferguson classification: distractive flexion injury stage IV). His paralysis gradually deteriorated from Frankel D to C 2 hours after the injury and from Frankl C to B 5 hours after the injury. His final neurological status immediately before reduction was Frankel B1 (complete motor paralysis with sensation only in the perianal region). Reduction was completed within 6 h and 5 min after injury, and spinal fusion was subsequently performed. The patient exhibited rapid motor recovery immediately after surgery, and was able to walk independently on postoperative day 14. CONCLUSIONS: This case suggests that there is a mixture of cases in which the spinal cord has not been catastrophically damaged, even if the patient has complete motor paralysis. Prompt reduction has the potential to improve neurological function in such cases.

Implantation of autogenous meniscal fragments wrapped with a fascia sheath induces fibrocartilage regeneration in a large meniscal defect in sheep: A histological and biomechanical study.
Eiji Kondo, Yasuyuki Kawaguchi, Masashi Yokota, Jun Onodera, Yasuhito Tanaka, Norimasa Iwasaki, Kazunori Yasuda
Orthopaedics & traumatology, surgery & research : OTSR, 108, 3, 103225, 103225, 2022年05月, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Currently, various studies have been reported to regenerate the meniscus tissue in a large defect after partial meniscectomy using biological or synthetic scaffolds with or without fibrochondrocytes. However, the clinical utility of those treatments has not been established as of yet. HYPOTHESIS: Purposes of this study were to develop a sheep model to evaluate feasibility of this new surgical strategy to treat the irreparable meniscus injury, and to test the hypothesis that implantation of autogenous meniscal fragments wrapped with a fascia sheath may significantly induce fibrocartilage regeneration in a large meniscal defect in the sheep model. METHODS AND METHODS: Twenty Suffolk sheep were used. In each animal, an anterior 10-mm width of the right medial meniscus was resected. Then, the animals were divided into the following 2 groups. In Group I, the defect was enveloped with a fascia from the left thigh. In Group II, the resected meniscus fragmented into small pieces was grafted into the defect. Then the defect was enveloped with a fascia. In each group, 5 of 10 sheep were used for histological and biomechanical evaluations, respectively, at 12 weeks after surgery. RESULTS: In Group I, the defect was incompletely filled with thin fibrous tissues, while fibrocartilage tissues rarely regenerated in the tissue. In Group II, all defects were completely filled with thick fibrocartilage tissues, which were richly stained with the safranin O staining. Both the gross and histological observation score of Group II was significantly (p=0.0005, p=0.0005) greater than that of Group I. Concerning the cross-sectional area of the regenerated tissue, Group II was significantly (p=0.0002) greater than Group I. In the biomechanical evaluation, the maximal load and the linear stiffness of the meniscus-tibia complex were significantly (p=0.0015, p=0.0283) greater in Group II than in Group I. DISCUSSION: Implantation of autogenous meniscal fragments wrapped with a fascia sheath significantly induces fibrocartilage regeneration into a large meniscal defect in the sheep model. LEVEL OF EVIDENCE: Not applicable; Controlled Laboratory Study, Experimental in vivo study.

Minimum 5-Year Outcomes of Dorsal Intercarpal Ligament Capsulodesis With Scapholunate Interosseous Ligament Repair for Subacute and Chronic Static Scapholunate Instability: A Clinical Series of 5 Patients
Hiroki Shibayama, Yuichiro Matsui, Daisuke Kawamura, Daisuke Momma, Takeshi Endo, Norimasa Iwasaki
Journal of Hand Surgery Global Online, 4, 3, 162, 165, Elsevier BV, 2022年05月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Treatment of subacute and chronic static scapholunate instability remains challenging. We aimed to determine 5- to 10-year outcomes of dorsal intercarpal ligament capsulodesis with scapholunate interosseous ligament repair for subacute and chronic static scapholunate instability. METHODS: Six patients with subacute and chronic static scapholunate instability underwent dorsal intercarpal ligament capsulodesis with scapholunate interosseous ligament repair between 2011 and 2015, and 5 of them were followed for at least 5 years after surgery. The clinical and radiological results were retrospectively investigated. All patients were male, and the mean age at surgery was 37 years (range, 21-47 years). The mean period from injury to surgery was 26.2 months (range, 2-113 months). The surgical procedure was a modification of a method reported by Szabo et al. RESULTS: The mean postoperative follow-up period was 8.1 years (range, 5.1-9.5 years). Median Disabilities of the Arm, Shoulder, and Hand and Mayo wrist scores improved from 23.3 to 1.7 and from 55 to 80, respectively, from before surgery to the final follow-up. Although the median flexion angle tended to be smaller, the median extension angle tended to be greater than before surgery. The median percent grip strength increased from 72.3% before surgery to 99.2% at the final follow-up. The median scapholunate gap improved from 4.2 mm before surgery to 2.1 mm at the final follow-up. The median scapholunate angle also improved from 95.7° before surgery to 71.3° at the final follow-up. Osteoarthritic changes were observed in 2 of 5 patients at the final follow-up. CONCLUSIONS: The scapholunate gap in all patients was within the normal range after a mean of 8.1 years of follow-up. Dorsal intercarpal ligament capsulodesis with scapholunate interosseous ligament repair is considered a good alternative for subacute and chronic static scapholunate instability based on these 5- to 10-year outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Clinical and radiological outcomes of posterior cervical decompression and fusion for severe cervical compressive-extension injury: A case series.
Takeru Tsujimoto, Kota Suda, Miki Komatsu, Satoko Matsumoto Harmon, Mitsuru Asukai, Masahiko Takahata, Norimasa Iwasaki, Akio Minami
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 28, 4, 733, 739, 2022年04月28日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Although severe cervical compressive-extension (CE) injuries are usually repaired using a combined anterior-posterior approach, the repair is possible using a posterior approach alone with reliable anchors. This study aimed to present the outcomes and imaging analysis results of posterior cervical decompression and fusion (PCDF) for severe CE injuries. METHODS: We retrospectively reviewed 16 patients who underwent PCDF surgery for severe CE injuries (>50% subluxation) between January 2012 and December 2018. All patients completed 1-year follow-up, and their mean age at the time of surgery was 63.5 years. American Spinal Injury Association Impairment Scale (AIS) grade, kyphotic angle of lower vertebra (KALV), and anterior defect area of lower vertebra (ADLV) were assessed preoperatively. RESULTS: Of 16 patients, nine patients improved at the final follow-up, and eight patients could walk with or without assistance. All patients achieved bone union postoperatively, but four patients showed progression of correction loss of ≥10°. Therefore, patients were divided into two groups: NL group with correction loss of <10°; L group with correction loss of ≥10°. All patients in L group showed KALV of ≥15°, while 10 of 12 patients in NL group showed KALV of <15°. Furthermore, all patients in L group showed ADLV of ≥50%, whereas all patients in NL group showed ADLV of <50%. CONCLUSIONS: PCDF is feasible and a favorable procedure for severe CE injuries that require early reduction and cervical spinal stabilization. However, in the cases of advanced destruction of the anterior vertebra, loss of correction after PCDF might occur postoperatively.

Does Primary Tumor Resection in Patients with Metastatic Primary Mobile Vertebral Column Sarcoma Improve Survival?
Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki
World neurosurgery, 163, e647-e654, 2022年04月18日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Primary mobile vertebral column sarcoma is an exceedingly rare malignancy. Although primary tumor resection has been reported to prolong survival in patients with metastatic bone sarcoma, whether primary tumor resection in patients with advanced primary mobile vertebral column sarcoma is associated with survival remains unclear owing to the rarity of this pathological entity. METHODS: Using the Surveillance, Epidemiology, and End Results database, 182 patients with metastatic primary mobile vertebral column sarcoma were identified between 1983 and 2015. Of the 182 patients enrolled, 101 patients (55%) underwent primary tumor resection (Surgery group) and 81 patients (45%) did not undergo resection (No Surgery group). To account for imbalances in the basic characteristics of patients between groups, propensity score matching was performed. Survival analysis was performed by weighted Cox proportional hazards modeling to calculate hazard ratios. RESULTS: After adjusting for patient background characteristics, 138 patients were included for the analysis (Surgery group: 69 patients; No Surgery group: 69 patients). The Surgery group did not show improved cancer-specific survival (hazard ratio = 0.73, 95% CI 0.49-1.10). Similarly, the Surgery group did not show improved overall survival compared with the No Surgery group (hazard ratio = 0.80, 95% CI 0.55-1.16). CONCLUSIONS: To our knowledge, this is the first study to indicate that surgical resection for advanced primary mobile vertebral column sarcoma does not have a positive impact on survival.

Comprehensive validation of a wearable foot sensor system for estimating spatiotemporal gait parameters by simultaneous three-dimensional optical motion analysis.
Kentaro Homan, Keizo Yamamoto, Ken Kadoya, Naoki Ishida, Norimasa Iwasaki
BMC sports science, medicine & rehabilitation, 14, 1, 71, 71, 2022年04月17日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Use of a wearable gait analysis system (WGAS) is becoming common when conducting gait analysis studies due to its versatility. At the same time, its versatility raises a concern about its accuracy, because its calculations rely on assumptions embedded in its algorithms. The purpose of the present study was to validate twenty spatiotemporal gait parameters calculated by the WGAS by comparison with simultaneous measurements taken with an optical motion capture system (OMCS). METHODS: Ten young healthy volunteers wore two inertial sensors of the commercially available WGAS, Physilog®, on their feet and 23 markers for the OMCS on the lower part of the body. The participants performed at least three sets of 10-m walk tests at their self-paced speed in the laboratory equipped with 12 high-speed digital cameras with embedded force plates. To measure repeatability, all participants returned for a second day of testing within two weeks. RESULTS: Twenty gait parameters calculated by the WGAS had a significant correlation with the ones determined by the OMCS. Bland and Altman analysis showed that the between-device agreement for twenty gait parameters was within clinically acceptable limits. The validity of the gait parameters generated by the WGAS was found to be excellent except for two parameters, swing width and maximal heel clearance. The repeatability of the WGAS was excellent when measured between sessions. CONCLUSION: The present study showed that spatiotemporal gait parameters estimated by the WGAS were reasonably accurate and repeatable in healthy young adults, providing a scientific basis for applying this system to clinical studies.

Machine Learning Algorithms: Prediction and Feature Selection for Clinical Refracture after Surgically Treated Fragility Fracture.
Hirokazu Shimizu, Ken Enda, Tomohiro Shimizu, Yusuke Ishida, Hotaka Ishizu, Koki Ise, Shinya Tanaka, Norimasa Iwasaki
Journal of clinical medicine, 11, 7, 2022年04月05日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The number of patients with fragility fracture has been increasing. Although the increasing number of patients with fragility fracture increased the rate of fracture (refracture), the causes of refracture are multifactorial, and its predictors are still not clarified. In this issue, we collected a registry-based longitudinal dataset that contained more than 7000 patients with fragility fractures treated surgically to detect potential predictors for clinical refracture. METHODS: Based on the fact that machine learning algorithms are often used for the analysis of a large-scale dataset, we developed automatic prediction models and clarified the relevant features for patients with clinical refracture. Formats of input data containing perioperative clinical information were table data. Clinical refracture was documented as the primary outcome if the diagnosis of fracture was made at postoperative outpatient care. A decision-tree-based model, LightGBM, had moderate accuracy for the prediction in the test and the independent dataset, whereas the other models had poor accuracy or worse. RESULTS: From a clinical perspective, rheumatoid arthritis (RA) and chronic kidney disease (CKD) were noted as the relevant features for patients with clinical refracture, both of which were associated with secondary osteoporosis. CONCLUSION: The decision-tree-based algorithm showed the precise prediction of clinical refracture, in which RA and CKD were detected as the potential predictors. Understanding these predictors may improve the management of patients with fragility fractures.

【レジデントが知るべき整形外科基本手技】身体診察・手技 手の診察・手技
遠藤 健, 岩崎 倫政
関節外科, 41, 4月増刊, 44, 55, (株)メジカルビュー社, 2022年04月
日本語, ＜文献概要＞Point ▼手は狭い範囲に,骨,靱帯,神経,血管,腱が存在しており,まず解剖を熟知する必要がある。▼解剖学的ランドマークを頼りに,触診で障害部位を正確に同定できるようにする。▼各疾患の代表的身体所見手技を習得することで,正確な診断が可能となる。

Superb Microvascular Imaging法を用いた手根管症候群での正中神経内血流評価の有用性　　　　　　　　　　　　　　　
遠藤 健, 松井 雄一郎, 河村 太介, 門間 太輔, 芝山 浩樹, 松居 祐樹, 岩崎 倫政
日本手外科学会雑誌, 39, 1, O45, 5, (一社)日本手外科学会, 2022年04月
日本語

全人工手関節手根骨ステムの至適なエントリーポイントの同定　　　　　　　　　　　　　　　
遠藤 健, 河村 太介, 松井 雄一郎, 門間 太輔, 芝山 浩樹, 松居 祐樹, 岩崎 倫政
日本手外科学会雑誌, 39, 1, O63, 5, (一社)日本手外科学会, 2022年04月
日本語

【発育性股関節形成不全の基礎と臨床】DDHの超音波検査
高橋 大介, 清水 智弘, 宮嵜 拓自, 岩崎 倫政
関節外科, 41, 4, 342, 352, (株)メジカルビュー社, 2022年04月
日本語, ＜文献概要＞発育性股関節形成不全(developmental dysplasia of the hip;DDH)の画像診断では超音波診断が最も有用である。近年の大規模研究により,処女歩行が開始される1歳以降に発見された「診断遅延症例」の増加が明らかとなり,乳児股関節脱臼検診において単純X線よりも診断精度の高い超音波検査(Graf法)の重要性が高まっている。本稿では,新生児期・乳児期の股関節の超音波解剖について述べた後に,Graf法について基本的手技から画像の読み方について概説する。

Intra-articular osteoid osteoma at the elbow mimicking arthritis: a case report
Ryuichi Fukuda, Masatake Matsuoka, Daisuke Kawamura, Takeshi Endo, Hiromi Kanno-Okada, Atsushi Urita, Yuichiro Matsui, Tomohiro Onodera, Norimasa Iwasaki
Annals of Joint, 7, 20, 20, AME Publishing Company, 2022年04月, ［国際誌］
英語, 研究論文（学術雑誌）, Osteoid osteomas are benign, typically intracortical lesions most often affecting the diaphysis of long bones. Nocturnal pain and characteristic symptoms that are relieved by administration of non-steroidal anti-inflammatory drugs (NSAIDs) are present and can help in the diagnosis of osteoid osteoma. We report a case of 18-year-old boy with an osteoid osteoma in the olecranon fossa with an atypical clinical manifestation. The initial manifestation was arthritis-like symptoms such as local heat, motion pain rather than pain at rest, and limited range-of-motion. Notably, NSAIDs were not effective at all for relieving his symptoms. Magnetic resonance imaging showed bone marrow edema around the elbow joint. The symptoms were resistant to conservative treatments, and thus, surgical resection was required. Histopathological examination showed that the lesion consisted of woven bones and osteoid tissues that anastomosed with each other. Combined with a tumor size that was less than 2 cm, clinicopathologically, the tumor was diagnosed as an osteoid osteoma. The pain was immediately relieved after the operation, and range-of-motion recovered at 2 months postoperatively. At 1 year after the surgery, the patient did not exhibit recurrence of the tumor or exacerbation of elbow pain and had a full range of elbow motion. Osteoid osteoma should be considered for the differential diagnosis of arthritis of the elbow in patients who are adolescents and young adults, which is the peak age of onset for osteoid osteoma.

Pulsating Spinal Arachnoid Cyst as a Hidden Aggravating Factor for Thoracic Spondylotic Myelopathy: A Report of 3 Cases.
Masahiko Takahata, Takamasa Watanabe, Tsutomu Endo, Yuki Ogawa, Souya Miura, Norimasa Iwasaki
JBJS case connector, 12, 2, 2022年04月01日, ［国際誌］
英語, 研究論文（学術雑誌）, CASE: We report 3 cases of thoracic myelopathy caused by vertebral osteophytes and coexisting intradural spinal arachnoid cyst (SAC), which was difficult to diagnose on preoperative magnetic resonance imaging. Intraoperative ultrasound sonography revealed spinal cord impingement because of osteophytes and a pulsating intradural SAC. Repeated pincer compression on the spinal cord seemed to be associated with their paraparetic symptoms. CONCLUSION: In treating patients presenting with unexplained progressive myelopathy with small ossified lesion in the thoracic spine, close attention should be paid to a coexisting SAC as a hidden aggravating factor for thoracic myelopathy.

Finite Element Analysis of Optimal Positioning of Femoral Osteotomy in Total Hip Arthroplasty With Subtrochanteric Shortening.
Daisuke Takahashi, Yoshihiro Noyama, Tomohiro Shimizu, Mohamad Alaa Terkawi, Norimasa Iwasaki
Arthroplasty today, 14, 105, 109, 2022年04月, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Total hip arthroplasty with femoral shortening is frequently recommended for patients with high hip dislocation. However, the possibility of postoperative rotational deviation of the stem presents a challenge for surgeons. We aimed to determine the optimal position for osteotomy in total hip arthroplasty under full weight-bearing and turning torque by using finite element analysis. Methods: Four models of femoral osteotomy with 30-mm transverse shortening at 30% (model 30), 40% (model 40), 50% (model 50), and 60% (model 60) from the proximal end of the full length of the Exeter stem were constructed. Using finite element analysis, the constructs were first analyzed under an axial load of 1500 N and then with an added torsional load of 10°. Results: The analyses under torsional loading conditions revealed that the maximum von Mises stress on the stem in each model occurred at the proximal end of the distal fragment and the distal side of the stem. The maximum stress values at the stem were 819 MPa (model 30), 825 MPa (model 40), 916 MPa (model 50), and 944 MPa (model 60). The maximum stress values at the osteotomy site of the medullary cavity side of the distal bone fragment were 761 MPa (model 30), 165 MPa (model 40), 187 MPa (model 50), and 414 MPa (model 60). Conclusions: The osteotomy level should be around the proximal 40% of the full length of the Exeter stem, which is most suitable for rotation stability in the early postoperative period.

Diagnostic Utility of Superb Microvascular Imaging and Power Doppler Ultrasonography for Visualizing Enriched Microvascular Flow in Patients With Carpal Tunnel Syndrome
Takeshi Endo, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Daisuke Momma, Mitsutoshi Ota, Hiroki Shibayama, Takahito Iwai, Mutsumi Nishida, Norimasa Iwasaki
Frontiers in Neurology, 13, 832569, 832569, Frontiers Media SA, 2022年03月31日, ［国際誌］
英語, 研究論文（学術雑誌）, Recent studies suggest that blood flow changes in the median nerve may help confirm a diagnosis of carpal tunnel syndrome (CTS). Herein, we examined the utility of superb microvascular imaging (SMI), a new ultrasonographic (US) technique for visualizing microvascular flow, for detecting blood flow differences between CTS patients and healthy controls. We performed a retrospective analysis of 28 hands with suspected CTS. Patients received both nerve conduction and US examinations. Ten healthy volunteers were enrolled as the control group. The nerve compression ratio and the blood flow signal area were quantified using color Doppler US (CDUS), power Doppler US (PDUS), and SMI. Correlation analyses between the blood flow signal area, the compound muscle action potential of the thenar muscle, and the nerve compression ratio were performed. As a result, the mean nerve compression ratio was found to be significantly higher in the CTS group. There were no differences in the blood flow signal area between the groups using CDUS, while PDUS and SMI showed higher blood flow signals in the CTS group. The blood flow signal area measured by SMI had stronger correlations with the compound muscle action potential amplitude and the nerve compression ratio than those for PDUS. The diagnostic utility of SMI was equivalent to PDUS, but superior to conventional CDUS. Nevertheless, the blood flow signal by SMI was more strongly correlated with the electrophysiological severity and compression ratio than for PDUS. Use of SMI in future studies may help clarify the underlying mechanisms of blood flow changes in CTS.

Bone biopsy findings in patients receiving long-term bisphosphonate therapy for glucocorticoid-induced osteoporosis.
Masahiko Takahata, Tomohiro Shimizu, Satoshi Yamada, Tomomaya Yamamoto, Tomoka Hasegawa, Ryo Fujita, Hideyuki Kobayashi, Tsutomu Endo, Yoshinao Koike, Norio Amizuka, Masahiro Todoh, Jun-Ichiro Okumura, Tomomichi Kajino, Norimasa Iwasaki
Journal of bone and mineral metabolism, 40, 4, 613, 622, 2022年03月25日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy. MATERIALS AND METHODS: We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7 years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group). RESULTS: Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group. CONCLUSION: Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality.

Optical coherence tomography evaluation of the spatiotemporal effects of 3D bone marrow stromal cell culture using a bioreactor.
Jun Yamaguchi, Tomohiro Onodera, Kentaro Homan, Xu Liang, Masatake Matsuoka, Takuji Miyazaki, Hosokawa Yoshiaki, Mitsuru Saito, Norimasa Iwasaki
Journal of biomedical materials research. Part B, Applied biomaterials, 110, 8, 1853, 1861, 2022年03月09日, ［国際誌］
英語, 研究論文（学術雑誌）, Performing cell culture in a three-dimensional (3D) environment has various advantages. In cartilage tissue engineering, 3D in vitro cultures utilizing biomaterials and bioreactors can mimic the biological environment. However, the biggest drawback of these 3D culture systems is a limited ability to evaluate 3D cell distribution. Optical coherence tomography (OCT) has recently been used to evaluate 3D cellular morphology and structure in a timely manner. Here, we showed that OCT could be used to visually assess the distribution and the morphology of bone marrow stromal cells under chondrogenic 3D cultivation using alginate gels and rotary culture. In particular, OCT was able to visualize living cells embedded in alginate gels in a non-destructive and 3D manner, as well as quantitatively evaluate cell distribution and spheroid volume. We also found that cells were centralized in rotary culture but peripherally distributed in static culture, while rotary culture enhanced the hypertrophy of marrow stromal cells (MSCs) embedded in alginate gels. Together, our findings demonstrate that OCT can be used to evaluate the spatiotemporal effects of 3D cultivation using alginate gels and rotary culture. Therefore, this method may allow the observation of pre-cultured tissue over time and the optimization of culture conditions for regenerative tissue engineering.

Changes in wrist joint contact area following radial shortening osteotomy for Kienböck's disease.
Junki Shiota, Daisuke Momma, Yuichiro Matsui, Nozomu Inoue, Eiji Kondo, Norimasa Iwasaki
Scientific reports, 12, 1, 4001, 4001, 2022年03月07日, ［国際誌］
英語, 研究論文（学術雑誌）, We hypothesized that the contact area of the articular surface of the wrist joint could be evaluated using a custom-designed analytical program. The aim of the study was to compare the articular contact area of the wrist joint before and after radial shortening osteotomy for Kienböck's disease. Nine wrists of 9 patients underwent radial shortening osteotomy for Kienböck's disease. Computed tomography (CT) images of the wrist joint were reconstructed using a 3D reconstruction software package. Radioscaphoid and radiolunate joint contact areas and translation of the joint contact area from preoperative to postoperative were calculated using customized software. The mean Modified Mayo Wrist Score was significantly improved from 50.6 preoperatively to 83.3 at final follow-up (p < .001). Preoperatively, the pain was reported as severe in five wrists and moderate in four wrists, while at final follow-up, five patients were free from pain and four patients had mild pain with vigorous activity. The preoperative radioscaphoid joint contact area was 133.4 ± 49.5 mm2 and the postoperative radioscaphoid joint contact area was 156.4 ± 73.1 mm2. The preoperative radiolunate joint contact area was 194.8 ± 92.1 mm2 and the postoperative radiolunate joint contact area was 148.3 ± 97.9 mm2. The radial translation distance was 0.4 ± 1.2 mm, the dorsal translation distance was 0.6 ± 1.2 mm, and the proximal translation distance was 0.2 ± 0.4 mm. CT-based analysis revealed that the center of the contact area translated radially following radial shortening.

Distinct progression pattern of ossification of the posterior longitudinal ligament of the thoracic spine versus the cervical spine: a longitudinal whole-spine CT study.
Yuichiro Hisada, Tsutomu Endo, Yoshinao Koike, Masahiro Kanayama, Ryota Suzuki, Ryo Fujita, Katsuhisa Yamada, Akira Iwata, Hiroyuki Hasebe, Hideki Sudo, Norimasa Iwasaki, Masahiko Takahata
Journal of neurosurgery. Spine, 37, 2, 1, 8, 2022年03月04日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Data regarding risk factors for the progression of ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine are scarce. Therefore, in this study, the authors aimed to elucidate the difference in the radiographic progression pattern of OPLL and its risk factors between cervical and thoracic OPLL using longitudinally acquired whole-spine CT scans. METHODS: Overall, 123 patients with symptomatic OPLL who underwent repeated whole-spine CT examinations, with an average interval of 49 months (at least 3 years) between scans, were retrospectively reviewed. Progression of OPLL was assessed to compare the distribution of OPLL over the entire spine on the initial and final CT scans. Patients were divided into a cervical OPLL (C-OPLL) group and a thoracic OPLL (T-OPLL) group according to the location of the main lesion. The progression pattern of OPLL and its risk factors were compared between the two groups using the Student t-test or Mann-Whitney U-test. RESULTS: In the C-OPLL group, 15 (22.1%) of 68 patients had OPLL progression, of whom 12 patients (80.0%) had progression only in the cervical spine and 3 patients (20.0%) had progression in multiple regions (cervical and thoracic/lumbar). In the T-OPLL group, 16 (29.1%) of 55 patients had OPLL progression, of which 3 patients (18.8%) had progression only in the thoracic spine and 8 patients (50.0%) had progression in multiple regions. Young age was a common risk factor for OPLL progression regardless of the location of OPLL, and this trend was more pronounced in the T-OPLL group than in the C-OPLL group. High BMI, male sex, and multilevel, severe T-OPLL were identified as independent risk factors for progression of T-OPLL (OR 1.19, 95% CI 1.03-1.37; OR 10.5, 95% CI 1.39-81.94; and OR 1.24, 95% CI 1.16-1.45, respectively). CONCLUSIONS: Patients with T-OPLL are predisposed to diffuse progression of OPLL over the entire spine, whereas patients with C-OPLL are likely to have progression in only the cervical spine. Young age and high BMI are significant risk factors for OPLL progression, especially in patients with T-OPLL. Our study highlights the need for continued follow-up in patients with T-OPLL, especially in young patients and those with obesity, for early detection of spinal cord and cauda equina symptoms due to the progression of OPLL throughout the spine.

全人工手関節手根骨ステムの至適なエントリーポイントの同定
遠藤 健, 河村 太介, 松井 雄一郎, 門間 太輔, 芝山 浩樹, 松居 祐樹, 岩崎 倫政
日本整形外科学会雑誌, 96, 2, S140, S140, (公社)日本整形外科学会, 2022年03月
日本語

Superb microvascular imaging法を用いた手根管症候群の正中神経内血流評価の有用性の検討
遠藤 健, 松井 雄一郎, 河村 太介, 門間 太輔, 芝山 浩樹, 松居 祐樹, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S650, S650, (公社)日本整形外科学会, 2022年03月
日本語

大菱形骨の骨形態の違いが母指CM関節における応力に及ぼす影響 CTOAM法を用いた解析
佃 幸憲, 松井 雄一郎, 遠藤 香織, 松居 祐樹, 平塚 重人, 濱崎 雅成, 宮野 真博, 河村 太介, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S685, S685, (公社)日本整形外科学会, 2022年03月
日本語

Modic type1の腰椎椎間板変性にアクネ菌は本当に存在するのか 141例の椎間板採取を用いたプロスペクティブ研究から
八尋 雄平, 須田 浩太, 松本 聡子, 小松 幹, 太田 昌博, 後迫 宏紀, 三浪 明男, 冨永 博之, 谷口 昇, 高畑 雅彦, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S1064, S1064, (公社)日本整形外科学会, 2022年03月
日本語

術前診断に苦慮し急性増悪をきたした悪性末梢神経鞘腫の一例
藤田 諒, 遠藤 努, 岩田 玲, 山田 勝久, 大西 貴士, 長谷部 弘之, 須藤 英毅, 高畑 雅彦, 岩崎 倫政
北海道整形災害外科学会雑誌, 63, 2, 151, 151, 北海道整形災害外科学会, 2022年03月
日本語

急速破壊型股関節症におけるインフラマソーム滑膜炎の関与について
横田 隼一, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 2, S131, S131, (公社)日本整形外科学会, 2022年03月
日本語

脆弱性骨折を来した関節リウマチ患者の再骨折リスク
石津 帆高, 清水 寛和, 清水 智弘, 村上 俊文, 松ヶ崎 圭純, 横田 隼一, 岩崎 倫政
日本整形外科学会雑誌, 96, 2, S144, S144, (公社)日本整形外科学会, 2022年03月
日本語

発育性股関節形成不全に対するangulated innominate osteotomy(AIO)の三次元的評価
小川 拓也, 高橋 大介, 清水 智弘, 宮崎 拓自, 中村 夢志郎, 岩崎 倫政
日本整形外科学会雑誌, 96, 2, S313, S313, (公社)日本整形外科学会, 2022年03月
日本語

関節リウマチ患者の下肢手術数の傾向と併存症発生に関する調査
糸賀 稜, 清水 智弘, 高橋 大介, 小野寺 智洋, 岩崎 倫政
日本整形外科学会雑誌, 96, 2, S334, S334, (公社)日本整形外科学会, 2022年03月
日本語

ハイブリッド人工知能を用いた寛骨臼形成不全の自動解析システムの開発
清水 寛和, 清水 智弘, 遠田 健, 児矢野 英典, 高橋 大介, 小川 拓也, 田中 伸哉, 岩崎 倫政
日本整形外科学会雑誌, 96, 2, S432, S432, (公社)日本整形外科学会, 2022年03月
日本語

Graf法における教育の有無による精度と検査時間の比較
清水 智弘, 中村 夢志郎, 小川 拓也, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S682, S682, (公社)日本整形外科学会, 2022年03月
日本語

大腿骨近位部骨折術後の骨粗鬆症治療状況と治療率改善への取り組み 骨折リエゾンサービス導入前後の比較
小川 裕生, 下段 俊, 福島 瑛, 池 翔太, 竹内 博紀, 百貫 亮太, 梅本 貴央, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S696, S696, (公社)日本整形外科学会, 2022年03月
日本語

大腿骨近位部骨折に対する骨折リエゾンサービスの達成度 主要実績評価指標(KPI)を用いた経時的推移評価
浅野 毅, 亀田 裕亮, 原谷 健太郎, 北原 圭太, 佐藤 恒明, 松岡 知樹, 高橋 大介, 清水 智弘, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S697, S697, (公社)日本整形外科学会, 2022年03月
日本語

大腿骨寛骨臼インピンジメントと発育性股関節形成不全の股関節応力分布に与える影響の比較
小川 裕生, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S737, S737, (公社)日本整形外科学会, 2022年03月
日本語

短縮骨切り併用人工股関節全置換術におけるセメントステムとセメントレスステムの中期成績の比較
宮崎 拓自, 高橋 大介, 清水 智弘, 中村 夢志郎, 大浦 久典, 片山 直行, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S789, S789, (公社)日本整形外科学会, 2022年03月
日本語

高齢者に対するPolished Taperセメントステムを用いた人工股関節全置換術の成績
山崎 秀, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S789, S789, (公社)日本整形外科学会, 2022年03月
日本語

本邦の乳児股関節健診推奨項目と臼蓋発育不全の関連
清水 智弘, 清水 寛和, 鈴木 久崇, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S930, S930, (公社)日本整形外科学会, 2022年03月
日本語

乳児股関節脱臼ハイリスク児における超音波とX線を用いた経時的な画像評価
大橋 佑介, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S932, S932, (公社)日本整形外科学会, 2022年03月
日本語

ハイブリッド人工知能を用いた乳児股関節X線画像の自動解析システムの開発
清水 寛和, 高橋 大介, 児矢野 英典, 遠田 健, 清水 智弘, 下段 俊, 佐藤 恒明, 田中 伸哉, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S932, S932, (公社)日本整形外科学会, 2022年03月
日本語

骨折リスクの高い閉経後骨粗鬆症に最適な骨粗鬆症治療
清水 智弘, 有田 皓介, 石津 帆高, 中村 夢志郎, 藤田 諒, 室田 栄宏, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 96, 3, S1166, S1166, (公社)日本整形外科学会, 2022年03月
日本語

骨粗鬆症と骨代謝 脆弱性骨折をきたした関節リウマチ患者の再骨折リスク　　　　　　　　　　　　　　　
石津 帆高, 清水 寛和, 清水 智弘, 岩崎 倫政
日本リウマチ学会総会・学術集会プログラム・抄録集, 66回, 382, 382, (一社)日本リウマチ学会, 2022年03月
日本語

変形性関節症・軟骨 関節リウマチと酷似する急速破壊型股関節症におけるインフラマソーム滑膜炎の比較検討　　　　　　　　　　　　　　　
横田 隼一, 清水 智弘, 松前 元, 高橋 大介, 照川 アラー, 岩崎 倫政
日本リウマチ学会総会・学術集会プログラム・抄録集, 66回, 428, 428, (一社)日本リウマチ学会, 2022年03月
日本語

関節リウマチの骨関節破壊におけるCCN3の機能解析　　　　　　　　　　　　　　　
松前 元, 照川 アラー, 横田 隼一, 清水 智弘, 高橋 大介, 岩崎 倫政
日本リウマチ学会総会・学術集会プログラム・抄録集, 66回, 569, 569, (一社)日本リウマチ学会, 2022年03月
日本語

関節リウマチ患者の下肢手術数の傾向と併存症に関する調査　　　　　　　　　　　　　　　
糸賀 稜, 清水 智弘, 小野寺 智洋, 岩崎 倫政
日本リウマチ学会総会・学術集会プログラム・抄録集, 66回, 623, 623, (一社)日本リウマチ学会, 2022年03月
日本語

Double-bundle anterior cruciate ligament reconstruction using autologous hamstring tendon hybrid grafts in a patient with hypermobile Ehlers-Danlos Syndrome: A case report.
Ryosuke Hishimura, Eiji Kondo, Masatake Matsuoka, Koji Iwasaki, Yasuyuki Kawaguchi, Yuki Suzuki, Tomohiro Onodera, Daisuke Momma, Norimasa Iwasaki
The Knee, 35, 81, 86, 2022年03月, ［国際誌］
英語, BACKGROUND: Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by skin hyperextensibility, joint hypermobility, and tissue friability. Hypermobile type Ehlers-Danlos syndrome (hEDS) is considered one of the EDS subtypes characterized by generalized joint hypermobility. Although there have been a few case reports which described surgical considerations for anterior cruciate ligament (ACL) reconstructions in patients with other types of EDS, no reports have described those in patients with hEDS. CASE PRESENTATION: We report a case of ACL injury in an 18-year-old male patient with hEDS. The patient was successfully treated with an anatomic double-bundle ACL reconstruction using autologous hamstring tendon hybrid grafts which consist of hamstring tendons connected in a series with commercially available polyester tape. The autogenous tendon portion of the anteromedial and posterolateral bundles were composed of 4 and 2 strands of hamstring tendons, respectively. After 2 weeks of knee joint immobilization, continuous passive motion exercise of the knee joint and partial weight-bearing was allowed. A hinged knee brace was used for a period of 5 months postoperatively. Second-look arthroscopy at 30 months showed that the ACL graft had no laceration and an excellent coverage of the synovium. At 36 months after surgery, the side-to-side differences in the anterior laxity was remarkably improved. The operated knee showed negative Lachman test and had a full range of motion. CONCLUSIONS: To the best of our knowledge, this represents the first report of anatomic double-bundle ACL reconstruction in patients with hEDS and demonstrates excellent clinical and functional outcomes.

Differential effects of anti-RANKL monoclonal antibody and zoledronic acid on necrotic bone in a murine model of Staphylococcus aureus-induced osteomyelitis.
Hideyuki Kobayashi, Ryo Fujita, Shigeto Hiratsuka, Tomohiro Shimizu, Dai Sato, Hiroki Hamano, Norimasa Iwasaki, Masahiko Takahata
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 40, 3, 614, 623, 2022年03月, ［国際誌］
英語, 研究論文（学術雑誌）, Osteomyelitis is characterized by progressive inflammatory bone destruction accompanied by severe pain and disability. However, with the exception of antibiotic therapies, there is no established therapy to protect the bone from infectious osteolysis. The anti-receptor activator of nuclear factor-kB ligand (RANKL) monoclonal antibody (anti-RANKL Ab) is a potential drug based on its proven effectiveness in preventing joint bone erosion in rheumatoid arthritis; however, the efficacy and adverse effects of anti-RANKL Ab in osteomyelitis remain to be investigated. In this study, we investigated the effects of anti-mouse RANKL Ab on acute osteomyelitis and compared them with those of zoledronic acid (ZA) using a murine model. Mice were inoculated with bioluminescent Staphylococcus aureus (Xen 29) on their left femur and then treated with ZA, anti-RANKL Ab, or phosphate-buffered saline as control. A 21-day longitudinal observational study using microcomputed tomography showed that both anti-RANKL Ab and ZA had an osteoprotective effect against infectious osteolysis. However, it was also demonstrated through bioluminescence imaging that ZA delayed the spontaneous reduction of bacterial load and through histology that it increased the amount of necrotic bone, while anti-RANKL Ab did not. Findings from histopathological and in vitro studies suggest that an intense inflammatory response around the necrotic bone could induce osteoclasts in a RANKL-independent manner, leading to the removal of necrotic bone, even after administration of the anti-RANKL Ab therapy. Collectively, anti-RANKL Ab may exert an osteoprotective effect without hampering the removal of the necrotic bone, which serves as a nidus for infection in osteomyelitis.

Association between obesity and ossification of spinal ligaments in 622 asymptomatic subjects: a cross-sectional study.
Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Ryo Fujita, Ryota Suzuki, Yuichiro Hisada, Yuichi Hasegawa, Hisataka Suzuki, Katsuhisa Yamada, Akira Iwata, Hideki Sudo, Daisuke Yoneoka, Norimasa Iwasaki
Journal of bone and mineral metabolism, 40, 2, 337, 347, 2022年03月, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Previous studies on patients with symptoms of spinal ligament ossification, including ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum (OLF), have not clarified whether obesity is a cause or consequence of these diseases and were limited by selection bias. Thus, we investigated the association between obesity and the prevalence of spinal ligament ossification in randomly selected asymptomatic subjects. MATERIALS AND METHODS: Between April 2020 and March 2021, 622 asymptomatic Japanese subjects who underwent computed tomography of neck to pelvis for medical check-up purposes were included. All subjects were divided into the following three groups: normal weight (body mass index [BMI] < 25 kg/m2), obese I (25 ≤ BMI < 30 kg/m2), and obese II (BMI ≥ 30 kg/m2). The relationship between factors affecting the presence of each spinal ligament ossification was evaluated using multivariate logistic regression analysis. RESULTS: The proportion of subjects with thoracic OPLL was significantly higher in the obese II group than in the other two groups (vs. normal weight, P < 0.001; vs. obese I, P < 0.001). BMI was associated with the prevalence of OLF, cervical OPLL, thoracic OPLL, and ossification of the anterior longitudinal ligament (OALL). BMI was most significantly associated with the prevalence of thoracic OPLL (β, 0.28; 95% confidence interval, 0.17-0.39). CONCLUSION: BMI was associated with the prevalence of OALL, cervical OPLL, thoracic OPLL, and OLF in asymptomatic subjects, suggesting that obesity is associated with the development of heterotopic ossification of the spinal ligaments.

Primary Malignant Osseous Neoplasms in the Hand.
Shota Ike, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki
Anticancer research, 42, 3, 1635, 1640, 2022年03月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Primary malignant osseous neoplasms of the hand are rare malignancies. Comprehensive demographic and survival data regarding primary malignant osseous neoplasms of the hand are lacking in the literature. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified all patients with primary malignant osseous neoplasms of the hand diagnosed between 1983 and 2015. Demographic data were searched for primary osseous neoplasms in the hand and higher incidence of histological subtype. RESULTS: A total of 197 patients were analyzed: 103 patients were diagnosed with histologically low-grade tumor, and 31 were diagnosed with high-grade tumor. Five-year cancer-specific and overall survival rates for the entire cohort were 91.4% and 81.9%, respectively. Histological high tumor grade and regional stage from SEER historic stage data were associated with unfavorable cancer-specific survival. CONCLUSION: Special caution is required if patients have histologically high-grade tumor or tumor extending beyond the periosteum into surrounding joints, as these features worsen cancer-specific mortality.

Inflammasome activation in the hip synovium of rapidly destructive coxopathy patients and its relationship with the development of synovitis and bone loss
Shunichi Yokota, Tomohiro Shimizu, Gen Matsumae, Taku Ebata, Hend Alhasan, Daisuke Takahashi, Mohamad Alaa Terkawi, Norimasa Iwasaki
The American Journal of Pathology, 192, 5, 794, 804, Elsevier BV, 2022年03月, ［国際誌］
英語, 研究論文（学術雑誌）, Rapidly destructive coxopathy (RDC), a rare disease of unknown etiology, is characterized by the rapid destruction of the hip joint. In the current study, the potential involvement of inflammasome signaling in the progression of RDC was investigated. Histopathologic changes and the gene expression of inflammasome activation markers in hip synovial tissues collected from patients with RDC were evaluated and compared with those of osteoarthritis and osteonecrosis of the femoral head patients. The synovial tissues of patients with RDC exhibited remarkable increases in the number of infiltrated macrophages and osteoclasts, and the expression of inflammasome activation markers was also increased compared with those of osteoarthritis and osteonecrosis of the femoral head patients. To further understand the histopathologic changes in the joint, a co-culture model of macrophages and synoviocytes that mimicked the joint environment was developed. Remarkably, the gene expression levels of NLRP3, GSDMD, IL1B, TNFA, ADMTS4, ADMTS5, MMP3, MMP9, and RANKL were significantly elevated in the synoviocytes that were co-cultured with activated THP-1 macrophages, suggesting the association between synovitis and inflammasome activation. Consistent with these findings, osteoclast precursor cells that were co-cultured with stimulated synoviocytes exhibited an increased number of tartrate-resistant acid phosphatase-positive cells, compared with cells that were co-cultured with non-stimulated synoviocytes. These findings suggest that the activation of inflammasome signaling in the synovium results in an increase in local inflammation and osteoclastogenesis, thus leading to the rapid bone destruction in RDC.

Four-dimensional computed tomography evaluation of shoulder joint motion in collegiate baseball pitchers.
Daisuke Momma, Alejandro A Espinoza Orías, Tohru Irie, Tomoyo Irie, Eiji Kondo, Norimasa Iwasaki, Nozomu Inoue
Scientific reports, 12, 1, 3231, 3231, 2022年02月25日, ［国際誌］
英語, 研究論文（学術雑誌）, The purpose of this study is to evaluate the glenohumeral contact area, center of glenohumeral contact area, and center of humeral head during simulated pitching motion in collegiate baseball pitchers using four-dimensional computed tomography (4D CT). We obtained 4D CT data from the dominant and non-dominant shoulders of eight collegiate baseball pitchers during the cocking motion. CT image data of each joint were reconstructed using a 3D reconstruction software package. The glenohumeral contact area, center of glenohumeral contact area, center of humeral head, and oblateness of humeral head were calculated from 3D bone models using customized software. The center of glenohumeral contact area translated from anterior to posterior during maximum external rotation to maximum internal rotation (0.58 ± 0.63 mm on the dominant side and 0.99 ± 0.82 mm on the non-dominant side). The center of humeral head translated from posterior to anterior during maximum external rotation to maximum internal rotation (0.76 ± 0.75 mm on the dominant side and 1.21 ± 0.78 mm on the non-dominant side). The increase in anterior translation of the center of glenohumeral contact area was associated with the increase in posterior translation of the center of humeral head. Also, the increase in translation of the center of humeral head and glenohumeral contact area were associated with the increase in oblateness of the humeral head. 4D CT analyses demonstrated that the center of humeral head translated in the opposite direction to that of the center of glenohumeral contact area during external rotation to internal rotation in abduction in the dominant and non-dominant shoulders. The oblateness of the humeral head may cause this diametric translation. 4D CT scanning and the software for bone surface modeling of the glenohumeral joint enabled quantitative assessment of glenohumeral micromotion and be used for kinematic evaluation of throwing athletes.

Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation.
Katsuhisa Yamada, Norimasa Iwasaki, Hideki Sudo
Cells, 11, 4, 2022年02月09日, ［国際誌］
英語, 研究論文（学術雑誌）, Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation.

Determination of optimal concentration of vitamin E in polyethylene liners for producing minimal biological response to prosthetic wear debris.
Gen Matsumae, Hiroaki Kida, Daisuke Takahashi, Tomohiro Shimizu, Taku Ebata, Shunichi Yokota, Hend Alhasan, Mahmoud Khamis Aly, Tomoyo Yutani, Keita Uetsuki, Mohamad Alaa Terkawi, Norimasa Iwasaki
Journal of biomedical materials research. Part B, Applied biomaterials, 110, 7, 1587, 1593, 2022年02月05日, ［国際誌］
英語, 研究論文（学術雑誌）, The introduction of vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) for use in prosthetic components of hip implants has resulted in the production of implants that have excellent mechanical properties and substantially less adverse cellular responses. Given the importance of a biological response to wear in the survival of a prosthesis, we generated wear debris from UHMWPE that had been prepared with different concentrations of vitamin E of 0.1, 0.3, 0.5, and 1% and evaluated their biological reaction in vitro and in vivo. All types of VE-UHMWPE debris promoted a significantly lower expression of Tnf-α in murine peritoneal macrophages than that induced by conventional UHMWPE debris. However, levels of Tnf-α were not significantly different among the macrophages that were stimulated with VE-UHMWPE wear at the concentrations tested. The ability of wear debris to induce inflammatory osteolysis was assessed in a mouse calvarial osteolysis model. The expressions of Tnf-α, Il-6, and Rankl in granulomatous tissue formed around the wear debris were significantly reduced in mice that had been implanted with 0.3%VE-UHMWPE debris as compared to the corresponding values for mice that had been implanted with UHMWPE debris. Consistent with this finding, 0.3%VE-UHMWPE debris showed the lowest osteolytic activity, as evidenced by the reduced bone resorption area, the degree of infiltration of inflammatory cells and the TRAP staining area. Our results suggested that a 0.3% vitamin E concentration is the most appropriate concentration for use in prosthetic components with a reduced adverse cellular response for prolonging the life-span of the implant.

Interplay between Inflammation and Pathological Bone Resorption: Insights into Recent Mechanisms and Pathways in Related Diseases for Future Perspectives.
M Alaa Terkawi, Gen Matsumae, Tomohiro Shimizu, Daisuke Takahashi, Ken Kadoya, Norimasa Iwasaki
International journal of molecular sciences, 23, 3, 2022年02月04日, ［国際誌］
英語, 研究論文（学術雑誌）, Bone is a mineralized and elastic connective tissue that provides fundamental functions in the human body, including mechanical support to the muscles and joints, protection of vital organs and storage of minerals. Bone is a metabolically active organ that undergoes continuous remodeling processes to maintain its architecture, shape, and function throughout life. One of the most important medical discoveries of recent decades has been that the immune system is involved in bone remodeling. Indeed, chronic inflammation has been recognized as the most significant factor influencing bone homeostasis, causing a shift in the bone remodeling process toward pathological bone resorption. Bone osteolytic diseases typified by excessive bone resorption account for one of the greatest causes of disability worldwide, with significant economic and public health burdens. From this perspective, we discuss the recent findings and discoveries highlighting the cellular and molecular mechanisms that regulate this process in the bone microenvironment, in addition to the current therapeutic strategies for the treatment of osteolytic bone diseases.

The effect of local injection of tranexamic acid into peri-articular tissue versus drain clamping in total knee arthroplasty: a randomized controlled trial.
Ryosuke Hishimura, Tomohiro Onodera, Yasumitsu Ohkoshi, Kazufumi Okada, Masatake Matsuoka, Shinji Matsubara, Koji Iwasaki, Eiji Kondo, Norimasa Iwasaki
BMC musculoskeletal disorders, 23, 1, 111, 111, 2022年02月02日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Tranexamic acid (TXA) is used as a synthetic anti-fibrinolytic agent for total knee arthroplasty (TKA) to reduce postoperative bleeding. Though the effects on bleeding reduction of several methods of administering TXA have been demonstrated, the optimal method remains controversial. Recently, the hemostatic effect of periarticular local injection of TXA during TKA was reported. Although this method can be expected to suppress postoperative bleeding without placing a drain, its hemostatic effect has not yet been assessed in comparison with local injection and other methods of administering TXA. The aim of this randomized, prospective study was to assess the efficacy of local injection of TXA during TKA. METHODS: To confirm the effect of the local injection of TXA, drain clamping was set as the control. The subjects included a prospective series of 109 patients randomly divided into 2 groups: the local injection (group L) and the drain clamping (group D). The main outcome measure was postoperative bleeding. Secondary outcomes included pain, physical measurements, and laboratory findings. RESULTS: The calculated total blood loss (CTBL) in groups L and D was nearly equal and did not show the non-inferiority of group L to group D (883 ± 248 vs. 841 ± 257 ml, P = .564). Drained blood loss was significantly higher in group L than in group D (395 ± 130 vs 276 ± 78.8 ml, P < .0001). There was no significant difference in hidden blood loss between the groups (488 ± 269 vs 565 ± 261 ml, P = .131). The other laboratory findings and physical measurements were identical between the groups. CONCLUSIONS: Although CTBL in group L did not show non-inferiority to group D, the local injection of TXA was considered to be superior for suppressing bleeding considering the risk of the adverse effects of using a drain. TRIAL REGISTRATION: This was a randomized, prospective study registered with UMIN Clinical Trials Registry (Registration number: UMIN000036146, date of disclosure: 10/3/2019).

変形性関節症の病態におけるマクロファージの役割　　　　　　　　　　　　　　　
小野寺 智洋, 江畑 拓, 濱崎 雅成, 照川 アラー, 岩崎 倫政
リウマチ科, 67, 2, 216, 220, (有)科学評論社, 2022年02月
日本語

Ulnar nerve morphology during elbow flexion in patients with and without cubital tunnel syndrome: a sonographic study.
Yuichiro Matsui, Tatsunori Horie, Norimasa Iwasaki
The Journal of hand surgery, European volume, 47, 2, 218, 220, 2022年02月, ［国際誌］
英語

Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration.
Daisuke Ukeba, Katsuhisa Yamada, Takashi Suyama, Darren R Lebl, Takeru Tsujimoto, Takayuki Nonoyama, Hirokazu Sugino, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Hideki Sudo
EBioMedicine, 76, 103845, 103845, 2022年02月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Lumbar intervertebral disc (IVD) herniations are associated with significant disability. Discectomy is the conventional treatment option for IVD herniations but causes a defect in the IVD, which has low self-repair ability, thereby representing a risk of further IVD degeneration. An acellular, bioresorbable, and good manufacturing practice (GMP)-compliant in situ-forming gel, which corrects discectomy-associated IVD defects and prevents further IVD degeneration had been developed. However, this acellular matrix-based strategy has certain limitations, particularly in elderly patients, whose tissues have low self-repair ability. The aim of this study was to investigate the therapeutic efficacy of using a combination of newly-developed, ultra-purified, GMP-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs) and the gel for IVD regeneration after discectomy in a sheep model of severe IVD degeneration. METHODS: RECs and nucleus pulposus cells (NPCs) were co-cultured in the gel. In addition, RECs combined with the gel were implanted into IVDs following discectomy in sheep with degenerated IVDs. FINDINGS: Gene expression of NPC markers, growth factors, and extracellular matrix increased significantly in the co-culture compared to that in each mono-culture. The REC and gel combination enhanced IVD regeneration after discectomy (up to 24 weeks) in the severe IVD degeneration sheep model. INTERPRETATION: These findings demonstrate the translational potential of the combination of RECs with an in situ-forming gel for the treatment of herniations in degenerative human IVDs. FUNDING: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.

Discrepancy in the Distribution Patterns of Subchondral Bone Density Across the Ankle Joint After Medial Opening-Wedge and Lateral Closing-Wedge High Tibial Osteotomy.
Shinji Matsubara, Tomohiro Onodera, Koji Iwasaki, Ryosuke Hishimura, Masatake Matsuoka, Eiji Kondo, Norimasa Iwasaki
The American journal of sports medicine, 50, 2, 478, 485, 2022年02月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: High tibial osteotomy (HTO) changes the alignment and dynamics of the ankle joint; however, differences in the stress distribution of the ankle joint after opening-wedge HTO (OWHTO) and closing-wedge HTO (CWHTO) are not understood. It is believed that subchondral bone density of the articular surface reflects the pattern of cumulative stress distribution across the joint surface. PURPOSE: To clarify the effects of OWHTO and CWHTO on the distribution patterns of subchondral bone density across the ankle joint using computed tomography (CT)-osteoabsorptiometry. STUDY DESIGN: Cohort study; Level of evidence, 4. METHODS: Radiographic and CT data of 18 cases who underwent OWHTO (OW group), 12 cases who underwent CWHTO (CW group), and 11 cases with unilateral anterior cruciate ligament injury serving as controls were retrospectively reviewed. The subchondral bone density of the distal tibia was assessed in the 3 groups using CT-osteoabsorptiometry. The distal tibial surface of the ankle joint was divided into 4 parts in the coronal direction, and the percentage of the high-density area (%HDA) to each subregion was compared before and after HTO. RESULTS: Preoperatively, comparing %HDA among the 3 groups, there were no significant differences in any regions. In the OW group, postoperative %HDA in the most medial region was significantly increased compared with preoperative %HDA (49.3% to 53.0%; P = .011), and postoperative %HDA in the most lateral region was significantly decreased (21.4% to 17.2%; P = .003). On the other hand, in the CW group, postoperative %HDA in the most medial region was significantly decreased (55.7% to 35.7%; P = .001), and %HDA in the second lateral region was significantly increased (23.6% to 29.2%; P = .002). CONCLUSION: The ankle distribution pattern of subchondral bone density shifted significantly medially after OWHTO without fibular osteotomy, whereas the distribution pattern shifted laterally after CWHTO with fibular osteotomy. When the OWHTO is performed for patients with medial ankle osteoarthritis, surgeons should pay attention to potential postoperative progression of ankle osteoarthritis due to medial shift of the stress distribution in the ankle joint.

Mature but not developing Schwann cells promote axon regeneration after peripheral nerve injury.
Takeshi Endo, Ken Kadoya, Tomoaki Suzuki, Yuki Suzuki, Mohamad Alaa Terkawi, Daisuke Kawamura, Norimasa Iwasaki
NPJ Regenerative medicine, 7, 1, 12, 12, 2022年01月28日, ［国際誌］
英語, 研究論文（学術雑誌）, Since Schwann cells (SCs) support axonal growth at development as well as after peripheral nerve injury (PNI), developing SCs might be able to promote axon regeneration after PNI. The purpose of the current study was to elucidate the capability of developing SCs to induce axon regeneration after PNI. SC precursors (SCPs), immature SCs (ISCs), repair SCs (RSCs) from injured nerves, and non-RSCs from intact nerves were tested by grafting into acellular region of rat sciatic nerve with crush injury. Both of developing SCs completely failed to support axon regeneration, whereas both of mature SCs, especially RSCs, induced axon regeneration. Further, RSCs but not SCPs promoted neurite outgrowth of adult dorsal root ganglion neurons. Transcriptome analysis revealed that the gene expression profiles were distinctly different between RSCs and SCPs. These findings indicate that developing SCs are markedly different from mature SCs in terms of functional and molecular aspects and that RSC is a viable candidate for regenerative cell therapy for PNI.

Effect of periacetabular osteotomy on the distribution pattern of subchondral bone mineral density in patients with hip dysplasia.
Tomohiro Shimizu, Daisuke Takahashi, Yumejiro Nakamura, Takuji Miyazaki, Shunichi Yokota, Hotaka Ishizu, Norimasa Iwasaki
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 40, 11, 2626, 2631, 2022年01月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Despite the availability of long-term follow-up data, the effect of pelvic osteotomy on the natural history of osteoarthritis is not yet fully understood, partly because there is untapped potential for radiographs to better describe osteoarthritis. Therefore, this study aimed to assess the distribution of subchondral bone mineral density (BMD) across the acetabulum in patients with hip dysplasia immediately (2 weeks) and 1 year after undergoing periacetabular osteotomy (PAO). To that end, we reviewed 40 hips from 33 patients with developmental dysplasia of the hip who underwent PAO between January 2016 and July 2019 at our institution. We measured subchondral BMD through the articular surface of the acetabulum using computed tomography osteoabsorptiometry, dividing the distribution map into nine segments. We then compared the subchondral BMD between 2 weeks and 1 year after PAO in each area. At 2 weeks after PAO, the high-density area tended to be localized particularly in the lateral part of the acetabulum, whereas 1 year after PAO, the high-density area moved to the central and lateral parts. The percentage ratios of the subchondral BMD for the central-posterior, lateral-central, and lateral-posterior areas relative to the central-central area were significantly decreased at 1 year after PAO, as compared to those at 2 weeks after PAO. These findings suggest that loading was altered by PAO to be more similar to physiological loading. A long follow-up observational study is warranted to confirm the association between early changes in subchondral BMD by PAO and joint degeneration.

Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review.
Takashi Ohnishi, Norimasa Iwasaki, Hideki Sudo
Cells, 11, 3, 2022年01月24日, ［国際誌］
英語, 研究論文（学術雑誌）, Intervertebral disc degeneration (IVDD) is a pathological condition that can lead to intractable back pain or secondary neurological deficits. There is no fundamental cure for this condition, and current treatments focus on alleviating symptoms indirectly. Numerous studies have been performed to date, and the major strategy for all treatments of IVDD is to prevent cell loss due to programmed or regulated cell death. Accumulating evidence suggests that several types of cell death other than apoptosis, including necroptosis, pyroptosis, and ferroptosis, are also involved in IVDD. In this study, we discuss the molecular pathway of each type of cell death and review the literature that has identified their role in IVDD. We also summarize the recent advances in targeted therapy at the RNA level, including RNA modulations through RNA interference and regulation of non-coding RNAs, for preventing cell death and subsequent IVDD. Therefore, we review the causes and possible therapeutic targets for RNA intervention and discuss the future direction of this research field.

Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration.
Daisuke Ukeba, Katsuhisa Yamada, Takashi Suyama, Darren R Lebl, Takeru Tsujimoto, Takayuki Nonoyama, Hirokazu Sugino, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Hideki Sudo
EBioMedicine, 76, 103845, 103845, 2022年01月24日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Lumbar intervertebral disc (IVD) herniations are associated with significant disability. Discectomy is the conventional treatment option for IVD herniations but causes a defect in the IVD, which has low self-repair ability, thereby representing a risk of further IVD degeneration. An acellular, bioresorbable, and good manufacturing practice (GMP)-compliant in situ-forming gel, which corrects discectomy-associated IVD defects and prevents further IVD degeneration had been developed. However, this acellular matrix-based strategy has certain limitations, particularly in elderly patients, whose tissues have low self-repair ability. The aim of this study was to investigate the therapeutic efficacy of using a combination of newly-developed, ultra-purified, GMP-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs) and the gel for IVD regeneration after discectomy in a sheep model of severe IVD degeneration. METHODS: RECs and nucleus pulposus cells (NPCs) were co-cultured in the gel. In addition, RECs combined with the gel were implanted into IVDs following discectomy in sheep with degenerated IVDs. FINDINGS: Gene expression of NPC markers, growth factors, and extracellular matrix increased significantly in the co-culture compared to that in each mono-culture. The REC and gel combination enhanced IVD regeneration after discectomy (up to 24 weeks) in the severe IVD degeneration sheep model. INTERPRETATION: These findings demonstrate the translational potential of the combination of RECs with an in situ-forming gel for the treatment of herniations in degenerative human IVDs. FUNDING: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.

Radical resection for solitary thoracic spinous-process metastasis: a case report and technical note.
Chikako Ishii, Akira Iwata, Katsuhisa Yamada, Tsutomu Endo, Takeru Tsujimoto, Hideki Sudo, Ai Shimizu, Norimasa Iwasaki, Masahiko Takahata
Spinal cord series and cases, 8, 1, 8, 8, 2022年01月17日, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Bone metastases confined to the posterior elements of the spine are rarely treated, as there exist no established radical surgical treatment options for this area. Herein, we present a case report of and technical note on a patient who underwent radical resection for a metastatic tumor in the thoracic spinous process. CASE PRESENTATION: A 34-year-old male presented with a nasopharyngeal carcinoma with a solitary metastatic focus in the spinous process of the 10th thoracic vertebra. Imaging revealed that the tumor was confined to the spinous process and the surrounding soft tissues. No tumor was noted in the pedicles, vertebral body, and cortical bone on the ventral side of the lamina, as well as within the spinal canal. As treatment for this solitary metastatic lesion, we decided to perform radical resection with sufficient margins that would include the involved spinous process and all surrounding soft tissues exhibiting evidence of tumor infiltration. The posterior elements of the 9th-11th vertebrae, multifidus muscles, and skin were widely resected en bloc using a T-saw. The posterior elements of the spinal column were resected at the level of pedicles without full visualization of the involved dural sac. The tumor-infiltrated soft tissues surrounding the T10 vertebral spinous process were excised without full visualization of the tumor. Adjuvant therapy was not administered postoperatively. During the second year of follow-up, no signs of recurrence or metastasis were noted. DISCUSSION: Our proposed technique allows wide resection of a solitary focus of metastasis in the posterior elements of the spine.

Cervical Myelopathy Caused by Non-Rheumatic Retro-Odontoid Pseudotumor: An Investigation of Underlying Mechanisms and Optimal Surgical Strategy.
Masahiko Takahata, Ryota Hyakkan, Shigeki Oshima, Itaru Oda, Masahiro Kanayama, Takahiko Hyakumachi, Ryo Fujita, Tsutomu Endo, Tomomichi Kajino, Norimasa Iwasaki
Global spine journal, 13, 7, 21925682211069542, 21925682211069542, 2022年01月10日, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Retrospective case-control study. OBJECTIVE: This study aimed to identify the underlying pathologies of non-rheumatic retro-odontoid pseudotumors (NRPs), which would help establish an appropriate surgical strategy for myelopathy caused by NRP. METHODS: We identified 35 patients with myelopathy caused by NRP who underwent surgery between 2006 and 2017. An age- and sex-matched control group of 70 subjects was selected from patients with degenerative cervical myelopathy. Radiographic risk factors for NRP were compared between cases and controls. We also assessed surgical outcomes following occipital-cervical (O-C) fusion, atlantoaxial (C1-2) fusion, or C1 laminectomy. RESULTS: Patients with NRP had significantly lower C1 sagittal inner diameter, C2-7 range of motion (ROM), C2-7 Cobb angle, and C7 tilt, as well as significantly higher C1-2 ROM, atlantodental interval (ADI), and C1-2 to O-C7 ROM ratio. Multivariate regression analysis revealed that ADI, C2-7 ROM, and C7 tilt were independent risk factors for NRP. Neurological recovery and pseudotumor size reduction were comparable among surgical procedures, whereas post-operative cervical spine function was significantly lower in the O-C fusion group than in the other groups. CONCLUSION: Non-rheumatic retro-odontoid pseudotumor was associated with an increase in ADI, suggesting that spinal arthrodesis surgery is a reasonable strategy for NRP. C1-2 fusion is preferable over O-C fusion because of the high prevalence of ankylosis in the subaxial cervical spine. Given that 29% of patients with NRP have C1 hypoplasia, such cases can be treated by posterior decompression alone. Our study highlights the need to select appropriate surgical procedures based on the underlying pathology in each case.

Risk factors of multidrug-resistant pyogenic spondylitis in thoraco-lumbar spine: A retrospective study of 122 cases.
Katsuhisa Yamada, Masahiko Takahata, Manabu Ito, Ken Nagahama, Akira Iwata, Tsutomu Endo, Hideki Sudo, Nobuhisa Ishiguro, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 27, 1, 95, 100, 2022年01月, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The number of spinal infections has been increasing in developed countries due to the increase of aged or immunosuppressed patients. Spondylitis caused by multidrug-resistant (MDR) bacterial infection often become intractable and require long-term antibiotic therapy and multiple surgeries. Therefore, it is of great importance to understand risk factors for MDR spinal infections. The aim of this study was to elucidate the risk factors for MDR bacterial spondylitis. METHODS: A total of 122 patients (82 men, 40 women; average age: 63.8 y) with thoracic/lumbar spondylitis who underwent posterolateral full-endoscopic debridement and irrigation were included. The organisms detected by this endoscopic procedure were investigated, and the incidence and risk factors for MDR bacterial infection were retrospectively analyzed. RESULTS: Cultures of specimens obtained by endoscopic procedures were positive in 78 patients (63.9%). Among 68 isolated bacteria, MDR bacteria accounted for 47.1%. Multivariate analysis showed that significant risk factors for MDR bacterial infection included autoimmune connective tissue disease (P = 0.03) and central venous catheter (P = 0.02). The incidence of MDR bacteria in patients who were administered a broad-spectrum antibiotic for more than 1 month preoperatively was 64.0%, which was significantly higher than in patients who were administered a broad-spectrum antibiotic for less than 1 month and patients who were administered a narrow-spectrum antibiotic (P < 0.01, P < 0.01, respectively). CONCLUSIONS: The significant risk factors for MDR bacterial spondylitis included immunosuppressed conditions, such as autoimmune connective tissue disease, presence of central venous catheter, and longer administration periods of a broad-spectrum antibiotic. In patients with pyogenic spondylitis who could not be controlled with previous antibiotics and whose result of culture was negative, administration of anti-MRSA antibiotics would be considered when they have the risk factors identified in this study.

Simultaneous Bilateral Proximal Humerus Fractures Treated with Single-Stage Bilateral Reverse Shoulder Arthroplasty.
Taiki Tokuhiro, Atsushi Urita, Yusuke Kameda, Makoto Motomiya, Naoya Watanabe, Norimasa Iwasaki
Case reports in orthopedics, 2022, 2162331, 2162331, 2022年, ［国際誌］
英語, INTRODUCTION: Simultaneous bilateral fractures of the proximal humerus are infrequent, and simultaneous bilateral three- or four-part fractures are even rarer. Reverse shoulder arthroplasty (RSA) is being used increasingly for the treatment of three- and four-part fractures of the proximal humerus. However, treatment of simultaneous bilateral fractures of the proximal humerus is difficult because of concern about postoperative immobilization and rehabilitation. Case Presentation. A 75-year-old woman presented with bilateral shoulder pain subsequent to a fall on the street. Physical examination and radiographs showed simultaneous bilateral fractures of the proximal humerus. The right side fracture was classified as a four-part fracture and the left side fracture as a three-part fracture, according to Neer's classification. The right shoulder had a risk of avascular necrosis of the humeral head. For the left shoulder, the fracture type had caused ischemia of the humeral head. Single-stage bilateral RSA was performed 9 days after the injury. An abduction pillow was applied for 5 weeks postoperatively. Passive motion exercises were permitted starting at 4 weeks postoperatively, and active range of motion exercises were permitted at 6 weeks postoperatively. At the patient's most recent follow-up 30 months after surgery, the patient reported no restriction of the activities of daily living. Radiographs revealed no lucent line on the humerus and glenoid components, although bone resorption and superior retraction of the tuberosities on both sides were observed. CONCLUSIONS: Single-stage bilateral RSA improved shoulder function, but healing of the greater tuberosity can affect the improvement in external rotation after the operation. Although a long-term follow-up is needed, single-stage bilateral RSA appears to be a viable treatment option.

Evaluation of biological responses to micro-particles derived from a double network hydrogel
Gen Matsumae, Mohamad Alaa Terkawi, Takayuki Nonoyama, Takayuki Kurokawa, Daisuke Takahashi, Tomohiro Shimizu, Ken Kadoya, Jian Ping Gong, Kazunori Yasuda, Norimasa Iwasaki
Biomaterials Science, 10, 9, 2182, 2187, Royal Society of Chemistry (RSC), 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, Double network hydrogels have been proven to be a substitute biomaterial for cartilage. For further applications as articular cartilages, it is essential to understand the biological reactions that might be initiated by their micro-particles.

Rheumatoid Arthritis is a Risk Factor for Refracture in Patients with Fragility Fractures.
Hotaka Ishizu, Hirokazu Shimizu, Tomohiro Shimizu, Taku Ebata, Yuki Ogawa, Masahiro Miyano, Kosuke Arita, Yusuke Ohashi, Norimasa Iwasaki
Modern rheumatology, 32, 6, 1017, 1022, 2021年12月03日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: To determine whether patients with rheumatoid arthritis (RA) who have had fragility fractures are at an increased risk of refractures. METHODS: Patients with fragility fractures who were treated surgically at ten hospitals from 2008 to 2017 and who underwent follow-up for more than 24 months were either categorized into a group comprising patients with RA or a group comprising patients without RA (controls). The groups were matched 1:1 by propensity score matching. Accordingly, 240 matched participants were included in this study. The primary outcome was the refracture rate in patients with RA as compared to in the controls. Multivariable analyses were also conducted on patients with RA to evaluate the odds ratios (ORs) for the refracture rates. RESULTS: Patients with RA were significantly associated with increased rates of refractures during the first 24 months (OR: 2.714, 95% confidence interval [95% CI]: 1.015-7.255; P = 0.040). Multivariable analyses revealed a significant association between increased refracture rates and long-term RA (OR: 6.308, 95% CI: 1.195-33.292; P=0.030). CONCLUSIONS: Patients with RA who have experienced fragility fractures are at an increased risk of refractures. Long-term RA is a substantial risk factor for refractures.

Bone Metabolism in the Healing Process of Lumbar Interbody Fusion: Temporal Changes of Bone Turnover Markers.
Ryota Hyakkan, Masahiro Kanayama, Masahiko Takahata, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki
Spine, 46, 23, 1645, 1652, 2021年12月01日, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: The aim of this study was to evaluate temporal changes of bone turnover markers (BTMs) after lumbar spinal fusion in patients without osteoporosis. SUMMARY OF BACKGROUND DATA: Radiological studies are the standard method to monitor bony fusion, but they do not allow a timely assessment of bone healing. BTMs react rapidly to changes in bone metabolism during fusion process and could be an additional tool to monitor this process. METHODS: A total of 78 nonosteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using computed tomography sagittal and coronal images. Serum levels of bone-specific alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP), and osteocalcin (OC) were measured to assess bone formation, and tartrate-resistant acid phosphatase 5b (TRACP-5b) was measured to assess bone resorption. Serum samples were obtained before surgery and at 1, 2, 4, 8, 13, 26, 39, and 52 weeks after surgery. RESULTS: A solid fusion was achieved in 71 of 78 patients (91%), and seven patients resulted in pseudarthrosis. In the fusion group, the level of all BTMs once decreased at 1 postoperative week. Then, BAP and P1NP reached a peak at 4 weeks after surgery, and TRACP-5b and OC peaked at 8 weeks. Thereafter, the level of P1NP and TRACP-5b gradually got closer to the baseline over a year, and BAP kept high until 52 postoperative weeks. In the pseudarthrosis group, peak level of BTMs was significantly higher and the increased level of BAP and P1NP was kept until 52 weeks. CONCLUSION: The present study demonstrated dynamics of BTMs after lumbar spinal fusion in patients without osteoporosis. These normal population data contribute as a baseline to evaluate the effect of osteogenic agents on bone metabolism after spinal fusion.Level of Evidence: 2.

Surgical resection of primary tumor in the extremities improves survival for metastatic soft-tissue sarcoma patients: a population-based study of the SEER database.
M Matsuoka, T Onodera, I Yokota, K Iwasaki, S Matsubara, R Hishimura, E Kondo, N Iwasaki
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 23, 12, 2474, 2481, 2021年12月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The objectives of this study were to clarify whether resection of primary tumor in the extremities for patients with metastatic soft-tissue sarcoma (STS) improves survival, and to clarify patient groups for whom primary tumor resection should be considered. METHODS/PATIENTS: Using the surveillance, epidemiology, and end results database, we identified 1453 patients with metastatic STS of the extremities at initial presentation between 1983 and 2016. Of these 1453 patients, 898 patients underwent primary tumor resection (Surgery group), and 555 patients did not (No-surgery group). RESULTS: After adjusting for patient background by propensity score matching, a total of 804 patients were included for analysis. Patients in the Surgery group showed improved survival (cancer-specific survival (CSS) hazard ratio (HR) = 0.59, 95% confidence interval (CI) 0.50-0.71 overall survival rate (OS) HR = 0.60, 95% CI 0.51-0.70). In subclass analysis, patients with high-grade STS, undifferentiated pleomorphic sarcoma, leiomyosarcoma, or synovial sarcoma showed improved survival in the Surgery group (high grade-CSS HR = 0.57, 95% CI 0.45-0.72, OS HR = 0.58, 95% CI 0.48-0.71; undifferentiated pleomorphic sarcoma-CSS HR = 0.60, 95% CI 0.42-0.84, OS HR = 0.61, 95% CI 0.46-0.82; leiomyosarcoma-CSS HR = 0.50, 95% CI 0.33-0.75, OS HR = 0.50, 95% CI 0.35-0.72; synovial sarcoma-CSS HR = 0.46, 95% CI 0.31-0.68, OS HR = 0.43, 95% CI 0.30-0.62). CONCLUSIONS: Our results indicated that primary tumor resection in metastatic STS exerts positive impacts on survival. Further clinical research is needed to confirm these results.

Quantification of Cartilage Surface Degeneration by Curvature Analysis Using 3D Scanning in a Rabbit Model.
Dawei Liang, Tomohiro Onodera, Masanari Hamasaki, Ryosuke Hishimura, Kentaro Homan, Liang Xu, Yuan Tian, Satoshi Kanai, Norimasa Iwasaki
Cartilage, 13, 2_suppl, 1734S-1741S, 2021年12月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Accurate analysis to quantify cartilage morphology is critical for evaluating degenerative conditions in osteoarthritis (OA). Three-dimensional (3D) optical scanning provides 3D data for the entire cartilage surface; however, there is no consensus on how to quantify it. Our purpose was to validate a 3D method for evaluating spatiotemporal alterations in degenerative cartilages in a rabbit OA model by analyzing their curvatures at various stages of progression. DESIGN: Twelve rabbits underwent anterior cruciate ligament transection (ACLT) unilaterally and were divided into 4 groups: 4 weeks control, 4 weeks OA, 8 weeks control, and 8 weeks OA. 3D scanning, India ink staining, and histological assessments were performed in all groups. In 3D curvature visualization, the surfaces of the condyles were divided into 8 areas. The standard deviations (SD) of mean curvatures from all vertices of condylar surfaces and subareas were calculated. RESULTS: Regarding the site of OA change, curvature analysis was consistent with India ink scoring. The SD of mean curvature correlated strongly with the India ink Osteoarthritis Research Society International (OARSI) score. In curvature histograms, the curvature distribution in OA was more scattered than in control. Of the 8 areas, significant OA progression in the posterolateral part of the lateral condyle (L-PL) was observed at 4 weeks. The histology result was consistent with the 3D evaluation in terms of representative section. CONCLUSIONS: This study demonstrated that 3D scanning with curvature analysis can quantify the severity of cartilage degeneration objectively. Furthermore, the L-PL was found to be the initial area where OA degeneration occurred in the rabbit ACLT model.

Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-κB signaling pathway.
Shunichi Yokota, Gen Matsumae, Tomohiro Shimizu, Tomoka Hasegawa, Taku Ebata, Daisuke Takahashi, Cai Heguo, Yuan Tian, Hend Alhasan, Masahiko Takahata, Ken Kadoya, Mohamad Alaa Terkawi, Norimasa Iwasaki
Bone, 153, 116140, 116140, 2021年12月, ［国際誌］
英語, 研究論文（学術雑誌）, A growing body of evidence suggests that immune factors that regulate osteoclast differentiation and bone resorption might be promising therapeutic agents for the treatment of osteoporosis. The expression of CLCF1, an immune cell-derived molecule, has been reported to be reduced in patients with postmenopausal osteoporosis. This suggests that it may be involved in bone remodeling. Thus, we explored the functional role of CLCF1 in osteoclastogenesis and bone loss associated with osteoporosis. Surprisingly, the administration of recombinant CLCF1 repressed excessive bone loss in ovariectomized mice and prevented RANKL-induced bone loss in calvarial mouse model. Likewise, the addition of recombinant CLCF1 to RANKL-stimulated monocytes resulted in a significant suppression in the number of differentiated osteoclasts with small resorption areas being observed on dentine slices in vitro. At the same dosage, CLCF1 did not exhibit any detectable negative effects on the differentiation of osteoblasts. Mechanistically, the inhibition of osteoclast differentiation by the CLCF1 treatment appears to be related to the activation of interferon signaling (IFN) and the suppression of the NF-κB signaling pathway. Interestingly, the expression of the main components of IFN-signaling namely, STAT1 and IRF1, was detected in macrophages as early as 1 h after stimulation with CLCF1. Consistent with these results, the blockade of STAT1 in macrophages abolished the inhibitory effect of CLCF1 on osteoclast differentiation in vitro. These collective findings point to a novel immunoregulatory function of CLCF1 in bone remodeling and highlight it as a potentially useful therapeutic agent for the treatment of osteoporosis.

Stress distribution pattern in the distal radioulnar joint before and after ulnar shortening osteotomy in patients with ulnar impaction syndrome
Kazutoshi Hontani, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Daisuke Momma, Hiroki Hamano, Norimasa Iwasaki
Scientific Reports, 11, 1, 17891, 17891, Springer Science and Business Media LLC, 2021年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Ulnar shortening osteotomy (USO) for ulnar impaction syndrome potentially leads to degenerative changes of the distal radioulnar joint (DRUJ). This study was performed to evaluate the effect of the sigmoid notch morphology on the stress distribution pattern of the DRUJ using computed tomography (CT) osteoabsorptiometry (CT-OAM). We reviewed the pre- and postoperative transverse CT images of 15 wrists that had undergone USO. The examined wrists were classified into two groups based on the sigmoid notch morphology: the linear-type notch (type L) and the curved-type notch (type C). We calculated and statistically compared the percentage of the high-density area (%HDA) in each divided region of the sigmoid notch. In type L, %HDA was significantly larger in the distal-dorsal region of the sigmoid notch before USO. Postoperatively, in type L, no specific regions showed a significantly different %HDA. In type C, %HDA was significantly larger in the distal-volar region of the sigmoid notch before USO. Postoperatively, %HDA of type C was significantly larger in the proximal-volar region. Our results suggest that in patients with ulnar impaction syndrome, morphological evaluation of the sigmoid notch can serve as a predictor of osteoarthritis in the DRUJ with or without USO.

No patella resurfacing total knee arthroplasty leads to reduction in the thickness of patellar cartilage to less than half within 5 years: a quantitative longitudinal evaluation using MRI.
Dai Sato, Masayuki Inoue, Takuro Sasaki, Jun Uchida, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
Journal of experimental orthopaedics, 8, 1, 107, 107, 2021年11月24日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Patellar resurfacing in total knee arthroplasty (TKA) remains controversial as recent meta-analyses have not shown its clear superiority; however, most authors recommend it because it is associated with less frequent anterior knee pain and need for reoperation. We aimed to clarify the changes in patellar cartilage thickness in no patellar resurfacing TKA using a ceramic femoral component on magnetic resonance imaging (MRI). METHODS: Between 2009 and 2014, 40 consecutive patients (59 knees) were included in this study. All patients underwent TKA using zirconia ceramic femoral implants without patellar resurfacing. Indications for no patellar resurfacing TKA were absence of anterior knee pain, patellar compression pain, and osteoarthritic changes in the patellofemoral joint on plain radiography. The mean postoperative follow-up duration was 81.5 months (range, 25-131 months). Clinical and radiological evaluations were performed preoperatively and 5 years after TKA. Patellar cartilage thickness was evaluated preoperatively and every year for 5 years after TKA using MRI T2-weighted imaging. The patellar cartilage was divided into three regions of interest: medial, central, and lateral. To standardise the variation in patellar thickness among patients, the percent cartilage thickness was calculated. RESULTS: The implant's position was appropriate in all cases. Compared to preoperative scores, 5 years postoperatively, the Japanese Orthopedic Association score and Oxford knee score significantly improved from 52.1 to 84.7; mean tilting angle and congruence angle did not change significantly; mean lateral shift ratio significantly increased from 7.1% to 14.6%; cartilage thickness significantly decreased (P < 0.05); and the percentage cartilage thickness of the central, medial, and lateral cartilage zones gradually thinned to less than half. Four patients underwent conversion to patellar resurfacing due to anterior knee pain, without loosening the femoral and tibial implants. CONCLUSION: The patellar cartilage thickness decreased to less than half its preoperative level within 5 years after no patellar resurfacing TKA; this would led to clinical problems and conversion to patellar resurfacing. LEVEL OF EVIDENCE: Level III.

Computed tomography revealed the correlation between radiolucency and alignment of all-polyethylene pegged glenoid component more than 10 years after total shoulder arthroplasty in the Japanese population.
Yuki Matsui, Daisuke Momma, Naoki Suenaga, Atsushi Urita, Chika Yoshioka, Naomi Oizumi, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 28, 1, 131, 137, 2021年11月24日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Anatomical total shoulder arthroplasty (TSA) provides successful long-term outcomes but complications can occur after 10 years that require revision. Computed tomography (CT) is a useful tool for assessing radiolucent lines around the glenoid component of TSA; however, the merits of long-term post-TSA follow up with CT are unclear. The purpose of this study was to evaluate the long-term outcomes after TSA of Japanese population and to identify factors related to radiolucency around the glenoid component using CT. METHODS: A retrospective review was conducted of TSA patients who had completed at least 10 years of clinical follow up. Radiographs and CT images of the affected shoulder obtained at the last follow up were evaluated for radiolucent lines around the stem and each peg, superior inclination and retroversion of the glenoid component, subluxation index, and critical shoulder angle (CSA). Shoulder ROM, Constant-Murley score and UCLA score were compared between the preoperative and last follow up period. RESULTS: Eighteen shoulders in 16 patients met the inclusion criteria. Mean patient age was 61 years, mean follow up period was 137 months, and mean Yian CT score was 19%. CT score was significantly highest in pegs located inferiorly (p < 0.05). Mean glenoid superior inclination was 12.6°, retroversion was -0.3°, subluxation index was 46%, and CSA was 33.7°. Glenoid superior inclination was significantly lower (p = 0.007) in shoulders with possible loosening than in cases with no loosening (5.0° vs 15.6°). Mean Constant score and UCLA score improved significantly after TSA, from 25.8 to 10.7 points preoperatively to 70.1 and 28.9 points postoperatively, respectively. Mean shoulder flexion, internal rotation, and external rotation also showed improvement postoperatively. CONCLUSION: TSA provides good long-term outcomes. Radiolucency was present most frequently around the inferior pegs of the glenoid component. Glenoid superior inclination may affect the formation of radiolucent lines around glenoid pegs. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment study.

Thrombocytopenia Associated with Unrecognized Non-Alcoholic Fatty Liver Disease Is an Independent Predictor of Perioperative Significant Blood Loss in Cervical Laminoplasty.
Ryota Suzuki, Yoshinao Koike, Masahiro Ota, Tsutomu Endo, Yuichiro Hisada, Takeru Tsujimoto, Masahiro Kanayama, Yoichi M Ito, Hideki Sudo, Akira Iwata, Katsuhisa Yamada, Norimasa Iwasaki, Masahiko Takahata
World neurosurgery, 155, e797-e804, 2021年11月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To identify risk factors for significant blood loss (SBL) in cervical laminoplasty, especially regarding thrombocytopenia and coagulopathy resulting from non-alcoholic fatty liver disease (NAFLD). METHODS: We retrospectively investigated differences in patient background data, laboratory data at the time of admission, and surgery-related data of 317 patients who underwent cervical laminoplasty and were divided into SBL (estimated blood loss [EBL] + drainage [D] ≥500 g) and non-SBL (EBL + D < 500 g) groups. To evaluate liver status, we used the fibrous 4 index and considered fibrous 4 index ≥1.85 as a representative phenotype for NAFLD with liver fibrosis. In addition, the risk factor for perioperative SBL was investigated using multiple logistic regression analysis, and the cutoff value was calculated. RESULTS: Incidence of perioperative SBL in cervical laminoplasty was 7.3% (23/317). Compared with the non-SBL group, the SBL group demonstrated significantly lower platelet count (PLT), lower aspartate aminotransferase, longer operation time, and greater number of opened laminae. According to multivariate analysis, lower PLT and a greater number of opened laminae were identified as significant risk factors for perioperative SBL. The cutoff value of PLT for predicting SBL was determined to be 16.7 × 104/μL using a receiver operating characteristic curve. The liver fibrosis group revealed significantly lower PLT and greater EBL + D than the non-liver fibrosis group. CONCLUSIONS: Thrombocytopenia is an independent predictor of perioperative SBL in cervical laminoplasty. Thus, patients with mild thrombocytopenia that may be associated with NAFLD must be carefully monitored to avoid perioperative SBL.

ハイブリット人工知能システムを用いた寛骨臼形成不全の自動解析システムの開発　　　　　　　　　　　　　　　
清水 寛和, 清水 智弘, 高橋 大介, 小川 拓也, 岩崎 倫政
日本小児整形外科学会雑誌, 30, 3, S56, S56, (一社)日本小児整形外科学会, 2021年11月
日本語

当院における発育性股関節形成不全に対するAngulated Innominate Osteotomy(AIO)の経時的変化の検討　　　　　　　　　　　　　　　
高橋 練也, 高橋 大介, 清水 智弘, 小川 拓也, 中村 夢志郎, 宮崎 拓自, 岩崎 倫政, 亀ヶ谷 真琴
日本小児整形外科学会雑誌, 30, 3, S70, S70, (一社)日本小児整形外科学会, 2021年11月
日本語

乳児股関節脱臼ハイリスク児における超音波とX線を用いた経時的な画像評価　　　　　　　　　　　　　　　
大橋 佑介, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本小児整形外科学会雑誌, 30, 3, S82, S82, (一社)日本小児整形外科学会, 2021年11月
日本語

発育性股関節形成不全に対するAngulated Innominate Osteotomy(AIO)の3次元的評価　　　　　　　　　　　　　　　
小川 拓也, 清水 智弘, 宮崎 拓自, 中村 夢志郎, 高橋 大介, 岩崎 倫政
日本小児整形外科学会雑誌, 30, 3, S85, S85, (一社)日本小児整形外科学会, 2021年11月
日本語

全身MRIを用いた特発性大腿骨頭壊死症患者の多発骨壊死の評価
横田 隼一, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 浅野 毅, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 40, 3, 214, 214, (一社)日本関節病学会, 2021年11月
日本語

Modular型S-ROMステム、またはPolishedセメントステム用いた短縮骨切り併用THAの中期成績の比較検討
宮崎 拓自, 清水 智弘, 中村 夢志郎, 高橋 要, 大浦 久典, 片山 直行, 岩崎 倫政
日本関節病学会誌, 40, 3, 264, 264, (一社)日本関節病学会, 2021年11月
日本語

偏心性寛骨臼回転骨切り術における応力分布の縦断的評価
中村 夢志郎, 清水 智弘, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 40, 3, 266, 266, (一社)日本関節病学会, 2021年11月
日本語

関節リウマチ患者の2010年以降の下肢手術数の動向と併存症発生に関する調査
糸賀 稜, 清水 智弘, 高橋 大介, 小野寺 智洋, 岩崎 倫政
日本関節病学会誌, 40, 3, 285, 285, (一社)日本関節病学会, 2021年11月
日本語

脆弱性骨折をきたした関節リウマチ患者の再骨折リスク
石津 帆高, 清水 寛和, 清水 智弘, 横田 隼一, 岩崎 倫政
日本関節病学会誌, 40, 3, 287, 287, (一社)日本関節病学会, 2021年11月
日本語

高齢者に対するPolished Taperセメントステムを用いた人工股関節全置換術の成績
山崎 秀, 清水 智弘, 中村 夢志郎, 宮崎 拓自, 高橋 大介, 岩崎 倫政
日本関節病学会誌, 40, 3, 300, 300, (一社)日本関節病学会, 2021年11月
日本語

Serum C-reactive protein is an early, simple and inexpensive prognostic marker for the progression of intramedullary lesion on magnetic resonance imaging from acute to subacute stage in patients with spinal cord injury.
Masahiro Ozaki, Kota Suda, Tsunehiko Konomi, Satoko Matsumoto Harmon, Miki Komatsu, Akio Minami, Morio Matsumoto, Masaya Nakamura, Masahiko Takahata, Norimasa Iwasaki
Spinal cord, 59, 11, 1155, 1161, 2021年11月, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Retrospective chart audit. OBJECTIVES: This study aimed to identify conventional routine blood testing biomarkers associated with the progression of intramedullary injured area in patients with spinal cord injury (SCI). SETTING: A spinal cord injury center in Hokkaido, Japan. METHODS: We retrospectively reviewed 71 consecutive adults with acute SCI who were admitted within 24 h after injury and diagnosed as American Spinal Injury Association Impairment Scale Grade A or B at admission. Participants were divided into the progression (P group) and no progression group (NP group) based on the change of the hyperintense signal abnormality in the spinal cord on magnetic resonance imaging from the time of admission to 4 weeks after injury. Individual characteristics and blood testing data obtained in the first 4 weeks after injury were compared between groups. RESULTS: The P and NP groups were comprised of 16 and 55 participants, respectively. In univariate analyses, white blood cell (WBC) count on day 3 was significantly higher in group P than group NP (P = 0.021), as was serum C-reactive protein (CRP) level on day 3 (P = 0.015) and day 7 (P = 0.047). Multivariable analysis identified serum CRP level on day 3 as a significant independent prognostic factor for the progression of secondary SCI (OR, 1.138; 95% confidence interval, 1.01-1.28; P = 0.034). CONCLUSIONS: Serum CRP level on day 3 after injury was a good predictor for the progression of intramedullary signal intensity change on MRI from acute to subacute stage in patients with SCI.

Brain Metastasis in Soft Tissue Sarcoma at Initial Presentation.
Ryo Itoga, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Shinji Matsubara, Ryosuke Hishimura, Yuki Suzuki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki
Anticancer research, 41, 11, 5611, 5616, 2021年11月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND/AIM: Brain metastasis is a rare condition among patients with soft tissue sarcoma (STS), and its precise incidence remains unclear. The aim of this study was to investigate which patients should be screened for brain metastasis. PATIENTS AND METHODS: We identified all patients with STS diagnosed between 2010 and 2015 in the SEER database. Incidence of brain metastasis at initial presentation and higher incidence of brain metastasis by histological subtype were investigated. In addition, risk factors for brain metastasis were examined. RESULTS: A total of 26,676 patients were included for analysis, of whom 162 patients (0.6%) had brain metastasis. Alveolar soft part sarcoma (6.3%), malignant hemangioendothelioma (3.1%) and malignant schwannoma (2.6%) showed higher incidence of brain metastasis. Deep-rooted tumor, trunk tumor, and histological high-grade tumor tended to show higher incidence of brain metastasis. CONCLUSION: Risk factors for brain metastasis were deep location, trunk development and histologically high-grade tumor, or specific histological subtypes.

Hydroxyapatite‐hybridized double‐network hydrogel surface enhances differentiation of bone marrow‐derived mesenchymal stem cells to osteogenic cells
Takuma Kaibara, Lei Wang, Masumi Tsuda, Takayuki Nonoyama, Takayuki Kurokawa, Norimasa Iwasaki, Jian Ping Gong, Shinya Tanaka, Kazunori Yasuda
Journal of Biomedical Materials Research Part A, 110, 4, 747, 760, Wiley, 2021年10月28日, ［国際誌］
英語, 研究論文（学術雑誌）, Recently, we have developed a hydroxyapatite (HAp)-hybridized double-network (DN) hydrogel (HAp/DN gel), which can robustly bond to the bone tissue in the living body. The purpose of this study is to clarify whether the HAp/DN gel surface can differentiate the bone marrow-derived mesenchymal stem cells (MSCs) to osteogenic cells. We used the MSCs which were harvested from the rabbit bone marrow and cultured on the polystyrene (PS) dish using the autogenous serum-supplemented medium. First, we confirmed the properties of MSCs by evaluating colony forming unit capacity, expression of MSC markers using flow cytometry, and multidifferential capacity. Secondly, polymerase chain reaction analysis demonstrated that the HAp/DN gel surface significantly enhanced mRNA expression of the eight osteogenic markers (TGF-β1, BMP-2, Runx2, Col-1, ALP, OPN, BSP, and OCN) in the cultured MSCs at 7 days than the PS surfaces (p < 0.0001), while the DN gel and HAp surfaces provided no or only a slight effect on the expression of these markers except for Runx2. Additionally, the alkaline phosphatase activity was significantly higher in the cells cultured on the HAp/DN gel surface than in the other three material surfaces (p < 0.0001). Thirdly, when the HAp/DN gel plug was implanted into the rabbit bone marrow, MSC marker-positive cells were recruited in the tissue generated around the plug at 3 days, and Runx2 and OCN were highly expressed in these cells. In conclusion, this study demonstrated that the HAp/DN gel surface can differentiate the MSCs into osteogenic cells.

Glenohumeral joint preservation using continuous intramedullary perfusion of high-concentration antibiotics in a patient with septic shoulder arthritis and proximal humerus osteomyelitis: A case report.
Mitsutoshi Ota, Atsushi Urita, Hiroki Shibayama, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 28, 6, 1548, 1551, 2021年10月26日, ［国内誌］
英語

Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity.
Tsutomu Endo, Yoshinao Koike, Yuichiro Hisada, Ryo Fujita, Ryota Suzuki, Masaru Tanaka, Takeru Tsujimoto, Yukitoshi Shimamura, Yuichi Hasegawa, Masahiro Kanayama, Katsuhisa Yamada, Akira Iwata, Hideki Sudo, Misaki Ishii, Norimasa Iwasaki, Masahiko Takahata
Global spine journal, 13, 5, 21925682211031514, 21925682211031514, 2021年10月06日, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVES: There is insufficient data on the clinical features of ossification of the ligamentum flavum (OLF) of the thoracic spine and the risk of progression of ossified lesions. The link between obesity and ossification of the posterior longitudinal ligament (OPLL), which frequently coexists with OLF, has been demonstrated. However, the link between obesity and OLF has not been recognized. We aimed to determine the prevalence of obesity in thoracic OLF and whether the severity of OLF is associated with the degree of obesity. METHODS: A total of 204 symptomatic Japanese subjects with thoracic OLF and 136 subjects without spinal ligament ossification as controls were included. OLF subjects were divided into 3 groups: 1) localized OLF (OLF <2-intervertebral regions); 2) multilevel OLF (OLF ≥3-intervertebral regions); and 3) OLF + OPLL. The severity of OLF was quantified using the OLF index using computed tomography imaging of the entire spine. RESULTS: The proportion of severely obese subjects (BMI ≥ 30 kg/m2) was significantly higher both in the multilevel OLF group (25.5%) and the OLF + OPLL group (44.3%) than in the localized OLF group (3.6%) and the control group (1.4%) (P < 0.01). BMI, age, and coexistence of cervical OPLL and lumbar OLF were associated with thoracic OLF index in the multiple regression analysis. CONCLUSIONS: Our findings demonstrated that obesity is a distinct feature of multilevel OLF in the thoracic spine and that the severity of OLF is associated with the degree of obesity.

Extrusion of the medial meniscus is a potential predisposing factor for post-arthroscopy osteonecrosis of the knee.
Jun Yamaguchi, Kazunori Yasuda, Eiji Kondo, Takuma Kaibara, Daisuke Ueda, Koji Yabuuchi, Jun Onodera, Norimasa Iwasaki, Mitsuru Saito, Tomonori Yagi
BMC musculoskeletal disorders, 22, 1, 852, 852, 2021年10月05日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Post-arthroscopic osteonecrosis of the knee (PAONK) is a rare condition. No studies have analyzed the relationship between the meniscus extrusion and PAONK. The purpose of this retrospective study is to test a hypothesis that the degree of the medial meniscus (MM) extrusion might be significantly greater in the knees with PAONK than in the matched control knees both before and after the meniscectomy. METHODS: Ten knees with PAONK were detected out of a total of 876 knees which had undergone arthroscopic partial meniscectomy of the MM. Ten matched control knees were randomly selected out of the remaining 866 knees without PAONK. The clinical data of these 20 patients were retrospectively collected from the medical records. To evaluate the location of the menisci on the joint line, Extrusion width and Inner width were defined on a coronal section of magnetic resonance imaging (MRI). The intra- and inter-rater reliability was evaluated by calculating the intra- and inter-class coefficients. Statistical comparisons between the 2 groups were made using the 3 non-parametric tests. RESULTS: Before the meniscectomy, the Extrusion width of the MM (mean 4.7 ± 1.4 mm) was significantly greater than that (3.0 ± 1.3 mm) in the Control group (P = 0.0195). In the MRI taken in a range from 3 to 50 weeks after the meniscectomy, the Extrusion width of the MM (5.9 ± 1.1 mm) in the PAONK group was significantly greater than that (3.4 ± 1.4 mm) in the Control group (P = 0.0009), and the Inner width of the MM (0.6 ± 1.7 mm) in the PAONK group was significantly less than that (3.9 ± 1.0 mm) in the Control group (P = 0.0001). CONCLUSION: A significant relationship was found between the degree of the MM extrusion and the onset of PAONK. This study suggested that the extrusion of the MM is a potential predisposing factor for PAONK.

Changes in elbow joint contact area in symptomatic valgus instability of the elbow in baseball players.
Kyosuke Numaguchi, Daisuke Momma, Yuki Matsui, Jun Oohinata, Takayoshi Yamaguchi, Nozomu Inoue, Eiji Kondo, Norimasa Iwasaki
Scientific reports, 11, 1, 19782, 19782, 2021年10月05日, ［国際誌］
英語, 研究論文（学術雑誌）, The aim of this study was to evaluate the joint contact area of the dominant side and that of the non-dominant side without valgus instability in symptomatic pitchers. Ten symptomatic elbow medial ulnar collateral ligament (UCL) deficient baseball pitchers participated in this study. Computed tomography (CT) data from the dominant and non-dominant elbows were obtained with and without elbow valgus stress. The CT imaging data of each elbow joint were reconstructed using a 3D reconstruction software package, and the radiocapitellar and ulnohumeral joint contact areas were calculated. The center of the contact area and the translation from the position without stress to the position with valgus stress were also calculated. With elbow valgus stress, the contact area changed, and the center of the radiocapitellar joint contact area translated significantly more laterally in the dominant elbow than in the non-dominant elbow (p = 0.0361). In addition, the center of the ulnohumeral joint contact area translated significantly more posteriorly in the dominant elbow than in the non-dominant elbow (p = 0.0413). These changes in contact areas could be the reason for cartilage injury at the posterior trochlea in pitchers with UCL deficiency.

関節リウマチにおける軟骨細胞の新たな役割 IL-6アンプとTMEM147　　　　　　　　　　　　　　　
太田 光俊, 田中 勇希, 岩崎 倫政, 村上 正晃
リウマチ科, 66, 4, 393, 403, (有)科学評論社, 2021年10月
日本語

Blood flow distribution after end-to-side anastomosis with wide arteriotomy in extremity free flap surgery.
Makoto Motomiya, Naoya Watanabe, Shunichi Nakamura, Yusuke Kameda, Daisuke Kawamura, Norimasa Iwasaki
Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 74, 10, 2495, 2503, 2021年10月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Although many studies have investigated the optimal anastomotic procedure for the end-to-side (ETS) procedure with a free flap, no study has focused on the size of the arteriotomy. Some surgeons have recently described the effectiveness of ETS with wide arteriotomy, but the postoperative haemodynamics remains unclear for free flaps created using this technique. The aim of this study was to use ultrasonography to evaluate the postoperative blood flow distribution after ETS with a wide arteriotomy in extremity free flap surgery. METHODS: We evaluated 20 free flaps in 18 consecutive patients who received an ultrasonographic examination after free flap surgery using the ETS technique with wide arteriotomy for arterial anastomosis. All flaps were examined after surgery and blood flow was calculated for the flap and recipient vessels. RESULTS: All 20 flaps survived, but one flap developed asymptomatic arterial thrombosis and 19 flaps were analysed. For the ETS technique with wide arteriotomy, peripheral circulation was well preserved in all flaps. Comparison of flap types showed that blood flow was significantly higher in myocutaneous flaps than in fasciocutaneous flaps, but there was no significant difference according to the size of the arteriotomy. CONCLUSIONS: Given the range of arteriotomy performed using the ETS with a wide arteriotomy technique, the blood flow volume in the flap depended on the type of flap but not on the size of the arteriotomy. A steal phenomenon related to the creation of a wide window in the receipt artery was not found in the analysed retrospective cohort.

Stress on the posteromedial region of the proximal tibia increased over time after anterior cruciate ligament injury.
Soya Miura, Koji Iwasaki, Eiji Kondo, Kaori Endo, Shinji Matsubara, Masatake Matsuoka, Tomohiro Onodera, Norimasa Iwasaki
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 30, 5, 1744, 1751, 2021年09月10日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Anterior cruciate ligament (ACL) injury induces anterior and rotatory instability of the knee. However, the effect of this instability on the stress distribution in the knee joint in living participants is not clear. The aim of this study was to compare the distribution pattern of subchondral bone density across the proximal tibia in the knees with and without ACL injury, and to investigate the correlation between the distribution patterns of the subchondral bone density and the duration of ACL-deficiency. METHODS: Radiographic and computed tomography (CT) data pertaining to 20 patients with unilateral ACL injury without combined injury (ACL-deficient group) and 19 nontraumatic subjects (control group) were collected retrospectively. Subchondral bone density of the proximal tibia was assessed using CT-osteoabsorptiometry. Both the medial and lateral compartments of the proximal tibia were divided into three subregions of equal width in the sagittal direction. The percentage of high subchondral bone density areas (HDA%) in each subregion was quantitatively analyzed. RESULTS: HDA% of the posteromedial region was significantly higher in the ACL-deficient group (mean: 21.6%) than in the control group (14.7%) (p = 0.002). In contrast, HDA% of the anteromedial region was significantly lower in the ACL-deficient group (9.4%) than in the control group (15.3%) (p = 0.048). The logarithm of the time elapsed from ACL injury to CT examination showed a significant correlation with HDA% in the posteromedial region (p = 0.032). CONCLUSIONS: Subchondral bone density in the posteromedial region significantly increased after ACL injury and correlated with the duration of ACL-deficiency in semi-log manner in meniscus intact knees. The increase in stress on the posteromedial region after ACL injury, which induces a change in the subchondral bone density, justifies early ACL reconstruction after ACL injury.

Stress distribution pattern in the distal radioulnar joint before and after ulnar shortening osteotomy in patients with ulnar impaction syndrome.
Kazutoshi Hontani, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Daisuke Momma, Hiroki Hamano, Norimasa Iwasaki
Scientific reports, 11, 1, 17891, 17891, 2021年09月09日, ［国際誌］
英語, 研究論文（学術雑誌）, Ulnar shortening osteotomy (USO) for ulnar impaction syndrome potentially leads to degenerative changes of the distal radioulnar joint (DRUJ). This study was performed to evaluate the effect of the sigmoid notch morphology on the stress distribution pattern of the DRUJ using computed tomography (CT) osteoabsorptiometry (CT-OAM). We reviewed the pre- and postoperative transverse CT images of 15 wrists that had undergone USO. The examined wrists were classified into two groups based on the sigmoid notch morphology: the linear-type notch (type L) and the curved-type notch (type C). We calculated and statistically compared the percentage of the high-density area (%HDA) in each divided region of the sigmoid notch. In type L, %HDA was significantly larger in the distal-dorsal region of the sigmoid notch before USO. Postoperatively, in type L, no specific regions showed a significantly different %HDA. In type C, %HDA was significantly larger in the distal-volar region of the sigmoid notch before USO. Postoperatively, %HDA of type C was significantly larger in the proximal-volar region. Our results suggest that in patients with ulnar impaction syndrome, morphological evaluation of the sigmoid notch can serve as a predictor of osteoarthritis in the DRUJ with or without USO.

Thrombocytopenia Associated with Unrecognized Non-Alcoholic Fatty Liver Disease Is an Independent Predictor of Perioperative Significant Blood Loss in Cervical Laminoplasty.
Ryota Suzuki, Yoshinao Koike, Masahiro Ota, Tsutomu Endo, Yuichiro Hisada, Takeru Tsujimoto, Masahiro Kanayama, Yoichi M Ito, Hideki Sudo, Akira Iwata, Katsuhisa Yamada, Norimasa Iwasaki, Masahiko Takahata
World neurosurgery, 155, e797-e804, 2021年09月09日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To identify risk factors for significant blood loss (SBL) in cervical laminoplasty, especially regarding thrombocytopenia and coagulopathy resulting from non-alcoholic fatty liver disease (NAFLD). METHODS: We retrospectively investigated differences in patient background data, laboratory data at the time of admission, and surgery-related data of 317 patients who underwent cervical laminoplasty and were divided into SBL (estimated blood loss [EBL] + drainage [D] ≥500 g) and non-SBL (EBL + D < 500 g) groups. To evaluate liver status, we used the fibrous 4 index and considered fibrous 4 index ≥1.85 as a representative phenotype for NAFLD with liver fibrosis. In addition, the risk factor for perioperative SBL was investigated using multiple logistic regression analysis, and the cutoff value was calculated. RESULTS: Incidence of perioperative SBL in cervical laminoplasty was 7.3% (23/317). Compared with the non-SBL group, the SBL group demonstrated significantly lower platelet count (PLT), lower aspartate aminotransferase, longer operation time, and greater number of opened laminae. According to multivariate analysis, lower PLT and a greater number of opened laminae were identified as significant risk factors for perioperative SBL. The cutoff value of PLT for predicting SBL was determined to be 16.7 × 104/μL using a receiver operating characteristic curve. The liver fibrosis group revealed significantly lower PLT and greater EBL + D than the non-liver fibrosis group. CONCLUSIONS: Thrombocytopenia is an independent predictor of perioperative SBL in cervical laminoplasty. Thus, patients with mild thrombocytopenia that may be associated with NAFLD must be carefully monitored to avoid perioperative SBL.

Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study.
Katsuhisa Yamada, Maeda Kenichiro, Yoichi M Ito, Fujio Inage, Toshiyuki Isoe, Nozomi Yokota, Osamu Sugita, Norihiro Sato, Khin Khin Tha, Norimasa Iwasaki, Teruyo Arato, Hideki Sudo
Contemporary clinical trials communications, 23, 100805, 100805, 2021年09月, ［国際誌］
英語, 研究論文（学術雑誌）, Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.

Short-term efficacy and safety of zoledronate acid or denosumab in Japanese patients with postmenopausal osteoporosis.
Yumejiro Nakamura, Tomohiro Shimizu, Tsuyoshi Asano, Shun Shimodan, Hotaka Ishizu, Daisuke Takahashi, Masahiko Takahata, Norimasa Iwasaki
Journal of bone and mineral metabolism, 39, 5, 824, 832, 2021年09月, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: We aimed to compare the efficacy after switching from either bisphosphonates (BPs) or non-BPs (NBPs) to combination therapies of denosumab (DMAb) or zoledronic acid (Zol) with eldecalcitol (ELD) in bone mineral density (BMD) and bone metabolism and investigate the prognostic and risk factors of side effects of this therapy. MATERIALS AND METHODS: One-hundred forty-eight patients with postmenopausal osteoporosis were recruited; their therapy was switched from BPs or NBPs to Zol or DMAb plus ELD (BP-Zol: 43, NBP-Zol: 32, BP-DMAb: 35, and NBP-DMAb: 38). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were evaluated. RESULTS: In the BP-Zol group, P1NP did not change after 6 months and increased by 38.9% after 12 months. TRACP-5b decreased 15.8% after 6 months, but came back to baseline values 12 months after administration. In the rest of the groups, the bone metabolic markers remained suppressed after 6 and 12 months. Compared with baseline, all groups showed increase in BMD after 6 and 12 months. Bone metabolic markers at baseline were correlated with %change in lumbar spine BMD from baseline to 12 months. P1NP and 25-hydroxy vitamin D levels at baseline were identified as potential predictors of development of acute-phase reactions. CONCLUSIONS: The combination therapy of Zol or DMAb and ELD may increase BMD at 12 months after the first administration in Japanese patients with postmenopausal osteoporosis, regardless of BPs pretreatment. Bone metabolic markers at baseline may be useful predictors for reaction to the therapy and side effects caused by these combination therapies in postmenopausal osteoporosis.

Effects after starting or switching from bisphosphonate to romosozumab or denosumab in Japanese postmenopausal patients.
Tomohiro Shimizu, Kosuke Arita, Eihiro Murota, Shigeto Hiratsuka, Ryo Fujita, Hotaka Ishizu, Tsuyoshi Asano, Daisuke Takahashi, Masahiko Takahata, Norimasa Iwasaki
Journal of bone and mineral metabolism, 39, 5, 868, 875, 2021年09月, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: We aimed to investigate the longitudinal changes in bone metabolic markers and bone mineral density (BMD) after starting or switching from bisphosphonate (BP) to romosozumab (ROMO) or denosumab (DENO) therapies over 12 months and to determine predictors that establish associations with changes in BMD among the patients received the ROMO therapy. METHODS: Postmenopausal osteoporosis patients with a high risk of fracture-154 in total-were recruited; their therapies were switched to ROMO or DENO from BP/naïve or vitamin D (ND) (ND-ROMO: 43, BP-ROMO: 38, ND-DENO: 38, and BP-DENO: 35). Longitudinal changes in bone metabolic markers and BMD were evaluated. RESULTS: ROMO groups showed significant increases in BMD of the lumbar spine at 6 and 12 months and femoral neck at 12 months compared to the DENO groups. Although BP-ROMO showed significant increase in the lumbar spine BMD compared to BP-DENO, there were no significant differences in femoral neck and total hip BMDs between BP-ROMO and BP-DENO. Among the ROMO groups, % changes of BMD from baseline to 12 months were associated with bone metabolic markers at baseline and changes in TRACP-5b from baseline to 3 months. CONCLUSIONS: ROMO continuously increased BMD for 12 months and performed better than DENO. On the other hand, effects of ROMO switched from BP on BMD of femoral neck and total hip were almost same with DENO. Bone metabolic markers at baseline and changes in TRACP-5b from baseline to 3 months may predict the efficacy of ROMO after 12 months of administration.

Risks vs. benefits of switching therapy in patients with postmenopausal osteoporosis.
Hotaka Ishizu, Kosuke Arita, Mohamad Alaa Terkawi, Tomohiro Shimizu, Norimasa Iwasaki
Expert review of endocrinology & metabolism, 16, 5, 217, 228, 2021年09月, ［国際誌］
英語, 研究論文（学術雑誌）, Introduction: Osteoporosis is characterized by the fragility of bones, leading to fractures and, consequently, the deterioration of functional capacity and quality of life. Postmenopausal women, in particular, are prone to osteoporosis and often require anti-osteoporosis treatment. In the last few decades, various anti-osteoporosis drugs have been approved for clinical use. In an aging society, osteoporosis cannot be treated using a single agent; therefore, switching therapy is an important treatment strategy.Areas covered: This review covers switching therapy in patients with postmenopausal osteoporosis. It's extremely important to understand the characteristics of each drug including; limitations on the duration of use, side effects due to long-term use (such as atypical femur fracture and osteonecrosis of the jaw) or discontinuation (such as rebound phenomenon), compliance, and ability to prevent fractures. We review and summarize the risks and benefits of switching therapy.Expert opinion: When switching therapy, the order of drug administration is important. Routine monitoring should be continued after switching treatments. We recommend first using osteoanabolic agents in postmenopausal women with severe osteoporosis. In addition, identifying predictors of the efficacy and side effects of treatment may help prevent the inappropriate use of drugs for the treatment of osteoporosis.

Targeting thymidine phosphorylase as a potential therapy for bone loss associated with periprosthetic osteolysis.
Gen Matsumae, Tomohiro Shimizu, Yuan Tian, Daisuke Takahashi, Taku Ebata, Hend Alhasan, Shunichi Yokota, Ken Kadoya, Mohamad Alaa Terkawi, Norimasa Iwasaki
Bioengineering & translational medicine, 6, 3, e10232, 2021年09月, ［国際誌］
英語, 研究論文（学術雑誌）, Macrophages are generally thought to play a key role in the pathogenesis of aseptic loosening through initiating periprosthetic inflammation and pathological bone resorption. The aim of this study was to identify macrophage-derived factors that promote osteoclast differentiation and periprosthetic bone destruction. To achieve this, we examined the effects of 12 macrophage-derived factors that were identified by RNA-seq analysis of stimulated macrophages on osteoclast differentiation. Surprisingly, thymidine phosphorylase (TYMP) was found to trigger significant number of osteoclasts that exhibited resorbing activities on dentine slices. Functionally, TYMP knockdown reduced the number of osteoclasts in macrophages that had been stimulated with polyethylene debris. TYMP were detected in serum and synovial tissues of patients that had been diagnosed with aseptic loosening. Moreover, the administration of TYMP onto calvariae of mice induced pathological bone resorption that was accompanied by an excessive infiltration of inflammatory cells and osteoclasts. The RNA-seq for TYMP-induced-osteoclasts was then performed in an effort to understand action mode of TYMP. TYMP stimulation appeared to activate the tyrosine kinase FYN signaling associated with osteoclast formation. Oral administration of saracatinib, a FYN kinase inhibitor, significantly suppressed formation of bone osteolytic lesions in a polyethylene debris-induced osteolysis model. Our findings highlight a novel molecular target for therapeutic intervention in periprosthetic osteolysis.

Close association between non-alcoholic fatty liver disease and ossification of the posterior longitudinal ligament of the spine.
Tsutomu Endo, Yoshinao Koike, Hideaki Miyoshi, Yuichiro Hisada, Ryo Fujita, Ryota Suzuki, Masaru Tanaka, Takeru Tsujimoto, Yukitoshi Shimamura, Yuichi Hasegawa, Masahiro Kanayama, Tomoyuki Hashimoto, Fumihiro Oha, Naoki Noro, Kiyofumi Komano, Misaki Ishii, Yoichi M Ito, Norimasa Iwasaki, Masahiko Takahata
Scientific reports, 11, 1, 17412, 17412, 2021年08月31日, ［国際誌］
英語, 研究論文（学術雑誌）, Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease of unknown etiology occurring frequently in individuals with metabolic disturbances. Obesity has been suggested as a potential risk factor for the severity of OPLL. We aimed to investigate whether non-alcoholic fatty liver disease (NAFLD) is associated with OPLL severity. We assessed the severity of NAFLD by a liver-to-spleen (L/S) ratio on computed tomography (CT) scans of 85 symptomatic OPLL patients at a single institution in Japan. We also assessed the severity of OPLL by CT reconstruction sagittal and axial images. The prevalence of NAFLD in middle-aged patients (age < 70 years, n = 50) was 80.3%, which was 2.5-8 times higher than that in the general Japanese population (9-30%). The ossification index of the spinal ligaments increased in proportion to the severity of fatty liver. The L/S ratio was revealed as a significant risk factor associated with the total ossification index (standardized β: -0.40, 95% confidence interval - 54.34 to - 4.22). This study suggests the potential contribution of NAFLD to the progression of OPLL. The close association between NAFLD and OPLL demonstrated in this study warrants further study to elucidate the causal nature of this relationship.

Functional reconstructions using only ulnar nerve and ulnar nerve-innervated muscles for traumatic musculocutaneous, median and radial nerve palsies.
Makoto Motomiya, Naoya Watanabe, Daisuke Kawamura, Norimasa Iwasaki
BMJ case reports, 14, 8, 2021年08月20日, ［国際誌］
英語, 研究論文（学術雑誌）, A 20-year-old right-handed fisherman experienced a severe injury in a high-energy traffic accident. These injuries included a shaft fracture of the right humerus, open comminuted fracture of the right forearm and multiple peripheral nerve palsies involving the musculocutaneous, median and radial nerves. Six months after the initial treatment, the patient was referred to our hand surgeons for further treatment. Several operations for functional reconstruction using only the ulnar nerve and ulnar nerve-innervated muscles were performed: the main procedures included a partial ulnar nerve transfer for elbow flexion, flexor carpi ulnaris transfer for reconstruction of wrist and finger extension and opponensplasty using the abductor digiti minimi. Three years after the initial injury, the patient had relatively good function including elbow flexion and stable side pinch and grasp. Functional reconstruction using a combination of the ulnar nerve and ulnar nerve-innervated muscles may be useful in specific cases involving multiple peripheral nerve injuries.

Medial closed-wedge distal femoral osteotomy with local bone grafts for large collapsed steroid-induced osteonecrosis of the lateral femoral condyle: A case report.
Takuma Kaibara, Eiji Kondo, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Daisuke Momma, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 28, 6, 1470, 1477, 2021年08月04日, ［国内誌］
英語

Radiological predictors associated with success of treatment for developmental dysplasia of hip using the Pavlik harness: A retrospective study.
Takuya Ogawa, Tomohiro Shimizu, Tsuyoshi Asano, Norimasa Iwasaki, Daisuke Takahashi
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 27, 5, 1067, 1072, 2021年08月04日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: While various predictors of treatment outcome of Pavlik harness have been reported, appropriate indications for treatment and relationships between patient characteristics and outcome are unclear. The present study aimed to identify radiological predictors for successful Pavlik harness treatment of DDH at the initiation of treatment and investigate the progression of radiological characteristics after successful treatment. METHODS: One-hundred-forty-two of 527 infants who visited our hospital for secondary screening of DDH were treated with the Pavlik harness. One-hundred-eight hips of 108 infants experienced successful treatment and could be followed up until 3 years of age (group S); treatment was unsuccessful within the first 2 weeks for 22 hips of 21 infants (group F). We investigated the Graf classification and radiological parameters. RESULTS: We observed the ipsilateral-side measurements of distance A and B as defined by Yamamuro and Chene's method to be significantly smaller and greater, respectively, in group F compared with those of group S. Group F tended to exhibit the smaller distance A and larger distance B compared to the group S among the same Graf type. The cut-off values for successful treatment at were >7.4 mm at initiation of treatment for distance A and <11.2 mm for distance B. The acetabular index (AI) of the ipsilateral side at the initiation of treatment was significantly correlated with that at 1 and 3 years of age. Patients with an AI of >32° at the initiation of harness treatment were more likely to exhibit hip dysplasia at 3 years of age. CONCLUSIONS: Radiographic parameters prior to the Pavlik harness could be predictors of treatment failure and DDH in the future. This study showed that AI at the initiation of treatment is associated with residual acetabular dysplasia, suggesting that radiographic assessment may be useful even considering the risks associated with radiation exposure.

軸索再生に至適な移植細胞の同定を目的とした新しい末梢神経再建モデル
遠藤 健, 角家 健, 鈴木 裕貴, 河村 太介, 岩崎 倫政
北海道整形災害外科学会雑誌, 63, 1, 1, 13, 北海道整形災害外科学会, 2021年08月
日本語, 中枢神経と比較すると,末梢神経の再生能力は旺盛であるが,近位部損傷や重度損傷例では,軸索再生の量および速度が十分でないため,臨床成績は不良である.また,医療の発展にも関わらず,半世紀以上,自家神経移植に優る末梢神経再建方法はなく,自家組織を犠牲にせずに,軸索再生を促進する新規治療法の開発が望まれている.なかでも,近年の幹細胞研究の発展から,細胞治療に対する期待は大きい.しかし,軸索再生に至適な移植細胞は未だ明らかでない.今回,各種細胞の軸索再生効果の比較に有用な実験モデルを作成した.本モデルでは,野生型LEWISラットの坐骨神経に2ヶ所の圧挫損傷(25mm間隔)を作成し,続いて圧挫に挟まれた範囲の無細胞化のために液体窒素を用いた凍結融解処理を行った.作成したモデルの妥当性を検討するため,同系RFP発現ラットから採取したa)シュワン細胞(SC)またはb)骨髄間葉系間質細胞(Mesenchymal stromal cell:MSC)を移植し,対照群としてc)線維芽細胞(Fibroblast:Fb)移植,d)細胞移植なし,e)無細胞処置なし(圧挫単独)の3群を作成した.処置後2週の軸索再生はSC移植群で最も良好で,一方MSC,Fb移植群に軸索再生効果は認めず,移植細胞の軸索再生効果を明瞭に検出可能な実験モデルであった.興味深いことに,移植細胞の有無,種類に関わらず,無細胞野には宿主SCが遊走し,SCの分布量と再生軸索数には強い正の相関を認めた.さらには,全ての再生軸索にはSCが密接していた.これらの結果は末梢神経の再生過程にSCが極めて重要であることを示唆する所見であった.本モデルは,移植細胞の軸索再生効果の同定,および軸索再生効果の生物学的評価に有用な実験モデルであることが示された.(著者抄録)

大腿骨顆間外側壁における骨密度分布 前十字靱帯の大腿骨付着部についての考察
菅原 悠太郎, 岩崎 浩司, 遠藤 香織, 菱村 亮介, 松原 新史, 松岡 正剛, 門間 太輔, 小野寺 智洋, 近藤 英司, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1715, S1715, (公社)日本整形外科学会, 2021年08月
日本語

Morphological analysis of Kambin's triangle using 3D CT/MRI fusion imaging of lumbar nerve root created automatically with artificial intelligence.
Katsuhisa Yamada, Ken Nagahama, Yuichiro Abe, Yoshinori Hyugaji, Masahiko Takahata, Norimasa Iwasaki
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 30, 8, 2191, 2199, 2021年08月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: We developed a software program that automatically extracts a three-dimensional (3D) lumbar nerve root image from magnetic resonance imaging (MRI) lumbar nerve volume data using artificial intelligence. The aim of this study is to evaluate the morphology of Kambin's triangle in three dimensions based on an actual endoscopic transforaminal surgical approach using three-dimensional (3D) computed tomography (CT)/ magnetic resonance imaging (MRI) fusion images of the lumbar spine and nerve tissue. METHODS: Three-dimensional lumbar spine/nerve images of 100 patients (31 males and 69 females; mean age, 66.8 years) were used to evaluate the relationship between the superior articular process (SAP), exiting nerve root (ENR), and dural canal at the L2/3, L3/4, and L4/5 levels at 45° and 60° approach angles. RESULTS: The SAP-ENR distance at 60° was the greatest at L4/5 and was significantly greater at L2/3 and L4/5 than at L3/4 (P < 0.01, P < 0.01, respectively). The SAP-ENR distance at 45° was the greatest at L2/3, and it was larger in L2/3 and L4/5 than in L3/4 (P < 0.01, P < 0.01, respectively). The SAP-ENR distances at L4/5 were significantly greater at 60° than at 45° (P < 0.01). The dural canal was located within Kambin's triangle on the plane of the upper endplate of the lower vertebra at L2/3 in 41.5% of the cases and at L3/4 in 14% of the cases at 60° but not at L4/5. CONCLUSION: The 3D lumbar spine/nerve image enabled a combined assessment of the positional relationship between the SAP, ENR, and dural canal to quantify the safety zone of practical endoscopic spinal surgery using a transforaminal approach. Three-dimensional lumbar spine/nerve images could be useful for examining parameters, including bones and nerves, to ensure the safety of surgery.

Exceptional Conditions for Favorable Neurological Recovery After Laminoplasty in Cases with Cervical Myelopathy Caused by K-line (-) Ossification of Posterior Longitudinal Ligament.
Takeru Tsujimoto, Tsutomu Endo, Yusuke Menjo, Masahiro Kanayama, Itaru Oda, Kota Suda, Ryo Fujita, Yoshinao Koike, Yuichiro Hisada, Norimasa Iwasaki, Masahiko Takahata
Spine, 46, 15, 990, 998, 2021年08月01日, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: A retrospective observational study. OBJECTIVE: To clarify the exceptional conditions for a favorable neurological recovery after laminoplasty (LMP) for cervical myelopathy caused by K-line (-) ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: The K-line-based classification of cervical OPLL was developed to predict insufficient neurological recovery after LMP. For patients with K-line (-) OPLL, LMP generally yields the least improvement because of inadequate decompression of the spinal cord; however, there are some exceptional cases wherein LMP promotes favorable neurological recoveries. METHODS: We retrospectively reviewed the medical records of 106 consecutive patients who underwent LMP for cervical OPLL to determine the demographic data, radiographic findings, and neurological recoveries of the patients as assessed preoperatively and 2 years postoperatively by their Japanese Orthopedic Association (JOA) scores. The factors associated with favorable outcomes after LMP in patients with K-line (-) were then investigated. RESULTS: Of 106 total patients, 31 were classified as K-line (-), of whom 21 achieved the least neurological recovery after LMP (JOA recovery rate <50%), while the remaining 10 patients achieved favorable outcomes (JOA recovery rate ≥50%). Among the K-line (-) group patients, those with ext-K-line (+), which changed to K-line (+) in the neck-extended position, and the patients with up-K-line (-), in whom the lesion responsible for myelopathy in the upper cervical spine (C3 or above), showed favorable neurological recoveries after LMP. CONCLUSION: Our data shows that, even for patients with K-line (-) OPLL, a favorable neurological recovery can be expected after LMP in cases in which the OPLL is in the upper cervical spine or the K-line changes to (+) in the neck-extended position. This means that K-line-based predictions of surgical outcomes after LMP should be indicated for patients with OPLL in the middle and lower cervical spine with limited extension mobility.Level of Evidence: 4.

Dynamic Evaluation of Intraneural Microvascularity of the Ulnar Nerve Using Contrast-Enhanced Ultrasonography in Patients With Cubital Tunnel Syndrome
Yuichiro Matsui, Tatsunori Horie, Tadanao Funakoshi, Daisuke Kawamura, Mutsumi Nishida, Norimasa Iwasaki
The Journal of Hand Surgery, 47, 7, 687.e1-687.e8, Elsevier BV, 2021年08月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The purpose of this study was to compare the intraneural microvascular patterns of the ulnar nerve at 2 elbow flexion angles in asymptomatic volunteers and patients with cubital tunnel syndrome (CuTS) and to evaluate the effects of surgery on the microvascular pattern in patients with CuTS by using contrast-enhanced ultrasonography (CEUS). METHODS: This study included 10 elbows in 10 asymptomatic volunteers (control group) and 10 elbows in 10 patients with CuTS who underwent anterior subcutaneous transposition of the ulnar nerve (CuTS group). The CuTS group underwent clinical and electrophysiologic examinations and CEUS before surgery and at 1, 2, and 3 months after surgery. The intraneural enhancement pattern was calculated as an area under the curve (AUC) value in the entrapment site of the ulnar nerve within the cubital tunnel and in the area 1 cm proximal to the site (proximal site) at elbow flexion angles of 20° and 110°. RESULTS: Serial electrophysiologic examinations showed improvements at 1, 2, and 3 months after surgery compared with before surgery. In the control group, the AUC values of the central part of the cubital tunnel and proximal sites showed no substantial changes with the increase in elbow flexion. In the CuTS group, the AUC in the proximal site at 110° of elbow flexion was decreased compared with that at 20° of flexion before surgery. The AUC values for both the entrapment and proximal sites at 20° and 110° of elbow flexion were the most increased at 2 months after surgery compared with before surgery. CONCLUSIONS: Increased elbow flexion in patients with CuTS influences the intraneural blood flow of the ulnar nerve. Surgery for CuTS alters the intraneural blood flow. CLINICAL RELEVANCE: Quantitative evaluation of the intraneural blood flow of the ulnar nerve using CEUS may be a new supplementary diagnostic tool for CuTS and an indicator for the evaluation of postoperative recovery from nerve damage.

Delayed Onset of Infectious Foreign Body Granuloma for Nonabsorbable Sutures After Open Achilles Tendon Repair: A Case Report.
Ryo Itoga, Masatake Matsuoka, Tomohiro Onodera, Ai Shimizu, Koji Iwasaki, Shinji Matsubara, Ryosuke Hishimura, Eiji Kondo, Norimasa Iwasaki
The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons, 60, 6, 1297, 1300, 2021年07月20日, ［国際誌］
英語, Foreign body granulomas from sutures are more common among non-absorbable sutures compared to absorbable sutures and have been reported as a postoperative complication in a variety of medical fields. However, only a few cases of delayed foreign body reaction have been reported and addressed with orthopedics. We present a patient with systemic lupus erythematosus who developed an infectious suture granuloma that extended to the entire Achilles tendon and was induced by nonabsorbable sutures that were used for open Achilles tendon repair 20 years before. This granuloma was resistant to antibiotic treatment and drainage and required surgical intervention. The tumor was marginally resected, and the continuity of the Achilles tendon was preserved. Histopathological examination detected many suture materials surrounded by xanthochromic necrotic lesions and the lesion was diagnosed as a foreign body granuloma. At 1 year after the operation, the patient did not exhibit exacerbation of infection or recurrence of the tumor, and she became able to walk by herself. To the best of our knowledge, this represents the first report of an infectious delayed foreign body granuloma in autoimmune disorder patient after open Achilles tendon repair. Surgical intervention should be considered, as treatment with conservative therapy such as antibiotics may be difficult.

Ultrapurified Alginate Gel Containing Bone Marrow Aspirate Concentrate Enhances Cartilage and Bone Regeneration on Osteochondral Defects in a Rabbit Model.
Liang Xu, Atsushi Urita, Tomohiro Onodera, Ryosuke Hishimura, Takayuki Nonoyama, Masanari Hamasaki, Dawei Liang, Kentaro Homan, Jian Ping Gong, Norimasa Iwasaki
The American journal of sports medicine, 49, 8, 2199, 2210, 2021年07月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects. HYPOTHESIS: The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks. RESULTS: The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; P < .05), the UPAL group (10.0 ± 3.3; P < .05), and the UPAL-MSC group (12.2 ± 2.9; P < .05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; P < .05), the UPAL group (14.2 ± 3.9; P < .05), and the UPAL-MSC group (16.3 ± 3.6; P < .05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups. CONCLUSION: The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model. CLINICAL RELEVANCE: These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation.

Ulnar nerve morphology during elbow flexion in patients with and without cubital tunnel syndrome: a sonographic study
Yuichiro Matsui, Tatsunori Horie, Norimasa Iwasaki
Journal of Hand Surgery (European Volume), 47, 2, 175319342110261, 175319342110261, SAGE Publications, 2021年06月30日, ［国際誌］
英語, 研究論文（学術雑誌）

Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis.
Taku Ebata, Mohamad Alaa Terkawi, Masanari Hamasaki, Gen Matsumae, Tomohiro Onodera, Mahmoud Khamis Aly, Shunichi Yokota, Hend Alhasan, Tomohiro Shimizu, Daisuke Takahashi, Kentaro Homan, Ken Kadoya, Norimasa Iwasaki
iScience, 24, 6, 102643, 102643, 2021年06月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Synovial macrophages that are activated by cartilage fragments initiate synovitis, a condition that promotes hypertrophic changes in chondrocytes leading to cartilage degeneration in OA. In this study, we analyzed the molecular response of chondrocytes under condition of this type of stimulation to identify a molecular therapeutic target. Stimulated macrophages promoted hypertrophic changes in chondrocytes resulting in production of matrix-degrading enzymes of cartilage. Among the top-upregulated genes, FliI was found to be released from activated chondrocytes and exerted autocrine/paracrine effects on chondrocytes leading to an increase in expression of catabolic and hypertrophic factors. Silencing FliI in stimulated cells significantly reduced expression of catabolic and hypertrophic factors in cocultured chondrocytes. Our further results demonstrated that the FliI-TLR4-ERK1/2 axis is involved in the hypertrophic signaling of chondrocytes and catabolism of cartilage. Our findings provide a new insight into the pathogenesis of OA and identify a potentially new molecular target for diagnostics and therapeutics.

In vivo deformation of anatomically pre-bent rods in thoracic adolescent idiopathic scoliosis.
Hideki Sudo, Hiroyuki Tachi, Terufumi Kokabu, Katsuhisa Yamada, Akira Iwata, Tsutomu Endo, Masahiko Takahata, Yuichiro Abe, Norimasa Iwasaki
Scientific reports, 11, 1, 12622, 12622, 2021年06月16日, ［国際誌］
英語, 研究論文（学術雑誌）, Some surgical strategies can maintain or restore thoracic kyphosis (TK); however, next-generation surgical schemes for adolescent idiopathic scoliosis (AIS) should consider anatomical corrections. A four-dimensional correction could be actively achieved by curving the rod. Thus, anatomically designed rods have been developed as notch-free, pre-bent rods for easier anatomical reconstruction. This study aimed to compare the initial curve corrections obtained using notch-free rods and manually bent, notched rods for the anatomical reconstruction of thoracic AIS. Two consecutive series of 60 patients who underwent anatomical posterior correction for main thoracic AIS curves were prospectively followed up. After multilevel facetectomy, except for the lowest instrumented segment, either notch-free or notched rods were used. Patient demographic data, radiographic measurements, and sagittal rod angles were analyzed within 1 week after surgery. Patients with notch-free rods had significantly higher postoperative TK than patients with notched rods (P < .001), but both groups achieved three-dimensional spinal corrections and significantly increased postoperative rates of patients with T6-T8 TK apex (P = .006 for notch-free rods and P = .008 for notched rods). The rod deformation angle at the concave side was significantly lower in the notch-free rods than in the notched rods (P < .001). The notch-free, pre-bent rod can maintain its curvature, leading to better correction or maintenance of TK after anatomical spinal correction surgery than the conventional notched rod. These results suggest the potential benefits of anatomically designed notch-free, pre-bent rods over conventional, manually bent rods.

Morphologic Changes in the Vertebral Artery Subsequent to Cervical Spine Degeneration and Aging: Analyses by Computed Tomography Angiography Using Multiplanar and 3-Dimensional Reconstructions.
Takashi Ohnishi, Kota Suda, Miki Komatsu, Satoko Matsumoto Harmon, Takamasa Watanabe, Mitsuru Asukai, Ken Kadoya, Masahiko Takahata, Norimasa Iwasaki, Akio Minami
World neurosurgery, 150, e686-e695, 2021年06月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To identify the morphologic changes in the vertebral artery (VA) subsequent to cervical spine degeneration and aging and to investigate the risk factors for iatrogenic VA injury or occlusion. METHODS: Eighty-eight consecutive patients (176 bilateral VAs) were retrospectively analyzed using radiographs, computed tomography, and computed tomography angiography images. The Kellgren and Lawrence (KL) score and its modified subscores were used to grade the severity of degenerative changes in the cervical spine. VA tortuosity widths and diameters were measured between the C2 and C6 transverse foramens. The outcome measures were statistically analyzed for difference, correlation, and explanatory variable. The level with a high prevalence of VA stenosis was also evaluated. RESULTS: There were significant positive correlations between the KL score and VA tortuosity width, and between age and VA tortuosity width. Osteophyte formation in the facet joint was the predominant explanatory variable for medial deviation of the VA. Significant positive correlations were evident between the dominant VA diameter and KL score or age. VA stenosis occurred at C3/C4 (24.5%) with the highest prevalence and it was caused by uncovertebral joint osteophytes (52.0%) with the highest incidence. CONCLUSIONS: The present study provides important evidence for decisions of surgical strategy and for avoiding catastrophic VA injury or occlusion in cervical spine surgeries.

An algorithm for using deep learning convolutional neural networks with three dimensional depth sensor imaging in scoliosis detection.
Terufumi Kokabu, Satoshi Kanai, Noriaki Kawakami, Koki Uno, Toshiaki Kotani, Teppei Suzuki, Hiroyuki Tachi, Yuichiro Abe, Norimasa Iwasaki, Hideki Sudo
The spine journal : official journal of the North American Spine Society, 21, 6, 980, 987, 2021年06月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND CONTEXT: Timely intervention in growing individuals, such as brace treatment, relies on early detection of adolescent idiopathic scoliosis (AIS). To this end, several screening methods have been implemented. However, these methods have limitations in predicting the Cobb angle. PURPOSE: This study aimed to evaluate the performance of a three-dimensional depth sensor imaging system with a deep learning algorithm, in predicting the Cobb angle in AIS. STUDY DESIGN: Retrospective analysis of prospectively collected, consecutive, nonrandomized series of patients at five scoliosis centers in Japan. PATIENT SAMPLE: One hundred and-sixty human subjects suspected to have AIS were included. OUTCOME MEASURES: Patient demographics, radiographic measurements, and predicted Cobb angle derived from the deep learning algorithm were the outcome measures for this study. METHODS: One hundred and sixty data files were shuffled into five datasets with 32 data files at random (dataset 1, 2, 3, 4, and 5) and five-fold cross validation was performed. The relationships between the actual and predicted Cobb angles were calculated using Pearson's correlation coefficient analyses. The prediction performances of the network models were evaluated using mean absolute error and root mean square error between the actual and predicted Cobb angles. The shuffling into five datasets and five-fold cross validation was conducted ten times. There were no study-specific biases related to conflicts of interest. RESULTS: The correlation between the actual and the mean predicted Cobb angles was 0.91. The mean absolute error and root mean square error were 4.0° and 5.4°, respectively. The accuracy of the mean predicted Cobb angle was 94% for identifying a Cobb angle of ≥10° and 89% for that of ≥20°. CONCLUSIONS: The three-dimensional depth sensor imaging system with its newly innovated convolutional neural network for regression is objective and has significant ability to predict the Cobb angle in children and adolescents. This system is expected to be used for screening scoliosis in clinics or physical examination at schools.

Stress-Distribution Pattern Across the Glenohumeral Joint in Collegiate and Professional Baseball Players: A Computed Tomography Osteoabsorptiometry Study.
Kyosuke Numaguchi, Daisuke Momma, Yuki Matsui, Masashi Yokota, Jun Oohinata, Eiji Kondo, Norimasa Iwasaki
Orthopaedic journal of sports medicine, 9, 6, 23259671211009185, 23259671211009185, 2021年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The influence of long-term loading conditions on the articular surfaces of the glenohumeral joint can be determined by measuring stress-distribution patterns. Long-term pitching activity changes the stress distribution across the glenohumeral joint surface; however, the influence of competitive level on stress-distribution patterns remains unclear. Purpose: To use computed tomography (CT) osteoabsorptiometry (CTOAM) to evaluate the distribution of subchondral bone density across the glenohumeral joint in collegiate and professional baseball players as well as to determine the effects of pitching activity on the articular surfaces. Study Design: Descriptive laboratory study. Methods: We evaluated 73 shoulders in 50 baseball players. CT imaging data were obtained from the dominant-side shoulder of 12 professional pitchers (PP group) and 15 professional fielders (PF group). CT imaging data were also obtained from both shoulders of 12 asymptomatic collegiate pitchers (CP group) and 11 collegiate fielders (CF group). The pattern of distribution of subchondral bone density across the articular surfaces of each glenohumeral joint was assessed by CTOAM. As a measure of bone density, the mean Hounsfield units (HU) were obtained for each joint surface, and the absolute values of the dominant shoulder were compared for each group. Results: Stress-distribution patterns over the articular surfaces differed between the dominant and nondominant sides in the CP group as well as between both collegiate groups versus the PP group. In the CP group, the mean HU of the humeral head surface were greater on the nondominant versus dominant side (P = .035). On the dominant side, the mean HU of the humeral head surface and glenoid were greater in the CP versus the PP group (P = .001 and .027, respectively). Conclusion: Stress distribution on the articular surface of the glenohumeral joint was affected by pitching ability and competitive level. Our analysis indicates that the traction force on the glenohumeral joint surface might be greater than compression force during pitching. Clinical Relevance: The present findings suggest that pitching activity results in low stress to the articular surfaces of the glenohumeral joint. This supports the notion that mechanical conditions play a crucial role in the etiology of disorders specific to pitching activity.

Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study
Katsuhisa Yamada, Maeda Kenichiro, Yoichi M. Ito, Fujio Inage, Toshiyuki Isoe, Nozomi Yokota, Osamu Sugita, Norihiro Sato, Khin Khin Tha, Norimasa Iwasaki, Teruyo Arato, Hideki Sudo
Contemporary Clinical Trials Communications, 23, 100805, 100805, Elsevier BV, 2021年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.

Ultrapurified Alginate Gel Containing Bone Marrow Aspirate Concentrate Enhances Cartilage and Bone Regeneration on Osteochondral Defects in a Rabbit Model
Liang Xu, Atsushi Urita, Tomohiro Onodera, Ryosuke Hishimura, Takayuki Nonoyama, Masanari Hamasaki, Dawei Liang, Kentaro Homan, Jian Ping Gong, Norimasa Iwasaki
The American Journal of Sports Medicine, 49, 8, 036354652110141, 036354652110141, SAGE Publications, 2021年06月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects.

The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects.

Controlled laboratory study.

A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks.

The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; P < .05), the UPAL group (10.0 ± 3.3; P < .05), and the UPAL-MSC group (12.2 ± 2.9; P < .05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; P < .05), the UPAL group (14.2 ± 3.9; P < .05), and the UPAL-MSC group (16.3 ± 3.6; P < .05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups.

The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model.

These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation.

Differential effects of anti-RANKL monoclonal antibody and zoledronic acid on necrotic bone in a murine model of Staphylococcus aureus-induced osteomyelitis.
Hideyuki Kobayashi, Ryo Fujita, Shigeto Hiratsuka, Tomohiro Shimizu, Dai Sato, Hiroki Hamano, Norimasa Iwasaki, Masahiko Takahata
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2021年05月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Osteomyelitis is characterized by progressive inflammatory bone destruction accompanied by severe pain and disability. However, with the exception of antibiotic therapies, there is no established therapy to protect the bone from infectious osteolysis. The anti-receptor activator of nuclear factor-kB ligand (RANKL) monoclonal antibody (anti-RANKL Ab) is a potential drug based on its proven effectiveness in preventing joint bone erosion in rheumatoid arthritis; however, the efficacy and adverse effects of anti-RANKL Ab in osteomyelitis remain to be investigated. In this study, we investigated the effects of anti-mouse RANKL Ab on acute osteomyelitis and compared them with those of zoledronic acid (ZA) using a murine model. Mice were inoculated with bioluminescent Staphylococcus aureus (Xen 29) on their left femur and then treated with ZA, anti-RANKL Ab, or phosphate-buffered saline as control. A 21-day longitudinal observational study using microcomputed tomography showed that both anti-RANKL Ab and ZA had an osteoprotective effect against infectious osteolysis. However, it was also demonstrated through bioluminescence imaging that ZA delayed the spontaneous reduction of bacterial load and through histology that it increased the amount of necrotic bone, while anti-RANKL Ab did not. Findings from histopathological and in vitro studies suggest that an intense inflammatory response around the necrotic bone could induce osteoclasts in a RANKL-independent manner, leading to the removal of necrotic bone, even after administration of the anti-RANKL Ab therapy. Collectively, anti-RANKL Ab may exert an osteoprotective effect without hampering the removal of the necrotic bone, which serves as a nidus for infection in osteomyelitis.

Predictive factors for irreversible motor paralysis following cervical spinal cord injury.
Tsunehiko Konomi, Kota Suda, Masahiro Ozaki, Satoko Matsumoto Harmon, Miki Komatsu, Seiji Iimoto, Osahiko Tsuji, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Morio Matsumoto, Masaya Nakamura
Spinal cord, 59, 5, 554, 562, 2021年05月, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: A retrospective observational study. OBJECTIVES: To elucidate predictive clinical factors associated with irreversible complete motor paralysis following traumatic cervical spinal cord injury (CSCI). SETTING: Hokkaido Spinal Cord Injury Center, Japan. METHODS: A consecutive series of 447 traumatic CSCI persons were eligible for this study. Individuals with complete motor paralysis at admission were selected and divided into two groups according to the motor functional outcomes at discharge. Initial findings in magnetic resonance imaging (MRI) and other clinical factors that could affect functional outcomes were compared between two groups of participants: those with and those without motor recovery below the level of injury at the time of discharge. RESULTS: Of the 73 consecutive participants with total motor paralysis at initial examination, 28 showed some recovery of motor function, whereas 45 remained complete motor paralysis at discharge, respectively. Multivariate logistic regression analysis showed that the presence of intramedullary hemorrhage manifested as a confined low intensity changes in diffuse high-intensity area and more than 50% of cord compression on MRI were significant predictors of irreversible complete motor paralysis (odds ratio [OR]: 8.4; 95% confidence interval [CI]: 1.2-58.2 and OR: 14.4; 95% CI: 2.5-82.8, respectively). CONCLUSION: The presence of intramedullary hemorrhage and/or severe cord compression on initial MRI were closely associated with irreversible paralysis in persons with motor complete paralysis following CSCI. Conversely, subjects with a negligible potential for recovery could be identified by referring to these negative findings.

Concomitant arthrodesis of the distal interphalangeal joint with surface replacement arthroplasty of the proximal interphalangeal joint: a comparative study in 11 patients.
Hiroki Hamano, Daisuke Kawamura, Norimasa Iwasaki
The Journal of hand surgery, European volume, 46, 4, 416, 417, 2021年05月, ［国際誌］
英語

Total shoulder arthroplasty with an anteriorly augmented glenoid component for glenohumeral osteoarthritis with anterior glenoid bone loss: a case report.
Shusei Kurashige, Atsushi Urita, Norimasa Iwasaki
JSES international, 5, 3, 365, 370, 2021年05月, ［国際誌］
英語

Patient characteristics affecting knowledge of the possibility of surgical reconstruction for rheumatoid hand and wrist deformities.
Makoto Motomiya, Naoki Nishimoto, Atsushi Urita, Daisuke Kawamura, Yuka Shimizu, Norimasa Iwasaki
Modern rheumatology, 31, 3, 614, 620, 2021年05月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: We aimed to investigate patient characteristics affecting their knowledge of surgical reconstruction for rheumatoid hand and wrist deformities, and to investigate such characteristics affecting their hope of receiving hand surgery if patients with rheumatoid arthritis (RA) knew surgical reconstruction options. METHODS: We carried out a questionnaire survey for all patients with RA who came to our outpatient department of rheumatology. Multivariate logistic regression analysis was performed to examine significant characteristics associated with the knowledge of surgical reconstruction and patients' hope of receiving hand surgery. RESULTS: In total, 687 patients were evaluated in this study and 337 (49%) reported knowledge about surgical reconstruction. A multivariate logistic regression analysis showed that patients with good control of disease activity and with long-lasting hand and wrist deformities were significantly associated with having knowledge of surgical reconstruction. Among the 337 patients with knowledge, only 122 (36%) expressed a hope of receiving hand surgery. The statistical analysis showed that younger age and surgical history were significantly associated with the hope of receiving surgery. CONCLUSION: Surgeons and rheumatologists should enlighten patients about the importance of hand surgery to achieve functional remission in this new era of treatment for patients with RA.

Efficacy and safety of sodium RISedronate for glucocorticoid-induced OsTeoporosis with rheumaTOid arthritis (RISOTTO study): A multicentre, double-blind, randomized, placebo-controlled trial.
Yuichiro Fujieda, Tetsuya Horita, Naoki Nishimoto, Kazuhide Tanimura, Yoshiharu Amasaki, Hideki Kasahara, Shin Furukawa, Tsuyoshi Takeda, Shinji Fukaya, Kazuo Matsui, Akito Tsutsumi, Akira Furusaki, Akira Sagawa, Kou Katayama, Kaoru Takeuchi, Kazuaki Katsumata, Takashi Kurita, Peter Shane, Masaru Kato, Kenji Oku, Shinsuke Yasuda, Masahiko Takahata, Norimasa Iwasaki, Tatsuya Atsumi
Modern rheumatology, 31, 3, 593, 599, 2021年05月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. METHODS: This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints. RESULTS: Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92-5.05] vs Placebo: 0.12% [95% CI: -2.07 to 2.30], p < .0001). No significant difference was found in the femoral neck and total hip BMD. Although adverse events were observed in 28 patients, none were considered serious. Non-traumatic vertebral fractures were identified in 10 patients. CONCLUSION: Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA.

Effect of High Tibial Osteotomy on the Distribution of Subchondral Bone Density Across the Proximal Tibial Articular Surface of the Knee With Medial Compartment Osteoarthritis.
Koji Iwasaki, Eiji Kondo, Shinji Matsubara, Masatake Matsuoka, Kaori Endo, Isao Yokota, Tomohiro Onodera, Norimasa Iwasaki
The American journal of sports medicine, 49, 6, 1561, 1569, 2021年05月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The effect of high tibial osteotomy (HTO) on the stress distribution across the knee joint is not completely understood. Subchondral bone density is considered to reflect the pattern of stress distribution across a joint surface. PURPOSE: To assess the distribution of subchondral bone density across the proximal tibia in nonarthritic knees and in the knees of patients with osteoarthritis (OA) before and after HTO. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We retrospectively collected radiological and computed tomography data from 16 patients without OA (control group) and 17 patients with OA. Data from the OA group were collected before and 1.5 years after HTO. Subchondral bone density of the proximal tibia was assessed with computed tomography-osteoabsorptiometry. The locations and percentages represented by high-density areas (HDAs) on the articular surface were quantitatively analyzed. RESULTS: The ratio of the HDA of the medial compartment to the total HDA (medial ratio) was significantly higher in the preoperative OA group (mean, 80.1%) than in the control group (61.3%) (P < .001). After HTO, the medial ratio decreased significantly to 75.1% (P = .035 in comparison with preoperative values) and was significantly correlated with the hip-knee-ankle angle in both groups: control (r = -0.551; P = .033) and OA (r = -0.528; P = .043). The change in medial ratio after HTO was significantly correlated with the change in hip-knee-ankle angle (r = 0.587; P = .035). In the medial compartment, the HDA in the most lateral region of 4 subregions increased after HTO, but that in 3 medial subregions decreased. CONCLUSION: In this exploratory study, HTO shifted the HDA of the medial compartment of the proximal tibial articular surface toward the lateral compartment. In contrast, the HDA of the most lateral region of the medial compartment increased after HTO. This change in subchondral bone density may result from the change in stress distribution.

Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis
Taku Ebata, Mohamad Alaa Terkawi, Masanari Hamasaki, Gen Matsumae, Tomohiro Onodera, Mahmoud Khamis Aly, Shunichi Yokota, Hend Alhasan, Tomohiro Shimizu, Daisuke Takahashi, Kentaro Homan, Ken Kadoya, Norimasa Iwasaki
iScience, 102643, 102643, Elsevier BV, 2021年05月
研究論文（学術雑誌）

Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review.
Takashi Ohnishi, Yuki Ogawa, Kota Suda, Miki Komatsu, Satoko Matsumoto Harmon, Mitsuru Asukai, Masahiko Takahata, Norimasa Iwasaki, Akio Minami
International journal of molecular sciences, 22, 9, 2021年04月24日, ［国際誌］
英語, 研究論文（学術雑誌）, Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.

Delayed lumbar plexus palsy due to giant psoas hematoma associated with vertebral compression fracture and direct oral anticoagulants: a case report.
Chikako Ishii, Miki Komatsu, Kota Suda, Masahiko Takahata, Satoko Matsumoto Harmon, Masahiro Ota, Takamasa Watanabe, Mitsuru Asukai, Norimasa Iwasaki, Akio Minami
BMC musculoskeletal disorders, 22, 1, 377, 377, 2021年04月22日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Osteoporotic vertebral compression fractures (VCFs) are commonly observed in elderly people and can be treated by conservatively with minimal risk of complications in most cases. However, utilization of direct oral anticoagulants (DOACs) increases the risks of secondary hematoma even after insignificant trauma. The use of DOACs increased over the past decade because of their approval and recommendation for both stroke prevention in non-valvular atrial fibrillation and treatment of venous thromboembolism. It is well known that DOACs are safer anticoagulants than warfarin in terms of major and nonmajor bleeding; however, we noted an increase in the number of bleeding events associated with DOACs that required medical intervention. This report describes the first case of delayed lumbar plexus palsy due to DOAC-associated psoas hematoma after VCF to draw attention to potential risk of severe complication associated with this type of common and stable trauma. CASE PRESENTATION: An 83-year-old man presented with his left inguinal pain and inability to ambulate after falling from standing position and was prescribed DOACs for chronic atrial fibrillation. Computed tomography angiography revealed a giant psoas hematoma arising from the ruptured segmental artery running around fractured L4 vertebra. Because of motor weakness of his lower limbs and expansion of psoas hematoma revealed by contrast computed tomography on day 8 of his hospital stay, angiography aimed for transcatheter arterial embolization was tried, but could not demonstrate any major active extravasation; therefore spontaneous hemostasis was expected with heparin replacement. On day 23 of his stay, hematoma turned to decrease, but dysarthria and motor weakness due to left side cerebral infarction occurred. His pain improved and bone healing was achieved about 2 months later from his admission, however the paralysis of the left lower limb and aftereffects of cerebral infarction remained after 1 year. CONCLUSION: In patients using DOACs with multiple risk factors, close attention must be taken in vertebral injury even if the fracture itself is a stable-type such as VCF, because segmental artery injury may cause massive psoas hematoma followed by lumbar plexus palsy and other complications.

Bone Marrow Aspirate Concentrate Combined with in Situ Forming Bioresorbable Gel Enhances Intervertebral Disc Regeneration in Rabbits.
Daisuke Ukeba, Katsuhisa Yamada, Takeru Tsujimoto, Katsuro Ura, Takayuki Nonoyama, Norimasa Iwasaki, Hideki Sudo
The Journal of bone and joint surgery. American volume, 103, 8, e31, 2021年04月21日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The current surgical procedure of choice for intervertebral disc (IVD) herniation is discectomy, which induces postoperative IVD degeneration. Thus, cell-based therapies, as a 1-step simple procedure, are desired because of the poor capacity of IVDs for self-repair. The aim of this study was to investigate the repair efficacy of ultra-purified alginate (UPAL) gels containing bone marrow aspirate concentrate (BMAC) for the treatment of discectomy-associated IVD degeneration in rabbits. METHODS: The mechanical properties of 3 types of gels-UPAL, UPAL containing bone marrow-derived mesenchymal stem cells (BMSCs), and UPAL containing BMAC-were evaluated. Forty rabbits were assigned to 5 groups: intact control, discectomy (to make the cavity), UPAL (implantation of the UPAL gel after discectomy), BMSCs-UPAL (implantation of a combination of autogenic BMSCs and UPAL gel after discectomy), and BMAC-UPAL (implantation of a combination of BMAC and UPAL gel after discectomy). The gels were implanted at 4 weeks after induction of IVD degeneration. At 4 and 12 weeks, magnetic resonance imaging (MRI) as well as histological and immunohistochemical analyses were performed to analyze IVD degeneration qualitatively and the viability of the implanted cells. RESULTS: There was no significant difference among the 3 types of gels in terms of the results of unconfined compression tests. The implanted cells survived for 12 weeks. The histological grades of the BMSCs-UPAL (mean and standard deviation, 2.50 ± 0.53; p < 0.001) and BMAC-UPAL (2.75 ± 0.64, p = 0.001) showed them to be more effective in preventing degeneration than UPAL gel alone (3.63 ± 0.52). The effectiveness of BMAC-UPAL was not significantly different from that of BMSCs-UPAL, except with respect to type-II collagen synthesis. CONCLUSIONS: BMAC-UPAL significantly enhanced the repair of IVD defects created by discectomy. This approach could be an effective therapeutic strategy owing to its simplicity and cost-effectiveness compared with cell therapy using culture-expanded BMSCs. CLINICAL RELEVANCE: Local administration of the BMAC combined with UPAL gel could be an effective therapeutic strategy to enhance IVD repair after discectomy.

Bone Metabolism in the Healing Process of Lumbar Interbody Fusion-Temporal changes of bone turnover markers.
Ryota Hyakkan, Masahiro Kanayama, Masahiko Takahata, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki
Spine, 46, 23, 1645, 1652, 2021年04月19日, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: The aim of this study was to evaluate temporal changes of bone turnover markers (BTMs) after lumbar spinal fusion in patients without osteoporosis. SUMMARY OF BACKGROUND DATA: Radiological studies are the standard method to monitor bony fusion, but they do not allow a timely assessment of bone healing. BTMs react rapidly to changes in bone metabolism during fusion process and could be an additional tool to monitor this process. METHODS: A total of 78 non-osteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using CT sagittal and coronal images. Serum levels of bone specific alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) and osteocalcin (OC) were measured to assess bone formation, and tartrate-resistant acid phosphatase 5b (TRACP-5b) was measured to assess bone resorption. Serum samples were obtained before surgery and at 1, 2, 4, 8, 13, 26, 39, and 52 weeks after surgery. RESULTS: A solid fusion was achieved in 71 of 78 patients (91%), and 7 patients resulted in pseudarthrosis. In the fusion group, the level of all BTMs once decreased at 1 postoperative week. Then, BAP and P1NP reached a peak at 4 weeks after surgery, and TRACP-5b and OC peaked at 8 weeks. Thereafter, the level of P1NP and TRACP-5b gradually got closer to the baseline over a year, and BAP kept high until 52 postoperative weeks. In the pseudarthrosis group, peak level of BTMs were significantly higher and the increased level of BAP and P1NP was kept until 52 weeks. CONCLUSIONS: The current study demonstrated dynamics of BTMs after lumbar spinal fusion in patients without osteoporosis. These normal population data contribute as a baseline to evaluate the effect of osteogenic agents on bone metabolism after spinal fusion.Level of Evidence: 2.

Changes in the Contact Stress Distribution Pattern of the Patellofemoral Joint After Medial Open-Wedge High Tibial Osteotomy: An Evaluation Using Computed Tomography Osteoabsorptiometry.
Toshiaki Kameda, Eiji Kondo, Tomohiro Onodera, Koji Iwasaki, Jun Onodera, Kazunori Yasuda, Norimasa Iwasaki
Orthopaedic journal of sports medicine, 9, 4, 2325967121998050, 2325967121998050, 2021年04月, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Medial open-wedge high tibial osteotomy (OWHTO) theoretically causes distalization and lateralization of the tibial tuberosity and the patella. Purpose/Hypothesis: The purpose of the study was to identify any changes in the stress distribution of subchondral bone density across the patellofemoral (PF) joint before and after OWHTO through the use of computed tomography (CT) osteoabsorptiometry. We hypothesized that OWHTO would alter the distribution of contact stress in the PF joint. Study Design: Case series; Level of evidence, 4. Methods: A total of 17 patients (17 knees) who underwent OWHTO were enrolled in this study between September 2013 and September 2015. All patients underwent radiologic examination preoperatively and at 1 year postoperatively, and the distribution patterns of subchondral bone density through the articular surface of the femoral trochlea and patella were assessed preoperatively and >1 year postoperatively using CT osteoabsorptiometry. The quantitative analysis of the obtained mapping data focused on location of the high-density area (HDA) through the articular surface of the PF joint. The percentage of HDA at each divided region of the articular surface of the femoral trochlea and the patella was calculated. Results: In the radiologic evaluation, the Blackburne-Peel ratio was significantly reduced (P < .001) after surgery, and the tilting angle of the patella was significantly decreased (P < .001). On CT evaluation, the percentage of HDA in the lateral notch and lateral trochlea of the femur and in the medial portion of the lateral facet of the patella increased significantly after OWHTO surgery (P ≤ .038). Conclusion: OWHTO significantly increased the stress distribution pattern of the lateral trochlea of the femur and the medial portion of the lateral facet of the patella. The procedure significantly lowered the patellar height and significantly decreased the patellar tilting angle after surgery.

Morphologic Changes in the Vertebral Artery Subsequent to Cervical Spine Degeneration and Aging: Analyses by Computed Tomography Angiography Using Multiplanar and 3-Dimensional Reconstructions.
Takashi Ohnishi, Kota Suda, Miki Komatsu, Satoko Matsumoto Harmon, Takamasa Watanabe, Mitsuru Asukai, Ken Kadoya, Masahiko Takahata, Norimasa Iwasaki, Akio Minami
World neurosurgery, 150, e686-e695, 2021年03月23日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To identify the morphologic changes in the vertebral artery (VA) subsequent to cervical spine degeneration and aging and to investigate the risk factors for iatrogenic VA injury or occlusion. METHODS: Eighty-eight consecutive patients (176 bilateral VAs) were retrospectively analyzed using radiographs, computed tomography, and computed tomography angiography images. The Kellgren and Lawrence (KL) score and its modified subscores were used to grade the severity of degenerative changes in the cervical spine. VA tortuosity widths and diameters were measured between the C2 and C6 transverse foramens. The outcome measures were statistically analyzed for difference, correlation, and explanatory variable. The level with a high prevalence of VA stenosis was also evaluated. RESULTS: There were significant positive correlations between the KL score and VA tortuosity width, and between age and VA tortuosity width. Osteophyte formation in the facet joint was the predominant explanatory variable for medial deviation of the VA. Significant positive correlations were evident between the dominant VA diameter and KL score or age. VA stenosis occurred at C3/C4 (24.5%) with the highest prevalence and it was caused by uncovertebral joint osteophytes (52.0%) with the highest incidence. CONCLUSIONS: The present study provides important evidence for decisions of surgical strategy and for avoiding catastrophic VA injury or occlusion in cervical spine surgeries.

Finite element analysis of double-plate fixation using reversed locking compression-distal femoral plates for Vancouver B1 periprosthetic femoral fractures.
Daisuke Takahashi, Yoshihiro Noyama, Tsuyoshi Asano, Tomohiro Shimizu, Tohru Irie, Mohamad Alaa Terkawi, Norimasa Iwasaki
BMC musculoskeletal disorders, 22, 1, 276, 276, 2021年03月13日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Internal fixation is recommended for treating Vancouver B1 periprosthetic femoral fractures. Although several fixation procedures have been developed with high fixation stability and union rates, long-term weight-bearing constructs are still lacking. Therefore, the aim of the present study was to evaluate the stability of a double-plate procedure using reversed contralateral locking compression-distal femoral plates for fixation of Vancouver B1 periprosthetic femoral fractures under full weight-bearing. METHODS: Single- and double-plate fixation procedures for locking compression-distal femoral plates were analysed under an axial load of 1,500 N by finite element analysis and biomechanical loading tests. A vertical loading test was performed to the prosthetic head, and the displacements and strains were calculated based on load-displacement and load-strain curves generated by the static compression tests. RESULTS: The finite element analysis revealed that double-plate fixation significantly reduced stress concentration at the lateral plate place on the fracture site. Under full weight-bearing, the maximum von Mises stress in the lateral plate was 268 MPa. On the other hand, the maximum stress in the single-plating method occurred at the defect level of the femur with a maximum stress value of 1,303 MPa. The principal strains of single- and double-plate fixation were 0.63 % and 0.058 %, respectively. Consistently, in the axial loading test, the strain values at a 1,500 N loading of the single- and double-plate fixation methods were 1,274.60 ± 11.53 and 317.33 ± 8.03 (× 10- 6), respectively. CONCLUSIONS: The present study suggests that dual-plate fixation with reversed locking compression-distal femoral plates may be an excellent treatment procedure for patients with Vancouver B1 fractures, allowing for full weight-bearing in the early postoperative period.

Evaluation of whole-body modalities for diagnosis of multifocal osteonecrosis-a pilot study.
Shunichi Yokota, Keita Sakamoto, Yukie Shimizu, Tsuyoshi Asano, Daisuke Takahashi, Kohsuke Kudo, Norimasa Iwasaki, Tomohiro Shimizu
Arthritis research & therapy, 23, 1, 83, 83, 2021年03月11日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: This study aimed to investigate the ability of whole-body bone scintigraphy (WB-BS) in the detection of multifocal osteonecrosis (ON) compared to whole-body magnetic resonance imaging (WB-MRI) and to clarify the characteristics of patients with multifocal ON among those with ON of the femoral head (ONFH) using WB-MRI. METHODS: Forty-six patients who had symptomatic ONFH and underwent surgery in our hospital from April 2019 to October 2020 were included in the study. Data on patient demographics, including age, sex, body mass index (BMI), history of corticosteroid intake, alcohol abuse, smoking, and symptomatic joints, were collected from their medical records. All patients underwent WB-MRI and WB-BS before surgery. RESULTS: The agreement in the detection of ON by WB-MRI vs the uptake lesions by WB-BS in the hip joints was moderate (κ = 0.584), while that in other joints was low (κ < 0.40). Among the 152 joints with ON detected by WB-MRI, 92 joints (60.5%) were symptomatic, and 60 joints (39.5%) were asymptomatic. Twelve out of the 46 (26.0%) patients had multifocal (three or more distinct anatomical sites) ON. Nonetheless, while WB-BS detected symptomatic ON detected by WB-MRI as uptake lesions in 82.6% (76/92) of the joints, asymptomatic ON detected by WB-MRI was detected as uptake lesions in 21.7% (13/60) of the joints. All patients with multifocal ON had a history of steroid therapy, which was significantly higher than that in patients with oligofocal ON (P = 0.035). The patients with a hematologic disease had multifocal ON at a higher rate (P = 0.015). CONCLUSIONS: It might be difficult for WB-BS to detect the asymptomatic ON detected by WB-MRI compared to symptomatic ON. Considering the cost, examination time, and radiation exposure, WB-MRI might be useful for evaluating multifocal ON. Larger longitudinal studies evaluating the benefits of WB-MRI for detecting the risk factors for multifocal ON are required.

Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model.
Yuan Tian, Tomohiro Onodera, Mohamad Alaa Terkawi, Koji Iwasaki, Ryosuke Hishimura, Dawei Liang, Takuji Miyazaki, Norimasa Iwasaki
International journal of molecular sciences, 22, 5, 2021年03月04日, ［国際誌］
英語, 研究論文（学術雑誌）, Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague-Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.

手指DIP関節固定がMP・PIP関節の可動域に及ぼす影響 Cadaverを用いた検討　　　　　　　　　　　　　　　
遠藤 健, 河村 太介, 松井 雄一郎, 瓜田 淳, 太田 光俊, 岩崎 倫政
日本手外科学会雑誌, 37, 5, 669, 671, (一社)日本手外科学会, 2021年03月
日本語, ハンドセラピー領域では,手指の関節可動域拡大を目的に,一部の関節を固定して隣接関節に作動する筋力を集中させる手法が用いられる.しかし,本法が関節可動域拡大に及ぼす効果を定量して明らかにした報告はない.今回,Thiel法固定献体を使用し,DIP関節固定がMP関節,PIP関節の可動域に及ぼす影響を検討した.MP～DIP関節が完全屈曲位をとるのに必要なFDP腱牽引距離を測定し,その20,40,60,80%の牽引距離での各関節の屈曲角度を測定した結果,60%以上の牽引時,DIP固定群でMP関節は有意に屈曲角度が増強した.PIP関節でも同様の傾向を認めた.屈曲角度が増すに従い,DIP関節固定の影響がMP,PIP関節の屈曲に正の作用をすることが示唆された.(著者抄録)

頸椎変性と加齢に伴い生じる椎骨動脈の形態的異常 術中椎骨動脈損傷と術後閉塞を回避するための新たなエビデンス
大西 貴士, 須田 浩太, 小松 幹, 松本 聡子, 渡辺 尭仁, 飛鳥井 光, 角家 健, 高畑 雅彦, 東條 泰明, 神谷 行宣, 岩崎 倫政, 三浪 明男
日本整形外科学会雑誌, 95, 3, S984, S984, (公社)日本整形外科学会, 2021年03月
日本語

Acellular Cartilage Repair Technique Based on Ultrapurified Alginate Gel Implantation for Advanced Capitellar Osteochondritis Dissecans
Daisuke Momma, Tomohiro Onodera, Daisuke Kawamura, Atsushi Urita, Yuichiro Matsui, Rikiya Baba, Tadanao Funakoshi, Makoto Kondo, Toshiya Endo, Eiji Kondo, Norimasa Iwasaki
Orthopaedic Journal of Sports Medicine, 9, 3, 232596712198967, 232596712198967, SAGE Publications, 2021年03月01日, ［国際誌］
英語, 研究論文（学術雑誌）, One of the most important limitations of osteochondral autograft transplant is the adverse effect on donor sites in the knee. Ultrapurified alginate (UPAL) gel is a novel biomaterial that enhances hyaline-like cartilage repair for articular defects. To avoid the need for knee cartilage autografting when treating osteochondritis dissecans (OCD) of the capitellum, we developed a surgical procedure involving a bone marrow stimulation technique (BMST) augmented by implantation of UPAL gel.

BMST augmented by UPAL gel implantation improves the cartilage repair capacity and provides satisfactory clinical outcomes in OCD of the capitellum.

Case series; Level of evidence, 4.

A total of 5 athletes with advanced capitellar OCD in the dominant elbow underwent BMST augmented by implantation of UPAL gel. The osteochondral defects were filled with UPAL gel after BMST. At a mean follow-up of 97 weeks, all patients were evaluated clinically and radiographically.

At final follow-up, all 5 patients had returned to competitive-level sports, and 4 patients were free from elbow pain. The mean Timmerman-Andrews score significantly improved from 100 to 194 points. Radiographically, all patients exhibited graft incorporation and a normal contour of the subchondral cortex. Magnetic resonance imaging showed that the preoperative heterogeneity of the lesion had disappeared, and the signal intensity had returned to normal. Arthroscopic examinations consistently exhibited improvement in the International Cartilage Regeneration and Joint Preservation Society (ICRS) grade of lesions from 3 or 4 to 1 or 2 in 4 patients at 85 weeks postoperatively. Histologic analysis of biopsy specimens revealed an average total ICRS Visual Assessment Scale II histologic score of 1060.

The acellular cartilage repair technique using UPAL gel for advanced capitellar OCD provided satisfactory clinical and radiographic results. The present results suggest that this novel technique is a useful, minimally invasive approach for treating cartilaginous lesions in athletes.

Impact of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis.
Terufumi Kokabu, Yuichiro Abe, Katsuhisa Yamada, Norimasa Iwasaki, Hideki Sudo
Clinical biomechanics (Bristol, Avon), 83, 105296, 105296, 2021年03月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The aim of this study was to intraoperatively assess the effects of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis. METHODS: Twenty patients who underwent posterior thoracic adolescent idiopathic scoliosis curve correction were evaluated. Compressive or distractive loaded force of 50N was applied on the handle of a compressor or distractor connected to the necks of pedicle screws inserted at T7 to T11. Segmental spinal flexibility rates were calculated based on the distance between screw heads under the loaded and unloaded conditions. In addition, the flexibility rates were obtained before and after multilevel facetectomy. FINDINGS: Absolute flexibility rates of all segments significantly increased after multilevel facetectomy under both compressive and distractive forces (P < 0.01). The absolute change in the flexibility rate was significantly higher at the concave side than at the convex side under both compressive (P < 0.01) and distractive loaded forces (P = 0.046). No significant correlation was found between change in the flexibility rates and preoperative Cobb angle or preoperative curve flexibility. INTERPRETATION: From a biomechanical point of view, multilevel facetectomy provides proper spinal flexibility to improve the correction rate of posterior adolescent idiopathic scoliosis surgery. The effects are higher at the concave side than at the convex side.

上腕骨外側上顆炎に対するステロイド注射後に輪状靱帯の弾発現象を生じた1例　　　　　　　　　　　　　　　
遠藤 健, 河村 太介, 瓜田 淳, 松井 雄一郎, 門間 太輔, 太田 光俊, 芝山 浩樹, 岩崎 倫政
日本肘関節学会雑誌, 28, 1, S60, S60, 日本肘関節学会, 2021年02月
日本語

Risk Factor Analysis of Proximal Junctional Kyphosis after Surgical Treatment of Adult Spinal Deformity with Oblique Lateral Interbody Fusion.
Yoshinao Koike, Yoshihisa Kotani, Hidemasa Terao, Norimasa Iwasaki
Asian spine journal, 15, 1, 107, 116, 2021年02月, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: A single-center retrospective study. PURPOSE: To investigate the prevalence of proximal junctional kyphosis (PJK) and its risk factors after surgical treatment of adult spinal deformity (ASD) with oblique lateral interbody fusion (OLIF). OVERVIEW OF LITERATURE: Correction of ASD using OLIF has been developed because it is less invasive, and enables correction of severe deformities. Although PJK is a well-recognized complication after the correction of spinal deformity, few studies have evaluated the prevalence and risk factors for PJK after OLIF for ASD. METHODS: We reviewed 74 patients who underwent surgery for ASD. PJK was defined as a proximal junction sagittal Cobb angle exceeding 10°, and at least 10° greater than the preoperative measurement. We investigated the following as risk factors: age, sex, body mass index, medical history, number of fused segments, number of interbody fusions, number of OLIFs, number of osteotomies, level of upper instrumented vertebrae, lowest instrumented vertebrae, and radiographic parameters. RESULTS: The mean follow-up duration was 22.4 months and the mean age of the patients was 73.6 years. PJK was present in 19/74 patients (25.7%) and absent in 55/74 (74.3%). In the univariate analysis, those with PJK had a significantly higher proportion of patients with a history of vertebral compression fracture (7/19 patients [36.8%] vs. 6/55 patients [10.9%], p=0.027). Those with PJK had a significantly higher proportion of patients with fusion to the pelvis (18/19 patients [94.7%] vs. 34/55 patients [61.8%], p=0.016). According to the multivariate analysis, fusion to the pelvis was a significant risk factor for PJK. CONCLUSIONS: Fusion to the pelvis was the most important risk factor for PJK. A history of vertebral compression fracture served as an additional risk factor for PJK. Clinicians should consider these factors before treating ASD patients with OLIF.

Comparison of Outcomes of Oblique Lateral Interbody Fusion with Percutaneous Posterior Fixation in Lateral Position and Minimally Invasive Transforaminal Lumbar Interbody Fusion for Degenerative Spondylolisthesis.
Yoshinao Koike, Yoshihisa Kotani, Hidemasa Terao, Norimasa Iwasaki
Asian spine journal, 15, 1, 97, 106, 2021年02月, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Single-center retrospective study. PURPOSE: To compare the physical function and quality of life (QOL) parameters of two minimally invasive surgical (MIS) procedures: oblique lateral interbody fusion with percutaneous posterior fixation in lateral position (OLIF-LPF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for single-level degenerative spondylolisthesis (DS). OVERVIEW OF LITERATURE: To date, many options for the surgical treatment of lumbar DS and reports have described the effectiveness of minimally invasive lateral access surgery and MIS-TLIF. However, there is still a paucity of comparative data regarding the physical function and QOL outcomes of OLIF and MIS-TLIF. METHODS: Eighty-six patients were enrolled in this study (group O: OLIF-LPF, n=38; group T: MIS-TLIF, n=48). We evaluated the operation time, estimated blood loss (EBL), postoperative laboratory data, preoperative and postoperative radiographic parameters, overall functional outcome with the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) effectiveness rate, and Visual Analog Scale (VAS) score for low back pain, leg pain, and leg numbness. RESULTS: No statistical differences in operation time, EBL, and C-reactive protein level, 5 days postoperatively, between groups O and T. With respect to radiological outcome, preoperative and postoperative disc height change was significantly greater in group O than in group T (3.8 vs. 1.8 mm, p<0.05). Both groups showed postoperative improvements in the clinical outcome scores of all JOABPEQ domains, but the effectiveness rate increase in the psychological domain was significantly higher in group O than in group T (47.1% vs. 14.6%, p<0.05). No differences in the preoperative and postoperative VAS score change were noted between the two groups in any of the items. CONCLUSIONS: The changes in physical function and QOL parameters after OLIF-LPF and MIS-TLIF were almost equivalent; however, OLIF-LPF had significant superiority in the psychological domain.

Association Between Vitamin A Intake and Disease Severity in Early-Onset Heterotopic Ossification of the Posterior Longitudinal Ligament of the Spine.
Tsutomu Endo, Shiro Imagama, Satoshi Kato, Takashi Kaito, Hiroaki Sakai, Shiro Ikegawa, Yoshiharu Kawaguchi, Masahiro Kanayama, Yuichiro Hisada, Yoshinao Koike, Kei Ando, Kazuyoshi Kobayashi, Itaru Oda, Kazufumi Okada, Ryo Takagi, Norimasa Iwasaki, Masahiko Takahata
Global spine journal, 12, 8, 2192568221989300, 2192568221989300, 2021年01月25日, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: A sex- and age-matched case-control study and a cross-sectional study. OBJECTIVE: In our previous study, patients with early-onset (<50 years of age) ossification of the posterior longitudinal ligament (OPLL) had distinct features such as morbid obesity, a high prevalence of lifestyle-related diseases, and diffuse ossified lesions mainly affecting the thoracic spine. Our goals were to determine whether early-onset OPLL patients have unbalanced dietary habits and to identify nutritional factors associated with OPLL exacerbation. METHODS: In Study 1, the simple brief-type self-administered diet history questionnaire (BDHQ) was used to compare nutrient intake levels of early-onset OPLL patients (n = 13) with those of sex- and age-matched non-OPLL controls (n = 39) or with those of common OPLL (onset age ≥ 50 years, n = 62). In Study 2, serological validation was conducted for thoracic OPLL patients (n = 77) and non-OPLL controls (n = 101) in a nationwide multicenter study in Japan. RESULTS: The BDHQ showed that the early-onset OPLL patients had significantly lower intakes of vitamins A and B6 than non-OPLL controls. These results were validated by lower serum vitamins A and B6 levels in the early-onset thoracic OPLL patients. The severity of OPLL negatively correlated with serum vitamin A levels in male early-onset OPLL patients. The multiple regression analysis revealed that the severity of thoracic OPLL had an association with onset age and serum vitamin A level. CONCLUSIONS: Vitamin A deficiency resulting from unbalanced dietary habits is associated with exacerbation of male early-onset OPLL.

Three-dimensional distribution of CT attenuation in the lumbar spine pedicle wall.
Tomoyo Y Irie, Tohru Irie, Alejandro A Espinoza Orías, Kazuyuki Segami, Norimasa Iwasaki, Howard S An, Nozomu Inoue
Scientific reports, 11, 1, 1709, 1709, 2021年01月18日, ［国際誌］
英語, 研究論文（学術雑誌）, This study investigated in vivo the three-dimensional distribution of CT attenuation in the lumbar spine pedicle wall measured in Hounsfield Unit (HU). Seventy-five volunteers underwent clinical lumbar spine CT scans. Data was analyzed with custom-written software to determine the regional variation in pedicle wall attenuation values. A cylindrical coordinate system oriented along the pedicle's long axis was used to calculate the pedicular wall attenuation distribution three-dimensionally and the highest attenuation value was identified. The pedicular cross-section was divided into four quadrants: lateral, medial, cranial, and caudal. The mean HU value for each quadrant was calculated for all lumbar spine levels (L1-5). The pedicle wall attenuation was analyzed by gender, age, spinal levels and anatomical quadrant. The mean HU values of the pedicle wall at L1 and L5 were significantly lower than the values between L2-4 in both genders and in both age groups. Furthermore, the medial quadrant showed higher HU values than the lateral quadrant at all levels and the caudal quadrant showed higher HU values at L1-3 and lower HU values at L4-5 than the cranial quadrant. These findings may explain why there is a higher incidence of pedicle screw breach in the pedicle lateral wall.

Ultra-purified alginate gel implantation decreases inflammatory cytokine levels, prevents intervertebral disc degeneration, and reduces acute pain after discectomy.
Katsuro Ura, Katsuhisa Yamada, Takeru Tsujimoto, Daisuke Ukeba, Norimasa Iwasaki, Hideki Sudo
Scientific reports, 11, 1, 638, 638, 2021年01月12日, ［国際誌］
英語, 研究論文（学術雑誌）, Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy.

Risk factors of multidrug-resistant pyogenic spondylitis in thoraco-lumbar spine: A retrospective study of 122 cases.
Katsuhisa Yamada, Masahiko Takahata, Manabu Ito, Ken Nagahama, Akira Iwata, Tsutomu Endo, Hideki Sudo, Nobuhisa Ishiguro, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 27, 1, 95, 100, 2021年01月06日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The number of spinal infections has been increasing in developed countries due to the increase of aged or immunosuppressed patients. Spondylitis caused by multidrug-resistant (MDR) bacterial infection often become intractable and require long-term antibiotic therapy and multiple surgeries. Therefore, it is of great importance to understand risk factors for MDR spinal infections. The aim of this study was to elucidate the risk factors for MDR bacterial spondylitis. METHODS: A total of 122 patients (82 men, 40 women; average age: 63.8 y) with thoracic/lumbar spondylitis who underwent posterolateral full-endoscopic debridement and irrigation were included. The organisms detected by this endoscopic procedure were investigated, and the incidence and risk factors for MDR bacterial infection were retrospectively analyzed. RESULTS: Cultures of specimens obtained by endoscopic procedures were positive in 78 patients (63.9%). Among 68 isolated bacteria, MDR bacteria accounted for 47.1%. Multivariate analysis showed that significant risk factors for MDR bacterial infection included autoimmune connective tissue disease (P = 0.03) and central venous catheter (P = 0.02). The incidence of MDR bacteria in patients who were administered a broad-spectrum antibiotic for more than 1 month preoperatively was 64.0%, which was significantly higher than in patients who were administered a broad-spectrum antibiotic for less than 1 month and patients who were administered a narrow-spectrum antibiotic (P < 0.01, P < 0.01, respectively). CONCLUSIONS: The significant risk factors for MDR bacterial spondylitis included immunosuppressed conditions, such as autoimmune connective tissue disease, presence of central venous catheter, and longer administration periods of a broad-spectrum antibiotic. In patients with pyogenic spondylitis who could not be controlled with previous antibiotics and whose result of culture was negative, administration of anti-MRSA antibiotics would be considered when they have the risk factors identified in this study.

Superb Microvascular Imaging法を用いた手根管症候群での正中神経内血流評価の有用性
遠藤 健, 松井 雄一郎, 河村 太介, 瓜田 淳, 門間 太輔, 太田 光俊, 芝山 浩樹, 岩崎 倫政
北海道整形災害外科学会雑誌, 63, 139th suppl, 16, 16, 北海道整形災害外科学会, 2021年
日本語

大腿骨顆間窩外側壁における骨密度分布 前十字靱帯の大腿骨付着部に関する考察
菅原 悠太郎, 遠藤 香織, 菱村 亮介, 松原 新史, 松岡 正剛, 小野寺 智洋, 岩崎 倫政, 岩崎 浩司, 門間 大輔, 近藤 英司
北海道整形災害外科学会雑誌, 63, 139th suppl, 36, 36, 北海道整形災害外科学会, 2021年
日本語

末梢神経損傷後の好中球の時空間的変化に関する検討
山本 康弘, 角家 健, 岩崎 倫政, 市原 理司, 石島 旨章
北海道整形災害外科学会雑誌, 63, 139th suppl, 61, 61, 北海道整形災害外科学会, 2021年
日本語

Hallux Valgus With Second Brachymetatarsia Discovered Accidentally: A Case Report.
Shinji Matsubara, Tomohiro Onodera, Koji Iwasaki, Ryosuke Hishimura, Masatake Matsuoka, Eiji Kondo, Norimasa Iwasaki
The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons, 60, 5, 1060, 1062, 2021年, ［国際誌］
英語, Hallux valgus deformity is one of the most common foot and ankle diseases, while brachymetatarsia is a rare foot anomaly with pathological shortening of a metatarsal bone. We present a case of hallux valgus deformity possibly due to second brachymetatarsia. As the hallux valgus was associated with dorsal dislocation of the second toe that made it difficult to evaluate the length of the second toe, the patient was unaware of the second metatarsal shortening until the lengths of the toes compared by manual reposition of the second MTP joint. In this case, proximal osteotomy of the first metatarsal on the hallux valgus and single-stage bone lengthening of the second metatarsal with iliac bone grafting on the second brachymetatarsia were performed. One year after the operation, the callosity of the third toe resolved and the clinical scores were improved. In the case of a hallux valgus deformity with second dorsal dislocation of the toes, surgeons should consider that there are rare cases with second metatarsal shortening. When hallux valgus associated with second brachymetatarsia is diagnosed, second metatarsal lengthening should be considered in addition to hallux valgus surgery.

Micro-computed tomography analysis of the lumbar pedicle wall.
Tomoyo Y Irie, Tohru Irie, Alejandro A Espinoza Orías, Kazuyuki Segami, Norimasa Iwasaki, Howard S An, Nozomu Inoue
PloS one, 16, 7, e0253019, 2021年, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Although the pedicle is routinely used as a surgical fixation site, the pedicle wall bone area fraction (bone area per unit area) and its distribution at the isthmus of the pedicle remain unknown. The bone area fraction at the pedicle isthmus is an important factor contributing to the strength of pedicle screw constructs. This study investigates the lumbar pedicle wall microstructure based on micro-computed tomography. METHODS: Six fresh-frozen cadaveric lumbar spines were analyzed. Left and right pedicles of each vertebra from L1 to L5 were resected for micro-computed tomography scanning. Data was analyzed with custom-written software to determine regional variation in pedicle wall bone area fraction. The pedicular cross-section was divided into four regions: lateral, medial, cranial, and caudal. The mean bone area fraction values for each region were calculated for all lumbar spine levels. RESULTS: The lateral region showed lower bone area fraction than the medial region at all spinal levels. Bone area fraction in the medial region was the highest at all levels except for L4, and the median values were 99.8% (95.9-100%). There were significant differences between the lateral region and the caudal region at L1, L2 and L3, but none at L4 and L5. The bone area fraction in the lateral region was less than 64% at all spinal levels and that in the caudal region was less than 67% at the L4 and L5 levels. CONCLUSIONS: This study provides initial detailed data on the lumbar pedicle wall microstructure based on micro-computed tomography. These findings may explain why there is a higher incidence of pedicle screw breach in the pedicle lateral and caudal walls.

Impact of Smoking History on Pulmonary Metastasis-free Survival in Patients With Soft-tissue Sarcoma.
Masatake Matsuoka, Masanori Okamoto, Tamotsu Soma, Isao Yokota, Ryuta Arai, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki, Hiroaki Hiraga
Cancer diagnosis & prognosis, 1, 2, 89, 94, 2021年, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND/AIM: Although smoking history is predictive of poor pulmonary metastasis-free survival (PMFS) in patients with epithelial tumors, the impact of smoking history on PMFS in those with soft-tissue sarcoma (STS) is not known. PATIENTS AND METHODS: Patients undergoing treatment for STS at our institutes between 2008 and 2017 were enrolled. Patients were excluded if they had metastatic lesion, or had a histopathological classification demonstrating small round-cell sarcoma. The impact of smoking history on PMFS and overall survival was examined with multivariate analysis using a Cox proportional hazards model. RESULTS: A total of 250 patients were retrospectively reviewed. Patients with smoking history had worse PMFS on multivariate analysis (hazard ratio=2.00, 95% confidence interval=1.12-3.60). On the other hand, smoking history did not significantly affect overall survival (hazard ratio=1.26, 95% confidence interval=0.61-2.58). CONCLUSION: Patients with STS need to be followed-up by frequent clinical assessments if they have a smoking history.

Surgical Outcome Prediction Using a Four-Dimensional Planning Simulation System With Finite Element Analysis Incorporating Pre-bent Rods in Adolescent Idiopathic Scoliosis: Simulation for Spatiotemporal Anatomical Correction Technique.
Hiroyuki Tachi, Koji Kato, Yuichiro Abe, Terufumi Kokabu, Katsuhisa Yamada, Norimasa Iwasaki, Hideki Sudo
Frontiers in bioengineering and biotechnology, 9, 746902, 746902, 2021年, ［国際誌］
英語, 研究論文（学術雑誌）, An optimal surgical strategy for adolescent idiopathic scoliosis (AIS) is to provide maximal deformity correction while preserving spinal mobile segments as much as possible and obtaining a balanced posture. From a spatiotemporal deformity correction standpoint, we recently showed that anatomical four-dimensional (4D) spinal correction could be accomplished by curving the rod. In the surgical procedure, two rods are bent identically to confirm spinal anatomical alignment without referring to the intraoperative alignment of the deformity. Therefore, anatomically designed rods have been developed as notch-free, pre-bent rods for easier anatomical reconstruction. In addition to providing the best spinal instrumentation configurations as pre-bent rods, prediction of surgical outcome along with its biomechanical impact can be obtained by simulation of the surgical procedures with computer modeling. However, an objective model that can simulate the surgical outcome in patients with AIS has not been completely elucidated. The present study aimed to compare simulated deformity corrections based on our newly developed spatiotemporal morphological 4D planning simulation system incorporating pre-bent rods and actual deformity corrections in patients with AIS. A consecutive series of 47 patients who underwent anatomical posterior correction for AIS curves were prospectively evaluated. After multilevel facetectomy, except for the lowest instrumented segment, 11 types of pre-bent rods were used. Patient demographic data, radiographic measurements, and sagittal rod angles were analyzed within 1 week of surgery. Our simulation system incorporating pre-bent rods showed a significant correlation with the actual postoperative spinal alignment. The present study demonstrated the feasibility of our simulation system and the ability to simulate the surgical procedure using the pre-bent rods. The simulation system can be used to minimize the differences between the optimal and possible outcomes related to the instrumentation levels and rod shapes. Preoperative assumption of rod shape and length can contribute to a reduction in operative time which decreases blood loss and risk of infection. The results of the finite element analysis in the simulation system measured for each individual patient would also provide a more realistic representation of the surgical procedures.

Unintentional Fusion in Preserved Facet Joints without Bone Grafting after Percutaneous Endoscopic Transforaminal Lumbar Interbody Fusion.
Katsuhisa Yamada, Ken Nagahama, Yuichiro Abe, Eihiro Murota, Shigeto Hiratsuka, Masahiko Takahata, Norimasa Iwasaki
Spine surgery and related research, 5, 6, 390, 396, 2021年, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: A percutaneous endoscopic transforaminal lumbar interbody fusion (PETLIF) procedure has been previously developed. During postoperative follow-up, in some patients, bone fusion occurred between opened facet joints, despite not having bone grafting in the facet joints. Here, we investigated facet fusion's frequency and tendencies following PETLIF. METHODS: A retrospective analysis was conducted on a prospectively collected, nonrandomized series of patients. Forty-two patients (6 males and 36 females, average age: 69.9 years) who underwent single-level PETLIF at our hospital from February 2016 to March 2019 were included in this study. Patients were assessed with lumbar X-ray images and computed tomography (CT) prior to, immediately after, and 1 year after surgery. RESULTS: Pseudarthrosis was not observed in any patients, and facet fusion was observed in 26 of 42 post-PETLIF patients (61.9%) by CT 1 year postoperatively. The average interfacet distance increased from 1.3 mm preoperatively to 4.5 mm postoperatively, and facet fusion was observed under the opened conditions of 3.8 mm at 1 year. Segmental lordotic angle of the fusion segment in the lumbar X-ray images was significantly larger in the facet fusion subgroup prior to surgery, immediately following surgery, and 1 year after surgery compared to the facet non-fusion group (p=0.02, p<0.01, p=0.01, respectively). There were no significant differences in patient background, correction loss of segmental lordosis, interfacet distance, or clinical score between the facet fusion and facet non-fusion subgroups. CONCLUSIONS: Facet fusion was achieved over time within the facet joints that were opened through indirect decompression after PETLIF. We hypothesized that the preserved facet joints potentially became the base bed for spontaneous bone fusion due to the preserved facet joint capsule and surrounding soft tissue, which maintained cranio-caudal facet traffic and blood circulation in the facet joints. The complete preservation of the facet joints was a key advantage of minimally invasive lumbar interbody fusion procedures. LEVEL OF EVIDENCE: Level III.

Angiosarcoma after revision total knee arthroplasty.
Ryuichi Fukuda, Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Daisuke Tanaka, Hiroaki Hiraga, Hiromi Kanno-Okada, Yoshihiro Matsuno, Eiji Kondo, Norimasa Iwasaki
The Knee, 28, 151, 158, 2021年01月, ［国際誌］
英語, BACKGROUND: Hemarthrosis after total knee arthroplasty (TKA) is a relatively rare complication. Although most cases are effectively treated with conservative therapy, some cases require angiographic embolization or surgical intervention. Angiosarcoma is a rare malignant tumor derived from the vascular endothelium with neovascular hyperplasia and mainly arises in the skin and superficial soft tissue, and less frequently in deep soft tissue and bone. Although malignant neoplasms such as angiosarcoma in the vicinity of orthopedic implants were reported, the causal relationship between development of the malignant tumor and the orthopedic implant is widely debated in the literature. CASE PRESENTATION: We report the case of a 68-year-old female with angiosarcoma that developed in the knee joint 2 years after revision TKA. The patient exhibited severe persistent bleeding, which reached 1000-1400 ml per day for 4 months. Histological analysis of the synovial tissue in the knee joint showed large cells with nuclear atypia. Immunohistochemical staining showed cells that were positive for CD31, CD34, and D2-40, and she was diagnosed with angiosarcoma. The patient underwent an amputation at the level of the thigh, and her general condition immediately improved after the operation. The patient did not exhibit bleeding from the site of amputation, and no local recurrence or distant metastases were detected 1 year after the amputation. CONCLUSIONS: To the best of our knowledge, this represents the first report of angiosarcoma 2 years after revision TKA. Further careful follow up is needed, given the high-grade malignancy.

Histological observation on the initial stage of vascular invasion into the secondary ossification of murine femoral epiphyseal cartilage.
Keiji Hashimoto, Tomoka Hasegawa, Tomomaya Yamamoto, Hiromi Hongo, Y Imin, Miki Abe, Alireza Nasoori, Ko Nakanishi, Haruhi Maruoka, Yasuhito Morimoto, Keisuke Kubota, Tomohiro Shimizu, Mai Haraguchi, Masahiko Takahata, Norimasa Iwasaki, Minqi Li, Toshiaki Fujisawa, Norio Amizuka
Biomedical research (Tokyo, Japan), 42, 4, 139, 151, 2021年, ［国内誌］
英語, 研究論文（学術雑誌）, It remains unknown whether the histology of vascular invasion during secondary ossification of epiphyseal cartilage is the same as that seen in primary ossification; we examined the initial processes of vascular invasion of secondary ossification in the murine femora. Many endomucin-immunoreactive blood vessels gathered at the central region of the articular surface, and buds of soft tissue, including glomerular loops of endomucin-immunoreactive blood vessels and TNALPase- immunopositive osteoblastic cells accompanied by TRAP-positive osteoclasts, had begun to invade the epiphyseal cartilage. The invading soft tissues formed cartilage canals displaying MMP9 immunoreactivity in the tip region, and cartilaginous collagen fibrils were not visible in the vicinity of the vascular wall of the blood vessels. Thus, the histological profile marked by invading glomerular vasculature and the erosion of the cartilage matrix near the vascular walls during secondary ossification differs from that seen during primary ossification.

Histochemical characteristics on minimodeling-based bone formation induced by anabolic drugs for osteoporotic treatment.
Tomomaya Yamamoto, Tomoka Hasegawa, Paulo Henrique Luiz de Fraitas, Hiromi Hongo, Shen Zhao, Tsuneyuki Yamamoto, Alireza Nasoori, Miki Abe, Haruhi Maruoka, Keisuke Kubota, Yasuhito Morimoto, Mai Haraguchi, Tomohiro Shimizu, Masahiko Takahata, Norimasa Iwasaki, Minqi Li, Norio Amizuka
Biomedical research (Tokyo, Japan), 42, 5, 161, 171, 2021年, ［国内誌］
英語, 研究論文（学術雑誌）, Modeling, the changes of bone size and shape, often takes place at the developmental stages, whereas bone remodeling-replacing old bone with new bone-predominantly occurs in adults. Unlike bone remodeling, bone formation induced by modeling i.e., minimodeling (microscopic modeling in cancellous bone) is independent of osteoclastic bone resorption. Although recently-developed drugs for osteoporotic treatment could induce minimodeling-based bone formation in addition to remodeling-based bone formation, few reports have demonstrated the histological aspects of minimodeling-based bone formation. After administration of eldecalcitol or romosozumab, unlike teriparatide treatment, mature osteoblasts formed new bone by minimodeling, without developing thick preosteoblastic layers. The histological characteristics of minimodeling-based bone formation is quite different from remodeling, as it is not related to osteoclastic bone resorption, resulting in convex-shaped new bone and smooth cement lines called arrest lines. In this review, we will show histological properties of minimodeling-based bone formation by osteoporotic drugs.

Superb microvascular imaging法を用いた手根管症候群での正中神経内血流評価の有用性
遠藤 健, 松井 雄一郎, 河村 太介, 瓜田 淳, 太田 光俊, 倉茂 秀星, 岩崎 倫政
末梢神経, 31, 2, 344, 344, 日本末梢神経学会, 2020年12月
日本語

Reliable free flaps using the microscopic parachute end-to-side technique in severe extremity injuries.
Makoto Motomiya, Naoya Watanabe, Daisuke Kawamura, Keigo Yasui, Akira Adachi, Norimasa Iwasaki
Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 73, 12, 2239, 2260, 2020年12月, ［国際誌］
英語, PURPOSE: Although end-to-side anastomosis is an essential method for the transfer of free flaps in traumatic extremity injuries, orthoplastic surgeons have no standard technique for performing this procedure. We describe a simple and reliable end-to-side technique is modified from that commonly used by cardiovascular surgeons for free-flap transfer. METHODS: Our microscopic parachute end-to-side technique consists primarily of two simple steps. First, the donor vessel is cut and widened with microscissors, and a wide slit is made in the recipient vessel. Second, the heel of the vessel is sutured using the parachute technique, followed by suturing of the vessel wall with a continuous suture to control blood leakage from the widely opened window. We retrospectively evaluated the clinical outcomes of 18 flaps in which the microscopic parachute end-to-side technique was used for both arterial and venous anastomoses. RESULTS: All microscopic parachute end-to-side procedures achieved flap survival without complications related to anastomosis. The mean size of the vesselotomy was 4.8 mm, and the mean expansion rate of the donor vessel was 2.7 times. CONCLUSIONS: Compared with the conventional end-to-side technique, the microscopic parachute end-to-side technique has three advantages: easy vesselotomy, avoidance of anastomotic narrowing, and easy control of blood leakage from the anastomotic site. We believe that the microscopic parachute end-to-side technique might make free flaps easier and improve their clinical outcomes in severe extremity injuries.

Alterations of Glycosphingolipid Glycans and Chondrogenic Markers during Differentiation of Human Induced Pluripotent Stem Cells into Chondrocytes.
Liang Xu, Hisatoshi Hanamatsu, Kentaro Homan, Tomohiro Onodera, Takuji Miyazaki, Jun-Ichi Furukawa, Kazutoshi Hontani, Yuan Tian, Rikiya Baba, Norimasa Iwasaki
Biomolecules, 10, 12, 2020年12月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Due to the limited intrinsic healing potential of cartilage, injury to this tissue may lead to osteoarthritis. Human induced pluripotent stem cells (iPSCs), which can be differentiated into chondrocytes, are a promising source of cells for cartilage regenerative therapy. Currently, however, the methods for evaluating chondrogenic differentiation of iPSCs are very limited; the main techniques are based on the detection of chondrogenic genes and histological analysis of the extracellular matrix. The cell surface is coated with glycocalyx, a layer of glycoconjugates including glycosphingolipids (GSLs) and glycoproteins. The glycans in glycoconjugates play important roles in biological events, and their expression and structure vary widely depending on cell types and conditions. In this study, we performed a quantitative GSL-glycan analysis of human iPSCs, iPSC-derived mesenchymal stem cell like cells (iPS-MSC like cells), iPS-MSC-derived chondrocytes (iPS-MSC-CDs), bone marrow-derived mesenchymal stem cells (BMSCs), and BMSC-derived chondrocytes (BMSC-CDs) using glycoblotting technology. We found that GSL-glycan profiles differed among cell types, and that the GSL-glycome underwent a characteristic alteration during the process of chondrogenic differentiation. Furthermore, we analyzed the GSL-glycome of normal human cartilage and found that it was quite similar to that of iPS-MSC-CDs. This is the first study to evaluate GSL-glycan structures on human iPS-derived cartilaginous particles under micromass culture conditions and those of normal human cartilage. Our results indicate that GSL-glycome analysis is useful for evaluating target cell differentiation and can thus support safe regenerative medicine.

Fibroma of tendon sheath of the hand in a 3-year-old boy: a case report.
Hiroki Shibayama, Yuichiro Matsui, Daisuke Kawamura, Atsushi Urita, Chikako Ishii, Tamotsu Kamishima, Mutsumi Nishida, Ai Shimizu, Norimasa Iwasaki
BMC musculoskeletal disorders, 21, 1, 732, 732, 2020年11月10日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Fibroma of tendon sheath (FTS) is a rare benign soft tissue tumor that often occurs in the upper extremities. It manifests as a slow-growing mass, often without tenderness or spontaneous pain. FTS occurs most commonly in people aged 20-40 years and is extremely rare in young children. Because FTS presents with atypical physical and imaging findings, it might be misdiagnosed as another soft tissue tumor such as a ganglion cyst or tenosynovial giant cell tumor (TSGCT). Although marginal resection is usually performed, a high rate of local recurrence is reported. CASE PRESENTATION: A boy aged 3 years and 1 month visited our outpatient clinic with a complaint of a mass of the left hand. An elastic hard mass approximately 20 mm in diameter could be palpated on the volar side of his left little finger. This mass was initially diagnosed as a ganglion cyst at another hospital. Ultrasonography revealed a well-circumscribed hypoechoic mass with internal heterogeneity on the flexor tendon. On magnetic resonance imaging (MRI), the mass showed iso signal intensity to muscle on T1-weighted images, and homogeneously low signal intensity to muscle on T2-weighted images. The mass was peripherally enhanced after contrast administration. FTS was initially suspected as the diagnosis on the basis of these imaging features. Because of the limited range of motion of his little finger, surgery was performed when he was 4 years old. Histopathological findings indicated the mass was well-circumscribed and contained scattered spindle cells embedded in a prominent collagenous matrix. The spindle cells contained elongated and cytologically bland nuclei with a fine chromatin pattern. Nuclear pleomorphism and multinucleated giant cells were not observed. On the basis of these findings, we made a diagnosis of FTS. One year after surgery, no signs of local recurrence were observed. CONCLUSIONS: We experienced an extremely rare case of FTS in the hand of a 3-year-old child. We especially recommend ultrasonography for hand tumors of young children to diagnose or eliminate ganglion cysts. MRI helped differentially diagnose FTS from TSGCT. Although marginal resection can be performed as a treatment, great care should be taken postoperatively because FTS has a high possibility of local recurrence.

Lactone-Driven Ester-to-Amide Derivatization for Sialic Acid Linkage-Specific Alkylamidation.
Jun-Ichi Furukawa, Hisatoshi Hanamatsu, Takashi Nishikaze, Hiroshi Manya, Nobuaki Miura, Hirokazu Yagi, Ikuko Yokota, Keiko Akasaka-Manya, Tamao Endo, Motoi Kanagawa, Norimasa Iwasaki, Koichi Tanaka
Analytical chemistry, 92, 21, 14383, 14392, 2020年11月03日, ［国際誌］
英語, 研究論文（学術雑誌）, Sialic acid attached to nonreducing ends of glycan chains via different linkages is associated with specific interactions and physiological events. Linkage-specific derivatization of sialic acid is of great interest for distinguishing sialic acids by mass spectrometry, specifically for events governed by sialyl linkage types. In the present study, we demonstrate that α-2,3/8-sialyl linkage-specific amidation of esterified sialyloligosaccharides can be achieved via an intramolecular lactone. The method of lactone-driven ester-to-amide derivatization for sialic acid linkage-specific alkylamidation, termed LEAD-SALSA, employs in-solution ester-to-amide conversion to directly generate stable and sialyl linkage-specific glycan amides from their ester form by mixing with a preferred amine, resulting in the easy assignments of sialyl linkages by comparing the signals of esterified and amidated glycan. Using this approach, we demonstrate the accumulation of altered N-glycans in cardiac muscle tissue during mouse aging. Furthermore, we find that the stability of lactone is important for ester-to-amide conversion based on experiments and density functional theory calculations of reaction energies for lactone formation. By using energy differences of lactone formation, the LEAD-SALSA method can be used not only for the sialyl linkage-specific derivatization but also for distinguishing the branching structure of galactose linked to sialic acid. This simplified and direct sialylglycan discrimination will facilitate important studies on sialylated glycoconjugates.

Stress Distribution Patterns Across the Shoulder Joint in Gymnasts: A Computed Tomography Osteoabsorptiometry Study.
Daisuke Momma, Wataru Iwamoto, Kaori Endo, Kazuki Sato, Norimasa Iwasaki
Orthopaedic journal of sports medicine, 8, 11, 2325967120962103, 2325967120962103, 2020年11月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The distribution pattern of subchondral bone density is an indicator of stress distribution over a joint surface under long-term physiologic loading. The biomechanical characteristics of the articular surfaces of the shoulder joint in gymnasts can be determined by measuring this distribution pattern. PURPOSE: To evaluate the distribution of subchondral bone density across the shoulder joint in male collegiate gymnasts and to determine the effects of gymnastic activities on its articular surfaces under long-term loading conditions using computed tomography osteoabsorptiometry (CTOAM). STUDY DESIGN: Descriptive laboratory study. METHODS: CT image data were obtained from both shoulders of 12 asymptomatic male collegiate gymnasts (gymnast group; mean age, 19.4 years; range, 18-22 years) and 10 male collegiate volunteers (control group; mean age, 20.2 years; range, 18-22 years). The distribution pattern of subchondral bone density across the articular surfaces of each shoulder joint was assessed by CTOAM. Quantitative analysis was performed of the locations and percentages of high-density areas on the articular surface. RESULTS: Stress distribution patterns over the articular surfaces differed between the gymnasts and the controls. In the gymnasts, high-density areas were detected on the posterosuperior articular surface of the humeral head and the anterosuperior and/or posterosuperior articular surface of the glenoid. Mean bone density was greater in the gymnasts than in the controls (P < .0001). CONCLUSION: Stress distribution over the articular surfaces of the shoulder joint was affected by gymnastic activities. Stress was concentrated over the superior part of the glenohumeral joint in male collegiate gymnasts. CLINICAL RELEVANCE: The present findings suggest that gymnastic activities increase stress to the articular surfaces of the superior glenohumeral joint. This supports the notion that mechanical conditions play a crucial role in the origin of disorders particular to gymnastic activities.

Long-term Stress Distribution Patterns Across the Ankle Joint in Soccer Players: A Computed Tomography Osteoabsorptiometry Study.
Junki Shiota, Daisuke Momma, Takayoshi Yamaguchi, Norimasa Iwasaki
Orthopaedic journal of sports medicine, 8, 11, 2325967120963085, 2325967120963085, 2020年11月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The distribution pattern of subchondral bone density is considered to accurately reflect the stress distribution over a joint under long-term physiologic loading. The biomechanical characteristics of the surface of the ankle joint in soccer players can be determined by measuring this distribution pattern under long-term loading. PURPOSE: To evaluate the distribution of subchondral bone density across the ankle joint in soccer players and to determine the effects of soccer activities, including kicking motion, on the ankle joint surface under long-term loading conditions by computed tomography (CT) osteoabsorptiometry (CTOAM). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: CT imaging data were obtained from both ankles of 10 soccer players (soccer group) and 10 nonathletic volunteers (control group). The distribution patterns of subchondral bone density across the articular surface of the ankle joints were assessed by CTOAM. Quantitative analysis was performed of the locations and percentages of high-density areas on the articular surface. RESULTS: Stress distribution patterns over the ankle joint differed between the soccer players and controls. In the soccer players, the high-density areas were found in the anterior part of the distal tibia and proximal talus as well as the distal fibula. The percentages of high-density areas were greater in the soccer players compared with controls (P < .0001). CONCLUSION: Stress distribution over the articular surface of the ankle joint was affected by soccer activities. A high stress concentration was seen in soccer players in the anterior part of the tibia and talus and in the fibula; such excessive stress may lead to anterior impingement.

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years: A cross-sectional nationwide study in Japan.
Keiko Yamada, Yoichi M Ito, Masao Akagi, Etsuo Chosa, Takeshi Fuji, Kenichi Hirano, Shinichi Ikeda, Hideaki Ishibashi, Yasuyuki Ishibashi, Muneaki Ishijima, Eiji Itoi, Norimasa Iwasaki, Ryoichi Izumida, Ken Kadoya, Masayuki Kamimura, Arihiko Kanaji, Hiroyuki Kato, Shunji Kishida, Naohiko Mashima, Shuichi Matsuda, Yasumoto Matsui, Toshiki Matsunaga, Naohisa Miyakoshi, Hiroshi Mizuta, Yutaka Nakamura, Ken Nakata, Go Omori, Koji Osuka, Yuji Uchio, Kazuteru Ryu, Nobuyuki Sasaki, Kimihito Sato, Masuo Senda, Akihiro Sudo, Naonobu Takahira, Hiroshi Tsumura, Satoshi Yamaguchi, Noriaki Yamamoto, Kozo Nakamura, Takashi Ohe
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 25, 6, 1084, 1092, 2020年11月, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

Usefulness of ultrasonography for diagnosing iatrogenic spinal accessory nerve palsy after lymph node needle biopsy: a case report.
Hisataka Suzuki, Yuichiro Matsui, Takahito Iwai, Mutsumi Nishida, Norimasa Iwasaki
BMC musculoskeletal disorders, 21, 1, 712, 712, 2020年10月31日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Spinal accessory nerve (SAN) palsy is rare in clinical settings. Iatrogenicity is the most common cause, with cervical lymph node biopsy accounting for > 50% of cases. However, SAN palsy after lymph node needle biopsy is extremely rare, and the injury site is difficult to identify because of the tiny needle mark. CASE PRESENTATION: A 26-year-old woman was referred to our hospital with left neck pain and difficulty abducting and shrugging her left shoulder after left cervical lymph node needle biopsy. Five weeks earlier, a needle biopsy had been performed at the surgery clinic because of suspected histiocytic necrotizing lymphadenitis. No trace of the needle biopsy site was found on the neck, but ultrasonography (US) showed SAN swelling within the posterior cervical triangle. At 3 months after the injury, her activities of daily living had not improved. Therefore, we decided to perform a surgical intervention after receiving informed consent. We performed neurolysis because the SAN was swollen in the area consistent with the US findings, and nerve continuity was preserved. Shoulder shrugging movement improved at 1 week postoperatively, and the trapezius muscle manual muscle testing score recovered to 5 at 1 year postoperatively. The swelling diameter on US gradually decreased from 1.8 mm preoperatively to 0.9 mm at 6 months. CONCLUSION: We experienced a rare case in which US was useful for iatrogenic SAN palsy. Our results suggest that preoperative US is useful for localization of SAN palsy and that postoperative US for morphological evaluation of the SAN can help assess recovery.

Three-dimensional hip joint congruity evaluation of the borderline dysplasia: Zonal-acetabular radius of curvature.
Tohru Irie, Alejandro A Espinoza Orías, Tomoyo Y Irie, Shane J Nho, Daisuke Takahashi, Norimasa Iwasaki, Nozomu Inoue
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 38, 10, 2197, 2205, 2020年10月, ［国際誌］
英語, 研究論文（学術雑誌）, In theory, a hemispherical acetabulum provides the ideal hip congruity in any hip position. However, it remains unknown how the three-dimensional acetabular morphology of borderline dysplastic and frank dysplastic hips compare to normal hips. This study inquires if borderline dysplastic zonal-acetabular curvatures in the anterior, superior, and posterior zones are different from normal or dysplastic hips three-dimensionally. One-hundred and fifteen hips, grouped as control (25°≤ LCEA <40°), 36 hips; borderline (20°≤ LCEA <25°), 32 hips; dysplasia (LCEA ≤20°), 47 hips were analyzed. The radii of acetabular curvature for the anterior, superior, and posterior zones were calculated as the zonal-acetabular radius of curvature (ZARC). The mean acetabular roof obliquity of the borderline (10.6 ± 4.3 [SD]°) was significantly larger than the control (3.0° ± 5.4°; P < .001) and smaller than the dysplasia (19.3° ± 5.7°; P < .001). Although the mean acetabular anteversion angle of the borderline (21.3° ± 3.7°) was significantly larger than control (17.9 ± 3.5°; P = .001), that of the borderline was not different from the dysplasia (23.3° ± 4.0°; P = .053). The mean anterior ZARC in the borderline (29.8 ± 2.6 mm) was significantly larger than the control (28.0 ± 2.2 mm; P = .011) and smaller than the dysplasia (31.5 ± 2.7 mm; P = .009). The mean superior ZARC in the borderline (25.7 ± 3.0 mm) was not different from the control (25.9 ± 2.2 mm; P = .934) or the dysplasia (25.8 ± 2.5 mm; P = .991). Although the mean posterior ZARC in the borderline (27.2 ± 2.5 mm) was not different from the control (26.4 ± 1.9 mm; P = .455), that of the borderline group was significantly smaller than the dysplasia (30.4 ± 3.3 mm; P < .001); that is, the severity of lateral under-coverage affects the anterior and/or posterior zonal-acetabular curvature.

Computed Tomography-Based Three-Dimensional Analyses Show Similarities in Anterosuperior Acetabular Coverage Between Acetabular Dysplasia and Borderline Dysplasia.
Tohru Irie, Alejandro A Espinoza Orías, Tomoyo Y Irie, Shane J Nho, Daisuke Takahashi, Norimasa Iwasaki, Nozomu Inoue
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 36, 10, 2623, 2632, 2020年10月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: (1) To compare the acetabular coverage between dysplasia, borderline dysplasia, and control acetabulum in a quantitative 3-dimensional manner; and (2) to evaluate correlations between the radiologic parameters and the 3-dimensional zonal-acetabular coverage. METHODS: We reviewed contralateral hip computed tomography images of patients 16 to 60 years of age who underwent 1 of 3 types of surgeries: eccentric rotational acetabular osteotomy, curved intertrochanteric varus osteotomy, and total hip replacement with minimum 1-year follow-up from January 2013 to April 2018. A point-cloud model of the acetabulum created from computed tomography was divided into 6 zones. Three-dimensional acetabular coverage was measured radially at intervals of 1°. Mean radial acetabular coverage for each zone was named ZAC (zonal acetabular coverage) and was compared among the 3 subgroups (control: 25° ≤lateral center-edge angle [LCEA] <40°; borderline: 20° ≤LCEA <25°; and dysplasia: LCEA ≤20°) statistically. Further, the correlations between the ZAC in each zone and the LCEA were analyzed using Pearson's correlation coefficient. RESULTS: One-hundred fifteen hips were categorized as control (36 hips), borderline (32 hips), and dysplasia (47 hips). The mean anterocranial ZAC in the borderline (87.5 ± 5.7°) was smaller than that in the control (92.6 ± 5.9°, P = .005) but did not differ compared with the dysplasia (84.5 ± 7.6°, P = .131). In contrast, the anterocaudal (71.2 ± 5.0°), posterocranial (85.0 ± 6.4°), and posterocaudal (82.4 ± 4.5°) mean ZACs in the borderline were not different from those in the control (anterocaudal, 74.3 ± 4.6°, P = .090; posterocranial, 87.9 ± 4.3°, P = .082; posterocaudal, 85.1 ± 5.0°, P = .069) respectively. Although there was a very strong positive correlation with supra-anterior ZAC and LCEA (r = 0.750, P < .001), the correlation between the anterocranial ZAC and LCEA was relatively weak (r = 0.574, P < .001). CONCLUSIONS: The anterosuperior acetabular coverage in the borderline dysplastic acetabulum is more similar to the dysplastic acetabulum than to the normal acetabulum. CLINICAL RELEVANCE: This study emphasizes the importance of evaluating not only the lateral but also the anterior coverage in borderline dysplasia.

Non-tuberculosis Mycobacterium Tenosynovitis with Rice Bodies in a Patient with Systemic Lupus Erythematosus
Yuichiro Fujieda, Keita Ninagawa, Yuichiro Matsui, Michihiro Kono, Tamotsu Kamishima, Norimasa Iwasaki, Tatsuya Atsumi
Internal Medicine, 59, 18, 2317, 2320, Japanese Society of Internal Medicine, 2020年09月15日, ［国内誌］
英語, 研究論文（学術雑誌）, Infectious disease with various presentations in systemic lupus erythematosus often resembles lupus flare. A 37-year-old woman presented with a swollen left index finger that had not resolved, despite 7 years of immunosuppressive treatment. MRI showed rice-body formation in the flexor tendon sheath and tenosynovectomy demonstrated chronic synovitis with epithelioid granuloma. A mycobacterial culture confirmed invasive mycobacterial tenosynovitis due to Mycobacterium chelonae. The patient was treated with moxifloxacin and clarithromycin and completely recovered.

摩耗軟骨片による滑膜炎が誘導する軟骨細胞新規分泌因子「Flightless I」の機能解析
江畑 拓, Terkawi Alaa, 小野寺 智洋, 木田 博朗, 松前 元, 田 園, Alhasan Hend, 濱崎 雅成, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S1690, S1690, (公社)日本整形外科学会, 2020年09月
日本語

XCL1/lymphotactin阻害による病的骨吸収抑制効果の検討
Terkawi Alaa, 田 園, 松前 元, 木田 博朗, 高橋 大介, 江畑 拓, Alhasan Hend, 清水 智弘, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S1706, S1706, (公社)日本整形外科学会, 2020年09月
日本語

人工関節術後無菌性緩みにおけるチミジンホスホリラーゼの機能と骨吸収メカニズムの解明
松前 元, Terkawi Alaa, 木田 博朗, 江畑 拓, 田 園, Alhasan Hend, 清水 智弘, 高橋 大介, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S1711, S1711, (公社)日本整形外科学会, 2020年09月
日本語

ビタミンE添加超高分子量ポリエチレンインプラントにおける人工関節置換術後無菌性緩みを抑制する至適濃度の検討
木田 博朗, Terkawi Alaa, 松前 元, 江畑 拓, 田 園, Alhasan Hend, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S2017, S2017, (公社)日本整形外科学会, 2020年09月
日本語

Superb microvascular imaging法を用いた手根管症候群での正中神経内血流評価の有用性
遠藤 健, 松井 雄一郎, 河村 太介, 瓜田 淳, 太田 光俊, 倉茂 秀星, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S1870, S1870, (公社)日本整形外科学会, 2020年09月
日本語

四次元CTを用いた肩甲上腕関節の解析
門間 太輔, 井上 望, 遠藤 香織, 河村 太介, 瓜田 淳, 松井 雄一郎, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S1900, S1900, (公社)日本整形外科学会, 2020年09月
日本語

Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts.
Wen Shi Lee, Masaru Kato, Eri Sugawara, Michihiro Kono, Yuki Kudo, Michihito Kono, Yuichiro Fujieda, Toshiyuki Bohgaki, Olga Amengual, Kenji Oku, Shinsuke Yasuda, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya Atsumi
Arthritis & rheumatology (Hoboken, N.J.), 72, 9, 1493, 1504, 2020年09月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Optineurin (OPTN) is an autophagy adaptor/receptor that acts as an intrinsic negative regulator of osteoclast differentiation. RANKL expressed by rheumatoid arthritis synovial fibroblasts (RASFs) is primarily responsible for the development of bone erosions in patients with RA. The aim of the present study was to explore the role of OPTN in the pathogenesis of joint destruction in RA. METHODS: RASFs were left untreated or incubated with tumor necrosis factor (TNF) or interferon-γ (IFNγ), and expression of OPTN by RASFs was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Expression of RANKL and osteoprotegerin (OPG) was evaluated in cultures of OPTN-reduced RASFs with or without TNF or IFNγ treatment. OPTN-reduced RASFs were cocultured with monocytes and stained for tartrate-resistant acid phosphatase (TRAP). IκBα, NF-κB1, and RelA protein levels were measured to evaluate NF-κB signaling. Expression of messenger RNA (mRNA) for matrix metalloproteinase 3 (MMP3), interleukin-6 (IL6), GATA binding protein 3 (GATA3), carbohydrate sulfotransferase 15 (CHST15), hyaluronan synthase 1 (HAS1), and GATA1 was analyzed by RT-qPCR. RESULTS: In RASFs incubated with TNF or IFNγ, OPTN expression was up-regulated and RANKL expression was increased, and these effects were further pronounced in OPTN-reduced RASFs (all P < 0.05 versus controls). OPG mRNA levels remained unchanged. Monocytes cocultured with OPTN-reduced RASFs differentiated to a greater extent into TRAP+ multinucleated cells compared to monocytes cocultured with control RASFs (P < 0.05). IκBα degradation and nuclear NF-κB1 expression following TNF treatment were both prolonged in OPTN-reduced RASFs (each P < 0.05 versus controls). MMP3 mRNA levels were up-regulated, while GATA3, CHST15, and HAS1 mRNA levels were down-regulated in OPTN-reduced RASFs (each P < 0.05 versus controls). CONCLUSION: OPTN plays a protective role in RA when it is up-regulated in RASFs in the presence of proinflammatory cytokines. Absence of OPTN might worsen RA by generating a joint-destructive state, as indicated by evidence of increased RANKL expression on RASFs and subsequent osteoclast differentiation.

An Acute Oblique Osteotomy and Suture Ligation Procedure to Shorten the Fibula in Lateral Closing-Wedge High Tibial Osteotomy.
Kazunori Yasuda, Eiji Kondo, Daisuke Ueda, Jun Onodera, Koji Yabuuchi, Yoshie Tanabe, Norimasa Iwasaki, Tomonori Yagi
Arthroscopy techniques, 9, 9, e1299-e1308, 2020年09月, ［国際誌］
英語, 研究論文（学術雑誌）, The purpose of this description is to report an "acute oblique osteotomy and ligation" (AOOL) procedure to shorten the fibula in high tibial osteotomy (HTO). A 4-cm longitudinal skin incision is made at the lateral aspect of the leg. After the central portion of the fibula is circumferentially isolated from all the periosteal tissues, a simple osteotomy is performed at the mid-portion of the fibular diaphysis in the quasi-frontal plane, which is inclined by 25 to 30° to the long axis of the fibula. Two thin holes are created beside the osteotomy line on the lateral surface of the fibula. A polyester thread is passed through the 2 holes. After the HTO is completed, the surgeon easily reduces the displaced fibular ends using this thread. This thread is securely tied to keep the contact between the 2 osteotomized surfaces. The AOOL procedure is technically easy and safely performed. We believe that the AOOL procedure is clinically useful to shorten the fibular shaft in HTO.

Large osteochondral defect in the lateral femoral condyle reconstructed by Atelocollagen-associated autologous chondrocyte implantation combined with anterior cruciate ligament reconstruction.
Takuma Kaibara, Eiji Kondo, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Daisuke Momma, Naoki Seito, Susumu Mikami, Norimasa Iwasaki
BMC musculoskeletal disorders, 21, 1, 494, 494, 2020年07月27日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Articular surface damage commonly associated with rupture of the anterior cruciate ligament (ACL). Large osteochondral defect, which consists of a severe depression fracture and a large cartilage defect, need to be treated due to deformation of the articular surface as it can impact the clinical outcome of ACL reconstruction. Although autologous chondrocyte implantation is one of the useful options in such cases, it can be questioned whether the reconstruction of the ACL and osteochondral defect should be performed in one procedure alone. CASE PRESENTATION: We report a case of a 38-year-old male with a deep depression fracture extending to the edge of the lateral femoral condyle associated with ACL injury after twisting his right knee while skiing. The patient was successfully treated with tissue-engineered cartilage transplantation covered by the periosteum with an iliac bone graft combined with anatomic double-bundle ACL reconstruction. Histopathological examination of the transplanted cartilage taken at second-look arthroscopy showed a cartilage-like tissue in the middle to deep zone in which the extracellular matrix was largely stained with Safranin O. The patient was able to return to his previous level of skiing activity without any experience of knee pain. Magnetic resonance imaging at 4 years after surgery showed that the graft integrated to the border zone and subchondral bone. The operated knee showed negative Lachman test and had a full range of motion. CONCLUSIONS: To our knowledge, this is the first report of anatomic double-bundle ACL reconstruction with tissue-engineered cartilage transplantation and an iliac bone graft to restore the lateral edge of the femoral condyle.

Association of neutrophil extracellular traps with the development of idiopathic osteonecrosis of the femoral head.
Mayu Nonokawa, Tomohiro Shimizu, Miku Yoshinari, Yamato Hashimoto, Yusuke Nakamura, Daisuke Takahashi, Tsuyoshi Asano, Yuka Nishibata, Sakiko Masuda, Daigo Nakazawa, Satoshi Tanaka, Utano Tomaru, Norimasa Iwasaki, Akihiro Ishizu
The American journal of pathology, 190, 11, 2282, 2289, 2020年07月20日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Idiopathic osteonecrosis of the femoral head (ONFH) is defined as necrosis of osteocytes due to a non-traumatic ischemia of the femoral head. Iatrogenic glucocorticoid administration and habitual alcohol intake are regarded as risk factors. It has been suggested that glucocorticoid-induced activation of platelets contribute to the local blood flow disturbance of the femoral head. Both activated platelets and alcohol can induce neutrophil extracellular traps (NETs). To determine the association of NETs with the development of idiopathic ONFH, surgically resected femoral heads of patients with idiopathic ONFH and osteoarthritis (OA) were assessed for existence of NET-forming neutrophils by immunofluorescent staining. As a result, NET-forming neutrophils were present in small vessels surrounding the femoral head of patients with idiopathic ONFH but not OA. Moreover, Wistar-Kyoto rats were intravenously injected with NET-forming neutrophils or neutrophils without NET induction, and then the ischemic state of the tissue around the femoral head was evaluated by immunohistochemistry for hypoxia-inducible factor-1α (HIF-1α). NET-forming neutrophils circulated into the tissue around the femoral head, and HIF-1α expression in the tissue was higher compared to that of rats intravenously administered with neutrophils without NET induction. Furthermore, ischemic change of osteocytes was observed in the femoral head of rats given an intravenous injection of NET-forming neutrophils. The collective findings suggest that NETs are possibly associated with the development of idiopathic ONFH.

Comparison of the Efficacy and Renal Safety of Bisphosphonate Between Low-Dose/High-Frequency and High-Dose/Low-Frequency Regimens in a Late-Stage Chronic Kidney Disease Rat Model.
Ryo Fujita, Masahiro Ota, Dai Sato, Daigo Nakazawa, Hiromi Kimura-Suda, Fumiya Nakamura, Tomohiro Shimizu, Hideyuki Kobayashi, Norimasa Iwasaki, Masahiko Takahata
Calcified tissue international, 107, 4, 389, 402, 2020年07月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The efficacy and renal safety of low-dose/high-frequency (LDHF) dosing and high-dose/low-frequency (HDLF) dosing of bisphosphonates (BPs) are comparable in patients with normal kidney function but might be different in patients with late-stage chronic kidney disease (CKD). This study aimed to compare the efficacy and renal safety of two different dosage regimens of a BP, alendronate (ALN), in stage 4 CKD using a rat model. Male, 10-week-old Sprague-Dawley rats were subjected to either 5/6 nephrectomy or sham surgery. The animals received subcutaneous administration of vehicle (daily) or ALN in LDHF dosage regimen (LDHF-ALN: 0.05 mg/kg/day) or HDLF dosage regimen (HDLF-ALN: 0.70 mg/kg/2 weeks). Medications commenced at 20 weeks of age and continued for 10 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum and urine assays were performed to examine the efficacy and renal safety of the ALN regimens. Both LDHF-ALN and HDLF-ALN increased bone mass, improved micro-structure, and enhanced mechanical properties, without causing further renal impairment in CKD rats. Histologically, however, HDLF-ALN more efficiently suppressed bone turnover, leading to more mineralized trabecular bone, than LDHF-ALN in CKD rats, whereas such differences between LDHF-ALN and HDLF-ALN were not observed in sham rats. Both LDHF-ALN and HDLF-ALN showed therapeutic effects on high bone turnover osteoporosis in CKD stage 4 rats without causing further renal impairment. However, as HDLF-ALN more efficiently suppressed bone turnover than LDHF-ALN in late-stage CKD, HDLF-ALN might be more appropriate than LDHF-ALN for fracture prevention in high bone turnover osteoporosis patients with late-stage CKD.

Predictive factors for irreversible motor paralysis following cervical spinal cord injury.
Tsunehiko Konomi, Kota Suda, Masahiro Ozaki, Satoko Matsumoto Harmon, Miki Komatsu, Seiji Iimoto, Osahiko Tsuji, Akio Minami, Masahiko Takahata, Norimasa Iwasaki, Morio Matsumoto, Masaya Nakamura
Spinal cord, 59, 5, 554, 562, 2020年07月06日, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: A retrospective observational study. OBJECTIVES: To elucidate predictive clinical factors associated with irreversible complete motor paralysis following traumatic cervical spinal cord injury (CSCI). SETTING: Hokkaido Spinal Cord Injury Center, Japan. METHODS: A consecutive series of 447 traumatic CSCI persons were eligible for this study. Individuals with complete motor paralysis at admission were selected and divided into two groups according to the motor functional outcomes at discharge. Initial findings in magnetic resonance imaging (MRI) and other clinical factors that could affect functional outcomes were compared between two groups of participants: those with and those without motor recovery below the level of injury at the time of discharge. RESULTS: Of the 73 consecutive participants with total motor paralysis at initial examination, 28 showed some recovery of motor function, whereas 45 remained complete motor paralysis at discharge, respectively. Multivariate logistic regression analysis showed that the presence of intramedullary hemorrhage manifested as a confined low intensity changes in diffuse high-intensity area and more than 50% of cord compression on MRI were significant predictors of irreversible complete motor paralysis (odds ratio [OR]: 8.4; 95% confidence interval [CI]: 1.2-58.2 and OR: 14.4; 95% CI: 2.5-82.8, respectively). CONCLUSION: The presence of intramedullary hemorrhage and/or severe cord compression on initial MRI were closely associated with irreversible paralysis in persons with motor complete paralysis following CSCI. Conversely, subjects with a negligible potential for recovery could be identified by referring to these negative findings.

Long-Term Clinical and Radiological Outcomes of Primary Total Hip Arthroplasty with Modular Femoral Stem in Middle-Aged Asian Patients.
Kaname Takahashi, Tomohiro Shimizu, Tsuyoshi Asano, Mohamad Alaa Terkawi, Norimasa Iwasaki, Daisuke Takahashi
The Journal of arthroplasty, 35, 12, 3650, 3655, 2020年06月30日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: There is insufficient information regarding the outcome of primary total hip arthroplasty (THA) with the modular femoral stem in middle-aged patients. This study aimed to assess long-term clinical and radiological outcomes of primary THA using the original or modified modular hip system (S-ROM) in middle-aged Asian patients. METHODS: A retrospective review identified 98 primary THAs that used a modular stem and were undertaken between 1997 and 2009 in patients younger than 58 years, for whom at least 5 years of follow-up data were available. Clinical data and radiograph assessments were reviewed to analyze differences between the original and modified modular stem groups. RESULTS: The mean patient follow-up duration was 148.3 months, and the follow-up ratio was 89.1%. The Kaplan-Meier analysis revealed that the survival rate of both stems was 98.9% at 10 years and 89.8% at 15 years. Although no statistically significant differences in the survival rate were observed between the stem designs, the original stem group had increased incidence of thigh pain compared with the modified stem group. In total, 12 and 54 hips showed change in stem alignment and osteolysis, respectively. CONCLUSION: The findings of this study show that the modular stems have a high survival rate, and results suggest positive outcomes among the Asian population over the long term. Although there were very few differences between the stem designs, the results suggest that the modified modular stem could prevent thigh pain and that selection of the implant based on the bone shape is important for THA.

Predictors of cartilage degeneration in patients with subchondral insufficiency fracture of the femoral head: a retrospective study.
Tomohiro Shimizu, Shunichi Yokota, Yosuke Kimura, Tsuyoshi Asano, Hirokazu Shimizu, Hotaka Ishizu, Norimasa Iwasaki, Daisuke Takahashi
Arthritis research & therapy, 22, 1, 150, 150, 2020年06月22日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: There is evidence that the cause of primary osteoarthritis (OA) is related to the changes in subchondral bone; however, the influence of subchondral insufficiency fracture (SIF) of the femoral head on the degeneration of the hip joint and the prognostic factors related to joint degeneration remain unclear. The objectives of this study were (1) to investigate the natural history of joint space width after the occurrence of SIF and (2) to investigate the associations between joint space narrowing and bone metabolic markers as well as magnetic resonance imaging (MRI) among the patients with SIF. METHODS: Between January 2010 and December 2019, 238 patients in whom band pattern of the femoral head were observed on MRI visited Hokkaido University Hospital. Among these patients, 44 hips in 41 patients were diagnosed with SIF and eligible for this retrospective study. We evaluated the joint space width (JSW) of the hip on the radiograph obtained at the first and last visits, length of the band lesion on MRI, bone mineral density by dual-energy X-ray absorptiometry, and bone metabolism markers. Similarly, the factors associated with the necessity of surgery and the progression of the narrowing of the joint space were evaluated. RESULTS: Fifteen of the 44 hips required total hip arthroplasty (THA). A significant decrease was observed in the JSW from the first visit to the final follow-up. Changes in the JSW were associated with the length of band patterns, serum type 1 procollagen-N-propeptide (P1NP), and tartrate-resistant acid phosphatase 5b (TRACP-5b) during diagnosis. Additionally, bone metabolic markers tended to be associated with the length of the band pattern. CONCLUSIONS: SIF could cause joint space narrowing and hip OA. In addition to MRI findings as prognostic predictors of SIF, as previously described, bone metabolic markers were equally associated with changes in JSW, suggesting that these parameters could be useful in predicting the prognosis of SIF. Considering that bone metabolic markers trended to be associated with the length of band pattern, they might reflect the local severity.

Impact of lowest instrumented vertebra tilt and rotation on uninstrumented lumbar curve and L4 tilt in thoracic adolescent idiopathic scoliosis.
Akira Iwata, Hideki Sudo, Kuniyoshi Abumi, Manabu Ito, Katsuhisa Yamada, Norimasa Iwasaki
Journal of neurosurgery. Spine, 1, 9, 2020年06月12日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Controversy exists regarding the effects of lowest instrumented vertebra (LIV) tilt and rotation on uninstrumented lumbar segments in adolescent idiopathic scoliosis (AIS) surgery. Because the intraoperative LIV tilt from the inferior endplate of the LIV to the superior sacral endplate is not stable after surgery, the authors measured the LIV angle of the instrumented thoracic spine as the LIV angle of the construct. This study aimed to evaluate the effects of the LIV angle of the construct and the effects of LIV rotation on the postoperative uninstrumented lumbar curve and L4 tilt in patients with thoracic AIS. METHODS: A retrospective correlation and multivariate analysis of a prospectively collected, consecutive, nonrandomized series of patients at a single institution was undertaken. Eighty consecutive patients with Lenke type 1 or type 2 AIS treated with posterior correction and fusion were included. Preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study. Outcome variables were postoperative uninstrumented lumbar segments (LIV tilt, LIV translation, uninstrumented lumbar curve, thoracolumbar/lumbar [TL/L] apical vertebral translation [AVT], and L4 tilt). The LIV angle of the construct was measured from the orthogonal line drawn from the upper instrumented vertebra to the LIV. Multiple stepwise linear regression analysis was conducted between outcome variables and patient demographics/radiographic measurements. There were no study-specific biases related to conflicts of interest. RESULTS: Predictor variables for postoperative uninstrumented lumbar curve were the postoperative LIV angle of the construct, number of uninstrumented lumbar segments, and flexibility of TL/L curve. Specifically, a lower postoperative uninstrumented lumbar curve was predicted by a lower absolute value of the postoperative LIV angle of the construct (p < 0.0001). Predictor variables for postoperative L4 tilt were postoperative LIV rotation, preoperative L4 tilt, and preoperative uninstrumented lumbar curve. Specifically, a lower postoperative L4 tilt was predicted by a lower absolute value of postoperative LIV rotation (p < 0.0001). CONCLUSIONS: The LIV angle of the construct significantly affected the LIV tilt, uninstrumented lumbar curve, and TL/L AVT. LIV rotation significantly affected the LIV translation and L4 tilt.

Therapeutic effects and adaptive limits of an acellular technique by ultrapurified alginate (UPAL) gel implantation in canine osteochondral defect models.
Tomohiro Onodera, Rikiya Baba, Yasuhiko Kasahara, Toshihiko Tsuda, Norimasa Iwasaki
Regenerative therapy, 14, 154, 159, 2020年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The aim of this study was to clarify the objective therapeutic effects of an acellular technique by ultrapurified alginate (UPAL) gel implantation in canine osteochondral defect models. Methods: Two osteochondral defects (diameters: 3.0 and 5.0 mm) were created on each patellar groove in both knees of 10 dogs. Defects were divided into four groups (n = 10 each): Group 1, untreated 3.0-mm defect; Group 2, 3.0-mm defect with UPAL gel; Group 3, untreated 5.0-mm defect; and Group 4, 5.0-mm defect with UPAL gel. All surgical procedures were performed by individuals unfamiliar with the technique at an independent institution. Articular surfaces were evaluated grossly and histologically at 27 weeks after operation. Results: UPAL gel-treated osteochondral defects showed significantly improved gross appearance in Group 4 and histological appearance in Groups 2 and 4. Reparative tissues in the 3.0-mm defect with UPAL gel were replaced by hyaline-like cartilage tissue. The 5.0-mm defects with UPAL gel were mostly covered with fibrocartilaginous tissue, whereas UPAL gel-untreated defects mostly remained uncovered by any tissue. Conclusions: Although an acellular technique using UPAL gel implantation significantly enhanced osteochondral repair in canines, reparative tissues of the large defect with alginate gel comprised of fibrocartilaginous tissue. This surgical technique is effective, especially for small cartilage injuries. Further improvements are required before clinical application in cases of severe osteochondral defects in humans.

Clinical Outcomes and Complications During and After Medial Open-Wedge High Tibial Osteotomy Using a Locking Plate: A 3- to 7-Year Follow-up Study.
Koji Yabuuchi, Eiji Kondo, Jun Onodera, Tomohiro Onodera, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda
Orthopaedic journal of sports medicine, 8, 6, 2325967120922535, 2325967120922535, 2020年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Outcomes and complications at mid- or long-term follow-up after medial open-wedge high tibial osteotomy (MOWHTO) with the TomoFix locking plate have not been fully evaluated. Purpose: To evaluate the complications and midterm clinical outcomes after MOWHTO using a TomoFix. Study Design: Case series; Level of evidence, 4. Methods: Enrolled in this study were 80 patients (85 knees) who underwent MOWHTO with the TomoFix locking plate between 2009 and 2013. There were 66 women and 14 men, with a mean age of 61.5 years at the time of surgery. The diagnosis was medial osteoarthritis in 76 knees and spontaneous osteonecrosis of the knee in 9 knees. Metal removal and second-look arthroscopy were performed in all cases. Clinical and radiological examinations were performed at final follow-up after surgery (mean, 4.5 years). Results: The mean Japanese Orthopaedic Association score and Knee injury and Osteoarthritis Outcome Score improved significantly from pre- to postoperatively (P < .0001). The weightbearing line percentage shifted to pass through a point 67.7% lateral from the medial edge of the tibial plateau. The Caton-Deschamps index changed significantly from 0.88 to 0.66 at final follow-up (P < .0001). The mean posterior tibial slope changed significantly from 8.9° to 11.9° at final follow-up (P < .0001). Limb length was significantly increased after MOWHTO (10.3 mm; P < .0001). During plate removal, 14 locking screws were found to be broken in 9 knees (10.6%). The articular cartilage grade of the patellofemoral joint was significantly higher in the second arthroscopy than in the first arthroscopy (P < .0001). The cumulative rate of all complications was 41.2%, with major complications (ie, those requiring additional or extended treatment) in 24.7%. Conclusion: Postoperative outcome scores indicated significant improvement after MOWHTO, although the cumulative rate of all complications was 41.2% and the rate of major complications was 24.7%. These results indicate that MOWHTO with the TomoFix is a technically demanding procedure. Careful preoperative planning and meticulous surgical technique are needed to decrease the incidence of complications associated with MOWHTO.

Siglec-15-targeting therapy protects against glucocorticoid-induced osteoporosis of growing skeleton in juvenile rats.
Dai Sato, Masahiko Takahata, Masahiro Ota, Chie Fukuda, Tomoka Hasegawa, Tomomaya Yamamoto, Norio Amizuka, Eisuke Tsuda, Akiko Okada, Yoshiharu Hiruma, Ryo Fujita, Norimasa Iwasaki
Bone, 135, 115331, 115331, 2020年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Effective treatment of juvenile osteoporosis, which is frequently caused by glucocorticoid (GC) therapy, has not been established due to limited data regarding the efficacy and adverse effects of antiresorptive therapies on the growing skeleton. We previously demonstrated that sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) targeting therapy, which interferes with osteoclast terminal differentiation in the secondary, but not primary, spongiosa, increased bone mass without adverse effects on skeletal growth, whereas bisphosphonate, a first-line treatment for osteoporosis, increased bone mass but impaired long bone growth in healthy growing rats. In the present study, we investigated the efficacy of anti-Siglec-15 neutralizing antibody (Ab) therapy against GC-induced osteoporosis in a growing rat model. GC decreased bone mass and deteriorated mechanical properties of bone, due to a disproportionate increase in bone resorption. Both anti-Siglec-15 Ab and alendronate (ALN) showed protective effects against GC-induced bone loss by suppressing bone resorption, which was more pronounced with anti-Siglec-15 Ab treatment, possibly due to a reduced negative impact on bone formation. ALN induced histological abnormalities in the growth plate and morphological abnormalities in the long bone metaphysis but did not cause significant growth retardation. Conversely, anti-Siglec-15 Ab did not show any negative impact on the growth plate and preserved normal osteoclast and chondroclast function at the primary spongiosa. Taken together, these results suggest that anti-Siglec-15 targeting therapy could be a safe and efficacious prophylactic therapy for GC-induced osteoporosis in juvenile patients.

Computed tomography osteoabsorptiometry changes following ulnar shortening osteotomy: observations in nine patients
Yuichi Hasegawa, Yuichiro Matsui, Norimasa Iwasaki
Journal of Hand Surgery (European Volume), 45, 5, 527, 529, SAGE Publications, 2020年06月
研究論文（学術雑誌）

Role of Chondrocytes in the Development of Rheumatoid Arthritis Via Transmembrane Protein 147-Mediated NF-κB Activation.
Mitsutoshi Ota, Yuki Tanaka, Ikuma Nakagawa, Jing-Jing Jiang, Yasunobu Arima, Daisuke Kamimura, Tomohiro Onodera, Norimasa Iwasaki, Masaaki Murakami
Arthritis & rheumatology (Hoboken, N.J.), 72, 6, 931, 942, 2020年06月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: We have previously reported that the coactivation of NF-κB and STAT3 in nonimmune cells, including synovial fibroblasts, enhances the expression of NF-κB target genes and plays a role in chronic inflammation and rheumatoid arthritis (RA). This study was undertaken to examine the role of NF-κB activation in chondrocytes and better understand the pathogenesis of RA. Furthermore, transmembrane protein 147 (TMEM147) was investigated as a representative NF-κB activator in chondrocytes. METHODS: Clinical samples from RA patients were analyzed by immunohistochemistry. Specimens obtained from patients with polydactyly were used as control samples. The functional contribution of chondrocytes and TMEM147 to arthritis was examined in several murine models of RA. In vitro experiments (quantitative polymerase chain reaction, RNA interference, immunoprecipitation, and confocal microscopy) were performed to investigate the mechanism of action of TMEM147 in chondrocytes. RESULTS: Samples obtained from RA patients and mouse models of RA showed coactivation of NF-κB and STAT3 in chondrocytes (P < 0.001). This coactivation induced a synergistic expression of NF-κB targets in vitro (P < 0.01). Chondrocyte-specific deletion of STAT3 significantly suppressed the development of cytokine-induced RA (P < 0.01). TMEM147 was highly expressed in chondrocytes from RA patient samples and the mouse models of RA. Gene silencing of TMEM147 or anti-TMEM147 antibody treatment inhibited the cytokine-mediated activation of NF-κB in vitro (P < 0.01) and suppressed cytokine-induced RA in vivo (P < 0.01). Mechanistically, TMEM147 molecules acted as scaffold proteins for the NF-κB complex, which included breakpoint cluster region and casein kinase 2, and enhanced NF-κB activity. CONCLUSION: These results suggest that chondrocytes play a role in the development of RA via TMEM147-mediated NF-κB activation and indicate a novel therapeutic strategy for RA.

Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis.
Masanari Hamasaki, Mohamad Alaa Terkawi, Tomohiro Onodera, Yuan Tian, Taku Ebata, Gen Matsumae, Hend Alhasan, Daisuke Takahashi, Norimasa Iwasaki
Scientific reports, 10, 1, 7558, 7558, 2020年05月05日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages play principal role in development of synovitis. Our earlier study suggests that interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechanisms by which cartilage fragments trigger cellular responses remain to be investigated. Therefore, the current study aims at analyzing molecular response of macrophages to cartilage fragments. To this end, we analyzed the transcriptional profiling of murine macrophages exposed to cartilage fragments by RNA sequencing. A total 153 genes were differentially upregulated, and 105 genes were down-regulated in response to cartilage fragments. Bioinformatic analysis revealed that the most significantly enriched terms of the upregulated genes included scavenger receptor activity, integrin binding activity, TNF signaling, and toll-like receptor signaling. To further confirm our results, immunohistochemical staining was performed to detected regulated molecules in synovial tissues of OA patients. In consistence with RNA-seq results, MARCO, TLR2 and ITGα5 were mainly detected in the intima lining layer of synovial tissues. Moreover, blockade of TLR2 or ITGα5 but not Marco using specific antibody significantly reduced production of TNF-α in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITGα5 might be promising therapeutic strategy for treating progressive osteoarthritis.

Atypical osteochondroma of the hamate that presented clinically as carpal tunnel syndrome: report of an extremely rare case and literature review.
Makoto Motomiya, Taiki Sakazaki, Norimasa Iwasaki
BMC musculoskeletal disorders, 21, 1, 231, 231, 2020年04月13日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Osteochondroma is a benign tumor that occurs mainly at the metaphysis of long bones and seldom arises from carpal bones. We describe an extremely rare case of osteochondroma of the hamate without a typical cartilaginous cap and with a spiky bony protrusion in an elderly patient. CASE PRESENTATION: A 78-year-old right-handed female housekeeper had a multilobed osteochondroma of the hamate, which caused carpal tunnel syndrome and irritation of the flexor tendons. Radiological examinations showed a morphological abnormality of the hamate comprising a spiky bony protrusion into the carpal tunnel and a free body proximal to the pisiform. Open carpal tunnel release and resection of the spiky bony protrusion on the hook of the hamate were performed. The flexor digitorum profundus tendons of the ring and little fingers displayed synovitis and partial laceration in the carpal tunnel. Histological examination also showed atypical findings: only a few regions of cartilaginous tissue were seen in the spiky bony protrusion, whereas the free body proximal to the pisiform contained thick cartilaginous tissue such as a cartilaginous cap typical of osteochondroma. We speculated that the bony protrusion to the carpal tunnel had been eroded by mechanical irritation caused by gliding of the flexor tendon and had resulted in the protruding spiky shape with less cartilaginous tissue. The fractured cartilaginous cap had moved into the cavity within the carpal tunnel proximal to the pisiform and had become a large free body. CONCLUSIONS: Osteochondroma of the carpal bone may take various shapes because the carpal bone is surrounded by neighboring bones and tight ligaments, which can restrict tumor growth. This type of tumor is likely to present with various symptoms because of the close proximity of important structures including nerves, tendons, and joints. The diagnosis of osteochondroma of the carpal bone may be difficult because of its rarity and atypical radiological and histological findings, such as the lack of a round cartilaginous cap. We suggest that surgeons should have a detailed understanding of this condition and should make a definitive diagnosis based on the overall findings.

Effects of Unweighting on Gait Kinematics During Walking on a Lower-Body Positive Pressure Treadmill in Patients with Hip Osteoarthritis
Yoshiaki Kataoka, Tomohiro Shimizu, Ryo Takeda, Shigeru Tadano, Yuki Saito, Satoshi Osuka, Tomoya Ishida, Mina Samukawa, Tohru Irie, Daisuke Takahashi, Norimasa Iwasaki, Harukazu Tohyama
BMC musculoskeletal disorders, 22, 1, 46, 46, Research Square, 2020年04月10日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）,
Background: Hip osteoarthritis (OA) is a musculoskeletal condition that makes walking difficult due to pain induced by weight-bearing activity. Treadmills that support body weight reduce the load on the lower limbs, and those equipped with a lower-body positive pressure (LBPP) device, developed as a new method for unweighting, significantly reduce pain in patients with knee OA. However, the effects of unweighting on gait kinematics remain unclear in patients with hip OA. Therefore, we investigated the effects of unweighting on kinematics in patients with hip OA during walking on a treadmill equipped with an LBPP device.Methods: Fifteen women with hip OA and fifteen age-matched female controls wore a three-dimensional motion analysis system and walked at a comfortable speed on the LBPP treadmill. Data regarding hip pain using a numeric rating scale under three different unweighting conditions (100%, 75%, and 50% bodyweight) were collected. Sagittal plane lower-limb kinematics under each condition were calculated and compared.Results: In the hip OA group, numerical rating scores at the unweighted condition were significantly decreased compared to the 100% bodyweight condition, and sagittal kinematics in the hip and knee joints significantly decreased compared to the healthy controls. In both groups, unweighting significantly decreased the peak hip flexion angle and increased the peak ankle plantarflexion angle during walking.Conclusions: Although unweighting by LBPP decreased pain in the hip OA group, gait kinematics did not improve despite less load on the hip joint. Therefore, clinicians should consider the benefits of pain reduction, rather than improved gait, when considering LBPP treadmill for patients with hip OA.

手指DIP関節固定がMP・PIP関節の可動域に及ぼす影響 Cadaverを用いた検討　　　　　　　　　　　　　　　
遠藤 健, 河村 太介, 松井 雄一郎, 瓜田 淳, 太田 光俊, 倉茂 秀星, 岩崎 倫政
日本手外科学会雑誌, 37, 1, O3, 6, (一社)日本手外科学会, 2020年04月
日本語

脊髄損傷治療の現状と脊髄再生-東京オリンピック、パラリンピックを記念して- 急性期病院が脊髄再生に果たすべき役割 つなぐべき希望
須田 浩太, 松本 聡子, 小松 幹, 大西 貴士, 渡辺 尭仁, 飛鳥井 光, 宇都宮 祥弘, 東條 泰明, 三浪 明男, 角家 健, 高畑 雅彦, 岩崎 倫政
日本整形外科学会雑誌, 94, 2, S26, S26, (公社)日本整形外科学会, 2020年03月
日本語

脊髄損傷患者における出血性イベントの危険因子とは? 完全運動麻痺と直接作用型傾向抗凝固薬はハイリスクである　　　　　　　　　　　　　　　
渡辺 尭仁, 須田 浩太, 小松 幹, 松本 聡子, 大西 貴士, 飛鳥井 光, 宇都宮 祥弘, 東條 泰明, 三浪 明男, 高畑 雅彦, 岩崎 倫政
Journal of Spine Research, 11, 3, 591, 591, (一社)日本脊椎脊髄病学会, 2020年03月
日本語

A Minimum 5-Year Longitudinal Study of a New Total Wrist Arthroplasty in Patients With Rheumatoid Arthritis
Yuichiro Matsui, Akio Minami, Makoto Kondo, Jyunichi Ishikawa, Makoto Motomiya, Norimasa Iwasaki
The Journal of Hand Surgery, 45, 3, 255.e1, 255.e7, Elsevier BV, 2020年03月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To evaluate the longitudinal clinical outcomes using a new semiconstrained wrist prosthesis for the treatment of severe rheumatoid arthritis of the wrist. METHODS: Twenty patients with rheumatoid arthritis (20 wrists) underwent total wrist arthroplasty with the prosthesis in a clinical trial. The preoperative Larsen classification was grade IV in 16 wrists and grade V in 4 wrists. Assessments were performed before surgery, 1.5 years after surgery, and at final follow-up (≥ 5 years after surgery) using the visual analog scale for pain, Figgie wrist score, Japanese version of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, and plain radiographs. RESULTS: At final follow-up, no patient had wrist pain. The preoperative flexion-extension arc at final follow-up was similar to the preoperative range. The mean 1.5-year postoperative Figgie score was significantly improved and was unchanged at final follow-up. The DASH score significantly improved from before surgery to 1.5 years after surgery; the DASH score was improved further at final follow-up, but not significantly. Five of the 19 wrists evaluated had radiographic findings indicating carpal component loosening at final follow-up; however, all patients with the loosening were asymptomatic and had not undergone revision surgery. CONCLUSIONS: Total wrist arthroplasty using this wrist prosthesis leads to favorable clinical outcomes regarding pain relief and retained range of wrist motion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Bone marrow mesenchymal stem cells combined with ultra-purified alginate gel as a regenerative therapeutic strategy after discectomy for degenerated intervertebral discs.
Daisuke Ukeba, Hideki Sudo, Takeru Tsujimoto, Katsuro Ura, Katsuhisa Yamada, Norimasa Iwasaki
EBioMedicine, 53, 102698, 102698, 2020年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Because the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs. METHODS: Rabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs. FINDINGS: Gene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs. INTERPRETATION: These findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs. FUNDING: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.

MicroRNA-9 ameliorates destructive arthritis through down-regulation of NF-κB1-RANKL pathway in fibroblast-like synoviocytes.
Wen Shi Lee, Shinsuke Yasuda, Michihiro Kono, Yuki Kudo, Sanae Shimamura, Michihito Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Tomohiro Shimizu, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya Atsumi
Clinical immunology (Orlando, Fla.), 212, 108348, 108348, 2020年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We investigated the effect of miR-9 on fibroblast-like synoviocytes (FLS) from RA patients and animal arthritis model. The binding of miR-9 to NF-κB1 3'UTR was analyzed by luciferase reporter assay and immunoprecipitation. ChIP assay and luciferase promoter assay were performed to identify the binding of NF-κB1 to RANKL promoter and its activity. FLS were treated with miR-9/anti-miR-9 to evaluate cell proliferation and the expression of RANKL. Therapeutic effect of intra-articular miR-9 was evaluated in type-II collagen-induced arthritis in rats. miR-9 bound to the 3'-UTR of NF-κB1 and downregulated NF-κB1. NF-κB1 bound to RANKL promoter and increased the promoter activity of RANKL. RANKL was downregulated by miR-9. Proliferation of FLS was increased by miR-9 inhibitor. miR-9 dampened experimental arthritis by lowering inflammatory state, reducing RANKL and osteoclasts formation. Our findings revealed miR-9-NF-κB1-RANKL pathway in RA-FLS, further, miR-9 ameliorated inflammatory arthritis in vivo which propose therapeutic implications of miR- 9 in RA.

Which Contributes to Meniscal Repair, the Synovium or the Meniscus? An In Vivo Rabbit Model Study With the Freeze-Thaw Method.
WooYoung Kim, Tomohiro Onodera, Eiji Kondo, Mohamad Alaa Terkawi, Kentaro Homan, Ryosuke Hishimura, Norimasa Iwasaki
The American journal of sports medicine, 363546520906140, 363546520906140, 2020年02月27日, ［査読有り］, ［国際誌］
英語, BACKGROUND: During meniscal tissue repair, the origin of the reparative cells of damaged meniscal tissue remains unclear. HYPOTHESIS: Comparison of the influence between meniscal and synovial tissues on meniscal repair by the in vivo freeze-thaw method would clarify the origin of meniscal reparative cells. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 mature Japanese white rabbits were divided into 4 groups according to the tissue (meniscal or synovial) that received freeze-thaw treatment. The meniscus of each group had a 2 mm-diameter cylindrical defect filled with alginate gel. Macroscopic and histologic evaluations of the reparative tissues were performed at 1, 3, and 6 weeks postoperatively. Additional postoperative measurements included cell density, which was the number of meniscal cells in the cut area per cut area (mm2) of meniscus; cell density ratio, which was the cell density of the sample from each group per the average cell density of the intact meniscus; and cell death rate, which was the number of cells stained by propidium iodide per the number of cells stained by Hoechst 33342 of the meniscal tissue adjacent to the defect. RESULTS: The macroscopic and histologic evaluations of the non-synovium freeze-thaw groups were significantly superior to those of the synovium freeze-thaw groups at 3 and 6 weeks postoperatively. Additionally, the meniscal cell density ratio and cell death rate in the freeze-thaw groups were significantly lower than those in the non-meniscal freeze-thaw groups at 3 and 6 weeks postoperatively. CONCLUSION: The freeze-thawed meniscus recovered few cells in its tissue even after 6 weeks. However, the defect was filled with fibrochondrocytes and proteoglycan when the synovium was intact. On the basis of these results, it is concluded that synovial cells are the primary contributors to meniscal injury repair. CLINICAL RELEVANCE: In meniscal tissue engineering, there is no consensus on the best cell source for meniscal repair. Based on this study, increasing the synovial activity and contribution should be the main objective of meniscal tissue engineering. This study can establish the foundation for future meniscal tissue engineering.

Two case reports of 'locked spondyloptosis': the most severe traumatic cervical spondyloptosis with locked spinous process and vertebral arch into the spinal canal.
Takeru Tsujimoto, Kota Suda, Satoko Matsumoto Harmon, Miki Komatsu, Masahiko Takahata, Norimasa Iwasaki, Akio Minami
Spinal cord series and cases, 6, 1, 10, 10, 2020年02月18日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Traumatic cervical spondyloptosis, including compressive-extension stage 5 of Allen's classification of cervical spine injuries, is commonly observed; however, cases involving locked spinous process and vertebral arch into the spinal canal are extremely rare. CASE PRESENTATION: We present two individuals with spondyloptosis of C7 with locked spinous process of C6 and the vertebral arch into the spinal canal. Closed reduction was unable to be performed due to rigid locking of the cervical spine in the first case, whereas preoperative closed reduction was achieved with mild traction in a prone position after general anaesthesia in the second case. These two individuals underwent spinal fusion via a posterior approach after open or closed reduction. Six months after surgery, both individuals exhibited significant neurological recovery and acquired a stable gait. DISCUSSION: To the best of our knowledge, this is the first report of traumatic 'locked spondyloptosis' of the spinous process and vertebral arch into the spinal canal. Although high-grade compressive-extension injuries are usually repaired using a combined anterior-posterior approach, repair is possible with a posterior approach alone with reliable anchors, such as pedicle screws or multiple lateral mass screws. Urgent open reduction may be required for locked spondyloptosis when closed reduction is invalid due to rigid locking of the cervical spine.

Is Bone Non-Union, Vertebral Deformity, or Spino-Pelvic Malalignment the Best Therapeutic Target for Amelioration of Low Back Pain after Osteoporotic Vertebral Fracture?
Akira Iwata, Masahiro Kanayama, Fumihiro Oha, Yukitoshi Shimamura, Tomoyuki Hashimoto, Masahiko Takahata, Norimasa Iwasaki
Spine, 45, 13, E760-E767, 2020年02月11日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Cohort study (level 3). OBJECTIVE: To identify independent risk factors for residual low back pain (LBP) following osteoporotic vertebral fracture (OVF). SUMMARY OF BACKGROUND DATA: Non-union has been proposed as the primary cause of residual LBP following OVF. However, LBP can occur even when union is maintained. Other reported causes of LBP after OVF include vertebral deformities and spino-pelvic malalignment. METHODS: Sixty-seven patients with single-level thoracolumbar OVF who had not received previous osteoporotic treatment were enrolled. Conservative treatment was conducted using a soft lumbosacral orthosis plus osteoporosis drugs, either weekly alendronate (bisphosphonate) or daily teriparatide. Pain scores, kyphosis angle of fractured vertebra (VKA), and spino-pelvic alignment, including pelvic incidence minus lumbar lordosis (PI-LL), were assessed periodically during treatment. Radiographic union was evaluated independently by three specialists at 24 weeks post-admission. Patients were divided by pain scores >40% at 24 weeks into the LBP (n = 36) and non-LBP (n = 31) groups. Temporal changes and statistical associations were examined to identify risk factors for LBP at 24 weeks. RESULTS: At 24 weeks, 25% of OVFs failed to achieve union. The LBP group consisted of 71% of non-union and 48% of union cases. Stepwise multinomial regression analysis showed VKA at 24 weeks over 25° was significant risk factor for the LBP group (odds ratio: 6.24, 95% confidence interval: 1.77 - 22.02, p = 0.004). Significant differences in VKA emerged during treatment in the LBP group, but PI-LL showed the tendency not to change throughout the treatment period. Non-union was correlated with VKA (area under the curve: 0.864). CONCLUSION: Although spino-pelvic malalignment is considered as a pre-existing factor for LBP, VKA exacerbated by non-union predominantly led to LBP after a new OVF. Each incidence of OVF should be treated to limit further morphological changes to the fractured vertebra. LEVEL OF EVIDENCE: 3.

長期経過した特発性前骨間神経麻痺に対し神経剥離術が有効であった1症例　　　　　　　　　　　　　　　
遠藤 健, 松井 雄一郎, 河村 太介, 瓜田 淳, 本谷 和俊, 太田 光俊, 岩崎 倫政
日本肘関節学会雑誌, 27, 1, S91, S91, 日本肘関節学会, 2020年02月
日本語

好中球由来細胞外小胞が軟骨細胞に与える影響
江畑 拓, テルカウイ・アラー, 松前 元, 木田 博朗, 田 園, ヘンド・アルハサン, 高橋 大介, 小野寺 智洋, 岩崎 倫政
北海道整形災害外科学会雑誌, 62, 138th suppl, 5, 5, 北海道整形災害外科学会, 2020年
日本語

人工関節置換術後無菌性緩みに対するビタミンE添加ポリエチレンインプラントの至適濃度の検討
木田 博朗, Alaa Terkawi, 松前 元, 江畑 拓, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 62, 138th suppl, 5, 5, 北海道整形災害外科学会, 2020年
日本語

長期経過した特発性前骨間神経麻痺に対し神経剥離術が有効であった1症例
遠藤 健, 松井 雄一郎, 河村 太介, 瓜田 淳, 本谷 和俊, 太田 光俊, 倉茂 秀星, 岩崎 倫政
北海道整形災害外科学会雑誌, 62, 138th suppl, 91, 91, 北海道整形災害外科学会, 2020年
日本語

Charcot Arthropathy of the Shoulder Joint in a Patient with Guillain-Barré Syndrome: A Case Report.
Tetsuya Yamaguchi, Atsushi Urita, Takeshi Endo, Mitsutoshi Ota, Norimasa Iwasaki
JBJS case connector, 10, 1, e0530, 2020年, ［国際誌］
英語, 研究論文（学術雑誌）, CASE: A 53-year-old woman presented with Charcot arthropathy of the shoulder joint secondary to residual sensory neuropathy of Guillain-Barré syndrome, which was accompanied by swollen shoulder and restricted range of motion of the right shoulder. We performed a reverse shoulder arthroplasty (RSA). The range of motion had improved 15 months postoperatively, and there was no postoperative complication after RSA. CONCLUSION: Clinicians should be aware that Guillain-Barré syndrome can cause Charcot arthropathy of the shoulder joint. RSA is regarded as a useful treatment, although careful follow-up is needed.

Three-dimensional curvature mismatch of the acetabular radius to the femoral head radius is increased in borderline dysplastic hips.
Tohru Irie, Alejandro A Espinoza Orías, Tomoyo Y Irie, Shane J Nho, Daisuke Takahashi, Norimasa Iwasaki, Nozomu Inoue
PloS one, 15, 4, e0231001, 2020年, ［国際誌］
英語, 研究論文（学術雑誌）, Whether borderline hip dysplasia is pathologic remains unclear. In order to evaluate the three-dimensional joint congruity, this study sought to answer the question: are borderline dysplastic hip curvature mismatch and eccentricity between the acetabulum and the femoral head different from dysplastic or control hips three-dimensionally? The 113 hips, categorized as: dysplastic (LCEA ≤ 20°), 47 hips; borderline (20° ≤ LCEA < 25°), 32 hips; and control (25° ≤ LCEA < 35°), 34 hips; were evaluated. Three-dimensional (3D) femoral and coxal bone models were reconstructed from CT images. Using a custom-written Visual C++ routine, the femoral head and acetabular radii of curvature, and the femoral head and the acetabular curvature center were calculated. Then the ratio of the acetabular radius to the femoral head radius (3D curvature mismatch ratio), and the distance between the acetabular curvature center and the femoral head center (3D center discrepancy distance) were calculated. These indices were compared statistically among the three groups using Tukey's post hoc test. The mean 3D curvature mismatch ratio in the borderline (1.13 ± 0.05) was smaller than in the dysplasia (1.23 ± 0.08, p < 0.001), and larger than in the control (1.07 ± 0.02, p < 0.001). The mean 3D center discrepancy distance in the borderline (3.2 ± 1.4 mm) was smaller than in the dysplasia (4.8 ± 2.3, p < 0.001) and larger than in the control (1.6 ± 0.7, p < 0.001). These results demonstrated that three-dimensional congruity of the borderline dysplastic hip is impaired, but its incongruity is not as severe as in dysplastic hips. The 3D curvature mismatch ratio and the 3D center discrepancy distance can be valuable signs of joint congruity in patients with borderline dysplasia. However, future studies are necessary to clarify any associations between curvature mismatch and pathogenesis of osteoarthritis in borderline dysplasia.

Coronal Hamate Fractures with Carpometacarpal Dislocation Treated Effectively Using Headless Compression Screws with Percutaneous Pinning Fixation by Using the 2-Directional Approach: A Report of 2 Cases.
Hirokazu Shimizu, Tomoya Matsuhashi, Akira Fukushima, Yusuke Menjo, Yoshihiro Hojo, Norimasa Iwasaki
JBJS case connector, 10, 2, e0361, 2020年, ［国際誌］
英語, 研究論文（学術雑誌）, CASE: Coronal shear fractures of the hamate are relatively rare injuries. Surgical intervention is recommended for displaced fractures. However, there is no established surgical procedure for the displaced coronal shear fractures of the hamate. Therefore, we present 2 cases of the displaced coronal hamate fracture with metacarpal dislocations, which were successfully managed with open reduction and internal fixation, using the headless compression screw by the 2-directional approach. CONCLUSION: Our procedure ensured that the screw's distal end captured the hamate hook, and the displaced bone fragments were reduced considerably in both cases.

Blockade of XCL1/Lymphotactin Ameliorates Severity of Periprosthetic Osteolysis Triggered by Polyethylene-Particles.
Yuan Tian, Mohamad Alaa Terkawi, Tomohiro Onodera, Hend Alhasan, Gen Matsumae, Daisuke Takahashi, Masanari Hamasaki, Taku Ebata, Mahmoud Khamis Aly, Hiroaki Kida, Tomohiro Shimizu, Keita Uetsuki, Ken Kadoya, Norimasa Iwasaki
Frontiers in immunology, 11, 1720, 1720, 2020年, ［国際誌］
英語, 研究論文（学術雑誌）, Periprosthetic osteolysis induced by orthopedic implant-wear particles continues to be the leading cause of arthroplasty failure in majority of patients. Release of the wear debris results in a chronic local inflammatory response typified by the recruitment of immune cells, including macrophages. The cellular mediators derived from activated macrophages favor the osteoclast-bone resorbing activity resulting in bone loss at the site of implant and loosening of the prosthetic components. Emerging evidence suggests that chemokines and their receptors are involved in the progression of periprosthetic osteolysis associated with aseptic implant loosening. In the current study, we investigated the potential role of chemokine C-motif-ligand-1 (XCL1) in the pathogenesis of inflammatory osteolysis induced by wear particles. Expressions of XCL1 and its receptor XCR1 were evident in synovial fluids and tissues surrounding hip-implants of patients undergoing revision total hip arthroplasty. Furthermore, murine calvarial osteolysis model induced by ultra-high molecular weight polyethylene (UHMWPE) particles was used to study the role of XCL1 in the development of inflammatory osteolysis. Mice received single injection of recombinant XCL1 onto the calvariae after implantation of particles exhibited significantly greater osteolytic lesions than the control mice. In contrast, blockade of XCL1 by neutralizing antibody significantly reduced bone erosion and the number of bone-resorbing mature osteoclasts induced by UHMWPE particles. In consistence with the results, transplantation of XCL1-soaked sponge onto calvariae caused osteolytic lesions coincident with excessive infiltration of inflammatory cells and osteoclasts. These results suggested that XCL1 might be involved in the development of periprosthetic osteolysis through promoting infiltration of inflammatory cells and bone resorbing-osteoclasts. Our further results demonstrated that supplementing recombinant XCL1 to cultured human monocytes stimulated with the receptor activator of nuclear factor kappa-B ligand (RANKL) promoted osteoclastogenesis and the osteoclast-bone resorbing activity. Moreover, recombinant XCL1 promoted the expression of inflammatory and osteoclastogenic factors, including IL-6, IL-8, and RANKL in human differentiated osteoblasts. Together, these results suggested the potential role of XCL1 in the pathogenesis of periprosthetic osteolysis and aseptic loosening. Our data broaden knowledge of the pathogenesis of aseptic prosthesis loosening and highlight a novel molecular target for therapeutic intervention.

Conservatively Treated Femoral Intertrochanteric Fracture With Early Asymptomatic Novel Coronavirus Disease 2019 (COVID-19): A Case Report.
Yuki Suzuki, Toshihiko Kasashima, Kazutoshi Hontani, Yasuhiro Yamamoto, Kanako Ito, Liang Xu, Masatake Matsuoka, Koji Iwasaki, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
Geriatric orthopaedic surgery & rehabilitation, 11, 2151459320969380, 2151459320969380, 2020年, ［国際誌］
英語, Introduction: The ongoing outbreak of novel coronavirus disease 2019 (COVID-19) is a worldwide problem. Although diagnosing COVID-19 in fracture patients is important for selecting treatment, diagnosing early asymptomatic COVID-19 is difficult. We describe herein a rare case of femoral intertrochanteric fracture concomitant with early asymptomatic novel COVID-19. Case presentation: An 87-year-old Japanese woman was transferred to our emergency room with a right hip pain after she fell. She had no fever, fatigue, or respiratory symptoms on admission and within the 14 days before presenting to our hospital, and no specific shadow was detected in chest X-ray. However, chest computed tomography (CT) was performed considering COVID-19 pandemic, and showed ground-glass opacities with consolidation in the dorsal segment of the right lower lung field. Then, qualitative real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) was carried out and turned out to be positive. She was diagnosed right femoral intertrochanteric fracture with concomitant COVID-19 infection. Conservative treatment was applied to the fracture due to infection. After admission, fever and oxygen demand occurred but she recovered from COVID-19. Throughout the treatment period, no cross-infection from the patient was identified in our hospital. Conclusion: This case highlights the importance of considering chest CT as an effective screening method for infection on hospital admission in COVID-19-affected areas, especially in trauma patients with early asymptomatic novel COVID-19.

Long-term pulmonary function after posterior spinal fusion in main thoracic adolescent idiopathic scoliosis.
Young Man Byun, Takahiro Iida, Katsuhisa Yamada, Kuniyoshi Abumi, Terufumi Kokabu, Akira Iwata, Norimasa Iwasaki, Hideki Sudo
PloS one, 15, 6, e0235123, 2020年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Adolescent idiopathic scoliosis (AIS) patients typically undergo surgical treatment as teenagers, follow-ups of >5 years are necessary to evaluate effects on peak pulmonary reserves. However, limited data is available regarding the long-term (>10 years) effects of surgical intervention on pulmonary function (PF) in patients with thoracic AIS. OBJECTIVE: To provide long-term (>10 years) information on the PF after posterior spinal fusion for treating main thoracic AIS. We especially investigated whether surgical correction for AIS led to impairment of the PF. METHODS: A total of 35 patients with main thoracic AIS treated with posterior spinal fusion were included. Radiographs and PF tests, which included measurements of absolute and percent-predicted values of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1), were evaluated. RESULTS: Mean age at surgery was 14.9 years (12-19 years). Mean follow-up period was 15.1 years (10-24 years). Although the final postoperative FVC and FEV1 absolute values were higher than the preoperative values, the differences were not statistically significant (p = 0.22 and p = 0.08, respectively). Percent-predicted FVC and FEV1 values between preoperative and final postoperative measurements were not statistically different (p = 0.63 and p = 0.29, respectively). However, for the patients who presented with pulmonary impairment preoperatively, both the FVC and FEV1 significantly increased at the final follow-up (p = 0.01 and p = 0.01, respectively). CONCLUSIONS: Long-term results of AIS patients who underwent posterior spinal fusion in main thoracic curves demonstrated absolute and percent-predicted PF test values similar to preoperative measurements; thus, indicating that posterior spinal fusion did not decrease PF 15 years after the initial surgery. Instead, patients with severe preoperative pulmonary impairment might show some degree of improvement after surgery.

Evaluation of Residual Human-Induced Pluripotent Stem Cells in Human Chondrocytes by Cell Type-Specific Glycosphingolipid Glycome Analysis Based on the Aminolysis-SALSA Technique.
Takuji Miyazaki, Hisatoshi Hanamatsu, Liang Xu, Tomohiro Onodera, Jun-Ichi Furukawa, Kentaro Homan, Rikiya Baba, Toshisuke Kawasaki, Norimasa Iwasaki
International journal of molecular sciences, 21, 1, 2019年12月28日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Cartilage damage may eventually lead to osteoarthritis because it is difficult to repair. Human-induced pluripotent stem cell (iPSC)-derived chondrocytes may potentially be used to treat cartilage damage, but the tumorigenicity of iPSCs is a major concern for their application in regenerative medicine. Many glycoconjugates serve as stem cell markers, and glycosphingolipids (GSLs) including H type 1 antigen (Fucα1-2Galβ1-3GlcNAc) have been expressed on the surface of iPSCs. The purpose of the present study was to investigate whether GSL-glycome analysis is useful for quality control of residual iPSCs in chondrocytes. We performed GSL-glycome analysis of undifferentiated iPSCs in chondrocytes by combining glycoblotting and aminolysis-sialic acid linkage-specific alkylamidation (SALSA) method, enabling the detection of small quantities of iPSC-specific GSL-glycans from 5 × 104 cells. Furthermore, we estimated the residual amount of iPSCs using R-17F antibody, which possesses cytotoxic activity toward iPSCs that is dependent on the Lacto-N-fucopentaose I (LNFP I) of GSL. Moreover, we could detect a small number of LNFP I during mesenchymal stem cells (MSCs) differentiation from iPSCs. This is the first demonstration that GSL-glycome analysis is useful for detecting undifferentiated iPSCs, and can thereby support safe regenerative medicine.

Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging.
Takashi Ohnishi, Katsuhisa Yamada, Koji Iwasaki, Takeru Tsujimoto, Hideaki Higashi, Taichi Kimura, Norimasa Iwasaki, Hideki Sudo
Scientific reports, 9, 1, 19324, 19324, 2019年12月18日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Approximately 40% of people under 30 and over 90% of people 55 or older suffer from moderate-to-severe levels of degenerative intervertebral disc (IVD) disease in their lumbar spines. Surgical treatments are sometimes effective; however, the treatment of back pain related to IVD degeneration is still a challenge; therefore, new treatments are necessary. Apoptosis may be important in IVD degeneration because suppressing cell apoptosis inside the IVD inhibits degeneration. Caspase-3, the primary effector of apoptosis, may be a key treatment target. We analyzed caspase-3's role in two different types of IVD degeneration using caspase-3 knockout (Casp-3 KO) mice. Casp-3 KO delayed IVD degeneration in the injury-induced model but accelerated it in the age-induced model. Our results suggest that this is due to different pathological mechanisms of these two types of IVD degeneration. Apoptosis was suppressed in the IVD cells of Casp-3 KO mice, but cellular senescence was enhanced. This would explain why the Casp-3 KO was effective against injury-induced, but not age-related, IVD degeneration. Our results suggest that short-term caspase-3 inhibition could be used to treat injury-induced IVD degeneration.

Perioperative complications of spine surgery in patients 80 years of age or older: a multicenter prospective cohort study.
Watanabe T, Kanayama M, Takahata M, Oda I, Suda K, Abe Y, Okumura J, Hojo Y, Iwasaki N
Journal of neurosurgery. Spine, 1, 9, 2019年12月17日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: The number of spine surgeries performed in elderly patients is consistently increasing. However, to date the prevalence of and risk factors for perioperative complications remain unclear, especially in patients 80 years of age or older. This study had two goals: 1) determine the perioperative complications of spine surgery associated with patients 80 years of age or older; and 2) investigate the risk factors for perioperative systemic complications. METHODS: In this paper, the authors describe a multicenter prospective cohort study. Seven spine centers with board-certified spine surgeons participated in this all-case investigation. A total of 270 consecutively enrolled patients (109 males and 161 females), 80 years of age or older, underwent spine surgery between January and December 2017. Patients with trauma, infection, or tumor were excluded in this cohort. Perioperative complications were defined as adverse events that occurred intraoperatively or within 30 days postoperatively. The patients' preoperative health status was determined using the following means of assessment: 1) the Charlson Comorbidity Index, 2) the American Society of Anesthesiologists Physical Status Classification System, 3) the Eastern Cooperative Oncology Group Performance Status (ECOG-PS), 4) the presence of sarcopenia, and 5) the Geriatric Nutritional Risk Index. Associations among patient age, preoperative health status, surgical factors (instrumentation surgery, operation time, number of spinal levels treated, and estimated blood loss), and perioperative systemic complications were analyzed. RESULTS: Overall perioperative, surgical site, and minor systemic complications were observed in 20.0%, 8.1%, and 14.8% of patients, respectively. Major systemic complications, on the other hand, were not observed. The reoperation rate was low-only 4.1%. Multivariate analysis revealed that the ECOG-PS (p = 0.013), instrumentation surgery (p = 0.024), and an operation time longer than 180 minutes (p = 0.016) were associated with minor systemic complications. CONCLUSIONS: To the best of the authors' knowledge, this is the first multicenter prospective all-case investigation of perioperative complications of spine surgery in elderly patients. Although decreased daily activity (ECOG-PS), instrumentation surgery, and longer operation time were associated with minor systemic complications, no major systemic complications were observed in these elderly patients. Thus, spine surgery can be safely performed in elderly patients 80 years of age or older.

分化度の異なる各種シュワン細胞の末梢神経軸索再生効果の検討
遠藤 健, 角家 健, 鈴木 智亮, 松井 祐樹, 袁 儒非, 山本 康弘, 河村 太介, 岩崎 倫政
末梢神経, 30, 2, 257, 257, 日本末梢神経学会, 2019年12月
日本語

Long-term stress distribution patterns across the wrist joint in gymnasts assessed by computed tomography osteoabsorptiometry.
Daisuke Momma, Wataru Iwamoto, Norimasa Iwasaki
The Journal of hand surgery, European volume, 44, 10, 1098, 1100, 2019年12月, ［国際誌］
英語

Trapeziectomy with Ligament Reconstruction and Interposition Arthroplasty Using the Palmaris Longus Tendon: An Average 5-Year Follow-up.
Daisuke Kawamura, Tadanao Funakoshi, Norimasa Iwasaki
Clinics in orthopedic surgery, 11, 4, 453, 458, 2019年12月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Trapeziectomy with ligament reconstruction and tendon interposition (LRTI) with the flexor carpi radialis (FCR) tendon is one of the most common procedures for the treatment of trapeziometacarpal osteoarthritis. We modified the LRTI, using the palmaris longus (PL) tendon instead of the FCR tendon. The aim of this retrospective study was to evaluate the clinical outcomes of trapeziectomy with our modified LRTI procedure at a mean follow-up of 5 years. METHODS: Fourteen thumbs in 13 patients (12 women) with a mean age of 64 years (range, 50 to 77 years) were available for assessment for a mean duration of 62 months (range, 41 to 97 months). The patients were evaluated subjectively and objectively. RESULTS: The modified LRTI procedure provided good pain relief, motion, strength, and stability without any severe complications related to the PL tendon harvesting. Radiography showed that compared to the preoperative status, the trapezial space decreased by about 40% at the final follow-up. CONCLUSIONS: The modified LRTI procedure provided significant subjective and objective improvements without severe complications particularly related to the harvesting of the PL tendon. This procedure is a valuable surgical option for trapeziometacarpal osteoarthritis and could be a useful salvage modality if the FCR tendon ruptures during the conventional LRTI procedure.

Breast cancer cells expressing cancer-associated sialyl-Tn antigen have less capacity to develop osteolytic lesions in a mouse model of skeletal colonization.
Fujita R, Hamano H, Kameda Y, Arai R, Shimizu T, Ota M, Sato D, Kobayashi H, Iwasaki N, Takahata M
Clinical & experimental metastasis, 36, 6, 539, 549, 2019年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Breast cancer is one of the most prevalent malignancies in women, and approximately 75-80% of patients with advanced breast cancer develop bone metastasis. Expression of the cancer-associated carbohydrate antigen sialyl-Tn (STn) in breast cancer is associated with a poor prognosis; however, involvement of STn in the development of metastatic bone lesions remains unclear. We investigated whether STn expression on breast cancer cells influences intraosseous tumor growth and bone response in mice models of skeletal colonization. STn-positive (STn+) breast cancer cells were generated by stable transfection of an expression vector encoding ST6GaLNAc I into the breast cancer cell line MDA-MB-231. Parental MDA-MB-231 cells not expressing STn antigen were used as STn-negative (STn-) breast cancer cells. Contrary to expectations, STn expression attenuated the development of destructive bone lesions in the in vivo mice models. An in vitro study demonstrated that STn expression impaired adhesion of MDA-MB-231cells to bone marrow stromal cells. This finding in vitro was also confirmed by another breast cancer cell line MCF-7. Cell adhesion to fibronectin and type I collagen was also impaired in STn+ MDA-MB-231 cells compared to that in STn- MDA-MB-231 cells, suggesting integrin dysfunction. Given that the integrin β1 subunit is the main carrier of the STn epitope, it is likely that changes in glycan structure impaired the adhesive capacity of β1 integrin in the bone environment, leading to attenuation of tumor cell engraftment. In conclusion, breast cancer cells expressing STn antigen had less capacity for skeletal colonization, possibly due to impaired adhesive capability.

人工関節置換術後の無菌性緩みにおけるマクロファージ由来チミジンホスホリラーゼの機能解析　　　　　　　　　　　　　　　
松前 元, Terkawi Alaa, 江畑 拓, 木田 博朗, 高橋 大介, 岩崎 倫政
日本バイオマテリアル学会大会予稿集, 41回, 180, 180, 日本バイオマテリアル学会, 2019年11月
日本語

人工関節置換術後のポリエチレン摩耗粉による炎症性骨吸収及び破骨細胞発現におけるannexin A1の機能解析　　　　　　　　　　　　　　　
Terkawi Alaa, Alhasan Hend, 松前 元, 江畑 拓, 木田 博朗, 高橋 大介, 岩崎 倫政
日本バイオマテリアル学会大会予稿集, 41回, 181, 181, 日本バイオマテリアル学会, 2019年11月
日本語

人工関節置換術後無菌性緩みに対するビタミンE添加ポリエチレンインプラントの至適濃度の検討　　　　　　　　　　　　　　　
木田 博朗, Terkawi Alaa, 松前 元, 江畑 拓, 高橋 大介, 岩崎 倫政
日本バイオマテリアル学会大会予稿集, 41回, 182, 182, 日本バイオマテリアル学会, 2019年11月
日本語

Impact of Surgical Timing on Clinical Outcomes in Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using Hamstring Tendon Autografts.
Rikiya Baba, Eiji Kondo, Koji Iwasaki, Zenta Joutoku, Jun Onodera, Tomohiro Onodera, Tomonori Yagi, Norimasa Iwasaki, Kazunori Yasuda
Orthopaedic journal of sports medicine, 7, 11, 2325967119880553, 2325967119880553, 2019年11月, ［国際誌］
英語, 研究論文（学術雑誌）, Background: To date, no studies have analyzed the influence on clinical outcomes of the interval between an anterior cruciate ligament (ACL) injury and double-bundle (DB) reconstruction with hamstring tendon autografts. Hypotheses: (1) Performing ACL reconstruction sooner after an injury will reduce postoperative anterior and rotatory knee instability, (2) postoperative range of knee motion or functional results will not be affected by different intervals between injury and surgery, and (3) preoperative isokinetic peak torque of the quadriceps and hamstring muscles will be lower in patients undergoing surgery earlier, while postoperative muscle strength will not be affected by surgery timing. Study Design: Cohort study; Level of evidence, 3. Methods: This study was conducted on a total of 171 patients who had undergone anatomic DB ACL reconstruction with hamstring tendon autografts. The patients were divided into 3 groups based on the time to surgery: (1) ≤1 month after the injury (group E; n = 25), (2) between 1 and 3 months after the injury (group M; n = 72), and (3) >3 months after the injury (group D; n = 74). Patients were assessed for a minimum of 2 years after surgery. Results: Concerning postoperative anterior laxity, 1-way analysis of variance demonstrated a significant difference (P = .0274) among the 3 groups. Anterior laxity was significantly less in group E than in group D (P = .0206). Spearman rank correlation analysis showed a significant correlation (ρ = 0.200; P = .0327) between anterior knee laxity and time to surgery. Also, a significant correlation (P = .0461) was found between the degree of the pivot-shift phenomenon and time to surgery. There were no significant differences in loss of knee extension or flexion among the 3 groups, nor were there any differences in the Lysholm knee score or International Knee Documentation Committee grade. Postoperatively, there were no significant differences in peak torque of the quadriceps or hamstring muscles among the 3 groups. Conclusion: Early DB reconstruction led to significantly less anterior laxity compared with delayed reconstruction. There were no significant differences in postoperative range of knee motion or functional results among the 3 time intervals between injury and surgery in this study.

Retrospective study to evaluate the clinical significance of a second rise in C-reactive protein level following instrumented spinal fusion surgery.
Fujita R, Takahata M, Kokabu T, Oda I, Kajino T, Hisada Y, Takeuchi H, Iwasaki N
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 24, 6, 963, 968, 2019年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: This study aimed to identify the incidence and causes of a second rise in C-reactive protein (CRP) levels following spinal instrumentation surgery and to help determine how an abnormal CRP response should be interpreted and managed during postoperative care. METHODS: The medical records of 948 patients who underwent instrumented spine fusion surgery and met the inclusion criteria were retrospectively reviewed to assess the frequency and causes of a second rise (SR) of CRP. A SR of CRP was defined when the CRP level after postoperative day 7 increased by more than 0.5 mg/dl from that at the previous time-point. The diagnostic cut-off value of CRP elevation for detection of surgical site infection (SSI) was determined. Cut-off values were analyzed using receiver operating characteristic (ROC) curves. Bayes' theorem was used to determine blood test posterior probabilities for SSI-positive cases using cutoff values of re-evaluated CRP levels. RESULTS: SR of CRP occurred in 107 of the 948 patients. Of the patients with SR of CRP, 38 (35%) patients had developed SSI, 33 (31%) patients had causes other than SSI, and the remaining 36 patients had unidentified causes. Among the patients with SR, excluding those with causes other than SSI, the best diagnostic cut-off value of SR for detection of SSI was 3.04 mg/dl (area under the curve was 0.74). The posterior test probability was 84.4%. CONCLUSIONS: For patients with SR of CRP, who had no causes other than SSI, an SR value of 3.04 mg/dl correlated with a high probability of developing SSI.

Assessment of valgus laxity after release of the medial structure in medial open-wedge high tibial osteotomy: an in vivo biomechanical study using quantitative valgus stress radiography.
Dai Sato, Eiji Kondo, Koji Yabuuchi, Jun Onodera, Tomohiro Onodera, Tomonori Yagi, Keita Sakamoto, Akira Takasawa, Norimasa Iwasaki, Kazunori Yasuda
BMC musculoskeletal disorders, 20, 1, 481, 481, 2019年10月27日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: To perform medial open-wedge high tibial osteotomy (OWHTO), surgeons expose the medial-proximal tibia by releasing or cutting the superficial layer of the medial collateral ligament (sMCL). Biomechanically, the sMCL provides primary restraint against valgus forces. Therefore, any release of the sMCL can cause valgus instability of the knee joint. The purpose of this study was to assess valgus laxity after release of the medial structure of the knee during OWHTO. METHODS: Between 2009 and 2015, 84 consecutive patients (93 knees) who underwent OWHTO using a locking plate were enrolled in this study. All patients underwent radiological examinations before surgery, during surgery, 1 year after surgery, and after plate removal to objectively assess valgus laxity. The medial joint space (MJS) and the joint line convergence angle (JLCA) of the knee were evaluated using quantitative valgus stress radiography. Clinical evaluation was performed 2 years after surgery. RESULTS: The mean functional knee score improved significantly, from 65.5 to 91.1 points (p < 0.0001). The mechanical axis percentage shifted to pass through a point 69.7% lateral from the medial edge of the tibial plateau. The MJS and JLCA increased significantly during OWHTO surgery (11.0 mm, 7.4 °, p < 0.0001). However, no significant differences were noted in the MJS and JLCA among preoperative, 1-year postoperative periods and after plate removal. CONCLUSION: Valgus laxity was significantly greater after release of the sMCL. However, no significant differences were noted in valgus laxity in preoperative, 1-year postoperative periods and after plate removal. Complete release of the sMCL did not cause postoperative valgus laxity after OWHTO surgery. TRIAL REGISTRATION: Trial registration number: No.012-0360.

Occipitoatlantoaxial rotatory fixation caused by minor traumatic occipitoatlantal rotatory fixation with compensatory counter-rotation in atlantoaxial joint: A case report.
Shimizu H, Endo T, Takahata M, Yasui K, Sodeyama Y, Iwasaki N
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 27, 4, 956, 959, 2019年10月10日, ［査読有り］, ［国内誌］
英語

Evidence for cell-contact factor involvement in neurite outgrowth of dorsal root ganglion neurons stimulated by Schwann cells.
Takeshi Endo, Ken Kadoya, Daisuke Kawamura, Norimasa Iwasaki
Experimental physiology, 104, 10, 1447, 1454, 2019年10月, ［国際誌］
英語, 研究論文（学術雑誌）, NEW FINDINGS: What is the central question of this study? Although the factors secreted from Schwann cells that promote axonal growth in the peripheral nervous system have been well studied, the effect of cell-contact factors on Schwann cells remains to be determined. What is the main finding and its importance? This study demonstrates that Schwann cells stimulate neurite outgrowth by direct contact with neurites and by secreting factors. Notably, the effect of cell-contact factors in neurite outgrowth is comparable to that of secreted factors, indicating that the identification of cell surface molecules on Schwann cells that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury. ABSTRACT: Schwann cells (SCs) play a variety of roles in the regeneration process after injury to the peripheral nervous system. The factors secreted from SCs that promote axonal growth have been well studied. However, the involvement of cell-contact factors on SCs remains to be determined. Here, we demonstrate a significant contribution of a cell-contact mechanism in the effect of SCs on promotion of neuronal outgrowth. Neurite outgrowth of adult sensory neurons from dorsal root ganglia was quantified during co-culture with adult SCs. Direct contact of SCs with neurons was eliminated by culturing SCs on an insert placed in the same well; this resulted in a 51% reduction in the length of neurite outgrowth. In addition, when dorsal root ganglion neurons were cultured on sparsely seeded SCs, neurons that made contact with SCs on their neurites had 118% longer neurites than neurons that lacked contacts with SCs. Collectively, these findings provide evidence that SCs stimulate neurite outgrowth via direct contact with neurites in addition to secreting factors. The identification of cell surface molecules on SCs that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury.

Ten years change in post-fracture care for hip fracture patients.
Shimodan S, Sato D, Takahashi K, Nakamura Y, Hyakkan R, Watanabe T, Hishimura R, Ota M, Shimizu H, Hojo Y, Hasegawa Y, Chubachi T, Yasui K, Tsujimoto T, Tsukuda Y, Asano T, Takahashi D, Takahata M, Iwasaki N, Shimizu T
Journal of bone and mineral metabolism, 38, 2, 222, 229, 2019年10月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: This multicenter, retrospective study aimed to clarify the changes in postoperative care provided by orthopaedic surgeons after hip fractures and clarify the incidence of secondary fractures requiring surgery. MATERIALS AND METHODS: Subjects were patients with hip fracture treated surgically in seven hospitals during the 10-year period from January 2008 to December 2017. Data on patient demographics, comorbidities, preoperative and postoperative osteoporosis treatments, and secondary fractures were collected from the medical records. RESULTS: In total, 4764 new hip fractures in 982 men and 3782 women (mean age: 81.3 ± 10.0 years) were identified. Approximately 10% of patients had a history of osteoporosis drug treatment and 35% of patients received postoperative drug treatment. The proportion of patients receiving postoperative drug therapy increased by approximately 10% between 2009 and 2010, 10% between 2010 and 2011, and 10% between 2011 and 2013. Although the rate of secondary fractures during the entire period and within 3 years decreased from 2011, the rate of secondary fracture within 1 year remained at around 2% every year. CONCLUSIONS: The approval of new osteoporosis drugs and the establishment of osteoporosis liaison services have had a positive effect on the use of postoperative drug therapy in the orthopedic field. Our finding that the rate of secondary fracture within 1 year of the initial fracture remained around 2% every year, despite improvements in postoperative drug therapy, suggests that both rehabilitation for preventing falls and early postoperative drug therapy are essential to prevent secondary fractures.

軟骨破片刺激モデルにおいて軟骨細胞は軟骨内骨化関連の遺伝子発現が上昇する
江畑 拓, 濱崎 雅成, Terkawi M. Alaa, 小野寺 智洋, 松前 元, 田 園, Alhasan Hend, 宮崎 拓自, 徐 亮, 菱村 亮介, 岩崎 倫政
日本整形外科学会雑誌, 93, 8, S1688, S1688, (公社)日本整形外科学会, 2019年09月
日本語

炎症収束性マクロファージ由来の新規骨吸収抑制因子の同定 骨粗鬆症に対する新たな治療法開発に向けて　　　　　　　　　　　　　　　
Terkawi M. Alaa, 松前 元, 田 園, Alhasan Hend, 濱崎 雅成, 江畑 拓, 高橋 大介, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 93, 8, S1834, S1834, (公社)日本整形外科学会, 2019年09月
日本語

インプラントの破片によって引き起こされる炎症性骨溶解の発生におけるケモカインXCL1/リンホタクチンの関与　　　　　　　　　　　　　　　
田 園, テルカウイ・アラー, 小野寺 智洋, アルハサン・ヘンド, 松前 元, 高橋 大介, 濱崎 雅成, 江畑 拓, 岩崎 倫政
日本骨代謝学会学術集会プログラム抄録集, 37回, 183, 183, (一社)日本骨代謝学会, 2019年09月
英語

整形外科用インプラントのポリエチレン摩耗粉により引き起こされる炎症性骨溶解および破骨細胞形成におけるアネキシンA1の調節的役割　　　　　　　　　　　　　　　
テルカウイ・モハマ・ドアラー, アルハサン・ヘンド, 田 園, 松前 元, 濱崎 雅成, 江畑 拓, 高橋 大介, 岩崎 倫政
日本骨代謝学会学術集会プログラム抄録集, 37回, 183, 183, (一社)日本骨代謝学会, 2019年09月
英語

Schwann細胞の接着因子を介した神経突起伸長効果の検討
遠藤 健, 角家 健, 鈴木 裕貴, 松居 祐樹, 袁 儒非, 鈴木 智亮, 福井 隆史, 山本 康弘, 河村 太介, 岩崎 倫政
日本整形外科学会雑誌, 93, 8, S1707, S1707, (公社)日本整形外科学会, 2019年09月
日本語

椎間板再生への挑戦 高純度硬化性ゲルによる椎間板再生
辻本 武尊, 須藤 英毅, 東藤 正浩, 山田 勝久, 大西 貴士, 岩崎 倫政
日本整形外科学会雑誌, 93, 8, S1595, S1595, (公社)日本整形外科学会, 2019年09月
日本語

A multi-centre study to explore the feasibility and acceptability of collecting data for complex regional pain syndrome clinical studies using a core measurement set: Study protocol.
Sharon Grieve, Florian Brunner, Lisa Buckle, Francois Gobeil, Hitoshi Hirata, Norimasa Iwasaki, Lorimer Moseley, Gudson Sousa, Jean-Jacques Vatine, Nicole Vaughan-Spickers, Jijun Xu, Candida McCabe
Musculoskeletal care, 17, 3, 249, 256, 2019年09月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: This international, multicentre study will inform the final data collection tools and processes which will comprise the first international, clinical research registry for complex regional pain syndrome (CRPS). This study will: (a) test the feasibility and acceptability of collecting outcome measurement data using a patient reported, questionnaire core measurement set (COMPACT [Core Outcome Measurement set for complex regional PAin syndrome Clinical sTudies]); and (b) test and refine an electronic data management system to collect and manage the data. METHODS: A maximum of 240 adults, meeting the Budapest diagnostic clinical criteria for CRPS type I or II, will be recruited across eight countries. The COMPACT questionnaire will be completed on two occasions: at baseline (T1) and 6 months later (T2). At T2, participants will choose to complete COMPACT using a paper or electronic version. Participants will be asked to feed back on their experience of completing COMPACT via a questionnaire. A separate questionnaire will ask clinicians to feed back their experience of data collection. ANALYSIS: The study is not aiming to derive statistically significant data but to ascertain the practicalities of collecting data, using the COMPACT questionnaire set, across a range of different cultures and populations. At the end of the study, a single workshop will be convened to review the findings and agree the final documents and processes for the international registry.

Minimum Ten-Year Outcomes of Partial Ulnar Nerve Transfer for Restoration of Elbow Flexion in Patients with Upper Brachial Plexus Injury.
Nagano Y, Kawamura D, Terkawi A, Urita A, Matsui Y, Iwasaki N
The journal of hand surgery Asian-Pacific volume, 24, 3, 283, 288, 2019年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Partial ulnar nerve transfer to the biceps motor branch of the musculocutaneous nerve (Oberlin's transfer) is a successful approach to restore elbow flexion in patients with upper brachial plexus injury (BPI). However, there is no report on more than 10 years subjective and objective outcomes. The purpose of this study was to clarify the long-term outcomes of Oberlin's transfer based on the objective evaluation of elbow flexion strength and subjective functional evaluation of patients. Methods: Six patients with BPI who underwent Oberlin's transfer were reviewed retrospectively by their medical records. The mean age at surgery was 29.5 years, and the mean follow-up duration was 13 years. The objective functional outcomes were evaluated by biceps muscle strength using the Medical Research Council (MRC) grade at preoperative, postoperative, and final follow-up. The patient-derived subjective functional outcomes were evaluated using the Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) questionnaire at final follow-up. Results: All patients had MRC grade 0 (M0) or 1 (M1) elbow flexion strength before operation. Four patients gained M4 postoperatively and maintained or increased muscle strength at the final follow-up. One patient gained M3 postoperatively and at the final follow-up. Although one patient achieved M4 postoperatively, the strength was reduced to M2 due to additional disorder. The mean score of QuickDASH was 36.5 (range, 7-71). Patients were divided into two groups; three patients had lower scores and the other three patients had higher scores of QuickDASH. Conclusions: Oberlin's transfer is effective in the restoration of elbow flexion and can maintain the strength for more than 10 years. Patients with upper BPI with restored elbow flexion strength and no complicated nerve disorders have over ten-year subjective satisfaction.

Effects of Intradiscal Injection of Local Anesthetics on Intervertebral Disc Degeneration in Rabbit Degenerated Intervertebral Disc.
Ura K, Sudo H, Iwasaki K, Tsujimoto T, Ukeba D, Iwasaki N
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 37, 9, 1963, 1971, 2019年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Analgesic discoblock is widely used for the diagnosis or treatment of discogenic low back pain by injecting local anesthetics. The purpose of this study was to investigate the deleterious effects of local anesthetics on degenerated rabbit intervertebral disks (IVDs) using an organotypic culture model and in vivo long-term follow-up model. To induce IVD degeneration, a rabbit annular puncture model was used. For the organotypic culture model, degenerated IVDs were harvested 1 month after the initial annular puncture and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine and 0.5% bupivacaine). To perform in vivo analysis, local anesthetics were injected into degenerated IVDs, and IVDs were prepared for histological analysis after 6 or 12 months. In the organotypic model, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive nucleus pulposus (NP) cells were significantly increased in the bupivacaine group compared with the other groups. In the in vivo study, the number of NP cells was significantly decreased in the saline and local anesthetics groups compared with the untreated control and puncture-only groups. However, there was no significant difference among the saline, lidocaine, and bupivacaine groups. In addition, histological analysis showed no significant difference of IVD degeneration among the puncture-only, saline, lidocaine, and bupivacaine groups. Although bupivacaine induced apoptotic NP cell death in the organotypic culture model, in vivo observations did not show any definitive proof to suggest that local anesthetics were capable of promoting degeneration in the degenerated IVD, except for pressurized injection-induced damage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1963-1971, 2019.

Mechanical Analysis of Notch-Free Pre-Bent Rods for Spinal Deformity Surgery.
Yamada K, Sudo H, Iwasaki N, Chiba A
Spine, 45, 6, E312-E318, 2019年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Experimental study of spinal rod as per the American Society for Testing Materials (ASTM) F2193 methodology for static and dynamic four-point bending. OBJECTIVE: The hypotheses underlying this study were that the notch-free, curved rod would have a significantly higher ultimate load and fatigue strength compared with conventional notched curved rods. This study aimed to analyze the mechanical properties of notch-free curved rods compared with conventional notched rods. SUMMARY OF BACKGROUND DATA: The goal of instrumented spinal fusion in the management of spinal deformities is to realign the spine and maintain the correction and stability in order to obtain arthrodesis. Although rod curvature could play an important role, intraoperative contouring of the straight rod induces notches into the rod, leading to decreased fatigue strength. METHODS: Commercially produced titanium alloy (ϕ6.0 mm) and cobalt chromium alloy (ϕ5.5 mm) spinal rods were assessed by four-point bending tests in accordance with the ASTM F2193. RESULTS: Static four-point bending tests for the curved spinal rods showed that cobalt chromium alloy rods had significantly higher stiffness compared with titanium alloy rods. Notch-free cobalt chromium alloy rods had a significantly higher ultimate load than the conventional notched cobalt chromium alloy and titanium alloy rods. The dynamic four-point bending test showed that force/displacement at a minimum force at 2,500,000 cycles was larger in the notch-free cobalt chromium alloy rod than in the notched cobalt chromium alloy rod. CONCLUSION: The notch-free curved cobalt chromium alloy rod is likely to maintain its curvature after spinal deformity surgery with a decreased risk of breakage and could overcome the problems of the conventional notched rod such as breakage and spring-back. LEVEL OF EVIDENCE: N/A.

人工関節由来ポリエチレン摩耗粉とマクロファージの共培養による網羅的遺伝子発現解析と骨吸収促進因子の同定
テルカウイ・アラー, 濱崎 雅成, 松前 元, 江畑 拓, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 61, 1, 1, 9, 北海道整形災害外科学会, 2019年08月
日本語, 人工関節置換術後の無菌性緩みは重大な合併症の一つであるが、その病態として局所マクロファージが人工関節摺動面において発生したポリエチレン摩耗粉と反応し、破骨細胞による過剰な骨吸収が惹起されることにより発生する。しかしながら、人工関節の無菌性緩みにおける骨吸収メカニズムの詳細は未だ不明である。そこで、ポリエチレン摩耗粉とマクロファージを共培養し、網羅的遺伝子発現解析を行うことで、無菌性緩みのメカニズム解明を目的に本研究を行った。その結果、サイトカイン、ケモカイン、成長因子、受容体関連の遺伝子発現上昇を認めた。さらに関節リウマチにおいて発現上昇を認める因子のデータベースと比較することで、共通に発現上昇を認める遺伝子を同定した。このことから、人工関節の無菌性緩みについても関節リウマチと同様の病的骨吸収が起こることが示唆された。本研究は、人工関節の無菌性緩みにおける新たな知見を与えるものである。(著者抄録)

Clinical characteristics of patients with thoracic myelopathy caused by ossification of the posterior longitudinal ligament.
Endo T, Takahata M, Koike Y, Iwasaki N
Journal of bone and mineral metabolism, 38, 1, 63, 69, 2019年07月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Although ossification of the posterior longitudinal ligament (OPLL) commonly develops in the cervical spine, it also occurs, albeit less commonly, in the thoracic spine. However, data are scarce regarding the characteristics of patients with thoracic OPLL. In the current study, we performed a cross-sectional study on a total of 133 patients with OPLL to clarify the clinical characteristics of patients with thoracic OPLL compared with those of patients with cervical OPLL. The subjects were divided into four groups according to the main region of OPLL and treatment type: C-OPLL-C, cervical OPLL treated conservatively; C-OPLL-S, cervical OPLL treated via surgery; T-OPLL-C, thoracic OPLL treated conservatively; and T-OPLL-S, thoracic OPLL treated via surgery. Symptoms developed at an earlier age in the T-OPLL-S group than in the C-OPLL groups. Current body mass index (BMI), maximum lifetime BMI, and BMI at the age of 20 years were significantly higher in the T-OPLL-S group than in the C-OPLL groups. Yearly weight gain from the age of 20 years to the age at which maximum body weight was attained was significantly greater in the T-OPLL-S group than in the C-OPLL groups. The T-OPLL group showed a higher rate of co-existence of OPLL at other regions or ossification of the ligamentum flavum compared to the C-OPLL groups. Our findings demonstrate that severe obesity, early-onset of symptoms, and diffuse ossification of spinal ligaments are distinct features of patients with myelopathy caused by thoracic OPLL.

Three-dimensional depth sensor imaging to identify adolescent idiopathic scoliosis: a prospective multicenter cohort study
Terufumi Kokabu, Noriaki Kawakami, Koki Uno, Toshiaki Kotani, Teppei Suzuki, Yuichiro Abe, Kenichiro Maeda, Fujio Inage, Yoichi M. Ito, Norimasa Iwasaki, Hideki Sudo
Scientific Reports, 9, 9678, 1, 8, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Adolescent idiopathic scoliosis is the most ordinary pediatric spinal disease that causes a three-dimensional deformity. Early detection of this potentially progressive deformity is considered crucial. The purpose of the present study was to report the potential for accurately diagnosis of adolescent idiopathic scoliosis using a newly developed, automated, noninvasive asymmetry-recognition system for the surface of the human back using a three-dimensional depth sensor. We included 170 subjects with suspected adolescent idiopathic scoliosis in this study. Outcomes measured included patient demographics, Cobbe angles from radiographic measurements, and asymmetry indexes. The coefficient of correlation between the asymmetry index and the Cobb angle was 0.85. For the prediction of scoliosis >10°, the area under the curve was 0.98, sensitivity was 0.97, specificity was 0.93, positive predictive value was 0.99, negative predictive value was 0.72, accuracy was 0.97, positive likelihood ratio was 13.55, and negative likelihood ratio was 0.04. The posterior test probability for the positive screen >10° was 98.9% if the asymmetry index was >1.268, three times in a row. This novel system automatically evaluated the back asymmetry. Therefore, this study demonstrates the outstanding discriminative ability of this newly developed system for deciding whether an examinee should undergo additional radiography to define scoliosis. This system can be used as an alternative to the forward bend test and scoliometer measurement in clinics. Future studies should seek to confirm these findings in a larger group and involve mass school scoliosis screening programs within the context of a multicenter trial.

Inclination of Blumensaat's line influences on the accuracy of the quadrant method in evaluation for anterior cruciate ligament reconstruction.
Iwasaki K, Inoue M, Kasahara Y, Tsukuda K, Kawahara H, Yokota I, Kondo E, Iwasaki N, Yasuda K
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 28, 6, 1885, 1893, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The quadrant method is used to evaluate the bone tunnel position with the grid based on the Blumensaat's line in anterior cruciate ligament (ACL) reconstruction. This study aimed to clarify the influence of variation in the Blumensaat's line on the accuracy of the quadrant method measurements. METHODS: A retrospective review of the radiological records of patients aged 18-30 years who underwent computed tomography (CT) scanning of the knee joint was conducted. The Blumensaat's line inclination angle (BIA), along with the most posterior point of the posterior condyle (point P) position using the quadrant method and morphology of the Blumensaat's line were measured on true lateral transparent three-dimensional CT images of the distal femoral condyle in 147 patients. Statistical analysis was conducted to determine associations among these measurements. RESULTS: BIA was 37.5° (standard deviation 4.2°; range 27°-48°). The point P position was significantly correlated with BIA in the high/low (R2 = 0.590, P < 0.0001) and deep/shallow (R2 = 0.461, P < 0.0001) directions. The morphology of the Blumensaat's line was straight in 35 knees (23.8%); whereas, the remaining 112 knees (76.2%) were not straight but had some hill on the Blumensaat's line. No significant difference among the morphological variation of the Blumensaat's line was observed in BIA and the point P position. CONCLUSION: There was a strong correlation between BIA and the point P measured using the quadrant method, suggesting the influence of the Blumensaat's line on the accuracy of the quadrant method measurements in ACL reconstruction. As for the clinical relevance, surgeons should be careful in application of the quadrant method for ACL reconstruction, because the variation of the Blumensaat's line inclination influences the accuracy of this method.

Alteration of the Total Cellular Glycome during Late Differentiation of Chondrocytes.
Homan K, Hanamatsu H, Furukawa JI, Okada K, Yokota I, Onodera T, Iwasaki N
International journal of molecular sciences, 20, 14, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, In normal articular cartilage, chondrocytes do not readily proliferate or terminally differentiate, and exhibit a low level of metabolism. Hypertrophy-like changes of chondrocytes have been proposed to play a role in the pathogenesis of osteoarthritis by inducing protease-mediated cartilage degradation and calcification; however, the molecular mechanisms underlying these changes are unclear. Glycans are located on the outermost cell surface. Dynamic cellular differentiation can be monitored and quantitatively characterized by profiling the glycan structures of total cellular glycoproteins. This study aimed to clarify the alterations in glycans upon late differentiation of chondrocytes, during which hypertrophy-like changes occur. Primary mouse chondrocytes were differentiated using an insulin-induced chondro-osteogenic differentiation model. Comprehensive glycomics, including N-glycans, O-glycans, free oligosaccharides, glycosaminoglycan, and glycosphingolipid, were analyzed for the chondrocytes after 0-, 10- and 20-days cultivation. The comparison and clustering of the alteration of glycans upon hypertrophy-like changes of primary chondrocytes were performed. Comprehensive glycomic analyses provided complementary alterations in the levels of various glycans derived from glycoconjugates during hypertrophic differentiation. In addition, expression of genes related to glycan biosynthesis and metabolic processes was significantly correlated with glycan alterations. Our results indicate that total cellular glycan alterations are closely associated with chondrocyte hypertrophy and help to describe the glycophenotype by chondrocytes and their hypertrophic differentiation. our results will assist the identification of diagnostic and differentiation biomarkers in the future.

Correction osteotomy for bilateral varus knee deformity caused by premature epiphyseal closure induced by hypervitaminosis A: a case report.
Masatake Matsuoka, Tomohiro Onodera, Tokifumi Majima, Koji Iwasaki, Daisuke Takahashi, Eiji Kondo, Norimasa Iwasaki
BMC musculoskeletal disorders, 20, 1, 287, 287, 2019年06月15日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: A vitamin A derivative, 13-cis-retinoic acid (isotretinoin), has been administered to treat several types of pediatric cancer and has improved survival rates in patients despite being known to induce premature epiphyseal closure. As the number of patients treated by 13-cis-retinoic acid increases, demands for salvage treatment after systemic retinoid therapy are emerging. However, few studies have described the surgical treatment of this disease. CASE PRESENTATION: We report a case with bilateral varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin for neuroblastoma. The patient was successfully treated with correction osteotomy using a Taylor spatial frame in the right knee joint and femoral closed wedge osteotomy using a locking plate in left knee joint. Histopathological examination of the growth plate showed polar irregularity of chondrocytes and decreased cartilage matrix without apoptosis. In contrast, arthroscopic findings showed an intact joint surface. No recurrence of varus deformity was evident on follow-up at 1 year. CONCLUSIONS: To the best of our knowledge, this represents the first report of correction osteotomy for varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin.

Autologous living chondrocytes contained in the meniscal matrix play an important role in in vivo meniscus regeneration induced by in situ meniscus fragment implantation.
Yasuyuki Kawaguchi, Eiji Kondo, Norimasa Iwasaki, Yasuhito Tanaka, Tomonori Yagi, Kazunori Yasuda
Orthopaedics & traumatology, surgery & research : OTSR, 105, 4, 683, 690, 2019年06月, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Implantation of autogenous meniscal fragments wrapped with a fascia sheath significantly enhances fibrocartilage regeneration in vivo in defect cases at 12 weeks after implantation. The specific effects of the implanted autologous living chondrocytes and meniscal matrix have not been elucidated, however. The aim of this study was to clarify the role of autologous living chondrocytes contained in the meniscal matrix in in vivo meniscus regeneration induced by in situ meniscus fragment implantation. HYPOTHESIS: Implantation of meniscus fragments containing autologous living chondrocytes may result in significant in vivo meniscus regeneration. MATERIALS AND METHODS: Seventy-five rabbits were used in this study. A partial meniscectomy of the anterior one-third of the medial meniscus including the part of the anterior horn was performed. The rabbits were divided into 3 groups. In Group I, no treatment was applied to the defect. In Group II, the autogenous meniscal fragments devitalized by freeze-thaw treatment were reimplanted into the defect. In Group III, the autogenous meniscal fragments were reimplanted. In each group, the defect was covered with a fascia. Five rabbits from each group were subjected to morphologic and histologic evaluations at 3, 6, and 12 weeks, and 5 rabbits from each group were subjected to biomechanical evaluations at 6 and 12 weeks. RESULTS: Histologically, no cells were seen in the grafted meniscal fragments at 3 weeks in Group II, whereas chondrocytes in the grafted meniscal fragments were alive at 3 weeks in Group III. Histologic and biomechanical data for Group II were slightly but significantly better than those of Group I at 12 weeks after implantation (p=0.007 and p=0.002, respectively), whereas the data for Group III were significantly superior to those of Groups I and II at 12 weeks (p<0.0014 and p<0.0029, respectively). DISCUSSIONS: Grafted autologous living chondrocytes contained in the meniscal matrix play an important role in in vivo meniscus regeneration induced by in situ meniscus fragment implantation. STUDY DESIGN: II, Controlled laboratory study.

Effects of femoral bone defect morphology on initial polished tapered stem stability in massive defect model: a biomechanical study.
アラーテルカウィ
BMC Musculoskeletal Disorders, 1;20(1):355, 1, 355, 355, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Good outcomes have been reported in revision total hip replacement with massive segmental defects using impaction bone grafting with circumferential metal meshes. However, the morphology of defects that require a mesh is poorly defined. The purpose of this study was to evaluate the effects of a variety of segmental defects on load transmission to the proximal femur under both axial and rotational loads. METHODS: Initial stability of the Exeter stem was investigated in a composite bone model using three medial bone defect morphologies: Long (length 5 cm × width 2 cm), Short (2.5 cm × 2 cm), Square (3.2 cm × 3.2 cm), Square with mesh (3.2 cm × 3.2 cm defect covered with metal mesh), and with no defect as control. Specimens (5 per group) were axially loaded and internally rotated up to 20° or to failure. Strain distributions of the femora were measured using a strain gauge. RESULTS: All Square group specimens failed while rotation was increasing. In the other four groups, failure was not observed in any specimens. Mean torsional stiffness in the Long (4.4 ± 0.3 Nm/deg.) and Square groups (4.3 ± 0.3 Nm/deg.) was significantly smaller than in the Control group (4.8 ± 0.3 Nm/deg.). In the medio-cranial region, the magnitude of the maximum principal strain in the Square group (1176.4 ± 100.9) was significantly the largest (Control, 373.2 ± 129.5, p < 0.001; Long, 883.7 ± 153.3, p = 0.027; Short, 434.5 ± 196.8, p < 0.001; Square with mesh, 256.9 ± 100.8, p < 0.001). Torsional stiffness, and both maximum and minimum principal strains in the Short group showed no difference compared to the Control group in any region. CONCLUSIONS: Bone defect morphology greatly affected initial stem stability and load transmission. If defect morphology is not wide and the distal end is above the lower end of the lesser trochanter, it may be acceptable to fill the bone defect region with bone cement. However, this procedure is not acceptable for defects extending distally below the lower end of the lesser trochanter or defects 3 cm or more in width.

Bilateral subchondral insufficiency fractures of the femoral head in a normally active adolescent patient: A case report.
アラーテルカウィ
The Journal of Orthopaedic Science, S0949-2658(19)30148-4, 2, 492, 494, 2019年06月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）

A CRISPR Screen Using Subtilase Cytotoxin Identifies SLC39A9 as a Glycan-Regulating Factor.
Toshiyuki Yamaji, Hisatoshi Hanamatsu, Tsuyoshi Sekizuka, Makoto Kuroda, Norimasa Iwasaki, Makoto Ohnishi, Jun-Ichi Furukawa, Kinnosuke Yahiro, Kentaro Hanada
iScience, 15, 407, 420, 2019年05月31日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Subtilase cytotoxin (SubAB) is a virulence factor produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli strains. The toxin recognizes sialoglycans for entry and cleaves an endoplasmic reticulum chaperon, binding immunoglobulin protein, to cause cell death. However, no systematic screening has yet been performed to identify critical host factors. Here, we performed a genome-wide CRISPR/Cas9 knockout screen for SubAB-induced cell death and identified various sialoglycan-related and membrane-trafficking genes. Analysis of glycan-deficient cells demonstrated that not only N-glycans but also O-glycans serve as SubAB receptors. In addition, SLC39A9, which is a predicted zinc transporter, as well as KDELRs and JTB, were required for SubAB to induce maximal cell death. Disruption of the SLC39A9 gene markedly reduced both complex-type N-glycans and core 1 O-glycans, and the O-glycan reduction was attributed to the reduction of core 1 synthase (C1GalT1). These results provide insights into the post-transcriptional regulation of glycosyltransferases by SLC39A9, as well as sialoglycan species as SubAB receptors.

骨粗鬆症性椎体骨折後早期に生じるドミノ骨折および椎体圧潰の病態　　　　　　　　　　　　　　　
高畑 雅彦, 岩田 玲, 遠藤 香織, 浦 勝郎, 岩崎 倫政
日本骨形態計測学会雑誌, 29, 1, S80, S80, 日本骨形態計測学会, 2019年05月
日本語

Chondrogenic differentiation of mouse induced pluripotent stem cells (iPSCs) using the three-dimensional culture with ultra-purified alginate gel (UPAL gel).
Hontani K, Onodera T, Terashima M, Momma D, Matsuoka M, Baba R, Joutoku Z, Matsubara S, Homan K, Hishimura R, Xu L, Iwasaki N
Journal of biomedical materials research. Part A, 107, 5, 1086, 1093, 2019年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, As articular cartilages have rarely healed by themselves because of their characteristics of avascularity and low cell density, surgical intervention is ideal for patients with cartilaginous injuries. Because of structural characteristics of the cartilage tissue, a three-dimensional culture of stem cells in biomaterials is a favorable system on cartilage tissue engineering. Induced pluripotent stem cells (iPSCs) are a new cell source in cartilage tissue engineering for its characteristics of self-renewal capability and pluripotency. However, the optimal cultivation condition for chondrogenesis of iPSCs is still unknown. Here we show that a novel chondrogenic differentiation method of iPSCs using the combination of three-dimensional cultivation in ultra-purified alginate gel (UPAL gel) and multi-step differentiation via mesenchymal stem cell-like cells (iPS-MSCs) could efficiently and specifically differentiate iPSCs into chondrocytes. The iPS-MSCs in UPAL gel culture sequentially enhanced the expression of chondrogenic marker without the upregulation of that of osteogenic and adipogenic marker and histologically showed homogeneous chondrogenic extracellular matrix formation. Our results suggest that the pluripotency of iPSCs can be controlled when iPSCs are differentiated into iPS-MSCs before embedding in UPAL gel. These results lead to the establishment of an efficient three-dimensional system to engineer artificial cartilage tissue from iPSCs for cartilage regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1086-1093, 2019.

Magnetic resonance imaging T1 and T2 mapping provide complementary information on the bone mineral density regarding cancellous bone strength in the femoral head of postmenopausal women with osteoarthritis.
Endo K, Takahata M, Sugimori H, Yamada S, Tadano S, Wang J, Todoh M, Ito YM, Takahashi D, Kudo K, Iwasaki N
Clinical biomechanics (Bristol, Avon), 65, 13, 18, 2019年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Since bone mass is not the only determinant of bone strength, there has been increasing interest in incorporating the bone quality into fracture risk assessments. We aimed to examine whether the magnetic resonance imaging (MRI) T1 or T2 mapping value could provide information that is complementary to bone mineral density for more accurate prediction of cancellous bone strength. METHODS: Four postmenopausal women with hip osteoarthritis underwent 3.0-T MRI to acquire the T1 and T2 values of the cancellous bone of the femoral head before total hip arthroplasty. After the surgery, the excised femoral head was portioned into multiple cubic cancellous bone specimens with side of 5 mm, and the specimens were then subjected to microcomputed tomography followed by biomechanical testing. FINDINGS: The T1 value positively correlated with the yield stress (σy) and collapsed stress (σc). The T2 value did not correlate with the yield stress, but it correlated with the collapsed stress and strength reduction ratio (σc/σy), which reflects the progressive re-fracture risk. Partial correlation coefficient analyses, after adjusting for the bone mineral density, showed a statistically significant correlation between T1 value and yield stress. The use of multiple coefficients of determination by least squares analysis emphasizes the superiority of combining the bone mineral density and the MRI mapping values in predicting the cancellous bone strength compared with the bone mineral density-based prediction alone. INTERPRETATION: The MRI T1 and T2 values predict cancellous bone strength including the change in bone quality.

遺残組織温存解剖学的二束前十字靱帯再建術の再鏡視所見 非温存群との年齢別検討
江畑 拓, 近藤 英司, 岩崎 浩司, 珍部 正嗣, 小野寺 智洋, 小野寺 純, 安田 和則, 八木 知徳, 岩崎 倫政
JOSKAS, 44, 2, 426, 427, (一社)日本関節鏡・膝・スポーツ整形外科学会, 2019年04月
日本語, 遺残組織温存二束ACL再建術(R法)と従来の二束再建術(D法)の再鏡視所見を年齢別に比較した。片側ACL損傷に対して膝屈筋腱ハイブリッド代用材料を用いて解剖学的二束ACL再建を行い、術後1年で再鏡視を行った171例を対象とした。遺残組織の連続性を認めないType IVの症例に対してはD法(89例、平均28歳)を、遺残組織の連続性があるType IからIIIの症例に対してはR法(82例、平均30歳)を行った。それぞれを24歳以下のY群、25歳以上39歳以下のM群、40歳以上のO群の三つの年齢群に分け、術後1年経過時の臨床成績および再鏡視所見を年齢別に評価した。30°屈曲位における膝前方不安定性の対健側差について各年齢群で比較したところ、両術式間に有意な差はなかった。また、Lysholm scoreおよびIKDC評価に関しても同様に両術式間で有意差を認めなかった。各術式の年齢群間の比較では、D法においてO群はY群と比べ有意に不良であったが、R法では3群間に有意な差はなかった。

シュワン細胞の接着因子を介した神経突起伸長効果の検討　　　　　　　　　　　　　　　
遠藤 健, 角家 健, 松居 祐樹, 袁 儒非, 鈴木 智亮, 永野 裕介, 河村 太介, 岩崎 倫政
日本手外科学会雑誌, 36, 1, O3, 5, (一社)日本手外科学会, 2019年04月
日本語

軸索再生に至適なシュワン細胞の分化度に関する検討　　　　　　　　　　　　　　　
遠藤 健, 角家 健, 鈴木 智亮, 松居 祐樹, 袁 儒非, 永野 裕介, 河村 太介, 岩崎 倫政
日本手外科学会雑誌, 36, 1, BP2, 4, (一社)日本手外科学会, 2019年04月
日本語

Late Subaxial Lesion after Overcorrected Occipitocervical Reconstruction in Patients with Rheumatoid Arthritis.
Iwata A, Abumi K, Takahata M, Sudo H, Yamada K, Endo T, Iwasaki N
Asian spine journal, 13, 2, 181, 188, 2019年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: Retrospective case-control study, level 4. PURPOSE: To clarify the risk factors for late subaxial lesion after occipitocervical (O-C) reconstruction. We examined cases requiring fusion-segment-extended (FE) reconstruction in addition to/after O-C reconstruction. OVERVIEW OF LITERATURE: Patients with rheumatoid arthritis (RA) frequently require O-C reconstruction surgery for cranio-cervical lesions. Acceptable outcomes are achieved via indirect decompression using cervical pedicle screws and occipital plate-rod systems. However, late subaxial lesions may develop occasionally following O-C reconstruction. METHODS: O-C reconstruction using cervical pedicle screws and occipital plate-rod systems was performed between 1994 and 2007 in 113 patients with RA. Occipito-atlanto-axial (O-C2) reconstruction was performed for 89 patients, and occipito-subaxial cervical (O-under C2) reconstruction was performed for 24 patients. We reviewed the cases of patients requiring FE reconstruction (fusion extended group, FEG) and 26 consecutive patients who did not require FE reconstruction after a follow-up of >5 years (non-fusion extended group, NEG) as controls. RESULTS: FE reconstructions were performed for nine patients at an average of 45 months (range, 24-180 months) after O-C reconstruction. Of the 89 patients, three (3%) underwent FE reconstruction in cases of O-C2 reconstruction. Of the 24 patients, five (21%) underwent FE reconstruction in cases of O-under C2 reconstruction (p=0.003, Fisher exact test). Age, sex, RA type, and neurological impairment stage were not significantly different between FEG and NEG. O-under C2 reconstruction, larger correction angle (4° per number of unfixed segment), and O-C7 angle change after O-C reconstruction were the risk factors for late subaxial lesions on radiographic assessment. CONCLUSIONS: Overcorrection of angle at fusion segments requiring O-C7 angle change was a risk factor for late subaxial lesion in patients with RA with fragile bones and joints. Correction should be limited, considering the residual mobility of the cervical unfixed segments.

CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults.
Joutoku Z, Onodera T, Matsuoka M, Homan K, Momma D, Baba R, Hontani K, Hamasaki M, Matsubara S, Hishimura R, Iwasaki N
Scientific reports, 9, 1, 5165, 5165, 2019年03月26日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Juvenile tissue healing is capable of extensive scarless healing that is distinct from the scar-forming process of the adult healing response. Although many growth factors can be found in the juvenile healing process, the molecular mechanisms of juvenile tissue healing are poorly understood. Here we show that juvenile mice deficient in the chemokine receptor CCR7 exhibit diminished large-scale healing potential, whereas CCR7-depleted adult mice undergo normal scar-forming healing similar to wild type mice. In addition, the CCR7 ligand CCL21 was transiently expressed around damaged cartilage in juvenile mice, whereas it is rarely expressed in adults. Notably, exogenous CCL21 administration to adults decreased scar-forming healing and enhanced hyaline-cartilage repair in rabbit osteochondral defects. Our data indicate that the CCL21/CCR7 axis may play a role in the molecular control mechanism of juvenile cartilage repair, raising the possibility that agents modulating the production of CCL21 in vivo can improve the quality of cartilage repair in adults. Such a strategy may prevent post-traumatic arthritis by mimicking the self-repair in juvenile individuals.

脊椎・椎間板外傷に対する細胞死をターゲットとした分子標的治療の可能性
大西 貴士, 須藤 英毅, 岩崎 浩司, 辻本 武尊, 山田 勝久, 岩崎 倫政
日本整形外科学会雑誌, 93, 3, S1177, S1177, (公社)日本整形外科学会, 2019年03月
日本語

頸椎化膿性脊椎炎の臨床的特徴と機能予後 後彎変形とQOLとの関連
山田 勝久, 高畑 雅彦, 楫野 知道, 袖山 洋平, 岩田 玲, 小甲 晃史, 遠藤 努, 大西 貴士, 須藤 英毅, 石黒 信久, 岩崎 倫政
日本整形外科学会雑誌, 93, 3, S1180, S1180, (公社)日本整形外科学会, 2019年03月
日本語

膿胸・縦隔膿瘍を併発した胸椎化膿性脊椎炎に対する治療 難治例では椎間板・胸腔ドレナージが必要
山田 勝久, 高畑 雅彦, 青木 佑介, 岩田 玲, 遠藤 努, 大西 貴士, 須藤 英毅, 石黒 信久, 岩崎 倫政
日本整形外科学会雑誌, 93, 3, S1181, S1181, (公社)日本整形外科学会, 2019年03月
日本語

胸椎特発性側彎症の固定下端椎の操作が腰椎非固定椎間配列と冠状面バランスに与える影響
岩田 玲, 須藤 英毅, 安倍 雄一郎, 伊東 学, 鐙 邦芳, 山田 勝久, 遠藤 努, 大西 貴士, 高畑 雅彦, 岩崎 倫政
Journal of Spine Research, 10, 3, 212, 212, (一社)日本脊椎脊髄病学会, 2019年03月
日本語

合併症を生じやすい脊椎腫瘍手術の条件
岩田 玲, 高畑 雅彦, 角家 健, 須藤 英毅, 山田 勝久, 遠藤 努, 大西 貴士, 伊東 学, 鐙 邦芳, 岩崎 倫政
Journal of Spine Research, 10, 3, 272, 272, (一社)日本脊椎脊髄病学会, 2019年03月
日本語

第5腰椎骨腫瘍摘出術における腸骨稜切離飜転の有用性
岩田 玲, 高畑 雅彦, 須藤 英毅, 山田 勝久, 遠藤 努, 大西 貴士, 岩崎 倫政
Journal of Spine Research, 10, 3, 396, 396, (一社)日本脊椎脊髄病学会, 2019年03月
日本語

膿胸・縦隔膿瘍を併発した胸椎化膿性脊椎炎に対する治療 あまり知られていない危険な病態
山田 勝久, 高畑 雅彦, 岩田 玲, 遠藤 努, 大西 貴士, 須藤 英毅, 石黒 信久, 岩崎 倫政
Journal of Spine Research, 10, 3, 663, 663, (一社)日本脊椎脊髄病学会, 2019年03月
日本語

若年発症の胸椎OPLL患者は高度肥満と強い骨化傾向の特徴をもつ
遠藤 努, 高畑 雅彦, 岩田 玲, 山田 勝久, 大西 貴士, 須藤 英毅, 岩崎 倫政
Journal of Spine Research, 10, 3, 687, 687, (一社)日本脊椎脊髄病学会, 2019年03月
日本語

経時的応力計測可能なラメラ構造二重膜ヒドロゲルを用いたヒト関節靱帯における内部応力解析
門間 太輔, 黒川 孝幸, 河村 太介, 瓜田 淳, 松井 雄一郎, 岩崎 倫政
日本整形外科学会雑誌, 93, 3, S1042, S1042, (公社)日本整形外科学会, 2019年03月
日本語

Identification of IL-27 as potent regulator of inflammatory osteolysis associated with vitamin E-blended ultra-high molecular weight polyethylene debris of orthopedic implants
Terkawi MA, Kadoya K, Takahashi D, Tian Y, Hamasaki M, Matsumae G, Alhasan H, Elmorsy S, Uetsuki K, Onodera T, Takahata M, Iwasaki N
Acta Biomaterialia, 89, 242, 251, 2019年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. STATEMENT OF SIGNIFICANCE: Aseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant.

Effects of Ultra-Purified Alginate Gel Implantation on Meniscal Defects in Rabbits.
Kim W, Onodera T, Kondo E, Kawaguchi Y, Terkawi MA, Baba R, Hontani K, Joutoku Z, Matsubara S, Homan K, Hishimura R, Iwasaki N
The American journal of sports medicine, 47, 3, 640, 650, 2019年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Many tissue-engineered methods for meniscal repair have been studied, but their utility remains unclear. HYPOTHESIS: Implantation of low-endotoxin, ultra-purified alginate (UPAL) gel without cells could induce fibrocartilage regeneration on meniscal defects in rabbits. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-two mature Japanese White rabbits were divided into 2 groups of 21 animals each. In each animal, a cylindrical defect measuring 2 mm in diameter was created with a biopsy punch on the anterior horn of the medial meniscus. In the control group, no treatment was applied on the left medial meniscal defect. In the UPAL gel group, the right medial meniscal defect was injected with the UPAL gel and gelated by a CaCl2 solution. Samples were evaluated at 3, 6, and 12 weeks postoperatively. For biomechanical evaluation, 6 additional samples from intact animals were used for comparison. RESULTS: The macroscopic score was significantly greater in the UPAL gel group than in the control group at 3 weeks (mean ± SE: 5.6 ± 0.82 vs 3.4 ± 0.83, P = .010), 6 weeks (5.9 ± 0.72 vs 2.5 ± 0.75, P = .026), and 12 weeks (5.2 ± 1.21 vs 1.0 ± 0.63, P = .020). The histological score was significantly greater in the UPAL group than in the control group at 3 weeks (2.1 ± 0.31 vs 1.2 ± 0.25, P = .029) and 12 weeks (2.2 ± 0.55 vs 0.3 ± 0.21, P = .016). The mean stiffness of the reparative tissue in the UPAL gel group was significantly greater than that in the control group at 6 weeks (24.325 ± 3.920 N/mm vs 8.723 ± 1.190 N/mm, P = .006) and at 12 weeks (27.804 ± 6.169 N/mm vs not applicable [because of rupture]). CONCLUSION: The UPAL gel enhanced the spontaneous repair of fibrocartilage tissues in a cylindrical meniscal defect in rabbits. CLINICAL RELEVANCE: These results imply that the acellular UPAL gel may improve the repair of traumatic meniscal injuries.

Preoperative radiographic and clinical factors associated with postoperative floating of the lesser toes after resection arthroplasty for rheumatoid forefoot deformity.
Onodera T, Nakano H, Homan K, Kondo E, Iwasaki N
BMC musculoskeletal disorders, 20, 1, 87, 87, 2019年02月19日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: This study aimed to clarify the characteristics associated with postoperative floating of the lesser toes, especially focusing on the medial and lateral lessor toes, after arthrodesis of the first metatarsophalangeal joint and resection arthroplasty of the lessor toes in rheumatoid forefoot deformity. METHODS: Fourty-seven feet of 43 people who underwent resection arthroplasty of the metatarsal head of the lesser toes for rheumatoid arthritis of the metatarsophalangeal joints were included. We retrospectively evaluated the preoperative radiographic findings and clinical characteristics of the patients, and the occurrence of postoperative floating of the lesser toes. The mean duration of follow-up was 36.5 (range 12 to 114) months. RESULTS: Preoperative dislocation grades of the second and third toes that demonstrated postoperative floating were significantly higher than those of toes that did not experience postoperative floating. The hallux valgus deformity before surgery was significantly more severe in toes with postoperative floating of the second and third lessor toes than those with no floating (p < 0.05). In addition, the Japanese Society for Surgery of the Foot (JSSF) hallux scale scores before surgery in toes with postoperative floating of the fourth and fifth lessor toes were significantly worse than those in non-dislocating toes (p < 0.05). CONCLUSIONS: The preoperative condition of the first metatarsophalangeal joint, including hallux valgus deformity, pain, range of motion, activity of daily living, and function is significantly different between postoperative floating of the lesser toes and non-floating of them after resection arthroplasty for rheumatoid forefoot deformity.

経時的応力計測可能なラメラ構造二重膜ヒドロゲルを用いたヒト関節靱帯における内部応力解析　　　　　　　　　　　　　　　
門間 太輔, 黒川 孝幸, 河村 太介, 瓜田 淳, 松井 雄一郎, 岩崎 倫政
日本肘関節学会雑誌, 26, 1, S4, S4, 日本肘関節学会, 2019年02月
日本語

Corticosteroid dose increase is a risk factor for nonalcoholic fatty liver disease and contralateral osteonecrosis of the femoral head: a case report.
Shimizu H, Shimizu T, Takahashi D, Asano T, Arai R, Takakuwa Y, Iwasaki N
BMC musculoskeletal disorders, 20, 1, 88, 88, 2019年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The incidence of bilateral corticosteroid-induced osteonecrosis of the femoral head (ONFH) is high. Although the precise mechanism of corticosteroid-induced ONFH development is unclear, hepatic enzyme abnormalities such as low activity of hepatic cytochrome P450 3A could be one cause. Herein, we report the case of a patient who developed ONFH in the contralateral hip after the dose of corticosteroids for idiopathic thrombocytopenic purpura was increased. Liver biopsy was done to rule out autoimmune hepatitis. CASE PRESENTATION: A 32-year-old woman had been treated with continuous corticosteroids of up to 10 mg/day for Sjögren's syndrome for 25 years and corticosteroid-induced ONFH in the left side. At age 33, idiopathic thrombocytopenia developed, which was treated by increasing the corticosteroid dose (40 mg/day). Two months later, liver enzyme level began to increase slightly and continued to increase. A year after corticosteroid dose increase, contralateral ONFH developed, and a liver biopsy demonstrated nonalcoholic fatty liver disease (NAFLD). CONCLUSIONS: The current case indicates that corticosteroid dose increase is a potential risk factor for NAFLD and contralateral ONFH. Therefore, it would be useful and important for to screen and monitor patients with hepatic enzyme abnormality for ONFH occurrence.

Long-term Changes in Vertebral Morphology after Cervical Spinal Fusion in Adolescent /Pediatric Patients: Retrospective Case Series with up to a Minimum 12 years of Follow-up.
Abe Y, Yamada K, Abumi K, Iwasaki N, Sudo H
World neurosurgery, 122, e765-e772, 2019年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: The mechanical alteration in the adolescent/pediatric cervical spine after spinal fusion remains unknown. The purpose of this study was to investigate morphologic changes in the cervical spine in adolescent/pediatric patients who underwent spinal fusion. METHODS: Ten adolescent/pediatric patients (9-18 years) who underwent cervical spinal fusion were included. The anteroposterior diameter (AP-D) of the vertebral body was evaluated using lateral radiographs. The AP-D ratio was defined as the ratio of the AP-D at final follow-up to the postoperative value. The kyphosis angles at the fused level and cervical spine (C2-C7) also were measured. RESULTS: The mean follow-up period was 20.0 years (range, 12-40 years). The AP-D was reduced in 4 patients and increased or remained unchanged in 6 patients. The AP-D reduction was usually seen at the middle of the fused levels and was remarkable in patients who underwent kyphosis correction using posterior instrumentation combined with anterior fusion. The AP-D ratio was significantly correlated to segments of anterior fusion (P = 0.029) and the kyphosis angle of the fused levels (P = 0.016). CONCLUSIONS: Cervical kyphosis correction using posterior instrumentation combined with endplate destruction by anterior bone grafting is a risk factor for atrophic morphologic changes in the vertebral body in adolescent/pediatric patients. Endplate destruction and instrumentation-induced stress shielding could alter bone remodeling.

Increased risk of symptomatic progression of instability following decompression for lumbar canal stenosis in patients receiving chronic glucocorticoids therapy.
Shigeto Hiratsuka, Masahiko Takahata, Yoshihiro Hojo, Tomomichi Kajino, Yuichiro Hisada, Akira Iwata, Katsuhisa Yamada, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 24, 1, 14, 18, 2019年01月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Lumbar decompression surgery is a commonly used treatment for degenerative lumbar spinal stenosis; however, some patients develop symptomatic spinal instability following decompression surgery. The objective of this study was to reveal risk factors for delayed instability following decompression surgery for lumbar spinal stenosis. METHODS: One hundred ten patients who underwent single-level lumbar decompression between 2008 and 2014 were retrospectively reviewed. Surgical indication for decompression surgery was symptomatic lumbar canal stenosis without spondylolisthesis or with minimum spondylolisthesis (less than 4 mm translation). Patients with gross segmental motion (>10° in disc angle, >2 mm translation) on flexion-extension lumbar radiographs were excluded. Age, sex, body mass index, smoking history, diabetes mellitus, autoimmune connective tissue diseases including rheumatoid arthritis, and the use of glucocorticoids were investigated. Radiographic measurements included disc angle, disc height, slippage, facet angle, segmental motion (flexion-extension), lumbar alignment, facet effusion, and disc degeneration. Data were analyzed using multivariate forward selection stepwise logistic regression, chi-square tests, and Student t-test. RESULTS: Six of 110 patients (5.5%) developed symptomatic spinal instability at the operative level and underwent spinal fusion surgery at an average of 2.1 years postoperatively. Autoimmune connective tissue disorders and chronic use of glucocorticoids were associated with the occurrence of symptomatic spinal instability requiring spine fusion surgery, while there was no significant difference in radiographic parameters and demographic factors excluding autoimmune connective tissue diseases between reoperation and non-reoperation groups. CONCLUSIONS: Patients with autoimmune connective tissue disorders receiving chronic glucocorticoid therapy are more likely to develop symptomatic spinal instability following decompression surgery for lumbar canal stenosis without or with minimal spondylolisthesis.

炎症性骨溶解及び骨吸収におけるNOV(Nephroblastoma overexpressed)の機能解析
松前 元, テルカウィ・アラー, 田 園, 濱崎 雅成, ヘンド・アルハサン, 江畑 拓, 高橋 大介, 角家 健, 岩崎 倫政
北海道整形災害外科学会雑誌, 61, 136th suppl, 29, 29, 北海道整形災害外科学会, 2019年
日本語

軟骨破片刺激モデルにおいて軟骨細胞は軟骨内骨化関連の遺伝子発現が上昇する
江畑 拓, 濱崎 雅成, アラー・テルカウイ, 小野寺 智洋, 松前 元, 田 園, ヘンド・アルハサン, 宮崎 拓自, 徐 亮, 細川 吉暁, 岩崎 倫政
北海道整形災害外科学会雑誌, 61, 137th suppl, 35, 35, 北海道整形災害外科学会, 2019年
日本語

シュワン細胞の接着因子を介した神経突起伸長効果の検討
遠藤 健, 角家 健, 鈴木 裕貴, 松居 祐樹, 袁 儒非, 鈴木 智亮, 福井 隆史, 山本 康弘, 河村 太介, 岩崎 倫政
北海道整形災害外科学会雑誌, 61, 136th suppl, 88, 88, 北海道整形災害外科学会, 2019年
日本語

Identification of il-27 as potent regulator of osteolysis triggered by of orthopaedic implants debris　　　　　　　　　　　　　　　
Daisuke Takahashi, Mohamad Alaa Terkawi, Gen Matsumae, Yuan Tian, Hend Alhasan, Norimasa Iwasaki.
Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium, 40, 612, Society for Biomaterials, 2019年
英語, 研究論文（国際会議プロシーディングス）, Statement of Purpose: Aseptic loosening due to inflammatory osteolysis remains the major postoperative complication of total joint arthroplasty that leads to prosthesis failure. Inflammation occurs when macrophages recognize wear debris derived from implant bearing surfaces and release an array of cytokines and chemokines that promote the recruitment of other inflammatory cells and the osteoclastic-bone resorbing activity [1]. Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly developed material for prosthetic components that has proven greater clinical performance with lesser adverse cellular responses than conventional polyethylene in short-term clinical studies as well as in experimental animal models [2]. However, the mechanisms by which VE-UHMWPE debris triggers reduced osteolytic activity are largely unclear and remain to be investigated. Therefore, the current study aims at exploring a possible mechanism by which VE-UHMWPE debris triggers a reduced adverse cellular response. with macrophage response to debris.

転移性脊椎腫瘍術後合併症の危険因子
岩田 玲, 山田 勝久, 遠藤 努, 大西 貴士, 角家 健, 高畑 雅彦, 岩崎 倫政, 須藤 英毅
北海道整形災害外科学会雑誌, 61, 136th suppl, 8, 8, 北海道整形災害外科学会, 2019年
日本語

若年発症の胸椎OPLL患者は高度な肥満と強い骨化傾向の特徴をもつ
遠藤 努, 高畑 雅彦, 岩田 玲, 山田 勝久, 大西 貴士, 須藤 英毅, 岩崎 倫政
北海道整形災害外科学会雑誌, 61, 136th suppl, 11, 11, 北海道整形災害外科学会, 2019年
日本語

環軸椎脱臼により呼吸障害を生じた新生児の1例
大西 貴士, 遠藤 努, 高畑 雅彦, 岩田 玲, 岩崎 倫政, 山田 勝久, 須藤 英毅
北海道整形災害外科学会雑誌, 61, 136th suppl, 11, 11, 北海道整形災害外科学会, 2019年
日本語

受傷直後に生じた後頭環軸椎回旋位固定の稀な1例
清水 寛和, 遠藤 努, 高畑 雅彦, 須藤 英毅, 岩田 玲, 山田 勝久, 大西 貴士, 岩崎 倫政, 安井 啓悟, 袖山 洋平
北海道整形災害外科学会雑誌, 61, 136th suppl, 13, 13, 北海道整形災害外科学会, 2019年
日本語

Septic embolizationによる脳塞栓を併発した腰椎化膿性脊椎炎の1例
佐藤 恒明, 山田 勝久, 遠藤 努, 大西 貴士, 岩田 玲, 須藤 英毅, 高畑 雅彦, 岩崎 倫政, 大嶌 祐貴, 脇田 雅大
北海道整形災害外科学会雑誌, 61, 136th suppl, 20, 20, 北海道整形災害外科学会, 2019年
日本語

胸椎骨化病変に合併した脊髄くも膜嚢胞の1例
宮野 真博, 高畑 雅彦, 山田 勝久, 遠藤 努, 大西 貴士, 岩崎 倫政, 岩田 玲, 須藤 英毅
北海道整形災害外科学会雑誌, 61, 136th suppl, 23, 23, 北海道整形災害外科学会, 2019年
日本語

A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury.
Takeshi Endo, Ken Kadoya, Yuki Suzuki, Daisuke Kawamura, Norimasa Iwasaki
Frontiers in cellular neuroscience, 13, 280, 280, 2019年, ［国際誌］
英語, 研究論文（学術雑誌）, Although peripheral nerves can regenerate, clinical outcomes after peripheral nerve injuries are not always satisfactory, especially in cases of severe or proximal injuries. Further, autologous nerve grafting remains the gold standard for the reconstruction of peripheral nerves, although this method is still accompanied by issues of donor-site morbidity and limited supply. Cell therapy is a potential approach to overcome these issues. However, the optimal cell type for promoting axon regeneration remains unknown. Here, we report a novel experimental model dedicated to elucidation of the axon-promoting effects of candidate cell types using simple and standardized techniques. This model uses rat sciatic nerves and consists of a 25 mm-long acellular region and a crush site at each end. The acellular region was made by repeated freeze/thaw procedures with liquid nitrogen. Importantly, the new model does not require microsurgical procedures, which are technically demanding and greatly affect axon regeneration. To test the actual utility of this model, red fluorescent protein-expressing syngeneic Schwann cells (SCs), marrow stromal cells, or fibroblasts were grafted into the acellular area, followed by perfusion of the rat 2 weeks later. All types of grafted cells survived well. Quantification of regenerating axons demonstrated that SCs, but not the other cell types, promoted axon regeneration with minimum variability. Thus, this model is useful for differentiating the effects of various grafted cell types in axon regeneration. Interestingly, regardless of the grafted cell type, host SCs migrated into the acellular area, and the extent of axon regeneration was strongly correlated with the number of SCs. Moreover, all regenerating axons were closely associated with SCs. These findings suggest a critical role for SCs in peripheral nerve axon regeneration. Collectively, this novel experimental model is useful for elucidating the axon-promoting effects of grafted cells and for analyzing the biology of peripheral nerve axon regeneration.

Glycans in osseous tissue and articulation
Tadahisa Mikami, Hiroshi Kitagawa, Norimasa Iwasaki
Glycoscience: Basic Science to Applications: Insights from the Japan Consortium for Glycobiology and Glycotechnology (JCGG), 221, 226, 2019年01月01日, ［査読有り］
論文集(書籍)内論文

Early surgical intervention may facilitate recovery of cervical spinal cord injury in DISH.
Tsuji O, Suda K, Takahata M, Matsumoto-Harmon S, Komatsu M, Menjo Y, Watanabe K, Ishii K, Nakamura M, Matsumoto M, Minami A, Iwasaki N
Journal of orthopaedic surgery (Hong Kong), 27, 1, 2309499019834783, 2309499019834783, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: A retrospective study of consecutive surgically managed cases of cervical spinal fractures and diffuse idiopathic skeletal hyperostosis (DISH) at our hospital from October 2006 to April 2016. SUMMARY OF BACKGROUND DATA: Prognostic factors have not been determined for cervical fractures in DISH. OBJECTIVES: To assess demographics, surgical techniques, and complications in cervical spinal cord injury with DISH and to evaluate factors affecting neurological prognosis. METHODS: Patients' medical records and radiographs were reviewed and analyzed for demographics, injury characteristics, surgical outcomes, perioperative complications, additional surgeries, and neurological prognosis. Neurological status was assessed by the American Spinal Injury Association (ASIA) grade at admission and discharge. RESULTS: Of 38 patients (mean age 71.9 ± 8.8), 20 had type 1 fractures (through the disc space), 8 had type 2 (through the vertebral body), and 10 had type 3 (through disc and vertebral body). ASIA grades at admission included 14 ASIA-A, 4 ASIA-B, 7 ASIA-C, 8 ASIA-D, and 5 ASIA-E. All patients underwent posterior fusion with an average of 4.5 ± 2.5 instrumented vertebrae (range, 2-7) and six patients required secondary halo-vest fixation. Of 14 ASIA-A patients, 12 developed serious postsurgical pulmonary complications and 4 of these died within 6 months of surgery. Of the 38 patients, 13 improved more than one grade after treatment, 24 did not improve, and 1 deteriorated. In the 18 ASIA-A/B cases (complete motor paralysis), neither fracture type nor injury mechanism (e.g. a ground-level fall or high-energy trauma) correlated with neurological prognosis, but a time of 8 h or less from injury to surgery correlated significantly with an improvement from ASIA A/B to C/D ( p  <  0.01, Pearson's χ2 test). CONCLUSION: Patients with complete motor paralysis after a cervical fracture with DISH may recover to partial paralysis if surgically treated within 8 h of injury.

Time Course of Respiratory Dysfunction and Motor Paralysis for 12 Weeks in Cervical Spinal Cord Injury without Bone Injury.
Ushiku C, Suda K, Matsumoto S, Komatsu M, Takahata M, Iwasaki N, Minami A
Spine surgery and related research, 3, 1, 37, 42, 2019年01月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Cervical spinal cord injury without bone injury (SCIWOBI) is a common cervical injury in the elderly population and is most likely to occur at the C3/C4 level. Respiratory dysfunction (RD) related to the damage of the spinal respiratory center, which is close to the C4 segment, is one of the greatest obstacles in improving the activities of daily living of patients with severe paralysis. We evaluated the time course of RD and motor function in cervical SCIWOBI to identify effective medical strategies. METHODS: We followed 54 patients (49 men, 5 women; mean age: 65 years old) who were treated for SCIWOBI at our medical center from 2011 to 2014. The patients were evaluated within 72 hours of injury and were monitored for at least 12 weeks. All patients began respiratory-muscle training the day after admission regardless of whether they were treated conservatively or surgically. The percent vital capacity (%VC), forced expiratory volume (FEV) in one second/forced vital capacity ratio (FEV 1.0%), and American Spinal Injury Association motor score (MS) were recorded at admission and again at weeks 4 and 12. We calculated the %VC rate of change and the MS improvement rate over the entire period. RESULTS: Fifty patients (92.6%) had restrictive ventilatory impairment at admission. The %VC correlated with the upper- and lower-limb MSs at admission, and the %VC and upper- and lower-limb MSs had improved by weeks 4 and 12 after the injury. The %VC rate of change was significantly correlated with the rate of improvement in lower-limb MS throughout the entire period. CONCLUSIONS: Lung capacity decreased in SCIWOBI owing to respiratory-muscle paralysis and upper- and lower-limb motor paralyses. Lung capacity improved as the lower limbs recovered their motor function. Respiratory rehabilitation should be continued for at least 12 weeks after SCIWOBI.

Depletion of glycosphingolipids induces excessive response of chondrocytes under mechanical stress
Matsubara S, Onodera T, Maeda E, Momma D, Matsuoka M, Homan K, Ohashi T, Iwasaki N
Journal of biomechanics, 94, 22, 30, 2019年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Glycosphingolipids (GSLs) are ubiquitous membrane components that play an indispensable role in maintaining chondrocyte homeostasis. To gain better insight into roles of GSLs, we studied the effects of GSL-deletion on the physiological responses of chondrocytes to mechanical stress. Mice lacking Ugcg gene (Ugcg-/-) were genetically generated to obtain GSL-deficient mice, and their chondrocytes from the joints were used for functional analyses in vitro culture experiments. The cells were seeded in a three-dimensional collagen gel and subjected to 5%, 10% or 16% cyclic tensile strain for either 3 or 24 h. The gene expressions of chondrocyte anabolic and catabolic factors, and the induction of Ca2+ signaling were analyzed. Our results revealed that chondrocytes derived from GSL-deficient mice exhibited an elevation in the expression of catabolic factors (ADAMTS-5, MMP-13) following the exposure to strain with amplitudes of 10%. Likewise, applying cyclic tensile strain with these amplitudes resulted in an increased Ca2+ oscillation ratio in chondrocytes from GSL-deficient as compared to the ratio from control mice. These results demonstrated that deletion of GSL stimulated the catabolic responses of chondrocytes to mechanical stress via the augmentation of the sensitivity to mechanical stress that may lead to the cartilage deterioration. These findings suggest that the regulation of the physiological responses of chondrocytes by GSLs could be a potential target in a therapeutic intervention in osteoarthritis.

A Novel Cartilage Fragments Stimulation Model Revealed that Macrophage Inflammatory Response Causes an Upregulation of Catabolic Factors of Chondrocytes In Vitro.
Hamasaki M, Terkawi MA, Onodera T, Homan K, Iwasaki N
Cartilage, 12, 1947603519828426, 354, 361, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Osteoarthritis is a progressive joint disease characterized by cartilage degradation and synovial inflammation. Presence of cartilage fragments in the joint due to degradation of cartilage is thought to be associated with local inflammatory response and progressive osteoarthritic process. Understanding the mechanism by which cartilage fragments elicit this destructive process should aid in designing novel therapeutic approaches. Therefore, objective of current study is to establish an in vitro model to examine the cross-talk between chondrocytes and cartilage fragments-stimulated macrophages. DESIGN: Cartilage fragments were prepared from femoral head cartilages of mice and analyzed using a scanning electron microscope and particle size analyzer. Bone marrow-derived macrophages were co-cultured with cartilage fragments and chondrocytes using transwell co-culture system. Macrophage inflammatory mediators in supernatant of cultures were determined by ELISA and gene expression of macrophages and chondrocyte were quantified by qRT-PCR. RESULTS: Shapes of cartilage fragments were irregular with sizes ranged between 0.54 and 55 μm. Macrophages cultured with cartilage fragments released significantly higher concentrations of TNF-α, IL-6, and NO than those of mock and control. Consistently, gene expressions of TNF-α, IL-6, and MMP-9 were significantly increased in stimulated macrophages. The elevation in production of pro-inflammatory molecules in stimulated macrophages cultures were coincident with an increase in gene expression of chondrocyte MMP-13, iNOS, and IL-6. CONCLUSION: We developed an in vitro co-culture model to study the impact of stimulation of macrophage by cartilage fragments on the expression of chondrocyte carbolic factors. Our results revealed that cartilage fragments triggered macrophages inflammatory response that enhanced the production of chondrocyte catabolic factors.

Rapidly progressive cervical myelopathy had a high risk of developing deep venous thrombosis: a prospective observational study in 289 cases with degenerative cervical spine disease.
Yamada K, Suda K, Matsumoto Harmon S, Komatsu M, Ushiku C, Takahata M, Minami A, Iwasaki N
Spinal cord, 57, 1, 58, 64, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, STUDY DESIGN: A prospective observational study. OBJECTIVES: To determine the incidence of deep venous thrombosis (DVT) and to evaluate the risk factors for DVT development associated with degenerative cervical spine disease. SETTING: Hokkaido Spinal Cord Injury Center, Japan. METHODS: Between April 2008 and March 2015, patients with degenerative cervical spine disease, such as compressive myelopathy or radiculopathy, who underwent surgical treatment were prospectively assessed. Leg vein ultrasonography and D-dimer tests were performed preoperatively and at 4 days after surgery. All patients received treatment with intermittent pneumatic compression and elastic stockings for primary DVT prophylaxis. No anticoagulation medications were used for DVT prophylaxis. RESULTS: A total of 289 patients (203 males, 86 females; median age: 67 years (interquartile range, 58-76)) were included. Nine patients (3.1%) exhibited DVT during the perioperative period. All 9 cases were women who had distal DVT. The incidences of preoperative and postoperative DVT were 1.1% and 2.1%, respectively. The univariate analysis showed that statistically significant risk factors for perioperative DVT included female gender (P < 0.01), advanced age (P = 0.04), a low Japanese Orthopaedic Association score (P = 0.03), rapidly progressive myelopathy (P < 0.01), and inability to walk (P = 0.01). The multivariate analysis showed that rapidly progressive myelopathy (P = 0.04) was the most important risk factor. CONCLUSION: Female gender and rapidly progressive myelopathy are high-risk factors that predict the development of DVT during the perioperative period of cervical spine surgery. This result indicates that screening and treatment for DVT are needed in such high-risk patients.

Osteochondral Autograft Transplantation Technique Augmented by an Ultrapurified Alginate Gel Enhances Osteochondral Repair in a Rabbit Model
Ryosuke Hishimura, Tomohiro Onodera, Kazutoshi Hontani, Rikiya Baba, Kentaro Homan, Shinji Matsubara, Zenta Joutoku, WooYoung Kim, Takayuki Nonoyama, Takayuki Kurokawa, Jian Ping Gong, Norimasa Iwasaki
American Journal of Sports Medicine, 47, 2, 468, 478, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: One of the most important limitations of osteochondral autograft transplantation (OAT) is the adverse effect on donor sites in the knee. To decrease the number and/or size of osteochondral defects, we devised a method with biomaterial implantation after OAT. HYPOTHESIS: OAT augmented by ultrapurified alginate (UPAL) gel enhances cartilage repair capacity. STUDY DESIGN: Controlled laboratory study. METHODS: Seventy-five osteochondral defects in rabbits were divided into 3 groups: osteochondral defects with OAT alone, defects with OAT augmented by UPAL gel (combined group), and defects without intervention as controls. Macroscopic and histological evaluations of the reparative tissues were performed at 4 and 12 weeks postoperatively. Histological evaluation of graft cartilage degradation was also performed. To evaluate the effects of UPAL gel on graft healing, repaired bone volumes and osseointegration of the graft were evaluated. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were also evaluated qualitatively. RESULTS: The macroscopic and histological evaluations of the combined group were significantly superior to the other groups at 12 weeks postoperatively. Regarding degenerative change of the graft, the histological scores of the combined group were significantly higher than those of the OAT-alone group. The values of repaired subchondral bone volumes and osseointegration of the graft were almost identical in both groups. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were significantly better in the combined group than in the other groups. CONCLUSION: Administration of UPAL gel in OAT enhanced cartilage repair and protected graft cartilage without inhibiting subchondral bone repair and graft survival. CLINICAL RELEVANCE: OAT augmented by UPAL gel decreases the number and/or size of osteochondral grafts, minimizing the risk of donor site morbidity. This combination technique has the potential to improve clinical outcomes and expand the surgical indications for OAT.

Ectopic RASGRP2 (CalDAG-GEFI) expression in rheumatoid synovium contributes to the development of destructive arthritis.
Hiroyuki Nakamura, Sanae Shimamura, Shinsuke Yasuda, Michihito Kono, Michihiro Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Tomohiro Shimizu, Norimasa Iwasaki, Tatsuya Atsumi
Annals of the rheumatic diseases, 77, 12, 1765, 1772, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel therapeutic strategy for treatment-resistant RA is still awaited. In this study, we analysed the expression and function of Ras guanine nucleotide-releasing proteins (RASGRPs), guanine exchange factors for small GTPase Ras, in FLS as a potential therapeutic target for RA. METHODS: The expression of RASGRPs mRNA was quantified by a real-time PCR assay in FLS isolated from synovial tissue samples. RASGRP2 protein was also evaluated immunohistochemically. Then, we transiently transfected FLS with RASGRP2 expression vector and assessed their proliferation, adhesion, migration and invasion by cellular functional assays and downstream signalling activation using immunoblot. Finally, the therapeutic effect of RASGRP2 silencing was evaluated in type-II collagen-induced arthritis rats. RESULTS: RASGRP2 was abundantly expressed in FLS from RA synovium, whereas scarcely found in those from osteoarthritis. Expression of RASGRP2 in RA-FLS was enhanced by transforming growth factor-beta. RASGRP2 activated RAP-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. RASGRP2-overexpressed FLS had increased abilities of adhesion, migration and interleukin (IL)-6 production. Silencing of RASGRP2 using the intra-articular injection of Rasgrp2-specific siRNAs dampened experimental arthritis in rats by inhibiting pannus formation. CONCLUSIONS: RASGRP2 was identified to be involved in the pathogenesis of RA by promoting adhesion, migration and IL-6 production from FLS, proposed as a potential novel non-immunosuppressive therapeutic target for RA.

Postoperative translation of the upper instrumented vertebra in thoracic adolescent idiopathic scoliosis.
Katsuhisa Yamada, Hideki Sudo, Kiyoshi Kaneda, Yasuhiro Shono, Yuichiro Abe, Norimasa Iwasaki
Journal of neurosurgery. Pediatrics, 22, 6, 694, 700, 2018年12月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVEThe aim of this retrospective study was to analyze the influence of upper instrumented vertebra (UIV) translation from the C7 plumb line (C7PL) on the long-term postoperative results of patients with main thoracic (MT) adolescent idiopathic scoliosis (AIS).METHODSTwenty-five patients had been treated surgically for AIS with a Lenke type 1 curve and had been followed up for a mean period of 18.2 years. Radiographic parameters, pulmonary function measurements, and clinical outcomes were compared between the patients (n = 15) with UIV translation < 20 mm and those (n = 10) with UIV translation ≥ 20 mm at the final follow-up. Correlations between UIV translation and radiographic or pulmonary function parameters were analyzed.RESULTSPatients with ≥ 20 mm UIV translation at the final follow-up had a significantly larger preoperative UIV translation than that in the patients with < 20 mm UIV translation at follow-up. The former group also had a significantly lower correction rate of the MT curve, higher chest cage ratio, and lower radiographic shoulder height (p = 0.01, 0.005, and 0.025, respectively) at the final follow-up. The Scoliosis Research Society (SRS)-30 Questionnaire scores were equivalent between the two groups. Correlation analysis showed that the following parameters were significantly associated with UIV translation: MT curve correction rate (r = -0.481, p = 0.015), chest cage ratio (r = 0.673, p < 0.001), and percent-predicted forced expiratory volume in 1 second (r = -0.455, p = 0.033).CONCLUSIONSThe UIV translation should be considered an important factor that influences postoperative results. In MT AIS patients whose preoperative upper end vertebra (UEV) is distant from the C7PL, the UIV should be selected above the UEV to prevent large UIV translation at the postoperative follow-up.