Oct. 2024, 日本整形外科学会, 第39回 日本整形外科基礎学術集会学会賞　　　　　　　　　　　　　　　
内臓脂肪は脊柱靭帯骨化症の重症化に強く関連する
遠藤努

Oct. 2022, 北海道大学, NA　　　　　　　　　　　　　　　
Development of novel therapeutic agent for treatment of osteoporosis
遠藤努

Oct. 2022, 日本整形外科学会, 第37回 日本整形外科基礎学術集会優秀演題賞　　　　　　　　　　　　　　　
脂質異常症と脊椎靭帯骨化症の発症との強い関連性について
遠藤努

Aug. 2019, The Kondou Kinen Medical Foundation, NA　　　　　　　　　　　　　　　
NA
Tsutomu Endo

Mar. 2018, The Japanese society of cartilage metabolism, The 23rd the Japanese society of cartilage metabolism award　　　　　　　　　　　　　　　
Syndecan-4 regulates B cell migration and germinal center formation in autoimmune arthritis
Tsutomu Endo

Feb. 2017, 北海道整形災害外科学会, NA　　　　　　　　　　　　　　　
Syndecan-4 regulates development of autoimmune arthritis by modulating B cell migration and germinal center formation
Tsutomu Endo

2015, 北大整形外科同門会, 北大整形外科同門会学術奨励賞　　　　　　　　　　　　　　　
遠藤努

Therapeutic Potential of Targeting Ferroptosis in Periprosthetic Osteolysis Induced by Ultra-High-Molecular-Weight Polyethylene Wear Debris
Takuya Ogawa, Shunichi Yokota, Liyile Chen, Yuki Ogawa, Yoshio Nishida, Taiki Tokuhiro, Hend Alhasan, Tomoyo Yutani, Tomohiro Shimizu, Daisuke Takahashi, Takuji Miyazaki, Tsutomu Endo, Ken Kadoya, Mohamad Alaa Terkawi, Norimasa Iwasaki
Biomedicines, 13, 1, 170, 170, MDPI AG, 13 Jan. 2025
Scientific journal, Background/Objectives: Periprosthetic osteolysis is the primary cause of arthroplasty failure in the majority of patients. Mechanistically, wear debris released from the articulating surfaces of a prosthesis initiates local inflammation and several modes of regulated cell death programs, such as ferroptosis, which represents a promising therapeutic target in various chronic inflammatory diseases. Thus, the current study aimed at exploring the therapeutic potential of targeting ferroptosis in a polyethylene-wear-debris-induced osteolysis model. Methods: Inverted cell culture model was used for stimulating the cells with wear debris in vitro, and calvarial osteolysis model was used for evaluating the therapeutic effects of inhibitors in vivo. Results: The immunostaining of periprosthetic bone tissues demonstrated a number of osteocytes expressing ferroptosis markers. Likewise, the expressions of ferroptosis markers were confirmed in polyethylene-wear-debris-stimulated osteocyte-like cells and primary osteoblasts in a direct stimulation model but not in an indirect stimulation model. Furthermore, polyethylene wear debris was implanted onto calvarial bone and mice were treated with the ferroptosis inhibitors DFO and Fer-1. These treatments alleviated the inflammatory and pathological bone resorption induced by the wear debris implantation. Conclusions: Our data broaden the knowledge of the pathogenesis of periprosthetic osteolysis and highlight ferroptosis as a promising therapeutic target.

Visceral fat obesity predicts ossification of the posterior longitudinal ligament: annual health examination data-based evidence
Soya Miura, Yoshinao Koike, Tsutomu Endo, Masahiko Takahata, Hideki Sudo, Ken Kadoya, Masahiro Kanayama, Ryo Fujita, Shotaro Fukada, M Alaa Terkawi, Katsuhisa Yamada, Takashi Ohnishi, Daisuke Ukeba, Hiroyuki Tachi, Yuichi Hasegawa, Misaki Ishii, Norimasa Iwasaki
The Spine Journal, Elsevier BV, Jan. 2025
Scientific journal

Adipokine dysregulation as an underlying pathology for diffuse ectopic ossification of spinal posterior longitudinal ligament in patients with obesity.
Masahiko Takahata, Yoshinao Koike, Tsutomu Endo, Shiro Ikegawa, Shiro Imagama, Satoshi Kato, Masahiro Kanayama, Kazuyoshi Kobayashi, Takashi Kaito, Hiroaki Sakai, Yoshiharu Kawaguchi, Itaru Oda, Chikashi Terao, Tomoya Kanto, Hiroshi Taneichi, Norimasa Iwasaki
The spine journal : official journal of the North American Spine Society, 25, 1, 80, 90, Jan. 2025, [International Magazine]
English, Scientific journal, BACKGROUND CONTEXT: Growing evidence suggests that obesity is implicated in the progression of heterotopic ossification of the posterior longitudinal ligament of the spine (OPLL), a major cause of myelopathy in Asians. However, it remains unclear whether dysregulation of adipokine production due to fat accumulation contributes to OPLL progression. PURPOSE: To determine whether adipose-derived biochemical signals are associated with OPLL development or severity. STUDY DESIGN/SETTING: A nationwide, multicenter, case-control study. PATIENT SAMPLE: Patients with symptomatic thoracic OPLL (T-OPLL) who received treatment between June 2017 and March 2021 and 111 controls without OPLL. OUTCOME MEASURES: OPLL severity index based on whole-spine computed tomography. METHODS: Serum concentrations of adipokines, including leptin (Lep), tumor necrosis factor α (TNFα), and adiponectin (Adpn), as well as the Adpn/Lep ratio-an indicator of adipokine production dysregulation-were compared between the multiple-region OPLL and the single-region OPLL groups. Regression analysis was performed to examine the correlation between adipokine concentrations and OPLL severity index, which was calculated using whole-spine computed tomography images of 77 patients with T-OPLL within 3 years of onset. Using propensity score matching, the adipokine profiles of 59 patients with T-OPLL were compared with those of 59 non-OPLL controls. RESULTS: Patients with multiple-region OPLL exhibited a higher body mass index (BMI), lower serum Adpn/Lep ratio, and higher serum concentration of osteocalcin (OCN) than those with single-region OPLL. The OPLL severity index exhibited a weak positive correlation with BMI and serum Lep levels and a weak negative correlation with the Adpn/Lep ratio. Serum TNFα and OCN concentrations were significantly higher in patients with T-OPLL than in controls with similar age, sex, and BMI. CONCLUSIONS: Patients with diffuse OPLL over the entire spine are often metabolically obese with low Adpn/Lep ratios. In patients with OPLL, TNFα and OCN serum concentrations were essentially elevated regardless of obesity, suggesting a potential association with OPLL development. Considering the absence of therapeutic drugs for OPLL, the findings presented herein offer valuable insights that can aid in identifying therapeutic targets and formulating strategies to impede its progression.

Cellular communication network factor 3 contributes to the pathological process of rheumatoid arthritis through promoting cell senescence and osteoclastogenesis in the joint.
Taiki Tokuhiro, Gen Matsumae, Tsutomu Endo, Yuki Ogawa, Takuya Ogawa, Chen Liyile, Yoshio Nishida, Hend Alhasan, Hideyuki Kobayashi, Taku Ebata, Tomohiro Shimizu, Daisuke Takahashi, Tomohiro Onodera, Ken Kadoya, M Alaa Terkawi, Norimasa Iwasaki
Journal of autoimmunity, 149, 103334, 103334, Dec. 2024, [International Magazine]
English, Scientific journal, Rheumatoid arthritis (RA) is a chronic systemic and autoimmune disease that primarily affects joints and causes pain, stiffness and swelling. The affected joints exhibit severe inflammation in the synovium and bone erosion, leading to joint deformity. Aging is an important factor facilitating the development of RA, as it is associated with an increase in the number of senescent cells and the production of the autoantibodies and proinflammatory cytokines in tissues. Given that CCN3 is highly expressed in RA joints and that its level is associated with the severity of the disease, we explored its molecular function in joints and therapeutic potential in RA. An analysis of public scRNA-seq data from the RA synovium revealed that CCN3 is expressed by an inflammatory fibroblast subset. Interestingly, stimulation with CCN3 resulted in the activation of the senescence pathway in synoviocytes and osteoclast differentiation in monocytes in vitro. Consistent with these results, the administration of CCN3 into the knee joint and onto the calvarial bone resulted in increased numbers of senescent synoviocytes in the joint and osteoclasts in the bone, respectively. Furthermore, the therapeutic potential of targeting CCN3 was evaluated in an experimental RA model. Administration of the CCN3 antibody significantly suppressed inflammation and osteoclast numbers in the joints of the RA model mice. Our findings suggest that CCN3 contributes to pathological processes in RA and represents a promising therapeutic target for the treatment of RA.

Correction: Bilateral lumbar pedicle fracture in a patient receiving long-term bisphosphonate therapy: a case report with pathological evaluation.
Ryo Fujita, Kota Suda, Zen-Ichi Tanei, Satoko Matsumoto Harmon, Miki Komatsu, Keiichi Nakai, Kento Inomata, Shin Matsushima, Tsutomu Endo, Katsuhisa Yamada, Masahiko Takahata, Norimasa Iwasaki
Archives of osteoporosis, 19, 1, 120, 120, 29 Nov. 2024, [International Magazine]
English

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, 27 Nov. 2024, [International Magazine]
English, Scientific journal, 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, 31 Oct. 2024, [International Magazine]
English, Scientific journal, 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.

Bilateral lumbar pedicle fracture in a patient receiving long-term bisphosphonate therapy: a case report with pathological evaluation.
Ryo Fujita, Kota Suda, Zen-Ichi Tanei, Satoko Matsumoto Harmon, Miki Komatsu, Keiichi Nakai, Kento Inomata, Shin Matsushima, Tsutomu Endo, Katsuhisa Yamada, Masahiko Takahata, Norimasa Iwasaki
Archives of osteoporosis, 19, 1, 103, 103, 24 Oct. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Bilateral pedicle fractures of the lumbar spine are uncommon and are typically associated with strenuous activities, traumatic events, or previous spinal surgery. This study reported a case of bilateral pedicle fracture in a patient with a long history of osteoporosis treatment with bisphosphonate and included a histological evaluation of the bone. CASE PRESENTATION: An 82-year-old woman with no history of trauma presented to our hospital with back pain that had worsened over the previous month. Computed tomography and magnetic resonance imaging revealed bilateral pedicle fractures of the third lumbar vertebra. She had osteoporosis and had been taking bisphosphonates for 9 years. The patient underwent posterior lumbar fusion, and her symptoms improved. Bone biopsy results from the spinous process revealed few osteoblasts and an absence of osteoclasts, indicating low bone turnover. CONCLUSIONS: Long-term use of bisphosphonates may contribute to the development of atypical bilateral pedicle fractures in patients with osteoporosis.

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, Jul. 2024, [International Magazine]
English, Scientific journal, 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.

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, 22 Jun. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

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, 08 Jun. 2024, [Domestic magazines]
English, Scientific journal, 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.

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, 28 May 2024, [Domestic magazines]
English, Scientific journal, 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.

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, 01 May 2024, [International Magazine]
English, Scientific journal, 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.

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, 04 Sep. 2023, [International Magazine]
English, Scientific journal, 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.

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, 10 Jul. 2023, [International Magazine]
English, Scientific journal, 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.

整形トピックス 脂質異常症と脊柱靱帯骨化症発症の強い関連性
遠藤 努, 高畑 雅彦, 小池 良直, 藤田 諒, 村上 俊文, 深田 翔太郎
整形外科, 74, 7, 790, 790, (株)南江堂, Jun. 2023
Japanese

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, 07 May 2023, [International Magazine]
English, Scientific journal, 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.

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, 28 Apr. 2023, [International Magazine]
English, Scientific journal, 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.

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, 16 Mar. 2023, [International Magazine]
English, Scientific journal, 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.

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, 09 Feb. 2023
Scientific journal, 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.

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, 12 Jan. 2023, [International Magazine]
English, Scientific journal, 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.

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, 07 Jan. 2023
Scientific journal, 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.

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, 30 Dec. 2022, [International Magazine]
English, Scientific journal, 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.

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, Springer Science and Business Media LLC, 24 Nov. 2022
Scientific journal

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, 219256822211355, 219256822211355, SAGE Publications, 15 Oct. 2022
Scientific journal, 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.

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, 27 Jun. 2022, [Domestic magazines]
English, Scientific journal, 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, Cold Spring Harbor Laboratory, 17 Jun. 2022
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.

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, 10 May 2022, [International Magazine]
English, Scientific journal, 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, 02 May 2022, [International Magazine]
English, Scientific journal, 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.

Pre-existing adjacent level foraminal stenosis does not affect the outcome of a single level lumbar interbody fusion.
Yukitoshi Shimamura, Masahiro Kanayama, Fumihiro Oha, Takeru Tsujimoto, Masaru Takana, Yuichi Hasegawa, Tsutomu Endo, Tomoyuki Hashimoto
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 22 Apr. 2022, [Domestic magazines]
English, Scientific journal, BACKGROUND: The aim of this study was to investigate whether or not pre-existing asymptomatic neuroforaminal stenosis adjacent to the fusion level develops adjacent segment disease (ASD) after single-level lumbar interbody fusion. SUMMARY AND BACKGROUND DATA: Risk factors of ASD after spinal fusion have been well investigated, but there have been few studies focused on the relationship between ASD and pre-existing asymptomatic neuroforaminal stenosis. METHODS: A total of 302 patients who had undergone a single-level lumbar interbody fusion were reviewed at a minimum of 2 year follow-up. They were 109 men and 193 women with a mean age of 68.8 years. Follow-up periods was averaged 53.5 months. ASD was defined as neurological deterioration related to adjacent segment pathologies which required an additional surgery. Based on the pathologies, patients were divided into three categories: ASD due to foraminal stenosis (ASD-FS), ASD due to central stenosis (ASD-CS), and ASD due to herniated disc (ASD-HD). Measured variables were age, gender, diagnosis, BMI, decompression procedures at adjacent segments, preoperative anterior/posterior slip, asymptomatic neuroforaminal stenosis, facet tropism, and postoperative spinopelvic parameters. RESULTS: Thirty-eight patients (12.6%) developed ASD. There were 15 patients with ASD-FS, 18 patients with ASD-CS, and five patients with ASD-HD. Lumbar lordosis (LL) and sacral slope (SS) were significantly smaller and pelvic tilt (PT) was significantly larger in ASD-FS. Asymptomatic neuroforaminal stenosis was detected preoperatively in 33.3% of the ASD-FS group, and 18.6% of non-ASD group; the incidence was not significantly different. CONCLUSIONS: Adjacent-level neuroforaminal stenosis was not a significant risk of ASD after single-level lumbar interbody fusion, and might not need to be fused if asymptomatic.

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, 01 Apr. 2022, [International Magazine]
English, Scientific journal, 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.

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, 25 Mar. 2022, [Domestic magazines]
English, Scientific journal, 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.

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, 1, 8, 04 Mar. 2022, [International Magazine]
English, Scientific journal, 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.

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, Mar. 2022, [Domestic magazines]
English, Scientific journal, 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.

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, 17 Jan. 2022, [International Magazine]
English, Scientific journal, 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, 21925682211069542, 21925682211069542, 10 Jan. 2022, [International Magazine]
English, Scientific journal, 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.

Therapeutic drug monitoring-enabled long-term use of linezolid for the successful treatment of refractory pyogenic spondylodiscitis without development of thrombocytopenia: A case report.
Takayuki Daisho, Keisuke Kagami, Koujiro Yamazaki, Nobuhisa Ishiguro, Tsutomu Endo, Masahiko Takahata, Hisataka Suzuki, Mitsuru Sugawara, Yoh Takekuma
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 15 Dec. 2021, [Domestic magazines]
English

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, 06 Oct. 2021, [International Magazine]
English, Scientific journal, 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.

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, 09 Sep. 2021, [International Magazine]
English, Scientific journal, 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.

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, 31 Aug. 2021, [International Magazine]
English, Scientific journal, 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.

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, 01 Aug. 2021, [International Magazine]
English, Scientific journal, 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.

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, 16 Jun. 2021, [International Magazine]
English, Scientific journal, 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.

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, 25 Jan. 2021, [International Magazine]
English, Scientific journal, 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.

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, 06 Jan. 2021, [Domestic magazines]
English, Scientific journal, 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.

Clinical Outcomes and Postoperative Radiographic Assessment of Osteoplastic Hemilaminectomy in the Treatment of Lumbar Foraminal Nerve Root Compression.
Masaru Tanaka, Masahiro Kanayama, Tomoyuki Hashimoto, Fumihiro Oha, Yukitoshi Shimamura, Tsutomu Endo, Takeru Tsujimoto, Hiroyuki Hara, Yuichi Hasegawa, Hidetoshi Nojiri, Muneaki Ishijima
Spine surgery and related research, 5, 6, 352, 358, 2021, [Domestic magazines]
English, Scientific journal, INTRODUCTION: Osteoplastic hemilaminectomy for the treatment of lumbar foraminal nerve root compression is a safe technique as the exiting nerve root can be directly observed during neuroforaminal decompression without spinal fusion. Moreover, this procedure allows anatomical reconstruction of the posterior elements. However, there might be a potential risk for the progression of lumbar segmental instability after performing this procedure. This study aimed to review the radiographic and clinical outcomes of osteoplastic hemilaminectomy for the treatment of lumbar foraminal nerve root compression. METHODS: We retrospectively reviewed 51 patients who underwent osteoplastic hemilaminectomy with a minimum follow-up of 2 years. The clinical outcomes were evaluated using the visual analog scale (VAS) for low back pain, leg pain, and numbness and the Japanese Orthopaedic Association (JOA) score. Lumbar segmental instability was evaluated as a radiographic assessment using functional radiography. The mean follow-up period was 65 months. RESULTS: The preoperative VASs for low back pain, leg pain, and numbness were 46±31, 72±26, and 43±34, respectively, which were improved to 24±23, 19±23, and 19±23, respectively. The JOA score was also improved from 14±5 to 22±4. Three patients (5.9%) were reoperated due to recurrent disc herniation within 2 years following surgery. In addition, three patients (5.9%) developed postoperative lumbar segmental instability but did not require additional surgery. CONCLUSIONS: The current study revealed that 94.1% of the patients who underwent osteoplastic hemilaminectomy achieved a significant improvement in the clinical outcomes and did not require additional surgery within 2 years following the procedure. Over a 5-year follow-up on average, 5.9% of the subjects developed postoperative lumbar segmental instability; however, they have maintained acceptable clinical conditions.

Clinical characteristics of patients with thoracic myelopathy caused by ossification of the posterior longitudinal ligament.
Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Norimasa Iwasaki
Journal of bone and mineral metabolism, 38, 1, 63, 69, Jan. 2020, [Domestic magazines]
English, Scientific journal, 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.

Occipitoatlantoaxial rotatory fixation caused by minor traumatic occipitoatlantal rotatory fixation with compensatory counter-rotation in atlantoaxial joint: A case report.
Hirokazu Shimizu, Tsutomu Endo, Masahiko Takahata, Keigo Yasui, Yohei Sodeyama, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 27, 4, 956, 959, 10 Oct. 2019, [Domestic magazines]
English, Scientific journal

Late Subaxial Lesion after Overcorrected Occipitocervical Reconstruction in Patients with Rheumatoid Arthritis.
Akira Iwata, Kuniyoshi Abumi, Masahiko Takahata, Hideki Sudo, Katsuhisa Yamada, Tsutomu Endo, Norimasa Iwasaki
Asian spine journal, 13, 2, 181, 188, Apr. 2019, [International Magazine]
English, Scientific journal, 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.

A novel technique of cervical pedicle screw placement with a pilot screw under the guidance of intraoperative 3D imaging from C-arm cone-beam CT without navigation for safe and accurate insertion.
Masahiko Takahata, Katsuhisa Yamada, Iwata Akira, Tsutomu Endo, Hideki Sudo, Hidetoki Yokoyama, 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, 27, 11, 2754, 2762, Nov. 2018, [International Magazine]
English, Scientific journal, PURPOSE: The cervical pedicle screw (CPS) requires careful and accurate placement because of the critical risk for neurovascular injury. This study aimed to introduce and evaluate the safety and efficacy of a new CPS placement technique using intraoperative C-arm cone-beam CT (CBCT) and a pilot screw without navigation system. METHODS: This was a case-control study to compare the accuracy and safety of intraoperative C-arm CBCT-guided CPS placement with freehand CPS placement under lateral fluoroscopy using control data from a previous multicenter study. A total of 166 CPSs were inserted under intraoperative C-arm CBCT guidance in 48 consecutive patients (20 rheumatoid arthritis, 16 degenerative spinal disorders, 6 spinal tumor, 2 congenital deformity, 2 ossification of posterior longitudinal ligament, and 2 fracture dislocation). Accuracy and safety of CPS placement were assessed. RESULTS: The overall malposition rate was 2.4% (4 screws in grade 1: malposition by less than half-screw diameter, 0 in grade 2: malposition by more than half-screw diameter), which was significantly lower than the reported malposition rate of 14.8% in lateral fluoroscopy-guided freehand placement. There were no complications directly related to CPS insertion. The average estimated effective radiation dose per surgery was 14.7 mSv. CONCLUSIONS: The novel technique enables intraoperative adjustment of the trajectory of the CPS as well as confirmation of the CPS path before penetrating the isthmus of the pedicle, resulting in accurate and safe CPS placement, which outweighs the demerits of radiation exposure. These slides can be retrieved under Electronic Supplementary Material.

18F-FDG-PET/CT localizes intervertebral disc space infection following posterior lumbar interbody fusion surgery leading to successful retention of percutaneously inserted pedicle screws: a case report.
Kentaro Haraya, Katsuhisa Yamada, Terufumi Kokabu, Akira Iwata, Tsutomu Endo, Hideki Sudo, Norimasa Iwasaki, Masahiko Takahata
Spinal cord series and cases, 4, 81, 81, 2018, [International Magazine]
English, Scientific journal, Introduction: Postoperative infection is a potentially devastating complication of spine surgery and an appropriate strategy and timely decision-making are essential for successful treatment of deep surgical site infection (SSI) after spinal instrumentation surgeries. However, there is a lack of consensus on implant removal or retention. We report on a case of deep SSI after posterior lumbar interbody fusion (PLIF) surgery in which we achieved clinical cure by debridement and removal of the interbody fusion cage without removing the percutaneously inserted pedicle screws (PPS). Case presentation: A case was a 53-year-old woman with deep SSI after PLIF surgery using the PPS system at the L4-5 level. Computed tomography (CT) showed no clear radiolucent line around the screws and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT demonstrated abnormal FDG uptake around the cages and no uptake around the pedicle screws. Intervertebral cages were removed and iliac bone grafts were inserted between the vertebral bodies, without removing the pedicle screws. The infection was cleared and bone fusion was achieved after the revision surgery. Discussion: Targeting active infection using FDG-PET/CT is considered useful in narrowing the surgical margins and determining whether to preserve instrumentation in revision surgery after SSI. PLIF using the PPS system could be useful in preventing the easy spread of infection from the intervertebral space to the insertion point of PPS through the interstitial space.

Death receptor 6 contributes to autoimmunity in lupus-prone mice.
Daisuke Fujikura, Masahiro Ikesue, Tsutomu Endo, Satoko Chiba, Hideaki Higashi, Toshimitsu Uede
Nature communications, 8, 13957, 13957, 03 Jan. 2017, [International Magazine]
English, Scientific journal, Expansion of autoreactive follicular helper T (Tfh) cells is tightly restricted to prevent induction of autoantibody-dependent immunological diseases, such as systemic lupus erythematosus (SLE). Here we show expression of an orphan immune regulator, death receptor 6 (DR6/TNFRSF21), on a population of Tfh cells that are highly expanded in lupus-like disease progression in mice. Genome-wide screening reveals an interaction between syndecan-1 and DR6 resulting in immunosuppressive functions. Importantly, syndecan-1 is expressed specifically on autoreactive germinal centre (GC) B cells that are critical for maintenance of Tfh cells. Syndecan-1 expression level on GC B cells is associated with Tfh cell expansion and disease progression in lupus-prone mouse strains. In addition, Tfh cell suppression by DR6-specific monoclonal antibody delays disease progression in lupus-prone mice. These findings suggest that the DR6/syndecan-1 axis regulates aberrant GC reactions and could be a therapeutic target for autoimmune diseases such as SLE.

Preventive Effect of Lactobacillus helveticus SBT2171 on Collagen-Induced Arthritis in Mice.
Maya Yamashita, Kurumi Matsumoto, Tsutomu Endo, Ken Ukibe, Tomohiro Hosoya, Yumi Matsubara, Hisako Nakagawa, Fumihiko Sakai, Tadaaki Miyazaki
Frontiers in microbiology, 8, 1159, 1159, 2017, [International Magazine]
English, Scientific journal, We recently reported that the intraperitoneal inoculation of Lactobacillus helveticus SBT2171 inhibited the development of collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA). In the present study, we evaluated the effect of the oral administration of L. helveticus SBT2171 on CIA development and on the regulation of antigen-specific antibody production and inflammatory immune cells, which have been implicated in the development of RA. Both oral administration and intraperitoneal inoculation of L. helveticus SBT2171 reduced joint swelling, body weight loss, and the serum level of bovine type II collagen (CII)-specific antibodies in the CIA mouse model. The intraperitoneal inoculation also decreased the arthritis incidence, joint damage, and serum level of interleukin (IL)-6. In addition, the numbers of total immune cells, total B cells, germinal center B cells, and CD4+ T cells in the draining lymph nodes were decreased following intraperitoneal inoculation of L. helveticus SBT2171. These findings demonstrate the ability of L. helveticus SBT2171 to downregulate the abundance of immune cells and the subsequent production of CII-specific antibodies and IL-6, thereby suppressing the CIA symptoms, indicating its potential for use in the prevention of RA.

ドクターズディレイにより遅発性に両側椎骨動脈が閉塞した頸椎脱臼骨折の一例
小松 幹, 須田 浩太, 松本 聡子, 牛久 智加良, 山根 淳一, 山田 勝久, 遠藤 努
北海道整形災害外科学会雑誌, 57, 2, 412, 413, 北海道整形災害外科学会, Apr. 2016
Japanese

Delayed bilateral vertebral artery occlusion after cervical spine injury: a case report.
Miki Komatsu, Kota Suda, Masahiko Takahata, Satoko Matsumoto, Chikara Ushiku, Katsuhisa Yamada, Junichi Yamane, Tsutomu Endo, Norimasa Iwasaki, Akio Minami
Spinal cord series and cases, 2, 16031, 16031, 2016, [International Magazine]
English, Scientific journal, INTRODUCTION: There are considerable risks for the secondary spinal cord injury and the initial and/or delayed vertebral artery occlusion in cases of cervical fracture dislocation. CASE PRESENTATION: An 86-year-old man was injured in a car accident and was diagnosed with no fracture or dislocation of the cervical spine by the emergency physician. However, he was transferred to our hospital 3 days later because he had motor weakness that was evaluated to be 32 points (out of 50 points) on the upper limb American Spinal Injury Association (ASIA) motor score and was diagnosed with spontaneously reduced fracture dislocation at C5/6. Magnetic resonance images revealed that the bilateral vertebral arteries were occluded, and there were some microinfarction lesions in the brain. On the first visit to his previous doctor, he was found to have a flow void in the right vertebral artery. This indicated that it was occluded during the waiting period at his previous doctor. On the day of his arrival at our hospital, the patient underwent a C5/6 posterior spinal fusion. Three months after surgery, he recovered to 46 points on the upper extremity ASIA motor score, and blood flow in the left vertebral artery was resumed. DISCUSSION: Early reduction and stabilization are necessary for cervical spine fracture dislocation; however, it is important not only for the prevention of the secondary injury but also for the reduction of the risk of vertebral artery occlusion.

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) mediates periarticular bone loss, but not joint destruction, in murine antigen-induced arthritis.
Tomohiro Shimizu, Masahiko Takahata, Yusuke Kameda, Tsutomu Endo, Hiroki Hamano, Shigeto Hiratsuka, Masahiro Ota, Norimasa Iwasaki
Bone, 79, 65, 70, Oct. 2015, [International Magazine]
English, Scientific journal, Osteoclastogenesis requires immunoreceptor tyrosine-based activation motif signaling. Multiple immunoreceptors associated with immunoreceptor tyrosine-based activation motif adaptor proteins, including DNAX-activating protein 12 kDa (DAP12) and Fc receptor common γ (FcRγ), have been identified in osteoclast lineage cells, and some are involved in arthritis-induced bone destruction. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption in association with DAP12. Whether Siglec-15 is involved in arthritis-induced bone lesions, however, remains unknown. Here we used a murine antigen-induced arthritis model to examine the role of Siglec-15 in the development of bone lesions induced by joint inflammation. Arthritis was unilaterally induced in the knee joints of 8-week-old female wild-type (WT) and Siglec-15(-/-) mice, and the contralateral knees were used as a control. The degree of joint inflammation, and cartilage and subchondral bone destruction in Siglec-15(-/-) mice was comparable to that in WT mice, indicating that Siglec-15 is not involved in the development of arthritis and concomitant cartilage and subchondral bone destruction. On the other hand, the degree of periarticular bone loss in the proximal tibia of the arthritic knee was significantly lower in Siglec-15(-/-) mice compared to WT mice. Although osteoclast formation in the metaphysis was enhanced in both WT and Siglec-15(-/-) mice after arthritis induction, mature multinucleated osteoclast formation was impaired in Siglec-15(-/-) mice, indicating impaired osteoclast bone resorptive function in the periarticular regions of the arthritic joint in Siglec-15(-/-) mice. Confirming this result, Siglec-15(-/-) primary unfractionated bone marrow cells harvested from arthritic femurs and tibiae failed to develop into mature multinuclear osteoclasts. Our findings suggest that Siglec-15 is a therapeutic target for periarticular bone loss, but not for joint destruction, in inflammatory arthritis, such as rheumatoid arthritis.

Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation.
Tsutomu Endo, Koyu Ito, Junko Morimoto, Masashi Kanayama, Daichi Ota, Masahiro Ikesue, Shigeyuki Kon, Daisuke Takahashi, Tomohiro Onodera, Norimasa Iwasaki, Toshimitsu Uede
Arthritis & rheumatology (Hoboken, N.J.), 67, 9, 2512, 22, Sep. 2015, [International Magazine]
English, Scientific journal, OBJECTIVE: Syndecan 4 has been implicated as a critical mediator of inflammatory responses because of its functions as a coreceptor and reservoir for growth factors and chemokines. Although syndecan 4 is known to be expressed on B cells, its role in immune responses remains unclear. The purpose of this study was to investigate the contribution of syndecan 4 to the development of immune arthritis in murine models. METHODS: The clinical severity of 3 immunopathologically distinct models, collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and collagen antibody-induced arthritis (CAIA), was evaluated in wild-type (WT) mice and in syndecan 4-deficient (Sdc4(-/-) ) mice. Germinal center (GC) formation, B cell profiles, humoral immune responses, and B cell migration were analyzed during the course of CIA. RESULTS: Sdc4(-/-) mice were resistant to the induction of CIA, which is T cell and B cell dependent, but AIA and CAIA, which are T cell dependent and T cell independent, respectively, occurred with equal frequency in WT mice and Sdc4(-/-) mice. Furthermore, Sdc4(-/-) mice had reduced numbers of B cells and deficient GC formation in draining lymph nodes (DLNs) during the course of CIA, resulting in reduced production of collagen-specific autoantibodies. Compared with B cells from WT mice, B cells from Sdc4(-/-) mice showed reduced chemotactic migration toward stromal cell-derived factor 1 (SDF-1) and reduced SDF-1-mediated Akt phosphorylation. Consistent with these findings, in vivo transfer experiments showed that fewer Sdc4(-/-) B cells than WT B cells were found in and around the follicles in the DLNs. CONCLUSION: Our findings suggest that syndecan 4 contributes to the development of CIA by promoting GC formation and autoantibody production through its regulation of SDF-1-mediated B cell migration.

Lactobacillus helveticus SBT2171 inhibits lymphocyte proliferation by regulation of the JNK signaling pathway.
Tomohiro Hosoya, Fumihiko Sakai, Maya Yamashita, Takuya Shiozaki, Tsutomu Endo, Ken Ukibe, Hiroshi Uenishi, Yukio Kadooka, Tomohiro Moriya, Hisako Nakagawa, Yosuke Nakayama, Tadaaki Miyazaki
PloS one, 9, 9, e108360, 2014, [International Magazine]
English, Scientific journal, Lactobacillus helveticus SBT2171 (LH2171) is a lactic acid bacterium with high protease activity and used in starter cultures in the manufacture of cheese. We recently reported that consumption of cheese manufactured using LH2171 alleviated symptoms of dextran sodium sulfate (DSS)-induced colitis in mice. In this study, we have examined whether LH2171 itself exerts an inhibitory effect on the excessive proliferation of lymphocytes. We found that LH2171 inhibited the proliferation of LPS-stimulated mouse T and B cells, and the human lymphoma cell lines, Jurkat and BJAB. Cell cycle analysis showed an accumulation of LH2171-treated BJAB cells in the G2/M phase. Further, phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun was reduced by LH2171 in BJAB cells. Subsequently, expression of cell division cycle 2 (CDC2), regulated by the JNK signaling pathway and essential for G2/M phase progression, was inhibited by LH2171. It was also demonstrated that intraperitoneal administration of LH2171 strongly alleviated symptoms of collagen-induced arthritis (CIA) in mice. These findings suggest that LH2171 inhibits the proliferation of lymphocytes through a suppression of the JNK signaling pathway and exerts an immunosuppressive effect in vivo.

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, Aug. 2023
(公社)日本整形外科学会, Japanese

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, Aug. 2023
(公社)日本整形外科学会, Japanese

ダンベル型神経原性腫瘍類似の画像所見を呈した胸椎脊索腫の一例
佐藤 知哉, 筌場 大介, 山田 勝久, 高畑 雅彦, 須藤 英毅, 遠藤 努, 大西 貴士, 浦 勝郎, 北海道整形災害外科学会雑誌, 65, 142nd suppl, 17, 17, 2023
北海道整形災害外科学会, Japanese

胸椎後縦靱帯骨化症の骨化進展に関与する補酵素(ビタミン)の血清学的評価
遠藤 努, 高畑 雅彦, 小池 良直, 久田 雄一郎, 岩崎 倫政, 今釜 史郎, 安藤 圭, 小林 和克, 加藤 仁志, 海渡 貴司, 金山 雅弘, 川口 善治, 坂井 宏旭, 池川 志郎, 北海道整形災害外科学会雑誌, 62, 138th suppl, 10, 10, 2020
北海道整形災害外科学会, Japanese

運動器疾患ゲノム研究の未来 胸椎後縦靱帯骨化症の病因探索研究
高畑 雅彦, 遠藤 努, 池川 志郎, 小池 良直, 中島 正宏, 今釜 史郎, 加藤 仁志, 坂井 宏旭, 海渡 貴司, 川口 善治, 岩崎 倫政, 日本整形外科学会雑誌, 93, 8, S1608, S1608, Sep. 2019
(公社)日本整形外科学会, Japanese

骨粗鬆症性椎体骨折後の遅発性麻痺 アライメント変化による非骨折高位の腰部脊柱管狭窄の症状顕在化　　　　　　　　　　　　　　　
山口 哲也, 遠藤 努, 高畑 雅彦, 岩田 玲, 山田 勝久, 辻本 武尊, 須藤 英毅, 岩崎 倫政, 東日本整形災害外科学会雑誌, 31, 3, 259, 259, Aug. 2019
東日本整形災害外科学会, Japanese

胸椎後縦靱帯骨化症にくも膜嚢胞を合併した胸髄症の2例　　　　　　　　　　　　　　　
小川 裕生, 高畑 雅彦, 岩田 玲, 山田 勝久, 遠藤 努, 辻本 武尊, 須藤 英毅, 岩崎 倫政, 東日本整形災害外科学会雑誌, 31, 3, 382, 382, Aug. 2019
東日本整形災害外科学会, Japanese

胸椎後縦靱帯骨化症後方除圧固定術後20年来の慢性骨髄炎に対する治療経験　　　　　　　　　　　　　　　
山本 真弘, 辻本 武尊, 高畑 雅彦, 岩田 玲, 山田 勝久, 遠藤 努, 須藤 英毅, 岩崎 倫政, 東日本整形災害外科学会雑誌, 31, 3, 384, 384, Aug. 2019
東日本整形災害外科学会, Japanese

単椎間経皮的椎弓根スクリュー固定と経皮的内視鏡下ドレナージ併用にて治癒し得た腰椎化膿性脊椎炎の2症例　　　　　　　　　　　　　　　
舘 弘之, 山田 勝久, 高畑 雅彦, 岩田 玲, 遠藤 努, 辻本 武尊, 須藤 英毅, 岩崎 倫政, 東日本整形災害外科学会雑誌, 31, 3, 413, 413, Aug. 2019
東日本整形災害外科学会, Japanese

迅速な整復固定の重要性を示唆した頚椎脱臼骨折の1例 : 例え運動完全麻痺であっても超早期手術により下肢筋力は完全回復する可能性がある
福井 隆史, 須田 浩太, 遠藤 努, 松本 聡子, 小松 幹, 牛久 智加良, 山根 淳一, 東條 泰明, 神谷 行宣, 三浪 明男, 高畑 雅彦, 岩崎 倫政, 北海道整形災害外科学会雑誌 : 北海道整形災害外科学会機関誌, 58, 2, 203, 206, Mar. 2017
北海道整形災害外科学会, Japanese

Syndecan-4regulates development of autoimmune arthritis by modulating B cell migration and germinal center formation-自己免疫性関節炎におけるシンデカン-4の機能解析-
遠藤努, 遠藤努, 伊藤甲雄, 森本純子, 金山剛士, 太田大地, 池末昌弘, 今重之, 小野寺智洋, 高橋大介, 岩崎倫政, 上出利光, 上出利光, 北海道整形災害外科学会雑誌, 59, 1, 11, 17, 2017
北海道整形災害外科学会, Japanese

The role of syndecan-4 in the development of rheumatoid arthritis
Tsutomu Endo, Junko Morimoto, Koyu Ito, Norimasa Iwasaki, Toshimitsu Uede, JOURNAL OF IMMUNOLOGY, 190, May 2013
English, Summary international conference

The role of Syndecan-4 in the development of rheumatoid arthritis
Tsutomu Endo, Junko Morimoto, Koyu Ito, Masashi Kanayama, Norimasa Iwasaki, Akio Minami, Toshimitsu Uede, JOURNAL OF IMMUNOLOGY, 188, May 2012
English, Summary international conference