研究者情報

マスター

アカウント（マスター）

• 氏名

  須藤　英毅(スドウ　ヒデキ), スドウ　ヒデキ

所属（マスター）

• 北海道大学病院　外科　整形外科

所属（マスター）

• 北海道大学病院　外科　整形外科

独自項目

syllabus

• 2021, 基本医学研究, Master's Thesis Research in Medical Sciences, 修士課程, 医学院, 整形外科学的研究，筋骨格系研究，脊髄末梢神経研究 Orthopedic research, Musculoskeletal research, Spinal cord and peripheral nerve research
• 2021, 基本医学総論, Basic Principles of Medicine, 修士課程, 医学院, 運動器，形態学，骨軟骨代謝学，免疫学，運動学，生体力学 Musculoskeletal system, Bone and Cartilage metabolism, Morphology, Immunology, Kinematics, Biomechanics
• 2021, 基本医学総論, Basic Principles of Medicine, 修士課程, 医学院, 脊椎再建医学、組織工学、分子生物学 Spinal reconstruction, Bioengineering, molecular biology
• 2021, 医学総論, Principles of Medicine, 博士後期課程, 医学院, 運動器，病態，治療法，臨床研究 Musculoskeletal system, etiology, treatment, clinical research
• 2021, 医学総論, Principles of Medicine, 博士後期課程, 医学院, 運動器，形態学、骨軟骨代謝学，免疫学、運動学、生体材料工学、生体力学，再生工学 Musculoskeletal system, bone and cartilage metabolism, immunology, kinematics, pathology, anatomy, biomechanics, bioengineering
• 2021, 基盤医学研究, Dissertation Research in Medical Sciences, 博士後期課程, 医学院, 運動器，形態学、骨・軟骨代謝学，免疫学、運動学、生体力学，生体工学，生体材料 Musculoskeletal organs, Morphology, Bone and Cartilage metabolism, Immunology, Kinematics, Biomechanics, Biomaterials
• 2021, 臨床医学研究, Dissertation Research in Clinical Medicine, 博士後期課程, 医学院, 脊椎再建医学、組織工学、骨代謝、分子生物学 Spinal reconstruction, tissue engineering, bone metabolism, molecular biology.

researchmap

プロフィール情報

学位

• 博士（医学）（北海道大学）

プロフィール情報

• 姓

  須藤, スドウ

• 名

  英毅, ヒデキ

• ID各種

  201301096887048795

対象リソース

https://www.hokudaiseikei.jp/pdf/researchmap202408.pdf

業績リスト

研究キーワード

• 再生医療   生体材料・生体力学   人工知能・情報科学   医工連携・産学連携   整形外科・脊椎脊髄外科   脊柱変形矯正   遺伝子治療・幹細胞治療   

研究分野

• ライフサイエンス / 整形外科学 / 脊椎脊髄病学

経歴

• 2024年04月 - 現在 北海道大学病院 整形外科 特任教授
• 2022年04月 - 2024年03月 北海道大学大学院医学研究院脊椎・脊髄先端医学分野 特任教授

委員歴

• 2023年 - 現在   日本整形外科学会代議員
• 2022年 - 現在   日本再生医療学会   代議員
• 2022年 - 現在   日本整形外科学会 移植・再生医療委員会委員
• 2019年 - 現在   日本側弯症学会 評議員
• 2017年04月 - 現在   北海道大学整形外科専門研修プログラム統括責任者
• 2016年11月 - 現在   厚労省/AMED臨床研究・治験従事者研修修了
• 2013年 - 現在   北海道整形災害外科学会   評議員
• 2013年 - 現在   北海道特定疾患対策協議会審査専門委員
• 2013年 - 現在   北海道医学会   評議員
• 2013年 - 現在   東日本整形災害外科学会   評議員
• 2012年 - 現在   共用試験医学系OSCE評価者認定講習会修了
• 2012年 - 現在   日本脊椎脊髄病学会   評議員
• 2011年 - 現在   北海道大学病院指導医のための教育ワークショップ修了
• 2020年 - 2022年   日本脊椎脊髄病学会 新技術評価検証委員会委員
• 2017年   Journal of Orthopaedic Research Spine Advisory Review Board
• 2014年12月 - 2015年03月   経産省高生体適合性[カスタムメイド]脊椎インプラント開発ワーキンググループ委員会
• Orthopaedic Research Society Established Member
• 日本側弯症学会 国際委員会委員

受賞

• 2023年05月 第96回日本整形外科学会学術総会最優秀口演賞（研究責任者）
   

  受賞者: 筌場大介
• 2022年11月 第56回日本側彎症学会学術集会 Short Symposium Award
   

  受賞者: 須藤英毅
• 2022年10月 第37回日本整形外科学会基礎学術集会最優秀演題賞（研究責任者）
   

  受賞者: 鈴木久崇
• 2022年09月 第71回東日本整形災害外科学会若手優秀演題アウォｰド最優秀賞（研究責任者）
   

  受賞者: 鈴木久崇
• 2022年07月 Computer-Aided Design and Applications, Annual CAD Conference Computer-Aided Design and Applications, Annual CAD Conference Best Paper Award
   

  受賞者: Ayane Soutome;Satoshi Kanai;Hiroaki Date;Terufumi Kokabu;Yuichiro Abe;Hiroshi Moridaira;Hiroshi Taneichi;Hideki Sudo
• 2022年04月 日本脊椎脊髄病学会奨励賞（論文責任著者）
   

  受賞者: 筌場大介、山田勝久、辻本武尊、浦勝郎、野々山貴行、岩崎倫政、須藤英毅
• 2021年12月 （厚生労働省、第一生命、朝日新聞厚生文化事業団、ＮＨＫ厚生文化事業団） 保健文化賞
   

  受賞者: 須藤英毅
• 2021年09月 North American Spine Society 2021 Best Paper Award (corresponding author)
   

  受賞者: Kokabu T, Kanai S, Kawakami N, Uno K, Kotani T, Suzuki T, Tachi H, Abe Y, Iwasaki N, Sudo H.
• 2021年03月 日本軟骨代謝学会賞（論文責任著者）
   Bone marrow mesenchymal stem cells combined with ultra-purified alginate gel as a regenerative therapeutic strategy after discectomy for degenerated intervertebral discs 

  受賞者: 筌場大介、須藤英毅、辻本武尊、浦勝郎、山田勝久、岩崎倫政
• 2020年04月 日本脊椎脊髄病学会奨励賞（論文責任著者）
   Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging 

  受賞者: 大西貴士,山田勝久,岩崎浩司,辻本武尊,東秀明,木村太一,岩崎倫政,須藤英毅
• 2020年04月 文部科学大臣表彰科学技術賞（研究部門）
   脊柱変形疾患に対する革新的医療機器の開発と実用化研究 

  受賞者: 須藤英毅(筆頭者)、金井理、千葉晶彦
• 2020年03月 日本軟骨代謝学会賞（論文責任著者）
   An acellular bioresorbable ultra-purified alginate gel promotes intervertebral disc repair: A preclinical proof-of-concept study 

  受賞者: 辻本武尊;須藤英毅;東藤正浩;山田勝久;岩崎浩司;大西貴士;廣浜直樹;野々山貴行;筌場大介;浦勝郎;伊藤陽一;岩崎倫政
• 2018年11月 Best Paper Award (17th International Conference on Precision Engineering)
   3D Asymmetry Analysis of Human’s Back Surface for Early Screening of Idiopathic Scoliosis 

  受賞者: Satoshi Kanai;Hideki Sudo;Terufumi Kokabu;Hiroshi Nagaeda;Takayuki Hayashi;Hajime Ohta
• 2018年02月 ORS/OREF Travel Grant in Orthopaedic Research Translation (Corresponding author, Orthopaedic Research Society, United States, 2018)
   The role of caspase 3 gene in intervertebral disc degeneration due to injury and aging 

  受賞者: Takashi Ohnishi;Hideki Sudo;Takeru Tsujimoto;Norimasa Iwasaki
• 2018年02月 ORS/OREF Travel Grant in Orthopaedic Research Translation (Corresponding author, Orthopaedic Research Society, United States, 2018)
   Acellular Ultra-purified Alginate Gels for Intervertebral Disc Regeneration in a Preclinical Animal Model 

  受賞者: Takeru Tsujimoto;Hideki Sudo;Masahiro Todoh;Katsuhisa Yamada;Koji Iwasaki;Takashi Ohnishi;Norimasa Iwasaki
• 2017年02月 Force & Motion Foundation/ORS Young Scientist Travel Grant (Orthopaedic Research Society, USA, Corresponding author)
   Effects of multilevel facetectomy and screw density on postoperative changes in spinal rod contour in thoracic adolescent idiopathic scoliosis surgery 

  受賞者: Kokabu Terufumi, Hideki Sudo, Yuichiro Abe, Manabu Ito, Norimasa Iwasaki
• 2017年 Biomaterials Science Presentation Prize (Royal Society of Chemistry)
   

  受賞者: 須藤英毅
• 2017年 日本バイオマテリアル学会ハイライト講演受賞
   

  受賞者: 須藤英毅
• 2017年01月 北海道大学研究総長賞
   

  受賞者: 須藤英毅
• 2016年 AOSpine Research Grant助成
   

  受賞者: 須藤英毅
• 2016年 北海道大学医学部医学科エクセレント・ティーチャー（優秀賞）
   

  受賞者: 須藤英毅
• 2015年02月 北海道科学技術奨励賞
   

  受賞者: 須藤英毅
• 2015年 John Moe Award (Scoliosis Research Society, USA)
   

  受賞者: 須藤英毅
• 2014年11月 日本医師会医学研究奨励賞
   

  受賞者: 須藤英毅
• 2012年 財団法人博慈会老人病研究所優秀論文賞（基礎部門）
   

  受賞者: 須藤英毅
• 2011年 The top scored ORS poster within Spine posters (Orthopaedic Research Society, United States)
   

  受賞者: 須藤英毅
• 2011年 第6回Asia Traveling Fellowship (日本脊椎脊髄病学会)
   

  受賞者: 須藤英毅
• 2008年 整形災害外科学研究助成財団研究助成エーザイ奨励賞
   

  受賞者: 須藤英毅
• 2005年 北海道大学医学部高桑榮松奨学基金奨励賞
   

  受賞者: 須藤英毅
• 2005年 北海道整形災害外科学会学術奨励賞
   

  受賞者: 須藤英毅

論文

• Deep learning-based detection of lumbar spinal canal stenosis using convolutional neural networks.

  Hisataka Suzuki, Terufumi Kokabu, Katsuhisa Yamada, Yoko Ishikawa, Akito Yabu, Yasushi Yanagihashi, Takahiko Hyakumachi, Hiroyuki Tachi, Tomohiro Shimizu, Tsutomu Endo, Takashi Ohnishi, Daisuke Ukeba, Ken Nagahama, Masahiko Takahata, Hideki Sudo, Norimasa Iwasaki

  The spine journal : official journal of the North American Spine Society 2024年06月22日 [査読有り]
   

  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 2024年06月08日 [査読有り]
   

  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.
• Bone Marrow Aspirate Concentrate Combined with Ultra-Purified Alginate Bioresorbable Gel Enhances Intervertebral Disc Repair in a Canine Model: A Preclinical Proof-of-Concept Study.

  Daisuke Ukeba, Yoko Ishikawa, Katsuhisa Yamada, Takashi Ohnishi, Hiroyuki Tachi, Khin Khin Tha, Norimasa Iwasaki, Hideki Sudo

  Cells 13 11 2024年06月05日 [査読有り]
   

  Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.
• Intervertebral Disc Degeneration and Regeneration: New Molecular Mechanisms and Therapeutics

  Hideki Sudo

  Cells 13 2 153 - 153 2024年01月15日 [査読有り][招待有り]
   

  The intervertebral disc (IVD) is a soft tissue that constitutes the spinal column together with the vertebrae, and consists of the central nucleus pulposus (gelatinous tissue) and the annulus fibrosus (rich in fibrous tissue) that surrounds the nucleus pulposus [...]
• Development of Notch-Free, Pre-Bent Rod Applicable for Posterior Corrective Surgery of Thoracolumbar/Lumbar Adolescent Idiopathic Scoliosis.

  Yoko Ishikawa, Satoshi Kanai, Katsuro Ura, Terufumi Kokabu, Katsuhisa Yamada, Yuichiro Abe, Hiroyuki Tachi, Hisataka Suzuki, Takashi Ohnishi, Tsutomu Endo, Daisuke Ukeba, Masahiko Takahata, Norimasa Iwasaki, Hideki Sudo

  Journal of clinical medicine 12 17 2023年09月04日 [査読有り][通常論文]
   

  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.
• A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration.

  Takashi Ohnishi, Kentaro Homan, Akira Fukushima, Daisuke Ukeba, Norimasa Iwasaki, Hideki Sudo

  Cells 12 17 2023年08月28日 [査読有り][通常論文]
   

  Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.
• High whole-body bone mineral density in ossification of the posterior longitudinal ligament.

  Ryo Fujita, Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Daisuke Yoneoka, Ryota Suzuki, Masaru Tanaka, Katsuhisa Yamada, Hideki Sudo, Tomoka Hasegawa, Mohamad Alaa Terkawi, Ken Kadoya, Norimasa Iwasaki

  The spine journal : official journal of the North American Spine Society 23 10 1461 - 1470 2023年07月10日 [査読有り]
   

  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.
• Factors Affecting Transcranial Motor-Evoked Potential Measurements Using Single-Train Stimulation with an Increased Number of Pulses during Adolescent Scoliosis Surgery: A Prospective Observational Study.

  Takayuki Toki, Noriaki Fujita, Tomohiro Ichikawa, Noriki Ochi, Isao Yokota, Hideki Sudo, Yuji Morimoto

  Journal of clinical medicine 12 13 2023年06月30日 [査読有り][通常論文]
   

  Measurement of transcranial motor-evoked potentials (TcMEPs) during scoliosis surgery helps detect postoperative new neurological defects. However, TcMEP interpretation is difficult owing to the influence of intraoperative physiological, pharmacological, and time-related factors as well as stimulation conditions. In this study, we aimed to investigate the effect of the abovementioned factors on TcMEP amplitude using single-train stimulation with an increased number of pulses (STS-INP) during adolescent scoliosis surgery; moreover, we evaluated the complications of TcMEP measurement. We included 50 patients and 706 TcMEP measurements. A total of 1412 TcMEP waveforms were analyzed, each on the bilateral abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles. We estimated the mean difference (95% confidence interval (CI)) and predicted mean difference (95% CI) evaluated using the interquartile range of each factor, based on a mixed-effect model with random intercepts for TcMEP amplitude. The predicted mean differences in TcMEP amplitude were clinically small compared with the actual TcMEP amplitude, suggesting that each factor had a limited effect on TcMEP amplitude. No intraoperative bite injuries or seizures were observed. Using STS-INP during adolescent scoliosis surgery may enable accurate measurement of TcMEP amplitude with neither complications nor the influence of various intraoperative factors.
• Quantitative Assessment of Intervertebral Disc Composition by MRI: Sensitivity to Diurnal Variation.

  Hiroyuki Hamaguchi, Maho Kitagawa, Daiki Sakamoto, Ulrich Katscher, Hideki Sudo, Katsuhisa Yamada, Kohsuke Kudo, Khin Khin Tha

  Tomography (Ann Arbor, Mich.) 9 3 1029 - 1040 2023年05月16日 [査読有り][通常論文]
   

  Whether diurnal variation exists in quantitative MRI indices such as the T1rho relaxation time (T1ρ) of the intervertebral disc (IVD) is yet to be explored. This prospective study aimed to evaluate the diurnal variation in T1ρ, apparent diffusion coefficient (ADC), and electrical conductivity (σ) of lumbar IVD and its relationship with other MRI or clinical indices. Lumbar spine MRI, including T1ρ imaging, diffusion-weighted imaging (DWI), and electric properties tomography (EPT), was conducted on 17 sedentary workers twice (morning and evening) on the same day. The T1ρ, ADC, and σ of IVD were compared between the time points. Their diurnal variation, if any, was tested for correlation with age, body mass index (BMI), IVD level, Pfirrmann grade, scan interval, and diurnal variation in IVD height index. The results showed a significant decrease in T1ρ and ADC and a significant increase in the σ of IVD in the evening. T1ρ variation had a weak correlation with age and scan interval, and ADC variation with scan interval. Diurnal variation exists for the T1ρ, ADC, and σ of lumbar IVD, which should be accounted for in image interpretation. This variation is thought to be due to diurnal variations in intradiscal water, proteoglycan, and sodium ion concentration.
• Dyslipidemia as a novel risk for the development of symptomatic ossification of the posterior longitudinal ligament.

  Shotaro Fukada, Tsutomu Endo, Masahiko Takahata, Masahiro Kanayama, Yoshinao Koike, Ryo Fujita, Ryota Suzuki, Toshifumi Murakami, Tomoka Hasegawa, Mohamad Alaa Terkawi, Tomoyuki Hashimoto, Kastuhisa Yamada, Hideki Sudo, Ken Kadoya, Norimasa Iwasaki

  The spine journal : official journal of the North American Spine Society 23 9 1287 - 1295 2023年05月07日 [査読有り][通常論文]
   

  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 2023年04月28日 [査読有り][通常論文]
   

  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.
• 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 2023年02月09日 [査読有り][通常論文]
   

  This study aimed to evaluate the lowest instrumented vertebra translation (LIV-T) in the surgical treatment of thoracolumbar/lumbar adolescent idiopathic scoliosis and to analyze the radiographic parameters in relation to LIV-T and L4 tilt and global coronal balance. A total of 62 patients underwent posterior spinal fusion (PSF, n = 32) or anterior spinal fusion (ASF, n = 30) and were followed up for a minimum of 2 years. The mean preoperative LIV-T was significantly larger in the ASF group than the PSF (p < 0.01), while the final LIV-T was equivalent. LIV-T at the final follow-up was significantly correlated with L4 tilt and the global coronal balance (r = 0.69, p < 0.01, r = 0.38, p < 0.01, respectively). Receiver-operating characteristic analysis for good outcomes, with L4 tilt <8° and coronal balance <15 mm at the final follow-up, calculated the cutoff value of the final LIV-T as 12 mm. The cutoff value of preoperative LIV-T that would result in the LIV-T of ≤12 mm at the final follow-up was 32 mm in PSF, although no significant cutoff value was calculated in ASF. ASF can centralize the LIV better than PSF with a shorter segment fusion, and could be useful in obtaining a good curve correction and global balance without fixation to L4 in cases with large preoperative LIV-T.
• Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model

  Hisataka Suzuki, Katsuro Ura, Daisuke Ukeba, Takashi Suyama, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Katsuhisa Yamada, Hideki Sudo

  Cells 12 3 505 - 505 2023年02月03日 [査読有り][通常論文]
   

  Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA (p < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (p < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (p < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.
• Protocol for treating lumbar spinal canal stenosis with a combination of ultrapurified, allogenic bone marrow-derived mesenchymal stem cells and in situ-forming gel: a multicentre, prospective, double-blind randomised controlled trial.

  Hideki Sudo, Takashi Miyakoshi, Yudai Watanabe, Yoichi M Ito, Kaoru Kahata, Khin Khin Tha, Nozomi Yokota, Hiroe Kato, Tomoko Terada, Norimasa Iwasaki, Teruyo Arato, Norihiro Sato, Toshiyuki Isoe

  BMJ open 13 2 e065476  2023年02月02日 [査読有り][通常論文]
   

  INTRODUCTION: In patients with combined lumbar spinal canal stenosis (LSCS), a herniated intervertebral disc (IVD) that compresses the dura mater and nerve roots is surgically treated with discectomy after laminoplasty. However, defects in the IVD after discectomy may lead to inadequate tissue healing and predispose patients to the development of IVD degeneration. Ultrapurified stem cells (rapidly expanding clones (RECs)), combined with an in situ-forming bioresorbable gel (dMD-001), have been developed to fill IVD defects and prevent IVD degeneration after discectomy. We aim to investigate the safety and efficacy of a new treatment method in which a combination of REC and dMD-001 is implanted into the IVD of patients with combined LSCS. METHODS AND ANALYSIS: This is a multicentre, prospective, double-blind randomised controlled trial. Forty-five participants aged 20-75 years diagnosed with combined LSCS will be assessed for eligibility. After performing laminoplasty and discectomy, participants will be randomised 1:1:1 into the combination of REC and dMD-001 (REC-dMD-001) group, the dMD-001 group or the laminoplasty and discectomy alone (control) group. The primary outcomes of the trial will be the safety and effectiveness of the procedure. The effectiveness will be assessed using visual analogue scale scores of back pain and leg pain as well as MRI-based estimations of morphological and compositional quality of the IVD tissue. Secondary outcomes will include self-assessed clinical scores and other MRI-based estimations of compositional quality of the IVD tissue. All evaluations will be performed at baseline and at 1, 4, 12, 24 and 48 weeks after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees of the institutions involved. We plan to conduct dissemination of the outcome data by presenting our data at national and international conferences, as well as through formal publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCT2013210076.
• Lumbar ossification of the ligamentum flavum reflects a strong ossification tendency of the entire spinal ligament.

  Kazuha Nakabachi, Tsutomu Endo, Masahiko Takahata, Ryo Fujita, Yoshinao Koike, Ryota Suzuki, Yuichi Hasegawa, Toshifumi Murakami, Katsuhisa Yamada, Hideki Sudo, Mohamad Alaa Terkawi, Ken Kadoya, Norimasa Iwasaki

  Scientific reports 13 1 638 - 638 2023年01月12日 [査読有り][通常論文]
   

  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 2023年01月07日 [査読有り][通常論文]
   

  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.
• Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.

  Yoshiro Yonezawa, Long Guo, Hisaya Kakinuma, Nao Otomo, Soichiro Yoshino, Kazuki Takeda, Masahiro Nakajima, Toshiyuki Shiraki, Yoji Ogura, Yohei Takahashi, Yoshinao Koike, Shohei Minami, Koki Uno, Noriaki Kawakami, Manabu Ito, Ikuho Yonezawa, Kei Watanabe, Takashi Kaito, Haruhisa Yanagida, Hiroshi Taneichi, Katsumi Harimaya, Yuki Taniguchi, Hideki Shigematsu, Takahiro Iida, Satoru Demura, Ryo Sugawara, Nobuyuki Fujita, Mitsuru Yagi, Eijiro Okada, Naobumi Hosogane, Katsuki Kono, Kazuhiro Chiba, Toshiaki Kotani, Tsuyoshi Sakuma, Tsutomu Akazawa, Teppei Suzuki, Kotaro Nishida, Kenichiro Kakutani, Taichi Tsuji, Hideki Sudo, Akira Iwata, Tatsuya Sato, Satoshi Inami, Masaya Nakamura, Morio Matsumoto, Chikashi Terao, Kota Watanabe, Hitoshi Okamoto, Shiro Ikegawa

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38 1 144 - 153 2023年01月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).
• Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments.

  Tsutomu Endo, Masahiko Takahata, Ryo Fujita, Yoshinao Koike, Ryota Suzuki, Yuichi Hasegawa, Toshifumi Murakami, Misaki Ishii, Katsuhisa Yamada, Hideki Sudo, Norimasa Iwasaki

  Scientific reports 12 1 22617 - 22617 2022年12月30日 [査読有り]
   

  Obesity and metabolic disturbances are prevalent in ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF); however, the involvement of dyslipidemia (DL) in OPLL/OLF remains uncertain. We investigated the association between dyslipidemia and OPLL/OLF using a dataset of 458 individuals receiving health screening tests, including computed tomography. Subjects were grouped according to the presence or location of OPLL/OLF: controls (no OPLL/OLF, n = 230), OLF (n = 167), cervical OPLL (n = 28), and thoracic OPLL (n = 33). They were also grouped according to the presence of dyslipidemia (DL[+], n = 215; DL[-], n = 243). The proportion of dyslipidemia in the OLF and OPLL groups was 1.6-2.2 times higher than that in the control group. The proportion of OLF and OPLL in the DL(+) group was significantly higher than that in the DL(-) group (OLF, 43% vs. 29%; cervical OPLL, 14.4% vs. 3.2%; thoracic OPLL, 11.1% vs. 3.7%). Multivariate logistic regression analysis showed an association between all ossification types and dyslipidemia. This study demonstrated an association of dyslipidemia with OPLL/OLF; further investigation on the causal relationship between dyslipidemia and ectopic spinal ligament ossification is warranted to develop a therapeutic intervention for OPLL/OLF.
• Effects of Posterior Spinal Correction and Fusion on Postural Stability in Patients with Adolescent Idiopathic Scoliosis.

  Satoshi Osuka, Hideki Sudo, Katsuhisa Yamada, Hiroyuki Tachi, Kentaro Watanabe, Fuma Sentoku, Takeshi Chiba, Norimasa Iwasaki, Masahiko Mukaino, Harukazu Tohyama

  Journal of clinical medicine 12 1 2022年12月29日 [査読有り][通常論文]
   

  The present study aimed to assess the effects of posterior spinal correction and fusion on postural stability in patients with adolescent idiopathic scoliosis (AIS). The study included 41 female patients with AIS at our institution. All patients performed three 10 s single-leg standing trials on a force plate. The center of pressure (COP) was measured preoperatively, and at 1 week and 6 months postoperatively. The postural stability parameters were absolute minimum time-to-boundary (TTB), mean of the minimum TTB, mean COP velocity, standard deviation, range, and 95% confidence ellipse area. One-way repeated analysis of variance or Friedman test was applied to the postural stability parameters. Multiple comparisons were performed using the Bonferroni correction. The absolute minimum TTB and the mean minimum TTB showed a significant increase 6 months post-operation as compared to preoperatively and 1 week postoperatively. The COP velocity significantly decreased at 6 months post-operation compared to preoperatively and 1 week postoperatively. These changes in postural stability indicate that spinal correction and fusion can be considered to improve postural stability during single-leg standing tests in the postoperative period.
• 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 2022年11月24日 [査読有り][通常論文]
  
• 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 2022年10月15日 [査読有り][通常論文]
   

  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.
• Dual-Rod Instrumentation Via the Anterior Approach in Thoracolumbar and Lumbar Adolescent Idiopathic Scoliosis

  Hideki Sudo

  JBJS Essential Surgical Techniques 2022年10月 [査読有り][通常論文]
  
• Preliminary shape similarity analysis and standardization for pre-bent rod design for adult spinal deformity correction

  Soutome A, Kanai S, Date H, Kokabu T, Abe Y, Moridaira H, Taneichi H, Sudo H

  Comput Aided Des Appl 2022年08月 [査読有り][通常論文]
  
• 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 2022年03月04日 [査読有り][通常論文]
   

  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.
• Four-dimensional anatomical spinal reconstruction in thoracic adolescent idiopathic scoliosis

  Hideki Sudo

  JBJS Essential Surgical Techniques 2022年02月 [査読有り][通常論文]
  
• Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review.

  Takashi Ohnishi, Norimasa Iwasaki, Hideki Sudo

  Cells 11 3 2022年01月24日 

  Intervertebral disc degeneration (IVDD) is a pathological condition that can lead to intractable back pain or secondary neurological deficits. There is no fundamental cure for this condition, and current treatments focus on alleviating symptoms indirectly. Numerous studies have been performed to date, and the major strategy for all treatments of IVDD is to prevent cell loss due to programmed or regulated cell death. Accumulating evidence suggests that several types of cell death other than apoptosis, including necroptosis, pyroptosis, and ferroptosis, are also involved in IVDD. In this study, we discuss the molecular pathway of each type of cell death and review the literature that has identified their role in IVDD. We also summarize the recent advances in targeted therapy at the RNA level, including RNA modulations through RNA interference and regulation of non-coding RNAs, for preventing cell death and subsequent IVDD. Therefore, we review the causes and possible therapeutic targets for RNA intervention and discuss the future direction of this research field.
• Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration.

  Daisuke Ukeba, Katsuhisa Yamada, Takashi Suyama, Darren R Lebl, Takeru Tsujimoto, Takayuki Nonoyama, Hirokazu Sugino, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Hideki Sudo

  EBioMedicine 76 103845 - 103845 2022年01月24日 [査読有り]
   

  BACKGROUND: Lumbar intervertebral disc (IVD) herniations are associated with significant disability. Discectomy is the conventional treatment option for IVD herniations but causes a defect in the IVD, which has low self-repair ability, thereby representing a risk of further IVD degeneration. An acellular, bioresorbable, and good manufacturing practice (GMP)-compliant in situ-forming gel, which corrects discectomy-associated IVD defects and prevents further IVD degeneration had been developed. However, this acellular matrix-based strategy has certain limitations, particularly in elderly patients, whose tissues have low self-repair ability. The aim of this study was to investigate the therapeutic efficacy of using a combination of newly-developed, ultra-purified, GMP-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs) and the gel for IVD regeneration after discectomy in a sheep model of severe IVD degeneration. METHODS: RECs and nucleus pulposus cells (NPCs) were co-cultured in the gel. In addition, RECs combined with the gel were implanted into IVDs following discectomy in sheep with degenerated IVDs. FINDINGS: Gene expression of NPC markers, growth factors, and extracellular matrix increased significantly in the co-culture compared to that in each mono-culture. The REC and gel combination enhanced IVD regeneration after discectomy (up to 24 weeks) in the severe IVD degeneration sheep model. INTERPRETATION: These findings demonstrate the translational potential of the combination of RECs with an in situ-forming gel for the treatment of herniations in degenerative human IVDs. FUNDING: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
• Radical resection for solitary thoracic spinous-process metastasis: a case report and technical note.

  Chikako Ishii, Akira Iwata, Katsuhisa Yamada, Tsutomu Endo, Takeru Tsujimoto, Hideki Sudo, Ai Shimizu, Norimasa Iwasaki, Masahiko Takahata

  Spinal cord series and cases 8 1 8 - 8 2022年01月17日 [査読有り]
   

  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.
• Association between obesity and ossification of spinal ligaments in 622 asymptomatic subjects: a cross-sectional study.

  Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Ryo Fujita, Ryota Suzuki, Yuichiro Hisada, Yuichi Hasegawa, Hisataka Suzuki, Katsuhisa Yamada, Akira Iwata, Hideki Sudo, Daisuke Yoneoka, Norimasa Iwasaki

  Journal of bone and mineral metabolism 40 2 337 - 347 2022年01月16日 [査読有り]
   

  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.
• Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation

  Yamada K, Iwasaki N, Sudo H

  Cells 11 4 2022年01月 [査読有り]
   

  Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation.
• Causes of and molecular targets for the treatment of intervertebral disc degeneration: a review

  Ohnishi T, Iwasaki N, Sudo H

  Cells 2022年01月 [査読有り][通常論文]
  
• Surgical outcome prediction using a four-dimensional planning simulation system with finite element analysis incorporating pre-bent rods in adolescent idiopathic scoliosis: Simulation for spatiotemporal anatomical correction technique

  Tachi H, Kato K, Abe Y, Kokabu T, Yamada K, Iwasaki N, Sudo H

  Frontiers in Bioengineering and Biotechnology 9 746902 - 746902 2021年10月 [査読有り][通常論文]
   

  An optimal surgical strategy for adolescent idiopathic scoliosis (AIS) is to provide maximal deformity correction while preserving spinal mobile segments as much as possible and obtaining a balanced posture. From a spatiotemporal deformity correction standpoint, we recently showed that anatomical four-dimensional (4D) spinal correction could be accomplished by curving the rod. In the surgical procedure, two rods are bent identically to confirm spinal anatomical alignment without referring to the intraoperative alignment of the deformity. Therefore, anatomically designed rods have been developed as notch-free, pre-bent rods for easier anatomical reconstruction. In addition to providing the best spinal instrumentation configurations as pre-bent rods, prediction of surgical outcome along with its biomechanical impact can be obtained by simulation of the surgical procedures with computer modeling. However, an objective model that can simulate the surgical outcome in patients with AIS has not been completely elucidated. The present study aimed to compare simulated deformity corrections based on our newly developed spatiotemporal morphological 4D planning simulation system incorporating pre-bent rods and actual deformity corrections in patients with AIS. A consecutive series of 47 patients who underwent anatomical posterior correction for AIS curves were prospectively evaluated. After multilevel facetectomy, except for the lowest instrumented segment, 11 types of pre-bent rods were used. Patient demographic data, radiographic measurements, and sagittal rod angles were analyzed within 1 week of surgery. Our simulation system incorporating pre-bent rods showed a significant correlation with the actual postoperative spinal alignment. The present study demonstrated the feasibility of our simulation system and the ability to simulate the surgical procedure using the pre-bent rods. The simulation system can be used to minimize the differences between the optimal and possible outcomes related to the instrumentation levels and rod shapes. Preoperative assumption of rod shape and length can contribute to a reduction in operative time which decreases blood loss and risk of infection. The results of the finite element analysis in the simulation system measured for each individual patient would also provide a more realistic representation of the surgical procedures.
• Thrombocytopenia associated with unrecognized non-alcoholic fatty liver disease is an independent predictor of perioperative significant blood loss in cervical laminoplasty.

  Ryota Suzuki, Yoshinao Koike, Masahiro Ota, Tsutomu Endo, Yuichiro Hisada, Takeru Tsujimoto, Masahiro Kanayama, Yoichi M Ito, Hideki Sudo, Akira Iwata, Katsuhisa Yamada, Norimasa Iwasaki, Masahiko Takahata

  World neurosurgery 155 e797-e804  2021年09月09日 [査読有り][通常論文]
   

  OBJECTIVE: This study aimed 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 (FIB-4) index and considered FIB-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 to the non-SBL group, the SBL group demonstrated significantly lower platelet count (PLT), lower AST, 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 x 104 /μL using a receiver operating characteristic curve. The liver fibrosis group revealed significantly lower PLT and higher EBL+D than the non-liver fibrosis group, CONCLUSIONS: Thrombocytopenia is an independent predictor of perioperative SBL in cervical laminoplasty. Thus, patients with mild thrombocytopenia that may be associated with NAFLD must be carefully monitored to avoid perioperative SBL.
• Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study.

  Katsuhisa Yamada, Maeda Kenichiro, Yoichi M Ito, Fujio Inage, Toshiyuki Isoe, Nozomi Yokota, Osamu Sugita, Norihiro Sato, Khin Khin Tha, Norimasa Iwasaki, Teruyo Arato, Hideki Sudo

  Contemporary clinical trials communications 23 100805 - 100805 2021年09月 [査読有り][通常論文]
   

  Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.
• Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use.

  Nao Otomo, Hsing-Fang Lu, Masaru Koido, Ikuyo Kou, Kazuki Takeda, Yukihide Momozawa, Michiaki Kubo, Yoichiro Kamatani, Yoji Ogura, Yohei Takahashi, Masahiro Nakajima, Shohei Minami, Koki Uno, Noriaki Kawakami, Manabu Ito, Tatsuya Sato, Kei Watanabe, Takashi Kaito, Haruhisa Yanagida, Hiroshi Taneichi, Katsumi Harimaya, Yuki Taniguchi, Hideki Shigematsu, Takahiro Iida, Satoru Demura, Ryo Sugawara, Nobuyuki Fujita, Mitsuru Yagi, Eijiro Okada, Naobumi Hosogane, Katsuki Kono, Masaya Nakamura, Kazuhiro Chiba, Toshiaki Kotani, Tsuyoshi Sakuma, Tsutomu Akazawa, Teppei Suzuki, Kotaro Nishida, Kenichiro Kakutani, Taichi Tsuji, Hideki Sudo, Akira Iwata, Kazuo Kaneko, Satoshi Inami, Yuta Kochi, Wei-Chiao Chang, Morio Matsumoto, Kota Watanabe, Shiro Ikegawa, Chikashi Terao

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 36 8 1481 - 1491 2021年08月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10-40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10-10 ) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10-8 ), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10-4 ). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).
• In vivo deformation of anatomically pre-bent rods in thoracic adolescent idiopathic scoliosis.

  Hideki Sudo, Hiroyuki Tachi, Terufumi Kokabu, Katsuhisa Yamada, Akira Iwata, Tsutomu Endo, Masahiko Takahata, Yuichiro Abe, Norimasa Iwasaki

  Scientific reports 11 1 12622 - 12622 2021年06月16日 [査読有り][通常論文]
   

  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.
• Impact of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis.

  Terufumi Kokabu, Yuichiro Abe, Katsuhisa Yamada, Norimasa Iwasaki, Hideki Sudo

  Clinical biomechanics (Bristol, Avon) 83 105296 - 105296 2021年03月 [査読有り]
   

  BACKGROUND: The aim of this study was to intraoperatively assess the effects of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis. METHODS: Twenty patients who underwent posterior thoracic adolescent idiopathic scoliosis curve correction were evaluated. Compressive or distractive loaded force of 50N was applied on the handle of a compressor or distractor connected to the necks of pedicle screws inserted at T7 to T11. Segmental spinal flexibility rates were calculated based on the distance between screw heads under the loaded and unloaded conditions. In addition, the flexibility rates were obtained before and after multilevel facetectomy. FINDINGS: Absolute flexibility rates of all segments significantly increased after multilevel facetectomy under both compressive and distractive forces (P < 0.01). The absolute change in the flexibility rate was significantly higher at the concave side than at the convex side under both compressive (P < 0.01) and distractive loaded forces (P = 0.046). No significant correlation was found between change in the flexibility rates and preoperative Cobb angle or preoperative curve flexibility. INTERPRETATION: From a biomechanical point of view, multilevel facetectomy provides proper spinal flexibility to improve the correction rate of posterior adolescent idiopathic scoliosis surgery. The effects are higher at the concave side than at the convex side.
• An algorithm for using deep learning convolutional neural networks with three dimensional depth sensor imaging in scoliosis detection

  Terufumi Kokabu, Satoshi Kanai, Noriaki Kawakami, Koki Uno, Toshiaki Kotani, Teppei Suzuki, Hiroyuki Tachi, Yuichiro Abe, Norimasa Iwasaki, Hideki Sudo

  Spine J 2021年02月 [査読有り][通常論文]
  
• Bone Marrow Aspirate Concentrate Combined with in Situ Forming Bioresorbable Gel Enhances Intervertebral Disc Regeneration in Rabbits.

  Daisuke Ukeba, Katsuhisa Yamada, Takeru Tsujimoto, Katsuro Ura, Takayuki Nonoyama, Norimasa Iwasaki, Hideki Sudo

  The Journal of bone and joint surgery. American volume 103 8 e31  2021年01月21日 [査読有り]
   

  BACKGROUND: The current surgical procedure of choice for intervertebral disc (IVD) herniation is discectomy, which induces postoperative IVD degeneration. Thus, cell-based therapies, as a 1-step simple procedure, are desired because of the poor capacity of IVDs for self-repair. The aim of this study was to investigate the repair efficacy of ultra-purified alginate (UPAL) gels containing bone marrow aspirate concentrate (BMAC) for the treatment of discectomy-associated IVD degeneration in rabbits. METHODS: The mechanical properties of 3 types of gels-UPAL, UPAL containing bone marrow-derived mesenchymal stem cells (BMSCs), and UPAL containing BMAC-were evaluated. Forty rabbits were assigned to 5 groups: intact control, discectomy (to make the cavity), UPAL (implantation of the UPAL gel after discectomy), BMSCs-UPAL (implantation of a combination of autogenic BMSCs and UPAL gel after discectomy), and BMAC-UPAL (implantation of a combination of BMAC and UPAL gel after discectomy). The gels were implanted at 4 weeks after induction of IVD degeneration. At 4 and 12 weeks, magnetic resonance imaging (MRI) as well as histological and immunohistochemical analyses were performed to analyze IVD degeneration qualitatively and the viability of the implanted cells. RESULTS: There was no significant difference among the 3 types of gels in terms of the results of unconfined compression tests. The implanted cells survived for 12 weeks. The histological grades of the BMSCs-UPAL (mean and standard deviation, 2.50 ± 0.53; p < 0.001) and BMAC-UPAL (2.75 ± 0.64, p = 0.001) showed them to be more effective in preventing degeneration than UPAL gel alone (3.63 ± 0.52). The effectiveness of BMAC-UPAL was not significantly different from that of BMSCs-UPAL, except with respect to type-II collagen synthesis. CONCLUSIONS: BMAC-UPAL significantly enhanced the repair of IVD defects created by discectomy. This approach could be an effective therapeutic strategy owing to its simplicity and cost-effectiveness compared with cell therapy using culture-expanded BMSCs. CLINICAL RELEVANCE: Local administration of the BMAC combined with UPAL gel could be an effective therapeutic strategy to enhance IVD repair after discectomy.
• Ultra-purified alginate gel implantation decreases inflammatory cytokine levels, prevents intervertebral disc degeneration, and reduces acute pain after discectomy.

  Katsuro Ura, Katsuhisa Yamada, Takeru Tsujimoto, Daisuke Ukeba, Norimasa Iwasaki, Hideki Sudo

  Scientific reports 11 1 638 - 638 2021年01月12日 [査読有り][通常論文]
   

  Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy.
• Risk factors of multidrug-resistant pyogenic spondylitis in thoraco-lumbar spine: A retrospective study of 122 cases.

  Katsuhisa Yamada, Masahiko Takahata, Manabu Ito, Ken Nagahama, Akira Iwata, Tsutomu Endo, Hideki Sudo, Nobuhisa Ishiguro, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 27 1 95 - 100 2021年01月06日 [査読有り]
   

  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.
• Aggravation of ossified ligamentum flavum lesion is associated with the degree of obesity

  Endo T, Koike Y, Hisada Y, Fujita R, Suzuki R, Tanaka M, Tsujimoto T, Shimamura Y, Hasegawa Y, Kanayama M, Yamada K, Iwata A, Sudo H, Ishii M, Iwasaki N, Takahata M

  Global Spine Journal 13 5 21925682211031514 - 21925682211031514 2021年 [査読有り]
   

  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.
• Expert consensus on surgical treatment for adolescent idiopathic scoliosis in Japan.

  Hideyuki Arima, Tetsuro Ohba, Daisuke Kudo, Hideki Shigematsu, Takashi Kaito, Wataru Saito, Hideki Sudo, Shoji Seki, Mitsuru Yagi, Manabu Ito, Daisuke Sakai

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 26 5 765 - 773 2020年09月18日 [査読有り]
   

  BACKGROUND: Surgical treatment for adolescent idiopathic scoliosis (AIS) has changed significantly with the advent of new medical devices and surgical procedures. Today, pre- and postoperative management differs widely between institutions. The purpose of this study is to establish consensus regarding the surgical management of AIS in Japan through the use of a questionnaire survey of experienced spine deformity surgeons. METHODS: From February to March 2020, experienced spine deformity surgeons who perform more than 25 cases of AIS surgery annually were asked to respond to a questionnaire request regarding AIS surgical management formulated by the International Affairs Committee of the Japanese Scoliosis Society. For each of the questions, consensus was achieved upon a 70% agreement among respondents. RESULTS: Responses were received from 25 of the 32 (78%) experienced spine deformity surgeons. The average age of the responding surgeons was 52 years with an average practice experience of 28 year. Consensus was achieved on 74 (76%) of the 97 aspects of care presented in the questionnaire and is broken down as follows: 12 of 17 items for preoperative management, all 5 items for perioperative management, 11 of 14 items for surgical technique, 9 of 15 items for implant selection, 6 of 8 items for bone grafting, 7 of 10 items for blood conservation, 5 of 7 items for postoperative management, all 17 items for postoperative evaluation, and 2 of 4 items for aftercare. CONCLUSIONS: Expert consensus was achieved on 74 aspects of the surgical management of AIS in Japan. In implant selection and aftercare, consensus was obtained in less than 70% of the aspects, revealing differences in AIS management between institutions. These findings on AIS surgery in Japan, informed by expert opinion, will conceivably help spine deformity surgeons determine appropriate surgical management of AIS.
• Impact of lowest instrumented vertebra tilt and rotation on uninstrumented lumbar curve and L4 tilt in thoracic adolescent idiopathic scoliosis.

  Akira Iwata, Hideki Sudo, Kuniyoshi Abumi, Manabu Ito, Katsuhisa Yamada, Norimasa Iwasaki

  Journal of neurosurgery. Spine 1 - 9 2020年06月12日 [査読有り][通常論文]
   

  OBJECTIVE: Controversy exists regarding the effects of lowest instrumented vertebra (LIV) tilt and rotation on uninstrumented lumbar segments in adolescent idiopathic scoliosis (AIS) surgery. Because the intraoperative LIV tilt from the inferior endplate of the LIV to the superior sacral endplate is not stable after surgery, the authors measured the LIV angle of the instrumented thoracic spine as the LIV angle of the construct. This study aimed to evaluate the effects of the LIV angle of the construct and the effects of LIV rotation on the postoperative uninstrumented lumbar curve and L4 tilt in patients with thoracic AIS. METHODS: A retrospective correlation and multivariate analysis of a prospectively collected, consecutive, nonrandomized series of patients at a single institution was undertaken. Eighty consecutive patients with Lenke type 1 or type 2 AIS treated with posterior correction and fusion were included. Preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study. Outcome variables were postoperative uninstrumented lumbar segments (LIV tilt, LIV translation, uninstrumented lumbar curve, thoracolumbar/lumbar [TL/L] apical vertebral translation [AVT], and L4 tilt). The LIV angle of the construct was measured from the orthogonal line drawn from the upper instrumented vertebra to the LIV. Multiple stepwise linear regression analysis was conducted between outcome variables and patient demographics/radiographic measurements. There were no study-specific biases related to conflicts of interest. RESULTS: Predictor variables for postoperative uninstrumented lumbar curve were the postoperative LIV angle of the construct, number of uninstrumented lumbar segments, and flexibility of TL/L curve. Specifically, a lower postoperative uninstrumented lumbar curve was predicted by a lower absolute value of the postoperative LIV angle of the construct (p < 0.0001). Predictor variables for postoperative L4 tilt were postoperative LIV rotation, preoperative L4 tilt, and preoperative uninstrumented lumbar curve. Specifically, a lower postoperative L4 tilt was predicted by a lower absolute value of postoperative LIV rotation (p < 0.0001). CONCLUSIONS: The LIV angle of the construct significantly affected the LIV tilt, uninstrumented lumbar curve, and TL/L AVT. LIV rotation significantly affected the LIV translation and L4 tilt.
• Mechanical Analysis of Notch-Free Pre-Bent Rods for Spinal Deformity Surgery.

  Katsuhisa Yamada, Hideki Sudo, Norimasa Iwasaki, Akihiko Chiba

  Spine 45 6 E312-E318  2020年03月15日 [査読有り][通常論文]
   

  STUDY DESIGN: Experimental study of spinal rod as per the American Society for Testing Materials (ASTM) F2193 methodology for static and dynamic four-point bending. OBJECTIVE: The hypotheses underlying this study were that the notch-free, curved rod would have a significantly higher ultimate load and fatigue strength compared with conventional notched curved rods. This study aimed to analyze the mechanical properties of notch-free curved rods compared with conventional notched rods. SUMMARY OF BACKGROUND DATA: The goal of instrumented spinal fusion in the management of spinal deformities is to realign the spine and maintain the correction and stability in order to obtain arthrodesis. Although rod curvature could play an important role, intraoperative contouring of the straight rod induces notches into the rod, leading to decreased fatigue strength. METHODS: Commercially produced titanium alloy (ϕ6.0 mm) and cobalt chromium alloy (ϕ5.5 mm) spinal rods were assessed by four-point bending tests in accordance with the ASTM F2193. RESULTS: Static four-point bending tests for the curved spinal rods showed that cobalt chromium alloy rods had significantly higher stiffness compared with titanium alloy rods. Notch-free cobalt chromium alloy rods had a significantly higher ultimate load than the conventional notched cobalt chromium alloy and titanium alloy rods. The dynamic four-point bending test showed that force/displacement at a minimum force at 2,500,000 cycles was larger in the notch-free cobalt chromium alloy rod than in the notched cobalt chromium alloy rod. CONCLUSION: The notch-free curved cobalt chromium alloy rod is likely to maintain its curvature after spinal deformity surgery with a decreased risk of breakage and could overcome the problems of the conventional notched rod such as breakage and spring-back. LEVEL OF EVIDENCE: N/A.
• Bone marrow mesenchymal stem cells combined with ultra-purified alginate gel as a regenerative therapeutic strategy after discectomy for degenerated intervertebral discs.

  Daisuke Ukeba, Hideki Sudo, Takeru Tsujimoto, Katsuro Ura, Katsuhisa Yamada, Norimasa Iwasaki

  EBioMedicine 53 102698 - 102698 2020年03月 [査読有り][通常論文]
   

  BACKGROUND: Because the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs. METHODS: Rabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs. FINDINGS: Gene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs. INTERPRETATION: These findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs. FUNDING: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
• Long-term pulmonary function after posterior spinal fusion in main thoracic adolescent idiopathic scoliosis.

  Young Man Byun, Takahiro Iida, Katsuhisa Yamada, Kuniyoshi Abumi, Terufumi Kokabu, Akira Iwata, Norimasa Iwasaki, Hideki Sudo

  PloS one 15 6 e0235123  2020年 [査読有り][通常論文]
   

  BACKGROUND: Adolescent idiopathic scoliosis (AIS) patients typically undergo surgical treatment as teenagers, follow-ups of >5 years are necessary to evaluate effects on peak pulmonary reserves. However, limited data is available regarding the long-term (>10 years) effects of surgical intervention on pulmonary function (PF) in patients with thoracic AIS. OBJECTIVE: To provide long-term (>10 years) information on the PF after posterior spinal fusion for treating main thoracic AIS. We especially investigated whether surgical correction for AIS led to impairment of the PF. METHODS: A total of 35 patients with main thoracic AIS treated with posterior spinal fusion were included. Radiographs and PF tests, which included measurements of absolute and percent-predicted values of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1), were evaluated. RESULTS: Mean age at surgery was 14.9 years (12-19 years). Mean follow-up period was 15.1 years (10-24 years). Although the final postoperative FVC and FEV1 absolute values were higher than the preoperative values, the differences were not statistically significant (p = 0.22 and p = 0.08, respectively). Percent-predicted FVC and FEV1 values between preoperative and final postoperative measurements were not statistically different (p = 0.63 and p = 0.29, respectively). However, for the patients who presented with pulmonary impairment preoperatively, both the FVC and FEV1 significantly increased at the final follow-up (p = 0.01 and p = 0.01, respectively). CONCLUSIONS: Long-term results of AIS patients who underwent posterior spinal fusion in main thoracic curves demonstrated absolute and percent-predicted PF test values similar to preoperative measurements; thus, indicating that posterior spinal fusion did not decrease PF 15 years after the initial surgery. Instead, patients with severe preoperative pulmonary impairment might show some degree of improvement after surgery.
• Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging.

  Takashi Ohnishi, Katsuhisa Yamada, Koji Iwasaki, Takeru Tsujimoto, Hideaki Higashi, Taichi Kimura, Norimasa Iwasaki, Hideki Sudo

  Scientific reports 9 1 19324 - 19324 2019年12月18日 [査読有り][通常論文]
   

  Approximately 40% of people under 30 and over 90% of people 55 or older suffer from moderate-to-severe levels of degenerative intervertebral disc (IVD) disease in their lumbar spines. Surgical treatments are sometimes effective; however, the treatment of back pain related to IVD degeneration is still a challenge; therefore, new treatments are necessary. Apoptosis may be important in IVD degeneration because suppressing cell apoptosis inside the IVD inhibits degeneration. Caspase-3, the primary effector of apoptosis, may be a key treatment target. We analyzed caspase-3's role in two different types of IVD degeneration using caspase-3 knockout (Casp-3 KO) mice. Casp-3 KO delayed IVD degeneration in the injury-induced model but accelerated it in the age-induced model. Our results suggest that this is due to different pathological mechanisms of these two types of IVD degeneration. Apoptosis was suppressed in the IVD cells of Casp-3 KO mice, but cellular senescence was enhanced. This would explain why the Casp-3 KO was effective against injury-induced, but not age-related, IVD degeneration. Our results suggest that short-term caspase-3 inhibition could be used to treat injury-induced IVD degeneration.
• Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.

  Nao Otomo, Kazuki Takeda, Shunsuke Kawai, Ikuyo Kou, Long Guo, Mitsujiro Osawa, Cantas Alev, Noriaki Kawakami, Noriko Miyake, Naomichi Matsumoto, Yukuto Yasuhiko, Toshiaki Kotani, Teppei Suzuki, Koki Uno, Hideki Sudo, Satoshi Inami, Hiroshi Taneichi, Hideki Shigematsu, Kei Watanabe, Ikuho Yonezawa, Ryo Sugawara, Yuki Taniguchi, Shohei Minami, Kazuo Kaneko, Masaya Nakamura, Morio Matsumoto, Junya Toguchida, Kota Watanabe, Shiro Ikegawa

  Journal of medical genetics 56 9 622 - 628 2019年09月 [査読有り][通常論文]
   

  BACKGROUND: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in TBX6 have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identify TBX6 variants in CS and SCD and examine their pathogenicity. METHODS: We recruited 200 patients with CS or SCD and investigated TBX6 variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments. RESULTS: We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of TBX6 and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype. CONCLUSIONS: Our study suggests that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss of TBX6 function.
• Effects of Intradiscal Injection of Local Anesthetics on Intervertebral Disc Degeneration in Rabbit Degenerated Intervertebral Disc.

  Ura K, Sudo H, Iwasaki K, Tsujimoto T, Ukeba D, Iwasaki N

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 37 9 1963 - 1971 2019年09月 [査読有り][通常論文]
   

  Analgesic discoblock is widely used for the diagnosis or treatment of discogenic low back pain by injecting local anesthetics. The purpose of this study was to investigate the deleterious effects of local anesthetics on degenerated rabbit intervertebral disks (IVDs) using an organotypic culture model and in vivo long-term follow-up model. To induce IVD degeneration, a rabbit annular puncture model was used. For the organotypic culture model, degenerated IVDs were harvested 1 month after the initial annular puncture and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine and 0.5% bupivacaine). To perform in vivo analysis, local anesthetics were injected into degenerated IVDs, and IVDs were prepared for histological analysis after 6 or 12 months. In the organotypic model, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive nucleus pulposus (NP) cells were significantly increased in the bupivacaine group compared with the other groups. In the in vivo study, the number of NP cells was significantly decreased in the saline and local anesthetics groups compared with the untreated control and puncture-only groups. However, there was no significant difference among the saline, lidocaine, and bupivacaine groups. In addition, histological analysis showed no significant difference of IVD degeneration among the puncture-only, saline, lidocaine, and bupivacaine groups. Although bupivacaine induced apoptotic NP cell death in the organotypic culture model, in vivo observations did not show any definitive proof to suggest that local anesthetics were capable of promoting degeneration in the degenerated IVD, except for pressurized injection-induced damage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1963-1971, 2019.
• Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese.

  Kou I, Otomo N, Takeda K, Momozawa Y, Lu HF, Kubo M, Kamatani Y, Ogura Y, Takahashi Y, Nakajima M, Minami S, Uno K, Kawakami N, Ito M, Yonezawa I, Watanabe K, Kaito T, Yanagida H, Taneichi H, Harimaya K, Taniguchi Y, Shigematsu H, Iida T, Demura S, Sugawara R, Fujita N, Yagi M, Okada E, Hosogane N, Kono K, Nakamura M, Chiba K, Kotani T, Sakuma T, Akazawa T, Suzuki T, Nishida K, Kakutani K, Tsuji T, Sudo H, Iwata A, Sato T, Inami S, Matsumoto M, Terao C, Watanabe K, Ikegawa S

  Nature communications 10 1 3685 - 3685 2019年08月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.
• Three-dimensional depth sensor imaging to identify adolescent idiopathic scoliosis: a prospective multicenter cohort study.

  Terufumi Kokabu, Noriaki Kawakami, Koki Uno, Toshiaki Kotani, Teppei Suzuki, Yuichiro Abe, Kenichiro Maeda, Fujio Inage, Yoichi M Ito, Norimasa Iwasaki, Hideki Sudo

  Scientific reports 9 1 9678 - 9678 2019年07月04日 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis is the most ordinary pediatric spinal disease that causes a three-dimensional deformity. Early detection of this potentially progressive deformity is considered crucial. The purpose of the present study was to report the potential for accurately diagnosis of adolescent idiopathic scoliosis using a newly developed, automated, noninvasive asymmetry-recognition system for the surface of the human back using a three-dimensional depth sensor. We included 170 subjects with suspected adolescent idiopathic scoliosis in this study. Outcomes measured included patient demographics, Cobbe angles from radiographic measurements, and asymmetry indexes. The coefficient of correlation between the asymmetry index and the Cobb angle was 0.85. For the prediction of scoliosis >10°, the area under the curve was 0.98, sensitivity was 0.97, specificity was 0.93, positive predictive value was 0.99, negative predictive value was 0.72, accuracy was 0.97, positive likelihood ratio was 13.55, and negative likelihood ratio was 0.04. The posterior test probability for the positive screen >10° was 98.9% if the asymmetry index was >1.268, three times in a row. This novel system automatically evaluated the back asymmetry. Therefore, this study demonstrates the outstanding discriminative ability of this newly developed system for deciding whether an examinee should undergo additional radiography to define scoliosis. This system can be used as an alternative to the forward bend test and scoliometer measurement in clinics. Future studies should seek to confirm these findings in a larger group and involve mass school scoliosis screening programs within the context of a multicenter trial.
• A multiethnic meta-analysis defined the association of rs12946942 with severe adolescent idiopathic scoliosis

  Kazuki Takeda, Ikuyo Kou, Nao Otomo, Anna Grauers, Yan-Hui Fan, Yoji Ogura, Yohei Takahashi, Yukihide Momozawa, Elisabet Einarsdottir, Juha Kere, Morio Matsumoto, Yong Qiu, You-Qiang Song, Paul Gerdhem, Kota Watanabe, Shiro Ikegawa, Noriaki Kawakami, Taichi Tsuji, Koki Uno, Teppei Suzuki, Manabu Ito, Shohei Minami, Toshiaki Kotani, Tsuyoshi Sakuma, Haruhisa Yanagida, Hiroshi Taneichi, Ikuho Yonezawa, Hideki Sudo, Kazuhiro Chiba, Naobumi Hosogane, Kotaro Nishida, Kenichiro Kakutani, Tsutomu Akazawa, Takashi Kaito, Kei Watanabe, Katsumi Harimaya, Yuki Taniguchi, Hideki Shigematsu, Satoru Demura, Takahiro Iida, Katsuki Kono, Eijiro Okada, Nobuyuki Fujita, Mitsuru Yagi

  JOURNAL OF HUMAN GENETICS 64 5 493 - 498 2019年05月 

  Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis. Controlling its curve progression is the most important clinical task. Although recent genome-wide association studies (GWASs) identified several susceptibility loci associated with the development of AIS, the etiology of curve progression has been still unknown. Our previous GWAS has identified that rs12946942 showed significant association with severe AIS. To confirm the association, we conducted an international meta-analysis using four cohorts with different ethnicity. We analyzed 2272 severe AIS cases and 13,859 controls in total, and found the replication of significant association of rs12946942 (combined P = 7.23x10(-13); odds ratio = 1.36, 95% confidence interval = 1.25-1.49). In silico analyses suggested that SOX9 is the most likely susceptibility gene for AIS curve progression in the locus.
• Simple method to construct process maps for additive manufacturing using a support vector machine

  Kenta Aoyagi, Hao Wang, Hideki Sudo, Akihiko Chiba

  Additive Manufacturing 27 353 - 362 2019年05月 [査読有り][通常論文]
   

  © 2019 Elsevier B.V. We propose a simple method to construct a process map for additive manufacturing using a support vector machine. By observing the surface of the built parts and classifying them into two classes (good or bad), this method enables a process map to be constructed in order to predict a process condition that is effective at fabricating a part with low pore density. This proposed method is demonstrated in a biomedical CoCr alloy system. We show that the proposed method is effective at reducing the number of experiments necessary to tailor an optimized process condition. This study also shows that the value of a decision function in a support vector machine has a physical meaning (at least in the proposed method) and is a semi-quantitative guideline for porosity density of parts fabricated by additive manufacturing.
• Long-Term Changes in Vertebral Morphology After Cervical Spinal Fusion in Adolescent Pediatric Patients: Retrospective Case Series with up to a Minimum 12 Years of Follow-up.

  Yuichiro Abe, Katsuhisa Yamada, Kuniyoshi Abumi, Norimasa Iwasaki, Hideki Sudo

  World neurosurgery 122 e765-e772 - e772 2019年02月 [査読有り][通常論文]
   

  OBJECTIVE: The mechanical alteration in the adolescent/pediatric cervical spine after spinal fusion remains unknown. The purpose of this study was to investigate morphologic changes in the cervical spine in adolescent/pediatric patients who underwent spinal fusion. METHODS: Ten adolescent/pediatric patients (9-18 years) who underwent cervical spinal fusion were included. The anteroposterior diameter (AP-D) of the vertebral body was evaluated using lateral radiographs. The AP-D ratio was defined as the ratio of the AP-D at final follow-up to the postoperative value. The kyphosis angles at the fused level and cervical spine (C2-C7) also were measured. RESULTS: The mean follow-up period was 20.0 years (range, 12-40 years). The AP-D was reduced in 4 patients and increased or remained unchanged in 6 patients. The AP-D reduction was usually seen at the middle of the fused levels and was remarkable in patients who underwent kyphosis correction using posterior instrumentation combined with anterior fusion. The AP-D ratio was significantly correlated to segments of anterior fusion (P = 0.029) and the kyphosis angle of the fused levels (P = 0.016). CONCLUSIONS: Cervical kyphosis correction using posterior instrumentation combined with endplate destruction by anterior bone grafting is a risk factor for atrophic morphologic changes in the vertebral body in adolescent/pediatric patients. Endplate destruction and instrumentation-induced stress shielding could alter bone remodeling.
• An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis

  Yoji Ogura, Kazuki Takeda, Ikuyo Kou, Anas Khanshour, Anna Grauers, Hang Zhou, Gang Liu, Yan-Hui Fan, Taifeng Zhou, Zhihong Wu, Yohei Takahashi, Morio Matsumoto, Noriaki Kawakami, Taichi Tsuji, Koki Uno, Teppei Suzuki, Manabu Ito, Shohei Minami, Toshiaki Kotani, Tsuyoshi Sakuma, Haruhisa Yanagida, Hiroshi Taneichi, Ikuho Yonezawa, Hideki Sudo, Kazuhiro Chiba, Naobumi Hosogane, Kotaro Nishida, Kenichiro Kakutani, Tsutomu Akazawa, Takashi Kaito, Kei Watanabe, Katsumi Harimaya, Yuki Taniguchi, Hideki Shigematsu, Satoru Demura, Takahiro Iida, Katsuki Kono, Eijiro Okada, Nobuyuki Fujita, Mitsuru Yagi, Masaya Nakamura, Lori A. Karol, Karl E. Rathjen, Daniel J. Sucato, John G. Birch, Charles E. Johnston, Benjamin S. Richards, Brandon Ramo, Amy L. McIntosh, John A. Herring, Todd A. Milbrandt, Vishwas R. Talwakar, Henry J. Iwinski, Ryan D. Muchow, J. Channing Tassone, X. C. Liu, Richard Shindell, William Schrader, Craig Eberson, Anthony Lapinsky, Randall Loder, Joseph Davey, Elisabet Einarsdottir, Juha Kere, Dongsheng Huang, Guixing Qiu, Leilei Xu, Yong Qiu, Carol A. Wise, You-Qiang Song, Nan Wu, Peiqiang Su, Paul Gerdhem, Kota Watanabe, Shiro Ikegawa

  Scientific Reports 8 1 2018年12月01日 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-Analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10-18 (odds ratio = 1.19, 95% confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.
• Automated noninvasive detection of idiopathic scoliosis in children and adolescents: A principle validation study.

  Sudo H, Kokabu T, Abe Y, Iwata A, Yamada K, Ito YM, Iwasaki N, Kanai S

  Scientific reports 8 1 17714 - 17714 2018年12月 [査読有り][通常論文]
   

  Idiopathic scoliosis is the most common pediatric musculoskeletal disorder that causes a three-dimensional deformity of the spine. Early detection of this progressive aliment is essential. The aim of this study is to determine outcomes using a newly developed automated asymmetry-evaluation system for the surface of the human back using a three-dimensional depth sensor. Seventy-six human subjects suspected to have idiopathic scoliosis were included in this study. Outcome measures include patient demographics, radiographic measurements, and asymmetry indexes defined in the automated asymmetry-recognition system. The mean time from scanning to analysis was 1.5 seconds. For predicting idiopathic scoliosis of greater than 25°, the area under the curve was 0.96, sensitivity was 0.97, and specificity was 0.88. The coefficient of variation for repeatability analyses using phantom models was 1-4%. The intraclass correlation coefficient obtained for intra-observer repeatability for human subjects was 0.995. The system three-dimensionally scans multiple points on the back, enabling an automated evaluation of the back's asymmetry in a few seconds. This study demonstrated discriminative ability in determining whether an examinee requires an additional x-ray to confirm diagnosis.
• Postoperative translation of the upper instrumented vertebra in thoracic adolescent idiopathic scoliosis.

  Katsuhisa Yamada, Hideki Sudo, Kiyoshi Kaneda, Yasuhiro Shono, Yuichiro Abe, Norimasa Iwasaki

  Journal of neurosurgery. Pediatrics 22 6 694 - 700 2018年12月01日 [査読有り][通常論文]
   

  OBJECTIVEThe aim of this retrospective study was to analyze the influence of upper instrumented vertebra (UIV) translation from the C7 plumb line (C7PL) on the long-term postoperative results of patients with main thoracic (MT) adolescent idiopathic scoliosis (AIS).METHODSTwenty-five patients had been treated surgically for AIS with a Lenke type 1 curve and had been followed up for a mean period of 18.2 years. Radiographic parameters, pulmonary function measurements, and clinical outcomes were compared between the patients (n = 15) with UIV translation < 20 mm and those (n = 10) with UIV translation ≥ 20 mm at the final follow-up. Correlations between UIV translation and radiographic or pulmonary function parameters were analyzed.RESULTSPatients with ≥ 20 mm UIV translation at the final follow-up had a significantly larger preoperative UIV translation than that in the patients with < 20 mm UIV translation at follow-up. The former group also had a significantly lower correction rate of the MT curve, higher chest cage ratio, and lower radiographic shoulder height (p = 0.01, 0.005, and 0.025, respectively) at the final follow-up. The Scoliosis Research Society (SRS)-30 Questionnaire scores were equivalent between the two groups. Correlation analysis showed that the following parameters were significantly associated with UIV translation: MT curve correction rate (r = -0.481, p = 0.015), chest cage ratio (r = 0.673, p < 0.001), and percent-predicted forced expiratory volume in 1 second (r = -0.455, p = 0.033).CONCLUSIONSThe UIV translation should be considered an important factor that influences postoperative results. In MT AIS patients whose preoperative upper end vertebra (UEV) is distant from the C7PL, the UIV should be selected above the UEV to prevent large UIV translation at the postoperative follow-up.
• 3D Asymmetry Analysis of Human’s Back Surface for Early Screening of Idiopathic Scoliosis

  Satoshi Kanai, Hideki Sudo, Terufumi Kokabu, Hiroshi Nagaeda, Takayuki Hayashi, Hajime Ohta

  International Conference on Precision Engineering (ICPE2018) D-5-2  2018年11月 [査読有り][通常論文]
  
• 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 2018年11月 [査読有り][通常論文]
   

  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.
• An acellular bioresorbable ultra-purified alginate gel promotes intervertebral disc repair: A preclinical proof-of-concept study.

  Takeru Tsujimoto, Hideki Sudo, Masahiro Todoh, Katsuhisa Yamada, Koji Iwasaki, Takashi Ohnishi, Naoki Hirohama, Takayuki Nonoyama, Daisuke Ukeba, Katsuro Ura, Yoichi M Ito, Norimasa Iwasaki

  EBioMedicine 37 521 - 534 2018年11月 [査読有り][通常論文]
   

  BACKGROUND: The current surgical procedure of choice for lumbar intervertebral disc (IVD) herniation is discectomy. However, defects within IVD produced upon discectomy may impair tissue healing and predispose patients to subsequent IVD degeneration. This study aimed to investigate whether the use of an acellular bioresorbable ultra-purified alginate (UPAL) gel implantation system is safe and effective as a reparative therapeutic strategy after lumbar discectomy. METHODS: Human IVD cells were cultured in a three-dimensional system in UPAL gel. In addition, lumbar spines of sheep were used for mechanical analysis. Finally, the gel was implanted into IVD after discectomy in rabbits and sheep in vivo. FINDINGS: The UPAL gel was biocompatible with human IVD cells and promoted extracellular matrix production after discectomy, demonstrating sufficient biomechanical characteristics without material protrusion. INTERPRETATION: The present results indicate the safety and efficacy of UPAL gels in a large animal model and suggest that these gels represent a novel therapeutic strategy after discectomy in cases of lumbar IVD herniation. FUND: Grant-in-Aid for the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
• Late Subaxial Lesion after Overcorrected Occipitocervical Reconstruction in Patients with Rheumatoid Arthritis.

  Iwata A, Abumi K, Takahata M, Sudo H, Yamada K, Endo T, Iwasaki N

  Asian spine journal 13 2 181 - 188 2018年11月 [査読有り][通常論文]
   

  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.
• Screening of known disease genes in congenital scoliosis.

  Takeda K, Kou I, Mizumoto S, Yamada S, Kawakami N, Nakajima M, Otomo N, Ogura Y, Miyake N, Matsumoto N, Kotani T, Sudo H, Yonezawa I, Uno K, Taneichi H, Watanabe K, Shigematsu H, Sugawara R, Taniguchi Y, Minami S, Nakamura M, Matsumoto M, Japan Early Onset, Scoliosis Research Group, Watanabe K, Ikegawa S

  Molecular genetics & genomic medicine 6 6 966 - 974 2018年09月 [査読有り][通常論文]
   

  BACKGROUND: Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5-1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of remaining CS is unknown. METHODS: We recruited 78 CS patients without TBX6 mutations and major comorbidities, and investigated the genes previously reported to be associated with CS and congenital vertebral malformations by whole-exome sequencing. RESULTS: We identified the compound heterozygous missense variants in LFNG in one patient. No likely disease-causing variants were identified in other patients, however. LFNG encodes a GlcNAc-transferase. The LFNG variants showed loss of their enzyme function. CONCLUSIONS: A LFNG mutation is reported in a case of spondylocostal dysostosis (SCD), a skeletal dysplasia with severe malformations of vertebra and rib. The CS patient with LFNG mutations had multiple vertebral malformations including hemivertebrae, butterfly vertebrae, and block vertebrae, and rib malformations. LFNG mutations may cause a spectrum of phenotypes including CS and SCD. The current list of known disease genes could explain only a small fraction of genetic cause of CS.
• Identification of optimized rod shapes to guide anatomical spinal reconstruction for adolescent thoracic idiopathic scoliosis.

  Kokabu T, Kanai S, Abe Y, Iwasaki N, Sudo H

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 36 12 3219 - 3224 2018年07月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional deformity of the spine. Although rod curvature could play an important role in anatomical spinal reconstruction in patients with thoracic AIS, intraoperative contouring of the straight rod induces notches into the rod, leading to decreased fatigue strength. Here, we analyzed pre-bent rod geometries from 46 intraoperative tracings of the rod geometry, which can provide anatomical spinal reconstruction in patients with thoracic AIS. The center point clouds of the rod shapes were extracted and approximated as arcs and straight lines. The difference between the center point clouds were evaluated using the iterative closest point methods. When the rod shapes were divided into six groups based on length followed by hierarchical cluster analysis, 10 representative rod shapes were obtained with a difference value of 5 mm. Thus, we identified optimized rod shapes to guide anatomical spinal reconstruction for thoracic AIS, which will reduce not only the risk of rod breakage but also operation time, leading to decreased patient burden. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3219-3224, 2018.
• A Replication Study for the Association of rs11190870 With Curve Severity in Adolescent Idiopathic Scoliosis in Japanese.

  Yohei Takahashi, Ikuyo Kou, Yoji Ogura, Atsushi Miyake, Kazuki Takeda, Masahiro Nakajima, Shohei Minami, Noriaki Kawakami, Koki Uno, Manabu Ito, Ikuho Yonezawa, Takashi Kaito, Haruhisa Yanagida, Kei Watanabe, Hiroshi Taneichi, Katsumi Harimaya, Yuki Taniguchi, Toshiaki Kotani, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Nobuyuki Fujita, Mitsuru Yagi, Kazuhiro Chiba, Katsuki Kono, Tsuyoshi Sakuma, Tsutomu Akazawa, Kotaro Nishida, Kenichiro Kakutani, Hideki Shigematsu, Takahiro Iida, Satoru Demura, Naobumi Hosogane, Eijiro Okada, Masaya Nakamura, Morio Matsumoto, Kota Watanabe, Shiro Ikegawa

  Spine 43 10 688 - 692 2018年05月15日 [査読有り][通常論文]
   

  STUDY DESIGN: Case-only study. OBJECTIVE: The aim of this study was to confirm the association of rs11190870 with adolescent idiopathic scoliosis (AIS) severity in Japanese patients with AIS. SUMMARY OF BACKGROUND DATA: Although the association of rs11190870 with AIS susceptibility is replicated in multiple ethnics, the association of rs11190870 with curve severity is controversial. Since the previous studies are of small, we performed a replication study using far larger number of patients than previous studies. METHODS: A total of 1860 Japanese patients with AIS who had reached skeletal maturity or undergone surgical fusion were included in the study. We evaluated the association between rs11190870 and AIS progression for the entire group, and then for patients grouped according to a severe curve (a Cobb angle of ≥40°) or mild curve (a Cobb angle <30°). Because braces could affect the results of the present study, patients in the mild-curve group were divided according to whether or not they had worn a brace. We then evaluated associations between rs11190870 genotype and curve severity in these groups. RESULTS: The mean Cobb angles were 54.8° ± 12.1° in the severe-curve group and 24.4° ± 4.0° in the mild-curve group. The difference in rs11190870 risk-allele frequency between the severe- and mild-curve groups was evaluated. No significant differences were observed. We then examined the association of rs11190870 risk-allele frequency between patients in the mild- and severe-curve groups using the χ test for three models, and found a marginal association between rs11190870 and curve severity in the dominant model (P = 0.035, odds ratio = 1.51). CONCLUSION: We found no association between rs11190870 and curve severity using the criteria of previous study. However, we found a marginal association between rs11190870 and curve severity. Large-scale replication studies that consider skeletal maturity and brace history, including replication studies in other ethnic groups, would be helpful for clarifying the association. LEVEL OF EVIDENCE: 4.
• Impact of Multilevel Facetectomy and Rod Curvature on Anatomical Spinal Reconstruction in Thoracic Adolescent Idiopathic Scoliosis.

  Sudo H, Abe Y, Kokabu T, Kuroki K, Iwata A, Iwasaki N

  Spine 43 19 E1135 - E1142 2018年03月 [査読有り][通常論文]
   

  STUDY DESIGN: A prospective, nonrandomized study. OBJECTIVE: The aim of this study was to assess surgical outcomes of multilevel facetectomy and rod curvature with simultaneous double-rod rotation technique for anatomical spinal reconstruction in thoracic adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Although some surgical techniques maintain or restore thoracic kyphosis (TK), next-generation strategies for thoracic AIS should include corrections in three anatomical planes. METHODS: The study included 39 consecutive patients with Lenke 1 or Lenke 2 thoracic AIS treated at our institution. After all-level facetectomy at instrumentation level, except for the lowest intervertebral segment, two rods were identically bent to guide postoperative anatomical TK without reference to the intraoperative coronal alignment of the AIS deformity. Outcome measures included patient demographics, radiographic measurements, and Scoliosis Research Society (SRS) questionnaire scores. RESULTS: After 2 years of follow-up, the average main thoracic Cobb angle correction rate was 83.5%, and the final correction loss was 2.2°. The average preoperative TK (T5-T12) significantly increased from 13.2° to 24.6° (P < 0.001) at final follow-up. The percentage of patients with a T6-T8 location of the TK apex significantly increased from 51.3% preoperatively to 87.2% at final follow-up. The average preoperative vertebral rotation angle significantly decreased from 18.7° to 12.8° postoperatively (P < 0.001). The average preoperative total SRS questionnaire score significantly increased from 3.5 to 4.5 (P < 0.001) at final follow-up. There was no implant breakage and vascular and neurologic complications, with all patients demonstrating solid fusion at final follow-up. CONCLUSION: Multilevel facetectomy and rod curvature play an important role in anatomical spinal reconstruction in patients with thoracic AIS. From the spatiotemporal point of view, four-dimensional correction could be actively performed by rod curvature under multilevel facetectomy and is expected to obtain an anatomical thoracic spine postoperatively, indicating that an anatomically designed rod could be supplied as a pre-bent rod. LEVEL OF EVIDENCE: 3.
• Age-related spontaneous lumbar intervertebral disc degeneration in a mouse model

  Takashi Ohnishi, Hideki Sudo, Takeru Tsujimoto, Norimasa Iwasaki

  Journal of Orthopaedic Research 36 1 224 - 232 2018年01月01日 [査読有り][通常論文]
   

  The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration. The magnetic resonance imaging index yielded a moderate correlation with our Age-related model score. The Pfirrmann grade and magnetic resonance imaging index had moderate correlations with age. However, our Age-related model score had a high correlation with age. Intervertebral disc level was not a significant variable for the severity of disc degeneration. Both Pfirrmann grade and the Age-related model score were higher in the ≥14-month-old group than in the 6-month-old group. The present results indicated that mild but significant intervertebral disc degeneration occurred in 14-month-old mice, and the degree of degeneration progressed slowly, reaching a moderate to severe condition for 22-month-old mice. At least a 14-month follow-up is mandatory for evaluating spontaneous age-related mouse intervertebral disc degeneration. The histological classification score can precisely detect the gradual progression of age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine, and is appropriate for evaluating it. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:224–232, 2018.
• 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.

  Haraya K, Yamada K, Kokabu T, Iwata A, Endo T, Sudo H, Iwasaki N, Takahata M

  Spinal cord series and cases 4 81 - 81 2018年 [査読有り][通常論文]
   

  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.
• A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is associated with progression of adolescent idiopathic scoliosis

  Yoji Ogura, Ikuyo Kou, Yohei Takahashi, Kazuki Takeda, Shohei Minami, Noriaki Kawakami, Koki Uno, Manabu Ito, Ikuho Yonezawa, Takashi Kaito, Haruhisa Yanagida, Kei Watanabe, Hiroshi Taneichi, Katsumi Harimaya, Yuki Taniguchi, Toshiaki Kotani, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Nobuyuki Fujita, Mitsuru Yagi, Kazuhiro Chiba, Michiaki Kubo, Yoichiro Kamatani, Masaya Nakamura, Morio Matsumoto, Kota Watanabe, Shiro Ikegawa

  HUMAN MOLECULAR GENETICS 26 20 4086 - 4092 2017年10月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is a common spinal deformity affecting millions of children. Since treatment and prognosis of AIS depend on curve progression, identifying factors related to AIS curve progression is important in its management. Although several genetic loci for AIS occurrence are reported, no locus for curve progression has been identified. To identify genes associated with AIS progression, we conducted a genome-wide association study followed by a replication study using a total of 2,543 AIS subjects who were evaluated for the curve progression. We identified a significantly associated locus on chromosome 11q14.1 (P = 1.98 x 10(-9), odds ratio = 1.56). In silico and in vitro analyses identified a functional variant, rs35333564 in MIR4300HG, the host gene of a microRNA, MIR4300. The genomic region containing rs35333564 had enhancer activity, which was decreased in its risk allele. Our data suggest that decrease of MIR4300 is related to AIS progression.
• Effective Repair of Dural Tear Using Bioabsorbable Sheet with Fibrin Glue

  Akira Iwata, Masahiko Takahata, Ken Kadoya, Hideaki Sudo, Terufumi Kokabu, Katsuhisa Yamada, Norimasa Iwasaki

  Spine 42 18 1362 - 1366 2017年09月15日 [査読有り][通常論文]
   

  Study Design. Basic science. Objective. This study aimed to compare the techniques of surgical repair of dural tear using bioabsorbable material and fibrin glue. Summary of Background Data. Cerebrospinal fluid (CSF) leakage caused by dural tear can often be difficult to manage even after repair when the same materials are used in a similar manner. Methods. Burst pressure was measured for repaired porcine dura with holes of different diameters using spray of combined fibrinogen and thrombin solution (fibrin spray) alone as a control and the 5-mm hole following different methods using fibrinogen and thrombin solutions plus polyglactin 910 sheet (PGS). For group 1, fibrinogen was applied on the dura followed by PGS and thrombin. For group 2, thrombin was followed by PGS and fibrinogen. For group 3, fibrinogen was followed by PGS and fibrin spray. For group 4, thrombin was followed by PGS and fibrin spray. Microscopic observation was conducted for each specimen. Results. Repair using fibrin spray alone was successful for the 0.3-mm diameter pinhole (breakdown pressure: 27.8 ± 8.6 mmHg), but was not able to cover the 2.7- and 5-mm holes. For a 5-mm diameter hole, the breakdown pressure was 54.4±38.8 mmHg in group 1, 26.3±19.4 mmHg in group 2, 147.7±65.0 mmHg in group 3, and 35.5±23.4 mmHg in group 4 (P< 0.001). There was little fibrin glue in the burst layer between the dural surface and PGS with thrombin on the dural surface (group 2 and group 4). Conclusion. Suppression of excessive CSF leakage could be successful by performing several cycles of the group 1 method (fibrinogen was applied on the dura followed by PGS and thrombin), followed by the group 3 method (fibrinogen was applied on the dura followed by PGS and fibrin spray), with thrombin solution wash each time.
• Compound Heterozygosity for Null Mutations and a Common Hypomorphic Risk Haplotype in TBX6 Causes Congenital Scoliosis

  Kazuki Takeda, Ikuyo Kou, Noriaki Kawakami, Aritoshi Iida, Masahiro Nakajima, Yoji Ogura, Eri Imagawa, Noriko Miyake, Naomichi Matsumoto, Yukuto Yasuhiko, Hideki Sudo, Toshiaki Kotani, Masaya Nakamura, Morio Matsumoto, Kota Watanabe, Shiro Ikegawa

  HUMAN MUTATION 38 3 317 - 323 2017年03月 [査読有り][通常論文]
   

  Congenital scoliosis (CS) occurs as a result of vertebral malformations and has an incidence of 0.5-1/1,000 births. Recently, TBX6 on chromosome 16p11.2 was reported as a disease gene for CS; about 10% of Chinese CS patients were compound heterozygotes for rare null mutations and a common haplotype defined by three SNPs in TBX6. All patients had hemivertebrae. We recruited 94 Japanese CS patients, investigated the TBX6 locus for both mutations and the risk haplotype, examined transcriptional activities of mutant TBX6 in vitro, and evaluated clinical and radiographic features. We identified TBX6 null mutations in nine patients, including a missense mutation that had a loss of function in vitro. All had the risk haplotype in the opposite allele. One of the mutations showed dominant negative effect. Although all Chinese patients had one or more hemivertebrae, two Japanese patients did not have hemivertebra. The compound heterozygosity of null mutations and the common risk haplotype in TBX6 also causes CS in Japanese patients with similar incidence. Hemivertebra was not a specific type of spinal malformation in TBX6-associated CS (TACS). A heterozygous TBX6 loss-of-function mutation has been reported in a family with autosomal-dominant spondylocostal dysostosis, but it may represent a spectrum of the same disease with TACS.
• Cervical myelopathy due to atraumatic odontoid fracture in patients with rheumatoid arthritis: A case series

  Masahiko Takahata, Kuniyoshi Abumi, Hideki Sudo, Ken Nagahama, Norimasa Iwasaki

  MODERN RHEUMATOLOGY 27 5 901 - 904 2017年 [査読有り][通常論文]
   

  To highlight the risk of cervical myelopathy due to occult, atraumatic odontoid fracture in patients with rheumatoid arthritis, we retrospectively reviewed radiographic findings and clinical observations for 7 patients with this disorder. This fracture tends to occur in patients with long-lasting rheumatoid arthritis and to be misdiagnosed as simple atlantoaxial dislocation. Since this fracture causes multidirectional instability between C1 and C2 and is expected to have poor healing potential due to bone erosion and inadequate blood supply, posterior spinal arthrodesis surgery is indicated upon identification of the fracture to prevent myelopathy.
• Effects of Multiple Intra-articular Injections of 0.5% Bupivacaine on Normal and Osteoarthritic Joints in Rats

  Koji Iwasaki, Hideki Sudo, Yasuhiko Kasahara, Katsuhisa Yamada, Takashi Ohnishi, Takeru Tsujimoto, Norimasa Iwasaki

  ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY 32 10 2026 - 2036 2016年10月 [査読有り][通常論文]
   

  Purpose: To determine the in vivo effects of multiple local anesthetic injections of 0.5% bupivacaine on normal and osteoarthritic articular cartilage. Methods: Rats with normal knee joints received an intra-articular injection of 0.9% saline solution or 0.5% bupivacaine in their right knees joint once a week for 5 consecutive weeks, starting 4 weeks after the beginning of the experiment. Rats were humanely killed at 8, 16, and 24 weeks. In a parallel experiment, rats underwent anterior cruciate ligament transection to induce osteoarthritic changes. These rats were subjected to the same protocol as those with normal knee joints, starting 4 weeks after the procedure. Static weight-bearing tests were performed on both hind limbs to evaluate changes in weight-bearing ability throughout the experiments. Rats were humanely killed at 8 and 16 weeks. Cell viability was assessed with confocal microscopy, using samples from the distal femur. Histologic assessment of osteoarthritis was performed using samples from the tibial plateau based on the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system (i.e., OARSI score). Results: Static weight-bearing tests showed no significant changes after intra-articular injection of saline solution or bupivacaine, and bupivacaine injection did not increase weight bearing compared with saline solution injection, regardless of whether there were osteoarthritic changes. There were also no significant differences in cell viability, cell density, or OARSI scores between the saline solution and bupivacaine groups at each time point, regardless of whether osteoarthritic changes were induced. Conclusions: This study suggested that single or intermittent intra-articular bupivacaine injections might not have deleterious effects on either osteoarthritic or normal joints.
• Correlation analysis between change in thoracic kyphosis and multilevel facetectomy and screw density in main thoracic adolescent idiopathic scoliosis surgery

  Hideki Sudo, Yuichiro Abe, Terufumi Kokabu, Manabu Ito, Kuniyoshi Abumi, Yoichi M. Ito, Norimasa Iwasaki

  SPINE JOURNAL 16 9 1049 - 1054 2016年09月 [査読有り][通常論文]
   

  BACKGROUND CONTEXT: Controversy exists regarding the effects of multilevel facetectomy and screw density on deformity correction, especially thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery. PURPOSE: This study aimed to evaluate the effects of multilevel facetectomy and screw density on sagittal plane correction in patients with main thoracic (MT) AIS curve. STUDY DESIGN: A retrospective correlation and comparative analysis of prospectively collected, consecutive, non-randomized series of patients at a single institution was undertaken. PATIENT SAMPLE: Sixty-four consecutive patients with Lenke type 1 AIS treated with posterior correction and fusion surgery using simultaneous double-rod rotation technique were included. OUTCOME MEASURES: Patient demographics and preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study. METHODS: Multiple stepwise linear regression analysis was conducted between change in TK (T5-T12) and the following factors: age at surgery, Risser sign, number of facetectomy level, screw density, preoperative main thoracic curve, flexibility in main thoracic curve, coronal correction rate, preoperative TK, and preoperative lumbar lordosis. Patients were classified into two groups: TK< 15 degrees group defined by preoperative TK below the mean degree of TK for the entire cohort (< 15 degrees) and the TK >= 15 degrees group, defined by preoperative TK above the mean degree of kyphosis (>= 15 degrees). Independent sample t tests were used to compare demographic data as well as radiographic outcomes between the two groups. There were no study-specific biases related to conflicts of interest. RESULTS: The average preoperative TK was 14.0 degrees, which improved significantly to 23.1 degrees (p<.0001) at the 2-year final follow-up. Greater change in TK was predicted by a low preoperative TK (p<.0001). The TK < 15 degrees group showed significant correlation between change in TK and number of facetectomy level (r=0.492, p=.002). Similarly, significant correlation was found between change in TK and screw density (r=0.333, p=.047). Conversely, in the TK >= 15 degrees group, correlation was found neither between change in TK and number of facetectomy level (r=0.047, p=.812), nor with screw density (r= 0.030, p=.880). Furthermore, in patients with preoperative TK< 15 degrees, change in TK was significantly correlated with screw density at the concave side (r=0.351, p=.036) but not at the convex side (r=0.144, p=.402). CONCLUSIONS: In patients with hypokyphotic thoracic spine, significant positive correlation was found between change in TK and multilevel facetectomy or screw density at the concave side. This indicates that in patients with AIS who have thoracic hypokyphosis as part of their deformity, the abovementioned factors must be considered in preoperative planning to correct hypokyphosis. (C) 2016 Elsevier Inc. All rights reserved.
• In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification

  Takashi Ohnishi, Hideki Sudo, Koji Iwasaki, Takeru Tsujimoto, Yoichi M. Ito, Norimasa Iwasaki

  PLOS ONE 11 8 e0160486  2016年08月 [査読有り][通常論文]
   

  Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region.
• Effects of Multilevel Facetectomy and Screw Density on Postoperative Changes in Spinal Rod Contour in Thoracic Adolescent Idiopathic Scoliosis Surgery

  Terufumi Kokabu, Hideki Sudo, Yuichiro Abe, Manabu Ito, Yoichi M. Ito, Norimasa Iwasaki

  PLOS ONE 11 8 e0161906  2016年08月 [査読有り][通常論文]
   

  Flattening of the preimplantation rod contour in the sagittal plane influences thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery. The effects of multilevel facetectomy and screw density on postoperative changes in spinal rod contour have not been documented. This study aimed to evaluate the effects of multilevel facetectomy and screw density on changes in spinal rod contour from before implantation to after surgical correction of thoracic curves in patients with AIS prospectively. The concave and convex rod shapes from patients with thoracic AIS (n = 49) were traced prior to insertion. Postoperative sagittal rod shape was determined by computed tomography. The angle of intersection of the tangents to the rod end points was measured. Multiple stepwise linear regression analysis was used to identify variables independently predictive of change in rod contour (Delta theta). Average Delta theta at the concave and convex side were 13.6 degrees +/- 7.5 degrees and 4.3 degrees +/- 4.8 degrees, respectively. The Delta theta at the concave side was significantly greater than that of the convex side (P < 0.0001) and significantly correlated with Risser sign (P = 0.032), the preoperative main thoracic Cobb angle (P = 0.031), the preoperative TK angle (P = 0.012), and the number of facetectomy levels (P = 0.007). Furthermore, a Delta theta at the concave side +/- 14 degrees significantly correlated with the postoperative TK angle (P = 0.003), the number of facetectomy levels (P = 0.021), and screw density at the concave side (P = 0.008). Rod deformation at the concave side suggests that corrective forces acting on that side are greater than on the convex side. Multilevel facetectomy and/or screw density at the concave side have positive effects on reducing the rod deformation that can lead to a loss of TK angle postoperatively.
• Maintenance of spontaneous lumbar curve correction following thoracic fusion of main thoracic curves in adolescent idiopathic scoliosis

  H. S. Sudo, M. M. Mayer, K. K. Kaneda, S. Nunez-Pereira, S. Y. Shono, W. H. Hitzl, N. I. Iwasaki, H. K. Koller

  BONE & JOINT JOURNAL 98B 7 997 - 1002 2016年07月 [査読有り][通常論文]
   

  Aims The aims of our study were to provide long-term information on the behaviour of the thoracolumbar/lumbar (TL/L) curve after thoracic anterior correction and fusion (ASF) and to determine the impact of ASF on pulmonary function. Patients and Methods A total of 41 patients (four males, 37 females) with main thoracic (MT) adolescent idiopathic scoliosis (AIS) treated with ASF were included. Mean age at surgery was 15.2 years (11 to 27). Mean follow-up period was 13.5 years (10 to 18). Results For the TL/L curve, the mean curve flexibility evaluated with supine pre-operative bending radiographs was 78.6% (standard deviation 16.5%), with no significant loss of correction observed. On comparing patients with an increase of the TL/L curve increase (> 4 degrees, n = 9, 22%) to those without, significant differences were observed in the correction rate of the MT curve at the final follow-up (p = 0.011), correction loss of the MT curve (p = 0.003) and the proportion of patients who had semi-rigid instrumentation (p = 0.003). Pre-operative percentage predicted forced vital capacity (% FVC) was 80%, dropping to 72% at final follow-up (p < 0.001). The Scoliosis Research Society questionnaire score was not significantly different between patients with and without a TL/L curve increase (p = 0.606). Spontaneous lumbar curve correction (SLCC) was maintained up to 18 years following selective ASF in most patients and demonstrated significant correlation with maintenance of MT curve correction. Conclusion Maintenance of MT curve correction using rigid instrumentation provided stable SLCC over time. An observed 8% decrease in % FVC indicates that ASF should be reserved for patients with no or only mild pulmonary impairment.
• Short fusion strategy for thoracolumbar and lumbar adolescent idiopathic scoliosis using anterior dual-rod instrumentation.

  H. Sudo, K. Kaneda, Y. Shono, N. Iwasaki

  BONE & JOINT JOURNAL 98B 3 402 - 409 2016年03月 [査読有り][通常論文]
   

  Aims A total of 30 patients with thoracolumbar/lumbar adolescent idiopathic scoliosis (AIS) treated between 1989 and 2000 with anterior correction and fusion surgery using dual-rod instrumentation were reviewed. Patients and Methods Radiographic parameters and clinical outcomes were compared among patients with lowest instrumented vertebra (LIV) at the lower end vertebra (LEV; EV group) (n = 13) and those treated by short fusion (S group), with LIV one level proximal to EV (n = 17 patients). Results The allocation of the surgical technique was determined by the flexibility of the TL/L curves and/or neutral vertebrae located one level above LEV as determined on preoperative radiographs. If these requirements were met a short fusion was performed. The mean follow-up period was 21.4 years (16 to 27). The mean correction rate at final follow-up was significantly lower in the S group (74 SD 11%) than in the EV group (88 SD 13%) (p = 0.004).Coronal and sagittal balance, thoracic kyphosis, lumbar lordosis, and clinical outcomes evaluated by the Scoliosis Research Society-22 questionnaire scores were equivalent between the two groups. Conclusion Short fusion strategy, which uses LIV one level proximal to LEV can be considered as an alternative to the conventional strategy, which includes LEV in the fusion, when highly flexible TL/L curves are confirmed and/or neutral vertebrae are located one level above LEV in patients with thoracolumbar/lumbar AIS curves. Take home message: Short fusion strategy can be considered as an alternative to the conventional strategy in patients with thoracolumbar/lumbar AIS curves undergoing anterior spinal fusion with dual-rod instrumentation.
• Selection of the upper vertebra to be instrumented in the treatment of thoracolumbar and lumbar adolescent idiopathic scoliosis by anterior correction and fusion surgery using dual-rod instrumentation: a minimum 12-year follow-up study

  Hideki Sudo, Kiyoshi Kaneda, Yasuhiro Shono, Norimasa Iwasaki

  SPINE JOURNAL 16 3 281 - 287 2016年03月 [査読有り][通常論文]
   

  BACKGROUND CONTEXT: Consensus regarding the optimal upper vertebra to be instrumented during surgical treatment of Lenke 5C thoracolumbar and lumbar adolescent idiopathic scoliosis (AIS) remains limited. PURPOSE: This study aimed to assess whether a short fusion strategy is appropriate for correction of a Lenke 5C AIS curve by anterior correction and fusion surgery using dual-rod instrumentation. STUDY DESIGN: This study design used retrospective comparative analysis of a prospectively collected, consecutive, non-randomized series of patients at a single institution. PATIENT SAMPLE: Thirty consecutive patients with Lenke 5C AIS treated with anterior correction and fusion surgery using dual-rod instrumentation were included. OUTCOME MEASURES: Patient demographics, radiographic measurements, and Scoliosis Research Society-22 questionnaire (SRS-22) scores were the outcome measures for this study. METHODS: Thirty patients were treated surgically for AIS with a Lenke 5C curve (mean age, 14.4 years [11-19 years)]) and followed up for a mean period of 17.2 years (12-23 years). Radiographical parameters and clinical outcomes were compared between patients treatment with the end vertebra (EV) instrumented (n=14) and those treated by short fusion (S group) with instrumentation starting at the vertebra one level caudal to the EV (n=16 patients). There were no study-specific biases related to conflicts of interest. RESULTS: In the EV group, a mean preoperative Cobb angle of 56 degrees was corrected to 5 degrees after surgery and to 8 degrees at the final follow-up. In the S group, a mean preoperative Cobb angle of 55 degrees was corrected to 10 degrees after surgery and 14 degrees at the final follow-up. The mean correction rate at the final follow-up was significantly lower in the S group (74%) than in the EV group (86%; p=.020). The coronal and sagittal balance, thoracic kyphosis, lumbar lordosis, and clinical outcomes evaluated using SRS-22 did not differ between the two groups. CONCLUSIONS: The short fusion strategy, which involves instrumentation of the vertebra one level caudal to the upper EV, can be considered as an alternative to the conventional strategy, which includes instrumentation of the upper EV, for treating Lenke 5C curves via anterior spinal fusion. (C) 2016 Elsevier Inc. All rights reserved.
• Surgical treatment of double thoracic adolescent idiopathic scoliosis with a rigid proximal thoracic curve

  Hideki Sudo, Yuichiro Abe, Kuniyoshi Abumi, Norimasa Iwasaki, Manabu Ito

  EUROPEAN SPINE JOURNAL 25 2 569 - 577 2016年02月 [査読有り][通常論文]
   

  There is limited consensus on the optimal surgical strategy for double thoracic adolescent idiopathic scoliosis (AIS). Recent studies have reported that pedicle screw constructs to maximize scoliosis correction cause further thoracic spine lordosis. The objective of this study was to apply a new surgical technique for double thoracic AIS with rigid proximal thoracic (PT) curves and assess its clinical outcomes. Twenty one consecutive patients with Lenke 2 AIS and a rigid PT curve (Cobb angle a parts per thousand yen30A(0) on side-bending radiographs, flexibility a parts per thousand currency sign30 %) treated with the simultaneous double-rod rotation technique (SDRRT) were included. In this technique, a temporary rod is placed at the concave side of the PT curve. Then, distraction force is applied to correct the PT curve, which reforms a sigmoid double thoracic curve into an approximate single thoracic curve. As a result, the PT curve is typically converted from an apex left to an apex right curve before applying the correction rod for PT and main thoracic curve. All patients were followed for at least 2 years (average 2.7 years). The average main thoracic and PT Cobb angle correction rate at the final follow-up was 74.7 and 58.0 %, respectively. The average preoperative T5-T12 thoracic kyphosis was 9.3A degrees, which improved significantly to 19.0A degrees (p < 0.0001) at the final follow-up. Although 71 % patients had preoperative level shoulders or a positive radiographic shoulder height, all patients had mildly imbalanced or balanced shoulders at the final follow-up. The average preoperative main thoracic apical vertebral rotation angle of 20.7A degrees improved significantly after surgery to 16.4A degrees (p = 0.0046), while the average preoperative total SRS questionnaire score of 3.7 improved significantly to 4.4 (p = 0.0012) at the final follow-up. Radiographic findings and patient outcomes were satisfactory. Thoracic kyphosis can be maintained or improved, while coronal and axial deformities can be corrected using SDRRT for Lenke 2 AIS with a rigid PT curve.
• A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis

  Yoji Ogura, Ikuyo Kou, Shigenori Miura, Atsushi Takahashi, Leilei Xu, Kazuki Takeda, Yohei Takahashi, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Ikuho Yonezawa, Haruhisa Yanagida, Hiroshi Taneichi, Zezhang Zhu, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Kota Watanabe, Naobumi Hosogane, Eijiro Okada, Aritoshi Iida, Masahiro Nakajima, Akihiro Sudo, Kazuhiro Chiba, Yuji Hiraki, Yoshiaki Toyama, Yong Qiu, Chisa Shukunami, Yoichiro Kamatani, Michiaki Kubo, Mono Matsumoto, Shiro Ikegawal

  AMERICAN JOURNAL OF HUMAN GENETICS 97 2 337 - 342 2015年08月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 x 10(-13); odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS.
• 18F-FDG-PET/CT better localizes active spinal infection than MRI for successful minimally invasive surgery

  Masayuki Nakahara, Manabu Ito, Naoya Hattori, Keiichi Magota, Masahiko Takahata, Ken Nagahama, Hideki Sudo, Tamotsu Kamishima, Nagara Tamaki, Norimasa Iwasaki

  ACTA RADIOLOGICA 56 7 829 - 836 2015年07月 [査読有り][通常論文]
   

  Background: Surgical debridement is often required to treat spinal infections. Successful surgery requires accurate localization of the active infections, however, current imaging technique still requires surgeons' experience to narrow the surgical fields to achieve less invasive procedures. Purpose: To investigate the use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for successful surgical planning. Material and Methods: Nine patients with suspected spinal infection underwent magnetic resonance imaging (MRI) and FDG-PET/CT before surgery to locate active foci of infections. The spinal structures were divided into seven compartments at each intervertebral disc level for a total of 315 compartments investigated. The same classification system was used to design operating fields for histological correlation. Results: FDG-PET/CT diagnosed fewer compartments as active infection (34 compartments, 10.8%) than MRI (62 compartments, 19.7%, P = 0.002). Surgical exploration was performed in 49 compartments, and demonstrated active infection in 25 compartments. The sensitivity / specificity of FDG-PET/CT was 100% / 79%, respectively, which was superior to those of MRI, 76% / 42%. Foci of active infection showed hypermetabolic activity with a SUVmax of 7.1 +/- 2.6 (range, 3.0-12.7). Receiver operating characteristic (ROC) analysis indicated an optimal threshold for active spinal infection at a SUVmax of 4.2, corresponding to a sensitivity of 90.3% and specificity of 91.2%. Conclusion: FDG-PET/CT demonstrated limited areas of abnormality allowing accurate delineation, and is thus useful to narrow the surgical fields. Since overall diagnostic accuracy of FDG-PET/CT was superior to that of MRI, FDG-PET/CT is a useful technique to narrow the surgical field for successful less invasive surgery.
• Right-convex thoracolumbar scoliosis

  Kei Kuroki, Hideki Sudo, Norimasa Iwasaki

  SPINE JOURNAL 15 5 1154 - 1155 2015年05月 [査読有り][通常論文]
  
• A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females

  Swarkar Sharma, Douglas Londono, Walter L. Eckalbar, Xiaochong Gao, Dongping Zhang, Kristen Mauldin, Ikuyo Kou, Atsushi Takahashi, Morio Matsumoto, Nobuhiro Kamiya, Karl K. Murphy, Reuel Cornelia, John A. Herring, Dennis Burns, Nadav Ahituv, Shiro Ikegawa, Derek Gordon, Carol A. Wise

  NATURE COMMUNICATIONS 6 6 6452  2015年03月 [査読有り][通常論文]
   

  Idiopathic scoliosis (IS) is a common paediatric musculoskeletal disease that displays a strong female bias. By performing a genome-wide association study (GWAS) of 3,102 individuals, we identify significant associations with 20p11.22 SNPs for females (P = 6.89 x 10(-9)) but not males (P = 0.71). This association with IS is also found in independent female cohorts from the United States of America and Japan (overall P = 2.15 x 10(-10), OR = 1.30 (rs6137473)). Unexpectedly, the 20p11.22 IS risk alleles were previously associated with protection from early-onset alopecia, another sexually dimorphic condition. The 174-kb associated locus is distal to PAX1, which encodes paired box 1, a transcription factor involved in spine development. We identify a sequence in the associated locus with enhancer activity in zebrafish somitic muscle and spinal cord, an activity that is abolished by IS-associated SNPs. We thus identify a sexually dimorphic IS susceptibility locus, and propose the first functionally defined candidate mutations in an enhancer that may regulate expression in specific spinal cells.
• Scoliosis corrective force estimation from the implanted rod deformation using 3D-FEM analysis

  Yuichiro Abe, Manabu Ito, Kuniyoshi Abumi, Hideki Sudo, Remel Salmingo, Shigeru Tadano

  Scoliosis 10 Suppl 2 S2  2015年02月11日 [査読有り][通常論文]
   

  Background: Improvement of material property in spinal instrumentation has brought better deformity correction in scoliosis surgery in recent years. The increase of mechanical strength in instruments directly means the increase of force, which acts on bone-implant interface during scoliosis surgery. However, the actual correction force during the correction maneuver and safety margin of pull out force on each screw were not well known. In the present study, estimated corrective forces and pull out forces were analyzed using a novel method based on Finite Element Analysis (FEA). Methods: Twenty adolescent idiopathic scoliosis patients (1 boy and 19 girls) who underwent reconstructive scoliosis surgery between June 2009 and Jun 2011 were included in this study. Scoliosis correction was performed with 6mm diameter titanium rod (Ti6Al7Nb) using the simultaneous double rod rotation technique (SDRRT) in all cases. The pre-maneuver and post-maneuver rod geometry was collected from intraoperative tracing and postoperative 3D-CT images, and 3D-FEA was performed with ANSYS. Cobb angle of major curve, correction rate and thoracic kyphosis were measured on X-ray images. Results: Average age at surgery was 14.8, and average fusion length was 8.9 segments. Major curve was corrected from 63.1 to 18.1 degrees in average and correction rate was 71.4%. Rod geometry showed significant change on the concave side. Curvature of the rod on concave and convex sides decreased from 33.6 to 17.8 degrees, and from 25.9 to 23.8 degrees, respectively. Estimated pull out forces at apical vertebrae were 160.0N in the concave side screw and 35.6N in the convex side screw. Estimated push in force at LIV and UIV were 305.1N in the concave side screw and 86.4N in the convex side screw. Conclusions: Corrective force during scoliosis surgery was demonstrated to be about four times greater in the concave side than in convex side. Averaged pull out and push in force fell below previously reported safety margin. Therefore, the SDRRT maneuver was safe for correcting moderate magnitude curves. To prevent implant breakage or pedicle fracture during the maneuver in a severe curve correction, mobilization of spinal segment by releasing soft tissue or facet joint could be more important than using a stronger correction maneuver with a rigid implant.
• Subaxial Sagittal Alignment After Atlantoaxial Fixation Techniques

  Shigeki Oshima, Hideki Sudo, Manabu Ito, Kuniyoshi Abumi

  JOURNAL OF SPINAL DISORDERS & TECHNIQUES 28 1 E49 - E55 2015年02月 [査読有り][通常論文]
   

  Study Design: A retrospective clinical case series. Objectives: To evaluate the association between C1-C2 fixation angle and postoperative C2-C7 alignment in the sagittal plane after C1 lateral mass screw with C2 pedicle screw fixation (C1-LMS) or Magerl with wiring technique. Summary of Background Data: Various techniques for posterior correction and fusion, such as the Magerl procedure with posterior wiring and C1-LMS procedures, are used for treating atlantoaxial instability. However, only few studies investigating the relationship between postoperative C1-C2 angle and C2-C7 sagittal alignment change after C1-C2 fixation have been reported. Methods: We retrospectively followed up 42 patients who underwent the C1-LMS (22 patients) or Magerl with wiring procedure (20 patients) to treat C1-C2 instability for > 2 years. The atlantodental interval, space available for the spinal cord, and O-C1, C1-C2, C2-C3, and C2-C7 angles were measured. Results: Significant reduction in atlantodental interval and increase in space available for the spinal cord were observed in both groups. Although the preoperative C1-C2 angles were similar, the angle at the final follow-up was higher in the Magerl with wiring group than in the C1-LMS group (P < 0.01). The C1-C2 fixation and postoperative C2-C7 angles were negatively correlated in both groups (C1-LMS group, r = -0.55, P < 0.01; Magerl with wiring, r = -0.62, P < 0.01). Conclusions: Increased lordotic change in the C1-C2 angle was associated with increased kyphotic changes in the C2-C7 angle after both procedures. The C1-LMS procedure effectively controlled C1-C2 sagittal alignment during surgery. To decrease the risk of postoperative subaxial kyphotic changes, the C1-C2 fixation angle should be carefully determined.
• Effects of Single Injection of Local Anesthetic Agents on Intervertebral Disc Degeneration: Ex Vivo and Long-Term In Vivo Experimental Study

  Koji Iwasaki, Hideki Sudo, Katsuhisa Yamada, Hideaki Higashi, Takashi Ohnishi, Takeru Tsujimoto, Norimasa Iwasaki

  PLOS ONE 9 10 e109851  2014年10月 [査読有り][通常論文]
   

  Background: Analgesic discography (discoblock) can be used to diagnose or treat discogenic low back pain by injecting a small amount of local anesthetics. However, recent in vitro studies have revealed cytotoxic effects of local anesthetics on intervertebral disc (IVD) cells. Here we aimed to investigate the deteriorative effects of lidocaine and bupivacaine on rabbit IVDs using an organotypic culture model and an in vivo long-term follow-up model. Methods: For the organotypic culture model, rabbit IVDs were harvested and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine or 0.5% bupivacaine). Nucleus pulposus (NP) cell death was measured using confocal microscopy. Histological and TUNEL assays were performed. For in vivo study, each local anesthetic was injected into rabbit lumbar IVDs under a fluoroscope. Six or 12 months after the injection, each IVD was prepared for magnetic resonance imaging (MRI) and histological analysis. Results: In the organotypic culture model, both anesthetic agents induced time-dependent NP cell death; when compared with injected saline solution, significant effects were detected within 7 days. Compared with the saline group, TUNEL-positive NP cells were significantly increased in the bupivacaine group. In the in vivo study, MRI analysis did not show any significant difference. Histological analysis revealed that IVD degeneration occurred to a significantly level in the saline-and local anesthetics-injected groups compared with the untreated control or puncture-only groups. However, there was no significant difference between the saline and anesthetic agents groups. Conclusions/Significance: In the in vivo model using healthy IVDs, there was no strong evidence to suggest that discoblock with local anesthetics has the potential of inducing IVD degeneration other than the initial mechanical damage of the pressurized injection. Further studies should be performed to investigate the deteriorative effects of the local injection of analgesic agents on degenerated IVDs.
• Surgical Treatment of Lenke 1 Thoracic Adolescent Idiopathic Scoliosis With Maintenance of Kyphosis Using the Simultaneous Double-Rod Rotation Technique

  Hideki Sudo, Manabu Ito, Yuichiro Abe, Kuniyoshi Abumi, Masahiko Takahata, Ken Nagahama, Shigeto Hiratsuka, Kei Kuroki, Norimasa Iwasaki

  SPINE 39 14 1163 - 1169 2014年06月 [査読有り][通常論文]
   

  Study Design. Retrospective analysis of a prospectively collected, consecutive, nonrandomized series of patients. Objective. To assess the surgical outcomes of the simultaneous double-rod rotation technique for treating Lenke 1 thoracic adolescent idiopathic scoliosis (AIS). Summary of Background Data. With the increasing popularity of segmental pedicle screw spinal reconstruction for treating AIS, concerns regarding the limited ability to correct hypokyphosis have also increased. Methods. A consecutive series of 32 patients with Lenke 1 main thoracic AIS treated with the simultaneous double-rod rotation technique at our institution was included. Outcome measures included patient demographics, radiographical measurements, and Scoliosis Research Society questionnaire scores. Results. All 32 patients were followed up for a minimum of 2 years (average, 3.6 yr). The average main thoracic Cobb angle correction rate and the correction loss at the final follow-up were 67.8% and 3.3 degrees, respectively. The average preoperative thoracic kyphosis (T5-T12) was 11.9, which improved significantly to 20.5 degrees (P < 0.0001) at the final follow-up. An increase in thoracic kyphosis was significantly correlated with an increase in lumbar lordosis at the final follow-up (r = 0.42). The average preoperative vertebral rotation angle was 19.7 degrees, which improved significantly after surgery to 14.9 degrees (P = 0.0001). There was no correlation between change in thoracic kyphosis and change in apical vertebral rotation (r = - 0.123). The average preoperative total Scoliosis Research Society questionnaire score was 3.0, which significantly improved to 4.4 (P < 0.0001) at the final follow-up. Throughout surgery and even after, there were no instrumentation failures, pseudarthrosis, infection of the surgical site, or clinically relevant neurovascular complications. Conclusion. The simultaneous double-rod rotation technique for treating Lenke 1 AIS provides significant sagittal correction of the main thoracic curve while maintaining sagittal profiles and correcting coronal and axial deformities.
• A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups

  Douglas Londono, Ikuyo Kou, Todd A. Johnson, Swarkar Sharma, Yoji Ogura, Tatsuhiko Tsunoda, Atsushi Takahashi, Morio Matsumoto, John A. Herring, Tsz-Ping Lam, Xingyan Wang, Elisa M. S. Tam, You-Qiang Song, Yan-Hui Fan, Danny Chan, Kathryn S. E. Cheah, Xusheng Qiu, Hua Jiang, Dongsheng Huang, Peiqiang Su, Pak Sham, Kenneth M. C. Cheung, Keith D. K. Luk, Derek Gordon, Yong Qiu, Jack Cheng, Nelson Tang, Shiro Ikegawa, Carol A. Wise

  JOURNAL OF MEDICAL GENETICS 51 6 401 - 406 2014年06月 [査読有り][通常論文]
   

  Background Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Methods Here, we report the first ICSG study, a meta-analysis of the LBX1 locus in six Asian and three non-Asian cohorts. Results We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22x10-43 for rs11190870, and P=2.94x10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a similar to 25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Conclusions Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.
• Fungal Spinal Infection Treated with Percutaneous Posterolateral Endoscopic Surgery

  Akira Iwata, Manabu Ito, Kuniyoshi Abumi, Hideki Sudo, Yoshihisa Kotani, Yasuhiro Shono, Akio Minami

  JOURNAL OF NEUROLOGICAL SURGERY PART A-CENTRAL EUROPEAN NEUROSURGERY 75 3 170 - 176 2014年05月 [査読有り][通常論文]
   

  BackgroundFungal infection in the spine is rare and its treatment is challenging. Conservative treatment with antifungal drugs often fails, with the result that surgical intervention is required in many cases. Since the general conditions of patients with fungal infections is bad due to their comorbid medical problems, surgical invasiveness should be minimized. We have reported the effectiveness of posterolateral endoscopic surgery in treating pyogenic and tuberculous spondylodiscitis. This study reports the clinical results of posterolateral endoscopic surgery in treating fungal spinal infection. MethodsBetween 2001 and 2009 we used posterolateral endoscopic surgery to treat four patients with fungal spinal infection. All were males, three in their 50s, and one in his 70s. The levels of infection were L2/3 and L5/S1 in one patient each, and L3/4 in two patients. As for the Griffiths classification, there was one patient in class 1, two in class 2, and one in class 3. Postoperative follow-up periods ranged from 26 to 92 months. Treatment history before surgery, species of causative fungus, selection of antifungal drugs and their duration, blood examinations, subsidence of infection, radiographic changes of the spine, and various complications were all investigated. ResultsAll patients had been treated with broad-spectrum antibiotics followed by anti-methicillin-resistant Staphylococcus aureus drugs for more than several months by previous doctors. From cultures of the tissues taken during endoscopic surgery, Candida species were detected in three patients and Paecilomyces species in one. After endoscopic surgery, the patients were administered antifungal drugs for 3 months, except for one patient who had a side effect. All patients showed successful subsidence of infection at the final follow-up. ConclusionFungal spinal infection occurred in patients with a lengthy use of broad-spectrum antibiotics and anti-methicillin-resistant Staphylococcus aureus drugs. Posterolateral endoscopic debridement and irrigation surgery successfully treated fungal spinal infection. This procedure is effective in treatment of fungal spinal infection with minimal invasiveness.
• Anomalous vertebral and posterior communicating arteries as a risk factor in instrumentation of the posterior cervical spine

  K. Nagahama, H. Sudo, K. Abumi, M. Ito, M. Takahata, S. Hiratsuka, K. Kuroki, N. Iwasaki

  BONE & JOINT JOURNAL 96B 4 535 - 540 2014年04月 [査読有り][通常論文]
   

  We investigated the incidence of anomalies in the vertebral arteries and Circle of Willis with three-dimensional CT angiography in 55 consecutive patients who had undergone an instrumented posterior fusion of the cervical spine. We recorded any peri-operative and post-operative complications. The frequency of congenital anomalies was 30.9%, abnormal vertebral artery blood flow was 58.2% and vertebral artery dominance 40%. The posterior communicating artery was occluded on one side in 41.8% of patients and bilaterally in 38.2%. Variations in the vertebral arteries and Circle of Willis were not significantly related to the presence or absence of posterior communicating arteries. Importantly, 18.2% of patients showed characteristic variations in the Circle of Willis with unilateral vertebral artery stenosis or a dominant vertebral artery, indicating that injury may cause lethal complications. One patient had post-operative cerebellar symptoms due to intra-operative injury of the vertebral artery, and one underwent a different surgical procedure because of insufficient collateral circulation. Pre-operative assessment of the vertebral arteries and Circle of Willis is essential if a posterior spinal fusion with instrumentation is to be carried out safely.
• Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

  Koji Iwasaki, Hideki Sudo, Katsuhisa Yamada, Manabu Ito, Norimasa Iwasaki

  PLOS ONE 9 3 e92442  2014年03月 [査読有り][通常論文]
   

  Background: Discography and discoblock are imaging procedures used to diagnose discogenic low back pain. Although needle puncture of the intervertebral disc (IVD) itself induces disc degeneration, the agents used in these procedures may also have harmful effects on IVD cells. The purpose of this study was to analyze whether radiocontrast agents and local anesthetic agents have detrimental effects on human nucleus pulposus (NP) cells. Methods: Healthy human NP cells were cultured for 7 days in three-dimensional (3D) cell-alginate bead composites, and were then exposed to clinically relevant doses of a radiocontrast agent (iotrolan) or local anesthetic (lidocaine or bupivacaine). Cell viability and apoptosis were measured by confocal microscopy and flow cytometry. On the basis of caspase expression profiles, the apoptotic pathways activated by the agents were identified by Western blot analysis. Results: The radiocontrast agent iotrolan did not affect NP cell viability or induce apoptosis. In contrast, both the anesthetic agents significantly decreased cell viability and increased the apoptotic cell number in a time-and dose-dependent manner. After 120 min, 2% lidocaine and 0.5% bupivacaine decreased percent live cells to 13% and 10%, respectively (p<0.05). The number of apoptotic cells was doubled by increasing lidocaine dosage from 1% to 2% (23% and 42%) and bupivacaine from 0.25% to 0.50% (25% and 48%) (p<0.05). Western blot analysis revealed that both anesthetic agents upregulated cleaved caspase-3 and caspase-8, whereas only bupivacaine upregulated cleaved caspase-9. Conclusions/Significance: The present study demonstrates that iotrolan does not affect the viability of healthy human NP cells. In contrast, the two anesthetic agents commonly used in discography or discoblock may cause extensive damage to IVDs by inducing apoptotic cell death.
• Caspase 3 Silencing Inhibits Biomechanical Overload-Induced Intervertebral Disk Degeneration

  Katsuhisa Yamada, Hideki Sudo, Koji Iwasaki, Naoki Sasaki, Hideaki Higashi, Yusuke Kameda, Manabu Ito, Masahiko Takahata, Kuniyoshi Abumi, Akio Minami, Norimasa Iwasaki

  AMERICAN JOURNAL OF PATHOLOGY 184 3 753 - 764 2014年03月 [査読有り][通常論文]
   

  Intervertebral disk (IVD) degeneration causes debilitating low back pain in much of the worldwide population. No efficient treatment exists because of an unclear pathogenesis. One characteristic event early in such degeneration is the apoptosis of nucleus pulposus (NP) cells embedded in IVDs. Excessive biomechanical loading may also be a major etiology of IVD degeneration. The present study used in vitro and in vivo models of compressive loading to elucidate the underlying mechanism of IVD degeneration. In addition, we investigated whether the inhibition of apoptosis is a potential clinical therapeutic strategy for the treatment of IVD degeneration induced by biomechanicaL stress. A TUNEL assay showed that NP cell agarose three-dimensional composite cultures subjected to uniaxiaL, unconfined, static, compressive loading exhibited a time-dependent increase in apoptosis. Western blot analysis revealed the upregulation of several extracellular matrix-degrading enzymes and down-regulation of tissue inhibitor of metaLloproteinase 1. These responses to compressive loading were all significantly inhibited by caspase 3 siRNA. In the in vivo model of compressive Loading-induced IVD degeneration, a single Localinjection of caspase 3 siRNA significantly inhibited IVD degeneration by magnetic resonance imaging, histological findings, IHC, and TUNEL assay. The present study suggests that caspase 3 siRNA attenuates overload-induced IVD degeneration by inhibiting NP cell apoptosis and the expression of matrix-degrading enzymes.
• Cervical spondylotic myelopathy with subacute combined degeneration

  Takuji Miyazaki, Hideki Sudo, Shigeto Hiratsuka, Norimasa Iwasaki

  SPINE JOURNAL 14 2 381 - 382 2014年02月 [査読有り][通常論文]
  
• Anomalous vertebral and posterior communicating arteries as a risk factor in instrumentation of the posterior cervical spine

  K. Nagahama, H. Sudo, K. Abumi, M. Ito, M. Takahata, S. Hiratsuka, K. Kuroki, N. Iwasaki

  Bone and Joint Journal 96 4 535 - 540 2014年 [査読有り][通常論文]
   

  We investigated the incidence of anomalies in the vertebral arteries and Circle of Willis with three-dimensional CT angiography in 55 consecutive patients who had undergone an instrumented posterior fusion of the cervical spine. We recorded any peri-operative and post-operative complications. The frequency of congenital anomalies was 30.9%, abnormal vertebral artery blood flow was 58.2% and vertebral artery dominance 40%. The posterior communicating artery was occluded on one side in 41.8% of patients and bilaterally in 38.2%. Variations in the vertebral arteries and Circle of Willis were not significantly related to the presence or absence of posterior communicating arteries. Importantly, 18.2% of patients showed characteristic variations in the Circle of Willis with unilateral vertebral artery stenosis or a dominant vertebral artery, indicating that injury may cause lethal complications. One patient had post-operative cerebellar symptoms due to intra-operative injury of the vertebral artery, and one underwent a different surgical procedure because of insufficient collateral circulation. Pre-operative assessment of the vertebral arteries and Circle of Willis is essential if a posterior spinal fusion with instrumentation is to be carried out safely.
• Anterior decompression and strut graft versus posterior decompression and pedicle screw fixation with vertebroplasty for osteoporotic thoracolumbar vertebral collapse with neurologic deficits

  Hideki Sudo, Manabu Ito, Kiyoshi Kaneda, Kuniyoshi Abumi, Yoshihisa Kotani, Ken Nagahama, Akio Minami, Norimasa Iwasaki

  Spine Journal 13 12 1726 - 1732 2013年12月01日 [査読有り][通常論文]
   

  Background context With the increase of the elderly population, osteoporotic vertebral fractures have been frequently reported. Surgical intervention is usually recommended in osteoporotic vertebral collapse with neurologic deficits. However, very few reports on surgical interventions exist. Purpose To compare surgical results of anterior and posterior procedures for treating osteoporotic thoracolumbar vertebral collapse with sustained neurologic deficits. Study design Retrospective comparative study. Patient sample Fifty patients who sustained osteoporotic thoracolumbar vertebral collapse with neurologic deficits were treated either by anterior decompression and strut graft (n=32) or by posterior decompression and pedicle screw fixation with vertebroplasty (n=18). Outcome measures Incidence of complications, sagittal Cobb angle, spinal canal encroachment, and Japanese Orthopedic Association score. Methods The authors retrospectively reviewed the results of a consecutive series of patients undergoing anterior decompression and strut graft or posterior decompression and pedicle screw fixation with vertebroplasty for osteoporotic thoracolumbar vertebral collapse with neurologic deficits. Operative notes, clinical charts, and radiographs were analyzed. Results Operative time was similar between the groups, but intraoperative blood loss was significantly lower in the posterior group. All patients showed neurologic recovery. No significant difference was observed in the neurologic improvement, kyphosis correction angle, and loss of correction. Perioperative respiratory complications were found in 11 patients (34%) in the anterior group. In the anterior group, early posterior reinforcement was required in patients with very low bone density below 0.60 g/cm2 and/or in those with three segments of instrumentation for two vertebral collapses. Posterior group patients did not undergo additional surgery. Conclusions Anterior reconstruction for osteoporotic vertebral collapse is significant because anterior elements, particularly those at the thoracolumbar junction, play a major role in load bearing. However, difficulties arise when anterior reconstruction is performed in cases with very low bone density and in those with multiple vertebral collapse.
• Primary spinal marginal zone lymphoma relapse at a different spinal level after remission of the primary lesion.

  Hojo Y, Ito M, Abumi K, Sudo H, Takahata M

  Global spine journal 3 4 261 - 264 4 2013年12月 [査読有り][通常論文]
  
• Severe fixed cervical kyphosis treated with circumferential osteotomy and pedicle screw fixation using an anterior-posterior-anterior surgical sequence

  Hiroyuki Yoshihara, Kuniyoshi Abumi, Manabu Ito, Yoshihisa Kotani, Hideki Sudo, Masahiko Takahata

  World Neurosurgery 80 5 654 - e21 2013年11月 [査読有り][通常論文]
   

  Background: Surgical treatment for severe circumferentially fixed cervical kyphosis has been challenging. Both anterior and posterior releases are necessary to provide the cervical mobility necessary for fusion in a corrected position. Objective: In two case reports, we describe the circumferential osteotomy of anterior-posterior-anterior surgical sequence, and the efficacy of this technique when cervical pedicle screw fixation for severe fixed cervical kyphosis is used. Case Description: Etiology of fixed cervical kyphosis was unknown in one patient and neurofibromatosis in one patient. Both patients had severe fixed cervical kyphosis as determined by cervical radiographs and underwent circumferential osteotomy and fixation via an anterior-posterior- anterior surgical sequence and correction of kyphosis by pedicle screw fixation. Conclusion: Severe fixed cervical kyphosis was treated successfully by the use of circumferential osteotomy and pedicle screw fixation. The surgical sequence described in this report is a reasonable approach for severe circumferentially fixed cervical kyphosis and short segment fixation can be achieved using pedicle screws.
• Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3

  Atsushi Miyake, Ikuyo Kou, Yohei Takahashi, Todd A. Johnson, Yoji Ogura, Jin Dai, Xusheng Qiu, Atsushi Takahashi, Hua Jiang, Huang Yan, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Naoya Hosono, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Ikuho Yonezawa, Michiaki Kubo, Tatsuhiko Tsunoda, Kota Watanabe, Kazuhiro Chiba, Yoshiaki Toyama, Yong Qiu, Morio Matsumoto, Shiro Ikegawa

  PLOS ONE 8 9 e72802  2013年09月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of similar to 12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P = 4.00x10(-8), odds ratio [OR] = 2.05). Its association was replicated in a Chinese population (combined P = 6.43x10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.
• A replication study for association of 53 single nucleotide polymorphisms in a scoliosis prognostic test with progression of adolescent idiopathic scoliosis in Japanese

  Yoji Ogura, Yohei Takahashi, Ikuyo Kou, Masahiro Nakajima, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Ikuho Yonezawa, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Kota Watanabe, Kazuhiro Chiba, Yoshiaki Toyama, Morio Matsumoto, Shiro Ikegawa

  Spine 38 16 1375 - 1379 2013年07月15日 [査読有り][通常論文]
   

  STUDY DESIGN.: A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS). OBJECTIVE.: To determine whether the association of 53 SNPs with curve progression reported in white patients with AIS are replicated in Japanese patients with AIS. SUMMARY OF BACKGROUND DATA.: Predicting curve progression is important in clinical practice of AIS. The progression of AIS is reported to be associated with a number of genes. Associations with 53 SNPs have been reported, and the SNPs are used for a progression test in white patients with AIS however, there has been no replication study for their association. METHODS.: We recruited 2117 patients with AIS with 10 or more (Cobb angle) of scoliosis curves. They were divided into progression and nonprogression groups according to their Cobb angle. We defined the progression of the curve as Cobb angle more than 50 for skeletally mature subjects and more than 40 for immature patients, subjects. We defined the nonprogression of the curve as Cobb angle 50 or less only for skeletally mature subjects. Of the 2117 patients, 1714 patients with AIS were allocated to either the progression or nonprogression group. We evaluated the association of 53 SNPs with curve progression by comparing risk allele frequencies between the 2 groups. RESULTS.: We evaluated the progression (N = 600) and nonprogression (N = 1114) subjects. Their risk allele frequencies were not different significantly. We found no replication of the association on AIS curve progression in any of the SNPs. CONCLUSION.: The associations of the 53 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression. Copyright © 2013 Lippincott Williams & Wilkins.
• Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis

  Ikuyo Kou, Yohei Takahashi, Todd A. Johnson, Atsushi Takahashi, Long Guo, Jin Dai, Xusheng Qiu, Swarkar Sharma, Aki Takimoto, Yoji Ogura, Hua Jiang, Huang Yan, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Naoya Hosono, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Ikuho Yonezawa, Douglas Londono, Derek Gordon, John A. Herring, Kota Watanabe, Kazuhiro Chiba, Naoyuki Kamatani, Qing Jiang, Yuji Hiraki, Michiaki Kubo, Yoshiaki Toyama, Tatsuhiko Tsunoda, Carol A. Wise, Yong Qiu, Chisa Shukunami, Morio Matsumoto, Shiro Ikegawa

  Nature Genetics 45 6 676 - 679 2013年06月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10 -10 odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10-14 OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS. © 2013 Nature America, Inc. All rights reserved.
• Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis

  Ikuyo Kou, Yohei Takahashi, Todd A. Johnson, Atsushi Takahashi, Long Guo, Jin Dai, Xusheng Qiu, Swarkar Sharma, Aki Takimoto, Yoji Ogura, Hua Jiang, Huang Yan, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Naoya Hosono, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Ikuho Yonezawa, Douglas Londono, Derek Gordon, John A. Herring, Kota Watanabe, Kazuhiro Chiba, Naoyuki Kamatani, Qing Jiang, Yuji Hiraki, Michiaki Kubo, Yoshiaki Toyama, Tatsuhiko Tsunoda, Carol A. Wise, Yong Qiu, Chisa Shukunami, Morio Matsumoto, Shiro Ikegawa

  Nature Genetics 45 6 676 - 679 2013年06月 [査読無し][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10 -10 odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10-14 OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS. © 2013 Nature America, Inc. All rights reserved.
• Long-term Outcomes of Anterior Spinal Fusion for Treating Thoracic Adolescent Idiopathic Scoliosis Curves Average 15-Year Follow-up Analysis

  Hideki Sudo, Manabu Ito, Kiyoshi Kaneda, Yasuhiro Shono, Masahiko Takahata, Kuniyoshi Abumi

  SPINE 38 10 819 - 826 2013年05月 [査読有り][通常論文]
   

  Study Design. Retrospective review. Objective. To assess the long-term outcomes of anterior spinal fusion (ASF) for treating thoracic adolescent idiopathic scoliosis (AIS). Summary of Background Data. Although ASF is reported to provide good coronal and sagittal correction of the main thoracic (MT) AIS curves, the long-term outcomes of ASF is unknown. Methods. A consecutive series of 25 patients with Lenke 1 MT AIS were included. Outcome measures comprised radiographical measurements, pulmonary function, and Scoliosis Research Society outcome instrument (SRS-30) scores (preoperative SRS-30 scores were not documented). Postoperative surgical revisions and complications were recorded. Results. Twenty-five patients were followed-up for 12 to 18 years (average, 15.2 yr). The average MT Cobb angle correction rate and the correction loss at the final follow-up were 56.7% and 9.2 degrees, respectively. The average preoperative instrumented level of kyphosis was 8.3 degrees, which significantly improved to 18.6 degrees (P = 0.0003) at the final follow-up. The average percent-predicted forced vital capacity and forced expiratory volume in 1 second were significantly decreased during long-term follow-up measurements (73% and 69%; P = 0.0004 and 0.0016, respectively). However, no patient had complaints related to pulmonary function. The average total SRS-30 score was 4.0. Implant breakage was not observed. All patients, except 1 who required revision surgery, demonstrated solid fusion. Late instrumentation-related bronchial problems were observed in 1 patient who required implant removal and bronchial tube repair, 13 years after the initial surgery. Conclusion. Overall radiographical findings and patient outcome measures of ASF for Lenke 1 MT AIS were satisfactory at an average follow-up of 15 years. ASF provides significant sagittal correction of the main thoracic curve with long-term maintenance of sagittal profiles. Percent-predicted values of forced vital capacity and forced expiratory volume in 1 second were decreased in this cohort; however, no patient had complaints related to pulmonary function.
• Long-term outcomes of anterior dual-rod instrumentation for thoracolumbar and lumbar curves in adolescent idiopathic scoliosis: A twelve to twenty-three-year follow-up study

  Hideki Sudo, Manabu Ito, Kiyoshi Kaneda, Yasuhiro Shono, Kuniyoshi Abumi

  Journal of Bone and Joint Surgery - Series A 95 8 e491 - e498 2013年04月17日 [査読有り][通常論文]
   

  Background: Anterior spinal fusion with instrumentation is used for the treatment of thoracolumbar/lumbar scoliosis. The aim of this long-term, retrospective, hospital-based cohort study was to determine the outcomes of anterior dual-rod instrumentation in a consecutive series of patients with thoracolumbar/lumbar adolescent idiopathic scoliosis managed by a single surgeon at a single institution. Methods: A consecutive series of thirty-two patients with Lenke type-5C thoracolumbar/lumbar adolescent idiopathic scoliosis were included. Outcome measures included patient demographics, radiographic measurements, adjacentsegment degeneration, pulmonary function, and Scoliosis Research Society outcome instrument (SRS-30) scores. Perioperative and postoperative complications were recorded. Results: Thirty patients were followed for a mean of 17.2 years (range, twelve to twenty-three years). The mean thoracolumbar/ lumbar Cobb angle correction rate and correction loss at the time of the latest follow-up were 79.8% and 3.4°, respectively. The average percent-predicted forced vital capacity and forced expiratory volume in one second were 91.8% and 81.8%, respectively. The average total SRS-30 score was 4.2. Mild degeneration below the fusion mass was observed in 23% of the patients. No instrumentation failure, pseudarthrosis, surgical site infection, or clinically relevant neurovascular complications were observed. Two patients required surgical revision with posterior spinal instrumentation, one because of subjacent disc wedging and the other because of progression of the thoracic curve deformity. Conclusions: Radiographic findings, pulmonary function, and clinical measures were satisfactory at the time of followup, at a minimum of twelve years. Anterior dual-rod instrumentation remains a useful surgical treatment for Lenke type-5C thoracolumbar/lumbar adolescent idiopathic scoliosis. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2014 by the journal of bone and joint surgery, incorporated.
• A Replication Study for Association of 5 Single Nucleotide Polymorphisms With Curve Progression of Adolescent Idiopathic Scoliosis in Japanese Patients

  Yoji Ogura, Yohei Takahashi, Ikuyo Kou, Masahiro Nakajima, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Ikuho Yonezawa, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Kota Watanabe, Kazuhiro Chiba, Yoshiaki Toyama, Morio Matsumoto, Shiro Ikegawa

  SPINE 38 7 571 - 575 2013年04月 [査読有り][通常論文]
   

  Study Design. A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS). Objective. To determine whether the association of 5 SNPs with curve progression reported in Chinese with AIS are replicated in Japanese patients with AIS. Summary of Background Data. AIS is a common spinal deformity and has a strong genetic predisposition. Predicting curve progression is important in clinical practice. The progression of AIS is reported to be associated with a number of genes. Associations with neurotrophin 3, G protein-coupled estrogen receptor, and tissue inhibitor of metalloproteinase 2 have been reported in Han Chinese with AIS; however, there has been no replication study for them. Methods. We recruited 2117 patients with AIS with a Cobb angle of 10 degrees or greater of scoliosis curves. They were grouped into progression and nonprogression groups according to their scoliosis curves. Patients whose scoliotic curves were 40 degrees or greater were included in the progression group, and those whose scoliotic curves were less than 30 degrees and had reached skeletal maturation in the nonprogression group. We evaluated the association of 5 SNPs (rs11063714 in neurotrophin 3, rs3808351, rs10269151, and rs4266553 in G protein-coupled estrogen receptor, and rs8179090 in tissue inhibitor of metalloproteinase 2 with curve progression by comparing risk allele frequencies between the 2 groups and the mean Cobb angle for each genotype. Results. We evaluated the progression (N = 880) and nonprogression (N = 492) subjects, and their risk allele frequencies were not significantly different. The mean Cobb angle for each genotype also did not have statistical difference. We found no replication of the association on AIS curve progression in any of the SNPs. Conclusion. The associations of the 5 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression.
• Global Identification of Genes Related to Nutrient Deficiency in Intervertebral Disc Cells in an Experimental Nutrient Deprivation Model

  Hideki Sudo, Katsuhisa Yamada, Koji Iwasaki, Hideaki Higashi, Manabu Ito, Akio Minami, Norimasa Iwasaki

  PLOS ONE 8 3 e58806  2013年03月 [査読有り][通常論文]
   

  Background: Intervertebral disc degeneration is a significant cause of degenerative spinal diseases. Nucleus pulposus (NP) cells reportedly fail to survive in large degenerated discs with limited nutrient availability. Therefore, understanding the regulatory mechanism of the molecular response of NP cells to nutrient deprivation may reveal a new strategy to treat disc degeneration. This study aimed to identify genes related to nutrient deprivation in NP cells on a global scale in an experimental nutrient deprivation model. Methodology/Principal Findings: Rat NP cells were subjected to serum starvation. Global gene expression was profiled by microarray analysis. Confirmation of the selected genes was obtained by real-time polymerase chain reaction array analysis. Western blotting was used to confirm the expression of selected genes. Functional interactions between p21(Cip1) and caspase 3 were examined. Finally, flow cytometric analyses of NP cells were performed. Microarray analysis revealed 2922 differentially expressed probe sets with >= 1.5-fold changes in expression. Serum starvation of NP cells significantly affected the expression of several genes involved in DNA damage checkpoints of the cell cycle, including Atm, Brca1, Cdc25, Gadd45, Hus1, Ppm1D, Rad 9, Tp53, and Cyclin D1. Both p27(Kip1) and p53 protein expression was upregulated in serum-starved cells. p21(Cip1) expression remained in NP cells transfected with short interfering RNA targeting caspase 3 (caspase 3 siRNA). Both G1 arrest and apoptosis induced by serum starvation were inhibited in cells transfected with caspase 3 siRNA. Conclusions/Significance: Nutrient deprivation in NP cells results in the activation of a signaling response including DNA damage checkpoint genes regulating the cell cycle. These results provide novel possibilities to improve the success of intervertebral disc regenerative techniques.
• Cervical myelopathy resulting from combined ossification of the ligamentum flavum and posterior longitudinal ligament: Report of two cases and literature review

  Yoshihisa Kotani, Masahiko Takahata, Kuniyoshi Abumi, Manabu Ito, Hideki Sudo, Akio Minami

  Spine Journal 13 1 -e6 - 6 2013年01月 [査読有り][通常論文]
   

  Background context: In the cervical spine, the combination of ossification of the ligamentum flavum (OLF) and ossification of the posterior longitudinal ligament (OPLL) is rarely seen. There have been only four cases reported in the English literature. Purpose: We describe two more cases that exhibited cervical myelopathy resulting from the combination of cervical OLF and OPLL and required surgery. A literature review with a comparative analysis between previous reports and present cases was also performed. Study design: Case report and literature review. Patient sample: Two patients with combined OLF and OPLL. Outcome measures: Preoperative computed tomography, magnetic resonance imaging, and pathological findings from operative specimens were used to confirm the diagnoses. Methods: A 76-year-old man (Case 1) presented with disturbance of gait and fine finger movement. Magnetic resonance imaging showed severe spinal canal stenosis and cord compression at the C3-C4 level. Computed tomography showed OPLL at the C2-C6 levels (segmental type) and OLF at the left C3-C4 level. The patient underwent posterior decompression and OLF resection. A 75-year-old man (Case 2) presented with sensory disturbance and muscle weakness in his bilateral upper extremities and disturbance in fine finger movements. Magnetic resonance imaging showed severe spinal canal stenosis and cord compression at the C2-C3 and C3 levels. Computed tomography showed OPLL at the C3-C7 levels (mixed type) and OLF at the left C2-C3 and C3 levels. The patient also underwent posterior decompression and OLF resection. Results: In both cases, histological examination of the surgical specimens showed osseous tissue and enchondral ossification within the ligamentum flavum, and the diagnosis in each case was OLF. After surgery, both patients' symptoms immediately improved, and no recurrence was observed at 2 years after surgery. Conclusions: We experienced two cases of cervical myelopathy resulting from the combination of OLF and OPLL in the cervical spine. The symptoms of myelopathy were treated successfully by laminectomy and laminoplasty with OLF resection in both cases. The literature review including the present two cases revealed that cervical OLF tended to occur adjacent or close to the margin of cervical OPLL, suggesting that the increased mechanical stress at the junction of OPLL may be a causative factor. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
• Impact of deep extensor muscle-preserving approach on clinical outcome of laminoplasty for cervical spondylotic myelopathy: comparative cohort study

  Yoshihisa Kotani, Kuniyoshi Abumi, Manabu Ito, Hideki Sudo, Masahiko Takahata, Ken Nagahama, Akira Iwata, Akio Minami

  EUROPEAN SPINE JOURNAL 21 8 1536 - 1544 2012年08月 [査読有り][通常論文]
   

  This study aimed to compare patients undergoing deep extensor muscle-preserving laminoplasty and conventional open-door laminoplasty for the treatment of cervical spondylotic myelopathy (CSM). We specifically assessed axial pain, cervical spine function, and quality of life (QOL) with a minimum follow-up period of 3 years. Ninety patients were divided into two groups and underwent either conventional open-door laminoplasty (CL group) or laminoplasty using the deep extensor muscle-preserving approach (MP group). The latter approach was undertaken by preserving the multifidus and semispinalis cervicis attachments followed by open-door laminoplasty and resuturing of the bisected spinous processes at each decompression level. The mean follow-up period was 7.7 years (range, 36-128 months). Preoperative and follow-up evaluations included the Japanese Orthopaedic Association (JOA) score, a tentative version of the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) including cervical spine function and QOL, and a visual analog scale (VAS) for axial pain. Radiological analyses included cervical lordosis and flexion-extension range of motion (C2-7), as well as deep extensor muscle areas on axial magnetic resonance imaging (MRI). The mean number of decompressed laminae was 3.9 and 3.3 in CL and MP groups, respectively, which was statistically equivalent. Japanese Orthopaedic Association recovery was statistically equivalent between the two groups. The MP group demonstrated a superior QOL score (57 vs. 46 %) compared with the CL group at final follow-up (p < 0.05). Mean VAS scores at final follow-up were 2.2 and 4.3 in MP and CL groups, respectively (p < 0.05). Cervical lordosis and flexion-extension range of motion were statistically equivalent. The percentage deep muscle area on MRI was significantly lesser in the CL group compared with the MP group (58 vs. 102 %; p < 0.01). We demonstrated the superiority of deep extensor muscle-preserving laminoplasty in terms of postoperative axial pain, QOL, and prevention of atrophy of the deep extensor muscles over conventional open-door laminoplasty for the treatment of CSM.
• A retrospective study of congenital osseous anomalies at the craniocervical junction treated by occipitocervical plate-rod systems

  Xianjun Ding, Kuniyoshi Abumi, Manabu Ito, Hideki Sudo, Masahiko Takahata, Ken Nagahama, Akira Iwata

  EUROPEAN SPINE JOURNAL 21 8 1580 - 1589 2012年08月 [査読有り][通常論文]
   

  To evaluate the effectiveness of posterior occipitocervical reconstruction using the anchors of cervical pedicle screws and plate-rod systems for patients with congenital osseous anomalies at the craniocervical junction. Twenty patients with congenital osseous lesions who underwent posterior occipitocervical fusion using the anchors of cervical pedicle screws and plate-rod systems for reduction and fixation from 1996 to 2009 were reviewed. The lesions included os odontoideum, occipitalization of the atlas, congenital C2-3 fusion, congenital atlantoaxial subluxation, congenital basilar invagination and combined anomalies. The clinical assessment and the measurements of the images were performed preoperatively, postoperatively and at most recent follow-up. The combined deformity of flexion of the occipitoatlantoaxial complex and invagination of the odontoid process associated with congenital osseous lesions at the craniocervical junction was corrected by application of combined forces of extension and distraction between the occiput and the cervical pedicle screws. Preoperative myelopathy improved in 94.7 % patients. The mean Ranawat value, Redlund-Johnnell value, atlantodental distance, occiput (O)-C2 angle, and C2-C7 lordosis angle improved postoperatively and was sustained at most recent follow-up. The mean cervicomedullary angle improved from 129.3A degrees preoperatively to 153.3A degrees postoperatively. The mean range of motion at the lower adjacent motion segment remained unchanged at most recent follow-up. The fusion rate was 95 %. The results of the present study indicate that posterior occipitocervical reconstruction using the anchors of cervical pedicle screws and plate-rod systems is an effective technique for treatment of deformities and/or instability caused by congenital osseous anomalies at the craniocervical junction.
• Post-traumatic lumbar subdural hematoma

  Hideki Sudo, Kuniyoshi Abumi, Yusuke Menjo, Manabu Ito

  SPINE JOURNAL 12 8 714 - 715 2012年08月 [査読有り][通常論文]
  
• Mid-term clinical results of minimally invasive decompression and posterolateral fusion with percutaneous pedicle screws versus conventional approach for degenerative spondylolisthesis with spinal stenosis

  Yoshihisa Kotani, Kuniyoshi Abumi, Manabu Ito, Hideki Sudo, Yuichiro Abe, Akio Minami

  EUROPEAN SPINE JOURNAL 21 6 1171 - 1177 2012年06月 [査読有り][通常論文]
   

  In order to minimize perioperative invasiveness and improve the patients' functional capacity of daily living, we have performed minimally invasive lumbar decompression and posterolateral fusion (MIS-PLF) with percutaneous pedicle screw fixation for degenerative spondylolisthesis with spinal stenosis. Although several minimally invasive fusion procedures have been reported, no study has yet demonstrated the efficacy of MIS-PLF in degenerative spondylolisthesis of the lumbar spine. This study prospectively compared the mid-term clinical outcome of MIS-PLF with those of conventional PLF (open-PLF) focusing on perioperative invasiveness and patients' functional capacity of daily living. A total of 80 patients received single-level PLF for lumbar degenerative spondylolisthesis with spinal stenosis. There were 43 cases of MIS-PLF and 37 cases of open-PLF. The surgical technique of MIS-PLF included making a main incision (4 cm), and neural decompression followed by percutaneous pedicle screwing and rod insertion. The posterolateral gutter including the medial transverse process was decorticated and iliac bone graft was performed. The parameters analyzed up to a 2-year period included the operation time, intra and postoperative blood loss, Oswestry-Disability Index (ODI), Roland-Morris Questionnaire (RMQ), the Japanese Orthopaedic Association score, and the visual analogue scale of low back pain. The fusion rate and complications were also reviewed. The average operation time was statistically equivalent between the two groups. The intraoperative blood loss was significantly less in the MIS-PLF group (181 ml) when compared to the open-PLF group (453 ml). The postoperative bleeding on day 1 was also less in the MIS-PLF group (210 ml) when compared to the open-PLF group (406 ml). The ODI and RMQ scores rapidly decreased during the initial postoperative 2 weeks in the MIS-PLF group, and consistently maintained lower values than those in the open-PLF group at 3, 6, 12, and 24 months postoperatively. The fusion rate was statistically equivalent between the two groups (98 vs. 100%), and no major complications occurred. The MIS-PLF utilizing a percutaneous pedicle screw system is less invasive compared to conventional open-PLF. The reduction in postoperative pain led to an increase in activity of daily living (ADL), demonstrating rapid improvement of several functional parameters. This superiority in the MIS-PLF group was maintained until 2 years postoperatively, suggesting that less invasive PLF offers better mid-term results in terms of reducing low back pain and improving patients' functional capacity of daily living. The MIS-PLF utilizing percutaneous pedicle screw fixation serves as an alternative technique, eliminating the need for conventional open approach.
• Spinal cord compression by hematoma in the cervical ligamentum flavum: a case report

  Yoshihisa Kotani, Hideki Sudo, Kuniyoshi Abumi, Manabu Ito, Shinji Matsubara, Akio Minami

  SPINE JOURNAL 12 4 E18 - E21 2012年04月 [査読有り][通常論文]
   

  BACKGROUND CONTEXT: There have been some reports describing hematoma in the thoracic and lumbar ligamentum flavum, but there have been only three reports of hematoma in the cervical ligamentum flavum. PURPOSE: We describe another case of the ligamentum flavum hematoma in the cervical spine with a different feature of occurrence that required surgical treatment. STUDY DESIGN: Case report. PATIENT SAMPLE: Patient with ligamentum flavum hematoma in the cervical spine. OUTCOME MEASURES: Preoperative magnetic resonance imaging and pathologic finding from operative specimen confirmed the diagnosis. METHODS: A 69-year-old man insidiously presented with pain in his left upper arm and difficulty in left shoulder abduction. Neurologic examination demonstrated a cervical myelopathy with diffuse muscle weakness of left upper extremity and sensory disturbance. Imaging studies revealed a mass of high intense on T1-weighted images and isointense on T2-weighted images posterior to the dura at C4 lower end level. The patient underwent C4-C5 hemilaminectomy and the removal of the mass. The mass existed within the ligamentum flavum and was connected toward the pedicle like the beads of a rosary. RESULTS: Histopathologic examination of the surgical specimen showed that the hematoma was present within the ligamentum flavum and contained macrophages that had phagocytosed red blood cells and hemosiderin. After surgery, the patients' symptoms immediately improved, and no recurrence was observed at 2 years postoperatively. CONCLUSIONS: We reported a very rare case of hematoma in the ligamentum flavum of the cervical spine that required surgery. Because the patient was without the history of trauma, it was suggested that the use of antiplatelet drugs was responsible for the occurrence of the disease. (C) 2012 Elsevier Inc. All rights reserved.
• Reconstruction of the Subaxial Cervical Spine Using Pedicle Screw Instrumentation

  Kuniyoshi Abumi, Manabu Ito, Hideki Sudo

  SPINE 37 5 E349 - E356 2012年03月 [査読有り][通常論文]
   

  Study Design. Review article. Objective. To review the indications, detailed techniques, and complications of cervical pedicle screw fixation procedure. Summary of Background Data. Although screw insertion into the cervical pedicles has been considered too risky for the neurovascular structures except C2 and C7, biomechanical studies revealed a superior stabilizing effect of pedicle screw fixation in the cervical spine to other fixation procedures including lateral mass screw fixation. In addition, several investigators reported superior reconstructive results of unstable cervical spine. Methods. A literature review and review of the authors' experience in the treatment of the patients with unstable cervical spine and/or cervical spinal deformities using cervical pedicle screw fixation procedure. Results. Pedicle screw fixation is biomechanically most reliable for reconstruction of the cervical spine in various kinds of disorders. Previously reported articles revealed that pedicle screw fixation is useful for reconstruction of unstable cervical spine and correction of cervical deformities. Neurovascular complication by this procedure cannot be completely eliminated; however, it can be minimized by sufficient preoperative imaging studies and strict control of screw placement during surgery. Modern technology of computer navigation system and newly developing aiming devices can be expected to increase the accuracy of screw placement. Conclusion. Pedicle screw provides excellent 3-dimensional fixations and is a useful procedure for reconstruction of the cervical spine in various kinds of disorders. Possible neurovascular complication can be minimized by sufficient preoperative imaging studies and strict control of screw placement during surgery.
• Cervical angina because of ossification of the posterior longitudinal ligament

  Hideki Sudo, Reo Goto

  SPINE JOURNAL 12 2 169 - 169 2012年02月 [査読有り][通常論文]
  
• A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis

  Yohei Takahashi, Ikuyo Kou, Atsushi Takahashi, Todd A. Johnson, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Kota Watanabe, Kazuhiro Chiba, Naoya Hosono, Naoyuki Kamatani, Tatsuhiko Tsunoda, Yoshiaki Toyama, Michiaki Kubo, Morio Matsumoto, Shiro Ikegawa

  NATURE GENETICS 43 12 1237 - U96 2011年12月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis is a pediatric spinal deformity affecting 2-3% of school-age children worldwide(1). Genetic factors have been implicated in its etiology(2). Through a genome-wide association study (GWAS) and replication study involving a total of 1,376 Japanese females with adolescent idiopathic scoliosis and 11,297 female controls, we identified a locus at chromosome 10q24.31 associated with adolescent idiopathic scoliosis susceptibility. The most significant SNP (rs11190870; combined P = 1.24 x 10(-19); odds ratio (OR) = 1.56) is located near LBX1 (encoding ladybird homeobox 1). The identification of this susceptibility locus provides new insights into the pathogenesis of adolescent idiopathic scoliosis.
• A novel cost-effective computer-assisted imaging technology for accurate placement of thoracic pedicle screws

  Yuichiro Abe, Manabu Ito, Kuniyoshi Abumi, Yoshihisa Kotani, Hideki Sudo, Akio Minami

  JOURNAL OF NEUROSURGERY-SPINE 15 5 479 - 485 2011年11月 [査読有り][通常論文]
   

  Object. Use of computer-assisted spine surgery (CASS) technologies, such as navigation systems, to improve the accuracy of pedicle screw (PS) placement is increasingly popular. Despite of their benefits, previous CASS systems are too expensive to be ubiquitously employed, and more affordable and portable systems are desirable. The aim of this study was to introduce a novel and affordable computer-assisted technique that 3-dimensionally visualizes anatomical features of the pedicles and assists in PS insertion. The authors have termed this the 3D-visual guidance technique for inserting pedicle screws (3D-VG TIPS). Methods. The 3D-VG technique for placing PSs requires only a consumer-class computer with an inexpensive 3D DICOM viewer; other special equipment is unnecessary. Preoperative CT data of the spine were collected for each patient using the 3D-VG TIPS. In this technique, the anatomical axis of each pedicle can be analyzed by volume-rendered 3D models, as with existing navigation systems, and both the ideal entry point and the trajectory of each PS can be visualized on the surface of 3D-rendered images. Intraoperative guidance slides are made from these images and displayed on a TV monitor in the operating room. The surgeon can insert PSs according to these guidance slides. The authors enrolled 30 patients with adolescent idiopathic scoliosis (AIS) who underwent posterior fusion with segmental screw fixation for validation of this technique. Results. The novel technique allowed surgeons, from office or home, to evaluate the precise anatomy of each pedicle and the risks of screw misplacement, and to perform 3D preoperative planning for screw placement on their own computer. Looking at both 3D guidance images on a TV monitor and the bony structures of the posterior elements in each patient in the operating theater, surgeons were able to determine the best entry point for each PS with ease and confidence. Using the current technique, the screw malposition rate was 4.5% in the thoracic region in corrective surgery for AIS. Conclusions. The authors found that 3D-VG TIPS worked on a consumer-class computer and easily visualized the ideal entry point and trajectory of PSs in any operating theater without costly special equipment. This new technique is suitable for preoperative planning and intraoperative guidance when performing reconstructive surgery with PSs. (DOI: 10.3171/2011.6.SPINE10721)
• Lack of Association between Adolescent Idiopathic Scoliosis and Previously Reported Single Nucleotide Polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese Population

  Yohei Takahashi, Morio Matsumoto, Tatsuki Karasugi, Kota Watanabe, Kazuhiro Chiba, Noriaki Kawakami, Taichi Tsuji, Koki Uno, Teppei Suzuki, Manabu Ito, Hideki Sudo, Shohei Minami, Toshiaki Kotani, Katsuki Kono, Haruhisa Yanagida, Hiroshi Taneichi, Atsushi Takahashi, Yoshiaki Toyama, Shiro Ikegawa

  JOURNAL OF ORTHOPAEDIC RESEARCH 29 7 1055 - 1058 2011年07月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is a spinal deformity most commonly arising in apparently healthy girls around puberty. AIS has a strong genetic predisposition. Several genetic associations between AIS and single nucleotide polymorphisms (SNPs) have been reported; common SNPs in the genes for matrilin 1 (MATN1), melatonin receptor 1B (MTNR1B), tryptophan hydroxylase 1 (TPH1), and insulin-like growth factor 1 (IGF1) are reported to be associated with AIS in Chinese. However, these associations have not been replicated so far. To confirm the associations, we compared these SNPs with AIS predisposition and curve severity in a population of Japanese females consisting of 798 AIS patients and 1,239 controls. All the subjects were genotyped using the PCR-based Invader assay. We found no association of any of the SNPs with AIS predisposition or curve severity. Considering the statistical power and sample size of the present study, we concluded that these SNPs are not associated with either AIS predisposition or curve severity in Japanese. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1055-1058, 2011
• A late neurological complication following posterior correction surgery of severe cervical kyphosis

  Yoshihiro Hojo, Manabu Ito, Kuniyoshi Abumi, Yoshihisa Kotani, Hideki Sudo, Masahiko Takahata, Akio Minami

  EUROPEAN SPINE JOURNAL 20 6 890 - 898 2011年06月 [査読有り][通常論文]
   

  Though a possible cause of late neurological deficits after posterior cervical reconstruction surgery was reported to be an iatrogenic foraminal stenosis caused not by implant malposition but probably by posterior shift of the lateral mass induced by tightening screws and plates, its clinical features and pathomechanisms remain unclear. The aim of this retrospective clinical review was to investigate the clinical features of these neurological complications and to analyze the pathomechanisms by reviewing pre- and post-operative imaging studies. Among 227 patients who underwent cervical stabilization using cervical pedicle screws (CPSs), six patients who underwent correction of cervical kyphosis showed postoperative late neurological complications without any malposition of CPS (ND group). The clinical courses of the patients with deficits were reviewed from the medical records. Radiographic assessment of the sagittal alignment was conducted using lateral radiographs. The diameter of the neural foramen was measured on preoperative CT images. These results were compared with the other 14 patients who underwent correction of cervical kyphosis without late postoperative neurological complications (non-ND group). The six patients in the ND group showed no deficits in the immediate postoperative periods, but unilateral muscle weakness of the deltoid and biceps brachii occurred at 2.8 days postoperatively on average. Preoperative sagittal alignment of fusion area showed significant kyphosis in the ND group. The average of kyphosis correction in the ND was 17.6A degrees per fused segment (range 9.7A degrees-35.0A degrees), and 4.5A degrees (range 1.3A degrees-10.0A degrees) in the non-ND group. A statistically significant difference was observed in the degree of preoperative kyphosis and the correction angles at C4-5 between the two groups. The diameter of the C4-5 foramen on the side of deficits was significantly smaller than that of the opposite side in the ND group. Late postoperative neurological complications after correction of cervical kyphosis were highly associated with a large amount of kyphosis correction, which may lead foraminal stenosis and enhance posterior drift of the spinal cord. These factors may lead to both compression and traction of the nerves, which eventually cause late neurological deficits. To avoid such complications, excessive kyphosis correction should not be performed during posterior surgery to avoid significant posterior shift of the spinal cord and prophylactic foraminotomies are recommended if narrow neuroforamina were evident on preoperative CT images. Regardless of revision decompression or observation, the majority of this late neurological complication showed complete recovery over time.
• Caspase 3 as a Therapeutic Target for Regulation of Intervertebral Disc Degeneration in Rabbits

  Hideki Sudo, Akio Minami

  ARTHRITIS AND RHEUMATISM 63 6 1648 - 1657 2011年06月 [査読有り][通常論文]
   

  Objective. Although the etiology of intervertebral disc degeneration is poorly understood, one possible approach for its regulation is apoptosis inhibition. This study was undertaken to investigate the antiapoptotic effects of caspase 3 in intervertebral disc degeneration in rabbits. Methods. We investigated the effects of caspase 3 small interfering RNA (siRNA) on rabbit nucleus pulposus cells in a serum-starved medium. The effects of direct injection of Alexa Fluor 555-labeled caspase 3 siRNA into the intervertebral disc were also determined in vivo using the rabbit anular needle puncture model. Results. Rabbit nucleus pulposus cells transfected with caspase 3 siRNA showed a significant decrease in serum-starved apoptotic cells. After local injection of caspase 3 siRNA into intervertebral discs, red fluorescence was observed in the nucleus pulposus upon treatment with Alexa Fluor 555-labeled caspase 3 siRNA. Caspase 3 messenger RNA and protein were down-regulated in the caspase 3 siRNA group. Magnetic resonance imaging and histologic evaluation showed that degenerative changes were significantly suppressed in the caspase 3 siRNA group 4 and 8 weeks after injection. Quantification of TUNEL staining showed that the caspase 3 siRNA group had significantly fewer apoptotic nucleus pulposus cells than the control siRNA group. Conclusion. Our findings indicate that caspase 3 knockdown in rabbit intervertebral disc cells is effective in preventing apoptotic cell death, thus regulating intervertebral disc degeneration.
• Replication Study of the Association between Adolescent Idiopathic Scoliosis and Two Estrogen Receptor Genes

  Yohei Takahashi, Mono Matsumoto, Tatsuki Karasugi, Kota Watanabe, Kazuhiro Chiba, Noriaki Kawakami, Taichi Tsuji, Koki Uno, Teppei Suzuki, Manabu Ito, Hideki Sudo, Shohei Minami, Toshiaki Kotani, Katsuki Kono, Haruhisa Yanagida, Hiroshi Taneichi, Atsushi Takahashi, Yoshiaki Toyama, Shiro Ikegawa

  JOURNAL OF ORTHOPAEDIC RESEARCH 29 6 834 - 837 2011年06月 [査読有り][通常論文]
   

  Adolescent idiopathic scoliosis (AIS) is a common disorder with a strong genetic predisposition. Associations between MS and common single nucleotide polymorphisms (SNPs) in estrogen receptor genes have been reported. rs9340799 in the gene for estrogen receptor alpha (ESR1) is reported to be associated with curve severity in Japanese and with AIS predisposition and curve severity in Chinese. In addition, rs1256120 in the gene for estrogen receptor beta (ESR2) is reported to be associated with MS predisposition and curve severity in Chinese. However, the sample sizes of these previous studies were small, and the associations of these SNPs have not been replicated. To examine the association between AIS and estrogen receptor genes, we investigated the association of rs9340799 and rs1256120 with AIS predisposition and curve severity using a large Japanese population, consisting of 798 AIS patients and 637 sex-matched controls. We found no association of either SNP with MS predisposition or curve severity in the Japanese population. Considering the statistical power of the present study and the limitations of the previous reports, we conclude that the associations of rs9340799 and rs1256120 with MS predisposition and curve severity are negative. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:834-837, 2011
• Regulation of Apoptosis in Nucleus Pulposus Cells by Optimized Exogenous Bcl-2 Overexpression

  Hideki Sudo, Akio Minami

  JOURNAL OF ORTHOPAEDIC RESEARCH 28 12 1608 - 1613 2010年12月 [査読有り][通常論文]
   

  Although the etiology of intervertebral disc degeneration is poorly understood, one possible approach to regulate the process of intervertebral disc degeneration may include the inhibition of apoptosis We investigated the anti apoptotic effects of bcl 2 in nucleus pulposus cells to enhance disc cell survival Rat nucleus pulposus cells were transfected in vitro with a codon optimized rat bcl 2 gene Forty eight hours after transfection, cells were cultured in serum deprived medium After serum withdrawal the cells were evaluated for bcl 2 protein levels and cell apoptosis To investigate the effects of bcl 2 overexpression on the final apoptotic pathways and on basic genes important for nucleus pulposus homeostasis, mRNA levels of caspase 3, type II collagen, and aggrecan were also quantified Nucleus pulposus cells were successfully transfected with codon optimized bcl 2 gene, which effectively reduced serum starvation induced cell apoptosis Overexpression of bcl 2 also reduced the mRNA expression level of caspase 3 mRNA levels of type II collagen and aggrecan were significantly higher in bcl 2 transfected groups compared to control plasmid vector groups after serum withdrawal We firstly showed that bcl 2 overexpression in intervertebral disc cells was effective in preventing in vitro apoptotic cell death, indicating the potential advantages of this therapeutic approach in regulating disc degeneration (c) 2010 Orthopaedic Research Society Published by Wiley Periodicals, Inc J Orthop Res 28 1608-1613 2010
• A widespread echinococcosis of the spine

  H. Sudo, A. Minami

  JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 81 8 892 - 892 2010年08月 [査読有り][通常論文]
  
• One-stage posterior instrumentation surgery for the treatment of osteoporotic vertebral collapse with neurological deficits

  Hideki Sudo, Manabu Ito, Kuniyoshi Abumi, Yoshihisa Kotani, Masahiko Takahata, Yoshihiro Hojo, Akio Minami

  EUROPEAN SPINE JOURNAL 19 6 907 - 915 2010年06月 [査読有り][通常論文]
   

  The number of reports describing osteoporotic vertebral fracture has increased as the number of elderly people has grown. Anterior decompression and fusion alone for the treatment of vertebral collapse is not easy for patients with comorbid medical problems and severe bone fragility. The purpose of the present study was to evaluate the efficacy of one-stage posterior instrumentation surgery for the treatment of osteoporotic vertebral collapse with neurological deficits. A consecutive series of 21 patients who sustained osteoporotic vertebral collapse with neurological deficits were managed with posterior decompression and short-segmental pedicle screw instrumentation augmented with ultra-high molecular weight polyethylene (UHMWP) cables with or without vertebroplasty using calcium phosphate cement. The mean follow-up was 42 months. All patients showed neurologic recovery. Segmental kyphotic angle at the instrumented level was significantly improved from an average preoperative kyphosis of 22.8-14.7 at a final follow-up. Spinal canal occupation was significantly reduced from an average before surgery of 40.4-19.1% at the final follow-up. Two patients experienced loosening of pedicle screws and three patients developed subsequent vertebral compression fractures within adjacent segments. However, these patients were effectively treated in a conservative fashion without any additional surgery. Our results indicated that one-stage posterior instrumentation surgery augmented with UHMWP cables could provide significant neurological improvement in the treatment of osteoporotic vertebral collapse.
• Simultaneous double-rod rotation technique in posterior instrumentation surgery for correction of adolescent idiopathic scoliosis Technical note

  Manabu Ito, Kuniyoshi Abumi, Yoshihisa Kotani, Masahiko Takahata, Hideki Sudo, Yoshihiro Hojo, Akio Minami

  JOURNAL OF NEUROSURGERY-SPINE 12 3 293 - 300 2010年03月 [査読有り][通常論文]
   

  The authors present a new posterior correction technique consisting of simultaneous double-rod rotation using 2 contoured rods and polyaxial pedicle screws with or without Nesplon tapes. The purpose of this study is to introduce the basic principles and surgical procedures of this new posterior surgery for correction of adolescent idiopathic scoliosis. Through gradual rotation of the concave-side rod by 2 rod holders, the convex-side rod simultaneously rotates with the the concave-side rod. This procedure does not involve any force pushing down the spinal column around the apex. Since this procedure consists of upward pushing and lateral translation of the spinal column with simultaneous double-rod rotation maneuvers, it is simple and can obtain thoracic kyphosis as well its favorable scoliosis correction. This technique is applicable not only to it thoracic single curve but also to double major curves in cases of adolescent idiopathic scoliosis. (DOI: 10.317112009.9.SPINE09377)
• Spinal Cord Compression by Ligamentum Flavum Hematoma in the Thoracic Spine

  Hideki Sudo, Kuniyoshi Abumi, Manabu Ito, Yoshihisa Kotani, Masahiko Takahata, Yoshihiro Hojo, Masatoshi Sanda, Akio Minami

  SPINE 34 25 E942 - E944 2009年12月 [査読有り][通常論文]
   

  Study Design. Case report. Objective. To report an extremely rare case of hematoma derived from the ligamentum flavum within the thoracic spine. Summary of Background Data. Only one previous case has been reported of a hematoma derived from the ligamentum flavum in the thoracic spine. Methods. A 61-year-old man presented with gait disturbance and numbness below the navel. Magnetic resonance imaging on the 16th day after the onset of the symptoms showed spinal cord compression at the T10-T11 level caused by a round mass. This intraspinal, extradural space occupying lesion, continuous with ligamentum flavum was centrally hypointense and marginal hyperintense on a T1-weighted image and central heterogeneous and marginal hypointense on a T2-weighted image. The wall of the lesion was slightly enhanced after use of a contrast medium. Results. The patient underwent a T10 laminectomy and the mass was carefully resected from the dura mater. Histologic examination showed that the wall of the mass comprised fibrous connective tissue that contained elastic fibers derived from a degenerative ligamentum flavum tear. It also revealed that evidence of previous hemorrhagic events within the mass. There was no evidence of neoplastic nor synovial tissue. After surgery, the patient's numbness and gait disturbance disappeared. Conclusion. This report identifies an extremely rare case of spinal cord compression by a hematoma from the ligamentum flavum within the thoracic spine.
• Minimally Invasive Surgical Treatment for Tuberculous Spondylodiscitis

  M. Ito, H. Sudo, K. Abumi, Y. Kotani, M. Takahata, M. Fujita, A. Minami

  MINIMALLY INVASIVE NEUROSURGERY 52 5-6 250 - 253 2009年10月 [査読有り][通常論文]
   

  The authors report the cases of 3 patients with tuberculous spondylodiscitis. All patients suffered from severe back or low back pain. Posterolateral endoscopic debridement and irrigation were performed followed by retention of a drainage tube at the affected sites. Additional puncture and drainage were conducted at the same time when extensive cold abscesses were identified around the paravertebral muscle. All patients experienced immediate pain relief postoperatively. This technique is effective for rapid pain relief and in obtaining neurological resolution for patients in the early stages of tuberculous spondylodiscitis and may also be a good method for preventing further vertebral collapse and kyphotic spinal deformity such as Gibbus vertebrae.
• Minimum 2-year outcome of cervical laminoplasty with deep extensor muscle-preserving approach: impact on cervical spine function and quality of life

  Yoshihisa Kotani, Kuniyoshi Abumi, Manabu Ito, Hideki Sudo, Masahiko Takahata, Shigeki Ohshima, Yoshihiro Hojo, Akio Minami

  EUROPEAN SPINE JOURNAL 18 5 663 - 671 2009年05月 [査読有り][通常論文]
   

  In this retrospective cohort study, two surgical methods of conventional open-door laminoplasty and deep extensor muscle-preserving laminoplasty were allocated for the treatment of cervical myelopathy, and were specifically compared in terms of axial pain, cervical spine function, and quality of life (QOL) with a minimum follow-up period of 2 years. Eighty-four patients were divided into two groups and received either a conventional open-door laminoplasty (CL group) or laminoplasty using a deep extensor muscle-preserving approach (MP group). The latter approach was performed by preserving multifidus and semispinalis cervicis attachments followed by open-door laminoplasty and re-suture of the bisected spinous processes at each decompression level. The average follow-up period was 38 months (25-53 months). The preoperative and follow-up evaluations included the original Japanese Orthopaedic Association (JOA) score, the new tentative JOA score including cervical spine function and QOL, and the visual analogue scale (VAS) of axial pain. Radiological analyses included cervical lordosis and flexion-extension range of motion (flex-ext ROM) (C2-7), and deep extensor muscle areas on MR axial images. The JOA recovery rates were statistically equivalent between two groups. The MP group demonstrated a statistically superior cervical spine function (84% vs 63%) and QOL (61% vs 45%) when compared to the CL group at final follow-up (P < 0.05). The average VAS scores at final follow-up were 2.3 and 4.9 in MP and CL groups (P < 0.05). The cervical lordosis and flex-ext ROM were statistically equivalent. The percent deep muscle area on MRI demonstrated a significant atrophy in CL group compared to that in MP group (56% vs 88%; P < 0.01). Laminoplasty employing the deep extensor muscle-preserving approach appeared to be effective in reducing the axial pain and deep muscle atrophy as well as improving cervical spine function and QOL when compared to conventional open-door laminoplasty.
• Two cases of postoperative MRSA infection after a transforaminal lumbar interbody fusion

  Katsuhisa Yamada, Yoshihisa Kotani, Manabu Ito, Kuniyoshi Abumi, Hideki Sudo, Masahiko Takahata, Shigeki Oshima, Akio Minami

  Hokkaido Journal of Orthopaedics and Traumatology 50 2 220 - 223 2009年03月 

  We report two cases of postoperative infection after a transforaminal lumbar interbody fusion (TLIF) .The first case is a 60 year-old man with postoperative MRSA infection after TLIF for L5-S1lumbar disk herniation recurrence and the second case is a 68 year-old woman after TLIF for L4-5 degenerative spondylolisthesis. In both cases, all implants were removed because the infection did not settle down after an irrigation and debridement. The interbody fusion through a posterior approach is often adopted for spinal fusion in the treatment of unstable lumbar segments. To approach the disk with less retraction of the nerve tissue, the TLIF requires a unilateral resection of a facet joint. The removal of all implants and cages leads to severely unstable spinal segment, being more difficult to revise it. It is necessary to examine thoroughly the necessity and suitability of an interbody fuion and a resection of a facet joint in posterior spine fusion.
• Clinical results and complications of circumferential spinal cord decompression through a single posterior approach for thoracic myelopathy caused by ossification of posterior longitudinal ligament

  Masahiko Takahata, Manabu Ito, Kuniyoshi Abumi, Yoshihisa Kotani, Hideki Sudo, Akio Minami

  SPINE 33 11 1199 - 1208 2008年05月 [査読有り][通常論文]
   

  Study Design. A retrospective review. Objective. This study examined the clinical outcomes of circumferential spinal cord decompression through a posterior approach for thoracic ossification of posterior longitudinal ligament ( OPLL), to determine the efficacy of this procedure and the incidence of complications. Summary of Background Data. Since posterior decompressive laminectomy is not always effective in the treatment of thoracic myelopathy caused by OPLL, circumferential spinal cord decompression through a single posterior approach seems to offer an effective treatment option. However, this procedure is technically demanding and has a high risk of postoperative neurologic deterioration. Long- term clinical outcome data and complication rates of this procedure are not well covered in the literature. Methods. Medical records of sequentially treated 30 patients, who had undergone circumferential spinal cord decompression through a single posterior approach, were reviewed to determine demographic data, neurologic examination, imaging findings, surgical procedure, and follow- up data. The Japanese Orthopedic Association ( JOA) score was used to assess physical dysfunction and neurologic impairment. Results. The mean follow- up period was 8 years; the average operative time was 389 minutes; the mean blood loss was 1883 mL. An average of 4- level spinal cord decompression was performed on all 30 patients. Posterior spinal fusion was performed on 26 of the 30 patients. The mean preoperative JOA score was 3.4/ 11, and it improved to an average of 7.1/ 11 at final evaluation. Clinical symptoms and the JOA score improved in 24 patients, but were unchanged or worsened in the other 6 patients compared to the preoperative conditions. Surgical complications included dural tear in 12 patients ( 40%), deep infection in 3 ( 10%), and postoperative neurologic deterioration in 10 ( 33%). Statistical analysis showed that a risk factor associated with the unfavorable surgical outcomes was multiple level circumferential spinal cord decompression of 5 or more vertebral levels. Conclusion. Despite circumferential spinal cord decompression through posterior approach for thoracic OPLL providing effective neurologic recovery, there was a high rate of complications such as postoperative neurologic deterioration. Risk factor analysis shows that multiple level circumferential decompression of 5 or more vertebral levels to be associated with unfavorable surgical outcome.
• Comparison of novel ultra-high molecular weight polyethylene tape versus conventional metal wire for sublaminar segmental fixation in the treatment of adolescent idiopathic scoliosis

  Masahiko Takahata, Manabu Ito, Kuniyoshi Aburni, Yoshihisa Kotani, Hideki Sudo, Shigeki Ohshima, Akio Minami

  JOURNAL OF SPINAL DISORDERS & TECHNIQUES 20 6 449 - 455 2007年08月 [査読有り][通常論文]
   

  Study Design: Retrospective study. Objectives: To compare the surgical outcomes of posterior translational correction and fusion using hybrid instrumentation systems with either sublaminar Nesplon tape or sublaminar metal wire to treat adolescent idiopathic scoliosis (AIS). Summary of Background Data: Nesplon tape, which consists of a thread of ultra-high molecular weight polyethylene fibers, has advantages over metal wire: (1) its soft and flexible properties avoid neural damage and (2) its flat configuration avoids focal distribution of the stresses to lamina; however, the efficacy of Nesplon tape in the correction of spinal deformity is as yet, still unclear. Methods: Thirty AIS patients at a single institution underwent posterior correction and fusion using hybrid instrumentation containing hook, pedicle screw, and either sublaminar polyethylene taping (15) or sublaminar metal wiring (15). Patients were evaluated preoperatively, immediately after surgery, and at a 2-year follow-up according to the radiographic changes in curve correction, operating time, intraoperative blood loss, complications, and the Scoliosis Research Society patient questionnaire (SRS-24) score. Results: The average correction rate was 63.0% in the Nesplon tape group and 59.9% in the metal wire group immediately after surgery (P = 0.62). Fusion was obtained in all the patients without significant correction loss in both groups. There was no significant difference in operative time, intraoperative blood loss, and postoperative SRS-24 scores between the 2 groups. Complications were superficial skin infection in a single patient in the Nesplon tape group, and transient sensory disturbance in I patient and temporal superior mesenteric artery syndrome in another patient in the metal wire group. Conclusions: The efficacy of Nesplon tape in correction of deformity is equivalent to that of metal wire, and fusion was completed without significant correction loss. The soft and flexible properties and flat configuration of Nesplon tape make this a safe application for the treatment of AIS with bone fragility or with the fusion areas containing the spinal cord.
• Accuracy analysis of pedicle screw placement in posterior scoliosis surgery - Comparison between conventional fluoroscopic and computer-assisted technique

  Yoshihisa Kotani, Kuniyoshi Abumi, Manabu Ito, Masahiko Takahata, Hideki Sudo, Shigeki Ohshima, Akio Minami

  SPINE 32 14 1543 - 1550 2007年06月 [査読有り][通常論文]
   

  Study Design. The accuracy of pedicle screw placement was evaluated in posterior scoliosis surgeries with or without the use of computer-assisted surgical techniques. Objective. In this retrospective cohort study, the pedicle screw placement accuracy in posterior scoliosis surgery was compared between conventional fluoroscopic and computer-assisted surgical techniques. Summary of Background Data. There has been no study systemically analyzing the perforation pattern and comparative accuracy of pedicle screw placement in posterior scoliosis surgery. Methods. The 45 patients who received posterior correction surgeries were divided into 2 groups: Group C, manual control (25 patients); and Group N, navigation surgery (20 patients). The average Cobb angles were 73.7 degrees and 73.1 degrees before surgery in Group C and Group N, respectively. Using CT images, vertebral rotation, pedicle axes as measured to anteroposterior sacral axis and vertebral axis, and insertion angle error were measured. In perforation cases, the angular tendency, insertion point, and length abnormality were evaluated. Results. The perforation was observed in 11% of Group C and 1.8% in Group N. In Group C, medial perforations of left screws were demonstrated in 8 of 9 perforated screws and 55% were distributed either in L1 or T12. The perforation consistently occurred in pedicles in which those axes approached anteroposterior sacral axis within 5 degrees. The average insertion errors were 8.4 degrees and 5.0 degrees in Group C and Group N, respectively, which were significantly different (P < 0.02). Conclusion. The medial perforation in Group C occurred around L1, especially when pedicle axis approached anteroposterior sacral axis. This consistent tendency was considered as the limitation of fluoroscopic screw insertion in which horizontal vertebral image was not visible. The use of surgical navigation system successfully reduced the perforation rate and insertion angle errors, demonstrating the clear advantage in safe and accurate pedicle screw placement of scoliosis surgery.
• Long-term follow up of surgical outcomes in patients with cervical disorders undergoing hemodialysis

  Hideki Sudo, Manabu Ito, Kuniyoshi Abumi, Yoshihisa Kotani, Tatsuto Takeuchi, Keigo Yasui, Akio Minami

  JOURNAL OF NEUROSURGERY-SPINE 5 4 313 - 319 2006年10月 [査読有り][通常論文]
   

  Object. As increasing numbers of patients receive long-term hemodialysis, the number of reports regarding hemodialysis-related cervical spine disorders has also increased. However, there have been few reports summarizing the surgical results in patients with these disorders. The objective of this study was to evaluate the long-term follow up and clinical results after surgical treatment of cervical disorders in patients undergoing hemodialysis. Methods. Seventeen patients in whom surgery was performed for cervical spine disorders while they received long-term hemodialysis therapy were enrolled in this study. Of these, 15 underwent follow-up review for more than 3 years after surgery, and these represent the study population. The remaining two patients died of postoperative sepsis. The average follow-up period was 120 months. Five patients without spinal instability underwent spinal cord decompression in which bilateral open-door laminoplasty was performed. Ten patients with destructive spondyloarthropathy (DSA) underwent reconstructive surgery involving pedicle screw (PS) fixation. In eight patients in whom posterior instrumentation was placed, anterior strut bone grafting was performed with autologous iliac bone to treat anterior-column destruction. Marked neurological recovery was obtained in all patients after the initial surgery. In the mobile segments adjacent to the site of previous spinal fusion, the authors observed progressive destructive changes with significant instability in four patients (40%) who underwent circumferential spinal fusion. No patients required a second surgery after laminoplasty for spinal canal stenosis without DSA changes. Conclusions. Cervical PS-assisted reconstruction provided an excellent fusion rate and good spinal alignment. During the long-term follow-up period, however, some cases required extension of the spinal fusion due to the destructive changes in the adjacent vertebral levels. Guidelines or recommendations to overcome these problems should be produced to further increase the survival rates of patients undergoing hemodialysis.
• Biomechanical study on the effect of five different lumbar reconstruction techniques on adjacent-level intradiscal pressure and lamina strain

  Hideki Sudo, Itaru Oda, Kuniyoshi Abumi, Manabu Ito, Yoshihisa Kotani, Akio Minami

  JOURNAL OF NEUROSURGERY-SPINE 5 2 150 - 155 2006年08月 [査読有り][通常論文]
   

  Object. The objectives of this study were to compare the biomechanical effects of five lumbar reconstruction models on the adjacent segment and to analyze the effects of three factors: construct stiffness, sagittal alignment, and the number of fused segments. Methods. Nondestructive flexion-extension tests were performed by applying pure moments to 10 calf spinal (L3-S1) specimens. One-segment (L5-6) or two-segment (L5-S1) posterior fusion methods were simulated: 1) one-segment posterolateral fusion (PLF); 2) one-segment PLF with interbody fusion cages (one-segment PLIF/PLF); 3) two-segment PLF; 4) two-segment PLIF/PLF; and 5) two-segment PLF in kyphosis (two-segment kyphotic PLF). The range of motion (ROM) of the reconstructed segments, intradiscal pressure (IDP), and lamina strain in the upper (L4-5) adjacent segment were analyzed. The ROM was significantly decreased in the PLIF/PLF models compared with that in the PLF alone models after both the one- and two-segment fusions. If the number of fused segments was increased, the pressure and strains were also increased in specimens subjected to the PLIF/PLF procedure, more so than the PLF-alone procedure. In the one-segment PLIF/PLF model the authors observed a reduced IDP and lamina strain compared with those in the kyphotic two-segment PLF model despite the latter's higher levels of initial stiffness. Conclusions. If the number of fused levels can be reduced by using PLIF to correct local kyphosis, then this procedure may be valuable for reducing adjacent-segment degenerative changes.
• Secondary medulla oblongata involvement following middle cervical spinal cord injury associated with latent traumatic instability in a patient with ossification of the posterior longitudinal ligament

  H Sudo, H Taneichi, K Kaneda

  SPINAL CORD 44 2 126 - 129 2006年02月 [査読有り][通常論文]
   

  Study design: A case report. Objectives: To report a rare case of extension of edema and hemorrhage from initial C4-5 spinal injury to the medulla oblongata. Setting: Center for Spinal Disorders and Injuries, Bibai Rosai Hospital, Japan. Methods: A 68-year-old man with ossification of the posterior longitudinal ligament (OPLL) had sustained tetraplegia after tumbling over a stone. Initially, the patient was diagnosed with an acute C4-5 spinal cord injury without radiological abnormalities and was treated conservatively. At 7 h after the injury, the patient had an ascending neurological deficit, which required respiratory assistance. Magnetic resonance imaging revealed a marked swelling of the spinal cord above C4-5 extending to the medulla oblongata. Results: Retrospective radiological assessment revealed that the spine was unstable at the injury level because of discontinuities in both anterior and posterior longitudinal ligaments. There was also signal intensity change within the retropharyngeal space at the C4-5 intervertebral disc. This injured segment was highly vulnerable to post-injury dynamic stenosis and easily sustained secondary neural damage. Conclusions: This case report emphasizes a careful radiological assessment of latent structural instability in patients with OPLL in order to detect and prevent deteriorative change in the spinal cord.
• Burkholderia pickettii spondylitis

  H Sudo, Y Hisada, M Ito, H Kotaki, A Minami

  SPINAL CORD 43 8 499 - 502 2005年08月 [査読有り][通常論文]
   

  Study design: Case report describing Burkholderia pickettii spondylitis in a healthy adult. Objectives: To describe this very rare form of spondylitis and to discuss some of the difficulties in the diagnosis of B. pickettii spondylitis. Setting: Department of Orthopaedic Surgery, Nayoro City General Hospital, Japan. Methods: A 48-year-old woman presented with a complaint of severe back pain radiating from the right side of her chest. Plain radiographs of the spine showed osteolytic destruction of the right side of the T10 vertebral body at T10 level, with an involvement of the pedicle. Magnetic resonance image of the spine showed a low signal intensity from the T10 vertebral body on a T1-weighted image and an increased signal intensity on T2-weighted sequence image. These lesions were enhanced when a contrast medium was used. The patient underwent open biopsy and specimens were collected through the right pedicle. Results: Diagnosis was established on the basis of direct identification of the microorganism. Histological findings were consistent with examination of B. pickettii spondylitis. Chemotherapy ( intravenous cefepime and per os minocycline) resulted in complete cure. Conclusion: B. pickettii is widely distributed in aqueous sources in nature and has not previously been considered to be an aggressive pathogen towards humans. This case report will help to improve our understanding of the ecology and virulent pathogenicity of this organism. A biopsy is an essential and reliable method for the early etiologic diagnosis, which will lead to prevent the development of more severe complications such as spinal cord compression.
• In vitro biomechanical effects of reconstruction on adjacent motion segment: comparison of aligned/kyphotic posterolateral fusion with aligned posterior lumbar interbody fusion/posterolateral fusion

  H Sudo, Oda, I, K Abumi, M Ito, Y Kotani, Y Hojo, A Minami

  JOURNAL OF NEUROSURGERY 99 2 221 - 228 2003年09月 [査読有り][通常論文]
   

  Object. Posterior lumbar interbody fusion (PLIF) was developed to overcome the limitations of posterolateral fusion in correcting spinal deformity and maintaining lumbar lordosis. In this study the authors compare the biomechanical effects of three different posterior reconstructions on the adjacent motion segment. Methods. Ten calf spinal (L2-S1) specimens underwent nondestructive flexion-extension testing (+/- 6 Nm). The specimens were destabilized at the L5-S1 levels after intact testing. This was followed by pedicle screw fixation with and without interbody cages as follows: 1) with straight rods ("aligned" posterolateral fusion); 2) with kyphotically prebent rods ("kyphotic" posterolateral fusion); and 3) with interbody cages combined with straight rods ("aligned" PLIF/posterolateral fusion). The range of motion (ROM) of the operative segments, the intradiscal pressure (IDP), and longitudinal lamina strain in the superior adjacent segment (L4-5) were analyzed. The ROM associated with aligned PLIF/posterolateral fusion-treated specimens was significantly less than both the aligned and kyphotic posterolateral fusion-treated procedures in both flexion and extension loading (p < 0.05). The aligned PLIF/posterolateral fusion was associated with greater IDP and the lamina strain compared with the aligned and kyphotic posterolateral fusion groups in flexion loading. Under extension loading, greater IDP and lamina strain were present in the kyphotic posterolateral fusion group than in the aligned posterolateral fusion group. The highest IDP and lamina strain were shown in the aligned PLIF/posterolateral fusion group. Conclusions. Compared with kyphotic posterolateral fusion, PLIF may lead to even higher load at the superior adjacent level because of the increased stiffness of the fixed segments even if local kyphosis is corrected by PLIF.
• Types of spinal instability that require interbody support in posterior lumbar reconstruction - An in vitro biomechanical investigation

  Oda, I, K Abumi, BS Yu, H Sudo, A Minami

  SPINE 28 14 1573 - 1580 2003年07月 [査読有り][通常論文]
   

  Study Design. Pedicle screw fixation alone for sequential spinal instabilities was biomechanically compared with pedicle screw fixation using interbody cages. Objective. To evaluate biomechanical effects of interbody cages on construct stiffness, pedicle-screw strain, and the adjacent level in posterior lumbar reconstruction using pedicle screw fixation. Summary of Background Data. It remains undetermined what types of spinal instability require interbody support in posterior lumbar reconstruction. Methods. For this study, 10 calf spines (L3-L6) were used. Sequential destabilization was performed at L4-L5 followed by posterior reconstruction using pedicle screw fixation (PS) and interbody cages as follows: intact + PS (I-PS), medial facetectomy + PS (MF-PS), total facetectomy + PS (TF-PS), partial discectomy + PS (D-PS), and D-PS + interbody cages (PLIF). Biomechanical testing was performed under flexion and extension loading modes. Construct stiffness (L4-L5), rod-screw bending strain, and range of motion (ROM) at the upper adjacent level (L3-L4) were analyzed. Results. In terms of construct stiffness (L4-L5), all the reconstructions except D-PS demonstrated higher construct stiffness than the intact spine (P < 0.05). The PLIF showed the highest stiffness among all the reconstructions (P < 0.05). In terms of ROM (L3-L4), all the reconstructions increased the ROM, as compared with the intact state (P < 0.05). Importantly, PLIF showed significantly greater ROM than all the other reconstructions except I-PS (P < 0.05). In terms of rod-screw strain, the D-PS resulted in higher strain than the other groups (P < 0.05). The PLIF presented less strain than the other reconstructions (P < 0.05). Conclusions. For spinal instability with preserved anterior load sharing, pedicle screw fixation alone is biomechanically adequate, and the interbody cages should not be used because they further increase segmental motion at the adjacent segment. However, PS alone provides insufficient stability and high implant strain in case of damaged anterior column. In such cases, additional interbody cages significantly increase construct stiffness and decrease hardware strain. However, they increase ROM at the adjacent segment as well.
• A moving middle finger

  H Sudo, M Ito, A Minami

  LANCET 361 9376 2202 - 2202 2003年06月 [査読有り][通常論文]
  
• NF-kappa B-dependent induction of cyclin D1 by retinoblastoma protein (pRB) family proteins and tumor-derived pRB mutants

  T Takebayashi, H Higashi, H Sudo, H Ozawa, E Suzuki, O Shirado, H Katoh, M Hatakeyama

  JOURNAL OF BIOLOGICAL CHEMISTRY 278 17 14897 - 14905 2003年04月 [査読有り][通常論文]
   

  The retinoblastoma protein (pRB) and its homologues, p107 and p130, prevent cell cycle progression from G(0)/G(1) to S phase by forming complexes with E2F transcription factors. Upon phosphorylation by G, cyclin-cyclin-dependent kinase (Cdk) complexes such as cyclin D1-Cdk4/6 and cyclin E-Cdk2, they lose the ability to bind E2F, and cells are thereby allowed to progress into S phase. Functional loss of one or more of the pRB family members, as a result of genetic mutation or deregulated phosphorylation, is considered to be an essential prerequisite for cellular transformation. In this study, we found that pRB family proteins have the ability to stimulate cyclin D1 transcription by activation of the NF-kappaB transcription factor. The cyclin D1-inducing activity of pRB is abolished by adenovirus E1A oncoprotein but not by the deletion of the A-box, the B-box, or the C-terminal region of the pocket, indicating that multiple pocket sequences are independently involved in cyclin D1 activation. Intriguingly, tumor-derived pRB pocket mutants retain the cyclin D1-inducing activity. Our results reveal a novel role of pRB family proteins as potential activators of NF-kappaB and inducers of G(1) cyclin. Certain pRB pocket mutants may give rise to a cellular situation in which deregulated E2F and cyclin D1 cooperatively promote abnormal cell proliferation.
• Spinal cord compression by multistrand cables after solid posterior atlantoaxial fusion - Report of three cases

  H Sudo, K Abumi, M Ito, Y Kotani, A Minami

  JOURNAL OF NEUROSURGERY 97 3 359 - 361 2002年10月 [査読有り][通常論文]
   

  The sublaminar wiring procedure has been commonly used for stabilizing the atlantoaxial complex. Multistrand braided cables were introduced in the early 1990s. In previous biomechanical studies these cables were demonstrated to be superior to monofilament wires in terms of their flexibility, mechanical strength, and fatigue-related characteristics. To the authors' knowledge, they are the first to describe clinically the occurrence of delayed spinal cord compression resulting from multistrand cables after the completion of rigid spinal arthrodesis in the upper cervical spine. Three patients underwent posterior atlantoaxial fusion in which two sublaminar multistrand cables were placed. Between 15 and 48 months postoperatively, they suffered from upper- and lower-extremity numbness as well as gait disturbance. Plain radiography and computerized tomography myelography revealed spinal cord compression caused by the sublaminar cables, although fusion was complete and physiological alignment was maintained at the fused segment. The radiographs obtained immediately after surgery demonstrated that the initial cable placement had been properly performed. The shape of the cable at the initial surgery was oval and then gradually became circular. The anterior are of the circular shape of the cable in fact led to the spinal cord compression. Considering the mechanism of this late complication, a cable tends to spring open because of its high flexibility and becomes circular shaped even after the complete arthrodesis. When applying multistrand cables for intersegmental fixation at the atlantoaxial complex, delayed complications related to bowing of the cables is possible.

MISC

• 骨髄由来間葉系幹細胞移植による再生医療を背景とした椎間板再生に有効な核酸ターゲットの探索

  大西貴士, 宝満健太郎, 福島瑛, 須藤英毅, 山田勝久, 岩崎倫政 Journal of Spine Research (Web) 15 (3) 2024年
• ウサギ椎間板ヘルニアモデルにおける高純度硬化性ゲルの椎間板内炎症抑制効果についての検討

  浦勝郎, 筌場大介, 辻本武尊, 岩崎倫政, 須藤英毅 北海道整形災害外科学会 138th 2020年
• ウサギ髄核摘出モデルにおける高純度硬化性ゲルと自家骨髄濃縮液による組織修復効果

  筌場大介, 浦勝郎, 辻本武尊, 岩崎倫政, 須藤英毅 北海道整形災害外科学会 138th 2020年
• 骨髄由来間葉系幹細胞による椎間板細胞治療

  須藤英毅, 須藤英毅, 筌場大介, 岩崎倫政 日本再生医療学会総会(Web) 19th 2020年
• 椎間板再生への挑戦 高純度硬化性ゲルによる椎間板再生

  辻本 武尊, 須藤 英毅, 東藤 正浩, 山田 勝久, 大西 貴士, 岩崎 倫政 日本整形外科学会雑誌 93 (8) S1595 -S1595 2019年09月 [査読無し][通常論文]
  
• 高純度硬化性ゲルと骨髄由来間葉系幹細胞による椎間板治療

  筌場 大介, 須藤 英毅, 浦 勝郎, 辻本 武尊, 岩崎 倫政 日本整形外科学会雑誌 93 (8) S1776 -S1776 2019年09月 [査読無し][通常論文]
  
• 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 2019年08月 [査読無し][通常論文]
  
• 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 2019年08月 [査読無し][通常論文]
  
• 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 2019年08月 [査読無し][通常論文]
  
• 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 2019年08月 [査読無し][通常論文]
  
• 4D‐有限要素解析シミュレーションによる術前計画と積層造形技術を含む脊柱変形矯正用カスタムメイドインプラントの開発

  須藤英毅, 金井理, 小甲晃史, 安倍雄一郎, 岩崎倫政, 千葉晶彦 別冊整形外科 (75) 218‐221 2019年04月 [査読無し][通常論文]
  
• 側弯検診システムの研究開発

  須藤英毅, 小甲晃史, 小甲晃史, 安倍雄一郎, 岩崎倫政, 金井理 臨床整形外科 54 (3) 306‐310 2019年03月 [査読無し][通常論文]
  
• 3次元スキャンと3次元対称性解析による脊柱側弯症高速・高感度検診システムの開発

  金井理, 須藤英毅 医科学応用研究財団研究報告(CD-ROM) 36 50‐57 2019年02月 [査読無し][通常論文]
  
• 椎間板ブロックが変性椎間板細胞・組織に与える影響

  浦勝郎, 須藤英毅, 筌場大介 Journal of Spine Research 10 (3) 2019年
• ウサギ椎間板ヘルニアモデルにおける高純度硬化性ゲルの椎間板内炎症抑制効果についての検討

  浦勝郎, 須藤英毅, 辻本武尊, 筌場大介, 岩崎倫政 整形外科バイオマテリアル研究会プログラム・抄録集 39th 2019年
• 高純度硬化性ゲルを併用した椎間板細胞治療における各種骨髄由来間葉系幹細胞の効果

  筌場大介, 浦勝郎, 辻本武尊, 岩崎倫政, 須藤英毅 北海道整形災害外科学会 137th 2019年
• TBX6遺伝子のmissense変異はTBX6の細胞内局在異常による機能の喪失により先天性側彎症を引き起こす

  大伴 直央, 武田 和樹, 小倉 洋二, 川上 紀明, 小谷 俊明, 須藤 英毅, 米澤 郁穂, 宇野 耕吉, 種市 洋, 渡辺 慶, 三宅 紀子, 南 昌平, 重松 英樹, 菅原 亮, 谷口 優樹, 中村 雅也, 松本 守雄, 渡邉 航太, 千葉 一裕, 池川 志郎 日本整形外科学会雑誌 92 (8) S1914 -S1914 2018年08月 [査読無し][通常論文]
  
• rs11190870が思春期特発性側彎症の重症度に関与するかの検討

  高橋 洋平, 小倉 洋二, 南 昌平, 川上 紀明, 宇野 耕吉, 伊東 学, 米澤 郁穂, 海渡 貴司, 柳田 晴久, 渡辺 慶, 種市 洋, 須藤 英毅, 播广谷 勝三, 谷口 優樹, 細金 直文, 小谷 俊明, 辻 太一, 鈴木 哲平, 武田 和樹, 岡田 英次朗, 藤田 順之, 八木 満, 中村 雅也, 松本 守雄, 渡邉 航太, 千葉 一裕, 池川 志郎 日本整形外科学会雑誌 92 (8) S1915 -S1915 2018年08月 [査読無し][通常論文]
  
• 整形外科領域におけるゲノム医療:現状と臨床への展開 先天性側彎症に対する遺伝子解析の現状

  武田 和樹, 黄 郁代, 小倉 洋二, 川上 紀明, 小谷 俊明, 須藤 英毅, 米澤 郁穂, 中村 雅也, 松本 守雄, 渡邉 航太, 千葉 一裕 日本整形外科学会雑誌 92 (8) S1853 -S1853 2018年08月 [査読無し][通常論文]
  
• 特発性側弯症手術に対して使用したロッドに対する形状類似分析手法の開発

  小甲晃史, 金井理, 安倍雄一郎, 岩崎倫政, 須藤英毅 Journal of Spine Research 9 (3) 239 2018年03月25日 [査読無し][通常論文]
  
• 北海道における整形外科基礎研究 基礎研究体制と概要 北海道大学整形外科

  角家 健, 近藤 英司, 高畑 雅彦, 須藤 英毅, 古川 潤一, 小野寺 智洋, アラー・テルカウイ, 岩崎 倫政 北海道整形災害外科学会雑誌 59 (2) 197 -204 2018年03月 [査読無し][通常論文]
  
• BNC2遺伝子は人種を超えて思春期特発性側弯症発症に関与する

  小倉洋二, 小倉洋二, 小倉洋二, 高橋洋平, 武田和樹, 武田和樹, 南昌平, 川上紀明, 宇野耕吉, 伊東学, 米澤郁穂, 海渡貴司, 柳田晴久, 渡辺慶, 種市洋, 須藤英毅, 播广谷勝三, 谷口優樹, 細金直文, 小谷俊明, 辻太一, 鈴木哲平, 岡田英次朗, 藤田順之, 八木満, 中村雅也, 松本守雄, 渡辺航太, 池川志郎 Journal of Spine Research 9 (3) 2018年
• RS11190870と思春期特発性側弯症の重症化に関する検討

  高橋洋平, 高橋洋平, 高橋洋平, 小倉洋二, 小倉洋二, 南昌平, 川上紀明, 宇野耕吉, 伊東学, 米澤郁穂, 海渡貴志, 柳田晴久, 渡辺慶, 種市洋, 須藤英毅, 播广谷勝三, 谷口優樹, 細金直文, 小谷俊明, 辻太一, 鈴木哲平, 武田和樹, 武田和樹, 岡田英次朗, 藤田順之, 八木満, 辻崇, 中村雅也, 松本守雄, 渡辺航太, 千葉一裕, 池川志郎 日本側彎症学会演題抄録集 52nd 2018年
• 先天性側弯症の新規原因遺伝子の探索

  武田和樹, 黄郁代, 小倉洋二, 小倉洋二, 川上紀明, 川上紀明, 小谷俊明, 小谷俊明, 須藤英毅, 須藤英毅, 米澤郁穂, 米澤郁穂, 宇野耕吉, 宇野耕吉, 種市洋, 種市洋, 渡辺慶, 渡辺慶, 三宅紀子, 南昌平, 南昌平, 重松英樹, 重松英樹, 菅原亮, 菅原亮, 谷口優樹, 谷口優樹, 中村雅也, 松本守雄, 渡辺航太, 池川志郎 日本側彎症学会演題抄録集 52nd 2018年
• RS12946942は多人種間で思春期特発性側弯症の重症化に関与する

  武田和樹, 武田和樹, 小倉洋二, 小倉洋二, 小倉洋二, 高橋洋平, 南昌平, 川上紀明, 宇野耕吉, 伊東学, 米澤郁穂, 海渡貴司, 柳田晴久, 渡辺慶, 種市洋, 須藤英毅, 播广谷勝三, 谷口優樹, 細金直文, 小谷俊明, 辻太一, 鈴木哲平, 岡田英次朗, 藤田順之, 八木満, 中村雅也, 松本守雄, 池川志郎, 渡辺航太 日本側彎症学会演題抄録集 52nd 2018年
• BNC2遺伝子は多人種で思春期特発性側弯症発症に関与する

  小倉洋二, 小倉洋二, 小倉洋二, 高橋洋平, 武田和樹, 武田和樹, 南昌平, 川上紀明, 宇野耕吉, 伊東学, 米澤郁穂, 海渡貴司, 柳田晴久, 渡辺慶, 種市洋, 須藤英毅, 播广谷勝三, 谷口優樹, 細金直文, 小谷俊明, 辻太一, 鈴木哲平, 岡田英次朗, 藤田順之, 八木満, 中村雅也, 松本守雄, 渡邉航太, 池川志郎 日本整形外科学会雑誌 92 (8) 2018年
• 腰椎後方椎体間固定術後に生じた手術部位感染の治療経験

  原谷健太郎, 山田勝久, 小甲晃史, 高畑雅彦, 岩田玲, 筌場大介, 須藤英毅 北海道整形災害外科学会雑誌 59 (2) 2018年
• 椎間板ブロックが変性椎間板細胞・組織に与える影響

  浦勝郎, 須藤英毅, 筌場大介, 辻本武尊, 岩崎倫政 日本整形外科学会雑誌 92 (8) 2018年
• 医工連携による椎間板再生治療用組織修復材の開発

  須藤英毅, 辻本武尊, 東藤正浩, 筌場大介, 浦勝郎, 岩崎倫政 日本整形外科学会雑誌 92 (8) 2018年
• 思春期特発性側弯症におけるロッド曲線形状の類似分析手法の開発

  小甲晃史, 金井理, 安倍雄一郎, 岩崎倫政, 須藤英毅 北海道整形災害外科学会 134th 41 2018年 [査読無し][通常論文]
  
• 特発性側弯症手術に対して使用したロッドに対する形状類似分析手法の開発

  小甲晃史, 金井理, 安倍雄一郎, 岩崎倫政, 須藤英毅 北海道整形災害外科学会 135th 28 2018年 [査読無し][通常論文]
  
• 3Dスキャナと非対称性解析に基づく脊柱側弯症早期検診システムの開発

  金井理, 須藤英毅, 小甲晃史, 長枝浩, 林隆行, 太田初 日本設計工学会北海道支部研究発表論文集 2018 (2) 13‐16 2018年 [査読無し][通常論文]
  
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  須藤英毅, 金井理, 小甲晃史, 青柳健太, WANG Hao, 岩崎倫政, 千葉晶彦 日本バイオマテリアル学会大会予稿集(Web) 40th 165 (WEB ONLY) 2018年 [査読無し][通常論文]
  
• 特発性側弯症手術に対して解剖学的脊柱配列獲得を目指して使用したロッドに対する形状類似分析手法の開発

  小甲晃史, 金井理, 安倍雄一郎, 岩崎倫政, 須藤英毅 日本側彎症学会演題抄録集 52nd 276 2018年 [査読無し][通常論文]
  
• Response to Lefebvre et al

  K. Takeda, I. Kou, N. Kawakami, Y. Yasuhiko, Y. Ogura, E. Imagawa, N. Miyake, N. Matsumoto, H. Sudo, T. Kotani, Japan Early Onset Scoliosis Research Group, M. Nakamura, M. Matsumoto, Kei Watanabe, S. Ikegawa, Shohei Minami, Hiroshi Taneichi, Hideki Shigematsu, Ikuho Yonezawa, Ryo Sugawara Clinical Genetics 92 (5) 563 -564 2017年11月01日 [査読無し][通常論文]
  
• 思春期特発性側弯症におけるロッド曲線形状の類似分析手法の開発

  小甲晃史, 金井理, 安倍雄一郎, 岩崎倫政, 須藤英毅 日本整形外科学会雑誌 91 (8) S1795 2017年08月31日 [査読無し][通常論文]
  
• 3D非対称性解析による革新的脊柱側弯症検診システムの研究開発

  須藤英毅, 小甲晃史, 林隆行, 安倍雄一郎, 岩田玲, 長枝浩, 岩崎倫政, 金井理 日本整形外科学会雑誌 91 (8) S1475 2017年08月31日 [査読無し][通常論文]
  
• 3D非対称性解析による革新的脊柱側弯症検診システムの研究開発

  須藤英毅, 小甲晃史, 林隆行, 安倍雄一郎, 岩田玲, 長枝浩, 岩崎倫政, 金井理 東日本整形災害外科学会雑誌 29 (3) 368 2017年08月15日 [査読無し][通常論文]
  
• 遺伝子改変マウスを用いた椎間板変性におけるcaspase 3遺伝子の果たす機能解析

  大西 貴士, 岩崎 浩司, 辻本 武尊, 岩崎 倫政, 須藤 英毅 北海道整形災害外科学会雑誌 58 (2) 270 -270 2017年03月 [査読無し][通常論文]
  
• 高純度硬化性ゲルによる無細胞移植椎間板組織自然再生誘導法

  辻本 武尊, 須藤 英毅, 岩崎 浩司, 大西 貴士, 岩崎 倫政 Journal of Spine Research 8 (3) 298 -298 2017年03月 [査読無し][通常論文]
  
• 電子ビーム積層造形によって作製された生体用CoCrMo合金の逆変態熱処理による組織微細化

  王昊, 青柳健太, 山中謙太, 千葉晶彦, 須藤英毅 日本金属学会講演概要(CD-ROM) 161st 2017年
• TBX6遺伝子関連の先天性側弯症における表現型と遺伝型の関連性の検討

  武田和樹, 武田和樹, 武田和樹, 黄郁代, 小倉洋二, 小倉洋二, 川上紀明, 川上紀明, 小谷俊明, 小谷俊明, 須藤英毅, 須藤英毅, 米澤郁穂, 米澤郁穂, 宇野耕吉, 宇野耕吉, 種市洋, 種市洋, 渡辺慶, 渡辺慶, 三宅紀子, 南昌平, 南昌平, 重松英樹, 重松英樹, 菅原亮, 菅原亮, 谷口優樹, 谷口優樹, 中村雅也, 松本守雄, 渡辺航太, 渡辺航太, 池川志郎 日本側彎症学会演題抄録集 51st 2017年
• TBX6遺伝子のnull mutationとhypomorphic risk haplotypeのcompound heterozygoteは先天性側弯症およびSpondylocostal dysostosisを引き起こす

  武田和樹, 武田和樹, 武田和樹, 黄郁代, 小倉洋二, 小倉洋二, 川上紀明, 川上紀明, 小谷俊明, 小谷俊明, 須藤英毅, 須藤英毅, 米澤郁穂, 米澤郁穂, 宇野耕吉, 宇野耕吉, 種市洋, 種市洋, 渡辺慶, 渡辺慶, 三宅紀子, 南昌平, 南昌平, 重松英樹, 重松英樹, 菅原亮, 菅原亮, 谷口優樹, 谷口優樹, 安彦行人, 中村雅也, 松本守雄, 渡邉航太, 渡邉航太, 池川志郎 日本整形外科学会雑誌 91 (8) 2017年
• 脊柱側弯症に対する遺伝子解析の現状

  武田和樹, 武田和樹, 黄郁代, 小倉洋二, 小倉洋二, 川上紀明, 小谷俊明, 須藤英毅, 中村雅也, 松本守雄, 渡辺航太, 池川志郎 日本小児整形外科学会雑誌 26 (3) 2017年
• 3D非対称性解析による革新的脊柱側弯症検診システムの研究開発

  須藤英毅, 小甲晃史, 林隆行, 安倍雄一郎, 岩田玲, 長枝浩, 岩崎倫政, 金井理 日本側彎症学会演題抄録集 51st 160 2017年 [査読無し][通常論文]
  
• 学術奨励賞・受賞記念論文 Anomalous vertebral and posterior communicating arteries as a risk factor in cervical instrumentation surgery

  Nagahama Ken, Sudo Hideki, Abumi Kuniyoshi, Ito Manabu, Takahata Masahiko, Iwasaki Norimasa 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 (1) 15 -19 2016年10月
• 局所麻酔薬0.5%ブピバカイン関節内頻回投与が膝関節軟骨に与える影響ラット正常膝関節及び外科的変形性関節症誘発モデルでの検討

  岩崎 浩司, 笠原 靖彦, 山田 勝久, 大西 貴士, 辻本 武尊, 岩崎 倫政, 須藤 英毅 北海道整形災害外科学会雑誌 58 (1) 82 -82 2016年10月 [査読無し][通常論文]
  
• 骨粗鬆症性椎体圧潰による遅発性麻痺の病態と治療 : 前方法vs.後方法 (シンポジウム 骨粗鬆症性椎体骨折後後弯症(OPK)の病態と治療戦略)

  伊東 学, 高畑 雅彦, 須藤 英毅, 金田 清志, 佐藤 栄修, 岩崎 倫政 日本整形外科学会雑誌 90 (9) 577 -583 2016年09月
• 思春期特発性側彎症の進行に関与する遺伝子の発見

  小倉 洋二, 黄 郁代, 高橋 洋平, 武田 和樹, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 南 昌平, 米澤 郁穂, 柳田 晴久, 種市 洋, 細金 直文, 岡田 英次朗, 辻 太一, 鈴木 哲平, 須藤 英毅, 小谷 俊明, 千葉 一裕, 戸山 芳昭, 中村 雅也, 松本 守雄, 池川 志郎, 渡邉 航太 日本整形外科学会雑誌 90 (8) S1502 -S1502 2016年08月 [査読無し][通常論文]
  
• 思春期特発性側彎症発症の分子機構の解明

  小倉 洋二, 黄 郁代, 高橋 洋平, 武田 和樹, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 南 昌平, 米澤 郁穂, 柳田 晴久, 種市 洋, 細金 直文, 岡田 英次朗, 三浦 重徳, 辻 太一, 鈴木 哲平, 須藤 英毅, 小谷 俊明, 千葉 一裕, 戸山 芳昭, 開 祐司, 宿南 知佐, 中村 雅也, 松本 守雄, 池川 志郎, 渡邉 航太 日本整形外科学会雑誌 90 (8) S1785 -S1785 2016年08月 [査読無し][通常論文]
  
• 遺伝子改変マウスを用いた椎間板変性におけるcaspase 3遺伝子の果たす機能解析

  大西 貴士, 須藤 英毅, 岩崎 浩司, 辻本 武尊, 岩崎 倫政 日本整形外科学会雑誌 90 (8) S1685 -S1685 2016年08月 [査読無し][通常論文]
  
• 0.5%ブピバカインは関節軟骨に変性変化を惹起するか ラット正常膝および変形性膝関節症誘発モデルを用いた検討

  岩崎 浩司, 須藤 英毅, 笠原 靖彦, 山田 勝久, 大西 貴士, 辻本 武尊, 岩崎 倫政 日本整形外科学会雑誌 90 (8) S1770 -S1770 2016年08月 [査読無し][通常論文]
  
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  小池 良直, 高畑 雅彦, 岩田 玲, 校條 祐輔, 小甲 晃史, 須藤 英毅, 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 57 (2) 279 -282 2016年04月
• 椎間板造影・ブロックが正常椎間板細胞・組織に与える長期的影響

  岩崎 浩司, 山田 勝久, 大西 貴士, 辻本 武尊, 岩崎 倫政, 須藤 英毅 北海道整形災害外科学会雑誌 57 (2) 290 -290 2016年04月 [査読無し][通常論文]
  
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  大西 貴士, 須藤 英毅, 岩崎 倫政 北海道整形災害外科学会雑誌 57 (2) 290 -291 2016年04月 [査読無し][通常論文]
  
• 新病理分類に基づいた再現性の高いin vivoマウス腰椎椎間板変性モデルの確立

  大西 貴士, 須藤 英毅, 岩崎 浩司, 辻本 武尊, 岩崎 倫政 Journal of Spine Research 7 (3) 387 -387 2016年03月 [査読無し][通常論文]
  
• 遺伝子改変マウスを用いた椎間板変性におけるcaspase 3遺伝子の果たす機能解析

  大西 貴士, 須藤 英毅, 岩崎 浩司, 辻本 武尊, 岩崎 倫政 Journal of Spine Research 7 (3) 558 -558 2016年03月 [査読無し][通常論文]
  
• 【運動器疾患のゲノム解析の最前線〜単一遺伝子病から、common disease、ビッグデータ解析まで〜】 Common diseaseのGWAS 思春期特発性側彎症

  小倉 洋二, 黄 郁代, 松本 守雄, 渡辺 航太, 池川 志郎, 河野 克己, 川上 紀明, 辻 太一, 宇野 耕吉, 鈴木 哲平, 伊東 学, 須藤 英毅, 南 昌平, 小谷 俊明, 米澤 郁穂, 柳田 晴久, 種市 洋, 千葉 一裕, 細金 直文, 岡田 英次朗, 高橋 洋平, 武田 和樹, 日本側彎症臨床研究グループ Clinical Calcium 26 (4) 553 -560 2016年03月 [査読無し][通常論文]
   

  思春期特発性側彎症(adolescent idiopathic scoliosis:AIS)は、多因子遺伝病である。多因子遺伝病の疾患感受性遺伝子の同定のために世界中で全ゲノム相関解析(genome-wide association study:GWAS)が行われてきた。われわれのグループは世界に先駆けAISのGWASを行い2011年に最初の疾患感受性遺伝子、LBX1を発見した。その後、サンプル、解析SNP数を増やすことで、計4つのAIS疾患感受性遺伝子を発見している。近年では、米国や中国など海外でもGWASによりいくつかの疾患感受性遺伝子が発見されている。疾患感受性遺伝子の同定後は、遺伝子の機能解析が行われており、徐々にAISの病態も明らかになってきた。本論文では、本邦ならびに海外でのAISのGWASの現況について概説する。加えて、AISの発症メカニズムについての研究も解説する。(著者抄録)
• TBX6のnull mutationとhypomorphic risk haplotypeのcompound heterozygoteは日本人においても先天性側弯症を引き起こす

  武田和樹, 武田和樹, 渡辺航太, 黄郁代, 小倉洋二, 三宅紀子, 川上紀明, 須藤英毅, 南昌平, 小谷俊明, 藤田順之, 池川志郎, 中村雅也, 松本守雄 Journal of Spine Research 7 (3) 2016年
• TBX6遺伝子のnull mutationとhypomorphic risk haplotypeのcompound heterozygoteは日本人においても先天性側弯症を引き起こす

  武田和樹, 渡辺航太, 小倉洋二, 川上紀明, 須藤英毅, 南昌平, 小谷俊明, 三宅紀子, 藤田順之, 池川志郎, 中村雅也, 松本守雄 日本側彎症学会演題抄録集 50th 2016年
• BNC2遺伝子の過剰発現が思春期特発性側弯症の発症リスクとなる

  小倉洋二, 小倉洋二, 小倉洋二, 高橋洋平, 武田和樹, 武田和樹, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 柳田晴久, 種市洋, 米澤郁穂, 辻太一, 鈴木哲平, 須藤英毅, 小谷俊明, 岡田英次朗, 細金直文, 中村雅也, 松本守雄, 池川志郎, 渡辺航太 日本側彎症学会演題抄録集 50th 2016年
• 思春期特発性側弯症のゲノム解析

  小倉洋二, 小倉洋二, 小倉洋二, 高橋洋平, 武田和樹, 武田和樹, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 柳田晴久, 種市洋, 米澤郁穂, 辻太一, 鈴木哲平, 須藤英毅, 小谷俊明, 岡田英次朗, 細金直文, 中村雅也, 松本守雄, 池川志郎, 渡辺航太 日本小児整形外科学会雑誌 25 (3) 2016年
• 非定型抗酸菌による化膿性脊椎炎の特徴と治療経過 3例の治療経験

  校條 祐輔, 高畑 雅彦, 須藤 英毅, 長濱 賢, 黒木 圭, 小甲 晃史, 岩崎 倫政, 伊東 学, 石黒 信久 北海道整形災害外科学会雑誌 57 (1) 152 -152 2015年12月 [査読無し][通常論文]
  
• 再現性の高いマウス椎間板穿刺変性モデルの作成

  大西 貴士, 須藤 英毅, 岩崎 浩司, 辻本 武尊 日本整形外科学会雑誌 89 (8) S1615 -S1615 2015年09月 [査読無し][通常論文]
  
• 脊椎脊髄疾患に対する病態解明の現状と未来 思春期特発性側彎症に対するオーダーメード医療実現に向けた取り組み

  松本 守雄, 渡辺 航太, 高橋 洋平, 小倉 洋二, 三宅 敦, 戸山 芳昭, 川上 紀明, 辻 太一, 宇野 耕吉, 鈴木 哲平, 伊東 学, 須藤 英毅, 種市 洋, 柳田 晴久, 南 昌平, 小谷 俊明, 河野 克己, 米澤 郁穂, 池川 志郎, 長嶋 比呂志, 梅山 一大, 西脇 祐司, 道川 武紘 Journal of Spine Research 6 (3) 206 -206 2015年03月 [査読無し][通常論文]
  
• 椎間板造影・ブロックが正常椎間板細胞・組織に与える長期的影響

  岩崎 浩司, 須藤 英毅, 山田 勝久, 大西 貴士, 辻本 武尊, 岩崎 倫政 Journal of Spine Research 6 (3) 590 -590 2015年03月 [査読無し][通常論文]
  
• 思春期特発性側彎症の新規の疾患感受性遺伝子の同定と発症機序の解明

  小倉 洋二, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 辻 太一, 鈴木 哲平, 須藤 英毅, 高橋 洋平, 渡辺 航太, 戸山 芳昭, 松本 守雄, 細金 直文, 南 昌平, 小谷 俊明, 米澤 郁穂, 柳田 晴久, 種市 洋, 千葉 一裕, 岡田 英次朗, 池川 志郎 Journal of Spine Research 6 (3) 535 -535 2015年03月 [査読無し][通常論文]
  
• 強皮症に合併した頚椎calcinosisの1例

  高橋要, 新井隆太, 校條祐輔, 高畑雅彦, 須藤英毅, 長濱賢, 黒木圭, 小甲晃史, 岩崎倫政 北海道整形災害外科学会 128th 107 2015年 [査読無し][通常論文]
  
• 思春期特発性側彎症のゲノムワイド相関解析 側彎の進行に関与する遺伝子の解析

  小倉 洋二, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 渡辺 航太, 戸山 芳昭, 松本 守雄, 辻 太一, 鈴木 哲平, 須藤 英毅, 高橋 洋平, 南 昌平, 小谷 俊明, 柳田 晴久, 米澤 郁穂, 細金 直文, 種市 洋, 千葉 一裕, 岡田 英次朗, 池川 志郎 Journal of Spine Research 5 (3) 251 -251 2014年03月 [査読無し][通常論文]
  
• 思春期特発性側彎症のゲノムワイド相関解析 側彎の発症に関与する遺伝子の解析

  小倉 洋二, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 渡辺 航太, 戸山 芳昭, 松本 守雄, 辻 太一, 鈴木 哲平, 須藤 英毅, 高橋 洋平, 南 昌平, 小谷 俊明, 柳田 晴久, 米澤 郁穂, 細金 直文, 種市 洋, 千葉 一裕, 岡田 英次朗, 池川 志郎 Journal of Spine Research 5 (3) 252 -252 2014年03月 [査読無し][通常論文]
  
• 思春期特発性側彎症の重症化に関連する領域を染色体17q24.3に同定

  三宅 敦, 高橋 洋平, 小倉 洋二, 黄 郁代, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 南 昌平, 柳田 晴久, 種市 洋, 辻 太一, 鈴木 哲平, 須藤 英毅, 小谷 俊明, 米澤 郁穂, 渡邉 航太, 千葉 一裕, 戸山 芳昭, 松本 守雄, 池川 志郎 Journal of Spine Research 5 (3) 421 -421 2014年03月 [査読無し][通常論文]
  
• 思春期特発性側弯症の大規模ゲノムワイド相関解析:新規の座位の同定

  小倉洋二, 小倉洋二, 松本守雄, 黄郁代, 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 米澤郁穂, 辻太一, 鈴木哲平, 須藤英毅, 渡邉航太, 戸山芳昭, 池川志郎 日本整形外科学会雑誌 88 (8) 2014年
• 思春期特発性側弯症の原因遺伝子-遺伝子診断の現況

  高橋洋平, 高橋洋平, 高橋洋平, 小倉洋二, 小倉洋二, 黄郁代, 高橋弘, 河野克己, 川上紀明, 辻太一, 宇野耕吉, 鈴木哲平, 伊東学, 須藤英毅, 南昌平, 小谷俊明, 柳田晴久, 種市洋, 米澤郁穂, 渡辺航太, 戸山芳昭, 松本守雄, 池川志郎 日本側彎症学会演題抄録集 48th 2014年
• 思春期特発性側弯症のゲノムワイド相関解析:新規の疾患受性遺伝子の発現

  小倉洋二, 小倉洋二, 小倉洋二, 河野克己, 川上紀明, 宇野耕吉, 伊藤学, 南昌平, 米澤郁穂, 柳田晴久, 種市洋, 岡田英次朗, 高橋洋平, 辻太一, 鈴木哲平, 須藤英毅, 小谷俊明, 渡辺航太, 細金直文, 千葉一裕, 戸山芳昭, 松本守雄, 池川志郎 日本側彎症学会演題抄録集 48th 2014年
• 側弯症矯正手術における内固定金属の力学分担:クロスリンクによる応力分散効果

  安倍雄一郎, 伊東学, 鐙邦芳, 藤崎和弘, REMEL Salmingo, 但野茂, 久田雄一郎, 高畑雅彦, 須藤英毅, 長濱賢, 中原誠之 J Spine Res 4 (3) 750 2013年03月25日 [査読無し][通常論文]
  
• 思春期特発性側彎症の進行に関する遺伝子マーカーの検討 日本人での大規模再現解析

  小倉 洋二, 高橋 洋平, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 南 昌平, 柳田 晴久, 米澤 郁穂, 種市 洋, 辻 太一, 鈴木 哲平, 須藤 英毅, 小谷 俊明, 渡辺 航太, 戸山 芳昭, 千葉 一裕, 松本 守雄, 池川 志郎 Journal of Spine Research 4 (3) 713 -713 2013年03月 [査読無し][通常論文]
  
• 思春期特発性側弯症の遺伝子解析

  高橋洋平, 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 柳田晴久, 種市洋, 米澤郁穂, 渡辺航太, 辻太一, 鈴木哲平, 須藤英毅, 戸山芳昭, 池川志郎, 松本守雄 Journal of Spine Research 4 (3) 2013年
• Caspase 3 をターデットとした椎間板組織に対する変性抑制効果

  須藤 英毅, 三浪 明男 北海道醫學雜誌 = Acta medica Hokkaidonensia 87 (6) 258 -258 2012年11月01日
• 椎弓根スクリュー法による軸椎下頸椎再建

  鐙 邦芳, 伊東 学, 須藤 英毅 北海道醫學雜誌 = Acta medica Hokkaidonensia 87 (6) 260 -260 2012年11月01日
• 2012(基礎部門優秀論文賞) Caspase 3 as a Therapeutic Target for Regulation of Intervertebral Disc Degeneration in Rabbits (平成24年度助成研究論文)

  須藤 英毅, 三浪 明男 未病と抗老化 : 財団法人博慈会老人病研究所紀要 21 101 -111 2012年06月
• 【後縦靱帯骨化症(OPLL)の治療】胸椎OPLLの治療 胸椎OPLLに対する後方進入全周性脊髄除圧

  鐙 邦芳, 高畑 雅彦, 伊東 学, 須藤 英毅, 長濱 賢 関節外科 31 (5) 578 -585 2012年05月 [査読無し][通常論文]
  
• 内固定金属形状追跡による側弯症矯正手術の力学解析

  安倍雄一郎, 伊東学, 鐙邦芳, 藤崎和弘, REMEL Salmingo, 但野茂, 小谷善久, 須藤英毅, 長濱賢, 岩田玲, 佐藤栄修, 三浪明男 J Spine Res 3 (3) 448 2012年03月25日 [査読無し][通常論文]
  
• 思春期特発性側彎症の全ゲノム相関解析

  高橋 洋平, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 南 昌平, 柳田 晴久, 種市 洋, 渡辺 航太, 辻 太一, 鈴木 哲平, 須藤 英毅, 小谷 俊明, 千葉 一裕, 戸山 芳昭, 池川 志郎, 松本 守雄 Journal of Spine Research 3 (3) 447 -447 2012年03月 [査読無し][通常論文]
  
• 思春期特発性側弯症の進行予測キットScoliscoreの有用性の検証:日本人での大規模再現解析

  小倉洋二, 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 渡辺航太, 戸山芳昭, 辻太一, 鈴木哲平, 須藤英毅, 松本守雄, 小谷俊明, 柳田晴久, 種市洋, 米澤郁穂, 池川志郎 日本側彎症学会演題抄録集 46th 2012年
• 中国人で同定された思春期特発性側弯症の進行に関与するSNP:日本人での大規模再現解析

  小倉洋二, 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 渡辺航太, 戸山芳昭, 松本守雄, 辻太一, 鈴木哲平, 須藤英毅, 小谷俊明, 柳田晴久, 種市洋, 米澤郁穂, 池川志郎 日本側彎症学会演題抄録集 46th 2012年
• 特発性側弯症後方矯正手術時における脊椎インプラントの応力評価

  伊東学, 安倍雄一郎, 鐙邦芳, 藤崎和弘, SALMINGO Remel, 但野茂, 小谷善久, 須藤英毅, 長濱賢, 岩田玲, 三浪明男 J Spine Res 2 (3) 609 2011年03月25日 [査読無し][通常論文]
  
• CT osteoabsorptmetry法を用いた小児特発性側弯症における椎体終板骨濃度分布の解析

  安倍雄一郎, 伊東学, 鐙邦芳, 藤崎和弘, 但野茂, 岩崎倫政, 小谷善久, 須藤英毅, 長濱賢, 岩田玲, 三浪明男 J Spine Res 2 (3) 615 2011年03月25日 [査読無し][通常論文]
  
• 特発性側弯症に対する後方矯正固定術の臨床成績 : 超高分子量ポリエチレンテープを用いた hybrid 法と椎弓根スクリュー法の比較

  大嶋 茂樹, 伊東 学, 高畑 雅彦, 鐙 邦芳, 小谷 善久, 須藤 英毅, 放生 憲博, 安倍 雄一郎, 三浪 明男 Journal of spine research 1 (11) 2074 -2078 2010年11月25日 [査読無し][通常論文]
  
• 脊椎手術後感染症に対する後側方鏡視下病巣掻爬洗浄術 (インプラント感染--その予防と対策) -- (骨折内固定後感染)

  伊東 学, 放生 憲博, 須藤 英毅 整形・災害外科 53 (5) 647 -653 2010年04月
• 内固定金属形状追跡による側弯症矯正手術の力学解析

  安倍雄一郎, 伊東学, 鐙邦芳, 藤崎和弘, SALMINGO Remel, 但野茂, 小谷善久, 須藤英毅, 長濱賢, 岩田玲, 三浪明男 日本側わん症学会演題抄録集 44th 69 2010年 [査読無し][通常論文]
  
• 【脊柱後彎症の病態と手術治療】脊椎高位による後彎症治療の特異性 頭蓋頸椎移行部の後彎変形 関節リウマチによる頭蓋頸椎移行部後彎の病態と矯正固定手術

  高畑 雅彦, 鐙 邦芳, 伊東 学, 小谷 善久, 須藤 英毅, 放生 憲博 脊椎脊髄ジャーナル 22 (5) 639 -645 2009年05月 [査読無し][通常論文]
  
• 超高分子量ポリエチレンケーブルを用いた脊柱再建術

  高畑 雅彦, 鐙 邦芳, 伊東 学, 小谷 善久, 須藤 英毅, 放生 憲博 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 19 (4) 724 -729 2008年12月25日 [査読無し][通常論文]
  
• 化膿性脊椎炎に対する後側方鏡視下病巣掻爬洗浄術

  伊東 学, 鐙 邦芳, 小谷 善久, 高畑 雅彦, 須藤 英毅, 放生 憲博 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 19 (4) 741 -747 2008年12月25日 [査読無し][通常論文]
  
• 臨床室 環軸椎高位で頚髄症をきたした強直性脊椎炎の1例

  林 晴久, 須藤 英毅, 鐙 邦芳 整形外科 59 (9) 1095 -1097 2008年08月
• Revision Surgery Using Pedicle Screw Fixation Systems for Previously Operated Cervical Spine

  ABUMI Kuniyoshi, ITO Manabu, KOTANI Yoshihisa, TAKAHATA Masahiko, SUDO Hideki, HOJO Yoshihiro, MINAMI Akio 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 19 (2) 359 -359 2008年03月20日
• 脊柱再建手術を要した頚髄腫瘍例の検討

  鐙 邦芳, 伊東 学, 小谷 善久, 高畑 雅彦, 須藤 英毅, 法生 憲博, 三浪 明男 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 19 (1) 41 -41 2008年03月20日 [査読無し][通常論文]
  
• 腰椎変性疾患に対する経皮的椎弓根スクリュー刺入による最小侵襲後方再建術 : 特に周術期侵襲とQOLに対する効果について

  小谷 善久, 鐙 邦芳, 伊東 学, 高畑 雅彦, 須藤 英毅, 放生 憲博, 三浪 明男 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 19 (1) 68 -68 2008年03月20日 [査読無し][通常論文]
  
• 骨粗鬆症性脊椎骨折に対する手術治療の変遷と将来像

  伊東 学, 鐙 邦芳, 小谷 善久, 高畑 雅彦, 須藤 英毅, 放生 憲博, 三浪 明男, 金田 清志 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 19 (2) 250 -250 2008年03月20日 [査読無し][通常論文]
  
• 椎弓根スクリューによる頚椎後弯変形の矯正術後に発生したC5麻痺の検討

  放生 憲博, 鐙 邦芳, 伊東 学, 小谷 善久, 高畑 雅彦, 須藤 英毅, 三浪 明男 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 19 (2) 488 -488 2008年03月20日 [査読無し][通常論文]
  
• 難治性化膿性脊椎炎に対するリネゾリドの有効性と適正使用に関する検討

  高畑 雅彦, 伊東 学, 鐙 邦芳, 小谷 善久, 須藤 英毅, 放生 憲博, 三浪 明男 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 19 (2) 491 -491 2008年03月20日 [査読無し][通常論文]
  
• 札幌市における側彎症学校検診の実態調査 : 平成元年から17年度までの検討

  祐川 敦, 伊東 学, 鐙 邦芳, 小谷 善久, 高畑 雅彦, 須藤 英毅, 大嶋 茂樹, 三浪 明男 脊柱変形 : 日本側彎症研究会会誌 = Spinal deformity : the journal of Japanese Scoliosis Society 22 (1) 31 -35 2007年12月20日 [査読無し][通常論文]
  
• プロテウス症候群様身体異常を合併した脊髄症・神経根症2例の治療経験

  新井隆太, 伊東 学, 小谷 善久, 高畑 雅彦, 須藤 英毅, 大嶋 茂樹, 三浪 明男, 鐙 邦芳 北海道整形災害外科学会雑誌 48 (2) 116 -117 2007年03月 [査読無し][通常論文]
  
• 後弯を伴う頚椎症性脊髄症の手術治療 : 後方除圧と後弯矯正の併用

  鐙 邦芳, 伊東 学, 小谷 善久, 須藤 英毅, 高畑 雅彦, 大嶋 茂樹, 三浪 明男 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 17 (1) 7 -8 2006年03月20日 [査読無し][通常論文]
  
• 当科における骨粗鬆症性椎体圧潰に対する手術治療法の変遷 : データに基づいた脊柱再建手術への提言

  伊東 学, 鐙 邦芳, 小谷 善久, 高畑 雅彦, 須藤 英毅, 大嶋 茂樹, 金田 清志, 藤谷 正紀, 三浪 明男 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 17 (1) 155 -156 2006年03月20日 [査読無し][通常論文]
  
• PLF単独およびPLIF併用の脊柱再建術が隣接椎間に与える生体力学的影響 (特集 脊椎脊髄病学最近の進歩 2003)

  須藤 英毅, 鐙 邦芳, 織田 格 臨床整形外科 38 (4) 487 -491 2003年04月
• 腰椎不安定性がpedicle screw systemへの応力と脊柱剛性に与える影響 : 椎体間固定の必要性の検討

  織田 格, 鐙 邦芳, 于 濱生, 須藤 英毅, 三浪 明男 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 13 (1) 2 -2 2002年04月26日 [査読無し][通常論文]
  
• PLF 単独およびPLIF 併用の脊柱再建術が隣接椎間に与える生体力学的影響

  須藤 英毅, 織田 格, 鐙 邦芳, 放生 憲博, 于 濱生, 三浪 明男 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 13 (1) 13 -13 2002年04月26日 [査読無し][通常論文]
  
• 骨粗鬆症性椎体圧潰発生のリスクファクター解析

  種市 洋, 金田 清志, 小熊 忠教, 古梶 正洋, 角家 健, 須藤 英毅, 白土 修 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society 12 (1) 215 -215 2001年04月27日
• スノーボードによる脊椎損傷の実態調査

  須藤 英毅, 金田 清志, 鐙 邦芳, 庄野 泰弘, 伊東 学, 小谷 善久, 高田 宇童, 須田 浩太, 柳橋 寧, 竹内 建人 日本脊椎外科学会雑誌 = The journal of the Japan Spine Research Society 11 (1) 356 -356 2000年04月28日 [査読無し][通常論文]
  

書籍等出版物

• 小児脊柱変形治療の最前線

  須藤英毅 (担当:手術治療,手術手技,Dual-rod Rotation, 179-183) (担当:単著範囲:手術治療，手術手技，Dual-rod Rotation,179-183)
  南江堂，東京 2021年
• 小児脊柱変形治療の最前線

  須藤英毅(担当:診療の考え方,トピック:3D対称性解析による脊柱側弯症検診システム,57-58) (担当:単著範囲:診療の考え方，トピック：3D対称性解析による脊柱側弯症検診システム,57-58)
  南江堂，東京 2021年
• 整形外科手術Knack and Pitfallsシリーズ，脊椎脊髄病における脊椎インストゥメンテーション手術

  須藤英毅(担当:脊柱変形に対する脊椎インストゥメンテーション手術,骨切り術を使用した矯正固定術,Ponte骨切り術(Grade 2),114-121) (担当:単著範囲:脊柱変形に対する脊椎インストゥメンテーション手術，骨切り術を使用した矯正固定術，Ponte骨切り術（Grade 2）)
  文光堂，東京 2021年
• Cervical Spine Surgery: Standard and Advanced Techniques. Chapter 37; SURGICAL TECHNIQUES - UPPER CERVICAL - C2 pedicle screw fixation technique

  Hideki Sudo, Kuniyoshi Abumi 
  Springer 2018年
• Neurological and vascular complications after surgery for cervical myelopathy

  Hideki Sudo (担当:分担執筆範囲:Chapter 20)
  Jaypee Medical Publishers 2016年
• Complications of Spinal Hydatidosis

  Hideki Sudo (担当:分担執筆範囲:Chapter 18,213-222)
  Springer-Verlag Berlin Heidelberg 2014年
• 講義録運動器学

  須藤英毅, 三浪明男 (担当:共著範囲:前腕遠位部骨折，165-168)
  medical view，東京 2006年
• 講義録運動器学

  須藤英毅, 三浪明男 (担当:共著範囲:手根骨骨折，169-172)
  medical view，東京 2006年

担当経験のある科目（授業）

整形外科学北海道大学大学院医学院
外科学北海道大学歯学部
診断学実習北海道大学医学部医学科
脊椎・脊髄病学北海道大学大学院医学院
整形外科北海道大学医学部医学科

所属学協会

• 日本再生医療学会   日本側弯症学会   日本脊椎脊髄病学会   日本整形外科学会   

共同研究・競争的資金等の研究課題

• 超高純度幹細胞・バイオマテリアルによる椎間板再生メカニズムの包括的解明

  科学研究費補助金基盤研究（A）

  研究期間 : 2024年04月 -2028年03月 

  代表者 : 須藤英毅
• 椎間板保水能評価のための非侵襲的イメージングシステム開発

  日本学術振興会：科学研究費助成事業

  研究期間 : 2024年04月 -2027年03月 

  代表者 : Tha KhinKhin, 須藤 英毅
• 高生体適合性三次元積層造形椎体間ケージの開発

  研究期間 : 2024年07月 -2025年03月 

  代表者 : 須藤英毅
• アナトミカルロッドとユニバーサルヘッドスクリューによる経皮的脊椎固定システムの開発・事業化

  北海道銀行中小企業技術活性化助成金

  研究期間 : 2024年03月 -2025年03月 

  代表者 : 須藤英毅
• アナトミカルロッドとユニバーサルヘッドスクリューによる経皮的脊椎固定システムの開発・事業化

  北洋銀行スタートアップ研究開発基金

  研究期間 : 2024年03月 -2025年03月 

  代表者 : 須藤英毅
• アナトミカルロッドとユニバーサルヘッドスクリューによる経皮的脊椎固定システムの開発・事業化

  日本医療研究開発機構(AMED)：医工連携イノベーション推進事業 開発･事業化事業（医療機器ベンチャー育成）

  研究期間 : 2023年10月 -2025年03月 

  代表者 : 須藤英毅
• 腰部脊柱管狭窄症に対するREC/dMD-001の安全性と有効性に係る探索的医師主導治験

  日本医療研究開発機構(AMED) 再生医療実用化研究事業：

  研究期間 : 2022年04月 -2025年03月 

  代表者 : 須藤英毅
• 自家骨髄濃縮液による低侵襲椎間板組織再生誘導法の開発と組織再生メカニズムの解明

  科学研究費補助金基盤研究（B）

  研究期間 : 2021年04月 -2024年03月 

  代表者 : 須藤英毅
• 高純度同種間葉系幹細胞(REC)と硬化性ゲルを用いた腰部脊柱管狭窄症に対する細胞治療

  日本医療研究開発機構(AMED)：再生医療実現拠点ネットワークプログラム （技術開発個別課題）

  研究期間 : 2020年06月 -2022年03月 

  代表者 : 須藤英毅
• 無形医療技術のデータ化及び分析に基づいた脊椎外科手術用高生体適合性医療機器の開発

  鈴木謙三記念医科学応用研究財団：

  研究期間 : 2022年 

  代表者 : 須藤英毅
• 混合性腰部脊柱管狭窄症に対する高純度同種間葉系幹細胞（REC）を用いた新規治療法の開発

  日本医療研究開発機構(AMED)：革新的医療技術創出拠点プロジェクト橋渡し研究戦略的推進プログラム preB

  研究期間 : 2020年04月 -2021年03月 

  代表者 : 須藤英毅
• 椎間板再生治療における組織修復材の開発

  日本医療研究開発機構(AMED)：革新的医療技術創出拠点プロジェクト 橋渡し研究戦略的推進プログラム シーズC

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 須藤英毅
• 椎間板変性に起因した痛みと関連する血清中糖鎖の網羅的解析

  文部科学省：科学研究費補助金挑戦的研究(萌芽)

  研究期間 : 2018年07月 -2020年03月 

  代表者 : 須藤英毅
• 高純度硬化性ゲルによる椎間板組織自然再生誘導法の開発と組織再生メカニズムの解明

  科学研究費補助金基盤研究（B）

  研究期間 : 2016年04月 -2019年03月 

  代表者 : 須藤英毅
• 高適合・短時間施術を実現する、3Dモデリング及び3D積層造形を応用したカスタムメイド脊柱変形矯正用インプラントの開発・事業化

  日本医療研究開発機構(AMED)：医工連携事業化推進事業

  研究期間 : 2016年 -2019年 

  代表者 : 須藤英毅
• 知財活用支援事業 大学等知財基盤強化支援（権利化支援）

  科学技術振興機構(JST)：

  研究期間 : 2018年 

  代表者 : 須藤英毅
• 知財活用支援事業 大学等知財基盤強化支援

  科学技術振興機構(JST)：

  研究期間 : 2017年02月 

  代表者 : 須藤英毅
• Factors affecting implant rod deformation in adolescent idiopathic scoliosis surgery

  AOSpine Research Grant：

  研究期間 : 2016年 -2017年 

  代表者 : 須藤英毅
• 椎間板再生治療における組織修復材の開発

  日本医療研究開発機構(AMED)：革新的医療技術創出拠点プロジェクト 橋渡し研究加速ネットワークプログラムシーズB

  研究期間 : 2016年 -2017年 

  代表者 : 須藤英毅
• 細胞周期関連遺伝子による椎間板恒常性維持制御機構の解明

  文部科学省：科学研究費補助金(挑戦的萌芽研究)

  研究期間 : 2014年 -2015年 

  代表者 : 須藤 英毅

   

  椎間板組織の中核を成す椎間板細胞の細胞増殖・維持機構は不明である。本研究では細胞周期関連遺伝子群の椎間板変性における機能解析を行った。すなわち、caspase 3とp27遺伝子に着目し、これらのKOマウスを作製した。また、その前段階として、野生型マウスを用いて再現性の高い椎間板変性モデルの作製を行った。この独自に作製したマウス椎間板変性モデルを用いて野生型マウスとcaaspase 3KOマウスとの比較では、初期にcaspase 3KOマウスで変性の抑制がみられ、p27KOマウスにおいても同様の結果が得られた。この結果から、これら細胞周期関連遺伝子群を対象として椎間板変性制御の可能性が示された。
• 生体力学的環境変化により生じる椎間板細胞・組織の変性制御に関する統合的研究

  武田科学振興財団医学系研究奨励継続助成：科学研究費助成事業

  研究期間 : 2013年 -2013年 

  代表者 : 須藤英毅

   

  椎間板変性には椎間板への過度の生体力学的応力集中が関与しているとの報告がある．一方，椎間板細胞のアポトーシスが椎間板組織の変性に関与しているとの報告もあり，今回これら生体力学的，分子生物学的側面から両者を統合したアプローチにより椎間板組織に対する変性抑制効果を検討した．その結果，椎間板細胞のアポトーシスを制御することにより，生体力学的荷重負荷を起因とした椎間板の組織変性を抑制することができた．生体力学的環境変化における椎間板変性に対しても今後有用な治療手段となりうることが示唆された．
• 生体力学的環境変化により生じる椎間板細胞・組織の変性制御に関する統合的研究

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2011年 -2013年 

  代表者 : 須藤 英毅

   

  椎間板変性疾患に対する今後の臨床応用を目標として，生体力学的環境変化により生じる椎間板細胞･組織の変性変化が遺伝子学的に制御可能かどうかを，生体力学的・分子生物学的手法を用いた多面的なアプローチにより統合的に検討することを本研究の目的とした． 具体的には椎間板細胞に力学的負荷を与え，アポトーシス関連遺伝子の発現変化を解析したのち，遺伝子強制発現およびノックダウンにより，椎間板細胞の増殖維持・誘導が起こるか検討し，アポトーシス関連遺伝子の相互作用を確認する．さらに生体力学的負荷を与えたin vivo動物実験で，これら遺伝子の椎間板組織内導入・干渉実験を行い，椎間板組織の経時的・質的変化についての調査を行う． 当該年度においてはin vivo実験として，日本白色家兎脊椎に自作の圧負荷装置を装着させ，ヒト椎間板組織にかかる生理的荷重と同等の圧負荷を椎間板組織にかけ，椎間板組織の変性変化を経時的に評価した．このモデルにより椎間板の変性を経時的にとらえることができることを病理学的，MRI画像評価から確認した． またin vitoro試験としてヒト椎間板細胞を単離・継代，3次元培養した上で自作の圧負荷装置により圧迫をかけ，細胞の状態について評価した． 最後に，ヒト細胞に対するsiRNA導入試験としてcaspase3 siRNAを作成し，ヒト椎間板細胞に導入し，RT-PCRおよびWestern blotにてその抑制効果を確認した．
• 中富健康科学振興財団 研究助成

  研究期間 : 2012年 

  代表者 : 須藤英毅
• 鈴木謙三記念医科学応用研究財団

  研究期間 : 2011年 

  代表者 : 須藤英毅
• 武田科学振興財団 医学系研究奨励

  研究期間 : 2011年 

  代表者 : 須藤英毅
• 椎間板細胞の再生を目指した細胞周期制御機構の解明

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2008年 -2010年 

  代表者 : 須藤 英毅

   

  椎間板障害に対する治療には従来から脊椎固定術や摘出術などの外科的治療が普及し一定の成果が確認できているが,その限界と代替医療の可能性に注目が集まっている.本研究では椎間板細胞を単離・継代し,血清非存在下における発現変動遺伝子の網羅的探索を行い,さらに得られた遺伝子群の発現を椎間板組織内で抑制させる機能解析を行った.その結果病理学的およびMRIにて椎間板組織の変性を抑制されていることが確認され,細胞周期をコントロールすることで椎間板組織の変性を抑制しうることが示唆された.
• 整形災害外科学研究助成財団

  研究期間 : 2008年 

  代表者 : 須藤英毅
• アポトーシス関連遺伝子を用いた椎間板組織の細胞周期・老化変性の制御機構の解明

  文部科学省：科学研究費補助金(若手研究(B))

  研究期間 : 2005年 -2007年 

  代表者 : 須藤 英毅

   

  これまで,椎間板の変性変化には椎間板細胞のアポトーシスが関与している可能性があることが示唆されていたが,その詳細なメカニズムは依然不明であった.本研究ではアポトーシスにおいて直接的な役割を果たす遺伝子群と,椎間板細胞を用いた遺伝子導入実験を行い,椎間板細胞のアポトーシス誘導機構の解析とこれらが椎間板変性に及ぼすメカニズムについての検討を行った.ラットアポトーシス抑制遺伝子:Bcl-2に対する最適化遺伝子合成を行い発現プラスミドを構築した.これをラット椎間板より採取拡大培養した椎間板細胞に遺伝子導入した.遺伝子導入48時間後に血清飢餓を開始しアポトーシスを誘導した.Bcl-2を過剰発現した系では,コントロール群に比べTunne1法にて断片化DNAが減少し,FACSにおいてもアポトーシス陽性細胞の減少が確認された.同時にRT-PCRにてCaspase3の発現量が低下していた.つまり,Bcl-2の過剰発現はCaspase3によるアポトーシスの実行を抑制することが明らかになった.椎間板細胞アポトーシスを遺伝子レベルで抑制することで椎間板変性に対する初期治療に応用できると思われる.
• 中富健康科学振興財団 研究助成

  研究期間 : 2005年 

  代表者 : 須藤英毅
• 上原記念生命科学財団研究奨励助成

  研究期間 : 2005年 

  代表者 : 須藤英毅

産業財産権

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