Updated on 2021/12/28

写真a

 
OZAKI Toshifumi
 
Organization
Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
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Degree

  • 医学博士 ( 岡山大学 )

  • 博士(医学) ( 岡山大学 )

Research Interests

  • 整形外科

  • Bone and soft tissue Tumor Spine

  • 脊椎

  • 骨軟部腫瘍

Research Areas

  • Life Science / Orthopedics

Research History

  • 岡山大学学術研究院医歯薬学域   教授

    2021

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  • - 岡山大学 副病院長(診療担当)

    2017 - 2019

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  • Okayama University

    2016 - 2017

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  • Okayama University   Okayama University Hospital

    2013 - 2016

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  • - 岡山大学医歯薬学総合研究科 教授

    2005

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  • - Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2005

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  • Senior Assistant Professor,Faculty of Medicine,Medical School,Okayama University

    2002 - 2005

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  • Okayama University   Medical School, Faculty of Medicine

    2002 - 2005

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  • Research Associate,Faculty of Medicine,Medical School,Okayama University

    1996 - 2002

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  • Okayama University   Medical School, Faculty of Medicine

    1996 - 2002

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Professional Memberships

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Committee Memberships

  • 国立研究開発法人量子科学技術研究開発機構QST病院   QST病院重粒子線治療臨床研究検討会骨軟部腫瘍班会議委員  

    2021.11 - 2023.3   

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  • 日本年金機構 障害年金センター   国民年金・特別障害給付金障害認定審査委員  

    2021.4 - 2022.3   

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  • 日本骨・関節感染症学会   監事  

    2021   

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  • 国立研究開発法人量子科学技術研究開発機構QST病院   重粒子線治療多施設共同臨床研究組織(J-CROS)運営委員会骨軟部腫瘍分科会委員  

    2020.4 - 2022.3   

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  • 岡山県医師会   理事  

    2018   

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  • 日本整形外科学会   理事  

    2017 - 2019   

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    Committee type:Academic society

    日本整形外科学会

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  •   - 日本臨床腫瘍グループ(JCOG) 代表(2017-)  

    2017   

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  • 日本骨折治療学会   評議員  

    2017   

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    Committee type:Academic society

    日本骨折治療学会

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  •   - 日本小児がん研究グループ(JCCG) 理事(2015-)  

    2015 - 2019   

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  • 日本股関節学会   評議員  

    2015   

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  • 日本軟骨代謝学会   理事  

    2014   

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    Committee type:Academic society

    日本軟骨代謝学会

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  •   - 日韓整形外科シンポジウム 理事(2014-)  

    2014   

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  • ISOLS   理事  

    2013   

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    Committee type:Academic society

    ISOLS

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  • 日本運動器科学会   理事  

    2013   

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    Committee type:Academic society

    日本運動器科学会

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  • 日本軟骨代謝学会   評議員  

    2013   

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    Committee type:Academic society

    日本軟骨代謝学会

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  • 日本人工関節学会   評議員  

    2013   

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    Committee type:Academic society

    日本人工関節学会

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  • 日本リウマチ学会   評議員  

    2013   

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    Committee type:Academic society

    日本リウマチ学会

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  • 日本癌治療学会   代議員  

    2013   

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    Committee type:Academic society

    日本癌治療学会

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  • 日本ユーイング肉腫研究グループ(JESS)   代表  

    2013   

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    Committee type:Academic society

    日本ユーイング肉腫研究グループ(JESS)

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  • 日本リハビリテーション医学会   代議員  

    2012   

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    Committee type:Academic society

    日本リハビリテーション医学会

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  • 日本関節病学会   理事  

    2012   

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    Committee type:Academic society

    日本関節病学会

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  • 日本整形外科スポーツ医学会   代議員  

    2011   

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    Committee type:Academic society

    日本整形外科スポーツ医学会

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  •   - 日本運動器移植・再生医学研究会 代表幹事(2011-)  

    2011   

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  •   - 日本リウマチ学会 評議員(2010-)  

    2010   

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  •   - 日本リウマチ学会中国・四国支部 評議員(2010-)  

    2010   

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  • 日本リハビリテーション医学会   評議員  

    2009   

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    Committee type:Academic society

    日本リハビリテーション医学会

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  • APMSTS   理事  

    2008   

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    Committee type:Academic society

    APMSTS

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  • 日本小児整形外科学会   評議員  

    2008   

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    Committee type:Academic society

    日本小児整形外科学会

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  • 日本バイオメカニクス学会   評議員  

    2007   

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    Committee type:Academic society

    日本バイオメカニクス学会

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  • 日本整形外科学会   代議員  

    2007   

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    Committee type:Academic society

    日本整形外科学会

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  • 日本骨・関節感染症研究会   評議員  

    2006   

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    Committee type:Academic society

    日本骨・関節感染症研究会

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  • 日本関節病学会   評議員  

    2006   

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    Committee type:Academic society

    日本関節病学会

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  • 中国・四国整形外科学会   理事  

    2005   

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    Committee type:Academic society

    中国・四国整形外科学会

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  • 中部日本整形外科災害外科学会   評議員  

    2003   

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    Committee type:Academic society

    中部日本整形外科災害外科学会

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  • 中部日本整形災害外科学会   評議員  

    1999   

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    Committee type:Academic society

    中部日本整形災害外科学会

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Papers

  • Relationship between clinical outcomes and nerve conduction studies before and after surgery in patients with carpal tunnel syndrome

    Masato Ise, Taichi Saito, Yoshimi Katayama, Ryuichi Nakahara, Yasunori Shimamura, Masanori Hamada, Masuo Senda, Toshifumi Ozaki

    BMC Musculoskeletal Disorders   22 ( 1 )   2021.12

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    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title><sec>
    <title>Background</title>
    Nerve conduction study (NCS) is the only useful test for objective assessment of carpal tunnel syndrome (CTS). However, the relationship between pre- and postoperative NCS and clinical outcomes was unclear. This study aimed to determine whether pre- and postoperative (6 months) NCS could predict patient-oriented and motor outcomes (6 and 12 months postoperatively) in patients with CTS.


    </sec><sec>
    <title>Method</title>
    Of the 85 patients with CTS, 107 hands were analyzed from March 2011 to March 2020. All patients underwent open carpal tunnel release and were examined using the disabilities of the arm, shoulder and hand (DASH) questionnaire and grip strength (GS) preoperatively and 6 and 12 months postoperatively. Moreover, NCS was examined preoperatively and 6 months postoperatively. Distal motor latency (DML) and sensory conduction velocity (SCV) were the parameters used for NCS. The correlation coefficient between NCS and DASH or GS was calculated. A receiver operating characteristic curve was utilized to determine the NCS threshold value to predict DASH and GS improvement.


    </sec><sec>
    <title>Results</title>
    The average scores of GS preoperatively and 6 and 12 months postoperatively were 21.3, 22.3, and 22.8, respectively. On the other hand, the average scores of DASH preoperatively and 6 and 12 months postoperatively were 28.8, 18.3, and 12.2, respectively. The average NCS scores (DML and SCV) preoperatively/6 months postoperatively were 7.3/5.4 and 27.8/36.7, respectively. Preoperative NCS did not correlate with DASH and GS. Postoperative SCV correlated with the change in grip strength (6–12 months, <italic>r</italic> = 0.67; 0–12 months, <italic>r</italic> = 0.60) and DASH (0–12 months, <italic>r</italic> = 0.77). Moreover, postoperative DML correlated with the change in DASH (6–12 months, <italic>r</italic> = − 0.33; 0–12 months, <italic>r</italic> = − 0.59). The prediction for the improvement of GS/DASH achieved a sensitivity of 50.0%/66.7% and a specificity of 100%/100%, at an SCV cutoff score of 38.5/45.0 or above. The prediction for improvement of GS/DASH achieved a sensitivity of 83.3%/66.7% and a specificity of 100%/66.7% at a DML cutoff score of 4.4/4.4 or below.


    </sec><sec>
    <title>Conclusion</title>
    NCS at 6 months postoperatively can be used to predict the improvement of clinical outcome after 6 months postoperatively in patients with CTS.


    </sec>

    DOI: 10.1186/s12891-021-04771-y

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    Other Link: https://link.springer.com/article/10.1186/s12891-021-04771-y/fulltext.html

  • A characteristic MRI finding to diagnose a partial tear of the medial meniscus posterior root: an ocarina sign

    Takayuki Furumatsu, Takaaki Hiranaka, Keisuke Kintaka, Yuki Okazaki, Naohiro Higashihara, Masanori Tamura, Toshifumi Ozaki

    Knee Surgery & Related Research   33 ( 1 )   2021.12

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    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title><sec>
    <title>Background</title>
    Diagnosing partial tears of the medial meniscus (MM) posterior root is difficult. The aim of this study was to evaluate diagnostic values involved in conventional magnetic resonance imaging (MRI) features of MM posterior root tears (MMPRTs) and find other MRI-based findings in patients with partial MMPRTs.


    </sec><sec>
    <title>Methods</title>
    Eighteen patients who had arthroscopically confirmed partial MMPRTs were included. As a control, 18 patients who underwent partial meniscectomy for other types of MM tears were evaluated. Isolated partial MMPRTs were classified into the following three types: type A, accurate partial stable tear (cleavage &lt; 1/2 of root width); type B, bridged unstable root tear (cleavage ≥ 1/2 of root width); type C, complex horn tear expanded to the root. Conventional MRI-based findings of MMPRTs were evaluated between two groups (<italic>n</italic> = 23). Posterior root irregularity, bone marrow spot, and ocarina-like appearance showing several condensed circles in triangular meniscal horn (ocarina sign) were also evaluated.


    </sec><sec>
    <title>Results</title>
    Posterior root irregularity and bone marrow spot were frequently observed in the partial MMPRTs (47.8%), compared with the other MM tears (<italic>P</italic> = 0.007 and 0.023, respectively). The ocarina sign was detected in 69.6% of patients with partial MMPRTs. A significant difference between two groups was observed in a positive ratio of ocarina sign (<italic>P</italic> &lt; 0.001). Types A, B, and C of the partial tear/damage were observed in three, eight, and seven patients, respectively. The ocarina sign was the most common MRI finding in each type of partial MMPRT.


    </sec><sec>
    <title>Conclusions</title>
    This study demonstrated that a characteristic MRI finding, “ocarina sign,” was frequently observed in patients with partial tear/damage of the MM posterior root. The ocarina sign was the most common MRI finding in several types of partial MMPRTs. Our results suggest that the ocarina sign may be useful to diagnose unnoticed partial MMPRTs.


    <italic>Level of evidence:</italic> IV, retrospective comparative study.


    </sec>

    DOI: 10.1186/s43019-021-00120-4

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    Other Link: https://link.springer.com/article/10.1186/s43019-021-00120-4/fulltext.html

  • Postoperative clinical outcomes of unicompartmental knee arthroplasty in patients with isolated medial compartmental osteoarthritis following medial meniscus posterior root tear. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Yuki Okazaki, Takaaki Tanaka, Masatsugu Ozawa, Kenji Masuda, Noritaka Seno, Haowei Xue, Toshifumi Ozaki

    Asia-Pacific journal of sports medicine, arthroscopy, rehabilitation and technology   26   15 - 20   2021.10

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    Background: Cartilage degradation progresses rapidly following medial meniscus posterior root tear (MMPRT). Unicompartmental knee arthroplasty (UKA) has been performed for medial compartmental osteoarthritis following MMPRT. We evaluated the clinical and radiographic outcomes of UKA for medial compartmental osteoarthritis after an untreated MMPRT. Methods: Twenty-one patients who underwent UKA for isolated medial compartment osteoarthritis following MMPRT were retrospectively investigated. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score and knee range of motion. The posterior tibial slope and tibial component inclination were evaluated using plain radiographs. Results: The mean follow-up periods were 25.5 ± 13.8 months. Clinical outcomes improved significantly postoperatively. The mean postoperative knee extension angle was -1.1° ± 2.1°, and the knee flexion angle was 134.3° ± 4.9°. The posterior tibial slope angle decreased from 9.0° ± 2.0° preoperatively to 5.4° ± 1.8° postoperatively, and postoperative tibial component inclination at the final follow-up was 2.9° ± 1.1° varus. No aseptic loosening or deep infections were observed. Conclusion: UKA significantly improved clinical outcomes and could be a viable surgical option for treating isolated medial compartmental osteoarthritis accompanied by untreated MMPRT.

    DOI: 10.1016/j.asmart.2021.07.005

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  • Mechanical stretching induces calcification and cartilage matrix metabolism, causing degeneration of the acetabular labrum

    Yoshi Kawamura, Tomonori Tetsunaga, Kazuki Yamada, Tomoaki Sanki, Yoshihiro Sato, Aki Yoshida, Takayuki Furumatsu, Toshifumi Ozaki

    HIP International   112070002110446 - 112070002110446   2021.9

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    Publishing type:Research paper (scientific journal)   Publisher:SAGE Publications  

    <sec><title>Purpose:</title> The acetabular labrum plays an important role in joint lubrication, and damage to this structure leads to osteoarthritis. This study aimed to histologically classify the degree of degeneration of the acetabular labrum and to investigate the changes in gene expression induced by mechanical stretching.

    </sec><sec><title>Methods:</title> We obtained acetabular labrum cells from patients with hip osteoarthritis during total hip arthroplasty ( n = 25). The labrum was stained with safranin O, and images were histologically evaluated using a new parameter, the red/blue (R/B) value. The samples were divided into the degenerated group (D group: n = 18) and the healthy group (H group: n = 7) in accordance with the Kellgren-Lawrence (KL) grade. The cultured acetabular labral cells were subjected to loaded uniaxial cyclic tensile strain (CTS). After CTS, changes in gene expression were examined in both groups.

    </sec><sec><title>Results:</title> Spearman’s correlation analysis revealed that the R/B value was significantly correlated with the KL grade and the Krenn score. The expression levels of genes related to cartilage metabolism, osteogenesis and angiogenesis significantly increased after CTS in the H group, while gene expression in the D group showed weaker changes after CTS than that in the H group compared to the nonstretched control group.

    </sec><sec><title>Conclusions:</title> The degree of labral degeneration could be classified histologically using the R/B value and the KL grade. Mechanical stretching caused changes in gene expression that support the pathological features of labral degeneration.

    </sec>

    DOI: 10.1177/11207000211044675

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    Other Link: http://journals.sagepub.com/doi/full-xml/10.1177/11207000211044675

  • Adipose-Derived Extract Suppresses IL-1β-Induced Inflammatory Signaling Pathways in Human Chondrocytes and Ameliorates the Cartilage Destruction of Experimental Osteoarthritis in Rats

    Hideki Ohashi, Keiichiro Nishida, Aki Yoshida, Yoshihisa Nasu, Ryuichi Nakahara, Yoshinori Matsumoto, Ayumu Takeshita, Daisuke Kaneda, Masanori Saeki, Toshifumi Ozaki

    International Journal of Molecular Sciences   22 ( 18 )   9781 - 9781   2021.9

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    Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    We investigated the effects of adipose-derived extract (AE) on cultured chondrocytes and in vivo cartilage destruction. AE was prepared from human adipose tissues using a nonenzymatic approach. Cultured human chondrocytes were stimulated with interleukin-1 beta (IL-1β) with or without different concentrations of AE. The effects of co-treatment with AE on intracellular signaling pathways and their downstream gene and protein expressions were examined using real-time PCR, Western blotting, and immunofluorescence staining. Rat AE prepared from inguinal adipose tissues was intra-articularly delivered to the knee joints of rats with experimental osteoarthritis (OA), and the effect of AE on cartilage destruction was evaluated histologically. In vitro, co-treatment with IL-1β combined with AE reduced activation of the p38 and ERK mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of the p65 subunit of nuclear factor-kappa B (NF-κB), and subsequently downregulated the expressions of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, IL-6, and IL-8, whereas it markedly upregulated the expression of IL-1 receptor type 2 (IL-1R2) in chondrocytes. Intra-articular injection of homologous AE significantly ameliorated cartilage destruction six weeks postoperatively in the rat OA model. These results suggested that AE may exert a chondroprotective effect, at least in part, through modulation of the IL-1β-induced inflammatory signaling pathway by upregulation of IL-1R2 expression.

    DOI: 10.3390/ijms22189781

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  • Transtibial pullout repair of medial meniscus posterior root tears: effects on the meniscus healing score and ICRS grade among patients with mild osteoarthritis of the knee. International journal

    Yuya Kodama, Takayuki Furumatsu, Yuki Okazaki, Shota Takihira, Takaaki Hiranaka, Shinichi Miyazawa, Yusuke Kamatsuki, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   29 ( 9 )   3001 - 3009   2021.9

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    PURPOSE: To assess the effects of transtibial pullout repair for medial meniscus posterior root tears (MMPRTs) among patients with early osteoarthritis of the knee as measured by the meniscus healing score and to determine whether the meniscus healing score correlates with the International Cartilage Repair Society (ICRS) grade progression. METHODS: Forty-seven patients with mild osteoarthritic knees (Kellgren-Lawrence grade ≤ 2 and varus alignment < 5°) who underwent transtibial pullout repair less than 3 months after MMPRT onset were assessed. The association between meniscus healing scores at 1 year postoperatively and cartilage damage of the medial compartment (medial femoral condyle [MFC] and medial tibial plateau [MTP]) were evaluated. The MFC was divided into six zones (A to F) and the MTP into two zones (G and H). The mean ICRS grade for each zone was compared between the primary surgery and second-look arthroscopy. The correlation between cartilage damage and meniscus healing status at the time of second-look arthroscopy in each zone was analysed. RESULTS: The mean time interval from injury to surgery was 63 days, and all clinical scores showed significant improvement. There were no significant differences in the extent of cartilage damage in areas B, C, E, or F (n.s.) for MFC or in areas G and H (n.s.) for MTP. The meniscus healing score and cartilage damage were correlated in the loading areas (B, C, E, and H; - 0.53, - 0.45, - 0.33, and - 0.38, respectively; p < 0.05). CONCLUSION: Transtibial pullout repair of MMPRTs among patients with mild osteoarthritic knees improved the clinical outcomes and showed a negative correlation between high meniscus healing scores and ICRS grades in the medial compartment loading area. This study suggests that early surgery should be undertaken for patients with mild osteoarthritic knee who develop MMPRTs. LEVEL OF EVIDENCE: Level IV.

    DOI: 10.1007/s00167-020-06332-7

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  • Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression. International journal

    Kazuhisa Sugiu, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Toshinori Omori, Tadashi Komatsubara, Yusuke Mochizuki, Hiroya Kondo, Shuhei Osaki, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Koji Ueda, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancer chemotherapy and pharmacology   88 ( 3 )   513 - 524   2021.9

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    BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53-expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells. MATERIALS AND METHODS: The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model. RESULTS: DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model. CONCLUSION: Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.

    DOI: 10.1007/s00280-021-04310-5

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  • Semi-quantitative arthroscopic scoring system is related to clinical outcomes in patients after medial meniscus posterior root repair

    Ximing Zhang, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Keisuke Kintaka, Haowei Xue, Shinichi Miyazawa, Toshifumi Ozaki

    Journal of Orthopaedic Science   2021.9

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jos.2021.07.023

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  • Effect of Patient Clinical Variables in Osteoporosis Classification Using Hip X-rays in Deep Learning Analysis. International journal

    Norio Yamamoto, Shintaro Sukegawa, Kazutaka Yamashita, Masaki Manabe, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Toshifumi Ozaki, Keisuke Kawasaki, Hitoshi Nagatsuka, Yoshihiko Furuki, Takashi Yorifuji

    Medicina (Kaunas, Lithuania)   57 ( 8 )   2021.8

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    Background and Objectives: A few deep learning studies have reported that combining image features with patient variables enhanced identification accuracy compared with image-only models. However, previous studies have not statistically reported the additional effect of patient variables on the image-only models. This study aimed to statistically evaluate the osteoporosis identification ability of deep learning by combining hip radiographs with patient variables. Materials andMethods: We collected a dataset containing 1699 images from patients who underwent skeletal-bone-mineral density measurements and hip radiography at a general hospital from 2014 to 2021. Osteoporosis was assessed from hip radiographs using convolutional neural network (CNN) models (ResNet18, 34, 50, 101, and 152). We also investigated ensemble models with patient clinical variables added to each CNN. Accuracy, precision, recall, specificity, F1 score, and area under the curve (AUC) were calculated as performance metrics. Furthermore, we statistically compared the accuracy of the image-only model with that of an ensemble model that included images plus patient factors, including effect size for each performance metric. Results: All metrics were improved in the ResNet34 ensemble model compared with the image-only model. The AUC score in the ensemble model was significantly improved compared with the image-only model (difference 0.004; 95% CI 0.002-0.0007; p = 0.0004, effect size: 0.871). Conclusions: This study revealed the additional effect of patient variables in identification of osteoporosis using deep CNNs with hip radiographs. Our results provided evidence that the patient variables had additive synergistic effects on the image in osteoporosis identification.

    DOI: 10.3390/medicina57080846

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  • CSF1/CSF1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-cell Infiltration in the Sarcoma Microenvironment. International journal

    Tomohiro Fujiwara, Mohamed A Yakoub, Andrew Chandler, Alexander B Christ, Guangli Yang, Ouathek Ouerfelli, Vinagolu K Rajasekhar, Aki Yoshida, Hiroya Kondo, Toshiaki Hata, Hiroshi Tazawa, Yildirim Dogan, Malcolm A S Moore, Toshiyoshi Fujiwara, Toshifumi Ozaki, Ed Purdue, John H Healey

    Molecular cancer therapeutics   20 ( 8 )   1388 - 1399   2021.8

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    Colony-stimulating factor 1 (CSF1) is a primary regulator of the survival, proliferation, and differentiation of monocyte/macrophage that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). Considering current advances in understanding the role of the inflammatory tumor microenvironment, targeting the components of the sarcoma microenvironment, such as TAMs, is a viable strategy. Here, we investigated the effect of PLX3397 (pexidartinib) as a potent inhibitor of the CSF1 receptor (CSF1R). PLX3397 was recently approved by the Food and Drug Administration (FDA) to treat tenosynovial giant cell tumor and reprogram TAMs whose infiltration correlates with unfavorable prognosis of sarcomas. First, we confirmed by cytokine arrays of tumor-conditioned media (TCM) that cytokines including CSF1 are secreted from LM8 osteosarcoma cells and NFSa fibrosarcoma cells. The TCM, like CSF1, stimulated ERK1/2 phosphorylation in bone marrow-derived macrophages (BMDMs), polarized BMDMs toward an M2 (TAM-like) phenotype, and strikingly promoted BMDM chemotaxis. In vitro administration of PLX3397 suppressed pERK1/2 stimulation by CSF1 or TCM, and reduced M2 polarization, survival, and chemotaxis in BMDMs. Systemic administration of PLX3397 to the osteosarcoma orthotopic xenograft model significantly suppressed the primary tumor growth and lung metastasis, and thus improved metastasis-free survival. PLX3397 treatment concurrently depleted TAMs and FOXP3+ regulatory T cells and, surprisingly, enhanced infiltration of CD8+ T cells into the microenvironments of both primary and metastatic osteosarcoma sites. Our preclinical results show that PLX3397 has strong macrophage- and T-cell-modulating effects that may translate into cancer immunotherapy for bone and soft-tissue sarcomas.

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  • Induction and expansion of human PRRX1+ limb-bud-like mesenchymal cells from pluripotent stem cells. International journal

    Daisuke Yamada, Masahiro Nakamura, Tomoka Takao, Shota Takihira, Aki Yoshida, Shunsuke Kawai, Akihiro Miura, Lu Ming, Hiroyuki Yoshitomi, Mai Gozu, Kumi Okamoto, Hironori Hojo, Naoyuki Kusaka, Ryosuke Iwai, Eiji Nakata, Toshifumi Ozaki, Junya Toguchida, Takeshi Takarada

    Nature biomedical engineering   5 ( 8 )   926 - 940   2021.8

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    Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1-tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1+ limb-bud-like mesenchymal cells under defined xeno-free conditions, and the prospective assessment of the cells' chondrogenic potential via the cell-surface markers CD90, CD140B and CD82. The cells, which proliferated stably and exhibited the potential to undergo chondrogenic differentiation, formed hyaline cartilaginous-like tissue commensurate to their PRRX1-expression levels. Moreover, we show that limb-bud-like mesenchymal cells derived from patient-derived induced hPSCs can be used to identify therapeutic candidates for type II collagenopathy and we developed a method to generate uniformly sized hyaline cartilaginous-like particles by plating the cells on culture dishes coated with spots of a zwitterionic polymer. PRRX1+ limb-bud-like mesenchymal cells could facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering.

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  • Letter regarding "Clinical outcomes and trans-syndesmotic screw frequency after posterior malleolar fracture osteosynthesis". International journal

    Norio Yamamoto, Yosuke Tomita, Tomoyuki Noda, Kohei Iwamoto, Toshifumi Ozaki

    Injury   52 ( 8 )   2479 - 2480   2021.8

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  • Two simple stitches for medial meniscus posterior root repair prevents the progression of meniscal extrusion and reduces intrameniscal signal intensity better than modified Mason-Allen sutures. International journal

    Yuki Okazaki, Takayuki Furumatsu, Takaaki Hiranaka, Yuya Kodama, Yusuke Kamatsuki, Keisuke Kintaka, Toshifumi Ozaki

    European journal of orthopaedic surgery & traumatology : orthopedie traumatologie   31 ( 6 )   1005 - 1013   2021.8

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    PURPOSE: Medial meniscus posterior root tears (MMPRTs) can cause severe medial extrusion of the medial meniscus (MMME) and the progression of knee degenerative changes, inducing a high signal intensity of the meniscus on magnetic resonance imaging (MRI). Although MMME and intrameniscal signal intensity (IMSI) reportedly decreased within 3 months after MMPRT repair, no previous studies have reported these changes after a 1-year follow-up. This study aimed to investigate the 1-year postoperative changes in MMME and IMSI on MRI after using different suture techniques. METHODS: Overall, 33 patients with MMPRT were evaluated, 22 underwent FasT-Fix-dependent modified Mason-Allen suture (F-MMA) repair, and 11 underwent two simple stitches (TSS) repair. MRI examinations were performed preoperatively and 1 year postoperatively. MMME and IMSI were determined using MRI. RESULTS: A significant decrease in postoperative MMME was observed in the TSS group (4.1 ± 1.0) relative to that in the F-MMA group (5.1 ± 1.4, P = 0.03). A significant decrease in postoperative IMSI (0.75 ± 0.14) was observed relative to preoperative IMSI in the TSS group (P < 0.01), whereas postoperative IMSI (0.94 ± 0.25) was similar to preoperative IMSI in the F-MMA group (P = 0.06). Furthermore, a significant decrease in postoperative IMSI was observed in the TSS group relative to that in the F-MMA group (P < 0.01). CONCLUSIONS: The most important finding of this study is that TSS repair yielded a greater decrease in MMME and IMSI than F-MMA repair in patients with MMPRT. These results suggest that TSS repair is more useful for restoring loading stress to the posterior horn of the medial meniscus.

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  • Medial meniscus posterior root repair using a modified Mason-Allen suture can prevent the progression of cartilage degeneration on the loading surface of the medial compartment: a second-look arthroscopic evaluation

    Takihira S, Furumatsu T, Okazaki Yuki, Hiranaka T, Kintaka K, Kodama Y, Kamatsuki Y, Miyazawa S, Ozaki T

    Acta Med Okayama   75 ( 4 )   423 - 430   2021.8

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  • Assessment of the concordance rate between intraoperative pathological diagnosis and the final pathological diagnosis of spinal cord tumors

    Muraoka S, Yamane K, Misawa H, Takigawa T, Tetsunaga T, Oda Y, Nakanishi K, Ozaki T, Tanaka T

    Acta Med Okayama   75 ( 4 )   455 - 460   2021.8

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  • Adjuvant and neoadjuvant chemotherapy for osteosarcoma: JCOG Bone and Soft Tissue Tumor Study Group. International journal

    Hiroaki Hiraga, Toshifumi Ozaki

    Japanese journal of clinical oncology   2021.7

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    The usefulness of adjuvant chemotherapy for high-grade osteosarcoma was established by two randomized, controlled trials conducted in the 1980s, which used six drugs, doxorubicin, cisplatin, high-dose methotrexate, bleomycin, cyclophosphamide and actinomycin D. Since then, development has been promoted in the direction of introducing preoperative chemotherapy, changing post-operative adjuvant chemotherapy according to histological effects, adding ifosfamide as a key drug and strengthening adjuvant chemotherapy. No clinical trials, however, have shown the effectiveness of study treatment, and the improvement of treatment results during that time has been slight, although the JCOG0905 study is now going to verify the effectiveness of introducing ifosfamide for patients who experienced limited preoperative therapeutic effects. We are desperately looking for a breakthrough.

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  • Psoas muscle index predicts osteoporosis and fracture risk in individuals with degenerative spinal disease. International journal

    Yuya Kajiki, Hironori Tsuji, Haruo Misawa, Ryuichi Nakahara, Tomoko Tetsunaga, Kentaro Yamane, Yoshiaki Oda, Shinichiro Takao, Toshifumi Ozaki

    Nutrition (Burbank, Los Angeles County, Calif.)   93   111428 - 111428   2021.7

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    OBJECTIVES: Skeletal muscle loss and osteoporosis are major medical and socioeconomic concerns as the global population ages. Studies have reported that skeletal muscle mass correlates to bone mineral density (BMD). The psoas muscle index (PMI), measured as the L3 cross-sectional areas of the right and left psoas divided by the square of height, has a positive correlation with the total volume of skeletal muscle in the body. This study aimed to evaluate relationships between PMI and BMD and fracture risk estimated by the Fracture Risk Assessment Tool (FRAX). METHODS: Preoperatively acquired, plain computed tomography images at the L3 level were used to measure PMI in 87 people with degenerative spinal diseases. We evaluated the correlation between PMI and BMD and fracture risk estimated by FRAX. RESULTS: PMI was significantly correlated with BMD in the entire lumbar spine and femoral neck (r = 0.413 and 0.525, both P < 0.001). People with osteoporosis showed significantly lower PMI than those without (P < 0.05). PMI was also significantly correlated with FRAX score (r = -0.545, P < 0.001). Furthermore, based on the recommendation of osteoporosis treatment, participants were divided into two groups: FRAX ≥15% (R group) and FRAX <15% (C group). The R group showed significantly lower PMI than the C group (P < 0.001). Receiver operating characteristic curve analysis revealed that PMI has moderate accuracy in diagnosing osteoporosis and FRAX ≥15%. CONCLUSIONS: PMI was significantly associated with BMD and fracture risk. PMI measurement is straightforward and may increase the diagnosis rate of osteoporosis and fracture risk.

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  • A Novel Radiographic Measurement Method for the Evaluation of Metatarsophalangeal Joint Dislocation of the Lesser Toe in Patients with Rheumatoid Arthritis. International journal

    Hideki Ohashi, Keiichiro Nishida, Yoshihisa Nasu, Kenta Saiga, Ryuichi Nakahara, Masahiro Horita, Shunji Okita, Toshifumi Ozaki

    International journal of environmental research and public health   18 ( 14 )   2021.7

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    Dorsal dislocation of metatarsophalangeal (MTP) joints of the lesser toe frequently occurs in patients with rheumatoid arthritis (RA), and may cause painful and uncomfortable plantar callosities and ulceration. The current study examined the reliability and clinical relevance of a novel radiographic parameter (the MTP overlap distance [MOD]) in evaluating the severity of MTP joint dislocation. The subjects of the current study were 147 RA patients (276 feet; 1104 toes). MOD, defined as the overlap distance of the metatarsal head and the proximal end of the phalanx, was measured on plain radiographs. The relationship between the MOD and clinical complaints (forefoot pain and/or callosity formation) was analyzed to create a severity grading system. As a result, toes with callosities had a significantly larger MOD. ROC analysis revealed that the MOD had a high AUC for predicting an asymptomatic foot (-0.70) and callosities (0.89). MOD grades were defined as follows: grade 1, 0 ≤ MOD < 5 mm; grade 2, 5 ≤ MOD < 10 mm; and grade 3, MOD ≥ 10 mm. The intra- and inter-observer reliability of the MOD grade had high reproducibility. Furthermore, the MOD and MOD grade improved significantly after joint-preserving surgeries for lesser toe deformities. Our results suggest that MOD and MOD grade might be useful tools for the evaluation of deformities of the lesser toe and the effect of surgical intervention for MTP joints in patients with RA.

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  • Cement augmentation of internal fixation for trochanteric fracture: a systematic review and meta-analysis. International journal

    Norio Yamamoto, Takahisa Ogawa, Masahiro Banno, Jun Watanabe, Tomoyuki Noda, Haggai Schermann, Toshifumi Ozaki

    European journal of trauma and emergency surgery : official publication of the European Trauma Society   2021.7

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    PURPOSE: This study aimed to determine the efficacy and safety of cement augmentation for internally fixed trochanteric fractures through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We searched the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases to identify RCTs, published until July 2020 that examined the effects of cement augmentation of internal fixation of trochanteric fractures. The primary outcomes were reoperation and Parker Mobility Score, whereas the secondary outcomes were 1-year mortality rate, EuroQol 5 Dimension, fixation failures, and adverse events. We conducted meta-analyses of the outcome measures using the random-effects models. We evaluated the certainty of evidence based on the Cochrane risk-of-bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: We included three RCTs (326 participants). No significant effect was observed in favor of cement augmentation on all these outcomes. The certainty of evidence for fixation failures was very low and that for the other outcomes was low. The overall risk of bias for each outcome was high or of some concern in all included studies. CONCLUSIONS: The effect of cement augmentation of internal fixation of trochanteric fractures was uncertain for the clinical outcomes due to the low certainty of evidence. Further RCTs with a low risk of selection bias may present convincing conclusions on the efficacy and safety of cement augmentation. LEVEL OF EVIDENCE: Level 1.

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  • Postoperative external tibial rotation is correlated with inferior meniscal healing following pullout repair of a medial meniscus posterior root tear. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Yuki Okazaki, Keisuke Kintaka, Yusuke Kamatsuki, Ximing Zhang, Haowei Xue, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   2021.7

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    PURPOSE: The purpose of this study was to evaluate the influence of tibial rotation on the postoperative healing status of the medial meniscus (MM) following pullout repair of the MM posterior root tear (MMPRT). METHODS: Ninety-one patients (68 women and 23 men; mean age 63.3 ± 8.8 years) who had undergone transtibial pullout repair of MMPRT were enrolled in the study. The tibial external rotation angle (ERA) in each patient was measured postoperatively using computed tomography in the extended knee position. The meniscal healing status following transtibial pullout repair was assessed by second-look arthroscopy (mean postoperative period 12 months) using a previously published scoring system (range 0-10). The association between the ERA and the meniscal healing score was investigated using univariate linear regression models. The ERA cut-off for improved meniscal healing score (≥ 7) was determined using receiver-operating characteristic analysis. RESULTS: The ERA and the meniscal healing score were significantly associated, confirming that increased ERAs were correlated with worse meniscal healing status (R =  - 0.28; P < 0.001). The optimum ERA cut-off value was 0.5°, with a sensitivity of 68% and a specificity of 63%. The mean meniscal healing scores were 7.3 and 6.2 among patients with ERAs < 0.5° and those with ERAs ≥ 0.5°, respectively (P < 0.001). CONCLUSION: This study demonstrated that the ERA was significantly correlated with the postoperative meniscal healing status. Postoperative tibial rotation could be one of the factors affecting postoperative outcomes of pullout repair of MMPRT. Controlling the tibial rotation may possibly improve meniscal healing. LEVEL OF EVIDENCE: III.

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  • Spinopelvic fixation with retention of external fixation in a lateral position for unstable pelvic fracture. International journal

    Norio Yamamoto, Hisanori Ikuma, Tomoyuki Noda, Tomoo Inoue, Keisuke Kawasaki, Toshifumi Ozaki

    Orthopaedics & traumatology, surgery & research : OTSR   103008 - 103008   2021.7

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    Anterior external fixation (EF), as the primary treatment for unstable pelvic fractures, is performed with patients in the supine position. In most cases, however, definitive surgery for posterior fixation is performed first in the prone position without EF. We report the case of a patient with unilateral and vertically unstable pelvic fracture whom we had treated with minimally invasive spinopelvic fixation, with retention of the anterior EF in a lateral position. Reduction of the residual displacement was performed with percutaneous spinal instrumentation, and acceptable reduction was achieved. At the 13-month follow-up, the functional outcome, calculated using the Majeed Score, was 87 points. The plain radiograph showed good bone union, except for the right superior pubic ramus. The radiological outcome, measured using the Matta rating, was excellent. Thus, retaining the EF facilitates safe and accurate reduction without major surgical complications and may offer surgeons an additional management option for such fractures.

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  • Symptomatic Venous Thromboembolism in Patients with Malignant Bone and Soft Tissue Tumors: A Prospective Multicenter Cohort Study

    Shintaro Iwata, Akira Kawai, Takafumi Ueda, Takeshi Ishii, Tsukasa Yonemoto, Tsukasa Yonemoto, Hiroto Kamoda, Yoshihisa Suzuki, Kazutaka Kikuta, Jungo Imanishi, Taketo Okubo, Yasuo Yazawa, Tsukasa Sotobori, Hiroaki Murata, Toshifumi Ozaki, Toshiyuki Kunisada, Tomohiro Fujiwara, Shigeki Kakunaga, Koji Hiraoka, Tetsuya Hamada, Kotaro Matsuda, Takashi Yanagawa, Kenichi Saito, Hirofumi Namba, Motohiro Kawasaki, Shunji Nishimura, Kazuhiko Hashimoto, Takeshi Okamoto, Ukei Anazawa, Itsuo Watanabe, Michiyuki Hakozaki, Yoshinori Imura, Yoshinori Imura, Eisuke Kobayashi, Koichi Ogura, Taketoshi Yasuda, Kayo Suzuki, Toru Akiyama, Masami Hosaka, Munenori Watanuki, Kou Hayashi, Toshiharu Shirai, Ryu Terauchi, Hisaki Aiba, Hiroaki Kimura, Kunihiro Asanuma, Tomoki Nakamura, Tomohito Hagi, Satoshi Abe, Kenji Sato, Yukihiro Yoshida, Yoshiyuki Suehara, Keisuke Akaike, Hiroaki Hiraga, Tamotsu Soma, Hiroshi Kobayashi, Yusuke Shinoda, Ryoko Sawada

    ANNALS OF SURGICAL ONCOLOGY   28 ( 7 )   3919 - 3927   2021.7

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    Background A prospective cohort study was conducted to determine the incidence and risk factors of symptomatic venous thromboembolism (sVTE) during the perioperative period in patients with malignant bone and soft tissue tumors. Methods Patients with newly diagnosed primary malignant bone and soft tissue tumors for whom definitive surgery was planned were consecutively registered among 27 tertiary hospitals specializing in musculoskeletal oncology. Clinicopathological information on each patient was collected prospectively, and careful follow-up was conducted for 6 months after surgery. The study endpoint was the occurrence of sVTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). Results Eleven of 929 patients developed sVTE, including 8 patients with DVT, 2 with PE, and 1 with both, making the incidence of sVTE 1.18%. The median time until the development of sVTE after tumor resection was 11 days, ranging from - 7 to 95 days. Multiple logistic regression analyses revealed that ischemic heart disease as a comorbidity, maximum tumor diameter exceeding 8 cm, and elevated preoperative platelet count were independent risk factors for sVTE. Conclusions The incidence of sVTE in this series of patients with bone and soft tissue sarcomas was 1.18%, which was relatively lower than in previous retrospective studies. We identified the risk factors for sVTE specific to patients with malignant bone and soft tissue tumors, and these included ischemic heart disease, tumor size, and elevation of the preoperative platelet count.

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  • Treatment for postoperative infection of pathological femoral fracture after radiotherapy: two case reports and review of the literature. International journal

    Minami Matsuhashi, Taichi Saito, Tomoyuki Noda, Takenori Uehara, Yasunori Shimamura, Toshifumi Ozaki

    Archives of orthopaedic and trauma surgery   141 ( 7 )   1139 - 1148   2021.7

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    INTRODUCTION: Radiation-induced pathological fractures show high nonunion and infection rates. Successful treatment of postoperative infections of these fractures without limb amputation is extremely rare. METHODS: We report two cases of postoperative infection of pathological femoral fracture after radiation therapy for soft tissue tumors. Considering the poor condition of the irradiated site, a two-staged operation was selected to create the optimal situation for bone union. The treatment involved the Masquelet technique, latissimus dorsi (LD) flap, and a free vascularized fibula graft (FVFG). In the first stage, we drastically resected the necrotic bone and the surrounding infected tissue and placed antibiotic polymethylmethacrylate space on the bone gap according to the Masquelet technique. Next, we used an Ilizarov external fixator as a temporizing stabilizer and performed the LD flap. Six weeks later, in the second stage, we changed the external fixation to plate fixation; packed the artificial bone (β-TCP) and autograft bone to the induced membrane; and performed FVFG on the other side of the plate. As postoperative therapy, toe touch was allowed immediately, and partial weight bearing was started 2 months after second surgery. RESULTS: Both patients achieved bone union and were able to walk without postoperative complications. At the 2-year follow-up, there was no recurrence of infection. CONCLUSION: Our treatment is effective for controlling postoperative infection of radiation-induced pathological fracture.

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  • Reduction quality and nail fixation ratio as bone-implant stability factors associated with reoperation for trochanteric fractures. International journal

    Norio Yamamoto, Yosuke Tomita, Tomoyuki Noda, Tomoo Inoue, Yusuke Mochizuki, Toshifumi Ozaki

    Injury   52 ( 7 )   1813 - 1818   2021.7

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    INTRODUCTION: Geriatric trochanteric fractures are a major global issue, and their incidence is steadily rising. Bone quality, fracture type, fracture reduction quality, implant selection, and implant placement affect bone-implant stability in osteoporotic fractures. Our aim in this study was to evaluate the association between bone-implant stability factors, including nail construct, and the rate of reoperation in a more extensive case series with comprehensive variables. METHODS: This was a retrospective cohort study of 390 patients with trochanteric fractures aged ≥60 years and treated with intramedullary nailing. The primary outcome was the rate of reoperation due to any cause. Univariate and multivariable logistic regression analyses were used to identify factors associated with reoperation. RESULTS: In this study, 15 patients (3.8%) required reoperation. Univariate analysis showed that the following variables were significantly different between patients who required reoperation and those who did not: T-score at the total hip and lumbar spine, cortical thickness index, fracture type, and reduction quality. Multivariable logistic regression analysis showed that the odds ratio (OR) for A3 fracture type was 2.76 (95% confidence interval [CI], 0.77-9.76; p=0.116) and that for inadequate reduction, assessed by computed tomography, was 2.94 (95% CI, 0.89-9.69; p=0.076). These were independent predictors of reoperation. There was only one case (6.7%) of reoperation among patients with a distal femoral fragment fixation ratio (FR) >0.8. Considering the intraoperative decision-making process, the combination of inadequate reduction and an FR ≤0.8 were associated with the highest reoperation at a rate of 9.3% (OR, 3.327; 95% CI, 1.091-10.142; p=0.043). CONCLUSIONS: Risk factors on bone-implant stability for reoperation were the reduction quality and fracture type. Regarding the intraoperative decision-making process, the selection of a nail length with an FR >0.8 is a better option when the intramedullary reduction has been maintained intraoperatively.

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  • Clinical prediction model for postoperative ambulatory ability outcomes in patients with trochanteric fractures. International journal

    Yosuke Tomita, Norio Yamamoto, Tomoo Inoue, Tomoyuki Noda, Keisuke Kawasaki, Toshifumi Ozaki

    Injury   52 ( 7 )   1826 - 1832   2021.7

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    INTRODUCTION: Regaining independent ambulatory ability is one of the primary goals of treatment in patients with trochanteric fractures. This study aimed to develop and evaluate the discriminative accuracy of a clinical prediction model for ambulatory ability outcomes 3 months after surgery for trochanteric fractures. METHODS: This retrospective cohort study included 346 patients treated with intramedullary nailing for trochanteric fractures who had independent ambulatory ability before their injury. Multiple regression models with preoperative and postoperative factors were used to predict ambulatory ability outcomes at 3 months. A clinical prediction model (CPM) was created based on a decision tree developed using a chi-square automatic interaction detector technique. RESULTS: Three months after surgery, 263 (76.0%) and 83 (24.0%) patients regained and lost independent ambulatory ability, respectively. Univariate analysis showed that the Barthel index (BI) total score at 2 weeks predicted the ambulatory ability outcome at 3 months with good discriminative accuracy (area under the receiver operating characteristic curve [AUROC]: 0.819; 95% confidence interval [CI]: [0.769, 0.868], cut-off value: 22.5; sensitivity: 69.5%; specificity: 82.3%). Multiple logistic regression analysis showed that preoperative factors (residence before injury, diagnosis of dementia, and serum albumin at admission) and postoperative factors (BI total score at 2 weeks) predicted ambulatory ability outcomes at 3 months (AUROC: 0.710; 95%CI: [0.636, 0.783]; sensitivity: 91.3%; specificity: 41.8%). The CPM with the BI total score at 2 weeks (≤10; 10<, ≤50; >50 points) and dementia status (present; absent) had a moderate discriminative accuracy (AUROC: 0.676; 95%CI: [0.600, 0.752]; sensitivity: 94.7%; specificity: 40.5%). CONCLUSIONS: We developed a CPM with moderate accuracy to predict ambulatory ability outcomes in patients 3 months after surgery for trochanteric fractures. Our results demonstrate the importance of the BI score measured soon after surgery and dementia status for the prediction of postoperative ambulation.

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  • Subjective and Objective Outcomes of Surgery for Rheumatoid Forefoot Deformities Under the Current Treatment Paradigm. International journal

    Masahiro Horita, Keiichiro Nishida, Daisuke Kaneda, Kenzo Hashizume, Yoshihisa Nasu, Ryuichi Nakahara, Kenta Saiga, Hideki Ohashi, Masahito Watanabe, Toshifumi Ozaki

    The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons   2021.6

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    We investigated the clinical outcomes of surgical procedures for the treatment of forefoot deformities in patients with rheumatoid arthritis. Twenty feet in 16 women (mean age 62.1 years) underwent corrective osteotomy of the first metatarsal bone with shortening oblique osteotomy of the lesser metatarsophalangeal joints (joint-preservation group), while 13 feet in 12 women (mean age 67.4 years) underwent arthrodesis of the first metatarsophalangeal joint with resection arthroplasty of the lesser metatarsophalangeal joints (joint-sacrifice group); mean follow-up for each group was 25.8 and 23.8 months, respectively. The mean total Japanese Society for Surgery of the Foot (JSSF) scale improved significantly from 64.2 to 89.2 in the joint-preservation group (p < .001), and from 54.2 to 74.2 in the joint-sacrifice group (p = .003). In the joint-preservation group, the postoperative range of motion (ROM) of the joint, walking ability, and activities of daily living scores of the JSSF scale were significantly higher than those in the joint-sacrifice group (p = .001, p = .001, and p = .019, respectively). There were no differences in the subscale scores of the self-administered foot evaluation questionnaire between 2 groups either pre- or postoperatively. No differences in the postoperative complications were found between 2 groups. Although the joint-sacrificing procedure resulted in lower objective outcomes than the joint-preserving procedure regarding the ROM of the joint, the walking ability, and the level of activities of daily living, both procedures resulted in similar treatment outcomes when evaluated by the subjective measures.

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  • Transtibial pullout repair techniques using two simple stitches for medial meniscus posterior root tear can prevent the progression of medial meniscus extrusion and obtain successful outcomes. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Shinichi Miyazawa, Yuki Okazaki, Keisuke Kintaka, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

    European journal of orthopaedic surgery & traumatology : orthopedie traumatologie   2021.6

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    PURPOSE: Transtibial pullout repairs using two simple stitches (TSS) and a combination of TSS with posteromedial pullout repair (TSS + PMP) using an all-inside meniscal repair device have been reported previously for the treatment of medial meniscus (MM) posterior root tears. This study aimed to investigate the postoperative clinical outcomes of these techniques including MM extrusion (MME). METHODS: Fifty-two patients who underwent transtibial pullout repair were investigated and divided into TSS (n = 27) and TSS + PMP (n = 25) groups. The clinical outcomes were assessed using the Lysholm knee score and Knee Injury and Osteoarthritis Outcome Score 1 year postoperatively and compared between two groups. MME was measured using magnetic resonance imaging at 1 year postoperatively and compared between two groups. RESULTS: A significant improvement in each clinical score was observed in both groups, and no significant difference was seen in clinical outcomes. Moreover, no significant difference in postoperative MME was observed in both groups (TSS and TSS + PMP: 3.5 mm and 3.8 mm, respectively). Though no significant progression of MME was observed in TSS group, a significant progression of it was observed in TSS + PMP group postoperatively. CONCLUSIONS: This study demonstrated that both techniques improved clinical outcomes in the short-term postoperative period. However, MME was progressed significantly in TSS + PMP group 1 year postoperatively, which indicated that PMP might not be a useful additional procedure for reducing the postoperative MME.

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  • Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors. International journal

    Rongsheng Huang, Atsushi Fujimura, Eiji Nakata, Shota Takihira, Hirofumi Inoue, Soichiro Yoshikawa, Takeshi Hiyama, Toshifumi Ozaki, Atsunori Kamiya

    Biochemical and biophysical research communications   557   199 - 205   2021.6

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    Malignant peripheral nerve sheath tumor (MPNST), a highly malignant tumor that arises in peripheral nerve tissues, is known to be highly resistant to radiation and chemotherapy. Although there are several reports on genetic mutations and epigenetic changes that define the pathogenesis of MPNST, there is insufficient information regarding the microenvironment that contributes to the malignancy of MPNST. In the present study, we demonstrate that adrenaline increases the cancer stem cell population in MPNST. This effect is mediated by adrenaline stimulation of beta-2 adrenergic receptor (ADRB2), which activates the Hippo transducer, YAP/TAZ. Inhibition and RNAi experiments revealed that inhibition of ADRB2 attenuated the adrenaline-triggered activity of YAP/TAZ and subsequently attenuated MPNST cells stemness. Furthermore, ADRB2-YAP/TAZ axis was confirmed in the MPNST patients' specimens. The prognosis of patients with high levels of ADRB2 was found to be significantly worse. These data show that adrenaline exacerbates MPNST prognosis and may aid the development of new treatment strategies for MPNST.

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  • Clinical outcome of patients with recurrent or refractory localized Ewing's sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group. International journal

    Katsutsugu Umeda, Takako Miyamura, Kenji Yamada, Hideki Sano, Ako Hosono, Minako Sumi, Hajime Okita, Tadashi Kumamoto, Akira Kawai, Junya Hirayama, Ryoji Jyoko, Akihisa Sawada, Hideki Nakayama, Yosuke Hosoya, Naoko Maeda, Nobuyuki Yamamoto, Chihaya Imai, Daiichiro Hasegawa, Motoaki Chin, Toshifumi Ozaki

    Cancer reports (Hoboken, N.J.)   4 ( 3 )   e1329   2021.6

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    BACKGROUND: Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. AIM: This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. METHODS AND RESULTS: Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed. The 5-year OS rate of the entire cohort was 48.3% (95% confidence interval, 29.9%-64.5%). Multivariate analysis of OS identified time to relapse or progression, but not stem cell transplantation (SCT), as the sole independent risk factor (hazard ratio, 35.8; P = .002). Among 31 patients who received salvage chemotherapy before local treatment, 21 received chemotherapy regimens that are not conventionally used for newly diagnosed ESFT. The objective response rate to first-line salvage chemotherapy was 55.2% in the 29 evaluable patients. Time to relapse or progression was significantly associated with response to first-line salvage chemotherapy (P = .006). CONCLUSIONS: The present study fails to demonstrate significant clinical benefit of SCT for recurrent or refractory localized ESFT. Recently established chemotherapy regimens may increase the survival rate of patients with recurrent or refractory localized ESFT while attenuating the beneficial effect of SCT.

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  • Postoperative computed tomography assessment of anteromedial cortex reduction is a predictor for reoperation after intramedullary nail fixation for pertrochanteric fractures. International journal

    Norio Yamamoto, Takahiro Imaizumi, Tomoyuki Noda, Tomoo Inoue, Keisuke Kawasaki, Toshifumi Ozaki

    European journal of trauma and emergency surgery : official publication of the European Trauma Society   2021.5

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    PURPOSE: Postoperative radiographs are routinely used to assess fracture reduction following intramedullary nail fixation for pertrochanteric fractures, even though computed tomography (CT) is a superior modality. We aimed to determine the association between reduction quality assessed by CT and rates of reoperation and to evaluate the association of reoperation and reduction quality according to the assessment modality (plain radiographs vs. CT). METHODS: A retrospective analysis of 299 consecutive patients treated with intramedullary nail fixation for pertrochanteric fractures was conducted. Fracture reduction measured by postoperative radiographs and CT was categorized as anatomical type, extramedullary type, or intramedullary type. Postoperative data for analysis included reduction status, tip-apex distance (TAD), screw position in the femoral head, sliding distance, and conditions associated with reoperation. RESULTS: Of the 299 patients included with a mean age of 83.1 ± 8.2 years, there were six patients who required reoperation (2.0%). According to the CT assessments, there were 42 intramedullary reductions (14.0%). Patients with a non-intramedullary reduction based on postoperative CT images were significantly more likely to have proper placement of the screw, a reduced TAD, a reduced sliding distance, and a lower reoperation rate than those with an intramedullary reduction (P < 0.05). The reduction quality assessed by postoperative CT was significantly associated with reoperation (95% CI, 1.45-29.31). CONCLUSIONS: Intramedullary reduction assessed by CT was associated with reoperation. The reduction quality based on CT findings was more predictive for reoperation than that from plain radiographs.

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  • A newly-developed guide can create tibial tunnel at an optimal position during medial meniscus posterior root repairs.

    Takaaki Hiranaka, Takayuki Furumatsu, Yuki Okazaki, Keisuke Kintaka, Tadashi Yamawaki, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   2021.5

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    BACKGROUND: During transtibial pullout repair of medial meniscus (MM) posterior root tears (MMPRTs), accurate tibial tunnel creation within the anatomic MM posterior root attachment seems critical. This study aimed to evaluate the tibial tunnel position created by a newly-developed Precision guide during pullout repair of MMPRTs. METHODS: In 40 patients who underwent transtibial pullout repairs, the tibial tunnel was created using the Unicorn Meniscal Root (UMR) (n = 20) or Precision guide (n = 20). Three-dimensional computed tomography images of the tibial surface were evaluated postoperatively, using Tsukada's measurement method. The expected anatomic center of the MM posterior root attachment was defined as the center of three tangential lines corresponding to anatomic bony landmarks. The expected anatomic center (AC) and the tibial tunnel center (TC) were evaluated using the percentage-based posterolateral location on the tibial surface. The difference in the mediolateral and anteroposterior percentage distance between the AC and TC was calculated, as was the absolute distance between the AC and TC. RESULTS: The mean AC was located 77.4% posterior and 40.1% lateral. The mean TC was similar in the UMR and Precision guide groups. There was no significant difference in the mediolateral percentage distance (UMR 3.9% vs. Precision 3.6%, p = 0.405), but a significant difference was observed in the anteroposterior percentage distance (UMR 3.5% vs. Precision 2.6%, p = 0.031). The mean absolute distance between the AC and TC was 3.9 mm and 3.5 mm (UMR and Precision guide groups, respectively) (p = 0.364). CONCLUSIONS: The new Precision guide can create tibial tunnel in an optimal and stable position during pullout repair of MMPRTs.

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  • Prevalence of Psychological Distress and Its Risk Factors in Patients with Primary Bone and Soft Tissue Tumors. International journal

    Masato Ise, Eiji Nakata, Yoshimi Katayama, Masanori Hamada, Toshiyuki Kunisada, Tomohiro Fujiwara, Ryuichi Nakahara, Shouta Takihira, Kohei Sato, Yoshiteru Akezaki, Masuo Senda, Toshifumi Ozaki

    Healthcare (Basel, Switzerland)   9 ( 5 )   2021.5

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    Psychological distress is common in patients with soft tissue and bone tumors. We first investigated its frequency and the associated risk factors in patients with pre-operative bone and soft tissue tumors. Participants included 298 patients with bone and soft tissue tumors who underwent surgery in our institution between 2015 and 2020. Psychological distress was evaluated by the Distress and Impact Thermometer (DIT) that consists of two types of questions (questions about the severity of the patient's distress (DIT-D) and its impact (DIT-I)). We used a cut-off point of 4 on the DIT-D and 3 on the DIT-I for screening patients with psychological distress. We therefore investigated: (1) the prevalence of psychological distress as assessed with DIT or distress thermometer (DT), which can be decided by DIT-D ≥ 4, (2) what are the risk factors for the prevalence of psychological distress, and (3) what is the number of patients who consulted a psychiatrist for psychological distress in patients with pre-operative bone and soft tissue tumors. With DIT and DT, we identified 64 patients (21%) and 95 patients (32%), respectively, with psychological distress. Multivariate logistic regression revealed that older age, sex (female), malignancy (malignant or intermediate tumor), a lower Barthel Index, and higher numeric rating scale were risk factors for psychological distress. Two patients (3%) consulted a psychiatrist after surgery. In conclusion, careful attention to psychological distress is needed, especially for female patients, older patients, and those with malignant soft or bone tissue tumors who have more than moderate pain.

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  • Comparison of posterior root remnant cells and horn cells of the medial meniscus. International journal

    Ximing Zhang, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Haowei Xue, Keisuke Kintaka, Shinichi Miyazawa, Toshifumi Ozaki

    Connective tissue research   1 - 10   2021.5

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    Purpose/Aim of the study: Previous studies have noted distinctions between medial meniscus posterior root and horn cells. However, the characteristics of root remnant cells have not been explored in detail. The purpose of this study was to evaluate the gene expression levels, proliferation, and resistance to mechanical stress of remnant and horn cells.Materials and Methods: Medial meniscus tissue samples were obtained from patients who underwent total or uni-compartmental knee arthroplasty. Cellular morphology, sry-type HMG box 9, type II collagen, and chondromodulin-I gene expression levels were analyzed. Collagen synthesis was assessed by immunofluorescence staining. Proliferation analysis after 4 h-cyclic tensile strain was performed.Results: Horn cells displayed triangular morphology, whereas root remnant cells appeared fibroblast-like. sry-type HMG box 9 mRNA expression levels were similar in both cells, but type II collagen and chondromodulin-I mRNA expressions were observed only in horn cells. The ratio of type II collagen-positive cells in horn cells was about 10-fold higher than that in root remnant cells, whereas the ratio of sry-type HMG box 9-positive cells was similar. A significant increase in proliferation was observed in root remnant cells compared to that in horn cells. Further, under cyclic tensile strain, the survival rate was higher in root remnant cells than in horn cells.Conclusions: Medial meniscus root remnant cells showed higher proliferation and resistant properties to cyclic tensile strain than horn cells and showed no chondromodulin-I expression. Preserving the medial meniscus posterior root remnant during pullout repair surgery might maintain mechanical stress-resistant tissue and support healing.

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  • Risk factors of postoperative delayed wound healing in patients with rheumatoid arthritis treated with a biological agent. International journal

    Shunji Okita, Hajime Ishikawa, Asami Abe, Satoshi Ito, Kiyoshi Nakazono, Akira Murasawa, Keiichiro Nishida, Toshifumi Ozaki

    Modern rheumatology   31 ( 3 )   587 - 592   2021.5

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    OBJECTIVES: This retrospective study aimed to investigate the risk factors associated with delayed wound healing (DWH) after orthopedic surgery in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We reviewed medical records of 276 orthopedic procedures for 187 RA patients treated with bDMARDs. As a preoperative nutritional status assessment, we evaluated body mass index, prognostic nutritional index (PNI), and controlling nutritional status (CONUT). We evaluated DAS28-CRP, DAS28-ESR, face scale, global health, and HAQ-DI to assess the disease activity. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors for DWH. RESULTS: In 276 procedures, DWH was identified in 24 patients (8.7%). Disease duration, foot and ankle surgery, and preoperative use of tocilizumab were significant in the univariate analyses. These variables were entered into a multivariate model, and it was revealed that preoperative use of tocilizumab and procedures in the foot and ankle were associated with an increased risk of DWH. CONCLUSION: The current retrospective study suggested that preoperative use of tocilizumab and procedures in the foot and ankle were risk factors for DWH.

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  • Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma. International journal

    Yusuke Mochizuki, Hiroshi Tazawa, Koji Demiya, Miho Kure, Hiroya Kondo, Tadashi Komatsubara, Kazuhisa Sugiu, Joe Hasei, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancer immunology, immunotherapy : CII   70 ( 5 )   1405 - 1417   2021.5

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    Immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1) antibody have recently improved clinical outcome in certain cancer patients; however, osteosarcoma (OS) patients are refractory to PD-1 blockade. Oncolytic virotherapy has emerged as novel immunogenic therapy to augment antitumor immune response. We developed a telomerase-specific replication-competent oncolytic adenovirus OBP-502 that induces lytic cell death via binding to integrins. In this study, we assessed the combined effect of PD-1 blockade and OBP-502 in OS cells. The expression of coxsackie and adenovirus receptor (CAR), integrins αvβ3 and αvβ5, and programmed cell death ligand 1 (PD-L1) was analyzed in two murine OS cells (K7M2, NHOS). The cytopathic activity of OBP-502 in both cells was analyzed using the XTT assay. OBP-502-induced immunogenic cell death was assessed by analyzing the level of extracellular ATP and high-mobility group box protein B1 (HMGB1). Subcutaneous tumor models for K7M2 and NHOS cells were used to evaluate the antitumor effect and number of tumor-infiltrating CD8+ cells in combination therapy. K7M2 and NHOS cells showed high expression of integrins αvβ3 and αvβ5, but not CAR. OBP-502 significantly suppressed the viability of both cells, in which PD-L1 expression and the release of ATP and HMGB1 were significantly increased. Intratumoral injection of OBP-502 significantly augmented the efficacy of PD-1 blockade on subcutaneous K2M2 and NHOS tumor models via enhancement of tumor-infiltrating CD8+  T cells. Our results suggest that telomerase-specific oncolytic virotherapy is a promising antitumor strategy to promote the efficacy of PD-1 blockade in OS.

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  • High body mass index is a risk factor for unfavorable clinical outcomes after medial meniscus posterior root repair in well-aligned knees.

    Ximing Zhang, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Yuya Kodama, Haowei Xue, Yoshiki Okazaki, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   26 ( 3 )   430 - 434   2021.5

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    BACKGROUND: Severe chondral lesions and varus knee alignment are associated with poor outcomes following transtibial pullout repair for medial meniscus posterior root tears and meniscus tear is strongly associated with body mass index. The prognostic factors in well-aligned knees (femorotibial angle < 180°) with mild chondral lesions are unknown. Therefore, we investigated the prognostic factors in these patients. We hypothesized that high body mass index would lead to poor clinical outcomes following pullout repair of medial meniscus posterior root tears. METHODS: We retrospectively reviewed the files of 28 patients who had undergone pullout repair of medial meniscus posterior root tears between October 2016 and December 2017. We recorded the baseline characteristics (age, gender, height, weight, and body mass index) and the time between injury and surgery. We recorded the International Knee Documentation Committee scores, Knee injury and Osteoarthritis Outcome Scores, and pain visual analog scale scores. Using magnetic resonance imaging preoperatively and 1 year after surgery, we measured the medial meniscus body width and absolute and relative medial meniscus extrusion. Pearson correlation and multivariate linear regression analyses were used to assess potential associations between these factors and clinical outcomes. RESULTS: Age positively correlated (coefficient = 0.49, P < 0.01) and body mass index negatively correlated with the postoperative International Knee Documentation Committee score (coefficient = -0.64, P < 0.01). In multivariate linear regression analysis, body mass index was a significant factor leading to poor postoperative International Knee Documentation Committee score (R2 = 0.29, P < 0.05). CONCLUSIONS: Body mass index > 30 kg/m2 is a risk factor for unfavorable clinical outcomes following pullout repair of medial meniscus posterior root tears in well-aligned knees. LEVEL OF EVIDENCE: III, Comparative retrospective study.

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  • A posterior shiny-corner lesion of the tibia is observed in the early phase after medial meniscus posterior root tear. International journal

    Yuki Okazaki, Takayuki Furumatsu, Yuya Kajiki, Takaaki Hiranaka, Keisuke Kintaka, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

    European journal of orthopaedic surgery & traumatology : orthopedie traumatologie   2021.4

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    BACKGROUNDS: Medial meniscus (MM) posterior root tear (PRT) results in joint overloading and degenerative changes in the knee, and pullout repair is recommended to prevent subsequent osteoarthritis. Diagnosing MMPRT is sometimes difficult, especially in the case of an incomplete tear. A posterior shiny-corner lesion (PSCL) is reported to be useful for diagnosis, although the association between MMPRT and PSCL is unknown. This study aimed to investigate the properties of PSCL, such as the location, volume, and duration from injury to the time of MRI (duration). We hypothesized that PSCL is observed in the early phase after the MMPRT onset. METHODS: T2-weighted fat-suppression magnetic resonance imaging (MRI) was obtained from 55 patients with MMPRT preoperatively. The prevalence of the PSCL; giraffe neck, cleft, and ghost signs; severe MM extrusion (> 3 mm); and the PSCL volume were evaluated. The PSCL lesion elliptical volume (mm3) was calculated by measuring the anteroposterior, transverse, and craniocaudal dimensions. RESULTS: PSCL was observed in 34 (62%) cases. The mean volume of the PSCL was 102.0 mm3. A significantly shorter duration was observed in the PSCL-positive group (5.6 weeks) than that in the PSCL-negative group (40.9 weeks, P < 0.01), although no significant correlation was observed between the PSCL volume and duration. The sensitivity for the MMPRT was 90.5% when the cut-off duration value was 3 weeks and 81.8% when the cut-off value was 8 weeks. CONCLUSIONS: MRI examination may detect PSCL if it is performed early following MMPRT onset. Detecting PSCL may be useful in diagnosing MMPRT with high sensitivity.

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  • Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma. International journal

    Suguru Yokoo, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Takuya Morita, Masahiro Kiyono, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Shintaro Iwata, Tsukasa Yonemoto, Koji Ueda, Toshifumi Ozaki

    Cancers   13 ( 8 )   2021.4

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    The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.

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  • Evaluation of the labrum on postoperative magnetic resonance images: a predictor of acetabular development in developmental dysplasia of the hip. International journal

    Tomonori Tetsunaga, Tomoko Tetsunaga, Hirofumi Akazawa, Kazuki Yamada, Takayuki Furumatsu, Toshifumi Ozaki

    Hip international : the journal of clinical and experimental research on hip pathology and therapy   11207000211004917 - 11207000211004917   2021.4

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    INTRODUCTION: Residual acetabular dysplasia of the hip after open reduction can complicate the treatment of developmental dysplasia of the hip (DDH) due to the potential need for corrective surgery. This retrospective study aimed to determine the predictive factors for acetabular development using postoperative radiographs and magnetic resonance imaging (MRI). METHODS: We retrospectively investigated 74 hips of patients with DDH who underwent open reduction after reaching walking age and were followed up radiologically until skeletal maturity. We evaluated the cartilaginous acetabulum and labrum using a new method that measures the cartilaginous and labral landmarks on coronal and axial MR T2*-weighted images in patients aged 5 years. The mean age at the time of surgery was 22 months and that at the final survey was 20 years. Severin classification was determined at the final follow-up. Groups with good (53 hips) and poor (21 hips) outcomes were compared using the postoperative radiographic and MRI parameters recorded at 5 years of age. Factors predicting acetabular development were identified using univariate and multiple logistic analyses. RESULTS: There were no significant differences in the bony-acetabular index (AI) and centre-edge (CE) angle between the good and poor outcome groups. However, the poor outcome group had significantly larger cartilaginous- and labral-AIs but significantly smaller cartilaginous- and labral-CE angles than the good outcome group (both p < 0.05). Multiple logistic regression analysis showed that labral-AI and labral-CE angle were predictors of acetabular development after open reduction for DDH, and their optimal cut-offs were 4° (77% sensitivity, 76% specificity) and 37° (68% sensitivity, 85% specificity), respectively. DISCUSSION: Normal cartilaginous acetabulum development occurs in childhood, and evaluation using only radiographs is difficult. However, labral-AI ⩾4° and labral-CE angle <37° on MRI at 5 years of age offer useful indications for corrective surgery in patients with DDH.

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  • Histologic Evaluation of Tibial Attachment in 11-Year Double-Bundle ACL Reconstruction with Hamstring Tendons: A Case Report. International journal

    Yuki Okazaki, Nobuhiro Abe, Kimihiko Makiyama, Takayuki Furumatsu, Shinichi Miyazawa, Toshifumi Ozaki

    JBJS case connector   11 ( 2 )   2021.4

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    CASE: A 49-year-old woman injured her anterior cruciate ligament (ACL) as a high-school student. Double-bundle ACL reconstruction (DBACLR) using hamstring tendon grafts was performed because of recurrent instability. Eleven years after DBACLR, total knee arthroplasty was performed because of osteoarthritis progression. Histologic analysis was completed to observe the osteointegration of the tendon in the obtained proximal tibia. The tibial tunnel showed Sharpey-like fibers anteriorly, connecting the tendon graft and lamellar bone, whereas the intraarticular exit revealed well-aligned chondrocytes posteriorly, indicating chondral metaplasia of the tendon graft. CONCLUSION: Tendon-bone healing can regenerate both fibrous insertion and chondral metaplasia in DBACLR.

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  • Immunotherapy for sarcomas. International journal

    Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Tastuo Ito, Shota Takihira, Toshifumi Ozaki

    Japanese journal of clinical oncology   51 ( 4 )   523 - 537   2021.4

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    Sarcomas are a heterogeneous group of malignancies of mesenchymal origin; their molecular and genomic mechanisms differ with regard to histology. These characteristics lead to the presentation of varied immunological profiles based on the tumor microenvironment. Various immunotherapies are considered for the treatment of sarcoma. These treatments are performed either in isolation or in combination with other methods such as cytotoxic chemotherapy or the use of molecular target agents. Among these, two recently emerging immunotherapies include T-cell receptor gene therapy and immune checkpoint inhibitor therapy, which are expected to be effective for many types of sarcoma. A sarcoma with a disease-specific translocation and a limited number of mutations, such as synovial sarcoma, expresses high levels of self-antigens, like the New York esophageal squamous cell carcinoma 1, which has been targeted in T-cell receptor gene therapy. On the other hand, sarcomas with a greater number of mutations, such as undifferentiated pleomorphic sarcomas, myxofibrosarcoma and dedifferentiated liposarcomas, can be good candidates for immune checkpoint inhibitors. Among immune checkpoint inhibitor therapies, programmed cell death-1 blockade (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte-associated antigen 4 blockade (ipilimumab) have been investigated most often in sarcoma. Although the sole use of immune checkpoint inhibitors provides limited efficacy, combined immunotherapy with immune checkpoint inhibitors or molecular target agents, especially antiangiogenic agents, has shown moderate results against some types of sarcoma, such as the alveolar soft part sarcoma. Several clinical trials utilizing immunotherapy, including T-cell receptor gene therapy and immune checkpoint inhibitors, in sarcomas are under progress. By clarifying the tumor microenvironment and biomarker-predictive capacity of immunotherapy in sarcomas, better clinical trials can be designed; this could lead to improved outcomes for immunotherapy in sarcoma.

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  • Placement of an anatomic tibial tunnel significantly improves the medial meniscus posterior extrusion at 90° of knee flexion following medial meniscus posterior root pullout repair. International journal

    Yusuke Kamatsuki, Takayuki Furumatsu, Takaaki Hiranaka, Yoshiki Okazaki, Yuki Okazaki, Yuya Kodama, Tomohito Hino, Shin Masuda, Shinichi Miyazawa, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   29 ( 4 )   1025 - 1034   2021.4

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    PURPOSE: The purpose of this study was to evaluate the influence of tibial tunnel position in pullout repair for a medial meniscus (MM) posterior root tear (MMPRT) on postoperative MM extrusion. METHODS: Thirty patients (median age 63 years, range 35-72 years) who underwent transtibial pullout repairs for MMPRTs were included. Three-dimensional computed tomography images of the tibial surface were evaluated using a rectangular measurement grid for assessment of tibial tunnel position and MM posterior root attachment. Preoperative and postoperative MM medial extrusion (MMME) and posterior extrusion (MMPE) at 10° and 90° knee flexion were measured using open magnetic resonance imaging. RESULTS: Tibial tunnel centers were located more anteriorly and more medially than the anatomic center (median distance 5.8 mm, range 0-9.3 mm). The postoperative MMPE at 90° knee flexion was significantly reduced after pullout repair, although there was no significant reduction in MMME or MMPE at 10° knee flexion after surgery. In the correlation analysis of the displacement between the anatomic center to the tibial tunnel center and improvements in MMME, and MMPE at 10° and 90° knee flexion, there was a significant positive correlation between percentage distance and improvement of MMPE at 90° knee flexion. CONCLUSION: This study demonstrated that the nearer the tibial tunnel position to the anatomic attachment of the MM posterior root, the more effective the reduction in MMPE at 90° knee flexion. Our results emphasize that an anatomic tibial tunnel should be created in the MM posterior root to improve the postoperative MMPE and protect the articular cartilage in a knee flexion position. Placement of an anatomic tibial tunnel significantly improves the MMPE at 90° of knee flexion after MM posterior root pullout repair. LEVEL OF EVIDENCE: IV.

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  • Steep medial tibial slope and prolonged delay to surgery are associated with bilateral medial meniscus posterior root tear. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Yuki Okazaki, Tadashi Yamawaki, Yoshiki Okazaki, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   29 ( 4 )   1052 - 1057   2021.4

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    PURPOSE: Contralateral medial meniscus posterior root tear (MMPRT) can sometimes occur after primary surgeries for MMPRT and lead to unsatisfactory outcomes. The incidence rate and risk factors for contralateral MMPRT have not been well investigated, despite their clinical importance. Therefore, the incidence and predictors of bilateral MMPRT were aimed to be evaluated. METHODS: Fourteen patients with bilateral MMPRT (group B) and 169 patients with unilateral MMPRT (group U) were enrolled in this study. Sex, age, body mass index, time between injury and surgery, and medial tibial slope angle (MTSA) were compared between the groups. MTSA was measured using lateral radiographs. RESULTS: The incidence rate of bilateral MMPRT was 6.2% among all patients with MMPRTs. Multivariate logistic regression analysis showed that a prolonged time between injury and surgery (odds ratio [OR], 1.0; 95% confidence interval [CI] 1.00-1.01; P < 0.05) and steeper MTSA (OR, 1.85; 95% CI 1.21-2.64; P < 0.01) were significantly associated with the development of bilateral MMPRT. Receiver operating characteristic curve analysis showed that MTSA > 10.0° was associated with bilateral MMPRT, with a sensitivity of 93% and specificity of 69%. CONCLUSION: A longer time between injury and surgery and steeper MTSA were risk factors for the development of bilateral MMPRT. Surgeons need to pay close attention to the contralateral knee in addition to the primary injured knees when treating knees with steep MTSA. Besides, early meniscal repair of primary MMPRT would be important to prevent the events of contralateral MMPRT. LEVEL OF EVIDENCE: III.

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  • Intraarticular lengths of double-bundle grafts can change during knee flexion: Intraoperative measurements in anatomic anterior cruciate ligament reconstructions. International journal

    Takayuki Furumatsu, Takaaki Hiranaka, Yuya Kodama, Yusuke Kamatsuki, Yuki Okazaki, Tadashi Yamawaki, Hirosuke Endo, Toshifumi Ozaki

    Orthopaedics & traumatology, surgery & research : OTSR   107 ( 2 )   102816 - 102816   2021.4

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    BACKGROUND: The lengths of the anteromedial bundle (AMB) and posterolateral bundle (PLB) change during knee motion in double-bundle anterior cruciate ligament (ACL) reconstruction. However, the actual intraarticular graft length would be affected by the bone tunnel position and tunnel creation angle during ACL reconstruction. The aim of this study was to investigate the intraarticular length change of the AMB and PLB in patients who underwent anatomic double-bundle ACL reconstruction. HYPOTHESIS: We hypothesized that the PLB would show a more dynamic length change pattern than the AMB during knee flexion at ACL reconstruction. METHODS: Thirty-two patients (16 men and 16 women) who had isolated ACL injuries with intact menisci were investigated. Anatomic double-bundle ACL reconstructions were performed using semitendinosus tendon autografts at a mean age of 30.6 years. The graft and tunnel lengths were measured intraoperatively. Intraarticular graft lengths and length changes were calculated at 0° and 90° of knee flexion during ACL reconstruction. Intraoperative data were collected prospectively, and analyses were performed retrospectively. RESULTS: The intraarticular length of the AMB at 0° of knee flexion was 28.1±5.5mm. At 90° of knee flexion, the AMB intraarticular length decreased to 25.6±4.8mm. The intraarticular length of the PLB decreased to 17.7±4.6mm at 90° of knee flexion compared to 22.0±4.2mm at 0° of knee flexion. Changes in the intraarticular graft length during knee flexion were detected more in the PLB (4.1mm) than in the AMB (2.0mm, p=0.01). DISCUSSION: This study demonstrated that the intraarticular length change of the PLB during knee motion was larger than that of the AMB in anatomic double-bundle ACL reconstructions with semitendinosus tendon autografts and suspensory femoral fixation devices. LEVEL OF EVIDENCE: IV; retrospective cohort study.

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  • Correction to: Steep medial tibial slope and prolonged delay to surgery are associated with bilateral medial meniscus posterior root tear. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Yuki Okazaki, Tadashi Yamawaki, Yoshiki Okazaki, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   29 ( 4 )   1058 - 1058   2021.4

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  • Osteosynthesis for Geriatric Acetabular Fractures: An Epidemiological and Clinico-Radiological Study Related to Marginal or Roof Impaction.

    Madoka Inoue, Tomoyuki Noda, Takenori Uehara, Tomonori Tetsunaga, Kazuki Yamada, Taichi Saito, Yasunori Shimamura, Yasuaki Yamakawa, Toshifumi Ozaki

    Acta medica Okayama   75 ( 2 )   177 - 185   2021.4

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    This retrospective study sought to elucidate the incidence rates of roof impaction (RI) and marginal impaction (MI) and radiological and clinical outcomes of open reduction and internal fixation (ORIF) for RI and MI in geriatric acetabular fractures. The cases of 68 patients aged ≥ 65 years (mean 71 years) treated with ORIF were analyzed. MI was present in 12 fractures (67%) and an RI of the weight-bearing surface was present in 24 (46%) of the potential fracture types. Regarding the reduction quality, 54% of the reductions were graded as anatomical, 37% as imperfect, and 9% as poor. In the clinical evaluations of the 45 patients who had > 1-year follow-up (follow-up rate: 66.2%), 18% were graded as excellent, 53% as good, 16% as fair, and 13% as poor. An anatomic reduction was strongly associated with good or excellent clinical and radiological outcomes. CT was superior to radiographs for detecting the residual displacement postoperatively. Postoperative deep infection occurred in four patients. Three patients (6.7%) underwent a total hip arthroplasty conversion due to secondary osteoarthritis of the hip. We recommend ORIF as the preferred surgical treatment option for displaced acetabular fractures in elderly patients.

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  • Steep posterior slope of the medial tibial plateau is associated with ramp lesions of the medial meniscus and a concomitant anterior cruciate ligament injury. International journal

    Yuki Okazaki, Takayuki Furumatsu, Takaaki Hiranaka, Keisuke Kintaka, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

    Asia-Pacific journal of sports medicine, arthroscopy, rehabilitation and technology   24   23 - 28   2021.4

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    Background: Medial meniscus (MM) tears are associated with both acute and chronic anterior cruciate ligament (ACL) insufficiency and can lead to degenerative changes in the knee. ACL reconstruction (ACLR) combined with the meniscal repair was reported to result in decreased anterior knee joint laxity with evidence of improved patient-reported outcomes in the long term. However, a subtle tear of the MM posterior segment, also known as a ramp lesion, is difficult to detect on conventional magnetic resonance imaging (MRI) and is frequently missed in ACL-deficient knees. However, there are few studies about the associations between bone geometry and ramp lesion of the MM. This study aimed to compare sagittal medial tibial slope (MTS), medial tibial plateau depth (MTPD), and coronal tibial slope (CTS) between ACL-injured knees with and without ramp lesion of the MM. We hypothesised that patients with ramp lesion of the MM and a concomitant ACL injury have a steeper MTS and shallower MTPD than those without ramp lesion of the MM. Methods: Twenty-seven patients who underwent ACLR (group A), and 15 patients with combined MM repair (group AM) were included in the study. Anterior tibial translation (ATT) was measured under general anaesthesia just before surgery using a knee arthrometer. MRI was performed in the 10°-knee-flexed position. The MTS and MTPD were measured on sagittal view, and the CTS was measured on coronal view. These parameters were compared between the groups. Differences in MRI measurements or patient demographics between the groups were evaluated using the Mann-Whitney U test. Results: No significant difference was observed in demographic data and post-operative side-to-side difference in ATT between both groups. Pre-operative ATT was significantly higher in group AM than in group A (P < 0.05), whereas post-operative ATT was similar in both groups. Further, Pre-operative ATT was significantly higher in patients with MTS ≥5.0° than in those with MTS <5.0° (P < 0.05). In groups A and AM, the MTS were 3.6° ± 1.8° and 6.2° ± 2.9°, the MTPD were 2.0 ± 0.5 mm and 2.1 ± 0.6 mm, and the CTS were 2.5° ± 1.8° and 2.4° ± 1.6°, respectively. Patients in group AM had a significantly steeper MTS compared to those in group A (P < 0.01), whereas MTPD and CTS were nearly the same in both groups. When the MTS cut-off value was set at 5.0°, the sensitivity and specificity for ACL injury with concomitant ramp lesion of the MM were 0.73 and 0.76, respectively. Conclusion: A steep posterior slope of the medial tibial plateau is a risk factor for ramp lesion of the MM associated with an ACL injury. Especially in patients with MTS ≥5.0°, an occult MM ramp lesion should be strongly suspected, and surgeons should prepare for MM repair in combination with ACLR.

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  • Knee Flexion-induced Translation of Pullout Sutures Used in the Repair of Medial Meniscus Posterior Root Tears.

    Haowei Xue, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Keisuke Kintaka, Masataka Fujii, Ximing Zhang, Toshifumi Ozaki

    Acta medica Okayama   75 ( 2 )   147 - 152   2021.4

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    Medial meniscus posterior root tears (MMPRTs) have recently attracted considerable interest in orthopedics. To date, no in vivo human study has investigated suture translation changes in repaired MMPRTs with different degrees of knee flexion. This study examined suture translation at various degrees of knee flexion in 30 patients undergoing medial meniscus posterior root repair using the modified Mason-Allen suture technique between August 2016 and September 2017. Intraoperatively, sutures were provisionally fixed to an isometric positioner at the tibial site of the desired meniscal attachment, and the suture translation was measured at 0°, 30°, 60°, and 90° of knee flexion. The results showed significant increases in mean suture translation at the knee flexion positions from 0° to 30°, 30° to 60°, and 60° to 90° (p<0.01 for all). Our findings indicate that surgeons should carefully assess the degree of knee flexion at the moment when the meniscus is refixed by surgical sutures.

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  • Maximal Resection of Intramedullary Lipoma Using Intraoperative Ultrasonography: A Technical Note.

    Haruo Misawa, Yoshiaki Oda, Kentaro Yamane, Tomoko Tetsunaga, Toshifumi Ozaki

    Acta medica Okayama   75 ( 2 )   239 - 242   2021.4

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    One of the problems during surgery for intramedullary lipoma is the ambiguous boundary between the lipoma and the spinal cord, resulting in either incomplete resection or damage to the spinal cord. We report a case of intramedullary lipoma resection on a 61-year-old man in which the boundary between the tumor and spinal cord was repeatedly visualized with intraoperative ultrasonography. We focused on the distinctive features of fat as hyperechoic, in contrast to low-echo neural tissue. Subtotal resection of the tumor was achieved without any aggravation of neurological symptoms. Intraoperative ultrasonography may be useful for confirming tumor boundaries during intramedullary lipoma resection.

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  • Histological Analysis of Repaired Tissue after Pullout Repair of a Medial Meniscus Posterior Root Tear.

    Haowei Xue, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Keisuke Kintaka, Ximing Zhang, Aki Yoshida, Toshifumi Ozaki

    Acta medica Okayama   75 ( 2 )   225 - 230   2021.4

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    A 65-year-old man presented with a left medial meniscus (MM) posterior root tear (PRT). Unicompartmental knee arthroplasty was performed 12 months after transtibial pullout repair of the MMPRT. Repaired MM posterior root tissue was subjected to histological analysis. Immunostaining and picrosirius red staining showed sufficient deposition of type I collagen, and hematoxylin-eosin staining using a polarized microscope showed well-aligned fiber orientation in the repaired tissue. The repaired posterior root (post-transtibial pullout repair) showed mature and well-aligned ligament-like tissue. Preserving the MM posterior root remnant to mimic the original posterior root tissue might be useful when performing pullout repair.

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  • Medial meniscus posterior root repair reduces the extruded meniscus volume during knee flexion with favorable clinical outcome. International journal

    Ximing Zhang, Takayuki Furumatsu, Yoshiki Okazaki, Yuki Okazaki, Takaaki Hiranaka, Haowei Xue, Keisuke Kintaka, Takatsugu Yamauchi, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   2021.3

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    PURPOSE: The volume of medial meniscus (MM) extrusion at 10° and 90° knee flexions using three-dimensional (3D) magnetic resonance imaging (MRI) and assessed relevant clinical outcomes at 1-year follow-up were evaluated. METHODS: Twenty-four patients who underwent MM posterior root repair were retrospectively reviewed. At 10° and 90° knee flexions, the meniscal extrusion distance and volume were measured using 3D meniscus models constructed by SYNAPSE VINCENT®. The correlation between Knee Injury and Osteoarthritis Outcome Score, Lysholm, International Knee Documentation Committee scores, Tegner activity, and pain visual analog scales and changes in MM extrusion were assessed. RESULTS: No significant differences in the MM medial extrusion were observed between 10° and 90° knee flexions postoperatively. MM posterior extrusion (MMPE) decreased significantly at 10° and 90° knee flexions postoperatively. At 90° knee flexion, the meniscus volume at the intra-tibial surface increased at 3 and 12 months postoperatively. The MM extrusion volume increased slightly at 10° knee flexion; however, the volume decreased significantly at 90° knee flexion postoperatively. The change in MMPE significantly correlated with clinical scores. All 12-month clinical scores were significantly improved compared to preoperative scores. CONCLUSIONS: The progression of meniscus posterior extrusion and reduction of its volume at 90° knee flexion can be suppressed by MM posterior root repair. Postoperative clinical scores correlated with reductions of the posterior extrusion. Regarding clinical relevance, the dynamic stability of the meniscus can be maintained by MM posterior root repair, which is an effective therapeutic method for improving its clinical status. LEVEL OF EVIDENCE: Level IV.

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  • Role of Tumor-Associated Macrophages in Sarcomas. International journal

    Tomohiro Fujiwara, John Healey, Koichi Ogura, Aki Yoshida, Hiroya Kondo, Toshiaki Hata, Miho Kure, Hiroshi Tazawa, Eiji Nakata, Toshiyuki Kunisada, Toshiyoshi Fujiwara, Toshifumi Ozaki

    Cancers   13 ( 5 )   2021.3

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    Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.

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  • Differences between the root and horn cells of the human medial meniscus from the osteoarthritic knee in cellular characteristics and responses to mechanical stress.

    Yuki Okazaki, Takayuki Furumatsu, Yusuke Kamatsuki, Keiichiro Nishida, Yoshihisa Nasu, Ryuichi Nakahara, Taichi Saito, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   26 ( 2 )   230 - 236   2021.3

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    BACKGROUND: Many histological, mechanical, and clinical studies have been performed on the medial meniscus posterior root attachment, as it often tears in patients with osteoarthritic knee. Medial meniscal root repair is recommended in clinical situations; however, to date, no studies have examined the differences between meniscal root and horn cells. The aim of this study was, therefore, to investigate the morphology, reaction to cyclic tensile strain, and gene expression levels of medial meniscal root and horn cells. METHODS: Meniscal samples were obtained from the medial knee compartments of 10 patients with osteoarthritis who underwent total knee arthroplasty. Root and horn cells were cultured in Dulbecco's modified Eagle's medium without enzymes. The morphology, distribution, and proliferation of medial meniscal root and horn cells, as well as the gene and protein expression levels of Sry-type HMG box 9 and type II collagen, were determined after cyclic tensile strain treatment. RESULTS: Horn cells had a triangular morphology, whereas root cells were fibroblast-like. The number of horn cells positive for Sry-type HMG box 9 and type II collagen was considerably higher than that of root cells. Although root and horn cells showed similar levels of proliferation after 48, 72, or 96 h of culture, more horn cells than root cells were lost following a 2-h treatment with 5% and 10% cyclic tensile. Sry-type HMG box 9 and α1(II) collagen mRNA expression levels were significantly enhanced in both cells after 2- and 4-h cyclic tensile strain (5%) treatment. CONCLUSIONS: Medial meniscal root and horn cells have distinct morphologies, reactions to mechanical stress, and cellular phenotypes. Our results suggest that physiological tensile strain is important to activate extracellular matrix production in horn cells.

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  • Prognostic and therapeutic factors influencing the clinical outcome of metastatic Ewing sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group. International journal

    Katsutsugu Umeda, Takako Miyamura, Kenji Yamada, Hideki Sano, Ako Hosono, Minako Sumi, Hajime Okita, Takuya Kamio, Naoko Maeda, Hiroyuki Fujisaki, Ryoji Jyoko, Atsuko Watanabe, Yosuke Hosoya, Daiichiro Hasegawa, Satoshi Takenaka, Shunsuke Nakagawa, Motoaki Chin, Toshifumi Ozaki

    Pediatric blood & cancer   68 ( 3 )   e28844   2021.3

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    BACKGROUND: The prognosis of patients with metastatic Ewing sarcoma family of tumors (ESFT) remains poor. PROCEDURE: We retrospectively analyzed 57 patients diagnosed with metastatic ESFT between 2000 and 2018 to identify prognostic and therapeutic factors affecting the clinical outcome. RESULTS: The 3-year overall survival (OS) rate of the entire cohort was 46.8% (95% confidence interval [CI], 33.0-59.4%). Treatment-related death was not observed. Multivariate analysis identified stem cell transplantation (SCT), response to first-line chemotherapy, and bone metastasis as independent risk factors for OS. Objective response rate to first-line chemotherapy was 65.1% in the 43 evaluable patients. There was no significant difference in the response to different types of first-line chemotherapy. Among patients with lung metastasis alone, the 3-year OS rate was higher in 13 patients who received local treatment than in four who did not, although the difference was not significant. CONCLUSIONS: One possible reason for the high OS rates was the absence of treatment-related mortality even in patients receiving SCT, which could be attributed to advances in the management of post-SCT complications. Novel first-line chemotherapy strategies need to be established to improve the disease status prior to SCT in a higher proportion of patients.

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  • 大腿骨頸部前捻角に左右差はあるか 3D計測による検討

    佐藤 浩平, 野田 知之, 近藤 宏也, 畑 利彰, 上原 健敬, 齋藤 太一, 雑賀 建多, 島村 安則, 尾崎 敏文

    日本整形外科学会雑誌   95 ( 3 )   S1125 - S1125   2021.3

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  • 不安定型骨盤輪損傷に対するCTナビゲーションガイド下スクリュー固定の治療成績

    上原 健敬, 野田 知之, 畑 利彰, 佐藤 浩平, 近藤 宏也, 齋藤 太一, 島村 安則, 尾崎 敏文

    日本整形外科学会雑誌   95 ( 3 )   S1116 - S1116   2021.3

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  • 寛骨臼骨折におけるroof-arc angle計測の妥当性の検討 単純X線写真計測と3D計測の比較と術後臨床評価との関連性

    近藤 宏也, 上原 健敬, 佐藤 浩平, 畑 利彰, 根津 智史, 松橋 美波, 齋藤 太一, 島村 安則, 野田 知之, 尾崎 敏文

    日本整形外科学会雑誌   95 ( 3 )   S1116 - S1116   2021.3

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  • The trend of treatment and conveyance system for upper extremity replantation in Japan: A nationwide population-based study from the Japan trauma data bank.

    Taichi Saito, Satoshi Nezu, Minami Matsuhashi, Ryuichi Nakahara, Yasunori Shimamura, Tomoyuki Noda, Tetsuya Yumoto, Atsunori Nakao, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   26 ( 2 )   271 - 275   2021.3

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    BACKGROUND: In Japan, microsurgical skill development and a system to transfer patients to an appropriate hospital for upper extremity amputation have been promoted; however, information about trends of replantation is limited. Therefore, the aim of this study was to clarify the trends in the treatment for upper extremity amputation using the Japan Trauma Data Bank (JTDB). METHODS: Data derived from JTDB (2004-2015) were used to quantify trends in the volume of replantation for upper extremity amputation including finger amputation. Trauma was diagnosed based on the Abbreviated Injury Scale code; a subgroup of patients who underwent replantation was delineated. We investigated patient demographics, infection rate, and characteristics of treating facilities. RESULTS: A total of 1240 patients underwent upper extremity amputation. Among these, 510 (41.1%) underwent replantation, and the rate of replantation did not change over the study period. The average age of patients who underwent or did not undergo replantation was 45.5 and 47.2 years, respectively. The proportion of the patients who were transferred to another hospital for treatment significantly decreased between 2004 (28.5%) and 2015 (16.3%) (P < 0.01). Time taken for transfer from the accident site to hospitals increased. The rate of patients who underwent replantation differed among different hospitals; however, higher-volume hospitals were more likely to perform replantation. CONCLUSION: The rate of patients transferred to another hospital decreased between 2004 and 2015; however, the rate of patients who underwent replantation remained unchanged. This suggests that the number of patients who were transported directly from the accident site to an appropriate hospital has increased, whereas the indication for care in each hospital remains unchanged. Common criteria for amputations are needed to address the differing rates of replantation among hospitals.

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  • An MRI-based suspension bridge sign can predict an arthroscopically favorable meniscal healing following the medial meniscus posterior root repair.

    Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Yuya Kodama, Yusuke Kamatsuki, Yoshiki Okazaki, Ximing Zhang, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   26 ( 2 )   237 - 242   2021.3

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    BACKGROUND: Medial meniscus (MM) posterior root repairs show favorable clinical outcomes in patients with MM posterior root tears (MMPRTs). However, there is no useful magnetic resonance imaging (MRI) finding to determine a functionally good meniscal healing following MM posterior root repairs. We hypothesized that a characteristic postoperative MRI finding can predict a good meniscal healing following pullout repairs. The aim of this study was to investigate a clinical usefulness of several MRI findings for estimating an actual meniscal healing following MMPRT repairs. METHODS: Fifty eight patients who had a posteromedial painful popping of the injured knee and underwent an arthroscopic pullout repair for the MMPRT were included. Arthroscopic meniscal healing was assessed according to the Furumatsu scoring system at 1 year postoperatively. We evaluated postoperative MRI-based meniscal healing using signal intensity, continuity, suspension bridge-like sign of the MM posterior root, and MM medial extrusion on coronal images. Postoperative clinical outcome evaluations were performed at second-look arthroscopy. RESULTS: Twenty three patients showed good arthroscopic healing scores (≥7 points). Thirty five patients had moderate/poor arthroscopic healing scores (<7 points). At 1-year follow-up period, clinical outcome scores were significantly higher in the good healing group than in the moderate/poor healing group. A characteristic meniscal shape, termed "suspension bridge sign", was highly observed in the good meniscal healing group (83%) compared with in the moderate/poor healing group (26%, P < 0.001). High signal intensity and continuity of the MM posterior root and MM medial extrusion showed no differences between both groups. CONCLUSIONS: Our study demonstrated that the MRI-based suspension bridge sign can predict an arthroscopically favorable meniscal healing following the MM posterior root repair. The suspension bridge-like MRI finding of the MM would be a useful indicator to evaluate the actual meniscal healing in patients who underwent pullout repairs for MMPRTs.

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  • 生物学的製剤と手術 当科におけるリウマチ外科手術1569例の患者背景

    那須 義久, 堀田 佳史, 渡辺 雅仁, 松橋 美波, 中原 龍一, 西田 圭一郎, 尾崎 敏文

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   343 - 343   2021.3

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  • 関節リウマチ超音波検査におけるデジタルカメラ画像とAIを用いたボディーマーク付与

    中原 龍一, 西田 圭一郎, 那須 義久, 渡辺 雅仁, 松橋 美波, 堀田 佳史, 尾崎 敏文

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   555 - 555   2021.3

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  • Radiological findings and outcomes of anterior wall fractures in pertrochanteric fractures.

    Norio Yamamoto, Ryu Tamura, Tomoo Inoue, Tomoyuki Noda, Hiroshi Nagano, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   26 ( 2 )   247 - 253   2021.3

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    BACKGROUND: Anterior wall fractures with comminution at the anterior cortex in pertrochanteric fractures are relatively rare. We aimed to investigate the prevalence and clinical findings of anterior wall fractures in this comparative cohort study. METHODS: We reviewed 516 consecutive patients who underwent internal fixation. Anterior wall fractures were classified into three types: proximal, distal, and proximal/distal. Outcome measures included demographic data, residual anterior cortex length, fracture reduction, tip-apex distance (TAD), sliding distance, bone union, and revision surgery. We compared radiological outcomes between patients with anterior wall fractures and posterior comminuted fractures without an anterior wall fracture. The groups were matched for age and sex. RESULTS: Anterior wall fractures were noted in 44 patients (8.5%). Residual anterior cortex length was shorter for the proximal/distal type. The distal type was the most common, was the most difficult to achieve an acceptable reduction status for, and was associated with the longest sliding distance. The proportion of unacceptable reduction status was higher for anterior wall fractures. However, there were no statistically significant differences between anterior wall fractures and posterior comminuted fractures without an anterior wall fracture in terms of TAD, sliding distance, bone union, and revision rate. CONCLUSIONS: This study suggests that anterior wall fracture is not a significant predictor of over-sliding distance.

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  • Medial meniscus posterior root repairs: A comparison among three surgical techniques in short-term clinical outcomes and arthroscopic meniscal healing scores.

    Takayuki Furumatsu, Takaaki Hiranaka, Yuki Okazaki, Keisuke Kintaka, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   2021.2

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    BACKGROUND: Medial meniscus (MM) posterior root repairs lead to favorable clinical outcomes in patients with MM posterior root tears (MMPRTs). However, there are few comparative studies in evaluating the superiority among several pullout repair techniques such as modified Mason-Allen suture, simple stitch, and concomitant posteromedial pullout repair. We hypothesized that an additional pullout suture at the MM posteromedial part would have clinical advantages in transtibial pullout repairs of the MMPRTs. The aim of this study was to compare the clinical usefulness among several types of pullout repair techniques in patients with MMPRTs. METHODS: Eighty-three patients who underwent arthroscopic pullout repairs of the MMPRTs were investigated. Patients were divided into three groups using different pullout repair techniques: a modified Mason-Allen suture using FasT-Fix all-inside meniscal repair device (F-MMA, n = 28), two simple stitches (TSS, n = 30), and TSS concomitant with posteromedial pullout repair using all-inside meniscal repair device (TSS-PM, n = 25). Postoperative clinical outcomes and semi-quantitative arthroscopic meniscal healing scores (0-10 points) were evaluated at second-look arthroscopies. RESULTS: No significant differences among the three groups were observed in patient demographics and preoperative clinical scores, except for preoperative Lysholm scores. At second-look arthroscopies, there were no significant differences among the three techniques in postoperative clinical outcomes and meniscal healing scores. CONCLUSIONS: This study demonstrated that the TSS-PM pullout repair technique did not show better scores in postoperative clinical outcomes and meniscal healings compared with the F-MMA and TSS techniques. Our results suggest that the concomitant posteromedial pullout suture may have no clinical advantage in the conventional pullout repairs for the patients with MMPRTs.

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  • Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. International journal

    Kazuhiro Tanaka, Toshifumi Ozaki

    Japanese journal of clinical oncology   51 ( 2 )   180 - 184   2021.2

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    The standard therapy for all localized soft tissue sarcomas is surgical resection of the tumor. For patients with soft tissue sarcomas who are at high risk for recurrence and/or metastasis, perioperative chemotherapy is a potential treatment option. Adriamycin plus ifosfamide is currently the most promising chemotherapy regimen for localized soft tissue sarcomas. Randomized controlled trials and meta-analyses of adjuvant postoperative chemotherapy for soft tissue sarcomas have suggested that adjuvant chemotherapy may provide an advantage, however small, compared with surgery alone. On the other hand, recent randomized trials have demonstrated the efficacy of neoadjuvant preoperative chemotherapy using full-dose anthracycline plus ifosfamide for high-risk soft tissue sarcomas and showed survival benefits in patients with large, deep-seated and high-grade soft tissue sarcomas of the trunk and extremities. In this review, adjuvant and neoadjuvant chemotherapies for soft tissue sarcomas and future perspectives are discussed.

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  • Bipolar Hip Arthroplasty Using a Conjoined Tendon-preserving Posterior Approach in Geriatric Patients.

    Tomonori Tetsunaga, Tomoko Tetsunaga, Kazuki Yamada, Tomoaki Sanki, Yoshi Kawamura, Toshifumi Ozaki

    Acta medica Okayama   75 ( 1 )   25 - 30   2021.2

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    In bipolar hemiarthroplasty (BHA), it is important to preserve soft tissue to reduce the risk of postoperative dislocation. A variety of surgical approaches for BHA are available, but extra care is needed with muscle- and tendon-preserving approaches in geriatric patients. We investigated the usefulness of BHA using a conjoined tendon-preserving posterior (CPP) approach, in which only the external obturator muscle is dissected, in geri-atric patients. We retrospectively analyzed the cases of 40 femoral neck fracture patients (10 men, 30 women) aged ≥ 80 years who underwent BHA using the CPP approach. The patients' average age was 85.8 years (80-94 years). We examined the operation time, bleeding, preservation of short external rotator muscles, complica-tions, and stem alignment and subsidence from postoperative radiographs. Although gemellus inferior muscle injury was detected in 4 patients (10%), the hip joint stability was very excellent in all cases. There was no intraoperative fracture or postoperative dislocation. On postoperative radiographs, all femoral stems were in a neutral position. There was no stem subsidence in all 40 patients. BHA using the CPP approach appeared to be useful even in geriatric patients.

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  • The Thickness of the Medial Wall of the Acetabulum Prevents Acetabular Fracture during the Insertion of a Cementless Cup in Total Hip Arthroplasty: A Biomechanical Study.

    Tomoaki Sanki, Tomonori Tetsunaga, Takayuki Furumatsu, Kazuki Yamada, Yoshi Kawamura, Toshifumi Ozaki

    Acta medica Okayama   75 ( 1 )   71 - 77   2021.2

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    Intra-operative acetabular fracture is a total hip arthroplasty complication that can occur during cementless cup insertion, especially in osteoporotic patients. We conducted this biomechanical study to investigate the impact resistance of the acetabulum with simulated bones of different density by drop-weight impact testing. Low- and high-density polyurethane foam blocks were used as osteoporotic and healthy bone models, respectively. Polyurethane blocks were used as the acetabular cancellous bone. Composite sheets were used as the acetabu-lum's medial cortex. The testing revealed that the osteoporotic bone model's impact resistance was significantly lower than that the healthy bone model'. In the healthy bone model, even thin acetabular cancellous bone with ≥ 1 mm acetabulum medial cortex was less likely to fracture. In the osteoporotic bone model, fracture was pos-sible without ≥ 1 mm medial cortex of the acetabulum and thick acetabular cancellous bone. Although impac-tion resistance differs due to bone quality, the impaction resistance in this osteoporotic bone model was equiv-alent to that healthy bone model's when a thick medial wall was present. To avoid intra-operative acetabulum fracture, surgeons should consider both the bone quality and the thicknesses of the medial cortex and acetabu-lar cancellous bone.

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  • Quantification of patellar tendon reflex using portable mechanomyography and electromyography devices. International journal

    Hironori Tsuji, Haruo Misawa, Tomoyuki Takigawa, Tomoko Tetsunaga, Kentaro Yamane, Yoshiaki Oda, Toshifumi Ozaki

    Scientific reports   11 ( 1 )   2284 - 2284   2021.1

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    Deep tendon reflexes are one of the main components of the clinical nervous system examinations. These assessments are inexpensive and quick. However, evaluation can be subjective and qualitative. This study aimed to objectively evaluate hyperreflexia of the patellar tendon reflex using portable mechanomyography (MMG) and electromyography (EMG) devices. This study included 10 preoperative patients (20 legs) who had a pathology that could cause bilateral patellar tendon hyperreflexia and 12 healthy volunteers (24 legs) with no prior history of neurological disorders. We attached MMG/EMG sensors onto the quadriceps and tapped the patellar tendon with maximal and constant force. Our results showed a significantly high amplitude of the root mean square (RMS) and low frequency of the mean power frequency (MPF) in the rectus femoris, vastus medialis, and vastus lateralis muscles in both EMG and MMG with both maximal and constant force. Especially in the patients with cervical and thoracic myelopathy, the receiver operating characteristic (ROC) curve for diagnosing hyperreflexia of the patellar tendon showed a moderate to very high area under the curve for all EMG-RMS, EMG-MPF, MMG-RMS, and MMG-MPF values. The use of EMG and MMG for objectively quantifying the patellar tendon reflex is simple and desirable for future clinical applications and could help diagnose neurological disorders.

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  • Accurate placement of a tibial tunnel significantly improves meniscal healing and clinical outcomes at 1 year after medial meniscus posterior root repair. International journal

    Yusuke Kamatsuki, Takayuki Furumatsu, Takaaki Hiranaka, Yuki Okazaki, Yuya Kodama, Keisuke Kintaka, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   2021.1

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    PURPOSE: A medial meniscus posterior root tear results in the loss of meniscal circumferential hoop stress and causes a pathological posteromedial extrusion of the medial meniscus. Although creating a tibial tunnel in the anatomic place improves postoperative medial meniscus posterior extrusion, no studies have evaluated the relationship between tibial tunnel position and clinical outcomes. This study aimed to evaluate how tibial tunnel positioning of medial meniscus posterior root pullout repair affects meniscal healing status and clinical outcomes. METHODS: Sixty-two patients with 64 medial meniscus posterior root tears (mean age 62.8 ± 7.9 years) who had undergone pullout repairs and second-look arthroscopies were included. All 62 patients were Lachman test negative. Three-dimensional computed tomography images of the tibial surface were evaluated using a rectangular measurement grid to assess the tibial tunnel centre and medial meniscus posterior root attachment centre. Spearman's rank correlation analysis was undertaken to determine displacement distance from the medial meniscus posterior root attachment centre to the tibial tunnel centre and a meniscal healing score, as well as clinical outcomes at 1 year post-repair. RESULTS: Tibial tunnel centres were located more anteriorly and medially than the medial meniscus posterior root attachment centre (mean distance 5.0 ± 2.2 mm). The mean meniscal healing score was 6.7 ± 1.8 of 10 possible points. The 1-year postoperative clinical scores showed significant improvement compared with preoperative scores for all the items. There was a significant negative correlation in the absolute distance between the medial meniscus posterior root attachment centre and the tibial tunnel centre with the meniscal healing score (ρ =  - 0.39, p = 0.002). Furthermore, there were significant positive correlations between the distance between the medial meniscus posterior root attachment centre and the tibial tunnel centre in the mediolateral direction and patient-based clinical outcomes (ρ = 0.25-0.43, p < 0.05). CONCLUSION: Accurate placement of a tibial tunnel, especially in the mediolateral direction, significantly improved meniscal healing and clinical outcomes at 1 year following medial meniscus posterior root repair. Surgeons should create a medial meniscus posterior root tibial tunnel at the anatomic attachment with particular attention to the mediolateral position. LEVEL OF EVIDENCE: Level IV.

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  • Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors. International journal

    Yoshihiro Nishida, Hiroshi Urakawa, Robert Nakayama, Eisuke Kobayashi, Toshifumi Ozaki, Keisuke Ae, Yoshihiro Matsumoto, Hiroyuki Tsuchiya, Takahiro Goto, Hiroaki Hiraga, Norifumi Naka, Shunji Takahashi, Yuichi Ando, Masahiko Ando, Yachiyo Kuwatsuka, Shunsuke Hamada, Takafumi Ueda, Akira Kawai

    International journal of cancer   148 ( 1 )   140 - 149   2021.1

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    Malignant peripheral nerve sheath tumor (MPNST) often does not respond well to chemotherapy and develops against a background of NF1. The purpose of our study was to examine the efficacy of pazopanib against MPNST. Our study was designed as a physician-initiated phase II clinical trial in patients with advanced MPNST. Patients were registered from 11 large hospitals. The primary endpoint was set to clarify the clinical benefit rate (CBR) at 12 weeks according to response evaluation criteria in solid tumors (RECIST). Progression-free survival (PFS), overall survival (OS) and the CBR based on modified Choi evaluation at week 12 were set as secondary endpoints along with treatment-related safety. The study enrolled 12 patients. Median age was 49 years. Seven had Grade 2 and five Grade 3 according to the FNCLCC evaluation. Median follow-up period was 10.6 months. CBR at 12 weeks was both 50.0% (RECIST and Choi). The median PFS was 5.4 months for both RECIST and Choi, and the median OS was 10.6 months. Of special interest, the median PFS was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 (both RECIST and Choi). Grade 4 adverse events of neutropenia and lipase elevation were noted in one patient each. The results of this pazopanib therapy were generally better than those of any of the other single molecular targeted therapies reported previously. Although accumulation of more cases remains necessary, we conclude pazopanib treatment for MPNST to be a safe and promising treatment after doxorubicin-based chemotherapy.

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  • Steep posterior slope and shallow concave shape of the medial tibial plateau are risk factors for medial meniscus posterior root tears. International journal

    Yuki Okazaki, Takayuki Furumatsu, Yuya Kodama, Yusuke Kamatsuki, Yoshiki Okazaki, Takaaki Hiranaka, Shota Takihira, Tomonori Tetsunaga, Kenta Saiga, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   29 ( 1 )   44 - 50   2021.1

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    PURPOSE: Bone morphological factors are important for menisci. Their association with medial meniscus posterior root tears, however, has not yet been studied. This study aimed to compare sagittal medial tibial slope and medial tibial plateau depth between knees with and without medial meniscus posterior root tears. METHODS: Nine healthy volunteers, 24 patients who underwent anterior cruciate ligament reconstruction, and 36 patients who underwent medial meniscus posterior root pullout repair were included. Magnetic resonance imaging examinations were performed in the 10°-knee-flexed position. The medial tibial slope and medial tibial plateau depth were compared among the groups. RESULTS: In healthy volunteers, the anterior cruciate ligament reconstruction group, and the medial meniscus posterior root tear group, the medial tibial slopes were 3.5° ± 1.4°, 4.0° ± 1.9°, and 7.2° ± 1.9°, respectively, and the medial tibial plateau depths were 2.1 ± 0.7 mm, 2.2 ± 0.6 mm, and 1.2 ± 0.5 mm, respectively. Patients with medial meniscus posterior root tears had a significantly steep medial tibial slope and shallow medial tibial plateau concavity compared to those of healthy volunteers (P < 0.01) and the anterior cruciate ligament group (P < 0.01). In the multivariate logistic regression analysis, body mass index, medial tibial slope, and medial tibial plateau depth were significantly associated with medial meniscus posterior root tears. CONCLUSIONS: A steep posterior slope and a shallow concave shape of the medial tibial plateau are risk factors for medial meniscus posterior root tear. LEVEL OF EVIDENCE: Level III: Case-control study.

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  • PRRX1 promotes malignant properties in human osteosarcoma. International journal

    Ryoji Joko, Daisuke Yamada, Masahiro Nakamura, Aki Yoshida, Shota Takihira, Tomoka Takao, Ming Lu, Kohei Sato, Tatsuo Ito, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki, Takeshi Takarada

    Translational oncology   14 ( 1 )   100960 - 100960   2021.1

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    Paired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.

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  • Preoperative morphologic changes of the medial meniscus correlate with suture translations during knee flexion in pullout repair of medial meniscus posterior root tear. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Yuki Okazaki, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

    The Knee   28   346 - 353   2021.1

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    BACKGROUND: Medial meniscus (MM) translates and extrudes posteriorly during knee flexion in MM posterior root tear (MMPRT) knees, and transtibial pullout repair of MMPRT has been performed to regulate the MM extrusion. This study aimed to calculate each suture translation during knee flexion in transtibial pullout repair of MMPRT, and to investigate the morphologic features of the MM that lead to longer suture translations during knee flexion. METHODS: Thirty patients with MMPRT who met the operative indication of pullout repair were enrolled and investigated prospectively. Pullout repair was performed by using two simple stitches (outer and inner sutures) and an all-inside suture in the posteromedial part of the MM. Each suture's translation from 0° to 90° of knee flexion was measured intraoperatively. The MM morphologic features, including MM medial extrusion (MMME) and MM posterior height (MMPH), were measured using preoperative magnetic resonance imaging, and the correlation between these values and each suture translation was evaluated. RESULTS: The average outer, inner, and all-inside suture translations were 4.8 mm, 3.9 mm, and 1.3 mm, respectively. Significant correlations were observed between the outer suture translation and MMME, and MMPH (p < 0.001 and <0.01, respectively). The thresholds for preoperative MMME and MMPH for longer outer suture translations (≥6 mm) were 2.1 mm and 5.4 mm, respectively. CONCLUSIONS: Preoperative longer MMME and higher MMPH were associated with longer meniscus translations during knee flexion during MMPRT repair.

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  • Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression. International journal

    Toshinori Omori, Hiroshi Tazawa, Yasuaki Yamakawa, Shuhei Osaki, Joe Hasei, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    PloS one   16 ( 4 )   e0250643   2021

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    Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.

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  • RANKL expression in chondrocytes and its promotion by lymphotoxin-α in the course of cartilage destruction during rheumatoid arthritis. International journal

    Ayumu Takeshita, Keiichiro Nishida, Aki Yoshida, Yoshihisa Nasu, Ryuichi Nakahara, Daisuke Kaneda, Hideki Ohashi, Toshifumi Ozaki

    PloS one   16 ( 7 )   e0254268   2021

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    We investigated the expression and localization of the receptor activator nuclear factor κB ligand (RANKL) in cartilage from patients with rheumatoid arthritis (RA) of relevance to cartilage degeneration. We also examined the role of exogenous lymphotoxin (LT)-α on RANKL expression in human chondrocytes and its effect on in vitro osteoclast differentiation. Cartilage and synovial fluid samples were obtained from 45 patients undergoing total joint replacement surgery or joint puncture, including 24 patients with osteoarthritis (OA) and 21 patients with RA. RANKL expression in articular cartilage was examined by immunohistochemistry. LT-α concentrations in synovial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). Normal human chondrocytes were stimulated with LT-α, and the relative mRNA levels of RANKL, osteoprotegerin (OPG), matrix metalloproteinase-9, and vascular endothelial growth factor were examined by real-time polymerase chain reaction. Soluble RANKL protein in culture media was measured using ELISA, and membrane-bound RANKL protein in cells was examined by western blotting. Co-cultures of human chondrocytes with peripheral blood mononuclear cells (PBMCs) were stimulated with macrophage-colony stimulating factor and LT-α, and osteoclast differentiation was evaluated by staining for tartrate-resistant acid phosphatase. LT-α concentrations were higher in RA synovial fluid than in OA samples. The population of RANKL-positive chondrocytes of RA cartilage was higher than that of OA cartilage, and correlated with cartilage degeneration. Stimulation of cultured human chondrocytes by LT-α increased RANKL expression, the RANKL/OPG ratio, and angiogenic factors. Membrane-bound RANKL in chondrocytes was up-regulated after stimulation of LT-α, whereas soluble RANKL in culture medium did not increase. Co-cultures of human chondrocytes and PBMCs demonstrated that LT-α stimulated human chondrocytes to produce RANKL and induced osteoclastic differentiation of PBMCs. RANKL produced by chondrocytes may contribute to cartilage destruction during RA and LT-α could promote the expression of RANKL in human chondrocytes.

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  • Radiographic and clinical assessment of unidirectional porous hydroxyapatite to treat benign bone tumors. International journal

    Toshiyuki Kunisada, Joe Hasei, Tomohiro Fujiwara, Eiji Nakata, Suguru Yokoo, Koji Demiya, Toshifumi Ozaki

    Scientific reports   10 ( 1 )   21578 - 21578   2020.12

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    Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

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  • Clinical Outcome of Patients with Recurrent/Refractory Localized Ewing's Sarcoma Family of Tumors: A Retrospective Report From the JESS Group

    Katsutsugu Umeda, Takako Miyamura, Kenji Yamada, Ako Hosono, Hideki Sano, Minako Sumi, Hajime Okita, Yosuke Hosoya, Motoaki Chin, Toshifumi Ozaki

    PEDIATRIC BLOOD & CANCER   67   2020.12

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  • Clinical Outcome of Patients with Metastatic Ewing's Sarcoma Family of Tumors: A Retrospective Report From the JESS Group

    Katsutsugu Umeda, Takako Miyamura, Ako Hosono, Hideki Sano, Minako Sumi, Hajime Okita, Yosuke Hosoya, Daiichiro Hasegawa, Motoaki Chin, Toshifumi Ozaki

    PEDIATRIC BLOOD & CANCER   67   2020.12

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  • Deep Learning for Osteoporosis Classification Using Hip Radiographs and Patient Clinical Covariates. International journal

    Norio Yamamoto, Shintaro Sukegawa, Akira Kitamura, Ryosuke Goto, Tomoyuki Noda, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Keisuke Kawasaki, Yoshihiko Furuki, Toshifumi Ozaki

    Biomolecules   10 ( 11 )   2020.11

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    This study considers the use of deep learning to diagnose osteoporosis from hip radiographs, and whether adding clinical data improves diagnostic performance over the image mode alone. For objective labeling, we collected a dataset containing 1131 images from patients who underwent both skeletal bone mineral density measurement and hip radiography at a single general hospital between 2014 and 2019. Osteoporosis was assessed from the hip radiographs using five convolutional neural network (CNN) models. We also investigated ensemble models with clinical covariates added to each CNN. The accuracy, precision, recall, specificity, negative predictive value (npv), F1 score, and area under the curve (AUC) score were calculated for each network. In the evaluation of the five CNN models using only hip radiographs, GoogleNet and EfficientNet b3 exhibited the best accuracy, precision, and specificity. Among the five ensemble models, EfficientNet b3 exhibited the best accuracy, recall, npv, F1 score, and AUC score when patient variables were included. The CNN models diagnosed osteoporosis from hip radiographs with high accuracy, and their performance improved further with the addition of clinical covariates from patient records.

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  • Medial meniscus posterior root repair prevents the progression of subchondral insufficiency fracture of the knee.

    Yuki Okazaki, Takayuki Furumatsu, Takaaki Hiranaka, Keisuke Kintaka, Shota Takihira, Yusuke Kamatsuki, Tomonori Tetsunaga, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   2020.11

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    BACKGROUND: Medial meniscus posterior root tear (MMPRT) causes medial meniscus extrusion (MME) and leads to subchondral insufficiency fracture of the knee (SIFK). However, the progression of SIFK after MMPRT pullout repair remains unknown. This study aimed to investigate the progression of SIFK and compare clinical outcomes in patients with SIFK to those without SIFK after MMPRT pullout repair. We hypothesized that the progression of SIFK would be prevented by MMPRT pullout repair, and clinical outcomes would improve in all patients. METHODS: The SIFK grade (1-4) was evaluated using T2-fat suppression magnetic resonance imaging. Thirty-eight patients without SIFK (n = 22) and with low-grade SIFK (1 and 2; n = 16) who underwent MMPRT pullout repair were included. Preoperative factors, such as the duration from injury to the time of magnetic resonance imaging/surgery (weeks), femorotibial angle (degree), MME (mm), and clinical outcomes were evaluated, as well as the progression of SIFK. RESULTS: SIFK was identified in only 9 patients (grade 1) postoperatively. Significantly improved clinical outcomes were observed in all patients. Preoperative femorotibial angle, MME, and duration from injury to the time of magnetic resonance imaging/surgery were 177.1 ± 1.5°, 3.2 ± 1.6 mm, and 6.4 ± 7.0/10.1 ± 7.5 weeks, respectively. No significant difference in preoperative factors and clinical outcomes was observed between patients with SIFK and those without SIFK. CONCLUSIONS: MMPRT pullout repair prevented the progression of low-grade SIFK and improved clinical outcomes in all patients, although bone contusions (grade 1 SIFK) were not completely healed within 1 year. MMPRT pullout repair could be a good treatment option for optimizing clinical outcomes in patients with low-grade SIFK.

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  • Medial meniscus posterior root repair restores the intra-articular volume of the medial meniscus by decreasing posteromedial extrusion at knee flexion. International journal

    Yoshiki Okazaki, Takayuki Furumatsu, Takatsugu Yamauchi, Yuki Okazaki, Yusuke Kamatsuki, Takaaki Hiranaka, Yuya Kajiki, Ximing Zhang, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   28 ( 11 )   3435 - 3442   2020.11

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    PURPOSE: Transtibial repair of a medial meniscus posterior root tear (MMPRT) can improve clinical outcomes, although meniscal extrusion remains. However, few studies have investigated the volume of meniscal extrusion. This study aimed to evaluate the effect of transtibial repair in reducing the volume using three-dimensional (3D) magnetic resonance imaging, at 10° and 90° knee flexion. METHODS: Twenty patients with MMPRTs and 16 volunteers with normal knees participated. The 3D models of meniscus were constructed using SYNAPSE VINCENT®. The meniscal extrusion and its volume were measured at 10° and 90° knee flexion. Differences between the pre- and postoperative examinations were assessed using the Wilcoxon signed-rank test. The postoperative parameters were compared to those in patients with normal knees. RESULTS: There were no significant pre- and postoperative differences in any parameter at 10° knee flexion. At 90° knee flexion, the posterior extrusion and its meniscal volume were decreased significantly after transtibial repair (p < 0.05), even though these parameters were larger than in the normal knees. On the other hand, intra-articular meniscal volume calculated by the extrusion volume was increased to the level of the normal knee. CONCLUSIONS: This study demonstrated that transtibial repairs improved the intra-articular/intra-tibial surface volume of the medial meniscus by reducing the posteromedial extrusion during knee flexion. This 3D analysis is clinically relevant in evaluating that, while transtibial root repair has a limited ability to reduce meniscal extrusion, it can restore the functional volume of the medial meniscus which contributes to the shock absorber postoperatively. LEVEL OF EVIDENCE: IV.

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  • What Are the Results of Resection of Localized Dedifferentiated Liposarcomas in the Extremities? International journal

    Eiji Nakata, Toshiyuki Kunisada, Joe Hasei, Ryuichi Nakahara, Hiroyuki Yanai, Tomohiro Toji, Hirofumi Inoue Ct, Toshifumi Ozaki

    Clinical orthopaedics and related research   478 ( 11 )   2550 - 2561   2020.11

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    BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a rare malignancy that transitions from an atypical lipomatous tumor to a sarcoma with a variable morphologic appearance. The behavior of this tumor in the retroperitoneum is aggressive, but the behavior of DDLPS in the extremities is less well-defined because it is rare. Few reports have assessed the imaging features and clinical outcomes of primary DDLPS in the extremities. QUESTIONS/PURPOSES: In patients with primary DDLPS of the extremity, we asked the following questions: (1) How frequently do additional primary malignancies occur in patients with DDLPS? (2) What is the rate of overall survival, metastases, and local recurrence in DDLPS? (3) What factors are associated with metastasis-free survival and local recurrence in DDLPS? METHODS: We defined DDLPS as a biphasic neoplasm that transitions from an atypical lipomatous tumor (ALT) to a sarcoma of variable morphologic appearance and histologic grades. We retrospectively evaluated the medical records of patients with DDLPS of the extremities who underwent surgery in our institution between 2003 and 2017. During that time, 16 patients were treated for this diagnosis; one was excluded from this study because the patient did not have an MRI, leaving 15 patients (nine men, six women; their median [range] age was 67 years [42 to 87]) for evaluation. All had a minimum of 2 years follow-up (median [range] 54 months [25 to 136]); 14 of 15 have been seen in the last 5 years (one patient, who was doing well at the time, was lost after 9 years of follow-up). In 11 patients, MRI demonstrated two components: an ALT component with high intensity on both T1-weighed and T2-weighted sequences and a dedifferentiated component low-to-intermediate intensity on T1-weighed and heterogeneous hyperintensity on T2-weighted sequence. Nine patients were evaluated using 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography (FDG-PET) combined with CT (PET/CT). PET/CT showed a biphasic pattern with a close relationship to MRI findings. The dedifferentiated component presented with high FDG uptake (median [range] maximum standardized uptake value 5.1 [1.9 to 22.6]), while the atypical lipomatous tumor component showed almost no FDG uptake. In all patients, immunohistochemical studies of p16 and cyclin-dependent kinase-4 (CDK4) were investigated. Positive staining for both p16 and CDK4 were seen in 13 of 15 patients.We retrospectively evaluated the electronic medical records of all patients in our institution for the presence of additional primary malignancies, local recurrence-free survival, metastasis-free survival, and overall survival. The survival rate was estimated using the Kaplan-Meier method. The Wilcoxon exact test was used to determine the prognostic importance of the following survival variables: age, sex, maximum tumor size, radiotherapy, and surgical margin. RESULTS: Seven additional primary malignancies developed in five of 15 patients (two lung cancers, two sarcomas, one renal cell cancer, one uterine cancer, and one non-Hodgkin lymphoma). The 3- and 5-year metastasis-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. With the numbers available, we found no factors associated with metastasis-free survival. The 3- and 5-year overall survival rates were 100% (95% CI 1.00 to 1.00) and 88% (95% CI 0.65 to 1.00), respectively. Three of 15 patients had local recurrence. The 3- and 5-year local recurrence-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. Large (> 15 cm) tumors were more likely to have a local recurrence (p = 0.04). CONCLUSIONS: In this small series, we found that the extremities are a favorable site for DDLPS compared with the retroperitoneum, although we did not directly compare the two sites. This rare tumor has a relatively high likelihood of being associated with other malignancies. We believe patients should be assessed and monitored carefully for this possibility. In the future, larger studies are needed to better define predictors of local recurrence, although the tumor's size may be associated with a greater propensity for local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study.

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  • What Factors Are Associated with Treatment Outcomes of Japanese Patients with Clear Cell Chondrosarcoma? International journal

    Robert Nakayama, Keiko Hayakawa, Eisuke Kobayashi, Makoto Endo, Naofumi Asano, Tsukasa Yonemoto, Hiroyuki Kawashima, Kenichiro Hamada, Itsuo Watanabe, Hiroyuki Futani, Takahiro Goto, Yoshihiro Nishida, Toshifumi Ozaki

    Clinical orthopaedics and related research   478 ( 11 )   2537 - 2547   2020.11

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    BACKGROUND: Clear cell chondrosarcoma is an extremely rare chondrosarcoma subtype; thus, its treatment outcomes and associated factors have not been widely studied. Knowing more about it is potentially important because clear cell chondrosarcomas are often misdiagnosed as other benign lesions and subsequently treated and followed inappropriately. QUESTIONS/PURPOSES: (1) What are the patient- and tumor-related characteristics of clear cell chondrosarcoma? (2) What proportion of patients with clear cell chondrosarcoma initially had a misdiagnosis or a misleading initial biopsy result? (3) What is the survivorship of patients with clear cell chondrosarcoma free from death, local recurrence, and distant metastasis, and what factors are associated with greater survivorship or a reduced risk of local recurrence? METHODS: Between 1985 and 2018, 12 Japanese Musculoskeletal Oncology Group (JMOG) hospitals treated 42 patients with a diagnosis of clear cell chondrosarcoma. All 42 patients had complete medical records at a minimum of 1 year or death, and were included in this multicenter, retrospective, observational study. No patients were lost to follow-up within 5 years of treatment but four were lost to follow-up greater than 5 years after treatment because their physicians thought their follow-up was sufficient. Clinical data were collected by chart review. The median (range) follow-up period was 69 months (2 to 392). In general, when a possibly malignant bone tumor was found on imaging studies, the histological diagnosis was made by biopsy before initiating treatment. Once the diagnosis had been made, the patients were treated by surgery only, complete resection if technically possible, because chondrosarcomas are known to be resistant to chemotherapy and radiotherapy. Unresectable tumors were treated with particle-beam radiation therapy. When patients with chondrosarcoma were referred after unplanned surgical procedures with inadequate surgical margins, immediate additional wide resection was considered before local recurrence developed. This diagnostic and treatment strategy is common to all JMOG hospitals and did not change during the study period. Primary wide resection was performed in 79% (33 of 42) patients, additional wide resection after initial inadequate surgery in 12% (five of 42), curettage and bone grafting in 5% (two of 42) patients, and radiotherapy was administered to 5% (two of 42). Surgical margins among the 40 patients who underwent surgery at JMOG hospitals were no residual tumor in 93% (37 of 42) of patients, microscopic residual tumor in 2% (one of 42), and macroscopic residual tumor or state after curettage or intralesional excision in 5% (two of 42). The oncological endpoints of interest were 5- and 10- year overall survival, disease-free survival, survival free of local recurrence, and survival free of distant metastases; these were calculated using the Kaplan-Meier method and compared using the log-rank test. Risk ratios with their respective 95% confidence intervals (CIs) were estimated in a Cox regression model. The Bonferroni adjustment was used for multiple testing correction. RESULTS: The sex distribution was 74% men and 26% women (31 and 11 of 42, respectively), with a mean age of 47 ± 17 years. Eighty one percent (34 of 42) of tumors occurred at the ends of long bones, and the proximal femur was the most common site accounting for 60% (25 of 42). The mean size of the primary tumors was 6.3 ± 2.7 cm. Definite pathologic fractures were present in 26% (10 of 42) and another 26% (10 of 42) had extraskeletal involvement. None had metastases at presentation. Twenty four percent (six of 25) tumors in the proximal femur were misdiagnosed as benign lesions and treated inadequately without biopsy. Twenty nine percent (10 of 35) patients had initial misdiagnoses by biopsy and core needle biopsies had a greater risk of resulting in inaccurate histological diagnoses. The study patients' 5- and 10-year overall survival rates were 89% (95% CI 74 to 96) and 89% (95% CI 74 to 96), respectively; 5- and 10- year disease-free survival rates 77% (95% CI 58 to 89) and 57% (95% CI 36 to 75), respectively; 5- and 10-year local recurrence-free survival rates 86% (95% CI 68 to 95) and 71% (95% CI 49 to 86), respectively; and 5- and 10-year distant metastasis-free survival rates 84% (95% CI 67 to 93) and 74% (95% CI 53 to 88), respectively. Notably, bone metastases (17%, seven of 42) were as common as pulmonary metastases (14%, six of 42); four patients developed both bone and pulmonary metastases. The difference between 10-year overall survival rates and 10-year disease-free survival indicated very late recurrence more than 5 years after the initial treatment. After controlling for multiple comparisons, the only factor we found that was associated with local recurrence-free survival was initial treatment (positive margin versus primary wide resection) (risk ratio 8.83 [95% CI 1.47 to 53.1]; p = 0.022 after the Bonferroni adjustment). Additional wide resection reduced the risk of local recurrence. CONCLUSIONS: The femoral head was the most common location of clear cell chondrosarcoma and had a high risk of misdiagnosis as common benign lesions that resulted in initial inadequate surgery and a consequent high risk of local recurrence. Immediate additional wide resection should be considered in patients who had initial inadequate surgery to reduce the risk of local recurrence. Because clear cell chondrosarcoma can recur locally or distantly in the bones and lungs in the long term, patients should be informed of the risk of very late recurrence and the necessity of decades-long with surveillance for local recurrence and lung and bone metastases. LEVEL OF EVIDENCE: Level IV, therapeutic study.

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  • Diagnostic performance of open MRI in the flexed knee position for the detection of medial meniscus ramp lesions. International journal

    Yuki Okazaki, Takayuki Furumatsu, Soichiro Okamoto, Takaaki Hiranaka, Keisuke Kintaka, Shinichi Miyazawa, Toshifumi Ozaki

    Skeletal radiology   49 ( 11 )   1781 - 1788   2020.11

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    OBJECTIVES: To identify the diagnostic performance of magnetic resonance imaging (MRI) in the knee-flexed position for the detection of meniscal ramp lesions in patients with anterior cruciate ligament tears. MATERIALS AND METHODS: Forty-three patients (mean age 24.5 ± 9.5 years; 21 males, 22 females) with an arthroscopically proven anterior cruciate ligament tear were included in this retrospective study. The presence of the following two important features on MRI was recorded: irregularity of the medial meniscus at the posterior margin, and complete fluid filling between the posterior horn of the medial meniscus and the capsule margin. Findings obtained in arthroscopy served as the reference standard. The diagnostic sensitivity, specificity, and inter-observer agreement were calculated. RESULTS: Sixteen ramp lesions were noted on arthroscopy (37.2%). With an irregularity of the medial meniscus at the posterior margin on MRI, the sensitivity and specificity were 87.5 and 59.3% at 10° knee flexion and 93.8 and 85.2% at 90° flexion, respectively. The complete fluid filling sign on MRI showed sensitivity and specificity of 31.3 and 100% at 10° knee flexion and 87.5 and 100% at 90° flexion, respectively. The concordance between the two observers for the two MRI features was very good (k = 0.70-0.88). CONCLUSION: MRI with the knee in the flexed position improves the diagnostic performance of the detection of meniscal ramp lesions compared with MRI with the knee in the extended position.

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  • A histological study of the medial meniscus posterior root tibial insertion. International journal

    Tomohito Hino, Takayuki Furumatsu, Shinichi Miyazawa, Masataka Fujii, Yuya Kodama, Yusuke Kamatsuki, Yoshiki Okazaki, Shin Masuda, Yuki Okazaki, Toshifumi Ozaki

    Connective tissue research   61 ( 6 )   546 - 553   2020.11

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    Purpose/Aim of the study: Posterior root injury of the medial meniscus often leads to articular cartilage degeneration due to altered biomechanics. To avoid dysfunction, the attachment must be repaired using the transtibial pullout technique. To guide appropriate placement of the tibial tunnel, additional details on the normal anatomy of the meniscus insertion are needed. Therefore, we performed a histological analysis of a tibial bone slice with the medial meniscus posterior insertion obtained during total knee arthroplasty surgery. Materials and methods: Horizontal slices of the proximal tibia were obtained from 7 patients with osteoarthritis who underwent total knee arthroplasty. After decalcification, the region of the posterior horn was cut out and segmented into four pieces (2.0 mm thickness; medial to lateral). Sagittal sections were evaluated by safranin O staining or immunohistochemistry with anti-type collagen antibody. Results: Safranin O staining showed that the insertion of the posterior root consisted primarily of fibrocartilaginous layers in segment 2. Anatomically, segment 2 corresponded to the sagittal plane passing through the peak of the medial intercondylar tubercle. In this section, safranin O staining and immunohistochemistry revealed that the anterior one-third of the posterior root insertion was richer in proteoglycans and type II collagen than the central and posterior one-third. Conclusions: Anatomical insertion of the posterior root of the medial meniscus was located at the sagittal plane passing through the peak of the medial intercondylar tubercle. The structure of the medial meniscus posterior insertion was mainly localized in the anterior one-third.

    DOI: 10.1080/03008207.2019.1631298

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  • Medial meniscus posterior root tear causes swelling of the medial meniscus and expansion of the extruded meniscus: a comparative analysis between 2D and 3D MRI. International journal

    Yoshiki Okazaki, Takayuki Furumatsu, Takuya Yamaguchi, Yuya Kodama, Yusuke Kamatsuki, Shin Masuda, Yuki Okazaki, Takaaki Hiranaka, Ximing Zhang, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   28 ( 11 )   3405 - 3415   2020.11

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    PURPOSE: This study aimed to clarify the advantages of three-dimensional (3D) magnetic resonance imaging (MRI) over two-dimensional (2D) MRI in measuring the size of the medial meniscus (MM) and to analyse the volumes of MM and the extruded meniscus in patients with MM posterior root tear (MMPRT), at 10° and 90° knee flexion. METHODS: This study included 17 patients with MMPRTs and 15 volunteers with uninjured knees. The MMs were manually segmented for 3D reconstruction; thereafter, the extruded part separated from the tibial edge was determined. The length, width, height, and extrusion of MM were measured by the 2D and 3D methods, and compared. The MM volume, extruded meniscus volume, and their ratio were also calculated using 3D analysis software in the two groups. RESULTS: The estimated length and posterior height of MM were larger with 3D MRI than with 2D MRI measurements. The MM volume was significantly greater in MMPRT knees than in normal knees, with increasing MM height. In MMPRT knees, the mean volume of the extruded meniscus and its ratio significantly increased by 304 mm3 (p = 0.02) and 9.1% (p < 0.01), respectively, during knee flexion. CONCLUSIONS: This study demonstrated that 3D MRI could estimate the precise MM size and that MMPRT caused swelling of the meniscus due to the increased thickness in the posteromedial part. The clinical significance of this study lies in its 3D evaluation of MM volume, which should help the surgeon understand the biomechanical failure of MM function and improve MMPRT repair technique. LEVEL OF EVIDENCE: III.

    DOI: 10.1007/s00167-019-05580-6

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  • Transtibial fixation for medial meniscus posterior root tear reduces posterior extrusion and physiological translation of the medial meniscus in middle-aged and elderly patients. International journal

    Yuya Kodama, Takayuki Furumatsu, Shin Masuda, Yoshiki Okazaki, Yusuke Kamatsuki, Yuki Okazaki, Takaaki Hiranaka, Shinichi Miyazawa, Masaharu Yasumitsu, Toshifumi Ozaki

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   28 ( 11 )   3416 - 3425   2020.11

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    PURPOSE: To investigate changes in meniscal extrusion during knee flexion before and after pullout fixation for medial meniscus posterior root tear (MMPRT) and determine whether these changes correlate with articular cartilage degeneration and short-term clinical outcomes. METHODS: Twenty-two patients (mean age 58.4 ± 8.2 years) diagnosed with type II MMPRT underwent open magnetic resonance imaging preoperatively, 3 months after transtibial fixation and at 12 months after surgery, when second-look arthroscopy was also performed. The medial meniscus medial extrusion (MMME) and the medial meniscus posterior extrusion (MMPE) were measured at knee 10° and 90° flexion at which medial meniscus (MM) posterior translation was also calculated. Articular cartilage degeneration was assessed using International Cartilage Research Society grade at primary surgery and second-look arthroscopy. Clinical evaluations included Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee subjective knee evaluation form, Lysholm score, Tegner activity level scale, and pain visual analogue scale. RESULTS: MMPE at 10° knee flexion was higher 12 months postoperatively than preoperatively (4.8 ± 1.5 vs. 3.5 ± 1.2, p = 0.01). MMPE at 90° knee flexion and MM posterior translation were smaller 12 months postoperatively than preoperatively (3.5 ± 1.1 vs. 4.6 ± 1.3, 7.2 ± 1.7 vs. 8.9 ± 2.0, p < 0.01). Articular cartilage degeneration of medial femoral condyle correlated with MMME in knee extension (r = 0.5, p = 0.04). All clinical scores significantly improved 12 months postoperatively. However, correlations of all clinical scores against decreased MMPE and increased MMME were not detected. CONCLUSIONS: MMPRT transtibial fixation suppressed the progression of MMPE and cartilage degeneration and progressed MMME minimally in knee flexion position at 1 year. However, in the knee extension position, MMME progressed and correlated with cartilage degeneration of medial femoral condyle. MMPRT transtibial fixation contributes to the dynamic stability of the MM in the knee flexion position. LEVEL OF EVIDENCE: IV.

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  • Letter regarding "Comparing the usefulness of a fluoroscopic navigation system in femoral trochanteric fracture for orthopaedic residents with the conventional method". International journal

    Norio Yamamoto, Yosuke Tomita, Keisuke Kawasaki, Toshifumi Ozaki

    Injury   51 ( 10 )   2348 - 2348   2020.10

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  • Cognitive factors associated with locomotive syndrome in chronic pain patients: A retrospective study.

    Hironori Tsuji, Tomoko Tetsunaga, Tomonori Tetsunaga, Haruo Misawa, Keiichiro Nishida, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   2020.9

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    BACKGROUND: Prevention and treatment for locomotive syndrome (LS) are important for extending healthy life expectancy. The 25-question geriatric locomotive function scale (GLFS-25) was developed to diagnose LS. The Fear-Avoidance model was proposed to explain pain chronicity. LS and chronic pain decrease activities of daily living; however, the relationships between LS and factors related to chronic pain in the Fear-Avoidance model are unknown. Objective of the current study was to assess the prevalence of LS and examine the factors of the Fear-Avoidance model and the GLFS-25 that affect the prevalence of LS in patients with chronic pain. METHODS: Participants included 281 patients (99 men, 182 women) aged over 40 years with chronic pain who visited our outpatient clinic for chronic pain. All participants completed the GLFS-25, numeric rating scale (NRS), pain catastrophizing scale (PCS), hospital anxiety and depression scale (HADS), and Athene insomnia scale (AIS). According to a GLFS-25 cutoff point, participants were divided into three groups (LS-2; GLFS-25 ≥ 16, LS-1; 7 ≤ GLFS-25 < 16, and non-LS; GLFS-25 < 7 points) and each parameter was compared among the groups, followed by multiple logistic regression analysis. Next, multiple linear regression analysis was performed to determine the factors associated with the GLFS-25. RESULTS: Of all 281 patients, 241 (85.8%) patients were diagnosed with LS-2. Univariate analysis revealed there were significant differences in NRS, PCS, HADS anxiety, HADS depression, and AIS among groups. Multiple logistic regression analyses showed PCS was significantly associated with LS-2 prevalence. The GLFS-25 was positively correlated with NRS, HADS depression, AIS in multiple linear regression analysis. CONCLUSIONS: We found that patients with chronic pain in our outpatient clinic had a significant rate of LS-2. The prevalence of LS-2 was significantly correlate with pain catastrophizing, and the GLFS-25 was significantly correlated with higher pain intensity, depression, and insomnia.

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  • Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. International journal

    Eiji Nakata, Shinsuke Sugihara, Yoshifumi Sugawara, Toshiyuki Kozuki, Daijiro Harada, Naoyuki Nogami, Ryuichi Nakahara, Takayuki Furumatsu, Tomonori Tetsunaga, Toshiyuki Kunisada, Toshifumi Ozaki

    Oncology letters   20 ( 3 )   2977 - 2986   2020.9

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    The effect of nivolumab and the relation between bone response and tumor control in patients with non-small-cell lung cancer (NSCLC) with bone metastases are not clear. The outcome of nivolumab monotherapy was investigated, and whether the response of bone metastases is useful as an early predictor of tumor control in patients with NSCLC with bone metastases was examined. The participants included 15 patients who received nivolumab monotherapy for NSCLC with bone metastases in our institution between 2015 and 2017. Tumor control was defined using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST1.1). Response of bone metastases was assessed by the MD Anderson response criteria (MDA criteria). Responses according to RECIST1.1 and the MDA criteria were classified as responder (complete response or partial response) and non-responder [progressive disease (PD) or stable disease]. Progression-free survival (PFS) was investigated using the Kaplan-Meier method. With RECIST1.1, the overall response rate was 20%. Multivariate analysis showed that the MDA criteria were the only risk factor for patients with PD (RECIST1.1). Median PFS was 1.9 months, with PFS of 20% at 6 months. Univariate analysis showed that being a non-responder according to the MDA criteria was the only risk factor for PFS. In patients who were responders (MDA criteria) within 3 months, PFS was 83 and 50% at 3 and 6 months, respectively, though all non-responder (MDA criteria) patients converted to PD (RECIST1.1) within 3 months. Response according to RECIST1.1 was significantly correlated with response according to the MDA criteria (P<0.05). In patients who were both responders according to RECIST1.1 and the MDA criteria, time to response with the MDA criteria (1.4-2.0 months) was earlier than with RECIST1.1 (2.8-3.0 months) in all patients. In conclusion, application of the MDA criteria within 2 months of nivolumab monotherapy is useful for early prediction of response and prognosis in patients with NSCLC with bone metastases.

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  • Phase II trial of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas: A Japanese Musculoskeletal Oncology Group study. International journal

    Hiroshi Urakawa, Akira Kawai, Takahiro Goto, Hiroaki Hiraga, Toshifumi Ozaki, Hiroyuki Tsuchiya, Robert Nakayama, Norifumi Naka, Yoshihiro Matsumoto, Eisuke Kobayashi, Tomotake Okuma, Toshiyuki Kunisada, Masahiko Ando, Takafumi Ueda, Yoshihiro Nishida

    Cancer science   111 ( 9 )   3303 - 3312   2020.9

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    Alveolar soft part sarcoma (ASPS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS) are known to be chemoresistant tumors. The aim of this study was to investigate the effect of pazopanib on these chemoresistant tumors. This study is designed as a single-arm, multicenter, investigator-initiated phase II trial. Patient enrollment was undertaken between July 2016 and August 2018 at 10 hospitals participating in the Japanese Musculoskeletal Oncology Group. The primary end-point is the CBR (CBR, including complete or partial response and stable disease) at 12 weeks after treatment with pazopanib according to RECIST. Eight patients were enrolled within the period. The histological subtypes were 5 ASPS, 2 ES, and 1 CCS. The median follow-up period was 22.2 (range, 4.9-24.9) months. All patients initially received pazopanib 800 mg once daily. The CBRs were 87.5% (7 of 8) and 75.0% (6 of 8) according to RECIST and Choi criteria at 12 weeks after pazopanib treatment, respectively. The CBRs at 12 weeks according to RECIST were 80.0%, 100.0%, and 100.0% in ASPS, ES, and CCS, respectively. Partial response was observed in 1 ASPS according to RECIST and 3 ASPS and 1 ES according to Choi criteria at 12 weeks after pazopanib treatment. This study documented antitumor activity of pazopanib, especially in ASPS. These results support the frontline use of pazopanib for ASPS. Prospective data collection is desired using both RECIST and Choi criteria for these rare chemoresistant tumors.

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  • Acetabular depth, an early predictive factor of acetabular development: MRI in patients with developmental dysplasia of the hip after open reduction. International journal

    Yoshi Kawamura, Tomonori Tetsunaga, Hirofumi Akazawa, Kazuki Yamada, Tomoaki Sanki, Yoshihiro Sato, Eiji Nakata, Toshifumi Ozaki

    Journal of pediatric orthopedics. Part B   2020.8

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    Early prediction of future acetabular development is important to determine an additional surgery for developmental dysplasia of the hip (DDH). The purpose of this study was to investigate the predictive factors of acetabular development using MRI. We retrospectively investigated dislocated 40 hips and 34 normal hips in 37 pediatric patients (9 males and 28 females) with DDH who underwent open reduction after walking age. We evaluated the cartilaginous acetabulum and labrum of the patients using coronal MRI T2*-weighted images at 5 years of age. The mean age at the time of surgery was 22 months, and the mean age at the final survey was 19 years. We divided patients into two groups in accordance with the Severin classification at the final follow-up. Groups with good outcomes (affected 26 hips and unaffected 27 hips) and poor outcomes (14 hips and 7 hips) were compared using the MRI parameters on each side. Predictive factors of acetabular development were identified using univariate and multiple logistic regression analyses. Using multiple logistic regression analysis, labral acetabular roof depth and labral hip center distance at 5 years of age represented predictors after open reduction (odds ratio 0.27, P = 0.035; odds ratio 3.4, P = 0.028, respectively) on the affected side, and bony hip center distance represented a predictor on the unaffected side (odds ratio 2.6, P = 0.049). Acetabular development in the unaffected side could be predicted by bony assessment, while acetabular development in the affected side had to be assessed by labrum using MRI.

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  • Tibial Tunnel Positioning Using the Posterolateral (PL) Divergence Guide in Anterior Cruciate Ligament Reconstruction.

    Takaaki Tanaka, Takayuki Furumatsu, Takaaki Hiranaka, Yuki Okazaki, Kenji Masuda, Noritaka Seno, Toshifumi Ozaki

    Acta medica Okayama   74 ( 4 )   345 - 350   2020.8

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    The aim of this study was to evaluate tunnel coalition and inter-tunnel distance by comparing the tibial tunnel position in double-bundle anterior cruciate ligament (ACL) reconstruction performed with a conventional guide versus a posterolateral (PL) divergence (PLD) guide. Subjects were 43 patients (ACL tip aimer: 20 knees; PLD guide: 23 knees) who underwent double-bundle ACL reconstruction between September 2014 and December 2017. In all cases, the tibial tunnel position, tunnel edge distance and tunnel angles were evaluated based on CT images. Clinical outcome was evaluated using the Lachman test, pivot-shift test, and Lysholm score. Tibial tunnel positions were similar between the conventional and PLD guide groups, while tibial tunnel edge distance was significantly less in the conventional group. Tunnel coalition was observed in 5 knees in the conventional and no knees in the PLD guide group. Distance between two tibial tunnel centers was 9.1 mm for the tip aimer, and 10.5 mm for the PLD guide. Creation of the PL tunnel tended to involve insertion from a more medial aspect for the PLD guide group than the conventional guide group. No differences in clinical outcomes were noted. The PLD guide can be used to create anatomically-positioned PL tunnels, and reduce the probability of occurrence of tunnel coalition.

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  • Risk factors of local recurrence after surgery in extraabdominal desmoid-type fibromatosis: A multicenter study in Japan. International journal

    Yoshihiro Nishida, Shunsuke Hamada, Akira Kawai, Toshiyuki Kunisada, Akira Ogose, Yoshihiro Matsumoto, Keisuke Ae, Junya Toguchida, Toshifumi Ozaki, Akihiro Hirakawa, Toru Motoi, Tomohisa Sakai, Eisuke Kobayashi, Tabu Gokita, Takeshi Okamoto, Tomoya Matsunobu, Koki Shimizu, Hiroshi Koike

    Cancer science   111 ( 8 )   2935 - 2942   2020.8

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    This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease desmoid-type fibromatosis. It was designed as a multiinstitutional joint research project with 7 major centers in Japan participating. The committee members of 7 major medical centers specializing in bone and soft tissue tumors formed this study group to develop clinical care guidelines. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathologic prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n = 3), 5-year local recurrence-free survival (LRFS) was 52.9%. No case had received pre- or postoperative radiotherapy. Univariate analysis revealed that extremity location (P < .001) and larger size (8 cm or more, P = .036) were significant adverse risk factors for LRFS. Multivariate analysis indicated that extremity location (P < .001) was a significantly adverse factor in addition to recurrent tumor (P = .041), S45F mutation (P = .028), and R1 surgical margin (P = .039). Preoperative drug treatment, including nonsteroidal antiinflammatory drugs, did not reduce the incidence of local recurrence (P = .199). This is the first study to analyze the factors correlating with outcomes of surgical treatment, including CTNNB1 mutation status, in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Europe and North America. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.

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  • 股関節の関節裂隙開大距離と関節弛緩性およびX線学的指標についての検討

    山田 和希, 遠藤 裕介, 鉄永 智紀, 三喜 知明, 河村 涌志, 佐藤 嘉洋, 尾崎 敏文

    Hip Joint   46 ( 1 )   566 - 570   2020.8

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  • Cam type FAIに対する骨軟骨形成術においてcam切除量を定量化した1例

    佐藤 嘉洋, 鉄永 智紀, 山田 和希, 三喜 知明, 河村 涌志, 尾崎 敏文

    Hip Joint   46 ( 1 )   428 - 430   2020.8

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  • A repair technique using two simple stitches reduces the short-term postoperative medial meniscus extrusion after pullout repair for medial meniscus posterior root tear. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Shin Masuda, Yoshiki Okazaki, Yuki Okazaki, Yuya Kodama, Yusuke Kamatsuki, Yuya Kajiki, Ximing Zhang, Toshifumi Ozaki

    European journal of orthopaedic surgery & traumatology : orthopedie traumatologie   30 ( 5 )   901 - 908   2020.7

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    BACKGROUND: Two types of repair techniques, FasT-Fix modified Mason-Allen (F-MMA) and two simple stitches (TSS), for the treatment of a medial meniscus posterior root tear (MMPRT) were previously reported. However, whether these techniques could prevent postoperative medial meniscus extrusion (MME) progression is unknown. This study investigated and compared postoperative MME of the two repair techniques. METHODS: Forty-seven knees that had undergone pullout repair for MMPRT were retrospectively reviewed. These knees were divided into two groups as follows: In 26 knees, MMPRT was treated using the F-MMA technique and fixed with the knee flexed at 45° and 20 N of tension [F-MMA (45°-20 N) group], and in 21 knees, MMPRT was treated using the TSS technique and fixed with the knee flexed at 20° and 30 N of tension [TSS (20°-30 N) group]. The medial meniscus body width (MMBW), absolute MME (aMME), and relative MME (rMME = absolute MME/MMBW) were measured and compared using magnetic resonance imaging 3 months postoperatively. The Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales for clinical outcomes were compared between the two groups at 6 months postoperatively. RESULTS: At 3 months postoperatively, the aMME and rMME significantly decreased in the TSS (20°-30 N) compared to the F-MMA (45°-20 N) group. The TSS (20°-30 N) group had better KOOS subscale scores than the F-MMA (45°-20 N) group at 6 months postoperatively. CONCLUSIONS: The TSS technique with appropriate tibial fixation can decrease MME soon after surgery. This may prevent osteoarthritis progression and improve clinical outcomes.

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  • Vacuum phenomenon in pelvic fractures. International journal

    Norio Yamamoto, Tomoyuki Noda, Shintaro Sukegawa, Tomohiro Inoue, Keisuke Kawasaki, Toshifumi Ozaki

    Injury   51 ( 7 )   1618 - 1621   2020.7

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    BACKGROUND: Vacuum phenomenon (VP) in closed pelvic fracture is a rare disorder. This study aimed to examine the prevalence and clinical findings of VP in closed pelvic fracture. METHODS: We retrospectively reviewed 197 patients with closed pelvic fracture who presented to our institution from January 2012 to December 2018. Pelvic fractures were diagnosed by plain radiography and computed tomography (CT). First, we investigated the prevalence and clinical findings of VP in pelvic fractures. Second, we compared the clinical findings between pelvic fracture with and without VP. Finally, VP in pelvic fracture was evaluated clinically and radiologically. RESULTS: VP in pelvic fractures was detected by CT in 9 (3.6%) of the 197 patients with pelvic fractures. Patients with VP had a significantly greater proportion of fracture progression than those without VP (42.9% vs. 11.3%, P = 0.02). Patients with VP had a greater proportion of fragility fractures of the pelvis (FFP), and a lesser proportion of bone union than those without VP, although the differences were not significant. In nine pelvic fractures with VP, all sacral fractures were classified as type 1 according to the Denis classification, and all pubic fractures were classified as type 1 according to the Nakatani classification. Two (22.2%) nonunion in nine pelvic fractures with VP occurred at the pubic fracture site alone. CONCLUSIONS: Orthopedic clinicians should be aware of the potential of CT for detecting VP in pelvic fractures, especially in the course of FFP progression.

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  • Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma. International journal

    Takuya Morita, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Toshifumi Ozaki

    Scientific reports   10 ( 1 )   9414 - 9414   2020.6

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    Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.

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  • The distance between the tibial tunnel aperture and meniscal root attachment is correlated with meniscal healing status following transtibial pullout repair for medial meniscus posterior root tear. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Yusuke Kamatsuki, Shinichi Miyazawa, Yoshiki Okazaki, Shin Masuda, Yuki Okazaki, Yuya Kodama, Toshifumi Ozaki

    The Knee   27 ( 3 )   899 - 905   2020.6

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    BACKGROUND: To investigate the relationship between tibial tunnel aperture location and postoperative meniscal healing. METHODS: We enrolled 25 patients (20 women and five men, mean age: 62.5 years) who underwent transtibial pullout repair for medial meniscus (MM) posterior root repair. The expected MM posterior root attachment center (AC) and tibial tunnel center (TC) were identified using three-dimensional computed tomography, and the minimum AC-TC distance was calculated. The meniscal healing status following transtibial pullout repair was assessed by second-look arthroscopy (mean postoperative period: 15 months) using a previously reported scoring system (meniscal healing score; range: 0-10). The association between AC-TC distance and meniscal healing score was investigated using univariate linear regression models. The optimal AC-TC distance cut-off for improved MM healing score (≥7) was determined using receiver operating characteristic analysis. RESULTS: The AC-TC distance and meniscal healing score were significantly associated (y = -0.42x + 9.48, R2 = 0.342; P = 0.002), with the optimum AC-TC distance being 5.8 mm. This cut-off had a sensitivity of 100% and specificity of 53%. CONCLUSIONS: This study demonstrates that AC-TC distance is significantly correlated with postoperative meniscal healing. Anatomical repair within 5.8 mm of the AC may result in improved meniscal healing.

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  • Comparison of the clinical outcomes of transtibial pull-out repair for medial meniscus posterior root tear: Two simple stitches versus modified Mason-Allen suture. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Shinichi Miyazawa, Yoshiki Okazaki, Yuki Okazaki, Shota Takihira, Yuya Kodama, Yusuke Kamatsuki, Shin Masuda, Taichi Saito, Toshifumi Ozaki

    The Knee   27 ( 3 )   701 - 708   2020.6

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    BACKGROUND: Transtibial pullout repair of a medial meniscus posterior root tear (MMPRT) is a commonly used procedure, and several techniques have been reported. We hypothesised that pull-out repairs using two simple stitches (TSS) would have similar postoperative outcomes as those using the modified Mason-Allen suture with FasT-Fix (F-MMA). We aimed to investigate the clinical outcomes of these techniques, including the meniscal healing status and osteoarthritic change. METHODS: The data of 68 patients who underwent transtibial pull-out repair were retrospectively investigated. The patients were divided into two groups of 41 and 27 patients using F-MMA and TSS, respectively. The clinical outcomes were assessed preoperatively and at second-look arthroscopy (the mean period from surgery was one year) using the Knee injury and Osteoarthritis Outcome Score. The meniscal healing status, evaluated at second-look arthroscopy, was compared between the two groups. The cartilage damage was graded as per the classification of the International Cartilage Repair Society and compared at the primary surgery and second-look arthroscopy. RESULTS: Both groups showed significant improvement in each clinical score. No significant difference was seen in the clinical outcome scores and the meniscal healing status between the two groups at second-look arthroscopy. Moreover, no significant progression of cartilage damage was observed in both groups. Fourteen patients in the F-MMA group developed a complication of suture bar failures postoperatively; however, there were no complications in the TSS group. CONCLUSIONS: The TSS and F-MMA techniques showed favourable clinical outcomes and would be established as clinically useful techniques for the MMPRT treatment.

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  • Effect of Lateral Gutter Osteophyte Resection on Correction of Varus Deformity in Arthroscopic Ankle Arthrodesis. International journal

    Kenta Saiga, Suguru Yokoo, Hideki Ohashi, Masahiro Horita, Takayuki Furumatsu, Toshifumi Ozaki

    Foot & ankle international   41 ( 6 )   683 - 688   2020.6

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    BACKGROUND: Recently, arthroscopic ankle arthrodesis has been performed for moderate-to-severe varus-deformed ankle osteoarthritis. However, the effect of osteophyte resection in the lateral gutter in arthroscopic ankle arthrodesis has not been clarified. We hypothesized that a varus-deviated ankle with lateral gutter osteophytes can be corrected by osteophyte resection. METHODS: Thirty-nine ankles of 38 patients were included. The mean age of patients was 70.0 (45-83) years. The patients were divided into the following groups: group with an osteophyte in the lateral gutter (osteophyte) and group with no osteophytes (nonosteophyte). Preoperative and postoperative tibiotalar angle, tibial plafond angle, and tibiotalar angle under valgus stress, as well as the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, were recorded. Twelve ankles underwent lateral gutter osteophyte resection, whereas the other 27 ankles did not require osteophyte resection. RESULTS: Preoperative tibiotalar angle was higher in the osteophyte group than in the nonosteophyte group (21.8 vs 11.2 degrees, P = .01). The tibiotalar angle in the preoperative valgus stress imaging was higher in the osteophyte group (12.9 vs 5.7, P < .01). However, the postoperative tibiotalar angle was similar between the 2 groups (7.1 vs 5.4, P = .183). JSSF ankle/hindfoot scale improved in both groups. CONCLUSION: Lateral gutter osteophyte resection enabled correction of the varus malalignment in arthroscopic ankle arthrodesis. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

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  • Short-term outcomes of mirogabalin in patients with peripheral neuropathic pain: a retrospective study. International journal

    Tomoko Tetsunaga, Tomonori Tetsunaga, Keiichiro Nishida, Haruo Misawa, Tomoyuki Takigawa, Kentaro Yamane, Hironori Tsuji, Yoshitaka Takei, Toshifumi Ozaki

    Journal of orthopaedic surgery and research   15 ( 1 )   191 - 191   2020.5

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    BACKGROUND: Mirogabalin, which is approved for the treatment of peripheral neuropathic pain in Japan, is a ligand for the α2δ subunit of voltage-gated calcium channels. Both pregabalin and mirogabalin act as nonselective ligands at the α2δ-1 and α2δ-2 subunits. Mirogabalin has a unique binding profile and long duration of action. Pregabalin has been reported to produce intolerable adverse effects in some patients. This study investigated outcomes associated with mirogabalin administration in patients with peripheral neuropathic pain who ceased treatment with pregabalin. METHODS: We retrospectively assessed peripheral neuropathic pain using the neuropathic pain screening questionnaire (NeP score) in 187 patients (58 men, 129 women) who were treated with mirogabalin. All patients had switched from pregabalin to mirogabalin due to lack of efficacy or adverse events. Differences in the treatment course (i.e., numeric rating scale (NRS) scores) were compared using one-way analysis of variance with Bonferroni post hoc tests. RESULTS: The mean age of the patients was 72.3 years (range, 30-94 years), and the mean duration of disease was 37 months (range, 3-252 months). After treatment with mirogabalin for 1 week, NRS scores significantly decreased compared with baseline and continued to decrease over time. After 8 weeks, NRS scores improved by ≥ 30% from baseline in 113 patients (69.3%). Twenty-four patients (12.8%) stopped mirogabalin treatment due to adverse events. Somnolence (26.7%), dizziness (12.3%), edema (5.9%), and weight gain (0.5%) were noted as adverse events of mirogabalin. CONCLUSIONS: The results of this investigation indicate that mirogabalin is safe and effective for reducing peripheral neuropathic pain.

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  • Definitive radiation therapy in patients with unresectable desmoid tumors: a systematic review. International journal

    Tomoya Matsunobu, Toshiyuki Kunisada, Toshifumi Ozaki, Yukihide Iwamoto, Masahiro Yoshida, Yoshihiro Nishida

    Japanese journal of clinical oncology   50 ( 5 )   568 - 573   2020.5

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    BACKGROUND: Desmoid tumors are rare soft tissue tumors. Wide local excision has been the standard surgical treatment for desmoid tumors. However, this procedure results in high local recurrence rates, so non-surgical treatments should be considered. The aim of this systematic review was to evaluate the effect of radiation therapy on patients with desmoid tumors, especially those with unresectable disease. METHODS: We evaluated studies published between 1 January 1990 and 31 August 2017 and cited in PubMed and Ichushi (in Japanese). All studies evaluating the effect of radiation therapy on desmoid tumors were included. Data regarding radiation dose, recurrence and adverse events were recorded. RESULTS: Among 218 identified studies, only 6 were finally included in this review. Local control was achieved in 253 of 317 patients with unresectable or unresected tumors who underwent definitive radiation therapy (the crude rate of local control was 79.8%). Toxicity was evaluated in patients who underwent definitive radiation therapy or surgery plus radiation therapy. One of the most common acute complications was skin toxicity. Frequent late complications of radiation therapy included fibrosis/contracture/joint stiffness, skin disorders, lymphedema and pain. Six patients developed secondary malignancies in the radiation field. CONCLUSIONS: In patients treated unsuccessfully with surgery, watchful waiting and pharmacotherapy, radiation therapy may be an option as salvage therapy because of the high rate of local control. Because desmoid tumors frequently develop in young individuals, children and young patients who receive radiation therapy for the treatment of desmoid tumors should be followed up on a long-term basis with periodic monitoring for late radiation toxicities.

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  • Results of a randomized phase II/III study comparing perioperative adriamycin plus ifosfamide and gemcitabine plus docetaxel for high-grade soft tissue sarcomas: Japan Clinical Oncology Group study JCOG1306.

    Kazuhiro Tanaka, Ryunosuke Machida, Akira Kawai, Robert Nakayama, Satoshi Tsukushi, Kunihiro Asanuma, Yoshihiro Matsumoto, Hiroaki Hiraga, Koji Hiraoka, Munenori Watanuki, Tsukasa Yonemoto, Satoshi Abe, Hirohisa Katagiri, Yoshihiro Nishida, Akihito Nagano, Yoshiyuki Suehara, Tomoko Kataoka, Haruhiko Fukuda, Toshifumi Ozaki, Yukihide Iwamoto

    JOURNAL OF CLINICAL ONCOLOGY   38 ( 15 )   2020.5

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  • Transtibial pullout repair of the lateral meniscus posterior root tear combined with anterior cruciate ligament reconstruction reduces lateral meniscus extrusion: A retrospective study. International journal

    Yuki Okazaki, Takayuki Furumatsu, Yusuke Kamatsuki, Yoshiki Okazaki, Shin Masuda, Takaaki Hiranaka, Yuya Kodama, Shinichi Miyazawa, Toshifumi Ozaki

    Orthopaedics & traumatology, surgery & research : OTSR   106 ( 3 )   469 - 473   2020.5

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    BACKGROUND: Lateral meniscus (LM) posterior root tear (PRT) is often associated with anterior cruciate ligament (ACL) injury and can result in rotational instability, joint overloading, and degenerative changes in the knee. Improved rotational stability and kinematics have been reported after LMPRT repair. However, it is unclear what repair technique can achieve the greatest reduction in LM extrusion (LME). HYPOTHESIS: We hypothesized that transtibial pullout repair would decrease LME to a greater extent than other repair techniques. PATIENTS AND METHODS: Seventeen patients with ACL injury and complete LMPRT were evaluated. Nine underwent ACL reconstruction (ACLR) and transtibial pullout repair, and eight underwent ACLR and other repairs such as inside-out suturing. Double-bundle ACLR was performed using hamstring tendons, and LMPRT pullout repair was performed through the bone tunnel for the posterolateral bundle. Magnetic resonance imaging was performed immediately preoperatively and at>6 months postoperatively, and LME was measured from coronal images only. RESULTS: A significantly greater decrease in the value of LME from pre- to postoperative measurement was observed in the transtibial pullout repair group (-0.5±0.7mm) than in the other-repair group (1.0±0.9mm, p<0.01). Pre- and postoperative LME measurements were not significantly different between the two groups. DISCUSSION: The most important finding of this study was that transtibial pullout repair resulted in a greater decrease in LME than other repair techniques in patients with ACL injury and LMPRT. This technique might be useful for restoring hoop tension by decreasing LME. LEVEL OF EVIDENCE: III, comparative retrospective study.

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  • Multimodal treatment including standard chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for the Ewing sarcoma family of tumors in Japan: Results of the Japan Ewing Sarcoma Study 04. International journal

    Motoaki Chin, Ryohei Yokoyama, Minako Sumi, Hajime Okita, Akira Kawai, Ako Hosono, Yuhki Koga, Hideki Sano, Hiroyoshi Watanabe, Toshifumi Ozaki, Hideo Mugishima

    Pediatric blood & cancer   67 ( 5 )   e28194   2020.5

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    BACKGROUND: The survival rate in patients with Ewing sarcoma family of tumors (ESFT) in Japan was reported to be < 50% in the 1990s. The Japan Ewing Sarcoma Study Group was established to improve the prognosis of ESFT in Japan. The aim of this phase II trial was to determine the efficacy and safety of multimodal treatment for nonmetastatic ESFT. PROCEDURE: Patients with ESFT aged < 30 years were eligible for participation. The chemotherapy regimen consisted of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) repeating every 21 days for 52 weeks. Local treatment included surgery and/or radiation therapy (0-55.8 Gy) based on the margin of resection and histologic response. The primary endpoint was progression-free survival (PFS) at three years. The study was designed to test whether the lower limit of the 90% confidence interval for PFS would exceed the threshold of 60%. The planned sample size was 53 patients, allowing for 10% of patients being ineligible. RESULTS: Of the 53 patients screened for entry, seven were deemed ineligible. Forty-six patients were considered as the per-protocol set and were used for the efficacy analysis. Three-year PFS was 71.7% (0.59-0.81). Estimated five-year PFS and overall survival were both 69.6%. Although no previously unknown adverse event was reported, three patients developed secondary malignancies (acute lymphoblastic leukemia, myelodysplastic syndrome, and osteosarcoma, one patient each). CONCLUSIONS: Multimodal treatment with standard VDC-IE chemotherapy improved the prognosis for patients with ESFT in Japan, although statistical confirmation of efficacy compared to historical control was not achieved.

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  • An accelerometer-based navigation system provides acetabular cup orientation accuracy comparable to that of computed tomography-based navigation during total hip arthroplasty in the supine position. International journal

    Tomonori Tetsunaga, Kazuki Yamada, Tomoko Tetsunaga, Tomoaki Sanki, Yoshi Kawamura, Toshifumi Ozaki

    Journal of orthopaedic surgery and research   15 ( 1 )   147 - 147   2020.4

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    BACKGROUND: Inadequate acetabular component orientation is associated with postoperative impingement, dislocation, and accelerated polyethylene wear. Computed tomography (CT)-based navigation systems provide accuracy for total hip arthroplasty (THA) but are not available in all facilities. Accelerometer-based navigation systems are inexpensive, but their accuracy remains undetermined. This study compares the accuracy of cup orientation in THA using CT-based and accelerometer-based navigation systems. METHODS: This retrospective study included 35 consecutive patients (11 males, 24 females; mean age, 65 years) who underwent primary cementless THA via an anterolateral approach in the supine position. Both CT-based and accelerometer-based navigation systems were used simultaneously. The accuracy of cup orientation was compared between the two systems using postoperative CT. RESULTS: The accuracy of cup inclination was 2.7° ± 2.0° in the CT-based group and 3.3° ± 2.4° in the accelerometer-based group. The accuracy of cup anteversion was 2.8° ± 2.6° in the CT-based group and 3.4° ± 2.2° in the accelerometer-based group. No significant difference was observed in cup inclination (p = 0.29) or cup anteversion (p = 0.34) between CT-based and accelerometer-based navigation. CONCLUSIONS: The accuracy of cup positioning did not differ significantly between CT-based and accelerometer-based navigation systems.

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  • Acute Calcific Retropharyngeal Tendinitis with Eggshell-like Calcification: Case Report and Literature Review on Time-course Changes in Imaging Findings. International journal

    Norio Yamamoto, Takashi Watari, Keisuke Kawasaki, Yuzuru Matsui, Toshifumi Ozaki

    Cureus   12 ( 4 )   e7611   2020.4

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    Acute calcific retropharyngeal tendinitis is a rare disease, and few studies have reported the radiological findings of its time-course in detail. These radiological findings vary according to the calcific stage. We report a case of acute calcific retropharyngeal tendinitis with eggshell-like calcification detected on follow-up computed tomography (CT). We also review pertinent literature on calcific retropharyngeal tendinitis, with a focus on time-course changes in imaging findings. A 54-year-old Japanese woman presented with acute severe neck pain. She also had a limited range of motion in the rotation of her neck and moderate pain and discomfort during swallowing. Plain radiographs of the cervical spine showed no apparent abnormality. CT revealed massive retropharyngeal calcification in front of the C1-C2 vertebrae. The patient was diagnosed with acute calcific retropharyngeal tendinitis and treated with a soft collar and non-steroidal anti-inflammatory drugs. Two weeks later, the neck pain and dysphagia improved. At the one-month follow-up, CT showed residual marginal calcification, which was diminishing in size, suggesting eggshell-like calcification. We believe that although the eggshell calcification appearance is extremely rare, it is important to note this atypical presentation of acute calcific retropharyngeal tendinitis.

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  • Letter to the editor concerning "Li P., lv Y., zhou F., et al. medial wall fragment involving large posterior cortex in Pertrochanteric femur fractures: A notable preoperative risk factor for implant failure. injury. 2020". International journal

    Norio Yamamoto, Tomoyuki Noda, Toshifumi Ozaki

    Injury   51 ( 4 )   1146 - 1146   2020.4

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  • Multidisciplinary treatment system for bone metastases for early diagnosis, treatment and prevention of malignant spinal cord compression. International journal

    Eiji Nakata, Shinsuke Sugihara, Yoshifumi Sugawara, Ryuichi Nakahara, Takayuki Furumatsu, Tomonori Tetsunaga, Toshiyuki Kunisada, Kazuo Nakanishi, Yoshiteru Akezaki, Toshifumi Ozaki

    Oncology letters   19 ( 4 )   3137 - 3144   2020.4

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    Malignant spinal cord compression (MSCC) is a serious complication of cancers. The present study aimed to establish a multidisciplinary treatment system for urgent magnetic resonance imaging (MRI) and referral to orthopedists in order to prevent neurological deficits caused by MSCC. In the present study, the extent to which this system achieved early diagnosis and treatment and prevented MSCC-caused neurological deficits was examined. The records from patients with neurological deficits caused by MSCC before (between April 2007 and March 2012; group A) and after (between April 2012 and March 2017; group B) the establishment of the multidisciplinary system at the Shikoku Cancer Center (Ehime, Japan) were retrospectively evaluated. The numbers of patients with neurological deficits were 38 and 7 in groups A and B, respectively. All patients received radiotherapy. The incidence of neurological deficits was 13.2 and 3.4% in groups A and B, respectively (P<0.001). The proportion of patients with improvement in the severity of neurological deficits was 5.3 and 28.6% in groups A and B, respectively (P<0.001). The interval between physicians' recognition of a neurological deficit and MRI and the start of treatment, the number of cases, and the severity of neurological deficits were evaluated in groups A and B. The median interval between recognition of a neurological deficit by physicians and MRI was 3 and 0 days in groups A and B, respectively (P<0.001). The median interval between physicians' recognition of a neurological deficit and the start of treatment was 3 and 0 days in groups A and B, respectively (P<0.001). By using a multidisciplinary treatment system, the incidence and severity of neurological deficits following treatment were significantly improved. Therefore, the multidisciplinary treatment system used in the present study may be useful for early diagnosis, treatment and prevention of MSCC in patients with bone metastases.

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  • Non-traumatic Atypical Peri-implant Femoral Fracture at the Distal Screw after Short Femoral Nail Fixation for a Pertrochanteric Fracture.

    Norio Yamamoto, Tomoyuki Dan'ura, Tomoyuki Noda, Toshifumi Ozaki

    Acta medica Okayama   74 ( 2 )   151 - 157   2020.4

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    This is the second report of an atypical peri-implant femoral fracture occurring at the distal screw after intramedullary nail fixation of a pertrochanteric fracture. A 94-year-old Japanese female with a 5-year history of alendronate intake presented with prodromal pain in her right thigh after intramedullary nail fixation. Plain radiographs showed an incomplete noncomminuted transverse fracture at the distal screw, suggesting an atypical peri-implant femoral fracture. The pathogenesis of an atypical peri-implant femoral fracture could be a combined systemic bone metabolism disorder and repetitive overloading at the screw, similar to the pathogenesis of an atypical periprosthetic femoral fracture around stem implantation.

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  • External iliac artery thrombosis following open reduction of acetabular fracture: a case report and literature review. International journal

    Norio Yamamoto, Tomoyuki Noda, Taichi Saito, Takenori Uehara, Yasunori Shimamura, Toshifumi Ozaki

    Archives of orthopaedic and trauma surgery   140 ( 4 )   481 - 485   2020.4

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    BACKGROUND: Postoperative thrombosis of the external iliac artery (EIA) following open reduction and internal fixation for acetabular fracture is extremely rare. PURPOSE: To report a patient with EIA thrombosis following open reduction and internal fixation using the modified ilioinguinal approach for acetabular fractures. STUDY DESIGN: This is a case report of a 69-year-old male with a left acetabular fracture who was treated surgically. METHODS: A 69-year-old male presented with left hip pain after a 1.5-m fall. Radiographs revealed left acetabular anterior wall and posterior hemitransverse fractures with dome impaction. Computed tomography (CT) showed atherosclerotic changes in many arteries. Open reduction and internal fixation were performed using the modified ilioinguinal approach. Adhesion around the external iliac vessels was severe, and the external iliac vein (EIV) ruptured during exposure. After EIV repair, anatomical reduction was achieved and the fracture was fixed using a reconstruction plate. Nine hours after surgery, the left lower limb showed acute ischemic symptoms. Contrast-enhanced CT indicated complete occlusion of the left EIA. The patient was immediately taken for a thrombectomy via EIA cut-down using a Fogarty catheter. Postoperatively, he had palpable dorsalis pedis and posterior tibial pulses; however, post-reperfusion compartment syndrome developed. Fasciotomy of the left leg was performed. RESULTS: At the 2-year and 4-month follow-up, he was pain-free in his hip and leg. Although he was walking with a cane, activity was limited due to a mild foot drop. CONCLUSIONS: It is very important for surgeons to consider EIA thrombosis as a potential complication following open reduction and internal fixation. In this case, EIA thrombosis could be explained by preoperative atherosclerotic changes and intraoperative vascular handling procedures. Preoperative screening and management, and meticulous surgical procedures are necessary for patients with a high risk of thrombosis.

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  • Early chondral damage following meniscus repairs with anterior cruciate ligament reconstruction. International journal

    Takaaki Hiranaka, Takayuki Furumatsu, Yusuke Kamatsuki, Kazuhisa Sugiu, Shinichi Miyazawa, Yoshiki Okazaki, Shin Masuda, Yuki Okazaki, Yuya Kodama, Toshifumi Ozaki

    Asia-Pacific journal of sports medicine, arthroscopy, rehabilitation and technology   20   1 - 5   2020.4

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    Background: Meniscal tears are commonly observed in patients with anterior cruciate ligament (ACL) injuries. Meniscal repair has become a common procedure for the injured meniscus, and good clinical outcomes have been reported in such cases when used concurrently with ACL reconstruction. However, it is unclear whether early chondral damage progression can be prevented following meniscal repair with ACL reconstruction, as meniscal damage is a potential risk factor for the development of osteoarthritis. The purpose of this study was to evaluate the zone-specific chondral damage that occurs after arthroscopic meniscal repair with concomitant ACL reconstruction. Our hypothesis was that meniscal repair with ACL reconstruction would not decrease the rate of progression of chondral damage compared to that observed in isolated ACL reconstruction with intact menisci. Methods: This study included 40 patients who underwent anatomic double-bundle ACL reconstruction. We divided the patients into the following two groups: Group A with an intact meniscus (20 knees) and Group M requiring meniscal repair (20 knees). Chondral damage was evaluated arthroscopically in six compartments and 40 sub-compartments, and these features were graded using the International Cartilage Repair Society lesion classification. The cartilage damage in each sub-compartment and compartment was compared between the two groups both at reconstruction and at second-look arthroscopy (average 16 months postoperatively). At the latest follow-up examination (average 37 months postoperatively), the International Knee Documentation Committee (IKDC) score was compared between the two groups. Results: Group M had a significantly worse cartilage status than Group A in five sub-compartments (mainly in the medial compartment) at reconstruction and in nine sub-compartments (mainly in the bilateral compartments) at second-look arthroscopy. The mean IKDC score was better in Group A than in Group M (Group A; 90 vs. Group M; 86). The overall success rate of meniscal repairs was 92% (23 of 25 menisci) at second-look arthroscopy. Conclusion: The progression of post-traumatic chondral damage may occur at a faster rate in patients who require ACL reconstruction and meniscal repair than in patients with intact menisci.

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  • Atypical ulnar fracture with atypical femoral fracture: A case report and literature review.

    Norio Yamamoto, Mika Yamauchi, Tomoyuki Noda, Yuzuru Matsui, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   2020.3

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  • Pulmonary resection in a prone position for lung cancer invading the spine. Reviewed

    Shunsaku Miyauchi, Junichi Soh, Kazuhiko Shien, Masato Tanaka, Hiromasa Yamamoto, Toshifumi Ozaki, Shinichi Toyooka

    General thoracic and cardiovascular surgery   68 ( 3 )   298 - 301   2020.3

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    The prone position is usually not selected for pulmonary resection. The intraoperative body position is an important issue in surgery for non-small cell lung cancer invading the spine because the standard intraoperative body position for a vertebrectomy is a prone position, while that for a pulmonary resection is a lateral decubitus position. Intraoperative changes in body position can cause several complications. Using an O-arm with a navigation system, a partial vertebrectomy was completed with the patient in a prone position thanks to the recognition of accurate surgical margins in the vertebral body; then, without changing the patient's body position, a lobectomy with systemic lymph node dissection was performed via a posterior approach. Especially for procedures requiring a wide resection of the chest wall, a prone position can be selected for a lobectomy with systemic lymph node dissection via a posterior approach without any significant difficulties.

    DOI: 10.1007/s11748-019-01113-7

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  • 腰椎変性後側彎症に対する前後合併手術後における静脈血栓塞栓症の検討

    三澤 治夫, 瀧川 朋亨, 鉄永 倫子, 山根 健太郎, 村岡 聡介, 辻 寛謙, 高尾 真一郎, 尾崎 敏文

    Journal of Spine Research   11 ( 3 )   442 - 442   2020.3

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  • 頸髄症が四肢体幹筋量及び身体機能に与える影響 サルコペニア、フレイルに注目した検討

    辻 寛謙, 三澤 治夫, 瀧川 朋亨, 山根 健太郎, 村岡 聡介, 上甲 良二, 高尾 真一郎, 尾崎 敏文

    Journal of Spine Research   11 ( 3 )   565 - 565   2020.3

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  • 脊髄損傷患者の骨密度と海綿骨スコアについての検討

    村岡 聡介, 瀧川 朋亨, 三澤 治夫, 山根 健太郎, 辻 寛謙, 高尾 真一郎, 尾崎 敏文

    Journal of Spine Research   11 ( 3 )   594 - 594   2020.3

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  • 側彎を有する成人脊柱変形患者における腰椎CTハンスフィールド値の検討

    山根 健太郎, 三澤 治夫, 瀧川 朋亨, 鉄永 倫子, 村岡 聡介, 辻 寛謙, 高尾 真一郎, 尾崎 敏文

    Journal of Spine Research   11 ( 3 )   504 - 504   2020.3

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  • 椎体CT値(Hounsfield Unit)は椎体内の高位に伴って変化する CT値による椎体骨強度の評価法を確立させるために

    高尾 真一郎, 三澤 治夫, 瀧川 朋亨, 山根 健太郎, 村岡 聡介, 辻 寛謙, 尾崎 敏文

    Journal of Spine Research   11 ( 3 )   520 - 520   2020.3

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  • 脊髄腫瘍の複数回手術症例についての検討

    村岡 聡介, 瀧川 朋亨, 三澤 治夫, 山根 健太郎, 辻 寛謙, 高尾 真一郎, 尾崎 敏文

    Journal of Spine Research   11 ( 3 )   282 - 282   2020.3

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  • Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy. Reviewed International journal

    Hiroshi Tazawa, Joe Hasei, Shuya Yano, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancers   12 ( 2 )   2020.2

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    Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.

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  • Comparison of the accuracy of CT- and accelerometer-based navigation systems for cup orientation in total hip arthroplasty. International journal

    Tomonori Tetsunaga, Kazuki Yamada, Tomoko Tetsunaga, Takayuki Furumatsu, Tomoaki Sanki, Yoshi Kawamura, Toshifumi Ozaki

    Hip international : the journal of clinical and experimental research on hip pathology and therapy   1120700020904940 - 1120700020904940   2020.2

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    BACKGROUND: The accuracies of various navigation systems in total hip arthroplasty (THA) have been described; however, the accuracy of cup orientation with an accelerometer-based navigation system has not been reported. The purpose of this study was to compare the accuracies of computed tomography (CT)- and accelerometer-based navigation systems for cup orientation in THA. METHODS: In this prospective study, 30 patients who underwent cementless THA via anterolateral approach in the lateral decubitus position were analysed. A CT-based navigation system (30 hips) and an accelerometer-based navigation system (30 hips) were used simultaneously. The accuracy of cup orientation (absolute difference between intraoperative vs. postoperative measurements) was compared between the navigation systems using postoperative CT. RESULTS: The accuracy of cup inclination was 3.2 ± 2.4° in the CT-based navigation group and 4.1 ± 3.7° in the accelerometer-based navigation group (p = 0.3035). The accuracy of cup anteversion was 3.0° ± 2.5° in the CT-based navigation group and 6.8° ± 4.8° in the accelerometer-based navigation group. Cup anteversion was significantly more accurate with the CT-based navigation system than with accelerometer-based navigation (p = 0.0009). Multiple regression analysis demonstrated that the malposition in cup anteversion was positively correlated with the change in pelvic tilt and loosening of the reference antenna. CONCLUSIONS: Although, these results are only true for this specific accelerometer system, cup positioning was significantly more accurate with the CT-based navigation system than an accelerometer-based navigation in the lateral decubitus position. This is because of considerable discrepancies in the sagittal pelvic tilt, resulting in variability in cup anteversion angle with the use of an accelerometer-based navigation system.

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  • Idiopathic Chondrolysis of the Hip Treated by Immunosuppressive Therapy and Arthroscopic Intervention.

    Hirosuke Endo, Hirofumi Akazawa, Masato Yashiro, Kazuki Yamada, Tomoaki Sanki, Tomonori Tetsunaga, Keiichiro Nishida, Takayuki Furumatsu, Toshifumi Ozaki

    Acta medica Okayama   74 ( 1 )   77 - 81   2020.2

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    Idiopathic chondrolysis of the hip (ICH), a very rare disorder of unknown etiology, occurs mainly in female adolescents. Characterized by pain, limp, stiffness and radiological narrowing joint space from the rapid destruction of the articular cartilage, ICH sometimes results in ankyloses. We present the case of a 10-year-old girl diagnosed with ICH based on arthroscopic inspection and synovium biopsy. The femoral deformity appeared gradually, like a cam-type femoroacetabular impingement. She was treated with intensive rehabilitation and immunosuppressive drug. We later performed an arthroscopic bumpectomy for residual symptoms. She achieved a favorable outcome as a 15-year-old at the latest follow-up.

    DOI: 10.18926/AMO/57957

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  • Ten-Year Outcomes of Total Hip Arthroplasty Using Fit-and-Fill Type Cementless Collared Straight Stem Implants: Relationship between the Initial Contact Status and Stress Shielding.

    Tomoaki Sanki, Hirosuke Endo, Tomonori Tetsunaga, Takayuki Furumatsu, Kazuki Yamada, Toshifumi Ozaki

    Acta medica Okayama   74 ( 1 )   7 - 15   2020.2

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    We investigated the relationship between the initial contact status and stress shielding in total hip arthroplasty (THA) using fit-and-fill type straight-stem implants. In addition we evaluated the clinical and radiographic outcomes. Subjects were 100 hips of 94 patients who underwent THA and were followed-up for ≥10 years. Contact areas with the femoral cortical bone were investigated according to the zonal distribution of Gruen using postoperative CT images. Depending on the number of contact areas, the patients were classified into high contact [HC], medium contact [MC], and low contact [LC] groups. Radiographic and clinical outcomes were evaluated. In the HC group (20 hips), severe stress shielding was observed in 12 hips, which was statistically significant (p=0.008). In the LC group (29 hips), mild stress shielding was observed in 27 hips which was statistically significant (p<0.001). No significant differences were observed among the 3 groups in clinical outcomes, Harris hip score (p=0.719) or Japanese Orthopedic Association (JOA) score (p=0.301). In insertion of cementless collared fit-and-fill type straight-stem implants, severe late stress shielding of the femoral bone may occur if high contact of the femoral component is achieved. However, the degree of stress shielding does not result in adverse clinical outcomes.

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  • The Masquelet technique for septic arthritis of the small joint in the hands: Case reports. International journal

    Taichi Saito, Tomoyuki Noda, Hiroya Kondo, Koji Demiya, Satoshi Nezu, Suguru Yokoo, Minami Matsuhashi, Takenori Uehara, Yasunori Shimamura, Masayuki Kodama, Toshifumi Ozaki

    Trauma case reports   25   100268 - 100268   2020.2

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    Septic arthritis in distal interphalangeal (DIP) joints sometimes occurs in association with mucous cysts or after the surgical treatment of mallet fingers. Recently, several studies have demonstrated the effectiveness of the Masquelet technique in the treatment of bone defects caused by trauma or infection. However, only few studies have reported the use of this technique for septic arthritis in small joints of the hand, and its effectiveness in treating septic arthritis in DIP joints remains unclear. We report the clinical and radiological outcomes of three patients who were treated with the Masquelet technique for septic arthritis in DIP joints. One patient had uncontrolled diabetes and another had rheumatoid arthritis treated with methotrexate and prednisolone. The first surgical stage involved thorough debridement of the infection site, including the middle and distal phalanx. We placed an external fixator from the middle to the distal phalanx and then packed the cavity of the DIP joint with antibiotic cement bead of polymethylmethacrylate (40 g) including 2 g of vancomycin and 200 mg of minocycline. At 4-6 weeks after the first surgical stage, the infection had cleared, and the second surgical stage was performed. The external fixator and cement bead were carefully removed while carefully preserving the surrounding osteo-induced membrane. The membrane was smooth and nonadherent to the cement block. In the second surgical stage, an autogenous bone graft was harvested from the iliac bone and inserted into the joint space, within the membrane. The bone graft, distal phalanx, and middle phalanx were fixed with Kirschner wires and/or a soft wire. Despite the high risk of infection, bone union was achieved in all patients without recurrence of infection. Although the Masquelet technique requires two surgeries, it can lead to favorable clinical and radiological outcomes for infected small joints of the hand.

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  • Bone microarchitectural analysis using ultra-high-resolution CT in tiger vertebra and human tibia. International journal

    Ryota Inai, Ryuichi Nakahara, Yusuke Morimitsu, Noriaki Akagi, Youhei Marukawa, Toshi Matsushita, Takashi Tanaka, Akihiro Tada, Takao Hiraki, Yoshihisa Nasu, Keiichiro Nishida, Toshifumi Ozaki, Susumu Kanazawa

    European radiology experimental   4 ( 1 )   4 - 4   2020.1

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    BACKGROUND: To reveal trends in bone microarchitectural parameters with increasing spatial resolution on ultra-high-resolution computed tomography (UHRCT) in vivo and to compare its performance with that of conventional-resolution CT (CRCT) and micro-CT ex vivo. METHODS: We retrospectively assessed 5 tiger vertebrae ex vivo and 16 human tibiae in vivo. Seven-pattern and four-pattern resolution imaging were performed on tiger vertebra using CRCT, UHRCT, and micro-CT, and on human tibiae using UHRCT. We measured six microarchitectural parameters: volumetric bone mineral density (vBMD), trabecular bone volume fraction (bone volume/total volume, BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and connectivity density (ConnD). Comparisons between different imaging resolutions were performed using Tukey or Dunnett T3 test. RESULTS: The vBMD, BV/TV, Tb.N, and ConnD parameters showed an increasing trend, while Tb.Sp showed a decreasing trend both ex vivo and in vivo. Ex vivo, UHRCT at the two highest resolutions (1024- and 2048-matrix imaging with 0.25-mm slice thickness) and CRCT showed significant differences (p ≤ 0.047) in vBMD (51.4 mg/cm3 and 63.5 mg/cm3 versus 20.8 mg/cm3), BV/TV (26.5% and 29.5% versus 13.8 %), Tb.N (1.3 l/mm and 1.48 l/mm versus 0.47 l/mm), and ConnD (0.52 l/mm3 and 0.74 l/mm3 versus 0.02 l/mm3, respectively). In vivo, the 512- and 1024-matrix imaging with 0.25-mm slice thickness showed significant differences in Tb.N (0.38 l/mm versus 0.67 l/mm, respectively) and ConnD (0.06 l/mm3 versus 0.22 l/mm3, respectively). CONCLUSIONS: We observed characteristic trends in microarchitectural parameters and demonstrated the potential utility of applying UHRCT for microarchitectural analysis.

    DOI: 10.1186/s41747-019-0135-0

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  • The role of chemotherapy and radiotherapy in localized extraskeletal osteosarcoma Reviewed

    Marilyn Heng, Abha Gupta, Peter W. Chung, John H. Healey, Max Vaynrub, Peter S. Rose, Matthew T. Houdek, Patrick P. Lin, Andrew J. Bishop, Francis J. Hornicek, Yen Lin Chen, Santiago Lozano-Calderon, Ginger E. Holt, Ilkyu Han, David Biau, Xiaohui Niu, Nicholas M. Bernthal, Peter C. Ferguson, Jay S. Wunder, Takafumi Ueda, Shigeki Kakunaga, Akira Kawai, Hideshi Sugiura, Teruki Kidani, Toshiyuki Kunisasa, Toshifumi Ozaki, Keisuke Ae, Akihito Nagano, Takatoshi Ohno, Koji Hiraoka, Norio Yamamoto, Hiroyuki Tsuchiya, Yoshihiro Matsumoto, Takashi Yanagawa, Robart Nakayama, Hideo Morioka, Tadahiko Kubo, Shoji Simose, Yoshiki Yamagami, Tetsuji Yamamoto, Motohiro Kawasaki, Tomoaki Torigoe, Yasuo Yazawa, Toru Akiyama, Tabu Gokita, Jun Manabe, Mitsunori Kaya, Makoto Emori, Tomoki Nakamura, Akihiko Matsumine, Shinsuke Sugihara, Masahiro Yokouchi, Setsuro Komiya, Yoshiyuki Suehara, Tatsuya Takagi, Teruya Kawamoto, Junji Wasa, Tsukasa Yonemoto, Takeshi Ishii, Ichiro Baba, Manabu Hoshi, Kenichiro Hamada, Norifumi Naka, Tsukasa Sotobori, Nobuhito Araki, Tomotake Okuma, Takahiro Goto, Hiroshi Kobayashi, Hirotaka Kawano, Masami Hosaka, Hiroyuki Futani, Hiroaski Hiraga, Yoshihiro Nishida, Anthony Griffin, Albiruni R.Abdul Razak, David Benjamin Shultz, Charles Catton, Steven Robinson, Shreyaskumar R. Patel, Valerae O. Lewis, B. Ashleigh Guadagnolo, Thomas DeLaney, Haotong Wang, Kevin Raskin, Alexandra K. Callan, Robert Henshaw, Marc Isler, Sophie Mottard, Wei Ming Chen, Frank Traub, Tom Wei Wu Chen, Robert E. Turcotte, Darin Davidson, Per Ulf Tunn, Herbert Loong, Michelle Ghert, Joel Werier, Paul Clarkson, John A. Abraham

    European Journal of Cancer   125   130 - 141   2020.1

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    © 2019 Elsevier Ltd Purpose: The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. Patients and methods: Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan–Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. Results: 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%–62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26–0.80], p = 0.01). Conclusion: Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.

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  • Medial meniscus posterior root repair decreases posteromedial extrusion of the medial meniscus during knee flexion. International journal

    Yuki Okazaki, Takayuki Furumatsu, Yoshiki Okazaki, Shin Masuda, Takaaki Hiranaka, Yuya Kodama, Yusuke Kamatsuki, Shinichi Miyazawa, Tomonori Tetsunaga, Toshifumi Ozaki

    The Knee   27 ( 1 )   132 - 139   2020.1

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    BACKGROUND: Medial meniscus (MM) medial extrusion in the coronal plane does not always improve, even after repair. This study aimed to determine the extent of posteromedial extrusion of the MM during knee flexion before and after MM pullout repair using three-dimensional magnetic resonance imaging (MRI). METHODS: Data from 14 patients (mean age, 63.4 years; 86% female) who had undergone MM pullout repair at the current institution between August 2017 and October 2018 were retrospectively reviewed. The MRIs were performed pre-operatively and ≥3 months postoperatively. Three-dimensional MRIs of the tibial surface and MM were evaluated using Tsukada's measurement method before and after pullout repair. The expected center of MM posterior root attachment (point A), the point on the extruded edge of the MM farthest away from point A (point E), and the point of intersection of a line through the posteromedial corner of the medial tibial plateau and a line connecting points A and E (point I) were identified. Subsequently, the pre-operative and postoperative AE and IE distances were calculated and compared. RESULTS: Point E was laterally shifted by the pullout repair, whereas point I showed no significant change. The postoperative IE distance (6.7 mm) was significantly shorter than the pre-operative one (9.1 mm, P < 0.01). The postoperative AE distance (29.3 mm) was significantly shorter than the pre-operative one (31.5 mm, P < 0.01). CONCLUSIONS: The AE and IE distances significantly decreased after MM posterior root repair, suggesting that transtibial pullout repair may be useful in reducing posteromedial extrusion of the MM.

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  • Relationship between oral condition and risk factors for jaw osteonecrosis in patients with hip fractures.

    Norio Yamamoto, Shintaro Sukegawa, Yuka Sukegawa-Takahashi, Toru Honda, Yoshihiko Furuki, Keisuke Kawasaki, Toshifumi Ozaki

    The journal of medical investigation : JMI   67 ( 3.4 )   328 - 331   2020

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    Purpose : Antiresorptive agents, such as bisphosphonates, are useful for the prevention of the recurrence of hip fractures. However, their administration has a risk of antiresorptive agent-related osteonecrosis of the jaw (ARONJ), and risk factors include poor oral hygiene. It is difficult for an orthopedic surgeon to examine a patient's oral condition thoroughly. This study evaluated the relationship between risk factors for ARONJ and intraoral findings in hip fracture patients. Materials and Methods : We evaluated 79 patients (average age of 82.2 years) with hip fracture surgery who underwent an oral assessment by dentists. The risk assessments of the intraoral findings were classified into four levels (levels 0-3), with levels 2 and 3 requiring dental treatment intervention. Data that could be extracted as risk factors of ARONJ were also examined. Results : Level 1 was found most frequently (54.4%), followed by level 0 (35.4%), level 2 (8.9%), level 3 (1.3%). The area under the receiver operating characteristic curve for the number of risk factors for the two groups (dental treatment intervention required and unnecessary) and oral findings were 0.732. When the cut-off value was set to two risk factors, the specificity and sensitivity was 53.5% and 87.5%. Conclusions : For hip fracture patients with a more than 2 risk factors, dental visits are recommended to prevent ARONJ. This is a useful evaluation method that can be used to screen for ONJ from data obtained from other risk factors, even if it is difficult to evaluate the oral condition in hospitals where dentists are absent. J. Med. Invest. 67 : 328-331, August, 2020.

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  • Medial and Lateral Meniscus Posterior Root Tears with an Intact Anterior Cruciate Ligament. International journal

    Yuki Okazaki, Takayuki Furumatsu, Yuya Kodama, Yoshinori Matsumoto, Motoki Takahashi, Toshifumi Ozaki

    Case reports in orthopedics   2020   8842167 - 8842167   2020

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    Background: Medial meniscus (MM) posterior root tear (PRT) is often caused by meniscal degeneration, whereas lateral meniscus (LM) PRT is mainly caused by trauma, especially trauma associated with anterior cruciate ligament (ACL) injuries. Although there are a few reports on PRTs of both menisci with an ACL injury, to our knowledge, there is no report on those with an intact ACL. Thus, the purpose of this study was to describe a rare case of both meniscal PRTs with an intact ACL. Case Presentation. A 67-year-old woman complained of right knee pain during weeding in a deep knee flexion position. At presentation, three days after the injury, physical examination revealed signs of meniscal injury without ACL rupture. Magnetic resonance imaging showed PRTs of both menisci and damaged cartilage, especially on the medial femoral condyle and lateral tibial plateau. MM was sutured using the FasT-Fix dependent modified Mason-Allen suture technique, and LM by a single simple stitch using the Knee Scorpion suture passer. Referring to previous cadaveric studies, transtibial pullout repair using a single tibial tunnel for MM fixation was performed. The stability of the repaired menisci was checked by probing during second-look arthroscopy at one year after the primary surgery, and no meniscal signs and symptoms were present at the last follow-up one year after the surgery. Conclusions: This rare case showed PRTs of both menisci with an intact ACL. We speculated that, in this case, both roots tore because of the degenerative menisci. A good clinical outcome was achieved after single-transtibial pullout repair. This technique may be an effective surgical approach for PRTs of both menisci.

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  • The factors driving self-efficacy in intractable chronic pain patients: a retrospective study. International journal

    Hironori Tsuji, Tomoko Tetsunaga, Tomonori Tetsunaga, Keiichiro Nishida, Haruo Misawa, Toshifumi Ozaki

    Journal of orthopaedic surgery and research   14 ( 1 )   473 - 473   2019.12

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    BACKGROUND: The fear-avoidance model is a theoretical paradigm for explaining acute and chronic pain. In this model, pain catastrophizing plays an important role. On the other hand, self-efficacy influences whether patients view their pain optimistically, ultimately preventing the conversion of pain into intractable pain. The aim of the present study was to evaluate the factors that influence self-efficacy in patients with chronic pain. METHODS: Study participants included 147 outpatients (35 men, 112 women) with intractable chronic pain who visited our hospital between September 2014 and July 2015. Their mean age was 71.0 (range 32-92) years. Pain sites were as follows: low back, 97 patients; knee, 71 patients; shoulder, 34 patients; and hip, 15 patients. All patients were assessed using the following measures: Numeric Rating Scale (NRS), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), Pain Disability Assessment Scale (PDAS), and Pain Self-Efficacy Questionnaire (PSEQ). All participants were further divided into two groups based on median PSEQ scores (group L: PSEQ of 35 points or less, n = 74; group H: PSEQ greater than 35 points, n = 73). The factors that influenced self-efficacy in these patients were analyzed using univariate and multiple linear regression analyses. RESULTS: Significant differences were observed in gender; pain duration; and NRS, PDAS, HADS, and PCS scores between group L and group H. Multiple linear regression analysis revealed that self-efficacy was correlated with PDAS score, HADS depression score, and pain duration. CONCLUSIONS: Patients with longer pain duration indicated greater self-efficacy and patients with higher pain disability and depression exhibited lower self-efficacy.

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  • Multipotent Neurotrophic Effects of Hepatocyte Growth Factor in Spinal Cord Injury. International journal

    Kentaro Yamane, Haruo Misawa, Tomoyuki Takigawa, Yoshihiro Ito, Toshifumi Ozaki, Akihiro Matsukawa

    International journal of molecular sciences   20 ( 23 )   2019.12

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    Spinal cord injury (SCI) results in neural tissue loss and so far untreatable functional impairment. In addition, at the initial injury site, inflammation induces secondary damage, and glial scar formation occurs to limit inflammation-mediated tissue damage. Consequently, it obstructs neural regeneration. Many studies have been conducted in the field of SCI; however, no satisfactory treatment has been established to date. Hepatocyte growth factor (HGF) is one of the neurotrophic growth factors and has been listed as a candidate medicine for SCI treatment. The highlighted effects of HGF on neural regeneration are associated with its anti-inflammatory and anti-fibrotic activities. Moreover, HGF exerts positive effects on transplanted stem cell differentiation into neurons. This paper reviews the mechanisms underlying the therapeutic effects of HGF in SCI recovery, and introduces recent advances in the clinical applications of HGF therapy.

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  • Transtibial Pullout Repair Reduces Posterior Extrusion of the Medial Meniscus.

    Shin Masuda, Takayuki Furumatsu, Yoshiki Okazaki, Yusuke Kamatsuki, Yuki Okazaki, Yuya Kodama, Takaaki Hiranaka, Eiji Nakata, Toshifumi Ozaki

    Acta medica Okayama   73 ( 6 )   495 - 501   2019.12

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    Medial meniscus posterior root tear causes rapid knee cartilage degradation by inducing posteromedial displacement of the medial meniscus. We evaluated medial meniscus posterior extrusion before and after pullout repair for medial meniscus posterior root tear using magnetic resonance images. Twenty-eight patients with symptomatic medial meniscus posterior root tear were included. The inclusion criteria were: acute (< 3 months) or chronic (≥3 months) medial meniscus posterior root tear after painful popping events. The exclusion criteria were: other meniscus and anterior cruciate ligament injuries. We measured medial meniscus posterior extrusion and medial meniscus anteroposterior interval at knee flexion angles of 10° and 90° preoperatively and at 3 months postoperatively. The posterior extrusion at 90° knee flexion decreased from 4.42±1.38 mm preoperatively to 3.09±1.06 mm (p<0.001) postoperatively, while at 10° knee flexion it was -4.17±1.63 mm preoperatively and -3.77±1.72mm postoperatively, showing no significant change. The anteroposterior interval at 10° knee flexion increased from 19.74±4.27 mm preoperatively to 22.15±5.10 mm postoperatively (p<0.001); at 90° knee flexion, it increased from 16.81±4.51 mm preoperatively to 19.20±4.30 mm postoperatively (p<0.001). Medial meniscus posterior extrusion and movement decreased after pullout repair. Pullout repair for medial meniscus posterior root tear improves medial meniscus posterior extrusion, especially at 90° knee flexion.

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  • Intra-articular 1 g tranexamic acid administration during total knee arthroplasty is safe and effective for the reduction of blood loss and blood transfusion. International journal

    Yusuke Kamatsuki, Shinichi Miyazawa, Takayuki Furumatsu, Yuya Kodama, Tomohito Hino, Yoshiki Okazaki, Shin Masuda, Yuki Okazaki, Toshifumi Ozaki

    European journal of orthopaedic surgery & traumatology : orthopedie traumatologie   29 ( 8 )   1737 - 1741   2019.12

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    INTRODUCTION: The effect of tranexamic acid (TXA) on the incidence of venous thromboembolic events (VTEs) in total knee arthroplasty (TKA) as assessed by contrast-enhanced computed tomography (CT) is unclear. Thus, we investigated the efficacy and safety profiles of TXA administration during TKA. We hypothesised that intra-articular 1 g TXA administration would have a sufficient effect on the reduction of blood loss and transfusion rates without increasing VTE risk. MATERIALS AND METHODS: We retrospectively analysed 86 patients who underwent primary TKA from January 2014 to September 2017. The study comprised control (n = 45) and TXA (n = 41) groups. All patients underwent navigation-assisted TKA via the medial parapatellar approach. In those who received TXA, 1 g of intra-articular TXA was injected via a drain immediately following wound closure. The drain was clamped for 2 h and then reopened. Contrast-enhanced CT was performed 5-6 days after surgery to detect deep venous thrombosis (DVT) and pulmonary embolism (PE). Blood loss was calculated using the haemoglobin balance method. RESULTS: The mean postoperative volume of blood loss was 900 ± 296 mL vs 1216 ± 445 mL in the TXA vs control group (p < 0.01). Allogeneic blood transfusion was required for 0 (0%) vs 6 (13.3%) patients in the TXA vs control group (p = 0.013). There were no significant inter-group differences regarding DVT and PE incidence (p > 0.05). No case of symptomatic PE occurred. CONCLUSIONS: This study demonstrated that intra-articular 1 g TXA administration during TKA is safe and effective for reducing blood loss and blood transfusion without increasing VTE risk.

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  • A novel suture technique to reduce the meniscus extrusion in the pullout repair for medial meniscus posterior root tears. International journal

    Yoshiki Okazaki, Takayuki Furumatsu, Shinichi Miyazawa, Shin Masuda, Yuki Okazaki, Takaaki Hiranaka, Toshifumi Ozaki

    European journal of orthopaedic surgery & traumatology : orthopedie traumatologie   29 ( 8 )   1805 - 1809   2019.12

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    The medial meniscus (MM) posterior root has important functions in preventing an excessive loading stress during knee motion and degeneration of the articular cartilage. Although the transtibial pullout repair has become the gold standard for MM posterior root tears (MMPRTs), MM extrusion remains. In addition, during knee extension to deep flexion, the MM posterior segment in the MMPRT knee has been shown to translate toward the posteromedial direction, causing a notable MM posterior extrusion. Thus, the reduction in the MM posteromedial extrusion is one of the important postoperative outcomes to restore the meniscal function and eventually prevent the progression of knee osteoarthritis. The present technical note describes an arthroscopic technique addition to the pullout repair, in which an all-inside suture is inserted into the posteromedial part of the MM to reduce the MM posteromedial extrusion.

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  • Calcaneal insufficiency fractures following total knee arthroplasty: Classification and clinical findings. International journal

    Norio Yamamoto, Sachiyuki Tsukada, Jun Kawai, Daisuke Ueda, Tomoyuki Noda, Toshifumi Ozaki

    Injury   50 ( 12 )   2339 - 2345   2019.12

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    BACKGROUND: Calcaneal insufficiency fracture (IF) following total knee arthroplasty (TKA) is a rare disorder. This study aimed to examine the prevalence and clinical findings of calcaneal IF following TKA. METHODS: We retrospectively reviewed 3,585 consecutive patients undergoing primary TKA between 2012 and 2017 in four hospitals. Calcaneal IF following TKA was diagnosed by plain radiography or magnetic resonance imaging. First, we investigated the prevalence and clinical findings of calcaneal IF following TKA. Second, we classified calcaneal IF into three types based on its location: type 1, fracture by traction force around the Achilles tendon insertion; type 2, compression fracture around the posterior subtalar joint; and type 3, fracture by ground reaction force at the bottom of the calcaneus. Finally, we compared the clinical findings between calcaneal IF with and without TKA. RESULTS: Calcaneal IF following TKA was seen in 17 (0.5%) of the 3,585 patients undergoing primary TKA. All patients were female, with a mean age of 76.5 ± 5.9 years, relatively high body mass index (BMI), and osteoporosis. All fractures achieved bone union with conservative treatment. Type 1 fractures were the most common. Calcaneal IFs following TKA were significantly shorter in height and the patients had higher BMI than those without TKA. The locations of calcaneal IF following TKA varied, while only type 1 calcaneal IFs were seen in cases without TKA. However, there were no significant differences with regard to the bone union period or malunion between the two groups. CONCLUSIONS: Calcaneal IF should be suspected in patients presenting with ipsilateral foot pain following TKA, particularly in female patients with a relatively high BMI and osteoporosis. Calcaneal IF can be classified into three types based on the fracture location. These variations in calcaneal IF may be due to differences in conditions and changes in mechanical loading of the lower extremity and bone quality following TKA.

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  • Bilateral Anterior Cruciate Ligament Tear Combined with Medial Meniscus Posterior Root Tear.

    Takaaki Hiranaka, Takayuki Furumatsu, Yoshiki Okazaki, Yusuke Kamatsuki, Shin Masuda, Yuki Okazaki, Shota Takihira, Shinichi Miyazawa, Eiji Nakata, Toshifumi Ozaki

    Acta medica Okayama   73 ( 6 )   523 - 528   2019.12

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    The case of an individual with a bilateral anterior cruciate ligament (ACL) tear combined with a medial meniscus (MM) posterior root tear is described. A 34-year-old Japanese man with bilateral ACL rupture that occurred > 10 years earlier was diagnosed with bilateral ACL tear combined with MM posterior root tear (MMPRT). We performed a transtibial pullout repair of the MMPRT with ACL reconstruction. The tibial tunnels for the MM posterior root repair and ACL reconstruction were created separately. Postoperatively, a good clinical outcome and meniscal healing were obtained. Our surgical technique may thus contribute to anatomical MM posterior root repair and ACL reconstruction.

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  • The Early Arthroscopic Pullout Repair of Medial Meniscus Posterior Root Tear Is More Effective for Reducing Medial Meniscus Extrusion.

    Yusuke Kamatsuki, Takayuki Furumatsu, Shinichi Miyazawa, Yuya Kodama, Tomohito Hino, Yoshiki Okazaki, Shin Masuda, Yuki Okazaki, Tomoyuki Noda, Yasuaki Yamakawa, Tomoko Tetsunaga, Toshifumi Ozaki

    Acta medica Okayama   73 ( 6 )   503 - 510   2019.12

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    Clinical studies have demonstrated that transtibial pullout repair led to favorable midterm outcomes in patients with medial meniscus posterior root tears (MMPRTs) although medial meniscal extrusion (MME) continued to be present. It has been unclear whether these residual postoperative MMEs existed after the pullout repair or had progressed at the very short-term evaluation after surgery. We sought to determine which characteristics of patients with MMPRTs influence the incidence of postoperative MME. The cases of 23 patients whose date of injury was known were analyzed. All patients underwent MMPRT pullout fixation. Preoperative and 3-month postoperative magnetic resonance imaging (MRI) examinations were performed. MME was retrospectively assessed on the mid-coronal plane of MRI scans. The preoperative and postoperative MME values were 4.2±1.2 mm and 4.3±1.5 mm, respectively (p=0.559). Pullout repair surgery was performed significantly earlier after the MMPRT-specific injury in patients whose postoperative MME improved compared to the patients whose MME did not improve (p<0.001). Our findings demonstrated that an early transtibial pullout repair of an MMPRT was more effective in reducing MME than a late repair. Surgeons should not miss the optimal timing for the pullout repair of an MMPRT, considering the period from the injury and the preoperative MME.

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  • Clinical outcomes of treatment with locking compression plates for distal femoral fractures in a retrospective cohort. International journal

    Masahiro Kiyono, Tomoyuki Noda, Hiroshi Nagano, Takashi Maehara, Yasuaki Yamakawa, Yusuke Mochizuki, Takahiko Uchino, Suguru Yokoo, Koji Demiya, Kenta Saiga, Yasunori Shimamura, Toshifumi Ozaki

    Journal of orthopaedic surgery and research   14 ( 1 )   384 - 384   2019.11

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    BACKGROUND: Plate fixation is one of the standard surgical treatments for distal femoral fractures. There are few reports on the relationship between the screw position and bone union when fixing by the bridging plate (relative stability) method. METHODS: This retrospective study included 71 distal femoral fractures of 70 patients who were treated with the locking compression plate for distal femur (DePuy Synthes Co., Ltd, New Brunswick, CA, USA). The following measurements were evaluated and analyzed: (1) bone union rate, (2) bridge span length (distance between screws across the fracture), (3) plate span ratio (plate length/bone fracture length), (4) number of empty holes (number of screw holes not inserted around the fracture), and (5) medial fracture distance (bone fracture distance on the medial side of the distal femur). Patient demographics (age), comorbidities (smoking, diabetes, chronic steroid use, dialysis), and injury characteristics (AO type, open fracture, infection) were obtained for all participants. Univariate analysis was performed on them. RESULTS: Of 71 fractures, 26 fractures were simple fractures, 45 fractures were comminuted fractures, and 7 fractures resulted in non-union. Non-union rate was significantly higher in comminuted fractures with bone medial fracture distance exceeding 5 mm. Non-union was founded in simple fractures with bone medial fracture distance exceeding 2 mm, but not significant (p = 0.06). In cases with simple fractures, one non-union case had one empty hole and one non-union case had four empty holes, whereas in cases with comminuted fractures, five non-union cases had two more empty holes. CONCLUSIONS: We concluded that bone fragment distance between fracture fragments is more important than bridge span length of the fracture site and the number of empty holes. Smoking and medial fracture distance are prognostic risk factors of nonunion in distal femoral fractures treated with LCP as bridging plate.

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  • Posttraumatic cartilage degradation progresses following anterior cruciate ligament reconstruction: A second-look arthroscopic evaluation.

    Takaaki Hiranaka, Takayuki Furumatsu, Yusuke Kamatsuki, Kazuhisa Sugiu, Yoshiki Okazaki, Shin Masuda, Yuki Okazaki, Shota Takihira, Shinichi Miyazawa, Eiji Nakata, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   24 ( 6 )   1058 - 1063   2019.11

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    BACKGROUND: Several studies have demonstrated that posttraumatic knee osteoarthritis progresses even after anterior cruciate ligament reconstruction. Few reports described zone-specific cartilaginous damages after anterior cruciate ligament reconstruction. This study aimed to compare the status of articular cartilage at anterior cruciate ligament reconstruction with that at second-look arthroscopy. METHODS: This study included 20 patients (20 knees, 10 males and 10 females, mean age 22.4 years, Body mass index 24.4 kg/m2) that underwent arthroscopic anatomic double-bundle anterior cruciate ligament reconstruction and second-look arthroscopy. Mean periods from injury to reconstruction and from reconstruction to second-look arthroscopy were 3.4 and 15.3 months, respectively. Cartilage lesions were evaluated arthroscopically in the 6 articular surfaces and 40 articular subcompartments independently, and these features were graded with the International Cartilage Repair Society articular cartilage injury classification; comparisons were made between the grades at reconstruction and at second-look arthroscopy. Furthermore, clinical outcomes were assessed at reconstruction and at second-look arthroscopy, using the Lysholm knee score, Tegner activity scale, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, side-to-side difference of the KT-2000 arthrometer, and pivot shift test. RESULTS: Each compartment showed a deteriorated condition at second-look arthroscopy compared with the pre-reconstruction period. A significant worsening of the articular cartilage was noted in all compartments except the lateral tibial plateau and was also observed in the central region of the medial femoral condyle and trochlea after reconstruction. However, each clinical outcome was significantly improved postoperatively. CONCLUSIONS: Good cartilage conditions were restored in most subcompartments at second-look arthroscopy. Furthermore, posttraumatic osteoarthritic changes in the patellofemoral and medial compartments progressed even in the early postoperative period, although good knee stability and clinical outcomes were obtained. Care is necessary regarding the progression of osteoarthritis and the appearance of knee symptoms in patients undergoing anterior cruciate ligament reconstruction.

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  • Preliminary diagnosis of medial meniscus posterior root tears using the Rosenberg radiographic view. International journal

    Yuya Kodama, Takayuki Furumatsu, Yusuke Kamatsuki, Takaaki Hiranaka, Tomohiro Takahata, Masayuki Sadakane, Haruhiko Ikuta, Masaharu Yasumitsu, Toshifumi Ozaki

    Knee surgery & related research   31 ( 1 )   9 - 9   2019.9

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    PURPOSE: To verify the effectiveness of detecting medial meniscus posterior root tears (MMPRTs) using weight-bearing posterior-anterior (PA) radiographs. MATERIALS AND METHODS: Twenty-three patients were diagnosed with an MMPRT using magnetic resonance imaging (Group A), with 23 matched individuals forming the control group (Group B). The distance between medial tibial eminence and the lateral edge of the medial femoral condyle (MTE-MFC distance) and medial joint space (MJS) width were measured on weight-bearing PA radiographs, with the knee flexed at 45° (Rosenberg view). Absolute medial meniscus extrusion (MME) was measured on magnetic resonance images. RESULTS: The MTE-MFC distance was greater and the MJS width was smaller in Group A than Group B (7.7 ± 1.7 mm versus 6.0 ± 1.24 mm and 3.2 ± 0.8 mm versus 4.5 ± 0.7 mm, respectively; P < 0.05). The MTE-MFC distance and MJS width correlated with MME (r = 0.603 and 0.579, respectively; P < 0.05), and the extent of MME was greater in Group A than Group B (4.1 ± 1.1 mm versus 1.8 ± 1.5 mm, respectively; P < 0.05). CONCLUSIONS: MMPRTs increase the MTE-MFC distance and decrease the MJS width, with these measurements correlating to the MME. Therefore, measurement of the MTE-MFC distance and MJS width on the Rosenberg view could be a useful preliminary method for the diagnosis of an MMPRT. LEVEL OF EVIDENCE: IV.

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  • Ten-year follow-up results of perioperative chemotherapy with doxorubicin and ifosfamide for high-grade soft-tissue sarcoma of the extremities: Japan Clinical Oncology Group study JCOG0304. Reviewed

    Tanaka K, Mizusawa J, Naka N, Kawai A, Katagiri H, Hiruma T, Matsumoto Y, Tsuchiya H, Nakayama R, Hatano H, Emori M, Watanuki M, Yoshida Y, Okamoto T, Abe S, Asanuma K, Yokoyama R, Hiraga H, Yonemoto T, Morii T, Ae K, Nagano A, Yoshikawa H, Fukuda H, Ozaki T, Iwamoto Y

    BMC cancer   19 ( 1 )   890   2019.9

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    Background Soft-tissue sarcomas (STS) are rare malignant tumors those are resistant to chemotherapy. We have previously reported the 3-year follow-up result on the efficacy of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-risk STS of the extremities (JCOG0304). In the present study, we analyzed the 10-year follow-up results of JCOG0304. Methods Patients with operable, high-risk STS (T2bN0M0, AJCC 6th edition) of the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy, which consisted of 60 mg/m(2) of DXR plus 10 g/m(2) of IFM over a 3-week interval. The primary study endpoint was progression-free survival (PFS) estimated by Kaplan-Meier methods. Prognostic factors were evaluated by univariable and multivariable Cox proportional hazards model. Results A total of 72 patients were enrolled between March 2004 and September 2008, with 70 of these patients being eligible. The median follow-up period was 10.0 years for all eligible patients. Local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. The 10-year PFS was 65.7% (95% CI: 53.4-75.5%) with no PFS events being detected during the last 5 years of follow-up. The 10-year overall survival was 78.1% (95% CI: 66.3-86.2%). Secondary malignancy was detected in 6 patients. The subgroup analysis demonstrated that there was significant difference in survival with regard to primary tumor size. Conclusions Only a few long-term results of clinical trials for perioperative chemotherapy treatment of STS have been reported. Our results demonstrate that the 10-year outcome of JCOG0304 for patients with operable, high-risk STS of the extremities was stable and remained favorable during the last 5 years of follow-up.

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  • The accuracy of a newly developed guide system in medial meniscus posterior root repair: a comparison between two aiming guides. International journal

    Takayuki Furumatsu, Yuki Okazaki, Yuya Kodama, Yoshiki Okazaki, Yusuke Kamatsuki, Shin Masuda, Takaaki Hiranaka, Toshifumi Ozaki

    Knee surgery & related research   31 ( 1 )   7 - 7   2019.8

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    PURPOSE: Posterior root repair of the medial meniscus (MM) can prevent rapid progression of knee osteoarthritis in patients with a MM posterior root tear (MMPRT). The anatomic reattachment of the MM posterior root is considered to be critical in a transtibial pullout repair. However, tibial tunnel creation at the anatomic attachment is technically difficult. We hypothesized that a newly developed point-contact aiming guide [Unicorn Meniscal Root (UMR) guide] can create the tibial tunnel at a better position rather than a previously designed MMPRT guide. The aim of this study was to compare the position of the created tibial tunnel between the two meniscal root repair guides. MATERIALS AND METHODS: Thirty-eight patients underwent transtibial pullout repairs. Tibial tunnel creation was performed using the UMR guide (19 cases) or MMPRT guide (19 cases). Three-dimensional computed tomography images of the tibial surface were evaluated using the Tsukada's measurement method postoperatively. The expected anatomic center of the MM posterior root attachment was defined as the center of three tangential lines referring to three anatomic bony landmarks (anterior border of the posterior cruciate ligament, lateral margin of the medial tibial plateau, and retro-eminence ridge). The expected anatomic center and tibial tunnel center were evaluated using the percentage-based posterolateral location on the tibial surface. The distance between the anatomic center and tunnel center was calculated. RESULTS: The anatomic center of the MM posterior root footprint was located at a position of 79.2% posterior and 39.5% lateral. The mean of the tunnel center in the UMR guide was similar to that in the MMPRT guide (posterior direction, P = 0.096; lateral direction, P = 0.280). The mean distances between the tunnel center and the anatomic center were 4.06 and 3.99 mm in the UMR and MMPRT guide group, respectively (P = 0.455). CONCLUSIONS: The UMR guide, as well as the MMPRT guide, is a useful device to create favorable tibial tunnels at the MM posterior root attachment for pullout repairs in patients with MMPRTs. LEVEL OF EVIDENCE: IV.

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  • Tuberosity-overlapping Fixation of the Humeral Shaft in Humeral Head Replacement Surgery.

    Takaaki Hiranaka, Keiichiro Nishida, Taizo Konishiike, Toshifumi Ozaki, Motohiko Mikasa

    Acta medica Okayama   73 ( 4 )   299 - 305   2019.8

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    The fixation technique of bony fragments is crucial for the bone union of the tuberosities after humeral head replacement (HHR) for a comminuted fracture of the proximal humerus. To increase the bone union rate, we reduce tuberosities to overlap on the humeral shaft by approx. 1 cm and fix them with cable wire. Herein, we retrospectively investigated the clinical and radiographic outcomes of our procedure. Twenty-six patients who underwent cementless HHR for the treatment of comminuted fractures of the proximal humerus were investigated. The Constant-Murley score, active shoulder mobility, and bone union rate were evaluated. The mean duration of follow-up was 56.3 months (range 24-197). At the final follow-up, the average Constant-Murley score was 58 (range 40-76). Forward elevation was 126° on average (range 35°-180°). Twenty-three cases (88%) showed bone union between the tuberosities and the shaft at an average follow-up of 4.1 months (range 4-5 months) after surgery. Non-union was noted in 1 case, and bone resorption was noted in 2 cases. The bone union rate and the clinical outcome of our procedure were relatively favorable.

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  • Possible reparative effect of low-intensity pulsed ultrasound (LIPUS) on injured meniscus. Reviewed

    Kamatsuki Y, Aoyama E, Furumatsu T, Miyazawa S, Maehara A, Yamanaka N, Nishida T, Kubota S, Ozaki T, Takigawa M

    Journal of cell communication and signaling   13 ( 2 )   193 - 207   2019.6

  • Post-traumatic Articular Cartilage Lesions Increase at Second-look Arthroscopy Following Primary Anterior Cruciate Ligament Reconstruction.

    Kazuhisa Sugiu, Takayuki Furumatsu, Yuya Kodama, Yusuke Kamatsuki, Yoshiki Okazaki, Yuki Okazaki, Takaaki Hiranaka, Toshifumi Ozaki

    Acta medica Okayama   73 ( 3 )   223 - 228   2019.6

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    Anterior cruciate ligament (ACL) reconstruction (ACLR) after ACL rupture improves the instability of the knee joint and decreases mechanical stress to the meniscus and articular cartilage. However, there are reports that post-traumatic osteoarthritis (PTOA) is observed over time following ACLR. In this study, we assessed changes in cartilage lesions by arthroscopic findings following anatomical double-bundle ACLR and at post-operative second-look arthroscopy about 14 months later. We retrospectively evaluated 37 knees in cases with patients <40 years of age who had undergone an anatomical double-bundle ACL reconstruction <1 year after ACL rupture injury from March 2012 to December 2016. Clinical results and arthroscopic cartilage/meniscal lesion were evaluated and compared between a cartilage lesion-detected group and intact-cartilage group. Surgery improved anteroposterior laxity and other clinical measures; however, cartilage lesions were detected at 11 sites during ACLR and at 54 sites at second-look arthroscopy. The periods from injury to second-look arthroscopy and from ACLR to second-look arthroscopy were significantly longer in the cartilage-lesion group (n=23) than in the intact-cartilage group (n=14). Conversely, 96% of meniscal damage observed during ACLR was cured at the time of second-look arthroscopy. Knee articular cartilage lesions after ACL rupture cannot be completely suppressed, even using the anatomical ACL reconstruction technique. This study suggested that articular cartilage lesions can progress to a level that can be confirmed arthroscopically at approximately 17 months after ACL injury. Therefore, in ACLR patients, the possibility of developing knee articular cartilage lesions and PTOA should be considered.

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  • Prevalence of and Risk Factors for the Progression of Upper Cervical Lesions in Patients with Rheumatoid Arthritis.

    Masahiro Horita, Keiichiro Nishida, Kenzo Hashizume, Yoshihisa Sugimoto, Yoshihisa Nasu, Ryuichi Nakahara, Ryozo Harada, Toshifumi Ozaki

    Acta medica Okayama   73 ( 3 )   235 - 240   2019.6

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    We investigated the prevalence of and risk factors for the progression of upper cervical lesions (UCLs) in patients with rheumatoid arthritis (RA). A retrospective analysis of 49 patients with RA (4 males, 45 females) was conducted. The UCLs included atlanto-axial subluxation and vertical subluxation. We investigated the clinical factors including the Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) and the modified Health Assessment Questionnaire-Disability Index as well as radiographic changes between the baseline (at May 2010 to April 2013) and final follow-up. Forty patients (81.6%) were classified as the non-progressive group, and the other 9 patients (18.4%) comprised the progressive group. The progressive group's final CRP values, baseline or final MMP-3 levels, DAS28-CRP, and rate of pre-existing lesions at baseline were all significantly higher than those of the non-progressive group (p=0.017, p=0.043, p=0.002, p=0.008, p<0.001, and p=0.008 respectively). A multivariate logistic regression analysis demonstrated that DAS28-CRP at baseline was a risk factor for radiographic progression (p=0.018, odds ratio: 2.54, 95% confidence interval: 1.17-5.51). Our findings indicate that higher disease activity might influence the progression of UCLs in patients with RA.

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  • 10-year follow-up results of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-grade soft tissue sarcomas (STS) in the extremities: Japan Clinical Oncology Group study JCOG0304.

    Kazuhiro Tanaka, Junki Mizusawa, Norifumi Naka, Akira Kawai, Hirohisa Katagiri, Toru Hiruma, Yoshihiro Matsumoto, Hiroyuki Tsuchiya, Robert Nakayama, Hiroshi Hatano, Makoto Emori, Masami Hosaka, Yukihiro Yoshida, Takeshi Okamoto, Satoshi Abe, Kunihiro Asanuma, Ryohei Yokoyama, Haruhiko Fukuda, Toshifumi Ozaki, Yukihide Iwamoto

    JOURNAL OF CLINICAL ONCOLOGY   37 ( 15 )   2019.5

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  • Osteosarcoma in patients over 50 years of age: Multi-institutional retrospective analysis of 104 patients. Reviewed

    Nagano A, Matsumoto S, Kawai A, Okuma T, Hiraga H, Matsumoto Y, Nishida Y, Yonemoto T, Hosaka M, Takahashi M, Yoshikawa H, Kunisada T, Asanuma K, Naka N, Emori M, Kubo T, Kawashima H, Kawamoto T, Yokoyama R, Tsukushi S, Sato K, Okamoto T, Hiraoka K, Morioka H, Tanaka K, Takagi T, Iwamoto Y, Ozaki T

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   25 ( 2 )   319 - 323   2019.5

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    BACKGROUND: Primary osteosarcoma in elderly patients are rare malignant tumors. Its optimal treatment has not yet been determined. METHODS: This retrospective study included 104 patients aged >50 years with resectable, non-metastatic osteosarcoma treated by the members of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group. The effects of adjuvant chemotherapy were estimated by comparing outcomes in patients who received surgery plus chemotherapy with those who underwent surgery alone. RESULTS: Median age at presentation was 59 years. Neoadjuvant and adjuvant chemotherapy was administered to 83 (79.8%) patients. Patients who underwent surgery plus chemotherapy and those who underwent surgery alone had 5-year overall survival (OS) rates of 68.6% and 71.7%, respectively (p = 0.780), and 5-year relapse free survival (RFS) rates of 48.2% and 43.6%, respectively (p = 0.64). Univariate analysis showed that resection with wide margins was significantly correlated with better prognosis. CONCLUSIONS: The addition of chemotherapy to surgery did not improve OS or RFS in patients aged >50 years with resectable, non-metastatic osteosarcoma. Surgery with wide margins was only significantly prognostic of improved survival. The effect of chemotherapy in elderly osteosarcoma patients was unclear.

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  • Arthroscopic scoring system of meniscal healing following medial meniscus posterior root repair. International journal

    Takayuki Furumatsu, Shinichi Miyazawa, Masataka Fujii, Takaaki Tanaka, Yuya Kodama, Toshifumi Ozaki

    International orthopaedics   43 ( 5 )   1239 - 1245   2019.5

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    PURPOSE: Medial meniscus posterior root tear (MMPRT) leads to a rapid degradation of articular cartilage. In the treatment of MMPRT, transtibial pullout repair demonstrates a high clinical survival rate. However, there is no reliable method to evaluate the meniscal healing after surgery. We propose an arthroscopic scoring system for evaluating the meniscal healing status. The aim of this study was to investigate the correlations between second-look arthroscopic scores and clinical outcomes after transtibial pullout repair. METHODS: Twenty patients who had MMPRTs underwent transtibial pullout repairs. Clinical outcomes were assessed using the Japanese Knee Injury and Osteoarthritis Outcome Score (KOOS) and pain score evaluated by visual analogue scale at preoperatively and 1 year postoperatively. The healing status of repaired MM was assessed at one year post-operatively using a semi-quantitative arthroscopic scoring system (total, 10 points) composed of three evaluation criteria: (i) anteroposterior width of bridging tissues, (ii) stability of the MM posterior root, and (iii) synovial coverage of the sutures. Linear regression analysis was used to assess the correlation between second-look arthroscopic scores and clinical outcomes. RESULTS: Transtibial pullout repairs of MMPRTs significantly improved clinical evaluation scores at one year post-operatively. A median of second-look arthroscopic scores was 6.5 (5.75-8). A good correlation was observed between the arthroscopic score and KOOS quality of life (QOL) subscale. A moderate negative correlation between the arthroscopic score and pain score was observed. CONCLUSIONS: This study demonstrated that our semi-quantitative scoring system of meniscal healing correlated with the KOOS QOL subscale following MMPRT transtibial pullout repair. Our results suggest that the second-look arthroscopic score using this system may be a useful scale to determine and compare the healing status of the MM posterior root.

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  • Nonunion fragility fracture of the pelvis with complication from bladder rupture: A case report. Reviewed

    Yamakawa Y, Noda T, Saito T, Saiga K, Nakahara R, Shimamura Y, Ozaki T

    Trauma case reports   20   100169   2019.4

  • Temporary External Fixation Can Stabilize Hip Transposition Arthroplasty After Resection of Malignant Periacetabular Bone Tumors. Reviewed

    Kunisada T, Fujiwara T, Hasei J, Nakata E, Senda M, Ozaki T

    Clinical orthopaedics and related research   2019.4

  • Involvement of ADAM12 in Chondrocyte Differentiation by Regulation of TGF-β1-Induced IGF-1 and RUNX-2 Expressions. Reviewed

    Horita M, Nishida K, Hasei J, Furumatsu T, Sakurai M, Onodera Y, Fukuda K, Salter DM, Ozaki T

    Calcified tissue international   2019.4

  • Posteromedial vertical capsulotomy selectively increases the extension gap in posterior stabilized total knee arthroplasty. Reviewed

    Masuda S, Miyazawa S, Yuya K, Kamatski Y, Tomohito H, Yoshiki O, Yuki O, Furumatsu T, Ozaki T

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   2019.4

  • Description of a surgical technique of medial meniscus root repair: a fixation technique with two simple stiches under an expected initial tension. Reviewed

    Okazaki Y, Furumatsu T, Kodama Y, Kamatsuki Y, Masuda S, Ozaki T

    European journal of orthopaedic surgery & traumatology : orthopedie traumatologie   29 ( 3 )   705 - 709   2019.4

  • A randomized phase III trial of denosumab before curettage for giant cell tumor of bone: Japan Clinical Oncology Group Study JCOG1610. Reviewed

    Urakawa H, Mizusawa J, Tanaka K, Eba J, Hiraga H, Kawai A, Nishida Y, Hosaka M, Iwamoto Y, Fukuda H, Ozaki T

    Japanese journal of clinical oncology   49 ( 4 )   379 - 382   2019.4

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    A randomized phase III trial was planned to commence in October 2017. Resectable giant cell tumor of bone (GCTB) without possible postoperative large bone defect has been treated by curettage with local adjuvant treatment, with the local recurrence rate found to be as high as 24.6-30.8%. The aim of this study is to confirm the superiority of preoperative denosumab for patients with GCTB without possible postoperative large bone defect. A total of 106 patients will be accrued from 34 Japanese institutions over 5 years. The primary endpoint is relapse-free survival (RFS). Secondary endpoints include overall survival, joint-preserved survival, local RFS, metastasis-free survival, adverse events, serious adverse events, surgical and postoperative complications, and discontinuation of denosumab. This trial is conducted by the Bone and Soft Tissue Tumor Study Group in the Japan Clinical Oncology Group and has been registered in the UMIN Clinical Trials Registry as UMIN000029451 [http://www.umin.ac.jp/ctr/index.htm].

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  • Metformin induces CD11b+-cell-mediated growth inhibition of an osteosarcoma: implications for metabolic reprogramming of myeloid cells and anti-tumor effects. Reviewed International journal

    Takenori Uehara, Shingo Eikawa, Mikako Nishida, Yuki Kunisada, Aki Yoshida, Tomohiro Fujiwara, Toshiyuki Kunisada, Toshifumi Ozaki, Heiichiro Udono

    International immunology   31 ( 4 )   187 - 198   2019.3

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    CD11b+ myeloid subpopulations, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), play crucial roles in the suppression of T-cell-mediated anti-tumor immunity. Regulation of these cell types is a primary goal for achieving efficient cancer immunotherapy. We found that metformin (Met) induces CD11b+-cell-mediated growth inhibition of a K7M2neo osteosarcoma independent of T cells, as growth inhibition of K7M2neo was still observed in wild-type (WT) mice depleted of T cells by antibodies and in SCID; this contrasted with the effect of Met on Meth A fibrosarcoma, which was entirely T-cell-dependent. Moreover, the inhibitory effect seen in SCID was abrogated by anti-CD11b antibody injection. PMN-MDSCs were significantly reduced in both spleens and tumors following Met treatment. In TAMs, production of IL-12 and TNF-α, but not IL-10, became apparent, and elevation of MHC class II with reduction of CD206 was observed, indicating a shift from an M2- to M1-like phenotype via Met administration. Metabolically, Met treatment decreased basal respiration and the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) ratio of CD11b+ cells in tumors, but not in the spleen. In addition, decreased reactive oxygen species (ROS) production and proton leakage in MDSCs and TAMs were consistently observed in tumors. Uptake of both 2-deoxy-2-d-glucose (2-NBDG) and BODIPY® decreased in MDSCs, but only BODIPY® incorporation was decreased in TAMs. Overall, our results suggest that Met redirects the metabolism of CD11b+ cells to lower oxidative phosphorylation (OXPHOS) while elevating glycolysis, thereby pushing the microenvironment to a state that inhibits the growth of certain tumors.

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  • Comparison of the postoperative analgesic efficacies of intravenous acetaminophen and fascia iliaca compartment block inhip fracture surgery: A randomised controlled trial. Reviewed International journal

    Yamamoto N, Sakura S, Noda T, Nishiyama A, Dan'ura T, Matsui Y, Ozaki T

    Injury   50 ( 10 )   1689 - 1693   2019.3

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    BACKGROUND: Managing pain during movement after hip fracture surgery is important for achieving earlier hip mobilisation and for preventing postoperative complications. In the present study, we tested the hypothesis that the fascia iliaca compartment block (FICB) would improve postoperative pain on movement compared with intravenous acetaminophen. METHODS: In this prospective, randomised, controlled, parallel trial, patients were assigned to either the intravenous acetaminophen or the ultrasound-guided FICB group. Visual analog scale (VAS) pain scores were evaluated at 6, 9, 12, 18, 24 h, 2 days, and 7 days postoperatively. The primary outcome was VAS scores on movement at 24 h after surgery. The secondary outcomes were VAS scores on movement at the other time points, VAS scores at rest, the total number of rescue analgesics required and incidence of delirium during the first 24 h postoperatively, potential drug or block-related complications, and the time to first standing. RESULTS: VAS scores on movement at 24 h after surgery were significantly lower in the FICB group than in the intravenous acetaminophen group [median (the 25th to 75th percentiles), 20 (10-30) vs 40 (30-53); P < 0.01]. The VAS scores on movement at any other time point and the scores at rest at 12 h after surgery were also significantly lower in the FICB group than in the intravenous acetaminophen group. The two groups did not differ in terms of the total number of rescue analgesics required or the incidence of delirium during the first 24 h postoperatively; complications; or the time to first standing. CONCLUSIONS: FICB improved postoperative pain on movement compared with intravenous acetaminophen without increasing the complication rate. However, the total number of rescue analgesics required and the time to first standing were not significantly different between the two groups.

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  • Predicting acetabular growth in developmental dysplasia of the hip following open reduction after walking age. Reviewed

    Miyake T, Tetsunaga T, Endo H, Yamada K, Sanki T, Fujiwara K, Nakata E, Ozaki T

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   24 ( 2 )   326 - 331   2019.3

  • Early response assessment of re-ossification after palliative conventional radiotherapy for vertebral bone metastases. Reviewed

    Nakata E, Sugihara S, Kataoka M, Yamashita N, Furumatsu T, Takigawa T, Tetsunaga T, Ozaki T

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   24 ( 2 )   332 - 336   2019.3

  • Mini-open excision of osteoid osteoma using intraoperative O-arm/Stealth navigation. Reviewed

    Fujiwara T, Kunisada T, Takeda K, Hasei J, Nakata E, Mochizuki Y, Kiyono M, Yoshida A, Ozaki T

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   24 ( 2 )   337 - 341   2019.3

  • Time-Dependent Increase in Medial Meniscus Extrusion after Medial Meniscus Posterior Root Tear Analyzed by Using Magnetic Resonance Imaging. Reviewed

    Okazaki Y, Furumatsu T, Shimamura Y, Saiga K, Ohashi H, Uchino T, Kamatsuki Y, Okazaki Y, Ozaki T

    Knee surgery & related research   2019.3

  • Pullout repair using modified Mason-Allen suture induces better meniscal healing and superior clinical outcomes: A comparison between two surgical methods. Reviewed

    Furumatsu T, Okazaki Y, Kodama Y, Okazaki Y, Masuda S, Kamatsuki Y, Takihira S, Hiranaka T, Yamawaki T, Ozaki T

    The Knee   2019.3

  • Injury patterns of medial meniscus posterior root tears. Reviewed

    Furumatsu T, Okazaki Y, Okazaki Y, Hino T, Kamatsuki Y, Masuda S, Miyazawa S, Nakata E, Hasei J, Kunisada T, Ozaki T

    Orthopaedics & traumatology, surgery & research : OTSR   105 ( 1 )   107 - 111   2019.2

  • Is immunohistochemical staining for β-catenin the definitive pathological diagnostic tool for desmoid-type fibromatosis? A multi-institutional study. Reviewed

    Koike H, Nishida Y, Kohno K, Shimoyama Y, Motoi T, Hamada S, Kawai A, Ogose A, Ozaki T, Kunisada T, Matsumoto Y, Matsunobu T, Ae K, Gokita T, Sakai T, Shimizu K, Ishiguro N

    Human pathology   84   155 - 163   2019.2

  • New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Reviewed International journal

    Tanaka K, Ozaki T

    Japanese journal of clinical oncology   49 ( 2 )   103 - 107   2019.2

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    The Cancer Staging Manual of the American Joint Committee on Cancer (AJCC) has recently been revised and updated to its eighth edition. This review focuses on the new staging system of bone and soft tissue sarcomas and outlines the revision points and caveats in the latest edition. The major changes in the eighth edition of the AJCC staging for bone and soft tissue sarcomas are the following four points. (i) Tumors are described separately according to the primary sites. For bone sarcoma, three tumor locations are described: (a) appendicular skeleton, trunk, skull and facial bones; (b) spine and (c) pelvis. Meanwhile, four tumor locations are described for soft tissue sarcoma: (1) trunk and extremity; (2) retroperitoneum; (3) head and neck and (4) visceral sites. (ii) Histologic grading system in bone sarcoma is changed to three-grade classifications. (iii) For soft tissue sarcoma, AnyTN1M0 tumor in the trunk and extremity is classified as stage IV, whereas for the retroperitoneal tumor, anyTN1M0 remains as stage IIIB. (iv) For soft tissue sarcomas in the trunk, extremity and retroperitoneum, tumor size was classified into four categories: (a) ≤5 cm; (b) >5 cm and ≤10 cm; (c) >10 cm and ≤15 cm and (d) >15 cm. In addition, the notation about the depth of the tumor (superficial or deep from the superficial fascia) has been eliminated.

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  • Meniscal repair concurrent with anterior cruciate ligament reconstruction restores posterior shift of the medial meniscus in the knee-flexed position. Reviewed

    Okazaki Y, Furumatsu T, Miyazawa S, Kodama Y, Kamatsuki Y, Hino T, Masuda S, Ozaki T

    Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA   27 ( 2 )   361 - 368   2019.2

  • Transtibial pullout repair of medial meniscus posterior root tear restores physiological rotation of the tibia in the knee-flexed position. Reviewed

    Okazaki Y, Furumatsu T, Kodama Y, Hino T, Kamatsuki Y, Okazaki Y, Masuda S, Miyazawa S, Endo H, Tetsunaga T, Yamada K, Ozaki T

    Orthopaedics & traumatology, surgery & research : OTSR   105 ( 1 )   113 - 117   2019.2

  • Sub-deltoid approach for removal of large lipoma around the proximal humerus: A report of three cases. Reviewed

    Hasei J, Kunisada T, Nakata E, Ozaki T

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   2019.2

  • Changes in acetabular component alignment due to screw fixation in patients with hip dysplasia. Reviewed

    Tetsunaga T, Fujiwara K, Endo H, Tetsunaga T, Miyake T, Yamada K, Sanki T, Ozaki T

    Hip international : the journal of clinical and experimental research on hip pathology and therapy   1120700019828708   2019.2

  • Minimally Invasive Percutaneous Spinopelvic Fixation for Unstable Pelvic Ring Fracture Performed With the Patient in a Lateral Position. Reviewed International journal

    Tsuji H, Takigawa T, Misawa H, Shiozaki Y, Yamakawa Y, Noda T, Ozaki T

    Clinical spine surgery   32 ( 5 )   191 - 197   2019.2

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    Spinopelvic fixation provides a strong fixation for unstable pelvic ring fractures. However, the technique is usually performed with the patient in the prone position, with the applied weight on the anterior superior iliac crests aggravating fracture displacement. We developed a novel approach for minimally invasive percutaneous spinopelvic fixation that is performed with the patient in a lateral (side lying) position. We describe the application of our technique for the treatment of a bilateral pelvic ring and acetabulum fracture in a 79-year-old woman injured in a traffic accident. Initial posterior fixation was performed with the patient in the left-side lying position, using bilateral pedicle screws at L3 and L4 and a left sacral-alar iliac screw and 2 right iliac screws inserted under navigation. The lateral and cranial displacement of the right pelvic ring was reduced percutaneously. One week after this initial surgery, we proceeded with an open anterior reduction and internal fixation of the left pelvic ring and acetabulum fracture. The postoperative course was uneventful and clinical outcomes were satisfactory. Reduction of a pelvic ring fracture in a lateral position, with subsequent spinopelvic fixation, is a reasonable option for the treatment of an unstable pelvic ring fracture.

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  • The morphology of the femur in elderly Japanese females: Analysis using 3D-CT. Reviewed

    Maehara T, Kiyono M, Noda T, Sato R, Kadota H, Hori T, Koga Y, Hidaka Y, Joko R, Muraoka S, Ozaki T

    Journal of orthopaedic surgery (Hong Kong)   27 ( 1 )   2309499018816488   2019.1

  • Avulsion fracture of the ischial tuberosity treated with the suture bridge technique: a case report. Reviewed

    Tetsunaga T, Endo H, Tetsunaga T, Yamada K, Furumatsu T, Ozaki T

    BMC musculoskeletal disorders   20 ( 1 )   9   2019.1

  • Clinical features and treatment outcome of desmoid-type fibromatosis: based on a bone and soft tissue tumor registry in Japan Reviewed

    Nishida Y, Kawai A, Toguchida J, Ogose A, Ae K, Kunisada T, Matsumoto Y, Matsunobu T, Takahashi K, Nishida K, Ozaki T

    International Journal of Clinical Oncology   24 ( 11 )   1498 - 1505   2019

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    BACKGROUND: Treatment modality of desmoid-type fibromatosis (DF) has changed from surgery with a wide surgical margin to conservative treatment. In this study, tumor characteristics of DF, transition of the treatment modality, and clinical outcome of surgical treatment were analyzed based on data obtained from the bone and soft tissue tumor registry established in Japan. METHODS: Data were collected as registration data and follow-up data. Five hundred and thirty registered cases of DF were identified, including 223 cases with follow-up data with or without surgical treatment. RESULTS: The number of registered patients increased gradually. The frequency of surgical treatment was gradually reduced year by year. The 3-year local recurrence free survival (LRFS) was 77.7%, with tumor location and size tending to correlate with LRFS. Interestingly, there was no significant difference in LRFS between wide and marginal margin (P = 0.34). CONCLUSIONS: The treatment modality has shifted from surgical to conservative treatment, with risk factors for surgical treatment similar to those noted in previous studies. The National registry system is crucial for a rare disease such as DF, and in the future, a population based registry system should be established to better comprehend the actual status of DF.

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  • Regeneration of the Fibula with Unidirectional Porous Hydroxyapatite. International journal

    Koji Demiya, Toshiyuki Kunisada, Eiji Nakata, Joe Hasei, Toshifumi Ozaki

    Case reports in orthopedics   2019   9024643 - 9024643   2019

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    A fibula graft is one of the most common orthopedic procedures for reconstruction of a bone defect, and some complications related to persistent defects of the fibula have been reported previously. We believe that regeneration of the fibula may be critical for postoperative function and prevention of complications. This report describes a 9-year-old female with Ewing sarcoma of the pelvis who was treated with the double-barrel fibula grafts for pelvic bone defect following tumor resection. The defect after fibular resection was filled with unidirectional porous hydroxyapatite (UDPHAp) implants. A plain radiograph revealed new bone formation and a callus-like structure at one month after surgery and bony union between each UDPHAp implant 5 months after surgery. Resorption of implanted UDPHAp was identified, and partial remodeling of the bone marrow cavity could be seen 1 year 2 months after surgery. A radiograph at final follow-up (5 years 10 months after surgery) demonstrated almost complete absorption of the implanted UDPHAp and clear formation of the cortex and bone marrow in the resected part of the fibula. The patient is able to walk well without any walking supports and to take part in sports activities.

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  • Difference between the Right and Left Phrenic Nerve Conduction Times, Latency, and Amplitude. Reviewed

    Katayama Y, Senda M, Kaneda D, Ozaki T

    Acta medica Okayama   72 ( 6 )   563 - 566   2018.12

  • Minimal Ablation of the Tibial Stump Using Bony Landmarks Improved Stability and Synovial Coverage Following Double-Bundle Anterior Cruciate Ligament Reconstruction. Reviewed

    Kodama Y, Furumatsu T, Hino T, Kamatsuki Y, Ozaki T

    Knee surgery & related research   30 ( 4 )   348 - 355   2018.12

  • Identification of Circulating Exosomal Marker in Synovial Sarcoma

    Suguru Yokoo, Tomohiro Fujiwara, Aki Yoshida, Masahiro Kiyono, Yusuke Mochizuki, Koji Demiya, Joe Hasei, Toshiyuki Kunisada, Yusuke Yoshioka, Koji Ueda, Takahiro Ochiya, Toshifumi Ozaki

    CANCER SCIENCE   109   570 - 570   2018.12

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  • Early response assessment of palliative conventional radiotherapy for painful uncomplicated vertebral bone metastases. Reviewed

    Nakata E, Sugihara S, Kataoka M, Yamashita N, Furumatsu T, Takigawa T, Tetsunaga T, Ozaki T

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   23 ( 6 )   912 - 917   2018.11

  • Intraoperative O-arm-navigated resection in musculoskeletal tumors. Reviewed

    Fujiwara T, Kunisada T, Takeda K, Hasei J, Nakata E, Nakahara R, Yoshida A, Ozaki T

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   23 ( 6 )   1045 - 1050   2018.11

  • A high incidence of extensor pollicis brevis insertion into the distal phalanx in rheumatoid arthritis patients who required the surgical reconstruction for thumb boutonnière deformity. Reviewed

    Okita S, Nishida K, Ohtsuka A, Ozaki T

    Modern rheumatology   1 - 15   2018.10

  • Drug dependence in patients with chronic pain: A retrospective study. Reviewed

    Tetsunaga T, Tetsunaga T, Nishida K, Kanzaki H, Misawa H, Takigawa T, Shiozaki Y, Ozaki T

    Medicine   97 ( 40 )   e12748   2018.10

  • Thymol turbidity test is associated with the risk of cyclops syndrome following anterior cruciate ligament reconstruction. Reviewed

    Kodama Y, Furumatsu T, Hino T, Kamatsuki Y, Okazaki Y, Masuda S, Okazaki Y, Ozaki T

    BMC musculoskeletal disorders   19 ( 1 )   367   2018.10

  • Pullout Repair of the Medial Meniscus Posterior Root Tear Reduces Proton Density-Weighted Imaging Signal Intensity of the Medial Meniscus. Reviewed

    Okazaki Y, Furumatsu T, Masuda S, Miyazawa S, Kodama Y, Kamatsuki Y, Hino T, Okazaki Y, Ozaki T

    Acta medica Okayama   72 ( 5 )   493 - 498   2018.10

  • Composition of Cell Clusters in Torn Menisci and Their Extracellular Matrix Components. Reviewed

    Kodama Y, Furumatsu T, Maehara A, Ozaki T

    Acta medica Okayama   72 ( 5 )   499 - 506   2018.10

  • An evaluation of anesthetic fade in motor evoked potential monitoring in spinal deformity surgeries. Reviewed

    Ugawa R, Takigawa T, Shimomiya H, Ohnishi T, Kurokawa Y, Oda Y, Shiozaki Y, Misawa H, Tanaka M, Ozaki T

    Journal of orthopaedic surgery and research   13 ( 1 )   227   2018.9

  • Carbon ion radiotherapy for unresectable localized axial soft tissue sarcoma Reviewed

    Reiko Imai, Tadashi Kamada, Nobuhito Araki, Satoshi Abe, Yukihide Iwamoto, Toshifumi Ozaki, Hirokazu Chuman, Hiroaki Hiraga, Toru Hiruma, Noriaki Kameda, Chihiro Kanehira, Mitsunori Kaya, Rikuo Machinami, Akihiko Matsumine, Seiichi Matsumoto, Hideo Morioka, Yoshihiro Nishida, Kazuhisa Takahashi, Masazumi Tsuneyoshi, Takehiko Yamaguchi, Tsukasa Yonemoto

    Cancer Medicine   7   4308 - 4314   2018.9

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    © 2018 The Authors. Cancer Medicine published by John Wiley &amp; Sons Ltd. Carbon ion radiotherapy is known for its high-precision dose distribution and high biological effectiveness. We evaluated the results of carbon ion radiotherapy in 128 patients with unresectable localized axial soft tissue sarcoma at a single institution. The patients’ median age was 54 years, and the median follow-up period was 49.4 (range 6.4-146.4) months. The median tumor volume was 356 cm3. The 5-year local control, overall survival, and disease-free survival rates were 65%, 46%, and 39%, respectively. In the univariate analysis, tumor volume, local control, and incidences of metastases were significantly related to overall survival. In the multivariate analysis, tumor volume and local control were significantly related to overall survival. We did not find any factors related to local control. Five patients required surgical intervention because of adverse events in the bones. Carbon ion radiotherapy may be a treatment option for unresectable axial soft tissue sarcoma.

    DOI: 10.1002/cam4.1679

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  • 当科における股関節鏡の合併症

    三喜 知明, 遠藤 裕介, 山田 和希, 鉄永 智紀, 河村 涌志, 尾崎 敏文

    中部日本整形外科災害外科学会雑誌   61 ( 秋季学会 )   112 - 112   2018.9

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  • Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304. Reviewed International journal

    Kazuhiro Tanaka, Gakuto Ogawa, Junki Mizusawa, Norifumi Naka, Akira Kawai, Mitsuru Takahashi, Toru Hiruma, Yoshihiro Matsumoto, Hiroyuki Tsuchiya, Robert Nakayama, Hiroshi Hatano, Makoto Emori, Masami Hosaka, Yukihiro Yoshida, Junya Toguchida, Satoshi Abe, Kunihiro Asanuma, Ryohei Yokoyama, Hiroaki Hiraga, Tsukasa Yonemoto, Takeshi Morii, Seiichi Matsumoto, Akihito Nagano, Hideki Yoshikawa, Haruhiko Fukuda, Toshifumi Ozaki, Yukihide Iwamoto

    World journal of surgical oncology   16 ( 1 )   162 - 162   2018.8

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    BACKGROUND: Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS. METHODS: We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities. RESULTS: Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival. CONCLUSION: In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

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  • Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study. Reviewed International journal

    Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, Takemoto A, Naka N, Matsumoto Y, Kawai A, Kunisada T, Kubo T, Emori M, Hiraga H, Hatano H, Tsukushi S, Nishida Y, Akisue T, Morii T, Takahashi M, Nagano A, Yoshikawa H, Sato K, Kawano M, Hiraoka K, Tanaka K, Iwamoto Y, Ozaki T

    World journal of surgical oncology   16 ( 1 )   160 - 160   2018.8

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    BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. METHODS: We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. RESULTS: Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2-41) and 6 (1-14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p < 0.001). CONCLUSION: The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

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  • A Multidisciplinary Approach to the Management of Chronic Pain through a Self-managed Behavioral Exercise Program : A Pilot Study in Japan. Reviewed

    Nishie H, Tetsunaga T, Kanzaki H, Oda K, Inoue S, Ryuo Y, Ota H, Miyawaki T, Arakawa K, Tetsunaga T, Kitamura Y, Sendo T, Morimatsu H, Ozaki T, Nishida K

    Acta medica Okayama   72 ( 4 )   343 - 350   2018.8

  • Venous Thromboembolism in Patients with Acute Thoracolumbar Spinal Cord Injury. Reviewed

    Morita T, Sugimoto Y, Takigawa T, Misawa H, Ito Y, Ozaki T

    Acta medica Okayama   72 ( 4 )   375 - 378   2018.8

  • 股関節鏡手術に際し電気凝固メスの破損を生じた2例

    遠藤 裕介, 山田 和希, 三喜 知明, 三宅 孝昌, 尾崎 敏文

    Hip Joint   44 ( 2 )   725 - 729   2018.8

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    症例1は初診時46歳女性で、特に誘因なく左股関節痛が出現し、49歳時に手術加療を希望された。X線上CE角0°と形成不全股であり、左寛骨臼回転骨切り術(RAO)前に股関節鏡を施行し関節唇断裂に対して電気凝固メス(VAPR)でシュリンケージを施行した。その後、スロットカニューラからVAPRを出す際に先端を回転させ破損した。関節内には破損片は認められず、関節内洗浄後にイメージで確認したところ外側ポータルの関節外に破損片が認められた。イメージ下にコッヘルでつかんで除去できており、器具が破損したが摘出できた旨を説明し、予定通り4週後に左RAOを施行した。症例2は初診時39歳女性で、特に誘因なく両股関節痛が出現し、40歳時に右RAOを施行、左側も41歳時に手術を希望された。骨切り術前に股関節鏡を施行し関節唇断裂に対してVAPRでシュリンケージを施行したが、ポータルの入れ替え時に助手がVAPRを入れる際に完全に先端がカニューラ先から出る前に回転させ破損した。関節内には破損片は認められたが深部へと落ち込み、器具が到達できない部位へ移動した。2週後の再入院時のX線像で破損片の関節内の移動を認め、RAO手術時に一部関節包を切開し破片を回収した。予定とおり左RAOを施行し、摘出した破損片は2.5mmのサイズで破損部に合致し術後X線像からも完全に除去できたと考えられた。

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  • Complete tear of the lateral meniscus posterior root is associated with meniscal extrusion in anterior cruciate ligament deficient knees. Reviewed

    Kamatsuki Y, Furumatsu T, Fujii M, Kodama Y, Miyazawa S, Hino T, Ozaki T

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society   36 ( 7 )   1894 - 1900   2018.7

  • Medial meniscus posterior root tear induces pathological posterior extrusion of the meniscus in the knee-flexed position: An open magnetic resonance imaging analysis Reviewed

    S. Masuda, T. Furumatsu, Y. Okazaki, Y. Kodama, T. Hino, Y. Kamatsuki, S. Miyazawa, T. Ozaki

    Orthopaedics and Traumatology: Surgery and Research   104 ( 4 )   485 - 489   2018.6

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    Background: A medial meniscus posterior root tear (MMPRT) is defined as an injury to the posterior meniscal insertion on the tibia. In MMPRT, the medial meniscus (MM) hoop function is damaged, and the MM undergoes a medial extrusion into the interior from the superior articular surface of the tibia. However, the details of MM position and movement during knee joint movement are unclear in MMPRT cases. The present study aims to evaluate MM position and movement via magnetic resonance imaging (MRI) examination of the MM posterior extrusion (MMPE) at knee flexion angles of 10° and 90°. We hypothesized that, during knee flexion, the MM will shift to the posterior and the posterior extrusion will increase compared to that when the knee is extended. Materials and methods: Twenty-four patients were diagnosed with symptomatic MMPRT on open MRI examination. Preoperative MMPE, anteroposterior interval (API) of the MM, and MM medial extrusion (MMME) at knee flexion angles of 10° and 90° were measured. Results: For patients with MMPRT, the MMPE increased from −4.77 ± 1.43 mm to 3.79 ± 1.17 mm (p &lt
    0.001) when the knee flexion angle increased from 10° to 90°. Further, flexing the knee from 10° to 90° decreased the API of the MM from 20.19 ± 4.22 mm to 16.41 ± 5.14 mm (p &lt
    0.001). MMME showed no significant change between knee flexion angles of 10° and 90°. Discussion: This study demonstrated that, in cases of MMPRT, the MMPE clearly increases when the knee is flexed to 90° while MMME does not change. Our results suggest that open MRI examination can be used to evaluate the dynamic position of the posterior MM by scanning the knee as it flexes to 90°. Level of evidence: IV: retrospective cohort study.

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  • Medial meniscus posterior root tear induces pathological posterior extrusion of the meniscus in the knee-flexed position: An open magnetic resonance imaging analysis Reviewed

    S. Masuda, T. Furumatsu, Y. Okazaki, Y. Kodama, T. Hino, Y. Kamatsuki, S. Miyazawa, T. Ozaki

    Revue de Chirurgie Orthopedique et Traumatologique   104 ( 4 )   339   2018.6

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    Background: A medial meniscus posterior root tear (MMPRT) is defined as an injury to the posterior meniscal insertion on the tibia. In MMPRT, the medial meniscus (MM) hoop function is damaged, and the MM undergoes a medial extrusion into the interior from the superior articular surface of the tibia. However, the details of MM position and movement during knee joint movement are unclear in MMPRT cases. The present study aims to evaluate MM position and movement via magnetic resonance imaging (MRI) examination of the MM posterior extrusion (MMPE) at knee flexion angles of 10° and 90°. We hypothesized that, during knee flexion, the MM will shift to the posterior and the posterior extrusion will increase compared to that when the knee is extended. Materials and methods: Twenty-four patients were diagnosed with symptomatic MMPRT on open MRI examination. Preoperative MMPE, anteroposterior interval (API) of the MM, and MM medial extrusion (MMME) at knee flexion angles of 10° and 90° were measured. Results: For patients with MMPRT, the MMPE increased from −4.77 ± 1.43 mm to 3.79 ± 1.17 mm (p &lt
    0.001) when the knee flexion angle increased from 10° to 90°. Further, flexing the knee from 10° to 90° decreased the API of the MM from 20.19 ± 4.22 mm to 16.41 ± 5.14 mm (p &lt
    0.001). MMME showed no significant change between knee flexion angles of 10° and 90°. Discussion: This study demonstrated that, in cases of MMPRT, the MMPE clearly increases when the knee is flexed to 90° while MMME does not change. Our results suggest that open MRI examination can be used to evaluate the dynamic position of the posterior MM by scanning the knee as it flexes to 90°. Level of evidence: IV retrospective cohort study.

    DOI: 10.1016/j.rcot.2018.04.006

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  • 中高齢者原発性悪性骨腫瘍に対する補助化学療法の検討 JCOG骨軟部腫瘍グループアンケート結果より

    永野 昭仁, 松本 誠一, 川井 章, 大隈 知威, 平賀 博明, 松本 嘉寛, 西田 佳弘, 米本 司, 保坂 正美, 高橋 満, 吉川 秀樹, 尾崎 敏文, 淺沼 邦洋, 中 紀文, 江森 誠人, 久保 忠彦, 川島 寛之, 河本 旭哉, 横山 良平, 筑紫 聡

    日本整形外科学会雑誌   92 ( 6 )   S1408 - S1408   2018.6

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  • Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan: A Case Study of Phase 2 Trial for Sarcoma Reviewed

    Akihiro Hirakawa, Tadaaki Nishikawa, Kan Yonemori, Taro Shibata, Kenichi Nakamura, Masashi Ando, Takafumi Ueda, Toshifumi Ozaki, Kenji Tamura, Akira Kawai, Yasuhiro Fujiwara

    Therapeutic Innovation and Regulatory Science   52 ( 3 )   334 - 338   2018.5

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    Investigational drugs for rare cancers are often approved based solely on a single-arm phase II trial that primarily evaluates response rate in Japan. Such trials typically use a fixed sample size determined on the basis of the frequentist manner. However, since predicting the speed of patient enrollment is challenging because of the disease rarity, the time needed to complete the enrollment of the fixed number of patients is prolonged in some cases. A Bayesian design without fixing the sample size is useful for single-arm phase II trials of rare cancers. However, the arbitrariness of prior distribution specifications and the frequentist operating characteristics are regulatory issues. We recently started a Bayesian single-arm phase II trial of nivolumab in patients with sarcoma for new drug application in Japan and examined the statistical rationale and design consideration. In the Bayesian design, we specify the minimum and maximum numbers of enrolled patients during the enrollment period and the prior distributions of response rates. Considering these parameters, we obtain the minimum number of responders needed for the positive conclusion of the efficacy of nivolumab for each sample size. Simulation studies demonstrated that the operating characteristics of this design would be acceptable from the frequentist view. The Bayesian design provided an adaptive decision rule for efficacy conclusion for the drug without fixing the sample size. We hope our trial’s success will provide a new drug development option for rare cancers in Japan.

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  • Relationship between displacement of the psoas major muscle and spinal alignment in patients with adult spinal deformity Reviewed

    Yoshiaki Oda, Tomoyuki Takigawa, Ryo Ugawa, Yasuyuki Shiozaki, Haruo Misawa, Yoshihisa Sugimoto, Masato Tanaka, Toshifumi Ozaki

    Asian Spine Journal   12 ( 2 )   335 - 342   2018.4

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    Study Design: Cross sectional study. Purpose: To clarify the difference in position of the psoas muscle between adult spinal deformity (ASD) and lumbar spinal stenosis (LSS). Overview of Literature: Although it is known that the psoas major muscle deviates in ASD patients, no report is available regarding the difference in comparison with LSS patients. Methods: This study investigates 39 patients. For evaluating spinal alignment, pelvic tilt (PT), pelvic incidence (PI), sacral slope, lumbar lordosis (LL), PI-LL, Cobb angle, and the convex side, the lumbar curves were measured. For measuring the position of the psoas major at the L4/5 disk level, magnetic resonance imaging was used. The displacements of psoas major muscle were measured separately in the anterior-posterior and lateral directions. We examined the relationship between the radiographic parameters and anterior displacement (AD) and lateral displacement (LD) of the psoas major muscle. Results: AD was demonstrated in 15 cases with ASD and nine cases with LSS (p &gt
    0.05). LD was observed in 13 cases with ASD and no cases with LSS (p &lt
    0.01). The Cobb angle was significantly greater in cases with AD than in those without AD (p =0.04). PT, LL, PI- LL, and Cobb angle were significantly greater in cases with LD (p &lt
    0.05). All cases with LD had AD, but no case without AD had LD (p &lt
    0.001). The side of greater displacement at L4/5 and the convex side of the lumbar curve were consistent in all cases. Conclusions: Despite AD being observed in LSS as well, LD was observed only in the ASD group. Radiographic parameters were worse when LD was seen, rather than AD.

    DOI: 10.4184/asj.2018.12.2.335

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  • Clinical and Functional Significance of Intracellular and Extracellular microRNA-25-3p in Osteosarcoma. Reviewed

    Yoshida A, Fujiwara T, Uotani K, Morita T, Kiyono M, Yokoo S, Hasei J, Nakata E, Kunisada T, Ozaki T

    Acta medica Okayama   72 ( 2 )   165 - 174   2018.4

  • MiRNA-133a-5p inhibits the expression of osteoblast differentiation-associated markers by targeting the 3′ UTR of RUNX2 Reviewed

    Wei Zhang, Yonggang Wu, Yasuyuki Shiozaki, Yoshihisa Sugimoto, Tomoyuki Takigawa, Masato Tanaka, Akihiro Matsukawa, Toshifumi Ozaki

    DNA and Cell Biology   37 ( 3 )   199 - 209   2018.3

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    Recent studies have recognized the involvement of microRNAs (miRNAs) in the development of osteoporosis, which regulate the balance between osteogenesis and osteoclasis. In this study, we investigated the regulation by miRNA-133a-5p on the osteoblast differentiation-associated markers in the mouse osteoblast-like MC3T3-E1 cells by RUNX2. First, we manipulated the miRNA-133a level in the MC3T3-E1 cells with 20 or 40 nM miR-133a-5p mimics, miR-133a-5p inhibitor, or scramble miRNA. Then, we quantified with real-time polymerase chain reaction (qRT-PCR) the expression of Collagen I, osteocalcin (OCN), and osteopontin (OPN) in the miR-133a-5p-manipulated MC3T3-E1 cells. And the confocal microscopy was also utilized to confirm the regulation by miR-133a-5p on the expression of the three molecules. We also investigated the extracellular matrix (ECM) mineralization and the alkaline phosphatase (ALP) activity in the miR-133a-5p-manipulated MC3T3-E1 cells. In addition, we explored the possible targeting by miR-133a-5p on RUNX2, which was a well-recognized promoter to osteoblast differentiation, with luciferase reporter, qRT-PCR, and Western blotting assay. Results demonstrated that the miRNA-133a-5p mimics markedly reduced, whereas the miRNA-133a-5p inhibitor significantly promoted the expression of Collagen I, OCN, and OPN, the ECM mineralization, and the ALP activity in MC3T3-E1 cells. The alignment analysis demonstrated a high homology between miRNA-133a-5p and the 3′ UTR of RUNX2. Moreover, the luciferase reporter assay demonstrated that miRNA-133a-5p targeted the 3′ UTR of RUNX2, and inhibited the expression of RUNX2 in both mRNA and protein levels. In conclusion, we identified the inhibition by miRNA-133a-5p to the expression of osteoblast differentiation markers, to the ECM mineralization, and to the ALP activity in MC3T3-E1 cells, by targeting the 3′ UTR of RUNX2. Our study suggests that miRNA-133a-5p might be an important target to inhibit osteoblast differentiation in osteoporosis.

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  • Outcomes of Resection and Joint-Preserving Arthroplasty for Forefoot Deformities for Rheumatoid Arthritis Reviewed

    Masahiro Horita, Keiichiro Nishida, Kenzo Hashizume, Yoshihisa Nasu, Kenta Saiga, Ryuichi Nakahara, Takahiro Machida, Hideki Ohashi, Toshifumi Ozaki

    Foot and Ankle International   39 ( 3 )   292 - 299   2018.3

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    Background: We investigated the clinical outcomes of resection and joint-preserving arthroplasty for forefoot deformities in patients with rheumatoid arthritis. Methods: Sixteen feet of 14 women (average age, 67.1 years
    range, 53-82) underwent resection arthroplasty of the metatarsal head (resection group), and 18 feet of 15 women (average age, 61.3 years
    range, 40-73) underwent a metatarsophalangeal joint-preserving procedure with shortening oblique metatarsal osteotomies of the lesser toes (joint preservation group). The mean disease duration in the resection and joint preservation groups was 23.6 and 19.1 years, and the average follow-up period was 37.3 and 33.5 months, respectively. The classification of Larsen was used to assess the severity of destruction of the metatarsophalangeal (MTP) joint. Preoperative and postoperative clinical evaluation included Japanese Society for Surgery of the Foot (JSSF) score and postoperative complications. Results: The number of preoperative radiographic destruction of the MTP joints (Larsen grade II, III, IV, and V) was 0, 29, 39, and 12 joints in the resection group and 13, 67, 9, and 1 joints in the joint preservation group. The mean JSSF score improved significantly from 61.3 to 83.9 points in the resection group (P &lt
    .001) and from 62.2 to 90.8 points in the joint preservation group (P &lt
    .001). In the resection group, recurrence of callosities and claw toe deformity was observed in 6 and 3 feet, respectively. In the joint-preserving group, recurrence of callosities and hammer toe deformity was observed in 1 foot each. Conclusion: The resection arthroplasty and joint-preserving procedure showed satisfactory clinical outcomes. However, whether both procedures can maintain the good clinical results without the recurrence of forefoot deformity will require longer follow-up. Level of Evidence: Level III, retrospective comparative series.

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  • Patients with osteosarcoma and soft tissue sarcoma might become “cancer refugees” in some japanese regional cities Reviewed

    Hiromichi Yamane, Toshiyuki Kunisada, Toshifumi Ozaki, Nobuaki Ochi, Yoshihiro Honda, Yasunari Nagasaki, Nozomu Nakagawa, Tomoko Yamagishi, Hidekazu Nakanishi, Nagio Takigawa

    Cancer Management and Research   10   353 - 359   2018.2

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    Purpose: “Rare cancer” is defined as malignancy with a disease prevalence (age-adjusted incidence rate) of less than six per 100,000 population. Proper treatments which these patients need cannot always be performed unless they find dedicated facilities. Patients tend to be desperate, searching for advice and care. Thus, they are called “cancer refugees”. Osteosarcoma and soft tissue sarcoma (OS/STS) are representative rare cancers in Japan. We conducted a retrospective analysis of patients with OS/STS to improve the current treatment modalities in a Japanese regional city. Patients and methods: Twenty-one patients with OS/STS who were hospitalized to receive standard chemotherapy or palliative treatment were enrolled between October 2011 and January 2017. Patients with non-Hodgkin’s lymphoma (NHL) and advanced cancer who were treated in the palliative care unit (PCU) of the Kawasaki Medical School General Medical Center were recruited as the control groups. We analyzed the difference in residential area between patients with OS/STS and the control groups. Results: Approximately one-third of patients with OS/STS were referred from hospitals outside of Okayama prefecture. The ratio of patients with OS/STS referred from Okayama city and/or the same medical administration area of Okayama prefecture was lower than that of patients with NHL and advanced cancer who were treated in the PCU. Conclusion: Because the medical environment of patients with OS/STS in Japanese local cities has not been consolidated, completing medical care within the patient’s own medical administration area is difficult. Thus, some patients with OS/STS may become “cancer refugees” who are unable to receive standard therapy near their residence.

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  • Improvement in the medial meniscus posterior shift following anterior cruciate ligament reconstruction Reviewed

    Hiroto Inoue, Takayuki Furumatsu, Shinichi Miyazawa, Masataka Fujii, Yuya Kodama, Toshifumi Ozaki

    Knee Surgery, Sports Traumatology, Arthroscopy   26 ( 2 )   434 - 441   2018.2

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    Purpose: Anterior cruciate ligament (ACL) reconstruction can reduce the risk of developing osteoarthritic knees. The goals of ACL reconstruction are to restore knee stability and reduce post-traumatic meniscal tears and cartilage degradation. A chronic ACL insufficiency frequently results in medial meniscus (MM) injury at the posterior segment. How ACL reconstruction can reduce the deformation of the MM posterior segment remains unclear. In this study, we evaluated the form of the MM posterior segment and anterior tibial translation before and after ACL reconstruction using open magnetic resonance imaging (MRI). Methods: Seventeen patients who underwent ACL reconstructions without MM injuries were included in this study. MM deformation was evaluated using open MRI before surgery and 3 months after surgery. We measured medial meniscal length (MML), medial meniscal height (MMH), medial meniscal posterior body width (MPBW), MM–femoral condyle contact width (M-FCW) and posterior tibiofemoral distance (PTFD) at knee flexion angles of 10° and 90°. Results: There were no significant pre- and postoperative differences during a flexion angle of 10°. At a flexion angle of 90°, MML decreased from 43.7 ± 4.5 to 41.4 ± 4.5 mm (P &lt
     0.001), MMH from 7.5 ± 1.4 to 6.9 ± 1.4 mm (P = 0.006), MPBW from 13.1 ± 2.0 to 12.2 ± 1.9 mm (P &lt
     0.001) and M-FCW from 10.0 ± 1.5 to 8.5 ± 1.5 mm (P &lt
     0.001) after ACL reconstruction. The PTFD increased from 2.1 ± 2.8 to 2.7 ± 2.4 mm after ACL reconstruction (P = 0.015). Conclusions: ACL reconstruction affects the contact pattern between the MM posterior segment and medial femoral condyle and can reduce the deformation of the MM posterior segment in the knee-flexed position by reducing abnormal anterior tibial translation. It possibly prevents secondary injury to the MM posterior segment and cartilage that progresses to knee osteoarthritis. Level of evidence: IV.

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  • Extensive Bilateral Patellar Tendon Ossification in a Spinal Cord Injury Patient.

    Norio Yamamoto, Takaaki Miki, Akihiro Nishiyama, Tomoyuki Dan'ura, Yuzuru Matsui, Toshifumi Ozaki

    Acta medica Okayama   72 ( 1 )   89 - 93   2018.2

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    This is the first report of extensive bilateral patellar tendon ossification occurring over a prolonged time after a unilateral knee injury. An 84-year-old Japanese man with a spinal cord injury caused by a burst fracture of the T12 vertebra presented with a bony hard prominence on the left knee, which was injured in a traffic accident when he was 77 years old. Radiography revealed extensive ossification of the bilateral patellar tendons. We review the English literature with a focus on the localization of bilateral heterotopic ossification of the knee in patients who had a central nervous system injury.

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  • Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin- furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury. Reviewed International journal

    Kentaro Yamane, Tetsuro Mazaki, Yasuyuki Shiozaki, Aki Yoshida, Kensuke Shinohara, Mariko Nakamura, Yasuhiro Yoshida, Di Zhou, Takashi Kitajima, Masato Tanaka, Yoshihiro Ito, Toshifumi Ozaki, Akihiro Matsukawa

    Scientific reports   8 ( 1 )   917 - 917   2018.1

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    The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.

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  • Accuracy of Cup Positioning With the Computed Tomography-Based Two-dimensional to Three-Dimensional Matched Navigation System: A Prospective, Randomized Controlled Study Reviewed

    Kazuki Yamada, Hirosuke Endo, Tomonori Tetsunaga, Takamasa Miyake, Tomoaki Sanki, Toshifumi Ozaki

    Journal of Arthroplasty   33 ( 1 )   136 - 143   2018.1

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    Background The accuracy of various navigation systems used for total hip arthroplasty has been described, but no publications reported the accuracy of cup orientation in computed tomography (CT)-based 2D-3D (two-dimensional to three-dimensional) matched navigation. Methods In a prospective, randomized controlled study, 80 hips including 44 with developmental dysplasia of the hips were divided into a CT-based 2D-3D matched navigation group (2D-3D group) and a paired-point matched navigation group (PPM group). The accuracy of cup orientation (absolute difference between the intraoperative record and the postoperative measurement) was compared between groups. Additionally, multiple logistic regression analysis was performed to evaluate patient factors affecting the accuracy of cup orientation in each navigation. Results The accuracy of cup inclination was 2.5° ± 2.2° in the 2D-3D group and 4.6° ± 3.3° in the PPM group (P =.0016). The accuracy of cup anteversion was 2.3° ± 1.7° in the 2D-3D group and 4.4° ± 3.3° in the PPM group (P =.0009). In the PPM group, the presence of roof osteophytes decreased the accuracy of cup inclination (odds ratio 8.27, P =.0140) and the absolute value of pelvic tilt had a negative influence on the accuracy of cup anteversion (odds ratio 1.27, P =.0222). In the 2D-3D group, patient factors had no effect on the accuracy of cup orientation. Conclusion The accuracy of cup positioning in CT-based 2D-3D matched navigation was better than in paired-point matched navigation, and was not affected by patient factors. It is a useful system for even severely deformed pelvises such as developmental dysplasia of the hips.

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  • Iatrogenic injury of the lateral meniscus anterior insertion following anterior cruciate ligament reconstruction: A case report Reviewed

    Takayuki Furumatsu, Toshifumi Ozaki

    Journal of Orthopaedic Science   23 ( 1 )   197 - 201   2018.1

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  • The clinical course of patients with rheumatoid arthritis who underwent orthopaedic surgeries under disease control by tofacitinib. Reviewed

    Nishida K, Harada R, Nasu Y, Takeshita A, Nakahara R, Matsumeda M, Ozaki T

    Modern rheumatology   28 ( 6 )   1 - 8   2018.1

  • Molecular radiosensitization of p53-armed telomerase-dependent oncolytic adenovirus against human soft-tissue sarcoma

    Tadashi Komatsubara, Hiroshi Tazawa, Yusuke Mochizuki, Kazuhisa Sugiu, Toshinori Omori, Yasuaki Yamakawa, Syuhei Osaki, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

    CANCER SCIENCE   109   454 - 454   2018.1

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  • Liquid biopsy using tumor-derived exosomes for Ewing sarcoma patients

    Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Shintaro Iwata, Yusuke Yoshioka, Koji Ueda, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Takahiro Ochiya, Toshifumi Ozaki

    CANCER SCIENCE   109   312 - 312   2018.1

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  • A rare manifestation of extraskeletal myxoid chondrosarcoma with a huge expanding hematoma Reviewed

    Toshinori Omori, Tomohiro Fujiwara, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Aki Yoshida, Hiroyuki Yanai, Toshifumi Ozaki

    Journal of Orthopaedic Science   24 ( 2 )   377 - 381   2018

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  • Intercondylar and central regions of complete discoid lateral meniscus have different cell and matrix organizations Reviewed

    Takayuki Furumatsu, Ami Maehara, Yuki Okazaki, Toshifumi Ozaki

    Journal of Orthopaedic Science   23 ( 5 )   811 - 818   2018

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    Background: A complete discoid lateral meniscus (DLM) has a high risk of horizontal tear. However, cellular phenotypes and extracellular matrix organizations in complete DLMs are still unclear. The aim of this study was to investigate histological and cellular biological characteristics in both the intercondylar and central regions of complete DLM. Materials and methods: Meniscal samples were obtained from the intercondylar and central regions of complete DLM (n = 6). Blood vessels and aggregated cell ratio were measured in each region. Depositions of type I/II collagens and safranin O-stained proteoglycans in the extracellular matrix were assessed. Experiments in gene expression, morphology, proliferation, and effect of mechanical stretch were performed using cultured cells derived from each region. Results: Blood vessel counts were significantly higher in the intercondylar region than in the central region. The ratio of aggregated cells was lower in the intercondylar region than in the central region. Deposition of type I collagen was comparable for both regions. The central region contained a larger quantity of type II collagen and safranin O staining density compared with the intercondylar region. Proliferation of the fibroblastic intercondylar cells was not affected by 5%-stretching. However, stretching treatments decreased relative proliferation of the chondrocytic central cells. Conclusions: This study demonstrated that the central region of complete DLM had different cellular properties and collagen components compared with the intercondylar region. Our results suggest that the central region of complete DLM may have a low healing potential like the inner avascular region of the meniscus.

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  • Meniscal Extrusion Progresses Shortly after the Medial Meniscus Posterior Root Tear. Reviewed

    Furumatsu T, Kodama Y, Kamatsuki Y, Hino T, Okazaki Y, Ozaki T

    Knee surgery & related research   29 ( 4 )   295 - 301   2017.12

  • Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells Reviewed

    Ken Morita, Mina Noura, Chieko Tokushige, Shintaro Maeda, Hiroki Kiyose, Gengo Kashiwazaki, Junichi Taniguchi, Toshikazu Bando, Kenichi Yoshida, Toshifumi Ozaki, Hidemasa Matsuo, Seishi Ogawa, Pu Paul Liu, Tatsutoshi Nakahata, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo

    SCIENTIFIC REPORTS   7 ( 1 )   16604   2017.11

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    Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-beta (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene silencing directly binds to CBFB promoter and stimulates its transcription as well as its translation, which in turn acts as a platform for the stabilization of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed, AML cells derived from relapsed cases exhibited higher CBFB expression levels compared to those from primary AML cells at diagnosis, and these CBFB expressions were positively correlated to those of p53. Our present results underscore the importance of RUNX1-p53-CBFB regulatory loop in the development and/or maintenance of AML cells, which could be targeted at any sides of this triangle in strategizing anti-leukemia therapies.

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  • Circulating MicroRNA-92b-3p as a Novel Biomarker for Monitoring of Synovial Sarcoma Reviewed

    Koji Uotani, Tomohiro Fujiwara, Aki Yoshida, Shintaro Iwata, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Kunihiko Numoto, Yutaka Nezu, Tsukasa Yonemoto, Takeshi Ishii, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki

    SCIENTIFIC REPORTS   7 ( 1 )   14634   2017.11

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    The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2. Animal experiments revealed a close correlation between serum miR-92b-3p levels and tumour dynamics. Clinical relevance was validated in two independent clinical cohorts, and we subsequently identified that serum miR-92b-3p levels were significantly higher in SS patients in comparison to that in healthy individuals. Moreover, serum miR-92b-3p was robust in discriminating patients with SS from the other STS patients and reflected tumour burden in SS patients. Overall, liquid biopsy using serum miR-92b-3p expression levels may represent a novel approach for monitoring tumour dynamics of SS.

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  • Inhibitory effect of JAK inhibitor on mechanical stress-induced protease expression by human articular chondrocytes. International journal

    Takahiro Machida, Keiichiro Nishida, Yoshihisa Nasu, Ryuichi Nakahara, Masatsugu Ozawa, Ryozo Harada, Masahiro Horita, Ayumu Takeshita, Daisuke Kaneda, Aki Yoshida, Toshifumi Ozaki

    Inflammation research : official journal of the European Histamine Research Society ... [et al.]   66 ( 11 )   999 - 1009   2017.11

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    OBJECTIVE: To investigate whether janus kinase (JAK) inhibitor exhibits a chondro-protective effect against mechanical stress-induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinase (MMPs) in human chondrocytes. MATERIALS AND METHODS: Normal human articular chondrocytes were seeded onto stretch chambers and incubated with or without tofacitinib (1000 nM) for 12 h before mechanical stimulation or cytokine stimulation. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 10% elongation, 30 min) was applied and the gene expression levels of type II collagen α1 chain (COL2A1), aggrecan (ACAN), ADAMTS4, ADAMTS5, MMP13, and runt-related transcription factor 2 (RUNX-2) were examined by real-time polymerase chain reaction. Nuclear translocation of RUNX-2 and nuclear factor-κB (NF-κB) was examined by immunocytochemistry, and phosphorylation of mitogen-activated protein kinase (MAPK) and signaling transducer and activator of transcription (STAT) 3 was examined by western blotting. The concentration of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the supernatant was examined by enzyme-linked immunosorbent assay. RESULTS: COL2A1 and ACAN gene expression levels were decreased by CTS, but these catabolic effects were canceled by tofacitinib. Tofacitinib significantly down-regulated CTS-induced expression of ADAMTS4, ADAMTS5, MMP13, and RUNX2, and the release of IL-6 in supernatant by chondrocytes. Tofacitinib also reduced CTS-induced nuclear translocation of RUNX-2 and NF-κB, and phosphorylation of MAPK and STAT3. CONCLUSION: Tofacitinib suppressed mechanical stress-induced expression of ADAMTS4, ADAMTS5, and MMP13 by human chondrocytes through inhibition of the JAK/STAT and MAPK cascades.

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  • Tibial eminence width can predict the presence of complete discoid lateral meniscus: A preliminary study.

    Tomohito Hino, Takayuki Furumatsu, Masataka Fujii, Yuya Kodama, Shinichi Miyazawa, Yusuke Kamatsuki, Kazuki Yamada, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   22 ( 6 )   1084 - 1088   2017.11

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    BACKGROUND: To compare the plain knee radiograph finding of tibial eminence width between knees with complete discoid lateral meniscus, incomplete discoid lateral meniscus, and normal lateral meniscus. MATERIALS AND METHODS: The study included 27 knees with discoid lateral meniscus, including 13 knees with complete discoid lateral meniscus and 14 knees with incomplete discoid lateral meniscus. A control group of 14 knees with normal lateral meniscus was also included. Tibial eminence width and the lateral slope angle of the medial tibial eminence were assessed using plain frontal knee radiographs. Individual differences in knee size were corrected by dividing tibial eminence width by tibial width to obtain the tibial eminence width percentage. RESULTS: Mean tibial eminence width and tibial eminence width percentage in the complete discoid lateral meniscus group was significant larger than other groups. Mean lateral slope angle in the complete discoid lateral meniscus group was significantly smaller than other groups. A tibial eminence width cut-off of 13.9 mm showed a sensitivity and specificity of 100% and 83%, respectively. A tibial eminence width percentage cut-off of 18.8% showed a sensitivity and specificity of 100% and 90%, respectively. A lateral slope angle cut-off of 27.1° showed a sensitivity and specificity of 71% and 83%, respectively. CONCLUSION: There were clear differences in tibial eminence width, tibial eminence width percentage, and lateral slope angle between the complete discoid lateral meniscus group and the other groups. The plain radiographic parameters identified by this study could be useful for complete discoid lateral meniscus screening. STUDY DESIGN: Clinical.

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  • Arthroscopic Repair of the Medial Meniscus Radial/Oblique Tear Prevents the Progression of Meniscal Extrusion in Mildly Osteoarthritic Knees Reviewed

    Takayuki Furumatsu, Yuya Kodama, Yusuke Kamatsuki, Tomohito Hino, Toshifumi Ozaki

    ACTA MEDICA OKAYAMA   71 ( 5 )   413 - 418   2017.10

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    Extrusion of the medial meniscus (MM) is associated with knee joint pain in osteoarthritic knees. The relationships among MM radial/ oblique tears, MM extrusion (MME), and the effect of arthroscopic meniscal repair are not established. Here we evaluated the effects of arthroscopic all-inside MM repair on MME and the clinical outcomes in patients with radially oriented MM tears and mildly osteoarthritic knees. Twenty patients with a symptomatic radial or oblique tear of the MM posterior segment, MME = 2.5 mm, and mildly osteoarthritic knees were treated using FasT-Fix 360 All-inside Meniscal Suture devices. We used magnetic resonance imaging (MRI) to measure the patients' MM body width (MMBW), absolute MME, and relative MME. The Japanese Knee Injury and Osteoarthritis Outcome Score, Lysholm, Tegner, IKDC Subjective Knee Evaluation, and Visual Analogue Scale scores were obtained. Arthroscopic all-inside MM repair prevented increases of absolute and relative MME. The preoperative and 3- and 12-month MRI-based MMBW values were similar. Over a 24-month follow-up after the MM repairs, the clinical scores showed significant improvements. Our results suggest that all-inside meniscal repairs would be useful in preventing the progression of MME in patients suffering from symptomatic MM radial/ oblique tears associated with mildly osteoarthritic knees.

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  • Tensile strength of the pullout repair technique for the medial meniscus posterior root tear: a porcine study. International journal

    Masataka Fujii, Takayuki Furumatsu, Haowei Xue, Shinichi Miyazawa, Yuya Kodama, Tomohito Hino, Yusuke Kamatsuki, Toshifumi Ozaki

    International orthopaedics   41 ( 10 )   2113 - 2118   2017.10

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    PURPOSE: The purpose of this study was to compare the load-to-failure of different common suturing techniques with a new technique for the medial meniscus posterior root tear (MMPRT). METHODS: Thirty porcine medial menisci were randomly assigned to three suturing techniques used for transtibial pullout repair of the MMPRT (n = 10 per group). Three different meniscal suture configurations were studied: the two simple suture (TSS) technique, the conventional modified Mason-Allen suture (MMA) technique, and the new MMA technique using the FasT-Fix combined with the Ultrabraid (F-MMA). The ultimate failure load was tested using a tensile testing machine. RESULTS: The MMA and F-MMA groups demonstrated significantly higher failure loads than the TSS group (P = 0.0003 and P = 0.0005, respectively). No significant differences were observed between the MMA and F-MMA groups (P = 0.734). CONCLUSIONS: The ultimate failure load was significantly greater in the F-MMA than the TSS group and similar to the conventional MMA technique.

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  • Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction. Reviewed

    Yamakawa Y, Tazawa H, Hasei J, Osaki S, Omori T, Sugiu K, Komatsubara T, Uotani K, Fujiwara T, Yoshida A, Kunisada T, Urata Y, Kagawa S, Ozaki T, Fujiwara T

    Cancer science   108 ( 9 )   1870 - 1880   2017.9

  • がん免疫療法の一段の進化へむけて 腫瘍浸潤免疫細胞の代謝は抗腫瘍免疫応答を制御する

    鵜殿 平一郎, 榮川 伸吾, 國定 勇希, 上原 健敬, 渡邉 元嗣, 木村 裕司, 佐々木 朗, 尾崎 敏文, 豊岡 伸一, 藤原 俊義

    日本癌学会総会記事   76回   S10 - 5   2017.9

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  • Cervical Spine Osteoradionecrosis Reviewed

    Masato Tanaka, Yoshihisa Sugimoto, Tomoyuki Takigawa, Yoshihiro Kimata, Toshifumi Ozaki

    ACTA MEDICA OKAYAMA   71 ( 4 )   345 - 349   2017.8

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    Osteoradionecrosis (ORN), a well-known complication of radiotherapy in the mandibular bone, is very rare in the cervical spine. The authors report the result of a 3-year follow-up of a 63-year-old female patient with ORN of the cervical spine. The patient had a history of laryngeal carcinoma and was treated with chemotherapy and radiation therapy with a total of 120 Gy. Eight years later, she developed acute, severe neck pain due to cervical spine necrosis. The authors performed vascularized fibular bone graft and posterior pedicle screw fixation to reconstruct her cervical spine. The patient was successfully treated with surgery, and cervical alignment was preserved. She had neither neurological deficits nor severe neck pain at her final follow-up 3 years later. Delaying treatment of ORN may be life threatening, so the early diagnosis of this condition is important for patients who receive radiotherapy. Otolaryngologists and spine surgeons should understand this potential complication to speed diagnosis and treatment as early as possible.

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  • An Analysis of the Characteristics and Improved Use of Newly Developed CT-based Navigation System in Total Hip Arthroplasty.

    Yosuke Fujii, Kazuo Fujiwara, Tomonori Tetsunaga, Takamasa Miyake, Kazuki Yamada, Hirosuke Endo, Nobuhiro Abe, Naohiko Sugita, Mamoru Mitsuishi, Takayuki Inoue, Yoshio Nakashima, Toshifumi Ozaki

    Acta medica Okayama   71 ( 4 )   279 - 289   2017.8

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    We developed a surface matching-type computed tomography (CT)-based navigation system for total hip arthroplasty (the N-navi; TEIJIN NAKASHIMA MEDICAL, Okayama, Japan). In the registration step, surface matching was performed with digitizing points on the pelvic bone surface after coarse paired matching. In the present study, we made model bones from the CT data of patients whose acetabular shapes had various deformities. We measured the distances and angles after surface matching from the fiducial points and evaluated the ability to correct surface-matching registration on each pelvic form, using several areas and numbers of points. When the surface-matching points were taken on the superior area of the acetabulum, the correction was easy for the external direction, but it was difficult to correct for the anterior and proximal directions. The correction was difficult for external and proximal directions on the posterior area. Each area of surface-matching points has particular directions that are easily corrected and other directions that are difficult to correct. The shape of the pelvis also affected the correction ability. Our present findings suggest that checking the position after coarse paired matching and choosing the surface-matching area and points that are optimal to correct will improve the accuracy of total hip arthroplasty and reduce surgical times.

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  • Location of the tibial tunnel aperture affects extrusion of the lateral meniscus following reconstruction of the anterior cruciate ligament. International journal

    Yuya Kodama, Takayuki Furumatsu, Shinichi Miyazawa, Masataka Fujii, Takaaki Tanaka, Hiroto Inoue, Toshifumi Ozaki

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society   35 ( 8 )   1625 - 1633   2017.8

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    The anterior root of the lateral meniscus provides functional stability to the meniscus. In this study, we evaluated the relationship between the position of the tibial tunnel and extrusion of the lateral meniscus after anterior cruciate ligament reconstruction, where extrusion provides a proxy measure of injury to the anterior root. The relationship between extrusion and tibial tunnel location was retrospectively evaluated from computed tomography and magnetic resonance images of 26 reconstructed knees, contributed by 25 patients aged 17-31 years. A measurement grid was used to localize the position of the tibial tunnel based on anatomical landmarks identified from the three-dimensional reconstruction of axial computed tomography images of the tibial plateaus. The reference point-to-tibial tunnel distance (mm) was defined as the distance from the midpoint of the lateral edge of the grid to the posterolateral aspect of the tunnel aperture. The optimal cutoff of this distance to minimize post-operative extrusion was identified using receiver operating curve analysis. Extrusion of the lateral meniscus was positively correlated to the reference point-to-tibial tunnel distance (r 2  = 0.64; p < 0.001), with a cutoff distance of 5 mm having a sensitivity to extrusion of 83% and specificity of 93%. The mean extrusion for a distance >5 mm was 0.40 ± 0.43 mm, compared to 1.40 ± 0.51 mm for a distance ≤5 mm (p < 0.001). Therefore, a posterolateral location of the tibial tunnel aperture within the footprint of the anterior cruciate ligament decreases the reference point-to-tibial tunnel distance and increases extrusion of the lateral meniscus post-reconstruction. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1625-1633, 2017.

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  • Residual Femoral Deformity and Femoroacetabular Impingement after Intertrochanteric Osteotomy for Slipped Capital Femoral Epiphysis.

    Yosuke Fujii, Hirosuke Endo, Shigeru Mitani, Hirofumi Akazawa, Tomonori Tetsunaga, Takamasa Miyake, Kazuki Yamada, Kiyoshi Aoki, Toshifumi Ozaki

    Acta medica Okayama   71 ( 4 )   315 - 323   2017.8

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    We retrospectively reviewed 29 hips in which intertrochanteric osteotomies were performed for severe slipped capital femoral epiphyses. Mean age at surgery: 12.6 years. Mean follow-up period: 6 years. At the final follow-up evaluation, one patient had coxalgia, and six hips showed a limited range of motion. A pistol-grip deformity was observed in 13 hips, osteoarthritis in two hips, and a bump existed in 19 hips on the latest radiographs. Gradual remodeling of the bumps was observed post-operatively in 22 hips. The mean α and β angles and offset α and β improved over time. The remodeling proceeded rapidly for 1 year post-surgery. We compared hips classified as β angles of ≥ 63° to < 63° at the final follow-up evaluation, the mean β angle 1 year post-surgery, and the mean ratio of improvement of the β angle per year from 1 year post-surgery to the final follow up, which differed significantly. Nearly all of the patients who underwent intertrochanteric osteotomies had residual morphologic abnormalities, but few had clinical symptoms. The β angle 1 year post-surgery and the ratio of remodeling of the bump from 1 year post-surgery to the final follow-up can be regarded as a potential predictor of morphologic results after intertrochanteric osteotomy.

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  • A giraffe neck sign of the medial meniscus: A characteristic finding of the medial meniscus posterior root tear on magnetic resonance imaging.

    Takayuki Furumatsu, Masataka Fujii, Yuya Kodama, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   22 ( 4 )   731 - 736   2017.7

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    BACKGROUND: The posterior root ligament of the medial meniscus (MM) has a critical role in regulating the MM movement. An accurate diagnosis of the MM posterior root tear (MMPRT) using magnetic resonance imaging (MRI) is important for preventing sequential osteoarthritis following the MMPRT. However, diagnosis of the MMPRT is relatively difficult even after using several characteristic MRI findings. The aim of this study was to identify a useful meniscal body sign of the MMPRT for improving diagnostic MRI reading. METHODS: Eighty-five patients who underwent surgical treatments for the MMPRT (39 knees) and other types of MM tears (49 knees) were included. The presence of characteristic MRI findings such as cleft sign, ghost sign, radial tear sign, medial extrusion sign, and new meniscal body shape-oriented "giraffe neck sign" was evaluated in 120 MRI examinations. RESULTS: Giraffe neck signs were observed in 81.7% of the MMPRTs and in 3.3% of other MM tears. Cleft, ghost, and radial tear signs were highly positive in the MMPRTs compared with other MM tears. Medial extrusion signs were frequently observed in both groups. Coexistence rates of any 2 MRI signs, except for medial extrusion sign, were 91.7% in the MMPRT group and 5% in other MM tears. CONCLUSIONS: This study demonstrated that a new characteristic MRI finding "giraffe neck sign" was observed in 81.7% of the MMPRT. Our results suggest that the combination of giraffe neck, cleft, ghost, and radial tear signs may be important for an accurate diagnostic MRI reading of the MMPRT.

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  • The distribution of vascular endothelial growth factor in human meniscus and a meniscal injury model.

    Zhichao Lu, Takayuki Furumatsu, Masataka Fujii, Ami Maehara, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   22 ( 4 )   715 - 721   2017.7

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    BACKGROUND: The meniscus plays an important role in controlling the complex biomechanics of the knee. Meniscus injury is common in the knee joint. The perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Angiogenesis factors, such as vascular endothelial growth factor (VEGF), have important roles in promoting vascularization of various tissues. VEGF-mediated neovascularization is beneficial to the healing of injured tissues. However, the distribution and angiogenic role of VEGF remains unclear in the meniscus and injured meniscus. We hypothesized that VEGF could affect meniscus cells and modulate the meniscus healing process. METHODS: Menisci were obtained from total knee arthroplasty patients. Meniscal injury was created ex vivo by a microsurgical blade. VEGF mRNA and protein expression were detected by the polymerase chain reaction and immunohistochemical analyses, respectively. RESULTS: In native meniscal tissue, the expression of VEGF and HIF-1α mRNAs could not be detected. However, VEGF and HIF-1α mRNAs were found in cultured meniscal cells (VEGF: outer > inner; HIF-1α: outer = inner). Injury increased mRNA levels of both VEGF and HIF-1α, with the increase being greatest in the outer area. Immunohistochemical analyses revealed that VEGF protein was detected mainly in the outer region and around injured areas of the meniscus. However, VEGF concentrations were similar between inner and outer menisci-derived media. CONCLUSIONS: This study demonstrated that both the inner and outer regions of the meniscus contained VEGF. HIF-1α expression and VEGF deposition were high in injured meniscal tissue. Our results suggest that injury stimulates the expression of HIF-1α and VEGF that may be preserved in the extracellular matrix as the healing stimulator of damaged meniscus, especially in the outer meniscus.

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  • Discrimination between Malignant and Benign Vertebral Fractures Using Magnetic Resonance Imaging. International journal

    Tomoyuki Takigawa, Masato Tanaka, Yoshihisa Sugimoto, Tomoko Tetsunaga, Keiichiro Nishida, Toshifumi Ozaki

    Asian spine journal   11 ( 3 )   478 - 483   2017.6

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    STUDY DESIGN: Retrospective analysis using magnetic resonance imaging (MRI). PURPOSE: To identify MRI features that could discriminate benign from malignant vertebral fractures. OVERVIEW OF LITERATURE: Discrimination between benign and malignant vertebral fractures remains challenging, particularly in patients with osteoporosis and cancer. Presently, the most sensitive means of detecting and assessing fracture etiology is MRI. However, published reports have focused on only one or a few discriminators. METHODS: Totally, 106 patients were assessed by MRI within six weeks of sustaining 114 thoracic and/or lumbar vertebral fractures (benign, n=65; malignant, n=49). The fractures were pathologically confirmed if malignant or clinically diagnosed if benign and were followed up for a minimum of six months. Seventeen features were analyzed in all fractures' magnetic resonance images. Single parameters were analyzed using the chi-square test; a logit model was established using multivariate logistic regression analysis. RESULTS: The chi-square test revealed 11 malignant and 4 benign parameters. Multivariate logistic regression analysis selected (i) posterior wall diffuse protrusion (odds ratio [OR], 48; 95% confidence interval [CI], 4.2-548; p=0.002), (ii) pedicle involvement (OR, 21; 95% CI, 2.0-229; p=0.01), (iii) posterior involvement (OR, 21; 95% CI, 1.5-21; p=0.02), and (iv) band pattern (OR, 0.047; 95% CI, 0.0005-4.7; p=0.19). The logit model was expressed as P=1/[1+exp (x)], x=-3.88×(i)-3.05×(ii)-3.02×(iii)+3.05×(iv)+5.00, where P is the probability of malignancy. The total predictive value was 97.3%. The only exception was multiple myeloma with features of a benign fracture. CONCLUSIONS: Although each MRI feature had a different meaning with a variable differentiation power, combining them led to an accurate diagnosis. This study identified the most relevant MRI features that would be helpful in discriminating benign from malignant vertebral fractures.

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  • Accuracy of pedicle screw insertion in posterior scoliosis surgery: a comparison between intraoperative navigation and preoperative navigation techniques. International journal

    Wei Zhang, Tomoyuki Takigawa, YongGang Wu, Yoshihisa Sugimoto, Masato Tanaka, Toshifumi Ozaki

    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   26 ( 6 )   1756 - 1764   2017.6

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    PURPOSE: This study was conducted to compare the efficacy and accuracy of intraoperative navigation (O-arm or Arcadis navigation) and preoperative CT-based navigation in adolescent idiopathic scoliosis (AIS) surgery. METHODS: Sixty-seven patients with scoliosis were grouped according to the method of navigation used in their fixation surgeries. A total of 492 pedicle screws were implanted in 27 patients using intraoperative navigation, and 626 screws were implanted in 40 patients using preoperative navigation. We analyzed the postoperative CT images for pedicle violations using the Gertzbein classification. RESULTS: There was no statistical difference in the accuracy of pedicle screw placement between two groups. However, in the apical region (the apex ± 2 vertebrae), the accuracy of safe pedicle screw placement (grades 0, 1) was significantly higher in the intraoperative navigation group than in the preoperative navigation group (94.8 vs 89.2%, respectively; P = 0.035). Intraoperative navigation significantly diminished medial perforation compared to preoperative navigation (P = 0.027), and the number of screws per vertebra that could be placed in the apical region was significantly higher in intraoperative navigation group (P < 0.001). In addition, the time required for the registration procedure and insertion of one pedicle screw was 11.3 ± 2.1 min in the preoperative group, but significantly decreased to 5.1 ± 1.1 min in the intraoperative group (P < 0.001). CONCLUSIONS: Both preoperative CT-based and intraoperative navigation systems provide sufficient accuracy and safety in pedicle screw insertion for AIS surgery. Intraoperative navigation systems facilitate pedicle screw insertion in the apical region and reduce registration time during AIS surgery which improves the efficacy and accuracy of pedicle screw insertion.

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  • Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma. International journal

    Tomohiro Fujiwara, Koji Uotani, Aki Yoshida, Takuya Morita, Yutaka Nezu, Eisuke Kobayashi, Akihiko Yoshida, Takenori Uehara, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Ken Takeda, Toshiyuki Kunisada, Machiko Kawamura, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki

    Oncotarget   8 ( 20 )   33375 - 33392   2017.5

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    BACKGROUND: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. METHODS: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. RESULTS: Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. CONCLUSIONS: Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

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  • A new aiming guide can create the tibial tunnel at favorable position in transtibial pullout repair for the medial meniscus posterior root tear Reviewed

    T. Furumatsu, Y. Kodama, M. Fujii, T. Tanaka, T. Hino, Y. Kamatsuki, K. Yamada, S. Miyazawa, T. Ozaki

    Revue de Chirurgie Orthopedique et Traumatologique   103 ( 3 )   248   2017.5

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    Introduction Injuries to the medial meniscus (MM) posterior root lead to accelerated cartilage degeneration of the knee. An anatomic placement of the MM posterior root attachment is considered to be critical in transtibial pullout repair of the medial meniscus posterior root tear (MMPRT). However, tibial tunnel creation at the anatomic attachment of the MM posterior root is technically difficult using a conventional aiming device. The aim of this study was to compare two aiming guides. We hypothesized that a newly-developed guide specifically designed creates the tibial tunnel at an adequate position rather than a conventional device. Materials and methods Twenty-six patients underwent transtibial pullout repairs. Tibial tunnel creation was performed using the Multi-use guide (8 cases) or the PRT guide that had a narrow twisting/curving shape (18 cases). Three-dimensional computed tomography images of the tibial surface were evaluated using the Tsukada's measurement method postoperatively. Expected anatomic center of the MM posterior root attachment and tibial tunnel center were evaluated using the percentage-based posterolateral location on the tibial surface. Percentage distance between anatomic center and tunnel center was calculated. Results Anatomic center of the MM posterior root footprint located at a position of 78.5% posterior and 39.4% lateral. Both tunnels were anteromedial but tibial tunnel center located at a more favorable position in the PRT group: percentage distance was significantly smaller in the PRT guide group (8.7%) than in the Multi-use guide group (13.1%). Discussion The PRT guide may have great advantage to achieve a more anatomic location of the tibial tunnel in MMPRT pullout repair. Level of evidence IV.

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  • Short-term outcomes of patients being treated for chronic intractable pain at a liaison clinic and exacerbating factors of prolonged pain after treatment.

    Tomoko Tetsunaga, Tomonori Tetsunaga, Keiichiro Nishida, Masato Tanaka, Yoshihisa Sugimoto, Tomoyuki Takigawa, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   22 ( 3 )   554 - 559   2017.5

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    BACKGROUND: Although a multidisciplinary approach is often recommended to treat intractable pain, this approach does not completely prevent uncontrolled pain in some patients. The aim of this retrospective study was to investigate the exacerbating factors of prolonged, intractable pain among patients being treated at a pain liaison clinic. METHODS: The participants of this study were 94 outpatients (32 men, 62 women) with chronic intractable pain who visited our hospital between April 2013 and February 2015. Demographic and clinical information was obtained from all patients at baseline. Experts in various fields, including anesthesia, orthopedic surgery, psychiatry, physical therapy, and nursing, were involved in the treatment procedures. All patients were assessed before and after a 6-month treatment period using the following measures: the Numeric Rating Scale (NRS); the Pain Catastrophizing Scale (PCS); the Hospital Anxiety and Depression Scale (HADS); the Pain Disability Assessment Scale (PDAS); and the Oswestry Disability Index (ODI). All participants were then divided into two groups based on their self-reported pain after treatment: a pain relief group (n = 70) and a prolonged pain group (n = 24). The exacerbating factors of prolonged pain after treatment in the pain liaison outpatient clinic were analyzed using univariate and multiple logistic regression analysis. RESULTS: A significant improvement in NRS scores was observed after the 6-month follow-up period. After treatment, 24 (25.5%) of the 94 patients reported having prolonged pain. Significant improvements were seen in the PCS, PDAS, and ODI scores in the pain relief group, and in the HADS depression scores in the prolonged pain group. On univariate and multiple regression analysis, HADS depression scores were identified as a factor related to prolonged pain after treatment. CONCLUSIONS: The results of the present study suggest that severe depression at the initial visit to the liaison outpatient clinic was an exacerbating factor for prolonged pain after treatment.

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  • Congenital double-level cervical spondylolysis: a case report and review of the literature. International journal

    Norio Yamamoto, Takaaki Miki, Yoshihisa Nasu, Akihiro Nishiyama, Tomoyuki Dan'ura, Yuzuru Matsui, Toshifumi Ozaki

    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   26 ( Suppl 1 )   181 - 185   2017.5

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    PURPOSE: We report a rare Japanese female who was affected with three genetic-linked diseases: double-level cervical bilateral spondylolysis in association with spina bifida occulta, cleft lip and monostotic fibrous dysplasia of the right proximal femur. The case was considered to be congenital in origin. We also review the pertinent literature of cervical spondylolysis, with a focus on the pathogenesis of multiple-level cervical spondylolysis. METHODS: A 40-year-old female presented with progressive clumsiness and numbness of the hands. Japanese Orthopedic Association (JOA) score for the cervical spine was 14.5. Plain radiographs of the cervical spine showed bilateral spondylolysis of the articular mass portion, with an adjacent dysplastic change and spina bifida occulta of C4 and C5. Cervical laminoplasty from C4 to C6 was performed. RESULTS: The postoperative course was uneventful, and the patient had some recovery of muscle power and sensation, with JOA score improving to 15.5. At the 8-year follow-up, the patient had no recurrence of symptoms, but did show kyphotic and degenerative changes at the C4/5 and C5/6 level with no apparent instability. CONCLUSIONS: This case is a rare presentation of bilateral cervical spondylolysis involving C4 and C5, presumably congenital, accompanied by combined dysplastic changes of the cervical spine, cleft lip, and fibrous dysplasia, possibly through an error involving an ossification center during the embryonic stage.

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  • 股関節鏡手術に際しVAPRの破損を生じた2例

    山田 和希, 遠藤 裕介, 尾崎 敏文

    JOSKAS   42 ( 4 )   692 - 692   2017.5

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  • Scoliosis in Patients with Severe Cerebral Palsy: Three Different Courses in Adolescents.

    Yoshiaki Oda, Tomoyuki Takigawa, Yoshihisa Sugimoto, Masato Tanaka, Hirofumi Akazawa, Toshifumi Ozaki

    Acta medica Okayama   71 ( 2 )   119 - 126   2017.4

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    Patients with cerebral palsy (CP) frequently present with scoliosis; however, the pattern of curve progression is difficult to predict. We aimed to clarify the natural course of the progression of scoliosis and to identify scoliosis predictors. This was a retrospective, single-center, observational study. Total of 92 CP patients from Asahikawasou Ryouiku Iryou Center in Okayama, Japan were retrospectively analyzed. Cobb angle, presence of hip dislocation and pelvic obliquity, and Gross Motor Function Classification System (GMFCS) were investigated. Severe CP was defined as GMFCS level IV or V. The mean observation period was 10.7 years. Thirtyfour severe CP patients presented with scoliosis and were divided into 3 groups based on their clinical courses: severe, moderate and mild. The mean Cobb angles at the final follow-up were 129°, 53°, and 13° in the severe, moderate, and mild groups, respectively. The average progressions from 18 to 25 years were 2.7°/year, 0.7°/year, and 0.1°/year in the severe, moderate, and mild curve groups, respectively. We observed the natural course of scoliosis and identified 3 courses based on the Cobb angle at 15 and 18 years of age. This method of classification may help clinicians predict the patients' disease progression.

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  • Charcot股関節に対しTHAを施行した1例

    山田 和希, 藤原 一夫, 鉄永 智紀, 藤井 洋佑, 三宅 孝昌, 遠藤 裕介, 塩田 直史, 佐藤 徹, 尾崎 敏文

    中国・四国整形外科学会雑誌   29 ( 1 )   145 - 145   2017.4

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  • Denosumab and alendronate treatment in patients with back pain due to fresh osteoporotic vertebral fractures.

    Tomoko Tetsunaga, Tomonori Tetsunaga, Keiichiro Nishida, Masato Tanaka, Yoshihisa Sugimoto, Tomoyuki Takigawa, Yoshitaka Takei, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   22 ( 2 )   230 - 236   2017.3

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    INTRODUCTION: Denosumab specifically inhibits the receptor activator for nuclear factor-kappa B ligand (RANKL), and prevents osteoporotic fractures. Several reports have analyzed the effects of denosumab and alendronate alone on bone mineral density (BMD) or reduction of fracture risk. The objective of this study was to analyze the effects of antiresorptive osteoporosis pharmacotherapy on pain relief in patients with fresh vertebral fracture. METHODS: This retrospective, single-center study included 80 patients (10 males, 70 females) with fresh osteoporotic vertebral fractures treated using denosumab at a dose of 60 mg subcutaneously every 6 months (40 patients) or alendronate at a dose of 35 mg orally every week (40 patients) for 6 months in our hospital. The mean age of subjects was 77 years (range, 55-92 years). The primary outcome was duration of back pain. Secondary outcomes included changes in BMD, serum type 1 collagen cross-linked N-telopeptide (NTX), and serum N-terminal propeptide of type 1 collagen (P1NP) from baseline to 6 months. Pain catastrophizing due to back pain was assessed using the Pain Catastrophizing Scale (PCS). The incidences of further vertebral fracture and adverse events were also assessed. RESULTS: Pain relief was obtained at a mean of 3.3 weeks with denosumab and 5.4 weeks with alendronate. Pain relief was achieved significantly earlier with denosumab than with alendronate. At 6 months, change in BMD was higher with denosumab (6.1%) than with alendronate (0.8%). No significant differences in changes in NTX and P1NP were observed between groups. Scores for PCS were significantly lower for denosumab than for alendronate. The incidence of further vertebral fractures was 5% with denosumab and 10% with alendronate. Adverse event rates were similar between groups. CONCLUSIONS: Denosumab enabled earlier pain relief than alendronate and avoided catastrophizing in patients with osteoporotic vertebral fractures after 6 months of treatment.

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  • Total hip arthroplasty after failed treatment of proximal femur fracture. International journal

    Tomonori Tetsunaga, Kazuo Fujiwara, Hirosuke Endo, Tomoyuki Noda, Tomoko Tetsunaga, Toru Sato, Naofumi Shiota, Toshifumi Ozaki

    Archives of orthopaedic and trauma surgery   137 ( 3 )   417 - 424   2017.3

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    INTRODUCTION: Total hip arthroplasty (THA) is a good option as a salvage procedure after failed treatment of proximal femur fracture. The anatomy of the proximal femur, however, makes this surgery complicated and challenging. The purpose of this study was to evaluate the radiographic and clinical outcomes of THA after failed treatment of proximal femur fractures. MATERIALS AND METHODS: We retrospectively analysed 50 consecutive THAs (42 women, 8 men; mean age 77 years) after failed treatment of a proximal femur fracture. Mean postoperative follow-up was 58.1 months. Preoperative diagnoses were femoral neck fracture in 18 hips and trochanteric fracture in 32 hips, including three that were infected. Failure resulted from cutout in 22 cases, osteonecrosis in 12, non-union with failed fixation in nine, postoperative osteoarthritis in four, and infection in three. Factors compared included radiographic assessment, complication rate, visual analogue scale (VAS), and Harris Hip Scores (HHS). Radiographic variables included femoral neck anteversion and cup and stem alignment. RESULTS: Absolute values of the differences in femoral neck anteversion between the affected and healthy sides were 6.0° in the femoral neck fracture group and 19.2° in the trochanteric fracture group (p = 0.01). There were no significant differences in cup anteversion (p = 0.20) or stem anteversion (p = 0.08). The complication rate was significantly higher in the trochanteric fracture group than in the femoral neck fracture group (25 vs 0%, p < 0.0001). Postoperative complications in the trochanteric fracture group included three periprosthetic fractures (9.4%), two dislocations (6.3%), two surgical-site infections (6.3%), and one stem penetration (3.1%). Although no significant differences between groups were seen in the VAS or HHS at final follow-up (p = 0.32, 0.09, respectively), these measures were significantly improved at final follow-up in both groups (p < 0.0001 for both). CONCLUSIONS: Performing THA after failed treatment of trochanteric fractures requires consideration of complication risk and incorrect femoral neck anteversion.

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  • Anatomic alignment法における脛骨骨切り面形状の解析 Mechanical alignment法との比較

    山田 和希, 古松 毅之, 宮澤 慎一, 藤井 政孝, 井上 博登, 児玉 有弥, 日野 知仁, 釜付 祐輔, 尾崎 敏文, 塩田 直史

    日本整形外科学会雑誌   91 ( 3 )   S918 - S918   2017.3

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  • Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression. International journal

    Kayoko Obora, Yuta Onodera, Toshiyuki Takehara, John Frampton, Joe Hasei, Toshifumi Ozaki, Takeshi Teramura, Kanji Fukuda

    Scientific reports   7   43604 - 43604   2017.2

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    Intracerebral inflammation resulting from injury or disease is implicated in disruption of neural regeneration and may lead to irreversible neuronal dysfunction. Analysis of inflammation-related microRNA profiles in various tissues, including the brain, has identified miR-155 among the most prominent miRNAs linked to inflammation. Here, we hypothesize that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells, we demonstrate that three important genes involved in NSC self-renewal (Msi1, Hes1 and Bmi1) are suppressed by miR-155. We also demonstrate that suppression of self-renewal genes is mediated by the common transcription factor C/EBPβ, which is a direct target of miR-155. Our study describes an axis linking inflammation and miR-155 to expression of genes related to NSC self-renewal, suggesting that regulation of miR-155 may hold potential as a novel therapeutic strategy for treating neuroinflammatory diseases.

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  • Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma. International journal

    Akira Kawai, Nobuhito Araki, Yoichi Naito, Toshifumi Ozaki, Hideshi Sugiura, Yasuo Yazawa, Hideo Morioka, Akihiko Matsumine, Kenichi Saito, Shun Asami, Kazuo Isu

    Japanese journal of clinical oncology   47 ( 2 )   137 - 144   2017.2

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    Objective: Eribulin, a microtubule dynamics inhibitor, is approved for the treatment of patients with breast cancer and soft tissue sarcoma. We investigated the efficacy and safety of eribulin in Japanese patients with soft tissue sarcoma. Methods: This open-label, multicenter, nonrandomized, Phase 2 study enrolled Japanese patients with measurable, advanced/metastatic soft tissue sarcoma of high/intermediate grade and ≥1 prior chemotherapy for advanced disease. Patients received eribulin mesilate 1.4 mg/m2 intravenously over 2–5 minutes on Days 1 and 8 of a 21-day cycle. The primary endpoint was progression-free rate at 12 weeks. Secondary endpoints included overall survival, progression-free survival and safety. Efficacy analyses were stratified by histology (liposarcoma or leiomyosarcoma, and other subtypes). Results: Overall, 52 patients were enrolled and 51 patients were treated. Patients with liposarcoma/leiomyosarcoma (n = 35) had similar characteristics to those with other subtypes (n = 16), except for a higher proportion of women (63% vs 38%, respectively) and patients with Eastern Cooperative Oncology Group performance status 0 (57% vs 44%). Progression-free rate at 12 weeks was 60% in liposarcoma/leiomyosarcoma patients, 31% in other subtypes and 51% overall. Median progression-free survival was 5.5 months in liposarcoma/leiomyosarcoma patients, 2.0 months in other subtypes and 4.1 months overall. Median overall survival was 17.0 months in liposarcoma/leiomyosarcoma patients, 7.6 months in other subtypes and 13.2 months overall. The most common Grade 3–4 adverse events were neutropenia (86%), leukopenia (75%), lymphopenia (33%), anemia (14%) and febrile neutropenia (8%). Conclusion: Eribulin showed clinical activity with a manageable safety profile in previously treated Japanese patients with advanced/metastatic soft tissue sarcoma.

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  • Results of Total Elbow Arthroplasty with Cementless Implantation of an Alumina Ceramic Elbow Prosthesis for Patients with Rheumatoid Arthritis.

    Keiichiro Nishida, Kenzo Hashizume, Masatsugu Ozawa, Ayumu Takeshita, Daisuke Kaneda, Ryuichi Nakahara, Yoshihisa Nasu, Yasunori Shimamura, Hajime Inoue, Toshifumi Ozaki

    Acta medica Okayama   71 ( 1 )   41 - 47   2017.2

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    We investigated the long-term clinical results of total elbow arthroplasty (TEA) by cementless fixation of alumina ceramic unlinked elbow prostheses (J-alumina ceramic elbows: JACE) for the reconstruction of elbow joints with rheumatoid arthritis (RA). Seventeen elbows in 17 patients (aged 44-72 years, average 54.8) replaced by JACE TEA without bone cement were investigated. The average follow-up period was 10.7 (range, 1.0-19.3) years. Clinical conditions of each elbow before and after surgery were assessed according to the Mayo Elbow Performance Index (MEPI). Radiographic loosening was defined as a progressive radiolucent line of more than 1 mm that was completely circumferential around the intramedullary stem. The average MEPI significantly improved from 46.8 points preoperatively to 66.8 points at final follow-up (p=0.0226). However, aseptic loosening was noted in 10 of 17 elbows (58.8%) and revision surgery was required in 7 (41.2%). Most loosening was observed on the humeral side. With radiographic loosening and revision surgery defined as the end points, the likelihoods of prosthesis survival were 41.2% and 51.8%, respectively, up to 15 years by Kaplan-Meier analysis. The clinical results of JACE implantation without bone cement were disappointing, with high revision and loosening rates of the humeral component.

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  • Verification of Implant Surface Modification by a Novel Processing Method.

    Yoshiki Okada, Nobuhiro Abe, Noriyuki Hisamori, Toshiaki Kaneeda, Shigeaki Moriyama, Hitoshi Ohmori, Masayoshi Mizutani, Hiroyuki Yanai, Yoshio Nakashima, Yusuke Yokoyama, Toshifumi Ozaki

    Acta medica Okayama   71 ( 1 )   49 - 57   2017.2

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    Metals have been used clinically as biomaterials, especially in the orthopaedic and dental fields. Metals used as implants wear at contact surfaces, producing metal particles and metal ions that may be harmful. Newly developed metal implants and methods of implant surface modification are currently under scrutiny. We evaluated the use of electrolytic in-process dressing (ELID) as a surface finishing method for metal implants. Metal implants processed using the ELID method (ELID group) or not processed (Non-ELID group) were inserted surgically into rabbit femurs. The rabbits were sacrificed postoperatively over a 24-week period. We assessed the concentrations of the cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, the resistance to implant pull-out, and histopathology at the implant site. There was no significant difference between the groups regarding the cytokine concentrations or implant pull-out resistance. Many particles indicating wear around the implant were noted in the Non-ELID group (n=10) but not the ELID group (n=13), while a fibrous membrane adhering to the every implant was noted in the ELID group. The formation of a fibrous membrane rather than metal particles in the ELID group may indicate improved biocompatibility, and it suggests that ELID may prevent corrosion in the areas of contact.

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  • Calcar femorale in patients with osteoarthritis of the hip secondary to developmental dysplasia Reviewed

    Tomonori Tetsunaga, Kazuo Fujiwara, Hirosuke Endo, Tomoko Tetsunaga, Naofumi Shiota, Toru Sato, Toshifumi Ozaki

    CiOS Clinics in Orthopedic Surgery   9 ( 4 )   413 - 419   2017

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    Background: We investigated whether the calcar femorale, a cortical septum in the region of the lesser trochanter of the femur, correlates with results of femoral stem implantation in patients with osteoarthritis of the hip secondary to developmental dysplasia using computed tomography. Methods: This retrospective study included 277 hips (41 males and 236 females
    age, 37 to 92 years) of patients who had presented to Okayama Medical Center with hip pain. Of these, a total of 219 hips (31 males and 188 females) had previously undergone total hip arthroplasty. According to the Crowe classification, 147 hips were classified as Crowe grade I, 72 hips as Crowe grade II– IV, and 58 hips as normal. Results: The calcar femorale was identified in 267 hips (96.4%). The calcar femorale was significantly shorter and more ante-verted in Crowe grade II–IV hips than in Crowe grade I or normal hips. Significant differences in the shape of the calcar femorale were found according to the severity of hip deformity. Three stem designs were analyzed: single-wedge (59 hips), double-wedge metaphyseal filling (147 hips), and modular (13 hips). Single-wedge stems were inserted more parallel to the calcar femorale rather than femoral neck anteversion, while other types of stems scraped the calcar femorale. Conclusions: The angle of the calcar femorale differs according to the severity of hip deformity, and the calcar femorale might thus serve as a more useful reference for stem insertion than femoral neck anteversion in total hip arthroplasty using a single-wedge stem.

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  • Neurological Recovery after Posterior Spinal Surgery in Patients with Metastatic Epidural Spinal Cord Compression Reviewed

    Noriyuki Watanabe, Yoshihisa Sugimoto, Masato Tanaka, Tetsuro Mazaki, Shinya Arataki, Tomoyuki Takigawa, Masaki Kataoka, Toshiyuki Kunisada, Toshifumi Ozaki

    ACTA MEDICA OKAYAMA   70 ( 6 )   449 - 453   2016.12

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    Metastatic epidural spinal cord compression (MESCC) is a common complication in patients with a malignant tumor, but it is difficult to decide the proper time to perform the necessary surgery. Here we analyzed the prognostic factors for postoperative walking ability. We retrospectively reviewed the cases of 112 MESCC patients treated surgically at our institute and divided them into ambulatory (n = 88) and non-ambulatory (n = 24) groups based on their American Spinal Injury Association (ASIA) Impairment Scale grades at the final follow-up. We also classified the patients preoperatively using the revised Tokuhashi score. We assessed the correlation between preoperative or intraoperative factors and postoperative walking ability in both groups. Of the 10 patients classified preoperatively as grade A or B, 2 (20) were ambulatory at the final follow-up. Of the 102 patients classified preoperatively as grade C, D or E, 86 (84) were ambulatory at the final follow-up (p &lt; 0.001). There were no significant differences between the groups in the average total Tokuhashi score. Our analysis revealed that the severity of paralysis significantly affects neurological recovery in patients with MESCC. Patients with MESCC should receive surgery before the preoperative ASIA Impairment Scale grade falls below grade C.

    DOI: 10.18926/AMO/54807

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  • Pullout repair of a medial meniscus posterior root tear using a FasT Fix® all-inside suture technique Reviewed

    Y. Kodama, T. Furumatsu, M. Fujii, T. Tanaka, S. Miyazawa, T. Ozaki

    Revue de Chirurgie Orthopedique et Traumatologique   102 ( 7 )   675   2016.11

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    A medial meniscus posterior root tear (MMPRT) may increase the tibiofemoral contact pressure by decreasing the tibiofemoral contact area. Meniscal dysfunction induced by posterior root injury may lead to the development of osteoarthritic knees. Repair of a MMPRT can restore medial meniscus function and prevent knee osteoarthritis progression. Several surgical procedures have been reported for treating a MMPRT. However, these procedures are associated with several technical difficulties. Here, we describe a technique to stabilize a torn MM posterior root using the FasT-Fix® all-inside meniscal suture device and a new aiming device. The uncut free-end of the FasT-Fix® suture can be used as a thread for transtibial pullout repair. Our procedure might help overcome the technical difficulties in arthroscopic treatment of a MMPRT.

    DOI: 10.1016/j.rcot.2016.07.020

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  • Acetabular development after open reduction to treat dislocation of the hip after walking age Reviewed

    Yohei Kagawa, Hirosuke Endo, Tomonori Tetsunaga, Yosuke Fujii, Takamasa Miyake, Toshifumi Ozaki

    JOURNAL OF ORTHOPAEDIC SCIENCE   21 ( 6 )   815 - 820   2016.11

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    Background: Treatment of hip dislocation diagnosed after walking age is often difficult. We report the surgical treatment of these patients by open reduction with a soft tissue surgical procedure without osteotomy.
    Methods: Thirty-eight children (43 hips) diagnosed with complete dislocation of the hip after walking age were included in this study. We radiographically analysed postoperative hip joint development up to 6 years of age. To assess the predictors of acetabular development, we evaluated the radiographs, using an acetabular index of &lt;= 35 degrees and a centre-edge angle of &gt;5 degrees at 6 years of age as satisfactory outcomes, and evaluated the advance of acetabular development over time.
    Results: AI on the affected side was improved with time after open reduction. The diameter of the capital femoral ossific nucleus on the affected side was almost equivalent to that on the unaffected side at 6-12 months after surgery, after which the centre -edge angle improved gradually from one year after surgery. We compared hips classified as satisfactory to unsatisfactory at 6 years of age, and found that the centre -edge angle at one year after open reduction was significantly associated with acetabular development (P = 0.044). The cut-off value was -2 degrees with sensitivity of 0.909 and specificity of 0.677.
    Conclusions: The results of the current study suggest that initial development of the capital femoral ossific nucleus after open reduction would be followed by improved joint congruity, and that this would facilitate acetabular development. The centre -edge angle at one year after surgery could be regarded as a potential predictor of acetabular development in open reduction surgery for late -diagnosed developmental dysplasia of the hip cases. (C) 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jos.2016.07.007

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  • 骨肉腫における腫瘍浸潤骨髄球型細胞を介したメトホルミンの抗腫瘍効果

    上原 健敬, 榮川 伸吾, 國定 勇希, 渡邉 元嗣, 友信 奈保子, 吉田 晶, 藤原 智洋, 国定 俊之, 尾崎 敏文, 鵜殿 平一郎

    日本癌学会総会記事   75回   P - 3220   2016.10

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  • CEMOVERの使用経験

    山田 和希, 遠藤 裕介, 藤井 洋佑, 井上 淳, 池田 吉宏, 尾崎 敏文

    中国・四国整形外科学会雑誌   28 ( 3 )   452 - 452   2016.9

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  • 低侵襲人工膝関節置換術におけるsemi-active骨切除ロボット操作で要求される術者の動作評価

    山田 和希, 藤原 一夫, 三宅 孝昌, 藤井 洋佑, 尾崎 敏文, 阿部 信寛, 江口 透, 山本 江, 杉田 直彦, 光石 衛

    日本整形外科学会雑誌   90 ( 8 )   S1700 - S1700   2016.8

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  • 解剖学的二重束前十字靱帯再建における脛骨骨孔位置と外側半月板逸脱に関する検討

    山田 和希, 古松 毅之, 宮澤 慎一, 田中 孝明, 井上 博登, 児玉 有弥, 釜付 祐輔, 日野 知仁, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 8 )   S1786 - S1786   2016.8

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  • 解剖学的二重束前十字靱帯再建における脛骨骨孔位置と術後外側半月板逸脱に関する比較検討

    山田 和希, 古松 毅之, 宮澤 慎一, 藤井 政孝, 田中 孝明, 井上 博登, 児玉 有弥, 釜付 祐輔, 日野 知仁, 尾崎 敏文

    日本整形外科スポーツ医学会雑誌   36 ( 4 )   509 - 509   2016.8

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  • Metforminは腫瘍内骨髄球系細胞の代謝を制御し骨肉腫形成を抑制する

    上原 健敬, 榮川 伸吾, 小松原 将, 森田 卓也, 杉生 和久, 魚谷 弘二, 大森 敏規, 吉田 晶, 藤原 智洋, 武田 健, 国定 俊之, 鵜殿 平一郎, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 8 )   S1555 - S1555   2016.8

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  • 骨肉腫における新規バイオマーカーおよび予後予測因子としてのcirculating microRNAの同定

    藤原 智洋, 魚谷 弘二, 吉田 晶, 森田 卓也, 清野 正晋, 上原 健敬, 杉生 和久, 小松原 将, 望月 雄介, 国定 俊之, 根津 悠, 岩田 慎太郎, 小林 英介, 川井 章, 落谷 孝広, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 8 )   S1553 - S1553   2016.8

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  • 網羅的解析による滑膜肉腫由来circulating cell-free microRNAの特定および検証

    魚谷 弘二, 藤原 智洋, 吉田 晶, 森田 卓也, 大森 敏規, 上原 健敬, 杉生 和久, 小松原 将, 武田 健, 国定 俊之, 根津 悠, 岩田 慎太郎, 川井 章, 落谷 孝広, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 8 )   S1560 - S1560   2016.8

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  • 解剖学的2重束前十字靱帯再建術における脛骨骨孔角度と骨孔位置の検討

    山田 和希, 古松 毅之, 宮澤 慎一, 田中 孝明, 井上 博登, 児玉 有弥, 釜付 祐輔, 尾崎 敏文

    JOSKAS   41 ( 4 )   164 - 164   2016.7

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  • 大腿骨骨幹部骨折髄内釘術後の回旋変形の検討

    小松原 将, 山川 泰明, 吉村 将秀, 杉生 和久, 上原 健敬, 野田 知之, 尾崎 敏文

    骨折   38 ( Suppl. )   S310 - S310   2016.7

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  • 介護老人福祉施設入所者の大腿骨骨折と要介護度との検討

    堅山 佳美, 千田 益生, 上原 健敬, 尾崎 敏文

    The Japanese Journal of Rehabilitation Medicine   ( JARM2016 )   I36 - I36   2016.6

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  • 健常者における横隔神経伝導速度の左右差の検討

    上原 健敬, 堅山 佳美, 千田 益生, 尾崎 敏文

    The Japanese Journal of Rehabilitation Medicine   ( JARM2016 )   I95 - I95   2016.6

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  • サルコペニアとリハビリテーション

    千田 益生, 堅山 佳美, 上原 健敬, 兼田 大輔, 尾崎 敏文

    The Japanese Journal of Rehabilitation Medicine   ( JARM2016 )   S261 - S261   2016.6

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  • メトホルミンの骨肉腫に対する免疫を介した抗腫瘍効果

    上原 健敬, 榮川 伸吾, 小松原 将, 森田 卓也, 杉生 和久, 魚谷 弘二, 吉田 晶, 藤原 智洋, 武田 健, 国定 俊之, 鵜殿 平一郎, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 6 )   S1259 - S1259   2016.6

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  • 術中ナビゲーションが有用であった脛骨原発phosphaturic mesenchymal tumorの1例

    藤原 智洋, 国定 俊之, 武田 健, 上原 健敬, 大森 敏規, 魚谷 弘二, 杉生 和久, 森田 卓也, 小松原 将, 吉田 晶, 西山 悠紀, 稲垣 謙一, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 6 )   S1398 - S1398   2016.6

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  • 手・足部発生の類骨骨腫の治療経験

    小松原 将, 武田 健, 森田 卓也, 杉生 和久, 魚谷 弘二, 大森 敏規, 上原 健敬, 吉田 晶, 藤原 智洋, 国定 俊之, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 6 )   S1396 - S1396   2016.6

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  • 軟部原発平滑筋肉腫の治療成績

    藤原 智洋, 国定 俊之, 武田 健, 上原 健敬, 大森 敏規, 魚谷 弘二, 杉生 和久, 森田 卓也, 小松原 将, 吉田 晶, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 6 )   S1308 - S1308   2016.6

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  • 大腿骨骨幹部骨折髄内釘治療後の回旋変形

    小松原 将, 山川 泰明, 吉村 将秀, 上原 健敬, 野田 知之, 尾崎 敏文

    日本外傷学会雑誌   30 ( 2 )   246 - 246   2016.5

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  • 上腕骨骨幹部骨折に対するMIPOによる治療成績

    島村 安則, 山川 泰明, 吉村 将秀, 原田 遼三, 堀田 昌宏, 竹下 歩, 上原 健敬, 雑賀 建多, 中原 龍一, 木浪 陽, 野田 知之, 尾崎 敏文

    中国・四国整形外科学会雑誌   28 ( 1 )   164 - 164   2016.4

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  • 大腿骨近位部骨折を伴う大腿骨骨幹部骨折の治療経験

    清野 正普, 野田 知之, 山川 泰明, 小松原 将, 吉村 将秀, 杉生 和久, 上原 健敬, 中原 龍一, 島村 安則, 尾崎 敏文

    中国・四国整形外科学会雑誌   28 ( 1 )   168 - 168   2016.4

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  • 骨肉腫における予後予測ノモグラムの開発と外的妥当性の検証

    小倉 浩一, 藤原 智洋, 康永 秀生, 松居 宏樹, Jeon Dae-Geun, 平賀 博明, 石井 猛, 米本 司, 鴨田 博人, 尾崎 敏文, 小澤 英史, 西田 佳弘, 森岡 秀夫, 比留間 徹, 角永 茂樹, 上田 孝文, 荒木 信人, 中 紀文, 津田 祐輔, 河野 博隆, 川井 章

    日本整形外科学会雑誌   90 ( 3 )   S1072 - S1072   2016.3

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  • 40歳以上の中高齢者発生骨肉腫の治療成績

    藤原 智洋, 国定 俊之, 武田 健, 魚谷 弘二, 杉生 和久, 森田 卓也, 小松原 将, 大森 敏規, 上原 健敬, 吉田 晶, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 3 )   S856 - S856   2016.3

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  • メトホルミンの骨肉腫に対する免疫を介した抗腫瘍効果

    上原 健敬, 榮川 伸吾, 杉生 和久, 魚谷 弘二, 吉田 晶, 藤原 智洋, 武田 健, 国定 俊之, 鵜殿 平一郎, 尾崎 敏文

    日本整形外科学会雑誌   90 ( 2 )   S143 - S143   2016.3

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  • Limb salvage surgery for pelvic osteosarcoma Reviewed

    Toshiyuki Kunisada, Ken Takeda, Tomohiro Fujiwara, Shinsuke Sugihara, Toshifumi Ozaki

    Osteosarcoma   135 - 147   2016.1

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    Patients with pelvic osteosarcoma have a poor outcome
    treatment is one of the most challenging problems for the orthopedic oncologist. The reconstructive approach varies according to anatomic location, extent of resection, the patient’s functional demands, and individual surgeon preference. The choice of optimal technique for reconstruction after acetabular tumor resection depends on numerous parameters and includes iliofemoral arthrodesis or pseudoarthrodesis, combined use of hip arthroplasty with massive allograft or recycled autograft, and pelvic and saddle prosthesis. The type of reconstruction modality can influence the rate of infection. Hip transposition resulted in the least incidence of complications after resection of the acetabulum, compared to the use of prosthesis or prosthesis and allograft. The absence of large implants and allografts helps reduce surgical time, facilitates closure, and may decrease the incidence of infection and late revision due to implant failure. These can lead to early postoperative systemic treatment and functional recovery and are critical for patients with a high incidence of local recurrence and distant metastases. We believe that resection arthroplasty should be indicated for the patient with acetabular osteosarcoma.

    DOI: 10.1007/978-4-431-55696-1_11

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  • Minimally invasive spinopelvic fixation for unstable bilateral sacral fractures Reviewed

    Koichiro Koshimune, Yasuo Ito, Yoshihisa Sugimoto, Takeshi Kikuchi, Takuya Morita, Shoichiro Mizuno, Toshifumi Ozaki

    Clinical Spine Surgery   29 ( 3 )   124 - 127   2016

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    Study Design: Retrospective case series. Objective: We present a minimally invasive spinopelvic fixation technique for unstable bilateral sacral fractures and describe a technical report. Summary of Background Data: Unstable sacral fractures are severe injuries with high mortality and morbidity due to pain and malunion. Galveston technique is useful for rigid fixation of an unstable sacral fracture. However, wound-related complications with this technique have been relatively common because of extensive contusion of the skin or poor blood supply after embolization. Materials and Methods: There were 34 patients with unstable pelvic fractures between 2005 and 2012. We performed conventional open surgery between 2005 and 2009. Minimally invasive spinopelvic fixation was performed between 2009 and 2012. Minimally invasive technique needs 4 small, lateral incisions for percutaneous lumbar pedicle screw insertion. We pushed a pure titanium rod into the paravertebral muscle. Results: The average surgical time was 345 minutes in the conventional fixation and 208 minutes with the minimally invasive fixation. The average intraoperative bleeding was 520mL in the conventional fixation and 290mL in minimally invasive fixation. When comparing deep wound infection, 3 of 8 (38%) patients who received conventional fixation had methicillin-resistant Staphylococcus aureus infections, whereas nobody who received the minimally invasive fixation acquired infection. Bony union was achieved in 15 of the 16 patients. Conclusions: In this study, minimally invasive spinopelvic fixation required a shorter surgical time, incurred less bleeding, and had a lower infection rate than fixation with the conventional Galveston technique.

    DOI: 10.1097/BSD.0000000000000090

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  • Postoperative change in the length and extrusion of the medial meniscus after anterior cruciate ligament reconstruction Reviewed

    Shinji Narazaki, Takayuki Furumatsu, Takaaki Tanaka, Masataka Fujii, Shinichi Miyazawa, Hiroto Inoue, Yasunori Shimamura, Kenta Saiga, Toshifumi Ozaki

    INTERNATIONAL ORTHOPAEDICS   39 ( 12 )   2481 - 2487   2015.12

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    Purpose The medial meniscus is a secondary stabilizer of anterior tibial translation in anterior cruciate ligament (ACL)-deficient knees. ACL reconstruction effectively restores an increased anterior tibial translation in the ACL-deficient knee. However, knee osteoarthritis sometimes develops in ACL-reconstructed patients during a long-term follow-up period. We hypothesized that the medial meniscal position would be different between the ACL-deficient and reconstructed knees. The aim of this study was to investigate pre-operative and postoperative location of the medial meniscus in patients who underwent ACL reconstruction.
    Methods ACL-reconstructed knees (28 knees) and normal knees (27 knees) were investigated. Medial tibial plateau length (MTPL) and medial tibial plateau width (MTPW) were determined using radiographic images. Magnetic resonance imaging (MRI)-based medial meniscal length (MML), medial meniscal width (MMW), and medial meniscal extrusion (MME) were measured. Postoperative change in the MML, MMW, and MME were evaluated and compared with those in normal knees.
    Results No significant differences between the ACL-deficient (pre-operative) and normal groups were noted. The ACL-reconstructed (postoperative) group showed an increase in the MML, in the percentage of the MML (%MML = 100 MML/MTPL), and in the MME. Significant differences between postoperative and normal groups were observed in the MML, %MML, and MME. MMW and MMW percentage (100 MMW/MTPW) were similar in all groups.
    Conclusions The anteroposterior length and radial extrusion of the medial meniscus increased after ACL reconstruction. Transposition of the medial meniscus may be a possible cause of developing further degenerative knee joint disorders after ACL reconstruction.

    DOI: 10.1007/s00264-015-2704-z

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  • Contrast-enhanced Computed Tomography Screening Is Effective for Detecting Venous Thromboembolism not Prevented by Prophylaxis after Total Knee Arthroplasty Reviewed

    Yukimasa Okada, Takayuki Furumatsu, Shinichi Miyazawa, Takaaki Tanaka, Masataka Fujii, Toshifumi Ozaki, Nobuhiro Abe

    ACTA MEDICA OKAYAMA   69 ( 6 )   355 - 359   2015.12

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    Venous thromboembolism (VTE) is a potential complication occurring after total knee arthroplasty (TKA). We investigated the incidence of VTE after TKA using contrast-enhanced computed tomography (CT), and assessed the efficacy of VTE prophylaxis (fondaparinux and enoxaparin). At our hospital, 189 patients (225 knees) underwent TKA between April 2007 and October 2011. The 225 knees were divided into a control group with no VTE prophylaxis (31 cases), a fondaparinux group (107 cases), and an enoxaparin group (87 cases). Contrast-enhanced CT screening for VTE was performed in all cases on day 5 or 6 after TKA. D-dimer levels were measured on day 5 after TKA, and were significantly lower in the fondaparinux (9.8 +/- 3.8) and enoxaparin groups (9.4 +/- 4.9) than in the control group (15.6 +/- 9.8) (p &lt; 0.001). However, no statistically significant difference in the incidence of VTE was observed among the groups (control, 61.3%; fondaparinux, 49.5%; enoxaparin, 50.6%). Prophylaxis was not effective for the prevention of VTE as detected by contrast-enhanced CT after TKA. CT should be performed after TKA, even when VTE prophylaxis is used.

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  • 股関節固定術30年後に人工股関節置換術を施行した1例

    遠藤 裕介, 香川 洋平, 上原 健敬, 藤原 一夫, 藤井 洋佑, 尾崎 敏文

    日本人工関節学会誌   45   865 - 866   2015.12

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    症例は57歳の女性で、両側の先天性股関節脱臼に対するギプス固定歴があり、左の末期股関節症に対し27歳時に股関節固定術を受け、47歳頃より腰痛と膝痛の隣接関節障害が生じていた。初診時のX線像では、右は末期股関節症、左股関節は完全に骨癒合した固定状態で、代償性の腰椎前彎と変性所見を認め、脚長差が2cm存在した。JOAスコアは右36点、左59点であった。右股関節に対しセメントレスカップとセメントステムによるハイブリッド人工股関節置換術(THA)を施行した。術後に右股関節痛は改善し、JOAスコアは68点となったが、腰痛と左膝関節痛が残存したため、術後10ヵ月に左ハイブリッドTHAを施行した。術後経過は良好で、JOAスコアは78点に改善し、腰痛や膝痛はなく、腰椎前彎も改善し、機能的脚長差も消失した。

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  • Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi-institutional study Reviewed

    Koichi Ogura, Tomohiro Fujiwara, Hideo Yasunaga, Hiroki Matsui, Dae-Geun Jeon, Wan Hyeong Cho, Hiroaki Hiraga, Takeshi Ishii, Tsukasa Yonemoto, Hiroto Kamoda, Toshifumi Ozaki, Eiji Kozawa, Yoshihiro Nishida, Hideo Morioka, Toru Hiruma, Shigeki Kakunaga, Takafumi Ueda, Yusuke Tsuda, Hirotaka Kawano, Akira Kawai

    CANCER   121 ( 21 )   3844 - 3852   2015.11

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    BACKGROUNDIn this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi-institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis-free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma.
    METHODSThis study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513).
    RESULTSA patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS.
    CONCLUSIONSThe nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery. Cancer 2015;121:3844-3852. (c) 2015 American Cancer Society.
    Prognostic nomograms for osteosarcoma have been developed and externally validated through multi-institutional collaboration. These prognostic nomograms are the first to be developed and externally validated for osteosarcoma.

    DOI: 10.1002/cncr.29575

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  • Bone engineering by phosphorylated-pullulan and β-TCP composite. Reviewed

    Takahata T, Okihara T, Yoshida Y, Yoshihara K, Shiozaki Y, Yoshida A, Yamane K, Watanabe N, Yoshimura M, Nakamura M, Irie M, Van Meerbeek B, Tanaka M, Ozaki T, Matsukawa A

    Biomedical materials (Bristol, England)   10 ( 6 )   065009   2015.11

  • 腫瘍局所のmyeloid-derived suppressor cells(MDSCs)に与えるメトホルミン投与の効果

    上原 健敬, 榮川 伸吾, 國定 勇希, 渡邉 元嗣, 一柳 朋子, 山崎 千尋, 尾崎 敏文, 鵜殿 平一郎

    日本癌学会総会記事   74回   P - 2109   2015.10

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  • 成年男性の横隔神経伝導速度の左右差の検討

    堅山 佳美, 千田 益生, 上原 健敬, 尾崎 敏文

    臨床神経生理学   43 ( 5 )   438 - 438   2015.10

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  • Establishment of a liaison clinic for patients with intractable chronic pain Reviewed

    Tomoko Tetsunaga, Tomonori Tetsunaga, Hiroyuki Nishie, Toshifumi Ozaki

    JOURNAL OF ORTHOPAEDIC SCIENCE   20 ( 5 )   907 - 913   2015.9

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    Background A multidisciplinary approach has been shown to be effective for the treatment of intractable pain. However, few hospitals in Japan have established liaison clinics for such patients. In this study, we investigated the short-term results of a liaison clinic for patients with intractable chronic pain.
    Methods Study participants comprised 53 outpatients (20 men, 33 women) with intractable chronic pain who visited our hospital between April 2012 and March 2013. At baseline, patients completed a self-reported questionnaire and provided demographic and clinical information. Experts in various fields (anesthesia, orthopedic surgery, psychiatry, physical therapy, and nursing) conducted examinations of patients and attended a weekly conference during which patients' physical, psychological, and social problems were discussed and courses of treatment were determined. All patients were assessed using the Numerical Rating Scale (NRS), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Pain Disability Assessment Scale (PDAS). Eligibility for the pain liaison outpatient clinic was evaluated using multiple logistic regression analysis.
    Results After a 6-month follow-up period, no significant changes were seen in scores for the NRS, PDAS, or HADS for depression. In contrast, scores for both the PCS and HADS for anxiety were significantly reduced after 6 months of treatment (p &lt; 0.05). HADS for anxiety was identified as a factor related to patient resistance to attending the pain liaison outpatient clinic (p &lt; 0.05).
    Conclusions This liaison clinic for patients with intractable chronic pain was able to improve patient anxiety. Severe anxiety at the initial visit represented a risk factor for dropout from the clinic.

    DOI: 10.1007/s00776-015-0748-y

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  • 胞巣状軟部肉腫に対する広範切除術前に血管内治療による腫瘍塞栓術を施行した2例

    宇川 諒, 武田 健, 藤原 智洋, 国定 俊之, 平木 隆夫, 尾崎 敏文

    中国・四国整形外科学会雑誌   27 ( 3 )   447 - 447   2015.9

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  • 骨盤輪骨折(救命から観血的治療まで) 骨盤輪損傷の内固定法

    野田 知之, 上原 健敬, 吉村 将秀, 島村 安則, 尾崎 敏文, 山川 泰明

    中部日本整形外科災害外科学会雑誌   58 ( 秋季学会 )   56 - 56   2015.9

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  • 寛骨臼骨折におけるposterior column screwの安全域 3DCTによる検討

    吉村 将秀, 上原 健敬, 野田 知之, 小松原 将, 杉生 和久, 山川 泰明, 雑賀 建多, 中原 龍一, 島村 安則, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 8 )   S1424 - S1424   2015.9

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  • 骨肉腫患者における腫瘍由来分泌型miRNAの特定と非侵襲的バイオマーカーとしての実験的検討

    藤原 智洋, 魚谷 弘二, 吉田 晶, 杉生 和久, 大森 敏規, 上原 健敬, 山川 泰明, 武田 健, 国定 俊之, 根津 悠, 川井 章, 落谷 孝広, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 8 )   S1798 - S1798   2015.9

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  • マウス乳がん骨転移モデルに対するリン酸化プルラン・ゾレドロン酸混和物の抗腫瘍効果の検討

    武田 健, 魚谷 弘二, 杉生 和久, 大森 敏規, 上原 健敬, 藤原 智洋, 国定 俊之, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 8 )   S1675 - S1675   2015.9

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  • 骨肉腫におけるmyeloid derived suppressor cell(MDSC)に対するmetforminの作用の検討

    上原 健敬, 榮川 伸吾, 藤原 智洋, 杉生 和久, 魚谷 弘二, 大森 敏規, 吉田 晶, 武田 健, 国定 俊之, 鵜殿 平一郎, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 8 )   S1670 - S1670   2015.9

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  • Scoliosis correction surgery for patients with McCune-Albright syndrome using pedicle screws: a report of two cases with different characteristics and a review of the literature Reviewed

    Kentaro Yamane, Masato Tanaka, Yoshihisa Sugimoto, Haruo Misawa, Toshifumi Ozaki

    EUROPEAN SPINE JOURNAL   24 ( 7 )   1362 - 1367   2015.7

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    Scoliosis can occur secondary to McCune-Albright syndrome (MAS); it can be progressive and sometimes requires surgical treatment. It is still unclear if pedicle screw (PS) fixation in these patients with poor bone quality can be considered an effective treatment for scoliosis. The purpose of this study is to report two MAS patients with spinal fibrous dysplasia (FD) who underwent scoliosis surgeries with the PS system.
    Case 1: a 12-year-old girl. Standing posteroanterior radiographs revealed a 58A degrees right curve from T7 to L2. Computed tomography (CT) showed small areas of FD throughout the spine. A posterior spinal arthrodesis from T4 to L3 using PS fixation was performed with a CT-based navigation system. Case 2: a 26-year-old woman. Radiographs in the standing position revealed a right 87A degrees curve from T8 to L2 and a 55A degrees kyphosis from T8 to T12. CT images showed multiple areas of severe spinal FD causing angular deformity and collapse of vertebral bodies. The patient underwent posterior spinal arthrodesis from T8 to her pelvis using a CT-based navigation system for PS fixation.
    Superior scoliosis corrections were obtained using PS instrumentation, attaining complete bony union in both cases without major complications. However, Case 2 had some technical difficulties in treating due to the multiple large FD lesions.
    PS fixation can be considered an effective treatment for correcting scoliosis and maintaining the correction at follow-up in MAS patients with poor bone quality. However, great care must be taken when performing correction and follow-up.

    DOI: 10.1007/s00586-015-3813-5

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  • Perioperative chemotherapy with ifosfamide and doxorubicin for high-grade soft tissue sarcomas in the extremities (JCOG0304). Reviewed International journal

    Tanaka K, Mizusawa J, Fukuda H, Araki N, Chuman H, Takahashi M, Ozaki T, Hiruma T, Tsuchiya H, Morioka H, Hatano H, Iwamoto Y

    Japanese journal of clinical oncology   45 ( 6 )   555 - 561   2015.6

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    OBJECTIVE: The efficacy of perioperative chemotherapy for soft tissue sarcomas is controversial and only a few prospective studies of pre-operative chemotherapy for soft tissue sarcomas in the extremities have been reported. We therefore carried out Phase II study of perioperative chemotherapy for patients with soft tissue sarcomas in the extremities. METHODS: Patients with Stage III non-round cell soft tissue sarcomas in the extremities were eligible. The patients were treated with pre-operative chemotherapy consisting doxorubicin 60 mg/m(2) and ifosfamide 10 g/m(2) for three courses. After the tumor resection, two additional courses of the same regimen were carried out. RESULTS: A total of 72 patients were enrolled and 70 patients were eligible. The median age of the patients was 49 years. The major pathological subtypes were synovial sarcoma in 20 and undifferentiated pleomorphic sarcoma in 17 patients. The protocol treatments were completed in 74% of the eligible cases. The 2 and 5-year progression-free survival rates were 75.7% (95% CI, 63.9-84.1%) and 63.8% (95% CI, 51.3-73.9%), respectively. The 5-year overall survival was 82.6% (95% CI, 71.3-89.7%). There was no treatment-related death. Grade 3 or 4 hematological toxicities (leukopenia and neutropenia) were observed in most of the patients. CONCLUSIONS: Although the toxicities of the regimen were significant, pre-operative chemotherapy followed by post-operative chemotherapy using doxorubicin and high-dose ifosfamide was feasible. The outcome of the trial for the patients with high-grade soft tissue sarcomas in the extremities was favorable, and this regimen is promising for further investigation. This trial was registered at the UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/) as C000000096.

    DOI: 10.1093/jjco/hyv042

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  • 骨肉腫における全生存率を予測する予後予測ノモグラムの開発

    小倉 浩一, 藤原 智洋, 松居 宏樹, 康永 秀生, 平賀 博明, 石井 猛, 米本 司, 鴨田 博人, 尾崎 敏文, 小澤 英史, 西田 佳弘, 森岡 秀夫, 比留間 徹, 角永 茂樹, 上田 孝文, 荒木 信人, 中 紀文, 津田 祐輔, 河野 博隆, 川井 章

    日本整形外科学会雑誌   89 ( 6 )   S1329 - S1329   2015.6

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  • 骨腫瘍切除後の骨欠損に対する配向連通気孔構造を有する新しい人工骨移植の治療成績

    武田 健, 国定 俊之, 小松原 将, 森田 卓也, 杉生 和久, 魚谷 弘二, 大森 敏規, 上原 健敬, 藤原 智洋, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 6 )   S1209 - S1209   2015.6

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  • 大腿骨遠位骨幹部骨折偽関節に対する骨移植併用exchange nailingの治療経験

    小松原 将, 野田 知之, 杉生 和久, 堀田 昌宏, 上原 健敬, 山川 泰明, 雑賀 建多, 中原 龍一, 木浪 陽, 尾崎 敏文

    骨折   37 ( Suppl. )   S89 - S89   2015.6

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  • 脆弱性骨折に対するトータルケアーの現状と理想 大腿骨近部骨折に対する外科的治療の最前線(手術手技の工夫)

    野田 知之, 吉村 将秀, 上原 健敬, 島村 安則, 尾崎 敏文, 山川 泰明

    骨折   37 ( Suppl. )   S19 - S19   2015.6

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  • 若年男性の横隔神経伝導速度の左右差についての検討

    堅山 佳美, 千田 益生, 上原 健敬, 尾崎 敏文

    運動器リハビリテーション   26 ( 2 )   241 - 241   2015.6

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  • 上腕骨骨幹部骨折における最小侵襲プレート骨接合術(MIPO)による治療成績

    島村 安則, 野田 知之, 山川 泰明, 中原 龍一, 木浪 陽, 上原 健敬, 吉村 将秀, 竹下 歩, 島村 好信, 尾崎 敏文

    骨折   37 ( Suppl. )   S263 - S263   2015.6

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  • 大腿骨ステム周囲骨折に対するロッキングプレートの治療経験

    児玉 有弥, 野田 知之, 島村 安則, 木浪 陽, 中原 龍一, 雑賀 建多, 山川 泰明, 上原 健敬, 杉生 和久, 尾崎 敏文

    骨折   37 ( Suppl. )   S191 - S191   2015.6

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  • 仙骨骨巨細胞腫に対する治療戦略

    藤原 智洋, 国定 俊之, 武田 健, 山川 泰明, 大森 敏規, 上原 健敬, 魚谷 弘二, 杉生 和久, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 6 )   S1308 - S1308   2015.6

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  • マウス骨肉腫におけるmyeloid derived suppressor cellsとmetforminの作用

    上原 健敬, 榮川 伸吾, 杉生 和久, 魚谷 弘二, 大森 敏規, 山川 泰明, 吉田 晶, 藤原 智洋, 武田 健, 国定 俊之, 鵜殿 平一郎, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 6 )   S1238 - S1238   2015.6

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  • The figure-of-nine leg position for anatomic anterior cruciate ligament reconstruction Reviewed

    T. Furumatsu, M. Fujii, T. Tanaka, S. Miyazawa, T. Ozaki

    ORTHOPAEDICS & TRAUMATOLOGY-SURGERY & RESEARCH   101 ( 3 )   391 - 393   2015.5

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    Anatomic double-bundle anterior cruciate ligament (ACL) reconstruction can restore the function and kinematics of the knee in ACL-deficient patients. Several outside-in drilling systems for accurate femoral tunnel creations have been developed. However, the femoral tunnel creation at the lower position of the intercondylar notch can be difficult in a usual leg position with the knee flexed at 90 degrees without varus stress. This technical note describes that the figure-of-nine leg position provides a better arthroscopic view to safely clean up the ACL femoral footprint located at the lower area of the lateral intercondylar wall. This position is useful to create the optimal femoral tunnels using the outside-in drilling technique, without damaging the lateral meniscus posterior root, lateral tibial eminence, and supplemental fibers that bridge the gap between the lateral meniscus and the ACL tibial insertion. (C) 2015 Elsevier Masson SAS. All rights reserved.

    DOI: 10.1016/j.otsr.2014.12.015

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  • 高度肥満症例の重度四肢骨盤外傷に対する骨折治療戦略

    小松原 将, 木浪 陽, 上原 健敬, 山川 泰明, 野田 知之, 尾崎 敏文

    日本外傷学会雑誌   29 ( 2 )   281 - 281   2015.5

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  • 骨盤輪骨折に対するナビゲーションを用いたiliosacral screwの有用性

    上原 健敬, 木浪 陽, 吉村 政秀, 杉生 和久, 山川 泰明, 野田 知之, 尾崎 敏文

    日本外傷学会雑誌   29 ( 2 )   234 - 234   2015.5

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  • 健常人の横隔神経伝導検査における左右差の検討

    堅山 佳美, 千田 益生, 原田 遼三, 上原 健敬, 西田 圭一郎, 尾崎 敏文

    The Japanese Journal of Rehabilitation Medicine   52 ( Suppl. )   S198 - S198   2015.5

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  • Intercondylar notch size influences cyclops formation after anterior cruciate ligament reconstruction Reviewed

    Masataka Fujii, Takayuki Furumatsu, Shinichi Miyazawa, Yukimasa Okada, Takaaki Tanaka, Toshifumi Ozaki, Nobuhiro Abe

    KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY   23 ( 4 )   1092 - 1099   2015.4

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    The purpose of this study was to investigate the incidence of cyclops lesions and its relationship with the cross-sectional area of the intercondylar notch.
    For this study, 55 patients (24 male and 31 female) underwent follow-up arthroscopy after bi-socket anterior cruciate ligament reconstruction with hamstring tendon grafts were included. All patients underwent magnetic resonance imaging measurements of intercondylar notch dimensions. We compared the femoral intercondylar notch sizes and bone tunnel sizes between knees with cyclops lesions (cyclops group) and those without cyclops lesions (no-cyclops group). The mean percentage of the tunnel size to the cross-sectional area of the femoral intercondylar notch was also compared between the groups. The median follow-up duration was 3.8 years.
    Cyclops lesions were found in 15 of the 55 knees (27.3 %) on second-look arthroscopy (cyclops group). Only 6 of the 55 knees (10.9 %) had extension loss (cyclops syndrome). The cyclops group included 3 men and 12 women. The two groups showed a statistical difference in sex variation (P = 0.04). No significant differences were found in the femoral and tibial tunnel sizes between the two groups. The cross-sectional area of the femoral intercondylar notch was significantly smaller in the cyclops group (251.7 +/- A 63.2 mm(2)) than in the no-cyclops group (335.6 +/- A 77.6 mm(2)) (P &lt; 0.001). The percentage of the total femoral tunnel size to the cross-sectional area of the femoral intercondylar notch was significantly higher in the cyclops group (18.6 +/- A 5.3 %) than in the no-cyclops group (13.2 +/- A 3.6 %) (P = 0.02).
    A smaller intercondylar notch size may be a potential risk factor for cyclops lesion formation.

    DOI: 10.1007/s00167-014-2891-y

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  • Inhibition of KRAS codon 12 mutants using a novel DNA-alkylating pyrrole-imidazole polyamide conjugate. Reviewed International journal

    Hiraoka K, Inoue T, Taylor RD, Watanabe T, Koshikawa N, Yoda H, Shinohara K, Takatori A, Sugimoto H, Maru Y, Denda T, Fujiwara K, Balmain A, Ozaki T, Bando T, Sugiyama H, Nagase H

    Nature communications   6   6706 - 6706   2015.4

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    Despite extensive efforts to target mutated RAS proteins, anticancer agents capable of selectively killing tumour cells harbouring KRAS mutations have remained unavailable. Here we demonstrate the direct targeting of KRAS mutant DNA using a synthetic alkylating agent (pyrrole-imidazole polyamide indole-seco-CBI conjugate; KR12) that selectively recognizes oncogenic codon 12 KRAS mutations. KR12 alkylates adenine N3 at the target sequence, causing strand cleavage and growth suppression in human colon cancer cells with G12D or G12V mutations, thus inducing senescence and apoptosis. In xenograft models, KR12 infusions induce significant tumour growth suppression, with low host toxicity in KRAS-mutated but not wild-type tumours. This newly developed approach may be applicable to the targeting of other mutant driver oncogenes in human tumours.

    DOI: 10.1038/ncomms7706

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  • Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1 beta production and subsequent NF-kappa B activation Reviewed

    Masatsugu Ozawa, Keiichiro Nishida, Aki Yoshida, Taichi Saito, Ryozo Harada, Takahiro Machida, Toshifumi Ozaki

    INFLAMMATION RESEARCH   64 ( 3-4 )   243 - 252   2015.4

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    To investigate the inhibitory effect of hyaluronan (HA) on mechanical stress- induced expression of a disintegrin and metalloproteinase with thrombospondin type1 motifs (ADAMTS)-4, -5 and matrix metalloproteinase (MMP)-13 by human chondrocytes.
    Normal human articular chondrocytes were pre-incubated with or without 1.0 mg/mL HA (2700 kDa) for 12 h at 37 A degrees C in stretch chambers, then they were exposed to uni-axial cyclic tensile strain (CTS, 0.5 Hz, 10 % elongation). The expression of ADAMTS-4, -5, and MMP-13 were analyzed by real-time polymerase chain reaction and Immunocytochemistry. The concentration of IL-1 beta in the supernatant was measured using enzyme-linked immunosorbent assay (ELISA). The nuclear translocation of runt-related transcription factor 2 (RUNX-2) and nuclear factor-kappa B (NF-kappa B) was examined by ELISA and immunocytochemistry, and phosphorylation of NF-kappa B was examined by western blotting.
    HA inhibited mRNA expression of ADAMTS-4, -5, and MMP13 after 24 h CTS via inhibition of IL-1 beta secretion and NF-kappa B activation. However, HA failed to inhibit CTS-induced RUNX-2 expression and subsequent expression of ADAMTS-5 and MMP-13 1 h after CTS.
    Our results demonstrated that HA significantly suppressed mechanical stress-induced expression of catabolic proteases by inhibition of the NF-kappa B-IL-1 beta pathway, but did not suppress mechanical stress-induced RUNX-2 signaling.

    DOI: 10.1007/s00011-015-0804-2

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  • Pneumocephalus and chylothorax complicating vertebrectomy for lung cancer. Reviewed

    Sugimoto S, Tanaka M, Suzawa K, Nishikawa H, Toyooka S, Oto T, Ozaki T, Miyoshi S

    The Annals of thoracic surgery   99 ( 4 )   1425 - 1428   2015.4

  • 3D-navigation systemを用いたtransiliac-transsacral screw固定の経験

    木浪 陽, 野田 知之, 上原 健敬, 山川 泰明, 尾崎 敏文

    中国・四国整形外科学会雑誌   27 ( 1 )   182 - 182   2015.4

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  • 不安定型骨盤輪骨折に対するnavigation systemを利用したIliosacral screwの有用性

    上原 健敬, 野田 知之, 山川 泰明, 井上 円加, 中原 龍一, 島村 安則, 尾崎 敏文, 木浪 陽

    中国・四国整形外科学会雑誌   27 ( 1 )   173 - 174   2015.4

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  • Efficacy of tramadol-acetaminophen tablets in low back pain patients with depression Reviewed

    Tomoko Tetsunaga, Tomonori Tetsunaga, Masato Tanaka, Toshifumi Ozaki

    JOURNAL OF ORTHOPAEDIC SCIENCE   20 ( 2 )   281 - 286   2015.3

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    Tramadol-acetaminophen tablets are currently used to treat pain, including that of degenerative lumbar disease. Although there are many reports on tramadol-acetaminophen tablets, treatment outcomes in low back pain (LBP) patients with depression remain uncertain. This study investigated the outcomes of LBP patients with depression treated with tramadol-acetaminophen tablets.
    Of 95 patients with chronic LBP, 70 (26 men, 44 women; mean age 64 years) who were judged as having depression by the Self-Rating Depression Scale (SDS) were included in this study. In this trial, patients received one of two randomly assigned 8-week treatment regimes: tramadol-acetaminophen (Tramadol group, n = 35) and non-steroidal anti-inflammatory drugs (NSAIDs) (NSAID group, n = 35). In addition to completing self-report questionnaires, patients provided demographic and clinical information. All patients were assessed using a Numerical Rating Scale (NRS), Oswestry Disability Index (ODI), Pain Disability Assessment Scale (PDAS), Hospital Anxiety and Depression Scale (HADS), SDS, and Pain Catastrophizing Scale (PCS).
    After 8 weeks' treatment, the NRS and SDS scores were lower in the Tramadol group than in the NSAID group (p &lt; 0.05). There were no significant differences in the ODI, PDAS, and PCS scores between the groups (p = 0.47, 0.09, 0.47). Although there was no difference in the anxiety component of the HADS between the groups (p = 0.36), the depression component was lower in the Tramadol group than in the NSAID group (p &lt; 0.05). There was no significant difference between groups in the percentage of patients with treatment-associated adverse events.
    This investigation found that tramadol-acetaminophen is effective for reducing LBP and provided a prophylactic antidepressant effect in chronic LBP patients with depression.

    DOI: 10.1007/s00776-014-0674-4

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  • 肘関節terrible triad損傷の手術的治療

    今谷 潤也, 森谷 史朗, 前田 和茂, 桐田 由季子, 林 正典, 尾崎 敏文, 二村 昭元, 秋田 恵一

    日本整形外科学会雑誌   89 ( 3 )   S1108 - S1108   2015.3

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  • 前十字靱帯再建術における骨孔内での再建靱帯の偏位について 大腿骨骨孔モデルを用いた検討

    藤井 政孝, 佐々木 祐介, 荒木 大輔, 古松 毅之, 宮澤 慎一, 尾崎 敏文, Fu Freddie H.

    JOSKAS   40 ( 1 )   98 - 99   2015.3

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    屍体膝から採取した半腱様筋腱をEndoButton CLを用いて二重折とし正確に径7mmであった8本(再建靱帯)を、大腿骨骨孔モデルとして作成したアルミニウム製立方体の径7mmの孔に通し、一端をEndoButtonで固定した。graft bending angleの変化を再現するため再建靱帯を15°、30°、45°、60°、75°の方向へ30Nで牽引し、デジタルカメラで骨孔開口部を骨孔軸の延長線上から撮影し、Image Jを用いて画像解析を行った。骨孔モデルの開口部の中心点と開口部における再建靱帯の中心点の2点間の距離を計測し、その値を再建靱帯の偏位量と定義した。再建靱帯の偏位量はgraft bending angle 15 °の時最小で0.7mm、75°の時に最大で1.1mmであった。

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  • microRNA-133aとその標的遺伝子は骨肉腫がん幹細胞分画の悪性形質を制御し骨肉腫患者の新規予後因子として機能する

    藤原 智洋, 小坂 展慶, 高橋 陵宇, 竹下 文彦, 吉田 朗彦, 窪田 大介, 小林 英介, 落谷 孝広, 川井 章, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 3 )   S861 - S861   2015.3

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  • 骨軟部腫瘍における画像評価最前線 シンチグラフィを用いた骨軟部腫瘍の機能的画像診断

    国定 俊之, 武田 健, 藤原 智洋, 上原 健敬, 大森 敏規, 尾崎 敏文

    臨床整形外科   50 ( 3 )   229 - 235   2015.3

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    骨軟部腫瘍の診断・治療では,骨シンチグラフィ,タリウムシンチグラフィが有用な画像診断法である.骨シンチグラフィは,骨腫瘍の活動性が評価可能であり,単発性・多発性発生の診断や悪性骨腫瘍では骨転移の診断に役立つ.タリウムシンチグラフィは腫瘍の活動性や悪性度を反映するため,術前治療の効果判定や良性・悪性の鑑別診断に有用である.術前治療が有効と判定可能であれば,縮小手術が可能となりうる.タリウムシンチグラフィとDMSAシンチグラフィを行うことで,軟骨系骨腫瘍の悪性度診断も可能とある.画像診断で良性・悪性の鑑別ができれば,外来診療での治療方針決定の一つの指標となる.(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01554&link_issn=&doc_id=20150304050011&doc_link_id=10.11477%2Fmf.1408200144&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1408200144&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 骨温存のため液体窒素処理骨と腫瘍用人工関節術を併用した2例

    上原 健敬, 国定 俊之, 大森 敏規, 藤原 智洋, 武田 健, 尾崎 敏文

    中部日本整形外科災害外科学会雑誌   58 ( 春季学会 )   224 - 224   2015.3

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  • Iliosacral screw挿入における仙骨安全域の検討

    上原 健敬, 野田 知之, 山川 泰明, 雑賀 建多, 中原 龍一, 木浪 陽, 島村 安則, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 3 )   S805 - S805   2015.3

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  • 患肢温存術を行った15歳以下小児悪性骨腫瘍の治療成績

    武田 健, 国定 俊之, 魚谷 弘二, 杉生 和久, 上原 健敬, 大森 敏規, 藤原 智洋, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 3 )   S687 - S687   2015.3

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  • 原発性悪性骨・軟部腫瘍に対するpolypropylene meshを用いた腫瘍用人工関節置換術の治療成績

    藤原 智洋, 国定 俊之, 武田 健, 山川 泰明, 上原 健敬, 大森 敏規, 魚谷 弘二, 杉生 和久, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 3 )   S682 - S682   2015.3

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  • 3D-navigation systemを用いたtransiliac-transsacral screw固定の経験

    木浪 陽, 野田 知之, 上原 健敬, 山川 泰明, 尾崎 敏文

    日本整形外科学会雑誌   89 ( 3 )   S485 - S485   2015.3

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  • MRI of Rheumatoid Arthritis: Comparing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) Scoring and Volume of Synovitis for the Assessment of Biologic Therapy Reviewed

    Ryuichi Nakahara, Keiichiro Nishida, Kenzo Hashizume, Ryouzou Harada, Takahiro Machida, Masahiro Horita, Aiji Ohtsuka, Toshifumi Ozaki

    ACTA MEDICA OKAYAMA   69 ( 1 )   29 - 35   2015.2

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    The outcome measures in rheumatology clinical trials (OMERACT) scores are the most mature quantitation system for rheumatoid arthritis (RA) on magnetic resonance imaging (MRI). Direct measuring techniques of synovial volume have been reported with good reproducibility, although few reports have demonstrated the changes of these measures in response to treatment. To assess these clinical responses, we evaluated the correlation of the changes of clinical activity score 28-joints disease activity score (DAS28-CRP) with the changes of OMERACT scores and with synovial volume measurements. Eight RA patients who were treated by biologic agents were examined with MRI of the dominant affected wrist and finger joints before and one year after the treatment. The total OMERACT score was reduced from 48.0 to 41.3, and synovial volume was reduced from 15.4 to 8.8 milliliters. Positive correlations were seen between the changes of DAS28-CRP and the changes of OMERACT synovitis score (r = 0.27), OMERACT total score (r = 0.43) and synovial volume (r = 0.30). Limited to synovium assessment, synovial volume showed a better correlation with DAS28-CRP than the OMERACT synovitis score. On the other hand, the OMERACT total score showed a higher correlation with DAS28-CRP than synovial volume, probably because the OMERACT total score includes scores for bone erosion and bone edema as well.

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  • MicroRNAs in Bone and Soft Tissue Sarcomas and Their Value as Biomarkers Reviewed

    Tomohiro Fujiwara, Yu Fujita, Yutaka Nezu, Akira Kawai, Toshifumi Ozaki, Takahiro Ochiya

    Epigenetic Biomarkers and Diagnostics   613 - 642   2015.1

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    Bone and soft tissue sarcomas are malignant neoplasms that are histologically and genetically heterogeneous, and various subtypes of them have been identified. Evidence of microRNA (miRNA) dysregulation in bone and soft tissue sarcomas has been recently described. miRNA dysregulation that is associated with genetic abnormalities unique to the specific subtypes of sarcomas, functionally important, or correlated with clinical prognosis has been gradually identified. Furthermore, the discovery of circulating miRNAs in patient blood has accelerated interest in their potential to transform clinical applications. Considering the lack of useful bone and soft tissue sarcoma biomarkers, the discovery of miRNA dysregulation may provide a diagnostic method that can be used at early disease stages to detect tumors, predict tumor response to chemotherapy, or identify prognoses. Such interventions would address some of the most important challenges in sarcoma management. In this review, we summarize the emerging evidence of miRNA dysregulation in bone and soft tissue sarcomas and discuss their potential as novel biomarkers and therapeutics.

    DOI: 10.1016/B978-0-12-801899-6.00030-9

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  • Modification of the cell adhesion and hydrophilic characteristics of poly(ether-ether-ketone) by 172-nm Xenon excimer radiation Reviewed

    Yukimasa Okada, Takayuki Furumatsu, Shinichi Miyazawa, Masataka Fujii, Hiroyuki Takahashi, Hiroomi Kimura, Toshifumi Ozaki, Nobuhiro Abe

    BIO-MEDICAL MATERIALS AND ENGINEERING   25 ( 2 )   169 - 175   2015

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    BACKGROUND: Poly-ether-ether-ketone (PEEK) has biomechanical and chemical properties that are excellent for biomedical applications; however, PEEK adhesion to bone or chondral tissue proceeds slowly due to poor hydrophilicity and other surface characteristics.
    OBJECTIVE: We investigated the structural change, hydrophilicity, and cytocompatibility of a PEEK surface after 172-nm xenon excimer UV-irradiation.
    METHODS: The surface characteristics before and after irradiation were evaluated by contact angle and ATR-FTIR measurements. Mouse osteoblast-like cells (MC3T3-E1) were cultured on PEEK plates and collected after 6, 12 and 24 h for cell adhesion analysis by crystal violet staining (CVS) and scanning electron microscopy (SEM).
    RESULTS: UV-irradiation improved PEEK surface hydrophilicity, as indicated by a significant drop in water contact angle (p &lt; 0.05). Irradiated PEEK showed additional peaks around 3370 cm(-1) and 1720 cm(-1), highlighting the generation of hydroxyl and carbonyl groups. CVS and SEM revealed improved adhesion to the PEEK surface after UV-irradiation.
    CONCLUSION: Our results suggest that 172-nm UV-irradiated PEEK may be used in biomedical applications that require good cell adhesion.

    DOI: 10.3233/BME-151267

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  • Kinematic analysis of total knee joint by means of navigation system Reviewed

    T. Inoue, N. Abe, S. Miyazawa, K. Fujiwara, Y. Nakajima, N. Sugita, M. Mitsuishi, T. Ozaki, Z. Chen

    Transactions of the JSME   81 ( 830 )   15-00229   2015

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    DOI: 10.1299/transjsme.15-00229

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  • Erratum. Venous Thromboembolism after Total Hip Arthroplasty Diagnosed by Enhanced Computed Tomography:Comparison of Selective Thromboprophylaxis and No Thromboprophylaxis. Reviewed

    Okada Y, Endo H, Tanaka T, Mitani S, Fujiwara K, Tetsunaga T, Kagawa Y, Fujii Y, Kunisada T, Ozaki T

    Acta medica Okayama   69 ( 5 )   325   2015

  • microRNAs and Soft Tissue Sarcomas. Reviewed

    Fujiwara T, Kunisada T, Takeda K, Ozaki T

    Advances in experimental medicine and biology   889   179 - 199   2015

  • Immunotherapy for Bone and Soft Tissue Sarcomas. Reviewed

    Uehara T, Fujiwara T, Takeda K, Kunisada T, Ozaki T, Udono H

    BioMed research international   2015   820813   2015

  • Venous thromboembolism after total hip arthroplasty diagnosed by enhanced computed tomography:comparison of selective thromboprophylaxis and no thromboprophylaxis. Reviewed

    Okada Y, Endo H, Mitani S, Fujiwara K, Tetsunaga T, Kagawa Y, Fujii Y, Kunisada T, Ozaki T

    Acta medica Okayama   69 ( 4 )   205 - 212   2015

  • Diagnostic value of Thallium-201 scintigraphy in differentiating malignant bone tumors from benign bone lesions. Reviewed

    Ryota Inai, Takayoshi Shinya, Akihiro Tada, Shuhei Sato, Tomohiro Fujiwara, Ken Takeda, Toshiyuki Kunisada, Hiroyuki Yanai, Toshifumi Ozaki, Susumu Kanazawa

    Annals of nuclear medicine   29 ( 8 )   674 - 681   2015

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    OBJECTIVE: This retrospective study aims to evaluate the diagnostic capacity of thallium-201 (201Tl) scintigraphy for differentiating malignant bone tumors from benign bone lesions. METHODS: Between January 2006 and December 2012, 279 patients with bone lesions (51 malignant and 228 benign) underwent 201Tl scintigraphy before treatment. To evaluate 201Tl uptake, we investigated tumor-to-background contrast (TBC) as well as TBC washout rate (WR). The differences of TBC on early and delayed images and WR were estimated by the Mann-Whitney U test. Receiver operating characteristic (ROC) analyses were used to determine the cut-off TBC values for differentiating malignant bone tumors from benign bone lesions. RESULTS: There were statistically significant differences in median TBC between malignant tumors and benign lesions. These differences occurred for early imaging (1.57 vs. 0.09, p < 0.001) as well as for delayed imaging (0.83 vs. 0.07, p < 0.001). However, there was no statistical difference in WR between malignant tumors and benign lesions (44 vs. 43 %, NS). The chosen TBC cut-off value was 0.68 for early imaging and 0.38 for delayed imaging. Using these cut-off values, the prediction of malignancy had a 77 % sensitivity, 74 % specificity, and 75 % accuracy for early imaging and an 80 % sensitivity, 76 % specificity, and 77 % accuracy for delayed imaging. CONCLUSIONS: 201Tl scintigraphy may have the ability to distinguish malignant bone tumors from benign bone lesions.

    DOI: 10.1007/s12149-015-0990-6

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  • Both a visual and a semiquantitative analysis for differentiating benign from malignant chondrogenic bone tumors using Tc-99m (V) DMSA scintigraphy: a prospective study. Reviewed International journal

    Takayoshi Shinya, Shuhei Sato, Toshiyuki Kunisada, Ryota Inai, Hiroyuki Yanai, Toshifumi Ozaki, Susumu Kanazawa

    Nuclear medicine communications   36 ( 8 )   802 - 807   2015

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    OBJECTIVE: The aims of this prospective study were to assess the relationship between tumor aggressiveness and Tc-99m (V) dimercaptosuccinic acid (DMSA) uptake in chondrogenic bone tumors and the value of Tc-99m (V) DMSA scintigraphy for differentiating benign from malignant tumors. METHODS: Twenty-four patients with chondrogenic tumors (19 benign and five malignant) underwent Tc-99m DMSA (V) scintigraphy. Radiopharmaceutical uptake was classified using a three-point scale to allow a visual-only analysis, and a tumor-to-background contrast (TBC) was computed using regions of interest to provide a semiquantitative analysis. Spearman's correlation coefficient was used to assess the correlation between tumor aggressiveness and TBC. The difference in TBC between benign and malignant tumors was analyzed with the Mann-Whitney U-test. An appropriate cutoff value of TBC was chosen for the diagnosis of malignancy of a tumor using receiver operating characteristic analysis. RESULTS: Six benign tumors showed negative uptake (uptake score 0), whereas 13 benign tumors showed positive uptake (n=10 uptake score 1; n=3 uptake score 2). All chondrosarcomas showed positive uptake (n=2 uptake score 1; n=3 uptake score 2). A significant correlation was found between tumor aggressiveness and TBC. A significant difference was seen in TBC between benign and malignant tumors. With the chosen cutoff value of TBC equal to 0.611, the sensitivity was 80.0%, specificity was 78.9%, the positive predictive value was 50.0%, and the negative predictive value was 93.8%. CONCLUSION: Tc-99m (V) DMSA scintigraphy may have the potential to improve diagnostic methods for detecting chondrosarcomas using visual and/or semiquantitative analyses.

    DOI: 10.1097/MNM.0000000000000328

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  • Automatic method to determine anterior pelvic plane of pelvis Reviewed

    T. Inoue, K. Fujiwara, Y. Fujii, N. Abe, T. Ozaki, Y. Nakajima, N. Sugita, M. Mitsuishi, Z. Chen

    Japanese Journal of Clinical Biomechanics   36   145 - 150   2015

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  • The figure-of-nine leg position for anatomic anterior cruciate ligament reconstruction Reviewed

    T. Furumatsu, M. Fujii, T. Tanaka, S. Miyazawa, T. Ozaki

    Revue de Chirurgie Orthopedique et Traumatologique   101 ( 3 )   249   2015

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    Anatomic double-bundle anterior cruciate ligament (ACL) reconstruction can restore the function and kinematics of the knee in ACL-deficient patients. Several outside-in drilling systems for accurate femoral tunnel creations have been developed. However, the femoral tunnel creation at the lower position of the intercondylar notch can be difficult in an usual leg position with the knee flexed at 90° without varus stress. This technical note describes that the figure-of-nine leg position provides a better arthroscopic view to safely clean up the ACL femoral footprint located at the lower area of the lateral intercondylar wall. This position is useful to create the optimal femoral tunnels using the outside-in drilling technique, without damaging the lateral meniscus posterior root, lateral tibial eminence, and supplemental fibers that bridge the gap between the lateral meniscus and the ACL tibial insertion.

    DOI: 10.1016/j.rcot.2014.12.013

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  • Role of Rho Small GTPases in Meniscus Cells Reviewed

    Tomoko Kanazawa, Takayuki Furumatsu, Emi Matsumoto-Ogawa, Ami Maehara, Toshifumi Ozaki

    JOURNAL OF ORTHOPAEDIC RESEARCH   32 ( 11 )   1479 - 1486   2014.11

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    We previously reported that mechanical stretch regulates Sry-type HMG box (SOX) 9-dependent 1(II) collagen (COL2A1) expression in inner meniscus cells. This study examined the role of the small Rho guanosine 5' triphosphatase Rac1 and Rho-associated kinase (ROCK) in the regulation of stretch-induced SOX9 gene expression in cultured human inner meniscus cells. COL2A1 and SOX9 gene expression was assessed by real-time PCR after application of uni-axial cyclic tensile strain (CTS) in the presence or absence of ROCK and Rac1 inhibitors. The subcellular localization of SOX9 and the Rac1 effector cyclic AMP response element-binding protein (CREB), the phosphorylation state of SOX9, Rac1 activation, and the binding of CREB to the SOX9 promoter were assessed. CTS increased the expression of COL2A1 and SOX9, which was suppressed by inhibition of Rac1. ROCK inhibition enhanced COL2A1 and SOX9 gene expression in the absence of CTS. CTS stimulated the nuclear translocation and phosphorylation of SOX9, and increased Rac1 activation. CTS also increased the binding of CREB to the SOX9 promoter. The results suggest that mechanical stretch-dependent upregulation of SOX9 by CREB in inner meniscus cells depends on the antagonistic activities of ROCK and Rac1. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1479-1486, 2014.

    DOI: 10.1002/jor.22703

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  • Spinal Metaplastic Meningioma with Osseous Differentiation in the Ventral Thoracic Spinal Canal Reviewed

    Kentaro Yamane, Masato Tanaka, Yoshihisa Sugimoto, Kouichi Ichimura, Toshifumi Ozaki

    ACTA MEDICA OKAYAMA   68 ( 5 )   313 - 316   2014.10

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    Ossified meningioma is classified histologically as a phenotype of metaplastic meningioma, and it is extremely rare. There are only 12 cases involving ossified spinal meningiomas in the literature. We present the case of a 61-year-old female with a primary tumor within the ventral spinal canal at T12. Although we performed a total tumor excision using an ultrasonic bone aspirator, a temporary deterioration of motor evoked potentials (MEPs) was observed during curettage with a Kerrison rongeur. The neurologic findings worsened immediately after surgery. Histologically, the tumor was diagnosed as a metaplastic meningioma with osseous differentiation. In order to avoid spinal cord injury, great care must be taken when removing an ossified meningioma located on the ventral spinal cord.

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  • Long-term follow-up of resection-replantation for sarcoma in the distal radius Reviewed

    Eiji Nakada, Shinsuke Sugihara, Toshiyuki Kunisada, Toshifumi Ozaki

    JOURNAL OF ORTHOPAEDIC SCIENCE   19 ( 5 )   832 - 837   2014.9

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    DOI: 10.1007/s00776-013-0378-1

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  • RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis Reviewed

    Tomohiro Fujiwara, Ryou-u Takahashi, Nobuyoshi Kosaka, Yutaka Nezu, Akira Kawai, Toshifumi Ozaki, Takahiro Ochiya

    MOLECULAR THERAPY-NUCLEIC ACIDS   3   e189   2014.9

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    Drug resistance and metastasis are lethal characteristics of tumors. We previously demonstrated that silencing of ribophorin II (RPN2), which is part of the N-oligosaccharyl transferase complex, efficiently induced apoptosis and reduced resistance to docetaxel in human breast cancer cells. Here, we report the clinical and functional correlations of RPN2 expression in osteosarcoma. Immunohistochemical evaluation of 35 osteosarcoma patient biopsies revealed that RPN2 was moderately to highly expressed in all specimens, and higher RPN2 mRNA expression was significantly correlated with poor prognosis. To investigate whether lethal phenotypes of osteosarcoma could be reduced by regulating the expression of RPN2, we conducted a study of RNAi-induced RPN2 knockdown in highly metastatic human osteosarcoma cells. The results indicated that RPN2 silencing reduced cell proliferation, sphere formation, cell invasion, and sensitized drug response in vitro. Mice bearing RPN2-silenced highly metastatic osteosarcoma xenografts showed reduced tumor growth and lung metastasis, and survived longer than mice bearing control tumor xenografts. Taken together, our data suggest that RPN2 silencing contributes to regulation of lethal osteosarcoma phenotypes and could be a novel target for RNAi-based therapeutics against osteosarcoma.

    DOI: 10.1038/mtna.2014.35

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  • Two-Directional Arthrographic Assessment for Treating Bilateral Development Dislocation of the Hips in Children after Walking Age Reviewed

    Hirosuke Endo, Hirofumi Akazawa, Shigeru Mitani, Yoshiki Okada, Kentaro Yamane, Toshifumi Ozaki

    ACTA MEDICA OKAYAMA   68 ( 4 )   201 - 206   2014.8

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    We reviewed the treatment outcome in 14 hips of 7 patients who were diagnosed as having bilateral developmental dislocation of the hip (DDH) after walking age and could be followed up until they were at least 14 years of age. Based on the results of two-directional arthrography of the hip, closed reduction was performed in 2 hips, and open reduction was performed without osteotomy in 12 hips. The final radiographic evaluations were made according to the Kalamchi and MacEwen classification and Severin classification. The mean age at the initial visit was 1 year and 9 months (range, 1 year and 5 months to 3 years). The outcome was satisfactory for one hip in Group I and 2 hips in Group II according to the Kalamchi and MacEwen classification, and in 83% of the Severin Class I and II hips. Arthrography was useful for identifying asymmetry, demonstrating the usefulness of a treatment strategy based on arthrography of the hip.

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  • 前十字靱帯再建術における大腿骨骨孔内での再建靱帯の偏位についての検討

    藤井 政孝, 佐々木 祐介, 荒木 大輔, 古松 毅之, 尾崎 敏文, Fu Freddie H.

    日本整形外科学会雑誌   88 ( 8 )   S1429 - S1429   2014.8

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  • マウス骨肉腫・軟骨肉腫における免疫抑制細胞MDSCに対するmetforminの作用

    上原 健敬, 榮川 伸吾, 大森 敏規, 山川 泰明, 武田 健, 国定 俊之, 尾崎 敏文, 鵜殿 平一郎

    日本整形外科学会雑誌   88 ( 8 )   S1739 - S1739   2014.8

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  • ANTITUMOR EFFECT OF TELOMERASE-SPECIFIC ONCOLYTIC ADENOVIRUS ON HUMAN BONE AND SOFT TISSUE SARCOMA CELLS Reviewed

    Hiroshi Tazawa, Tsuyoshi Sasaki, Jo Hasei, Yuuri Hashimoto, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

    JOURNAL OF GENE MEDICINE   16 ( 7-8 )   261 - 262   2014.7

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  • Postoperative change in medial meniscal length in concurrent all-inside meniscus repair with anterior cruciate ligament reconstruction Reviewed

    Takayuki Furumatsu, Shinichi Miyazawa, Takaaki Tanaka, Yukimasa Okada, Masataka Fujii, Toshifumi Ozaki

    INTERNATIONAL ORTHOPAEDICS   38 ( 7 )   1393 - 1399   2014.7

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    Meniscus repair can restore meniscal function that transfers the axial compressive force to circumferential tensile strain. However, few reports have investigated the relationship between concurrent meniscus repair with acute anterior cruciate ligament (ACL) reconstruction and postoperative meniscal position. This study aimed to evaluate medial meniscal size and clinical results in patients who underwent ACL reconstruction and concomitant all-inside medial meniscus repair.
    Twenty patients underwent ACL reconstruction and concurrent medial meniscus repair of a peripheral longitudinal tear using the FasT-Fix meniscal repair device. Medial tibial plateau length (MTPL) and width (MTPW) were determined by radiographic images. We evaluated the Lysholm score, anteroposterior instability, meniscal healing and magnetic resonance imaging (MRI)-based medial meniscal length (MML) and width (MMW). Correlations between MRI-based meniscal size, radiographic measurement and height were investigated.
    All patients showed complete healing of the repaired meniscus in arthroscopic evaluation. However, one patient needed a subsequent meniscus repair during the follow-up period. Lysholm score and anteroposterior instability improved significantly. A better correlation was observed between MMW and MTPW than between MML and MTPL. Concurrent all-inside medial meniscus repair with ACL reconstruction significantly increased MML percentage (%MML) (100 MML/MTPL) but did not affect MMW percentage (%MMW) (100 MMW/MTPW).
    Concurrent all-inside medial meniscus repair with ACL reconstruction had satisfactory clinical results. %MML was increased by concurrent medial meniscus repair without affecting %MMW. Our results suggest that medial meniscus repair associated with ACL reconstruction may restore meniscal function by adjusting the anteroposterior length of the torn medial meniscus.

    DOI: 10.1007/s00264-013-2238-1

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  • 大腿骨骨孔モデルを用いた前十字靱帯再建術における骨孔内での再建靱帯の偏位についての検討

    藤井 政孝, 佐々木 祐介, 荒木 大輔, 古松 毅之, 尾崎 敏文, Fu Freddie

    JOSKAS   39 ( 4 )   368 - 368   2014.7

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  • 神経線維腫症1型に合併した巨大血腫に対して動脈塞栓術による止血を行った2例

    武田 健, 篠原 健介, 長谷井 嬢, 平木 隆夫, 国定 俊之, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 6 )   S1252 - S1252   2014.6

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  • 不安定型骨盤輪骨折に対するnavigation systemを利用したIliosacral screwの有用性

    上原 健敬, 木浪 陽, 野田 知之, 山川 泰明, 井上 円加, 中原 龍一, 島村 安則, 尾崎 敏文

    骨折   36 ( Suppl. )   S368 - S368   2014.6

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  • 上腕骨近位部発生の悪性骨腫瘍に対する患肢温存術の治療成績

    武田 健, 国定 俊之, 大森 敏規, 上原 健敬, 山川 泰明, 尾崎 修平, 長谷井 嬢, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 6 )   S1134 - S1134   2014.6

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  • 骨・軟部腫瘍切除術時のstaple使用は創合併症に影響しない

    国定 俊之, 上原 健敬, 武田 健, 長谷井 嬢, 山川 泰明, 井上 円加, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 6 )   S1242 - S1242   2014.6

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  • 骨盤Ewing肉腫に対して創外固定術を併用し腓骨移植術(non-vascularized)で再建した1例

    大森 敏規, 武田 健, 上原 健敬, 山川 泰明, 長谷井 嬢, 吉田 晶, 国定 俊之, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 6 )   S1294 - S1294   2014.6

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  • Ilioinguinal approach変法(Kloen変法)が有用であった寛骨臼前壁骨折の治療経験

    井上 円加, 野田 知之, 上原 健敬, 山川 泰明, 木浪 陽, 島村 安則, 土井 武, 尾崎 敏文

    骨折   36 ( Suppl. )   S154 - S154   2014.6

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  • 下腿骨幹部骨折の治療成績 腓骨骨折高位が治療成績に影響するか?

    山川 泰明, 野田 知之, 杉生 和久, 堀田 昌宏, 上原 健敬, 町田 崇博, 中原 龍一, 木浪 陽, 島村 安則, 尾崎 敏文

    骨折   36 ( Suppl. )   S129 - S129   2014.6

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  • トラブルから学ぶ骨折治療 トラブルから学ぶ骨盤・寛骨臼骨折治療

    野田 知之, 上原 健敬, 山川 泰明, 島村 安則, 尾崎 敏文, 木浪 陽

    骨折   36 ( Suppl. )   S32 - S32   2014.6