Faculty Profiles - NISHIDA Keiichiro

Papers - NISHIDA Keiichiro

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関節リウマチとして加療後、掌蹠膿疱症性骨関節炎と診断した1例の関節鏡視所見

那須義久, 志水紀之, 浪花崇一, 堀田佳史, 中原龍一, 西田圭一郎

関節の外科 49 ( 2 ) 94 - 94 2022

Both microRNA-455-5p and -3p repress hypoxia-inducible factor-2α expression and coordinately regulate cartilage homeostasis Reviewed International coauthorship International journal

Yoshiaki Ito, Tokio Matsuzaki, Fumiaki Ayabe, Sho Mokuda, Ryota Kurimoto, Takahide Matsushima, Yusuke Tabata, Maiko Inotsume, Hiroki Tsutsumi, Lin Liu, Masahiro Shinohara, Yoko Tanaka, Ryo Nakamichi, Keiichiro Nishida, Martin K. Lotz, Hiroshi Asahara

Nature Communications 12 ( 1 ) 4148 - 4148 2021.12

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

<title>Abstract</title>Osteoarthritis (OA), the most common aging-related joint disease, is caused by an imbalance between extracellular matrix synthesis and degradation. Here, we discover that both strands of microRNA-455 (miR-455), -5p and -3p, are up-regulated by Sox9, an essential transcription factor for cartilage differentiation and function. Both miR-455-5p and -3p are highly expressed in human chondrocytes from normal articular cartilage and in mouse primary chondrocytes. We generate miR-455 knockout mice, and find that cartilage degeneration mimicking OA and elevated expression of cartilage degeneration-related genes are observed at 6-months-old. Using a cell-based miRNA target screening system, we identify hypoxia-inducible factor-2α (HIF-2α), a catabolic factor for cartilage homeostasis, as a direct target of both miR-455-5p and -3p. In addition, overexpression of both miR-455-5p and -3p protect cartilage degeneration in a mouse OA model, demonstrating their potential therapeutic value. Furthermore, knockdown of HIF-2α in 6-month-old miR-455 knockout cartilage rescues the elevated expression of cartilage degeneration-related genes. These data demonstrate that both strands of a miRNA target the same gene to regulate articular cartilage homeostasis.

DOI： 10.1038/s41467-021-24460-7

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Other Link： http://www.nature.com/articles/s41467-021-24460-7

骨粗鬆症性椎体骨折に対する骨折リエゾンサービスー骨粗鬆症マネージャーが果たす役割―

鉄永倫子, 鉄永智紀, 高尾真一郎, 小橋靖子, 西田圭一郎

整形外科最小侵襲手術ジャーナル 101 2021.12

股関節痛を契機に診断された強直性脊椎炎の1例

山田和希, 那須義久, 鉄永智紀, 佐藤嘉洋, 廣瀬一樹, 中原龍一, 西田圭一郎, 尾崎敏文

日本小児整形外科学会雑誌 30 ( 2 ) 166 - 170 2021.12

Language：Japanese Publisher：(一社)日本小児整形外科学会

股関節痛を契機に診断に至った、強直性脊椎炎:ankylosing spondylitis(以下、AS)の1例を経験したので報告する。症例は16歳男子で、右股関節痛のため近医を受診した。大腿骨寛骨臼インピンジメントの診断で当科に紹介された。当科初診時、右股関節痛は安静時と夜間に強く、運動時には感じなかった。右股関節の可動域制限を認め疼痛誘発テストは陽性であった。詳細に問診したところ、過去に腰臀部痛と両股関節痛を繰り返していた。単純X線では左仙腸関節に硬化像を認め、MRIでは右股関節水腫と両仙腸関節周囲の骨髄浮腫像を認めた。血液検査では炎症反応が上昇し、HLA-B27は陽性であった。ASと診断し、疾患活動性が高かったため、Infliximabの適応とした。治療は奏効し、現在も継続している。詳細な病歴聴取により早期の診断と治療が行えたため、短期の成績ではあるが経過良好であった。(著者抄録)

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Difficult-to-treat RA の定義，臨床的特徴とマネジメント

西田圭一郎, 堀田佳史, 浪花崇一, 那須義久

臨床リウマチ 33 ( 4 ) 271 - 277 2021.12

Authorship：Lead author Language：Japanese Publisher：(一社)日本臨床リウマチ学会

治療が困難なRA(Difficult t-to-treat rheumatoid arthritis;D2T RA)とは、数種類の治療を行っても症状が改善せず、患者および経済的負担が大きいRA患者を指す新しい概念である。欧州リウマチ学会議(EULAR)では(1)治療不成功の病歴があり、(2)活動性/症候性の特性を有し、(3)臨床的に認識されていること、の3つの基準がすべて揃うものをD2T RAとした。D2T RAはRA患者の5～10%程度に発生するという報告が多く、患者は社会生活、労働能力、QOLに直接影響する症状に悩まされ続ける他、年間にかかる医療コストが非D2T RA患者より高額である。臨床的背景として、呼吸器障害、心血管系障害などの合併症、薬剤に対する有害事象、治療に対するアドヒアランスの低さの他、線維筋痛症や変形性関節症なとの疼痛症候群の合併、喫煙、肥満、抑うつなどが報告されている。治療にあたっては、患者教育、運動療法、心理学的介入、患者ケアの強化や医療従事者とのコミュニケーションの強化を基本として、個々の患者において過去の薬剤歴やmode of actionを考慮した薬剤選択や、整形外科的介入などによるカスタマイズを行って治療の最適化を図る必要がある。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J02269&link_issn=&doc_id=20220204090002&doc_link_id=10.14961%2Fcra.33.271&url=https%3A%2F%2Fdoi.org%2F10.14961%2Fcra.33.271&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

周術期の投薬コントロールと合併症対策特集:関節リウマチ診療ガイドライン2020 ―整形外科医から見るガイドラインアップデート ― Reviewed

西田圭一郎, 中原龍一, 那須義久, 原田遼三

Loco Cure 7 ( 4 ) 314 - 318 2021.11

Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(株)先端医学社

人工関節感染の有意なリスク因子として、BMI、DM、ステロイド、低アルブミン、関節リウマチ(RA)、輸血、悪性腫瘍、免疫低下、手術時間の延長、過去の手術歴などが指摘されており、疾患活動性のコントロールを含めて術前に可能な限り改善しせめて手術に臨むべきである。抗リウマチ薬には免疫抑制効果の懸念があり、長期の休薬はRAの再燃を惹起する可能性があるため、周術期の薬剤マネジメントが重要である。メトトレキサート(MTX)については、わが国のガイドラインでは12.5mg/週以下の使用量であれば再燃のリスクを抑制し、術後感染症、創傷治癒遅延に影響しないとされているため、休薬の必要はない。生物学的製剤、JAK阻害薬は免疫抑制作用によってSSIのリスクを増大させる可能性があるが、現時点では休薬期間を設けることによって安全に整形外科手術が可能である。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J06622&link_issn=&doc_id=20211203480007&doc_link_id=%2Fae6locoe%2F2021%2F000704%2F008%2F0314-0318%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6locoe%2F2021%2F000704%2F008%2F0314-0318%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

関節リウマチに対するAVANTAとINTEGRAを用いたMP人工指関節置換術の術後可動域の比較

浪花崇一, 堀田佳史, 中原龍一, 那須義久, 西田圭一郎

日本関節病学会誌 40 ( 3 ) 304 - 304 2021.11

AIを用いた単純X線画像における骨端線変化の自動生成

中原龍一, 西田圭一郎, 長谷井嬢, 中澤慎二, 韓昌煕, 藏品豊, 那須義久, 尾崎敏文

日本関節病学会誌 40 ( 3 ) 308 - 308 2021.11

AIを用いた単純X線画像における骨端線変化の自動生成

中原龍一, 西田圭一郎, 長谷井嬢, 中澤慎二, 韓昌煕, 藏品豊, 那須義久, 尾崎敏文

日本関節病学会誌 40 ( 3 ) 308 - 308 2021.11

関節リウマチに対するAVANTAとINTEGRAを用いたMP人工指関節置換術の術後可動域の比較

浪花崇一, 堀田佳史, 中原龍一, 那須義久, 西田圭一郎

日本関節病学会誌 40 ( 3 ) 304 - 304 2021.11

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

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

Authorship：Corresponding author Language：English 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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日本人関節リウマチ患者におけるボディイメージ・アセスメントツールの信頼性の検討

小橋靖子, 西田圭一郎, 堀田昌宏, 那須義久, 原田遼三, 渡辺美紀, 菊地真佑花, 片上香里, 中原龍一, 尾﨑敏文

臨床リウマチ 33 ( 3 ) 221 - 232 2021.9

Language：Japanese Publisher：(一社)日本臨床リウマチ学会

【目的】関節リウマチ(RA)患者におけるボディイメージ・アセスメントツール(BIAT)の信頼性と有効性を検証すること。【方法】本研究は横断的観察研究である。外来通院中(非手術群)および入院中(手術群)のRA患者265例および健常人62名を対象にBIAT質問用紙への回答を依頼した。信頼性の評価として、内部一貫法にはRA患者265例のbaselineのデータを、再テスト法には健常群62名のbaseline・3週後、および非手術群76例のbaseline・半年・1年後のデータを用いた。既存の評価法としてBDI-II(Beck Depression Inventory-II、ベック抑うつ質問票)を用いてBIATの臨床評価としての妥当性を検討した。RA患者265例をDAS28-CRPに基づき、寛解、低疾患活動性、中疾患活動性、高疾患活動性に群別し、BIATとの関連を検討した。さらに非手術群と手術群でBIATに差があるかどうかを検討した。【結果】BIATは全体の評価でも各構成概念の評価でもα係数は0.8以上を示しており、高い一貫性を有していた。再テスト法ではBIAT全体平均において、健常群のbaselineと3週後で相関係数0.75、非手術群のbaselineと半年後および1年後で相関係数0.79および0.78であり、比較的高い信頼性が確認できた。BIAT全体スコアはBDI-IIと有意な負の相関(r=-0.64、P<0.001)を示した。BIATは疾患活動性が高いほど低値となる傾向があることが示された。手術群でのbaselineの平均BIATの値はいずれの構成概念においても非手術群よりも有意に低値であった。【結論】RA患者に対するBIATは、高い一貫性、安定性を有する評価ツールであることが確認された。(著者抄録)

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Comprehensive risk analysis of postoperative complications in patients with rheumatoid arthritis for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis. International journal

Hiromu Ito, Koichi Murata, Yasumori Sobue, Toshihisa Kojima, Keiichiro Nishida, Isao Matsushita, Yutaka Kawahito, Masayo Kojima, Shintaro Hirata, Yuko Kaneko, Mitsumasa Kishimoto, Masataka Kohno, Masaaki Mori, Akio Morinobu, Atsuko Murashima, Yohei Seto, Takahiko Sugihara, Eiichi Tanaka, Takeo Nakayama, Masayoshi Harigai

Modern rheumatology 32 ( 2 ) 1 - 11 2021.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To examine the risk factors of surgical site infection (SSI), delayed wound healing, and death after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: We identified articles indexed in the Cochrane Library, PubMed, and Japan Centra Revuo Medicina Web published from 2013 to 2019 and other articles. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised according to the Grading of Recommendations Assessment, Development, and Evaluation system with some modifications. RESULTS: After inclusion and exclusion by full-text review, 29 articles were analyzed. Use of biological disease modifying antirheumatic drugs was a risk factor of SSI (risk ratio 1.66, 95% confidence interval 1.25-2.19), but not of delayed wound healing. RA itself was a risk factor of SSI, and oral glucocorticoid use was a risk factor of SSI in three of the four studies analyzed and of postoperative death. Age, male sex, comorbidities such as diabetes mellitus and chronic obstructive pulmonary disease, surgical factors such as foot/ankle and spine surgery and longer operative time were risk factors of those postoperative complications. CONCLUSION: Patients with those factors should be dealt with appropriate cautions to strike a risk-benefit balance of orthopedic surgeries.

DOI： 10.1080/14397595.2021.1913824

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教師なし学習を用いたAIによる超音波画像撮像部位自動検出

中原龍一, 高橋康, 西田圭一郎, 那須義久, 渡辺雅仁, 松橋美波, 堀田佳史, 品岡玲, 尾崎敏文

日本整形外科学会雑誌 95 ( 8 ) S1726 - S1726 2021.8

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.3390/ijerph18147520

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Patients' perspectives of rheumatoid arthritis treatment: a questionnaire survey for the 2020 update of the Japan college of rheumatology clinical practice guidelines. International journal

Masayo Kojima, Mieko Hasegawa, Shintaro Hirata, Hiromu Ito, Yuko Kaneko, Mitsumasa Kishimoto, Masataka Kohno, Toshihisa Kojima, Isao Matsushita, Masaaki Mori, Akio Morinobu, Atsuko Murashima, Keiichiro Nishida, Yohei Seto, Yasumori Sobue, Takahiko Sugihara, Eiichi Tanaka, Takeo Nakayama, Yutaka Kawahito, Masayoshi Harigai

Modern rheumatology 32 ( 2 ) 1 - 6 2021.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: This study aimed to evaluate patients' opinions regarding their rheumatoid arthritis (RA) therapy and to reflect the patients' perspectives in the 2020 update of the Japan College of Rheumatology clinical practice guidelines. METHODS: A self-administered questionnaire was mailed to 1600 members of the Japan Rheumatology Friendship Association, who were randomly selected by age and prefecture. RESULTS: A total of 1156 patients returned the questionnaire (response rate, 72.3%; mean age, 63.0 ± 11.9 years). Those who reported having discussed their treatment goals with their doctors (450 respondents, 38.9%) were more likely to be satisfied with their current medical care (odds ratio, 7.13; 95% CI 4.72-10.8) compared with those who had not discussed their goals nor had them explained (287 respondents, 24.8%). The benefits exceeded the adverse effects for all pharmacotherapy (methotrexate, corticosteroids, conventional synthetic antirheumatic drugs, biological agents, Janus kinase inhibitor, and anti-RANKL antibodies). However, while 74.2% of the respondents using biological agents perceived that 'the favorable aspects outweighed the unfavorable aspects,' most of those taking anti-RANKL antibodies (69.2%) felt uncertain. CONCLUSIONS: The questionnaire successfully collected information regarding patients' perceptions regarding their therapy. Further implementation of treat-to-target is necessary in Japan to improve patient satisfaction.

DOI： 10.1080/14397595.2021.1913276

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Systematic review for the treatment of older rheumatoid arthritis patients informing the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis. International journal

Takahiko Sugihara, Yutaka Kawahito, Akio Morinobu, Yuko Kaneko, Yohei Seto, Toshihisa Kojima, Hiromu Ito, Masataka Kohno, Takeo Nakayama, Yasumori Sobue, Keiichiro Nishida, Isao Matsushita, Atsuko Murashima, Masaaki Mori, Eiichi Tanaka, Shintaro Hirata, Mitsumasa Kishimoto, Hisashi Yamanaka, Masayo Kojima, Masayoshi Harigai

Modern rheumatology 32 ( 2 ) 1 - 15 2021.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults. METHODS: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications. RESULTS: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] - 3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively. CONCLUSION: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults.

DOI： 10.1080/14397595.2021.1912922

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Relationship between the physician-based clinical scale for foot and ankle surgery and patient-reported outcomes in patients with long-standing rheumatoid arthritis: Results from a multicenter prospective observational cohort study

Kojima, T., Ishikawa, H., Tanaka, S., Haga, N., Nishida, K., Yukioka, M., Hashimoto, J., Miyahara, H., Niki, Y., Kimura, T., Oda, H., Asai, S., Funahashi, K., Kojima, M., Ishiguro, N.

Modern Rheumatology 31 ( 3 ) 607 - 613 2021.5

運動器疼痛を対象とした医療体制腰痛に対するチームアプローチ

鉄永倫子, 鉄永智紀, 西田圭一郎

ペインクリニック 42 ( 別冊春 ) 247 - 254 2021.5

Language：Japanese Publisher：真興交易(株)医書出版部

腰痛、特に3ヵ月以上症状が持続する慢性腰痛においては、器質的な要因のみならず、心理社会的な因子(psychological and social factors)が少なからず影響している。したがって、治療にあたり生物心理社会モデルに沿って病態を評価し、多職種が連携したチームでの集学的アプローチが有用である。われわれは、2012年より運動器慢性痛に対する集学的アプローチとして「痛みリエゾン外来」を開設し、多角的集学的な外来を多職種で行っている。慢性腰痛の患者さんの一例を提示しながら当センターでのチームアプローチを紹介する。(著者抄録)

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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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1080/14397595.2020.1790138

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Papers - NISHIDA Keiichiro