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

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

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

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

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

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

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

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

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

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

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

Language：English  

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

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

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

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

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

Publisher：Journal of Translational Autoimmunity  

Objective: Dysregulated T cell homeostasis has long been implicated in the pathogenesis of rheumatoid arthritis (RA), in the joint of which peripheral helper T (Tph) cells accumulate and form ectopic lymphoid organs. We examined whether homeostatic signals are involved in the development of Tph cells. Methods: Human peripheral blood mononuclear cells were cultured with IL-7, the critical cytokine for T cell homeostasis. Development of Tph-like cells was assessed by flow cytometry, gene expression, and functional analysis. Chemotaxis of the Tph-like cells to RA synovial fluid (RASF) and the effect of RASF on the development of Tph-like cells was examined. Results: PD-1highCXCR5- Tph-like cells developed from human peripheral blood CD4 T cells after proliferation in response to IL-7. Signals from self-MHC recognition and CD28 co-stimulation were also involved. The IL-7-induced Tph-like (IL-7-Tph) cells produced CXCL13 and IL-21 and helped B cells produce IgG. Comprehensive gene expression analysis further supported the similarity with Tph cells in RA joint. IL-7-Tph cells exhibited chemotaxis toward synovial fluid from RA patients (RASF), and RASF promoted the development of IL-7-Tph cells, which were also induced from CD4 T cells residing in non-inflamed joints. Conclusions: Our results demonstrate an antigen-nonspecific developmental pathway of Tph cells triggered by homeostatic signals and promoted by the local environment of RA, which accounts for the accumulation of Tph cells in inflamed joints.

DOI： 10.1016/j.jtauto.2024.100258

Scopus

Language：English  

DOI： 10.1186/s42836-024-00277-9

Web of Science

PubMed

Language：English   Publisher：Bone and Joint Journal  

Aims The Coronal Plane Alignment of the Knee (CPAK) classification has been developed to predict individual variations in inherent knee alignment. The impact of preoperative and postoperative CPAK classification phenotype on the postoperative clinical outcomes of total knee arthroplasty (TKA) remains elusive. This study aimed to examine the effect of postoperative CPAK classification phenotypes (I to IX), and their pre- to postoperative changes on patient-reported outcome measures (PROMs). Methods A questionnaire was administered to 340 patients (422 knees) who underwent primary TKA for osteoarthritis (OA) between September 2013 and June 2019. A total of 231 patients (284 knees) responded. The Knee Society Score 2011 (KSS 2011), Knee injury and Osteoarthritis Outcome Score-12 (KOOS-12), and Forgotten Joint Score-12 (FJS-12) were used to assess clinical outcomes. Using preoperative and postoperative anteroposterior full-leg radiographs, the arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated and classified based on the CPAK classification. To investigate the impact on PROMs, multivariable regression analyses using stepwise selection were conducted, considering factors such as age at surgery, time since surgery, BMI, sex, implant use, postoperative aHKA classification, JLO classification, and changes in aHKA and JLO classifications from preoperative to postoperative. Results The preoperative and postoperative CPAK classifications were predominantly phenotype I (155 knees; 55%) and phenotype V (73 knees; 26%), respectively. The change in the preoperative to postoperative aHKA classification was a significant negative predictive factor for KOOS-12 and FJS-12, while postoperative apex proximal JLO was a significant negative predictive factor for KSS 2011 and KOOS-12. Conclusion In primary TKA for OA, preoperative and postoperative CPAK phenotypes were associated with PROMs. Alteration in varus/valgus alignment from preoperative to postoperative was recognized as a negative predictive factor for both KOOS-12 and FJS-12. Moreover, the postoperative apex proximal JLO was identified as a negative factor for KSS 2011 and KOOS-12. Determining the target alignment for each preoperative phenotype with reproducibility could improve PROMs.

DOI： 10.1302/0301-620X.106B10.BJJ-2023-1425.R1

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PubMed

Language：English   Publisher：Journal of Experimental Orthopaedics  

Purpose: This study assessed rotational mismatch between components after total knee arthroplasty (TKA) in the supine and standing positions and aimed to investigate the effect of rotational mismatch in the standing position on postoperative patient-reported outcome measures (PROMs). Methods: Seventy-one patients (71 knees) who underwent TKA for medial knee osteoarthritis were used to investigate rotational mismatches between components. Rotational mismatches between components were examined on postoperative standing whole-leg and supine knee radiographs using a three-dimensional-to-two-dimensional model image registration technique, and the angles between the reference axes of the components were measured. Component alignment was evaluated using postoperative computed tomography images, and a questionnaire (2011 version of the Knee Society Score: [KSS 2011]) was mailed to investigate postoperative PROMs. Results: In the entire cohort, rotational mismatches in the supine and standing positions were similar (p = 0.9315). In 15% of patients, the mismatch was large (>5°) in the supine position but small (<5°) in the standing position (overestimated group). However, in 23% of patients, the mismatch was small (<5°) in the supine position and large (>5°) in the standing position (underestimated group). The underestimated group had severe preoperative varus deformity, resulting in external rotation of both femoral and tibial components. Rotational mismatch in the standing position (p = 0.0032) was a significant risk factor for unfavourable PROMs. Patients with a mismatch in the standing position had significantly lower scores than those without a mismatch (p = 0.0215), exceeding the minimal clinically important difference values. Conclusions: The underestimated group is clinically important because the surgical procedure and intraoperative assessment of component placement are performed in the supine position. In cases of severe preoperative varus deformity, care should be taken not to place the component in malrotation to avoid rotational mismatch in the standing position. Level of Evidence: Ⅳ, Case series.

DOI： 10.1002/jeo2.12069

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PubMed

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1408203032

CiNii Research

Language：English   Publisher：Taylor & Francis  

Language：English  

DOI： 10.1093/mr/roae048

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PubMed

Language：English   Publisher：Archives of Orthopaedic and Trauma Surgery  

Introduction: The optimal lower-limb alignment after unicompartmental knee arthroplasty (UKA) remains controversial. This study aimed to investigate the optimal lower-limb alignment for functional improvement in the early post-UKA period. We hypothesized that a small change (Δ) in the arithmetic hip-knee-ankle (aHKA) angle during surgery would result in better postoperative knee function. Materials and methods: This single-centered, retrospective study analyzed 91 patients (91 knees) who underwent UKA from April 2021 and December 2022. Preoperative and postoperative standing whole-leg radiographs were used to evaluate the mechanical HKA angle and aHKA angle. The aHKA angle was calculated from the medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA). We defined restored aHKA angle as a postoperative aHKA angle within ± 3° of the preoperative aHKA angle. Functional improvement was evaluated using the preoperative and one-year postoperative Knee Society Scoring 2011 (KSS 2011). A multivariate regression analysis was performed to investigate the optimal lower-limb alignment for functional improvement. Result: Postoperative restored aHKA angle (p = 0.020) was the only significant factor for improved KSS 2011 scores. Postoperative restored aHKA angle was obtained in 64 patients (70%). ΔMPTA (p < 0.001) and ΔLDFA (p = 0.037) were significant factors associated with a postoperative restored aHKA angle. Conclusions: UKA restores the native knee, including resurfacing constitutional alignment and medial collateral ligament tension. Minimal change in the aHKA angle during UKA improves the functional outcomes of the knee during the early postoperative period, consistent with the minimally invasive surgical concept of UKA.

DOI： 10.1007/s00402-024-05309-2

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PubMed

Language：English   Publisher：Arthroscopy Techniques  

We present a knee osteotomy procedure that we have termed the interlocking open-wedge distal tibial tuberosity osteotomy. In this context, the term interlocking pertains to the manner in which the repositioned segments of the retro-tubercle seamlessly fit together as the transverse osteotomy opens to the intended corrective angle. This interlocking mechanism, serving as a distinctive feature, engenders a stable retro-tubercle configuration resembling a mortise-and-tenon joint. The distal end of the tibial tuberosity fits snugly behind the tibial diaphysis, augmenting stability and promoting the healing process. Consequently, poor union of the retro-tubercle caused by the widening of the retro-tubercle gap and an increase in posterior tibial slope are effectively prevented. In addition, the need for complementary hardware such as anteroposterior screw fixation, which is used to secure the retro-tubercle during the healing process, is notably eliminated. This elimination not only simplifies the surgical procedure but also eliminates potential complications that could arise from its use.

DOI： 10.1016/j.eats.2024.102939

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PubMed

Language：English   Publisher：Immunological Medicine  

Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro. STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.

DOI： 10.1080/25785826.2023.2300853

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PubMed

Language：Japanese   Publisher：(一社)日本関節病学会  

目的:個人で異なる生来のアライメントを予測するために提唱されたCoronal Plane Alignment of the Knee(CPAK)分類に基づくTKA術前後のphenotypeが,術後中期以降の患者立脚型アウトカムに影響するか否かを検討すること。方法:2013年から2019年に当院で変形性膝関節症に対して初回TKAをmechanical alignment(MA)法で施行した187名231膝(年齢74±8歳,術後経過期間4.2±1.8年)を対象とし,患者立脚型アウトカムとしてKSS 2011,KOOS-12,FJS-12を調査した。術前後全下肢正面X線画像よりMPTA,LDFAを計測,aHKA,JLOを算出,CPAK分類phenotypeを同定した。患者背景,術前後aHKA,JLOを因子として,ステップワイズ法を用いた多変量解析を行い,KSS 2011,KOOS-12に及ぼす影響を調査した。結果:術前CPAK分類はphenotype(I)が最も多く53%,術後CPAK分類はMA法の目標であるphenotype(V)が最も多く26%であった。多変量解析の結果,術前後でaHKAが変化しないことがすべての患者立脚型アウトカムへの有意な正の影響因子であり,術後JLOが内方傾斜またはニュートラルであることがKSS 2011への有意な正の影響因子であった。考察:TKA術前後のCPAK分類phenotypeは術後中期以降の患者立脚型アウトカムに影響していた。術後aHKAは術前と分類が変わる,術後JLOは外方傾斜になると患者立脚型アウトカムが低下するため,CPAK分類に基づく術前計画および再現のある達成は患者立脚型アウトカムのさらなる改善に有用であると示された。(著者抄録)

Language：English   Publisher：Elsevier B.V.  

膝関節全置換術(TKA)において、3Dシミュレーション解析を用いて円形と解剖学的楕円形の2種類のコンポーネントの明確な設定ランドマークについて検討した。内反型変形性膝関節症に対してTKAを施行された54例68膝関節(男性17関節、女性51関節、平均75.7±8.2歳)の術前CTデータを用いて膝蓋切除面の3Dシミュレーションを行った。オリジナルの膝蓋隆線の内外側位置を測定し、内側縁、膝蓋隆線および最大サイズの各設定時の円形・楕円形コンポーネントをアライメントとした。シミュレーション上での膝蓋切除厚は9.2±0.9mmで、実際の手術での値とほぼ一致しており、膝蓋隆線は切除面の内側縁から約40%の位置に局在していた。円形膝蓋コンポーネントのアライメントでは、内側縁、膝蓋隆線、最大サイズの順に内側に位置しており、コンポーネントサイズは内側縁、膝蓋隆線、最大サイズの順に小さかった。解剖学的楕円形膝蓋コンパートメントでは、内側縁の方が最大サイズより有意に内側に位置しており、コンポーネントサイズも有意に小さかった。コンポーネントでカバーされない内側骨幅の約4mmを解剖学的ランドマークとして設定するのが望ましいと考えられた。

Language：English   Publisher：Oxford University Press  

Language：English   Publisher：Modern Rheumatology  

Objectives: The treatments for rheumatoid arthritis (RA) have been greatly improved, and the tight control of disease activity yields superior clinical outcomes. This study aimed to elucidate the accompanying changes in hip destruction following the implementation of a treat-to-target strategy for patients with RA. Methods: We extracted 190 hips over two periods, i.e. the early period (1998–2003) and the late period (2013–19), with 103 and 87 hips, respectively. The observed rheumatic changes, such as inward migration, upward migration, and femoral head collapse, were quantitatively evaluated, while osteoarthritic changes, such as the formation of a capital drop, were investigated from radiographs before primary total hip arthroplasty. Results: A comparison of the two periods’ data showed that the degree of inward migration (−3.44 vs. −7.45 mm; P < .001) and upward migration (+4.3 vs. +0.95 mm; P < .001) significantly decreased in the late-period group. The collapse of the femoral head was not significantly different. The incidence of capital drops was significantly higher in the late-period group (7.8% vs. 27.5%; P < .001). Conclusions:The degree of inward and upward migration representative of rheumatic changes reduced, whereas the frequency of capital drops as osteoarthritic changes increased during the late period.

DOI： 10.1093/mr/road021

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PubMed

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

Language：Japanese   Publisher：日本関節病学会  

<p><b>目的：</b>個人で異なる生来のアライメントを予測するために提唱されたCoronal Plane Alignment of the Knee（CPAK）分類に基づくTKA術前後のphenotypeが，術後中期以降の患者立脚型アウトカムに影響するか否かを検討すること。</p><p><b>方法：</b>2013年から2019年に当院で変形性膝関節症に対して初回TKAをmechanical alignment（MA）法で施行した187名231膝（年齢74±8歳，術後経過期間4.2±1.8年）を対象とし，患者立脚型アウトカムとしてKSS 2011，KOOS-12，FJS-12を調査した。術前後全下肢正面X線画像よりMPTA，LDFAを計測，aHKA，JLOを算出，CPAK分類phenotypeを同定した。患者背景，術前後aHKA，JLOを因子として，ステップワイズ法を用いた多変量解析を行い，KSS 2011，KOOS-12に及ぼす影響を調査した。</p><p><b>結果：</b>術前CPAK分類はphenotype（Ⅰ）が最も多く53%，術後CPAK分類はMA法の目標であるphenotype（Ⅴ）が最も多く26%であった。多変量解析の結果，術前後でaHKAが変化しないことがすべての患者立脚型アウトカムへの有意な正の影響因子であり，術後JLOが内方傾斜またはニュートラルであることがKSS 2011への有意な正の影響因子であった。</p><p><b>考察：</b>TKA術前後のCPAK分類phenotypeは術後中期以降の患者立脚型アウトカムに影響していた。術後aHKAは術前と分類が変わる，術後JLOは外方傾斜になると患者立脚型アウトカムが低下するため，CPAK分類に基づく術前計画および再現のある達成は患者立脚型アウトカムのさらなる改善に有用であると示された。</p>

DOI： 10.11551/jsjd.43.24

CiNii Research

Publisher：金原出版  

DOI： 10.18888/se.0000002770

CiNii Research

Language：English   Publisher：Journal of Orthopaedic Science  

DOI： 10.1016/j.jos.2021.12.012

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Scopus

PubMed

Language：English   Publisher：(公社)日本整形外科学会  

症例1は72歳女性で、数年前より内側コンパートメント変形性膝関節症による左膝関節痛を自覚しており、前医で遠位結節骨切りによる内側楔状開大式高位脛骨骨切り術(OWHTO)を施行された。開大楔状角は11°とし、多孔性β-リン酸三カルシウム(TCP)足場を楔状ギャップに挿入された。術後1週より歩行訓練を開始し、4週後には全荷重下に歩行可能となった。術後1ヵ月で創部治癒が得られたが、X線所見でTakeuchi I型の外側ヒンジ部骨折(LHF)を認め、3ヵ月後、足場周囲にlow bandが観察された。12ヵ月後もlow bandの存在が確認され、足場の再吸収を伴う骨リモデリングがlow band領域で遅延していることが示唆された。ロッキングプレートの抜去時にlow band領域を含めて生検を行った結果、足場の再吸収のほか、low band領域における新規骨と軟部組織による置換が認められた。症例2は52歳女性で、数年前から左膝関節痛をきたしており、内側OWHTOを受けβ-TCP足場を楔状ギャップに挿入された。6週後に歩行可能となったが、左膝に軽度疼痛が残存し杖歩行の状況であった。術後1ヵ月目のX線検査でTakeuchi III型のLHFと足場周囲のlow bandが認められ、骨切り部の治癒遷延および足場の非感染性ゆるみと診断された。6ヵ月後に再手術を施行し、楔状ギャップ領域の生検を行った。その結果、足場とホスト骨との間に骨統合の遅延が生じ、low band領域で統合が進展しなかったことが示唆された。

Language：English   Publisher：Scientific Reports  

No report has clarified the frequency and interacting factors affecting sleep disturbance among Asian patients at midterm after total knee arthroplasty (TKA). This study aimed to evaluate the frequency of sleep disturbance at midterm after TKA in a Japanese cohort and to identify intervening factors for sleep. We hypothesized that residual knee pain and decreased functional capability negatively interact with sleep quality after TKA. A total of 209 Japanese participants (average age: 77.1 ± 8.3 years; postoperative follow-up period: 4.5 ± 1.9 years) who underwent primary TKA for knee osteoarthritis were included in this study. Sleep quality, satisfaction, pain, functional capability, joint awareness, and mental condition were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Knee Society Score (KSS) 2011, Forgotten Joint Score (FJS)-12, and 12-Item Short-Form Health Survey (SF-12) Mental Component Summary (MCS). Multivariable analysis was performed to determine the influencing factors on PSQI. The scores for the PSQI, satisfaction with pain level while lying in bed, pain during level walking, functional activity category in the KSS 2011, awareness of the artificial joint in bed at night in the FJS-12, and SF-12 MCS were 6.7 ± 3.0, 5.8 ± 1.8, 1.6 ± 2.3, 62 ± 22, 1.5 ± 1.4, and 56 ± 9.3 on average, respectively. Sleep disturbance (PSQI ≥ 5.5) occurred in 54% of the Japanese participants. Multivariable analysis revealed that high functional capability was a significant factor associated with sleep quality improvement (p < 0.05). Decreased functional capability, not residual knee pain, negatively interacted with sleep quality. The sleep disturbance rate was high during the middle postoperative period after TKA in the Japanese cohort.

DOI： 10.1038/s41598-023-45603-4

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

Language：Japanese   Publisher：西日本整形・災害外科学会  

<p>【背景】人工膝関節全置換術（TKA）において，大腿骨前方切除面の‘Grand piano sign’が回旋設置を確認する指標として提唱されているが，これは内側型変形性膝関節症（OA）で提唱された指標であり，外側型膝OAでも同様であるか，検討したものはない．【方法】外側型膝OAでTKAを施行した30例の術前CTを用いて，三次元術前計画ソフト（Zed Knee）内でsurgical epicondylar axis（SEA）に平行（NR），3°内旋（IR），3°外旋（ER）での前方切除面をsimulationし，内側顆/外側顆の高さの比率（M/L比）を検討した．【結果】M/L比は，NRで0.59±0.11，IRで0.68±0.12と増大，ERで0.49±0.09と減少し，数値・傾向とも過去の内側型OAの報告と同様であった．【考察】外側型膝OAにおいても‘Grand piano sign’は有用な指標となり得た．</p>

DOI： 10.5035/nishiseisai.72.433

CiNii Research

Language：Japanese   Publisher：西日本整形・災害外科学会  

【背景】人工膝関節全置換術(TKA)において,大腿骨前方切除面の'Grand piano sign'が回旋設置を確認する指標として提唱されているが,これは内側型変形性膝関節症(OA)で提唱された指標であり,外側型膝OAでも同様であるか,検討したものはない.【方法】外側型膝OAでTKAを施行した30例の術前CTを用いて,三次元術前計画ソフト(Zed Knee)内でsurgical epicondylar axis(SEA)に平行(NR),3°内旋(IR),3°外旋(ER)での前方切除面をsimulationし,内側顆/外側顆の高さの比率(M/L比)を検討した.【結果】M/L比は,NRで0.59±0.11,IRで0.68±0.12と増大,ERで0.49±0.09と減少し,数値・傾向とも過去の内側型OAの報告と同様であった.【考察】外側型膝OAにおいても'Grand piano sign'は有用な指標となり得た.(著者抄録)

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

Language：English   Publisher：Knee Surgery, Sports Traumatology, Arthroscopy  

Purpose: The “Grand-piano sign” is a popular indicator of the appropriate rotational alignment of the femoral component during total knee arthroplasty (TKA). The aim of the study was to investigate the shape of the anterior femoral resection surface of varus and valgus knees. Methods: A cohort of 80 varus knees and 40 valgus knees (hip–knee–ankle angle > 2° for varus and < − 2° for valgus knees) matched for age, sex, height, body weight, and KL grade was made using propensity score matching. Virtual TKA was performed using 3 patterns of components (anterior flange flexion angles of 3°, 5°, and 7°). The anterior femoral resection surface was evaluated for 3 patterns of rotational alignments: parallel to the surgical epicondylar axis (NR, neutral rotation), 3° internal rotation (IR), and 3°external rotation (ER) relative to the surgical epicondylar axis. In each anterior femoral resection surface, the vertical height of medial and lateral condyles was measured, and the ratio of the medial to the lateral height (M/L ratio) was evaluated. Results: The M/L ratio in NR for both varus and valgus knees was 0.57 to 0.64, with no significant difference between the cohorts (p value > 0.05). The M/L ratio showed a similar pattern of increasing at IR and decreasing at ER in both varus and valgus knees. The variation in the M/L ratio with malrotation in valgus knees was smaller than in varus knees. Conclusion: During TKA, the anterior femoral resection surface was similar in varus and valgus knees; however, the variation with malrotation was smaller in valgus knees than in varus knees. TKA for valgus knees requires precise surgical technique and careful intraoperative assessment. Level of evidence: IV, Case series.

DOI： 10.1007/s00167-023-07365-4

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Language：English   Publisher：Arthritis and Rheumatology  

Objective: NF-κB signaling is an important modulator in osteoarthritis (OA), and IκB kinase ε (IKKε) regulates the NF-κB pathway. This study was undertaken to identify the functional involvement of IKKε in the pathogenesis of OA and the effectiveness of IKKε inhibition as a modulatory treatment. Methods: IKKε expression in normal and OA human knee joints was analyzed immunohistochemically. Gain- or loss-of-function experiments were performed using human chondrocytes. Furthermore, OA was surgically induced in mice, followed by intraarticular injection of BAY-985, an IKKε/TANK-binding kinase 1 inhibitor, into the left knee joint every 5 days for 8 weeks. Mice were subsequently examined for histologic features of cartilage damage and inflammation. Results: IKKε protein expression was increased in human OA cartilage. In vitro, expression levels of OA-related factors were down-regulated following knockdown of IKKε with the use of small interfering RNA in human OA chondrocytes or following treatment with BAY-985. Conversely, IKKε overexpression significantly increased the expression of OA-related catabolic mediators. In Western blot analysis of human chondrocytes, IKKε overexpression increased the phosphorylation of IκBα and p65. In vivo, intraarticular injection of BAY-985 into the knee joints of mice attenuated OA-related cartilage degradation and hyperalgesia via NF-κB signaling. Conclusion: These results suggest that IKKε regulates cartilage degradation through a catabolic response mediated by NF-κB signaling, and this could represent a potential target for OA treatment. Furthermore, BAY-985 may serve as a major disease-modifying compound among the drugs developed for OA. (Figure presented.).

DOI： 10.1002/art.42421

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Language：English   Publisher：Oxford University Press  

脛骨の楔状開大型骨切り術または人工膝関節置換術を受けた60歳以上の患者を対象に、患者立脚型評価法(KOOS)を用いて短期治療成績を評価した。炎症性および外傷性関節炎の症例は除外した。患者を術式に応じて高位脛骨骨切り術(HTO)群162例と人工膝関節置換術(TKA)群134例の2群に分類した。患者背景に有意な群間差を認めたため、傾向スコアマッチング法により55組の患者群を選出した。マッチング後は年齢、性別、BMI、術前のKOOSスコアに有意な群間差はなかった。いずれの群においても術前に比べて術後1年におけるKOOSの5項目(症状、疼痛、ADL、スポーツ・娯楽活動、QOL)の平均値は有意に上昇した。術後1年の上記5項目はいずれもHTO群とTKA群の間に有意差はなく、症状に関するKOOSスコアはHTO群で78.8、TKA群で79.2で、ADLおよびQOLの項目に関しても同等であった。疼痛はTKA群(83.4)の方がHTO群(79.4)より高く、スポーツ・娯楽活動はHTO群(53.3)の方がTKA群(47.9)より高かったが、いずれも統計的に有意でなかった(それぞれP=0.20とP=0.29)。

Language：English   Publisher：Modern Rheumatology  

Objectives: The purpose of the present study was to evaluate improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) after open-wedge high tibial osteotomy (HTO) in comparison with total knee arthroplasty (TKA) in cohorts over age 60 matched by pre-operative age, gender, body mass index (BMI), hip-knee-ankle angle (HKAA), KOOS sub-scores, and osteoarthritis (OA) grade. Methods: Propensity score matching was performed between 162 HTO patients and 134 TKA patients. When calculating the propensity score by multivariate logistic regression analysis, the following pre-operative confounders were included: age, gender, BMI, HKAA, KOOS sub-scores, and OA grade. Consequently, a total of 55 patients were included in each group. The Student's t-test was used to analyse differences in the post-operative KOOS sub-scores between groups. Results: After propensity score matching, all matched pre-operative valuables were identical, with no significant differences between the HTO and TKA groups. None of the post-operative KOOS sub-scores at 1 year after surgery showed a significant difference between the HTO and TKA groups. Both groups demonstrated significant and comparable post-operative improvement in every KOOS sub-score. Conclusions: In patients over age 60, there was no significant difference in short-term pain relief and improvements in activity and quality of life between HTO and TKA after propensity score matching including pre-operative age, KOOS sub-scores, and OA grade. HTO is a joint preservation procedure that is valid for knee OA even in individuals over age 60.

DOI： 10.1093/mr/roac052

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Language：Japanese   Publisher：西日本整形・災害外科学会  

<p>【目的】当院における関節リウマチ（RA）に対する人工膝関節全置換術（TKA）の患者背景の変遷を調査し，長期患者立脚評価を行った．【対象と方法】2001年～2015年に当院で施行されたTKA数の推移を調査した．同期間に施行されたRAに対するTKA（RA-TKA）158例で術前の患者背景を解析した．同158例から現在の年齢が80歳以下である52例72膝を抽出し，Knee Society Score（KSS）を送付した．返答のあった28例38膝でKSSの各項目（膝の症状，満足度，手術に関する期待度）における点数，各項目に影響を与えうる因子に関して統計解析を行った．【結果】RA-TKAの症例数は減少し，TKA患者の術前の血液検査で炎症所見は有意に低下傾向であった．術後平均14年のRA-TKAのKSSのスコアは，当院にて施行された変形性膝関節症に対するTKAの術後平均4年成績と同等であった．【考察】薬物療法の変遷の影響と思われるRA-TKA数の減少傾向を認めた．術後長期のKSSは比較的良好であったが，その影響因子の解明が今後の課題である．</p>

DOI： 10.5035/nishiseisai.72.212

CiNii Research

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

Language：Japanese   Publisher：西日本整形・災害外科学会  

【目的】当院における関節リウマチ(RA)に対する人工膝関節全置換術(TKA)の患者背景の変遷を調査し,長期患者立脚評価を行った.【対象と方法】2001年～2015年に当院で施行されたTKA数の推移を調査した.同期間に施行されたRAに対するTKA(RA-TKA)158例で術前の患者背景を解析した.同158例から現在の年齢が80歳以下である52例72膝を抽出し,Knee Society Score(KSS)を送付した.返答のあった28例38膝でKSSの各項目(膝の症状,満足度,手術に関する期待度)における点数,各項目に影響を与えうる因子に関して統計解析を行った.【結果】RA-TKAの症例数は減少し,TKA患者の術前の血液検査で炎症所見は有意に低下傾向であった.術後平均14年のRA-TKAのKSSのスコアは,当院にて施行された変形性膝関節症に対するTKAの術後平均4年成績と同等であった.【考察】薬物療法の変遷の影響と思われるRA-TKA数の減少傾向を認めた.術後長期のKSSは比較的良好であったが,その影響因子の解明が今後の課題である.(著者抄録)

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

Language：English   Publisher：Annals of the Rheumatic Diseases  

Objectives Osteoarthritis (OA) features ageing-related defects in cellular homeostasis mechanisms in articular cartilage. These defects are associated with suppression of forkhead box O (FoxO) transcription factors. FoxO1 or FoxO3 deficient mice show early onset OA while FoxO1 protects against oxidative stress in chondrocytes and promotes expression of autophagy genes and the essential joint lubricant proteoglycan 4 (PRG4). The objective of this study was to identify small molecules that can increase FoxO1 expression. Methods We constructed a reporter cell line with FoxO1 promoter sequences and performed high-throughput screening (HTS) of the Repurposing, Focused Rescue and Accelerated Medchem (ReFRAME) library. Hits from the HTS were validated and function was assessed in human chondrocytes, meniscus cells and synoviocytes and following administration to mice. The most promising hit, the histone deacetylase inhibitor (HDACI) panobinostat was tested in a murine OA model. Results Among the top hits were HDACI and testing in human chondrocytes, meniscus cells and synoviocytes showed that panobinostat was the most promising compound as it increased the expression of autophagy genes and PRG4 while suppressing the basal and IL-1β induced expression of inflammatory mediators and extracellular matrix degrading enzymes. Intraperitoneal administration of panobinostat also suppressed the expression of mediators of OA pathogenesis induced by intra-articular injection of IL-1β. In a murine OA model, panobinostat reduced the severity of histological changes in cartilage, synovium and subchondral bone and improved pain behaviours. Conclusion Panobinostat has a clinically relevant activity profile and is a candidate for OA symptom and structure modification.

DOI： 10.1136/ard-2021-221269

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Language：English   Publisher：Modern Rheumatology Case Reports  

To our knowledge, only one previous report described the treatment of osteochondral autograft for steroid-induced osteonecrosis of the humeral head (ONHH) in a middle-aged patient. The present report describes a 20-year-old man who was found to have avascular osteonecrosis of the right humeral head after corticosteroid pulse treatment, followed by oral corticosteroid therapy. The patient complained of serious right shoulder pain and limited range of motion (ROM). Anteroposterior (AP) radiographs of the right shoulder revealed a crescent sign at the humeral head, indicating subchondral bone collapse with a linear sclerotic change and normal articular surface of the glenoid. The case was categorized as Stage 3 according to the Cruess classification. In general, Cruess classification Stage 3 is treated with humeral head replacement and shoulder arthroplasty. The patient underwent surgical treatment involving osteochondral autograft transplantation. Autografts were harvested from the right knee. At the 1.5-year follow-up, the patient was pain-free and showed an improved active ROM. Furthermore, AP radiographs demonstrated that the glenohumeral joint space was maintained, and no progression of humeral head collapse was observed. This case may be helpful in decision-making if young patients with ONHH require surgical treatment. Furthermore, osteochondral autograft transplantation may be an effective treatment for ONHH.

DOI： 10.1093/mrcr/rxac037

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Language：English   Publisher：Oxford University Press  

症例は20歳男性で、重度の右肩関節痛と可動域(ROM)制限を訴えた。1年前に皮膚筋炎と診断されてステロイドパルス療法を開始されたが、その後、両側肩関節痛、股関節痛、軽度膝関節痛をきたした。両側上腕骨頭、大腿骨頭、大腿顆に生じた骨壊死と診断され、肩関節のUCLAスコアは17点、JOAスコアは48点を示し、肩関節前後方向X線検査では上腕骨頭にcrescent sign、CTにて軟骨下骨挫滅を認め、右上腕骨頭のステロイド誘発性骨壊死と診断した。本例は若年で忍容性が高いと判断し、人工関節置換術ではなく自家骨を用いた骨軟骨カラム移植を行う方針とした。術中所見では長軸に沿って22mm、短軸に沿って20mmの範囲で軟骨下骨の挫滅が認められ、内側滑車と外側滑車の非荷重領域より計三つの自家骨を採取し、骨壊死部に埋入した。術後、右上肢に三角巾をかけて固定し、2週後に振り子運動、3週後にROM運動を許可した。1年後のCTでは自家骨の完全癒合がみられ、1年半後、無痛状態を維持しておりROM改善が得られていた。

Language：English   Publisher：Knee Surgery, Sports Traumatology, Arthroscopy  

Purpose: To identify the factors impacting changes in valgus laxity between before and after open-wedge high tibial osteotomy (OW-HTO) using quantitative valgus stress radiographs. Methods: A total of 40 knees from 38 patients who underwent OW-HTO were assessed. The study population comprised 14 men and 24 women, with a mean age of 61.5 years. Valgus stress radiographs before and 1 year after OW-HTO were performed using a Telos device. The difference between pre- and postoperative joint line convergence angle (JLCA) was expressed as ΔJLCA (post–pre). As indicators of the proximal detachment of superficial medial collateral ligament (sMCL) on radiographs, two distances were defined: the distance from the level of the osteotomy starting point to the tangent line of the proximal tibial plateau (Distance A), or to the medial edge of the proximal tibial plateau (Distance B). Correlations between ΔJLCA and radiographic parameters or KOOS sub-scores were assessed using Spearman’s rank correlation coefficient analysis. Receiver operator curves were generated to evaluate the predictive strength of the significant factor for an increase in ΔJLCA > 1°. Results: Pre-operative OA severity consisted of Kellgren–Lawrence grade 2 (n = 18), 3 (n = 16), and 4 (n = 6). The average ΔJLCA (post–pre) was 0.5°, and ranged from − 1.4° to + 3.0°. The maximum systemic measurement error and limits of agreement were 0.07° and 0.20°, respectively. There were significant correlations between ΔJLCA and Distance A (36.9 ± 3.9 mm, R = − 0.46, p = 0.002), between ΔJLCA and Distance B (39.9 ± 4.0 mm, R = − 0.49, p = 0.001). The cut-off value for Distance A was determined to be 35 mm below the tibial plateau; the AUC was 0.804, with a sensitivity of 0.75 and a specificity of 0.82. Distance B correlated strongly with Distance A (R = 0.96, p < 0.001). There was no significant correlation between ΔJLCA and KOOS sub-scores 1 year after OW-HTO. Conclusions: Transverse osteotomy closer to tibial plateau was associated with larger valgus joint laxity postoperatively. This finding implies that sMCL proximal detachment, which was related to the level of the osteotomy starting point on the proximal tibia, potentially affected postoperative valgus laxity. Level of evidence: IV.

DOI： 10.1007/s00167-021-06810-6

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Language：English   Publisher：Clinical Anatomy  

It is important to investigate anatomical differences of the femur and tibia three-dimensionally between varus and valgus knees to enhance surgical approaches and better understand structural factors related to specific patterns of osteoarthritis progression. Three-dimensional femoral and tibial bone models were reconstructed from transverse computed-tomography scans in varus osteoarthritis (43 knees), valgus osteoarthritis (40 knees), and healthy (32 knees) groups. Different coordinate systems were defined in each femoral bone model (“Knee” and “Hip” Coordinate System). Femoral neck inclination, lateral bowing, anterior bowing, and neck anteversion were measured and compared between knee and hip coordinate systems. Those parameters were also compared between varus, valgus, and healthy groups. The tibial anterior and lateral bowing, external torsion and the fibular axis relative to the tibial mechanical axis were measured and compared between varus and valgus groups. Femoral neck anteversion was significantly 1–2° greater in the hip coordinate system compared to the knee coordinate system. Femoral neck anteversion was significantly smaller in varus knees than in healthy or valgus knees, with average difference of approximately 5°. The knee and hip joint are often rotated externally relative to the trunk axis in patients with varus osteoarthritis, perhaps maintaining the geometric relations between pelvis and proximal femur (including peripheral hip muscles) regardless of knee deformities. The fibular axis was inclined slightly valgus and posteriorly in two groups. The results may inform hypotheses on, and future studies of, skeletal morphologic development and factors contributing to the progression of knee osteoarthritis.

DOI： 10.1002/ca.23862

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Language：English   Publisher：Arthroplasty Today  

Background: The purpose of this study was to investigate the size differences of 19 different femoral component placements from the standard position in total knee arthroplasty using 3-dimensional virtual surgery. Methods: Three-dimensional bone models were reconstructed from the computed tomography data of 101 varus osteoarthritic knees. The distal femoral bone was cut perpendicular to the femoral mechanical axis (MA) in the coronal plane. Twenty different component placements consisting of 5 cutting directions (perpendicular to MA, 3° and 5° extension relative to MA [3°E-MA and 5°E-MA, respectively], and 3° and 5° flexion relative to MA [3°F-MA and 5°F-MA, respectively]) in the sagittal plane, 2 rotational alignments (clinical epicondylar axis [CEA] and surgical epicondylar axis [SEA]), and 2 rotational types of anterior reference guide (central [CR] and medial [MR]) were simulated. Results: The mean anteroposterior dimension of femur ranged from 54.3 mm (5°F-MA, SEA, CR) to 62.5 mm (5°E-MA, CEA, MR). The largest and smallest differences of anteroposterior dimension from the standard position (3°F-MA, SEA, and CR) were 7.1 ± 1.3 mm (5°E-MA, CEA, and MR) and −1.2 ± 0.2 mm (5°F-MA, SEA, and CR), respectively. Multiple regression analysis revealed that flexion cutting direction, SEA, and CR were associated with smaller component size. Conclusions: The femoral component size can be affected easily by not only cutting direction but also the reference guide type and the target alignment. Our findings could provide surgeons with clinically useful information to fine-tune for unintended loose or tight joint gaps by adjusting the component size.

DOI： 10.1016/j.artd.2022.07.008

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Language：Japanese   Publisher：西日本整形・災害外科学会  

<p>内側楔状開大式高位脛骨骨切り術（Open wedge high tibial osteotomy以下OW-HTO）後の満足度・期待度を評価した報告は少ない．今回当科でのOW-HTO術後の満足度・期待度を調査し，影響因子を探索した．当院で2014年8月～2019年12月の期間中にOW-HTO手術を受けた80膝に対し，2011 Knee Society scoreアンケートを送付した．手術時年齢，手術時BMI，術前可動域，術前K-L分類，術中開大角，術前後X線計測値（％MA，HKA angle，MPTA，JLCA），62.5-術後％MAの絶対値（outlier）を計測し，KSSの満足度スコア，期待度スコアに相関する因子を評価した．計54膝の返信（67.5％）を得られ，術後フォロー期間は平均3.6年であった．62.5-術後％MAの絶対値が大きいほど，術後の期待度除痛スコアが有意に低かった（p＝0.01）．術後％MAが62.5％から10％以上外れているoutlier群とそうでない群の群間比較にて期待度除痛スコアに有意差がみられた（p＝0.0292）．術後％MAのoutlierは，OW-HTO術後の期待する除痛に影響する重要な指標である．</p>

DOI： 10.5035/nishiseisai.71.584

CiNii Research

Language：Japanese   Publisher：西日本整形・災害外科学会  

内側楔状開大式高位脛骨骨切り術(Open wedge high tibial osteotomy以下OW-HTO)後の満足度・期待度を評価した報告は少ない.今回当科でのOW-HTO術後の満足度・期待度を調査し,影響因子を探索した.当院で2014年8月～2019年12月の期間中にOW-HTO手術を受けた80膝に対し,2011 Knee Society scoreアンケートを送付した.手術時年齢,手術時BMI,術前可動域,術前K-L分類,術中開大角,術前後X線計測値(%MA,HKA angle,MPTA,JLCA),62.5-術後%MAの絶対値(outlier)を計測し,KSSの満足度スコア,期待度スコアに相関する因子を評価した.計54膝の返信(67.5%)を得られ,術後フォロー期間は平均3.6年であった.62.5-術後%MAの絶対値が大きいほど,術後の期待度除痛スコアが有意に低かった(p=0.01).術後%MAが62.5%から10%以上外れているoutlier群とそうでない群の群間比較にて期待度除痛スコアに有意差がみられた(p=0.0292).術後%MAのoutlierは,OW-HTO術後の期待する除痛に影響する重要な指標である.(著者抄録)

Language：English   Publisher：BMC Pharmacology and Toxicology  

Background: Adipose-derived mesenchymal stem cells (ADMSCs) are a promising source of material source for medical regeneration of cartilage. Growth factors, including transforming growth factor-β (TGFβ) subfamily members and bone morphogenetic proteins (BMPs), play important roles in inducing and promoting chondrogenic differentiation of MSCs. However, these exogenous growth factors have some drawbacks related to their cost, biological half-life, and safety for clinical application. Several studies have reported that statins, the competitive inhibitors of 3-hydroxy-2-methylglutaryl coenzyme A (HMG-CoA) reductase, induce the expression of BMP2 in multiple cell types as the pleotropic effects. The objective of this study was to investigate the effects of fluvastatin during chondrogenic differentiation of human ADMSCs (hADMSCs). Methods: The effects of fluvastatin were analyzed during chondrogenic differentiation of hADMSCs in the pellet culture without exogenous growth factors by qRT-PCR and histology. For functional studies, Noggin, an antagonist of BMPs, mevalonic acid (MVA) and geranylgeranyl pyrophosphate (GGPP), metabolites of the mevalonate pathway, ROCK inhibitor (Y27632), or RAC1 inhibitor (NSC23766) were applied to cells during chondrogenic differentiation. Furthermore, RhoA activity was measured by RhoA pulldown assay during chondrogenic differentiation with or without fluvastatin. Statistically significant differences between groups were determined by Student’s t-test or the Tukey–Kramer test. Results: Fluvastatin-treated cells expressed higher levels of BMP2, SOX9, ACAN, and COL2A1 than control cells, and accumulated higher levels of glycosaminoglycans (GAGs). Noggin significantly inhibited the fluvastatin-mediated upregulation of ACAN and COL2A1. Both MVA and GGPP suppressed the effects of fluvastatin on the expressions of BMP2, SOX9, ACAN, and COL2A1. Furthermore, fluvastatin suppressed the RhoA activity, and inhibition of RhoA–ROCK signaling by Y27632 increased the expressions of BMP2, SOX9, ACAN, and COL2A1, as well as fluvastatin. Conclusions: Our results suggest that fluvastatin promotes chondrogenic differentiation of hADMSCs by inducing endogenous BMP2, and that one of the mechanisms underlying the effects is inhibition of RhoA–ROCK signaling via suppression of GGPP. Fluvastatin is a safe and low-cost compound that holds promise for use in transplantation of hADMSCs for cartilage regeneration.

DOI： 10.1186/s40360-022-00600-7

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Language：English   Publisher：BMC Musculoskeletal Disorders  

Background: The coronal whole-leg radiograph is generally used for preoperative planning in total knee arthroplasty. The distal femoral valgus angle (DFVA) is measured for distal femoral bone resection using an intramedullary guide rod. The effect of coronal and sagittal femoral shaft bowing on DFVA measurement in the presence of malrotation or knee flexion contracture has not been well reported. The objectives of this study were: (1) to investigate the effects of whole-leg malrotation and knee flexion contracture on the DFVA in detail, (2) to determine the additional effect of coronal or sagittal femoral shaft bowing. Methods: We studied 100 consecutive varus and 100 valgus knees that underwent total or unicompartmental knee arthroplasty. Preoperative CT scans were used to create digitally reconstructed radiography (DRR) images in neutral rotation (NR, parallel to the surgical epicondylar axis), and at 5° and 10° external rotation (ER) and internal rotation (IR). The images were also reconstructed at 10° femoral flexion. The DFVA was evaluated in each DRR image, and the angular variation due to lower limb malposition was investigated. Results: The DFVA increased as the DRR image shifted from IR to ER, and all angles increased further from extension to 10° flexion. The DFVA variation in each position was 1.3° on average. A larger variation than 2° was seen in 12% of all. Multivariate regression analysis showed that sagittal femoral shaft bowing was independently associated with a large variation of DFVA. Receiver operating characteristic analysis showed that more than 12° of sagittal bowing caused the variation. Conclusion: If femoral sagittal bowing is more than 12°, close attention should be paid to the lower limb position when taking whole-leg radiographs. Preoperative planning with whole-leg CT data should be considered.

DOI： 10.1186/s12891-022-05542-z

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

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

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

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

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

Language：English   Publisher：BMC Musculoskeletal Disorders  

Background: In performing primary constrained total knee arthroplasties (TKA) to imbalanced knees, the offset stem is sometimes compelled to use, although this is associated with surgical difficulties. We developed a modified procedure which might be able to fit the anteroposterior (AP) and mediolateral (ML) position of the femoral component simultaneously with the straight stem. Purposes of this study were to evaluate usefulness of the modified procedure both in computer simulations and actual surgeries. Methods: We included 32 knees that had undergone primary TKA using constrained implants because of the coronal imbalance. In the component-first procedure, the distal femur was prepared to fit the AP and ML position of the femoral component simultaneously at first, as in primary TKA. Finally, the stem hole is created based on the femoral component position (the component-first procedure). The femoral component and extension stem were simulated using the three-dimensional planning software (ZedKnee) following the component-first procedure. We investigated the suitability of the straight stem through computer simulation and evaluation of actual surgeries. Clinical and radiographical outcomes were also evaluated at the latest follow-up. Results: The component-first procedure enabled the AP and ML position of the femoral component to be fitted simultaneously with the straight stem in simulations and actual surgeries in all cases. The stem diameter was not significantly different between simulations and actual surgeries (13.9 and 13.7 mm on average, respectively, p = 0.479) and almost similar from intraclass correlation coefficient analysis (kappa value 0.790). Clinical and radiographical outcomes were almost similar to primary TKA cases and there was no case of component loosening, cortical bone hypertrophy around the stem and stem-tip pain. Conclusions: Our improved surgical procedure may facilitate use of the constrained implant for more cases of primary TKA in imbalanced knees without the usual surgical difficulties. Trial registration: Retrospectively registered.

DOI： 10.1186/s12891-022-05367-w

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PubMed

Language：English   Publisher：Journal of Orthopaedic Science  

Background: The purpose of the present study was to evaluate the accuracy of the measurements associated with leg alignment on a teleoroentgenogram and an orthoroentgenogram. Methods: The models being irradiated were manufactured and represented 10° varus and 15° varus leg alignment, in which the true values of hip-knee-ankle angle (HKAA), mechanical axis (MA) length, and percentage of MA (%MA) were already known. HKAA, MA length, and %MA were measured in various radiographic conditions of the teleoroentgenogram and orthoroentgenogram. Then, the differences between the radiographic measurement values and the corresponding true values were analyzed. Results: Regarding HKAA, the teleoroentgenogram provided accurate angular measurements with minimal differences between the measurement and true value in both the 10° and 15° varus models, irrespective of the radiographic condition. In the orthoroentgenogram, the modified method measured accurate HKAA; however, the standard method showed significant angular measurement errors with a 0.6° and 1.0° difference from the true value in the 10° and 15° varus models, respectively. This angular measurement error of HKAA in the standard orthoroentgenogram became significantly larger with object-to-image distance. Regarding MA length, the orthoroentgenogram exhibited accurate length measurements. In contrast, the teleoroentgenogram showed a significant length measurement error for the MA length. Regarding %MA, significant differences from the true values of 2.0% and 2.4% were observed in the modified orthoroentgenograms of the 10° and 15° varus models, respectively. The teleoroentgenogram and standard orthoroentgenogram reproduced the accurate measurement value of %MA in the 10° and 15° varus models. Conclusion: A teleoroentgenogram is a reliable modality for accurate angular measurements such as HKAA and %MA. An orthoroentgenogram has the potential to measure both HKAA and length accurately if the radiographic condition was modified; however, measurement error in %MA may occur.

DOI： 10.1016/j.jos.2021.02.011

Web of Science

Scopus

PubMed

Language：English   Publisher：(公社)日本整形外科学会  

遠距離X線像と実大X線像を用いた脚部アライメントにおける測定角度の精度を比較検討した。アライメントを内反10°および15°に設定したモデルを作成し、股関節-膝関節-足関節角(HKAA)、機能軸(MA)長、MA率(%MA)をそれぞれ遠隔X線撮影と実大X線撮影によって測定した。HKAAに関して標準遠距離X線撮影では精度の高い測定値が得られており、内反10°、15°のいずれでも真値との差は最小にとどまっていた。実大X線撮影では修正法においてHKAAの測定精度は遠距離X線撮影とほぼ同等であったが、標準法では真値との間に有意な誤差が生じていた。MA長の評価では、実大X線像は標準法でも修正法でも測定精度は高かったが、遠距離X線像は内反10°で61.5mm、15°で58.9mmの誤差が認められ、被写体との距離が長くなるのに伴い誤差も大きくなっていた。%MAは修正実大X線像において内反10°で2.0%、15°で2.4%の誤差がみられ、遠距離X線像と標準実大X線像の測定精度は高かった。

Language：Japanese   Publisher：西日本整形・災害外科学会  

<p>【目的】関節リウマチ（以下RA）患者において，Sauvé-Kapandji法（以下，SK法）術後3年以上経過後のX線学的変化を検討すること．【対象と方法】2007年から2019年にSK法を施行したRA17例18手の内3年以上の経過観察をし得た6例6手である．全例女性，手術時平均年齢は60歳（45-70歳），平均経過観察期間は100か月（36-160か月）であった．術後1週，最終経過観察時の単純X線を用いてCarpal height ratio（CHR），Palmar carpal subluxation ratio（PCSR），Ulnar translation index（UTI）の各値について術後1週を1とし変化率を評価した．また，この6例を含む17例18手について，術前と術後1週にて術前を1とし変化率の評価を行った．統計学的検討にはWilcoxon検定を用いて5%未満を有意差ありとした．【結果】術後1週と最終経過ではCHRは－1%，PCSRは＋7%，UTIは＋23%であり，UTIにて有意差を認めた（p＝0.0028）．また術前と術後1週の比較ではCHRは－4%，PCSRは＋11%，UTIは±0%であり，PCSRのみ有意差を認めた．【考察】RAにおけるSK法では3年以上の経過例で，術直後に対して尺側偏位が進行することが示唆された．</p>

DOI： 10.5035/nishiseisai.71.29

CiNii Research

Language：Japanese   Publisher：西日本整形・災害外科学会  

【目的】関節リウマチ(以下RA)患者において,Sauve-Kapandji法(以下,SK法)術後3年以上経過後のX線学的変化を検討すること.【対象と方法】2007年から2019年にSK法を施行したRA17例18手の内3年以上の経過観察をし得た6例6手である.全例女性,手術時平均年齢は60歳(45-70歳),平均経過観察期間は100ヵ月(36-160ヵ月)であった.術後1週,最終経過観察時の単純X線を用いてCarpal height ratio(CHR),Palmar carpal subluxation ratio(PCSR),Ulnar translation index(UTI)の各値について術後1週を1とし変化率を評価した.また,この6例を含む17例18手について,術前と術後1週にて術前を1とし変化率の評価を行った.統計学的検討にはWilcoxon検定を用いて5%未満を有意差ありとした.【結果】術後1週と最終経過ではCHRは-1%,PCSRは+7%,UTIは+23%であり,UTIにて有意差を認めた(p=0.0028).また術前と術後1週の比較ではCHRは-4%,PCSRは+11%,UTIは±0%であり,PCSRのみ有意差を認めた.【考察】RAにおけるSK法では3年以上の経過例で,術直後に対して尺側偏位が進行することが示唆された.(著者抄録)

Language：English   Publisher：Arthritis Research and Therapy  

Background: To further improve rheumatoid arthritis (RA) treatment, it is necessary to understand each RA patient’s satisfaction and to identify the factors affecting their satisfaction. Despite the rise in medical costs for RA, little is known about the factors that influence patient satisfaction with the cost of treatment in RA patients. Methods: This is a multicenter observational study of Japanese RA patients from the FRANK Registry with data analyzed from March 2017 to August 2020. We collected data on demographic characteristics, clinical data, quality of life which was evaluated using the EuroQol 5-dimensional questionnaire (EQ5D), and patient satisfaction. The four categories of patient satisfaction were evaluated individually (i.e., cost, treatment efficacy, activities of daily living [ADL], and global treatment satisfaction). We analyzed the factors that affected each patient’s satisfaction, such as age, sex, EQ5D, disease duration, disease activity, and treatment. Results: This study included 2235 RA outpatients (406 males, 1829 females). In RA patients, “very satisfied” and “satisfied” were given for nearly half of each satisfaction aspect (cost 49%; efficacy 72%; ADL 58%; global treatment 66%) at the time of the initial registration. To investigate the factors influencing each satisfaction, multivariate analysis has revealed that the use of b/tsDMARDs increased satisfaction of treatment effect (odds ratio [OR] 0.66) and ADL (OR 0.78) but decreased cost satisfaction (OR 2.21). Age (50–64 years; OR 0.91; 65–74 years, 0.55: ≥ 75 years, 0.35), female (OR 0.81), and history of musculoskeletal surgery (OR 0.60) all increased cost satisfaction. Patients with lower disease activity and higher EQ5D scores had higher levels of satisfaction in all areas. Conclusions: In this study, patient satisfaction in terms of cost, treatment effect, ADL, and overall treatment was generally higher, but some patients were dissatisfied. The cost of satisfaction increased with age and a history of musculoskeletal surgery, while it decreased with a lower EQ5D score and the use of b/tsDMARDs.

DOI： 10.1186/s13075-022-02746-5

Web of Science

Scopus

PubMed

Language：English   Publisher：FASEB Journal  

Osteoarthritis (OA), the most prevalent joint disease, is characterized by the progressive loss of articular cartilage. Autophagy, a lysosomal degradation pathway, maintains cellular homeostasis, and autophagic dysfunction in chondrocytes is a hallmark of OA pathogenesis. However, the cause of autophagic dysfunction in OA chondrocytes remains incompletely understood. Recent studies have reported that decidual protein induced by progesterone (C10orf10/DEPP) positively regulates autophagic functions. In this study, we found that DEPP was involved in mitochondrial autophagic functions of chondrocytes, as well as in OA pathogenesis. DEPP expression decreased in human OA chondrocytes in the absence or presence of pro-inflammatory cytokines, and was induced by starvation, hydrogen peroxide (H2O2), and hypoxia (cobalt chloride). For functional studies, DEPP knockdown decreased autophagic flux induced by H2O2, whereas DEPP overexpression increased autophagic flux and maintained cell viability following H2O2 treatment. DEPP was downregulated by knockdown of forkhead box class O (FOXO) transcription factors and modulated the autophagic function regulated by FOXO3. In an OA mouse model by destabilization of the medial meniscus, DEPP-knockout mice exacerbated the progression of cartilage degradation with TUNEL-positive cells, and chondrocytes isolated from knockout mice were decreased autophagic flux and increased cell death following H2O2 treatment. Subcellular fractionation analysis revealed that mitochondria-located DEPP activated mitochondrial autophagy via BCL2 interacting protein 3. Taken together, our data demonstrate that DEPP is a major stress-inducible gene involved in the activation of mitochondrial autophagy in chondrocytes, and maintains chondrocyte viability during OA pathogenesis. DEPP represents a potential therapeutic target for enhancing autophagy in patients with OA.

DOI： 10.1096/fj.202100896R

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Scopus

PubMed

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞NF-κBシグナルの亢進は,細胞の炎症性異化反応の主軸として変形性関節症(OA)の病態生理に広く関与する。本稿で着目した治療標的のG protein-coupled receptor kinase 5(GRK5)およびIκB kinase-ε(IKKε)は,IκBαをリン酸化してNF-κBシグナルの活性化を促進する。また近年,GRK5とIKKεを阻害する化合物として既存薬のアンレキサノクスが特定された。これらの背景から,われわれはGRK5とIKKεがOA病態にどう関与しているか,そしてアンレキサノクスがOA疾患修飾効果をもつか,どう実薬化していくかを研究している。これまでの成果として,(1)ヒトOA軟骨およびマウスOAモデルにおける病態特異的強発現があり,(2)軟骨細胞に対するgain-and loss-of-function mutationによる双方向作用を認め,(3)IκBのリン酸化に機能的に関与し,(4)マウスOAモデルへのアンレキサノクスの関節内投与が軟骨変性抑制に有効であることなどを明らかにした。以上から,アンレキサノクスはGRK5とIKKεを阻害することで,NF-κB経路を制御するOA治療薬として期待できる。

Language：Japanese   Publisher：(株)北隆館  

NF-κBシグナルの過剰活性化は,変形性関節症(以下OA)の病態生理に広く関与しています。本研究では,新たなOA治療の標的としてG protein-coupled Receptor Kinase 5(GRK5)とIκB Kinase-ε(IKKε)に焦点を当てています。これらはIκBαをリン酸化し,NF-κBシグナルの活性化を促進します。さらに,最近,GRK5とIKKεの両方を阻害する既存薬であるアンレキサノクスが特定されました。これらの背景から,我々はGRK5とIKKεがOAの病態悪化に与える影響を研究し,またアンレキサノクスのOA疾患修飾効果をどう実薬化していくかを研究しています。(著者抄録)

Language：Japanese   Publisher：(有)科学評論社  

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：10

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：5