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

【はじめに】妊婦や授乳婦への診療にあたっては,使用できる薬剤に制限を受けることがある.今回,比較的稀な妊婦の手指化膿性関節炎を経験したので報告する.【症例】27歳女性妊娠8ヵ月授乳中.特に誘因なく左中指PIP関節痛・腫脹が出現し,第9病日に近医の整形外科を受診しステロイド局注施行される.その後も症状が増悪し第11病日に当院紹介となった.関節穿刺にて黄白色混濁した膿汁6mLが引け,後の培養でA群溶連菌が検出された.関節切開洗浄を行い,点滴による抗生剤治療を開始した.術後8日で内服の抗生剤に切り替え,5週間投与を行った.抗生剤中止後も再燃なく治癒した.【考察】手指化膿性関節炎は比較的稀であり鑑別を要する.妊婦や授乳婦に使用可能な薬剤は限られ,注意が必要である.(著者抄録)

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

Web of Science

Scopus

PubMed

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

Web of Science

Scopus

PubMed

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

Web of Science

Scopus

PubMed

Language：Japanese  

Language：Japanese