Long-Term Implant Fracture Rates Following Silicone Metacarpophalangeal Joint Arthroplasty in Rheumatoid Arthritis.

PURPOSE: The primary objective of this study was to compare the long-term survival rates of silicone metacarpophalangeal (MCP) arthroplasties between two major implants in patients with rheumatoid arthritis, using implant fracture as an end point. We also evaluated the difference in postoperative function between patients with fractured and intact implants as a secondary objective. METHODS: A retrospective cohort study was conducted on 372 fingers of 133 hands that underwent silicone MCP arthroplasty between January 2000 and June 2019 (mean follow-up, 7.6 years). The survival rates of Swanson-type and Sutter-type implants were compared, using implant fracture as the end point after a radiographic evaluation. Clinical measures and upper limb functional assessments using the Disabilities of the Arm, Shoulder, and Hand (DASH) score were performed in the nested cohort. RESULTS: The 10.6-year survival rates for implant fracture of Swanson- and Sutter-type implants were 86.2% and 9.4%, respectively, with significantly higher survival noted for Swanson-type implants. The Sutter-type implant showed increased susceptibility to fracture in all four fingers compared to the Swanson-type implant. Implant fractures were primarily observed at the stem-hinge junction. There were no significant differences in upper limb function between the fractured and intact implant groups. CONCLUSIONS: Sutter-type implants were found to be more prone to fracture compared with Swanson-type implants. However, implant fractures did not significantly affect upper limb function. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognosis IV.

Adherence to methotrexate and associated factors considering social desirability in patients with rheumatoid arthritis: a multicenter cross-sectional study.

BACKGROUND: Assessing medication adherence in rheumatoid arthritis (RA) is clinically significant as low adherence is associated with high disease activity. Self-reported medication adherence surveys have been shown to have problems with overestimation of adherence due to social desirability bias. However, no MTX adherence studies adjusted for social desirability have been conducted to date. This study aimed to evaluate adherence to MTX and perform an investigatory search for factors associated with MTX adherence including social desirability. METHODS: This cross-sectional multicenter study was conducted among adult RA patients consuming oral MTX for ≥ 3 months. We examined the distribution of MTX adherence, according to the eight-item Morisky Medication Adherence Scale (MMAS-8). Social desirability was using the Social Desirability Scale (SDS). Furthermore, an exploratory factor analysis involving social desirability was examined to identify factors associated with MTX adherence using linear regression analysis. To deal with missing values, we used multiple imputations with chained equations methods. RESULTS: A total of 165 RA patients were enrolled. The median age was 64 years, and 86.1% were women. Based on the MMAS-8, low, medium, and high adherences were noted in 12.1%, 60.0%, and 27.9% of participants, respectively. High social desirability (coefficient, 0.14; 95% confidence interval [CI], 0.05-0.23; p < 0.05) and high age (coefficient per 10 years, 0.16; 95% CI, 0.01-0.03; p < 0.05) were associated with high MTX adherence, whereas full-time work was negatively associated with high MTX adherence (coefficient, -0.50; 95% CI, -0.95--0.05; p < 0.05). CONCLUSIONS: A large proportion of patients with RA do not take MTX as prescribed. High social desirability, high educational level, and non-full-time work may be associated with high MTX adherence. Physicians should confirm MTX adherence before switching or adding disease-modifying anti-rheumatic drugs in cases of uncontrolled disease activity.

Factors associated with frailty in Japanese patients with rheumatoid arthritis: results from the Institute of Rheumatology Rheumatoid Arthritis cohort study.

This study aimed to evaluate the prevalence of, and the factors associated with, frailty in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires, which included the 5-item frailty screening index. Patients were classified as frail, prefrail, or robust based on the 5 components of the frailty screening index. Logistic regression analyses were used to evaluate associations between clinical variables and frailty. Among 3,290 Japanese patients with RA (86.7% female, mean age 62.4 years) who participated this frailty study, 549 (16.7%) patients were categorized as frailty, 2,063 (62.7%) as prefrailty, and 678 (20.6%) as robust. In multivariable models, body mass index (BMI) ≥ 25 kg/m2 (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.41 to 2.47), BMI < 18.5 kg/m2 (OR 1.31, 95% CI 1.00 to 1.71), disease activity scores in 28 joints (DAS28) (OR 1.32, 95% CI 1.18 to 1.47), Japanese version of Health Assessment Questionnaire disability index (J-HAQ) (OR 1.26, 95% CI 1.04 to 1.52), the European Quality of Life-5 Dimensions (EQ-5D) (OR 0.80, 95% CI 0.74 to 0.85), non-steroidal anti-inflammatory drug (NSAID) use (OR 1.59, 95% CI 1.23 to 1.98), and methotrexate (MTX) use (OR 0.75, 95% CI 0.60 to 0.94) were significantly (P < 0.05) associated with frailty. BMI (both overweight and underweight), DAS28, J-HAQ, EQ-5D, NSAID use, and MTX nonuse appear to be associated with frailty in Japanese patients with RA. Key Points • This is the largest study showing the prevalence and the associated factors of frailty in patients with RA. • Maintaining normal BMI appears to be important for preventing frailty in patients with RA. • We confirmed the significant associations of frailty with high disease activity, high degree of disability, and poor health related QOL in Japanese patients with RA. • NSAID use and MTX nonuse were associated with the frailty in Japanese patients with RA, which could be explained by patients' background.

Efficacy of golimumab for preventing large joint destruction in patients with rheumatoid arthritis as determined by the ARASHI score.

OBJECTIVES: The objective of this study is to investigate the inhibitory effect of golimumab on large joint destruction in patients with rheumatoid arthritis. METHODS: We recruited 45 patients with rheumatoid arthritis and evaluated the radiographic severity of large joint destruction using the assessment of rheumatoid arthritis by scoring of large joint destruction and healing in radiographic imaging (ARASHI) score. We evaluated 450 large joints including the elbow, shoulder, hip, knee, and ankle at baseline and 52 weeks after treatment with golimumab. Rapid radiographic progression (RRP) and rapid radiographic improvement (RRI) were calculated and the correlation between large joint destruction and clinical factors was analyzed. RESULTS: The mean age of the study population was 61.29 ± 14.71 years old, and most patients (91.1%) were female. The mean disease duration was 12.6 ± 12.48 years. The cohort included patients in all clinical stages of disease as defined by the Steinbroker criteria (I:7, II:10, III:9, IV:19) as well as clinical classes 2 (n = 18), 3 (n = 26), and 4 (n = 1) and the mean disease activity score-CRP (DAS28-CRP) was 4.431 ± 1.044. Patients were treated with methotrexate (mean dose 6.44 ± 1.78 mg/week), prednisolone (PSL) (mean dose 1.078 ± 1.871 mg/d), and golimumab (44.4% of 100 mg). RRP was evident in 20% of the large joints treated with golimumab, and, therefore, golimumab was effective at inhibiting large joint destruction in 80% of joints. RRI was evident in 33.3% of large joints following golimumab treatment. We also observed that EULAR response criteria significantly correlated with the ARASHI change score at 52 weeks after treatment. The total ARASHI status score significantly correlated with the Sharp-van der Heijde score, but not with the delta total sharp score. Multiple regression analyses revealed that the total ARASHI change score was only correlated with EULAR response criteria significantly. CONCLUSIONS: Golimumab therapy was effective at inhibiting large joint destruction of RA patients who have good clinical response, including higher improvement of the shoulder and ankle joints than other large joints.

Analysis of Mitogen-Activated Protein Kinases in Bone and Cartilage of Patients with Rheumatoid Arthritis Treated with Abatacept.

The aim of this study was to analyze the histological changes related to mitogen-activated protein (MAP) kinases in bone and cartilage treated with abatacept for rheumatoid arthritis (RA). A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control). The histology of bone and cartilage was observed by staining with hematoxylin and eosin and analyzed immunohistochemically for the expression of tumor necrosis factor-α, interleukin-6, CD4 (T cell), CD68 (macrophage), receptor activator of nuclear kappa-B ligand, osteoprotegerin, osteopontin, CD29 (ß-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (extracellular signal-regulated kinase, ERK1/ERK2), and phosphor-c-Jun N-terminal kinase. The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control. These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept.

Assessment of malalignment at the metacarpophalangeal joint of the rheumatoid hand using three-dimensional computed tomogram.

OBJECTIVE: For the assessment of rheumatoid hand, three-dimensional (3D) malalignment including flexed or rotational deformities and dislocation at the finger joint is one of the important findings. The objective of this study is to prove usefulness of 3D computed tomography (3DCT) for the accurate measurement of palmoulnar flexion deformity at the metacarpophalangeal (MP) joint of the rheumatoid hand. METHODS: Swanson implant arthroplasty at the 2nd through the 5th MP joints was performed at 179 joints in 46 hands of 40 patients with rheumatoid arthritis. Pre-and postoperatively, evaluations included Larsen grade and ulnar flexion angle by an x-ray; and ulnar flexion angle, palmar flexion angle, and resected bone length by a 3DCT. RESULTS: With progression of Larsen grade and the joint dislocation, ulnar flexion angle increased. Average ulnar flexion angle was 18.7 ± 16.0° (mean ± SD) in grade III, 38.4 ± 21.2° in grade IV, and 40.1 ± 21.1° in grade V, 29.6 ± 16.0°in "subluxation," 24.8 ± 21.2° in "dislocation," and 41.1 ± 22.2° in "severe dislocation." There was no significant difference between grade of the MP joint dislocation and palmar flexion angle. With progression of the MP joint dislocation, resected bone length increased. CONCLUSION: A 3DCT gives accurate information about deformity of the rheumatoid hand. Also, an appropriate length of bone resection can be determined in the preoperative planning.

The rate of decrease in the disease activity of rheumatoid arthritis during treatment with adalimumab depends on the dose of methotrexate.

OBJECTIVE: The aim of this study was to analyze the efficacy of adalimumab (ADA) in patients with rheumatoid arthritis treated with or without methotrexate (MTX) and determine impact of the MTX dose. METHODS: Pearson's product-moment correlation coefficient was used to assess the correlations between the improvement in the Disease Activity Score (DAS) 28- erythrocyte sedimentation rate (ESR) score and the MTX dose in patients receiving treatment with MTX at a dose of <8 mg/week, 8 mg/week and >8 mg/week. PATIENTS: ADA therapy was initiated in 68 rheumatoid arthritis patients between July 2008 and June 2013. The mean MTX dose was 9.6 ± 2.6 mg/week, and the patients were followed for 24 weeks. RESULTS: The mean DAS28-ESR scores at baseline and week 24 were 4.6 ± 1.3 and 2.7 ± 1.2 in the 60 patients treated with MTX and 4.5 ± 1.0 and 4.2 ± 1.5 in the eight patients treated without MTX, respectively. Clinical remission was achieved in 48% and 25% of the patients, respectively, by week 24. Moreover, 90.0% of the patients taking MTX continued to receive ADA until week 24, while 50.0% of the patients not taking MTX continued to receive ADA until week 24. Among the 35 patients receiving MTX at a dose of >8 mg/week, the DAS28-ESR scores decreased rapidly from 4.4 ± 1.2 at baseline to 3.2 ± 1.1 at week 4 and further decreased to 2.4 ± 1.0 at week 24. Meanwhile, clinical remission was achieved in 57% of the patients receiving MTX at a dose of >8 mg/week and 36% of those receiving MTX at a dose of ≤8 mg/week. A significant correlation was noted between the improvement in the DAS-ESR score and the MTX dose. CONCLUSION: In this study population, enhanced clinical efficacy of ADA was achieved in combination with the administration of a sufficient dose of MTX, determined to be >8 mg/week.

A disintegrin and metalloprotease-10 is correlated with disease activity and mediates monocyte migration and adhesion in rheumatoid arthritis.

A disintegrin and metalloproteases (ADAMs) are a family of proteins that have been reported to be involved in several inflammatory conditions. We examined the secretion of ADAM-10 in biological fluids from patients with rheumatoid arthritis (RA) and the role it plays in monocyte migration. ADAM-10 levels were measured using enzyme-linked immunosorbent assays and immunofluorescence. To examine the role of ADAM-10 in RA synovial fluids (SFs), we studied THP-1 (human acute monocyte leukemia cell line) and monocyte chemotaxis. To determine whether ADAM-10 plays a role in cell proliferation in the RA synovium, we assayed the proliferation of ADAM-10 small interfering RNA (siRNA)-transfected RA fibroblast-like synoviocytes (FLSs). The ADAM-10 level in RA serum was significantly higher than that in normal serum and was correlated with a disease activity score of 28. ADAM-10-depleted RA SFs showed a decrease in THP-1 and monocyte migratory activity compared with that of sham-depleted controls. ADAM-10 siRNA inhibited monocyte adhesion to RA FLSs. Finally, blocking ADAM-10 secretion in RA FLSs resulted in decreased production of fractalkine/CX3CL1 and vascular endothelial cell growth factor. These data indicate that ADAM-10 plays a role in monocyte migration in RA and suggest that targeting ADAM-10 may provide a method of decreasing inflammation and potentially treating other inflammatory diseases.

Posterior Tibial Artery Perforator-Based Fascial Flap for Skin Necrosis and Exposed Extensor Tendon After Revision Total Ankle Replacement.

CASE: Delayed wound-healing of anterior ankle incisions can be problematic for patients who have undergone total ankle replacement. We describe the case of a patient in whom a posterior tibial artery perforator-based fascial flap was effectively used to cover skin necrosis and to repair the extensor retinaculum in a wound following revision total ankle replacement. CONCLUSION: When a tendon is exposed in the ankle, a skin flap is generally required. The creation of a perforator-based fascial flap is a useful technique for covering a wound with an exposed tendon and is an alternative to a musculocutaneous flap.

Posterior Tibial Artery Perforator-Based Fascial Flap for Skin Necrosis and Exposed Extensor Tendon After Revision Total Ankle Replacement: A Case Report.

CASE: Delayed wound-healing of anterior ankle incisions can be problematic for patients who have undergone total ankle replacement. We describe the case of a patient in whom a posterior tibial artery perforator-based fascial flap was effectively used to cover skin necrosis and to repair the extensor retinaculum in a wound following revision total ankle replacement. CONCLUSION: When a tendon is exposed in the ankle, a skin flap is generally required. The creation of a perforator-based fascial flap is a useful technique for covering a wound with an exposed tendon and is an alternative to a musculocutaneous flap.

Hydrophilic-interaction liquid chromatography-tandem mass spectrometric determination of erythrocyte 5-phosphoribosyl 1-pyrophosphate in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency.

Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease (LND) and its variants (LNV). Due to the technical problems for measuring the HPRT activity in vitro, discordances between the residual HPRT activity and the clinical severity were found. 5-Phosphoribosyl 1-pyrophosphate (PRPP) is a substrate for HPRT. Since increased PRPP concentrations were observed in erythrocytes from patients with LND and LNV, we have turned our attention to erythrocyte PRPP as a biomarker for the phenotype classification. In the present work, a method for determination of PRPP concentration in erythrocyte was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM). Packed erythrocyte samples were deproteinized by heating and the supernatants were injected into the LC-MS/MS system. All measurement results showed good precision with RSD <6%. PRPP concentrations of nine normal male subjects, four male patents with LND and six male patients with LNV were compared. The PRPP concentrations in erythrocyte from patients with LND were markedly increased compared with those from normal subjects, and those from patients with LNV were also increased but the degree was smaller than those with LND. The increase pattern of PRPP concentration in erythrocyte from patients with HPRT deficiency was consistent with the respective phenotypes and was correlated with the disease severity. PRPP concentration was suggested to give us supportive information for the diagnosis and the phenotype classification of LND and LNV.

Effects of antibody to receptor activator of nuclear factor κ-B ligand on inflammation and cartilage degradation in collagen antibody-induced arthritis in mice.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that leads to destruction of both articular cartilage and bone tissues. In rheumatic joints, synoviocytes and T-lymphocytes as well as bone cells produce the receptor activator of nuclear factor κ-B (RANK) ligand (RANKL), which binds to RANK on the surface of osteoclasts and their precursor cells to induce differentiation and activation of osteoclasts. Hence, inhibition of RANKL may be a promising approach to suppress osteolysis in RA. On the other hand, RANKL production by lymphocytes indicates the possibility that its inhibition would be effective to suppress inflammation in RA. In addition, it has been reported that cathepsin K, a predominant cysteine protease in osteoclasts, is involved in cartilage destruction in RA model mice. Here, we evaluated the effects of an anti-RANKL antibody on inflammation in footpads and degradation of articular cartilage in RA model mice. RESULTS: We induced arthritis in mice by injection of anti-type II collagen antibodies and lipopolysaccharide (LPS). Inhibition of RANKL by an anti-RANKL antibody (OYC1, Oriental Yeast, Tokyo, Japan) was confirmed by increased bone volume in the metaphysis of tibias. Swelling in either limb until day 14 was seen in 5 of 6 mice injected with anti-collagen antibodies and LPS without treatment with OYC1, while that was seen in 4 of 5 mice treated with OYC1. The average arthritis scores on day 14 in those groups were 2.17 and 3.00, respectively, indicating that OYC1 did not ameliorate inflammation in the limbs. Histological analyses indicated that OYC1 does not protect articular cartilage from destruction in mice with arthritis. CONCLUSIONS: Our present study failed to show the effectiveness of an anti-RANKL antibody to ameliorate inflammation in the limbs or protect articular cartilage from degradation in a collagen antibody-induced arthritis mouse model.

Effects of surgical intervention on disease activity of rheumatoid arthritis: cases of surgery for rheumatoid arthritis of the lower limbs treated with biologics.

OBJECTIVES: In order to verify combination therapy with drugs and surgery for rheumatoid arthritis (RA), we evaluated changes in clinical outcome affected by surgical intervention in the patient treated with biologics and investigated the effects of surgery on disease activity. METHODS: Fifty-five lower limb joint surgeries were performed in 48 patients under biological therapy. DAS28-ESR, modified Health Assessment Questionnaire (mHAQ) score, PtGA and serum CRP were examined just before surgery, at 6 months and at 12 months after surgery. A kind of suitable medication and its dose were investigated. RESULTS: Preoperative DAS28-ESR significantly decreased from 3.71 ± 1.19 (mean ± SD) to 3.37 ± 1.22 at 6 months and to 3.24 ± 1.05 at 12 months postoperatively. mHAQ score did not change, but, PtGA and serum CRP improved. In 43 (78.2%) patients in whom no change or decrease in medication during the follow-up period, excluding the effect of drugs, DAS28-ESR also decreased significantly from 3.53 ± 1.17 to 3.16 ± 1.16 at 6 months, and to 3.16 ± 0.98 at 12 months. CONCLUSIONS: Lower limb surgery performed under biological therapy enhances the effects of not only improving joint function but also of ameliorating systemic disease activity.