A preliminary survey of rheumatologists on the management of late-onset rheumatoid arthritis in Japan.

Objectives We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice. Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses. Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation. Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA.

Consensus statement on the management of late-onset rheumatoid arthritis.

OBJECTIVES: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. METHODS: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. RESULTS: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. CONCLUSIONS: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases.

High Fracture Rate of AVANTA Silicone Implant Following Arthroplasty of the Thumb MCP Joint of Rheumatoid Arthritis Patients with Boutonniere Deformities.

We retrospectively investigated the mid-term outcomes of arthroplasty using the AVANTA silicone implant for thumb metacarpophalangeal (MCP) joints with boutonniere deformity in patients with rheumatoid arthritis (RA). This study involved 36 thumbs of 33 RA patients with a mean follow-up period of 5.1 years (range, 2.0-13.3). Postoperatively, the mean extension was significantly increased and the mean flexion was significantly decreased (p<0.001, p<0.001, respectively), resulting in the mean arc of range of motion (ROM) shifting in the direction of extension after surgery. Implant fracture was observed in 10 thumbs (28%), and 4 of these (11%) underwent revision surgery. The survivorship with implant fracture and revision surgery as endpoints were 73.4% and 91.8% at 5 years, respectively. The preoperative arc of ROM and the postoperative flexion range of the implant-fracture group were significantly greater than those in the no-implant-fracture group (p=0.039, 0.034, respectively). These results suggest the importance of patient education and careful rehabilitation to prevent excessive flexion. Overall, the AVANTA silicone implant showed a relatively high rate of implant fracture at our institute.

Influence of Janus kinase inhibitors on early postoperative complications in patients with rheumatoid arthritis undergoing orthopaedic surgeries.

OBJECTIVE: We retrospectively reviewed the records of rheumatoid arthritis (RA) patients who underwent orthopaedic surgery to examine the influence of the perioperative use of Janus kinase (JAK) inhibitors on early postoperative complications. PATIENTS AND METHODS: Thirty-two patients with RA under disease control with JAK inhibitors who underwent 49 orthopaedic procedures were included in the study. Patient records after surgery were investigated for surgical site infection (SSI), delayed wound healing (DWH), a flare-up of the disease, preoperative and postoperative absolute lymphocyte counts (ALCs), venous thromboembolism, and other postoperative complications. RESULTS: JAK inhibitors were continued during the perioperative period in 31 procedures. In the remaining 18 procedures, JAK inhibitors were discontinued perioperatively with a mean discontinuation period of 2.4 days. No instances of SSI were identified in any patient during at least 90 days' follow-up, while DWH was seen in one patient. Disease flare-up was noted in two patients after 3 and 9 days of discontinuation of JAK inhibitors, respectively. The ALCs significantly decreased on postoperative Day 1 (P < .0001), and there was a significant correlation between pre- and post-one-day ALCs (r = 0.75, P < .0001). CONCLUSION: JAK inhibitors seem to be safe during the perioperative period of orthopaedic surgery.

Wrist arthrodesis combined with a bulk bone allograft for implant loosening after total wrist arthroplasty: A case report.

Total wrist arthroplasty (TWA) is a challenging procedure for wrist joints severely destroyed by rheumatoid arthritis. The most common postoperative complication of TWAs is the loosening of the carpal component. Revision surgeries for failed TWAs can be complicated owing to severe bone loss and concomitant soft-tissue problems. Here, we report a case (68-year-old woman with a history of rheumatoid arthritis for 24 years) of severe aseptic loosening of semi-constrained TWA and its salvage surgery. During the primary arthroplasty procedure, severe instability at the second through fifth carpometacarpal joints was observed and arthrodesis of these joints was required. The radiographs obtained 9 months after surgery showed loosening of the carpal component. Subsequently, she suffered a stroke, resulting in a loss of follow-up, and higher stress was loaded on her upper extremities during standing and walking. In the radiograph taken at her revisit 25 months after the primary surgery, the subsidence of the carpal component progressed and loosening of the radial component was observed. Total wrist arthrodesis was performed using a bulk bone allograft of the femoral head, combined with a penetrating Wrist Fusion Rod®. Rapid bone union was achieved without soft-tissue irritation. We conclude that wrist arthrodesis with a bulk bone allograft combined with an intramedullary nail is a reasonable option for failed total wrist arthroplasty.

Fracture Line Distributions of Undisplaced Distal Radius Fractures in Relation to Rupture of the Extensor Pollicis Longus Tendon.

Rupture of the extensor pollicis longus (EPL) tendon is a known complication after undisplaced distal radius fracture (DRF). However, no report has revealed the relationship between EPL tendon rupture and the fracture pattern. Thus, this study aimed to investigate the characteristics of fractures at risk of EPL tendon rupture using fracture line mapping of undisplaced DRFs. This study used computed tomography imaging data of undisplaced DRFs with (n=18) and without EPL tendon rupture (n=52). Fracture lines obtained from 3D reconstruction data were drawn manually after matching with a 2D template wrist model. Fracture maps represented the fracture line distribution by superimposing the fracture lines of all 70 patients. Heat maps showed the relative frequency of the fracture lines as a gradual color change. Fracture lines of cases with EPL tendon rupture were concentrated in the proximal border of Lister's tubercle. By contrast, fracture lines of cases without EPL tendon rupture were relatively dispersed.

Late-onset rheumatoid arthritis registry study, LORIS study: study protocol and design.

BACKGROUND: Although drug treatment strategies for rheumatoid arthritis (RA) are relatively well established, there is a paucity of evidence on the treatment in older patients. The purpose of this study is to build a registry for late-onset RA (LORA), which is expected to increase rapidly worldwide. In addition, we aim to propose optimal treatment strategies according to the patient background including frailty, thereby contributing to improving the quality of treatment and daily living in patients with RA. METHODS/DESIGN: The LORIS (Late-onset Rheumatoid Arthritis Registry) Study is a prospective nation-wide multicenter observational study of patients with LORA. The inclusion criteria were patients aged ≥ 65 years at onset, meeting 2010 ACR/EULAR classification criteria for RA, and starting either any disease-modifying antirheumatic drugs (DMARDs) in a DMARD-naïve patient or the first biologic/targeted synthetic DMARDs during the study period. Enrollment was started on 11 January, 2022 and will be closed on 31 December, 2023. Patients will undergo a comprehensive baseline assessment including clinical data, medication, cognitive and physical function, psychosocial factors, and frailty. Data will be collected at baseline, Month 3, 6, 12, 18, 24, 36, and summarized descriptively. The factors associated with adverse events and achieving remission will be determined. DISCUSSION: A multi-disciplinary panel including patients, rheumatologists, and geriatric specialists will discuss the results and build a consensus regarding the treatment goals of LORA. We expect to provide a broad range of information for evidence-based shared decision making in the treatment of LORA. STUDY REGISTRATION: Registered at the UMIN registry (UMIN000046086) on 1 January 2022.

Japanese version of Patient-Rated Elbow Evaluation is a useful outcome measure that potentially reflects hand function in patients with rheumatoid arthritis who underwent total elbow arthroplasty.

OBJECTIVES: We examined the relationship between the Japanese version of Patient-Rated Elbow Evaluation (PREE-J) and other established subjective and objective outcome measures in Japanese patients with rheumatoid arthritis (RA) who underwent total elbow arthroplasty (TEA). MATERIALS AND METHODS: This study involved 46 elbows of 40 RA patients. We collected clinical data 1 year after surgery, including the PREE-J, the Mayo Elbow Performance Score (MEPS), Disability of the Arm, Shoulder, and Hand (DASH), and Hand20. The correlation and responsiveness to PREE-J were evaluated compared with other outcome measures preoperatively and postoperatively. RESULTS: Almost all outcome measures were improved significantly after surgery. Preoperative PREE-J was significantly correlated with preoperative DASH, Hand20, and MEPS. Interestingly, postoperative PREE-J did not correlate with postoperative MEPS. Multiple regression analyses revealed that preoperative grip strength [B = -0.09; 95% confidence interval (95% CI) -0.17 to -0.01, p = 0.03] and preoperative Hand20 (B = 0.31, 95% CI 0.03-0.58, p = 0.03) were significant factors that might influence the postoperative PREE-J. CONCLUSIONS: The PREE-J was shown to correlate well with other preoperative outcome measures among the RA patients included in the current study. The postoperative PREE-J after TEA was influenced by the preoperative grip strength and function of the hand.

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

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

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

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

Clinical and radiographic study of partial arthrodesis for rheumatoid wrists.

OBJECTIVES: To retrospectively investigate the clinical and radiographic results of partial arthrodesis for the wrists with rheumatoid arthritis (RA). METHODS: Forty-one wrists with RA were treated by radiolunate (RL) or radiolunotriquetral (RLT) arthrodesis with ulnar head resection. The average follow-up period after surgery was 7.1 years. Preoperative radiographs of all wrists were classified according to Schulthess classification. We performed RL arthrodesis for all Type II (n = 26) and Type III wrists (n = 7), and RLT arthrodesis for Type III wrists (n = 8). Pre- and postoperative pain score (visual analog scale), grip strength, range of motion, and radiographic parameters were statistically compared. RESULTS: Pain scores in all groups were significantly improved at final follow-up (P < 0.05). Grip strength increased from 5.9 to 12.4 (kg) significantly in Type II wrists (P < 0.01), from 7.2 to 9.1 in Type III wrists after RLT arthrodesis, but decreased from 6.9 to 6.0 in Type III wrists after RL arthrodesis. In all groups, the arc of pronation and supination improved significantly (P < 0.05), and all radiographic parameters improved. CONCLUSIONS: RL arthrodesis for Type II wrists showed satisfactory clinical results. RLT arthrodesis would be a reliable method in case of unstable wrist joint.

Risk factors for surgical site infection and delayed wound healing after orthopedic surgery in rheumatoid arthritis patients.

OBJECTIVE: To investigate the prevalence and the risk factors of surgical-site infection (SSI) and delayed wound healing (DWH) in patients with rheumatoid arthritis (RA) underwent orthopedic surgery. METHODS: We reviewed the records of 1036 elective orthopedic procedures undertaken in RA patients. Risk factors for SSI and DWH were assessed by logistic regression analysis using age, body mass index, disease duration, pre-operative laboratory data, surgical procedure, corticosteroid use, co-morbidity, and use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) as variables. RESULTS: SSI and DWH were identified in 19 cases and 15 cases, respectively. One case of SSI and three cases of DWH were recorded among 196 procedures in patients using bDMARDs. Foot and ankle surgery was associated with an increased risk of SSI (odds ratio (OR), 3.167; 95% confidence interval (CI), 1.256-7.986; p = 0.015). Total knee arthroplasty (TKA; OR, 4.044; 95% CI, 1.436-11.389; p = 0.008) and disease duration (OR, 1.004; 95% CI, 1.000-1.007; p = 0.029) were associated with an increased risk of DWH. CONCLUSIONS: Our results indicated foot and ankle surgery, and TKA and disease duration as risk factors for SSI and DWH, respectively. bDMARDs was not associated with an increased risk of SSI and DWH.

Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1ß production and subsequent NF-κB activation.

OBJECTIVE: To investigate the inhibitory effect of hyaluronan (HA) on mechanical stress- induced expression of a disintegrin and metalloproteinase with thrombospondin type 1 motifs (ADAMTS)-4, -5 and matrix metalloproteinase (MMP)-13 by human chondrocytes. MATERIALS AND METHODS: Normal human articular chondrocytes were pre-incubated with or without 1.0 mg/mL HA (2700 kDa) for 12 h at 37 °C in stretch chambers, then they were exposed to uni-axial cyclic tensile strain (CTS, 0.5 Hz, 10% elongation). The expression of ADAMTS-4, -5, and MMP-13 were analyzed by real-time polymerase chain reaction and Immunocytochemistry. The concentration of IL-1ß in the supernatant was measured using enzyme-linked immunosorbent assay (ELISA). The nuclear translocation of runt-related transcription factor 2 (RUNX-2) and nuclear factor-κB (NF-κB) was examined by ELISA and immunocytochemistry, and phosphorylation of NF-κB was examined by western blotting. RESULTS: HA inhibited mRNA expression of ADAMTS-4, -5, and MMP13 after 24 h CTS via inhibition of IL-1ß secretion and NF-κB activation. However, HA failed to inhibit CTS-induced RUNX-2 expression and subsequent expression of ADAMTS-5 and MMP-13 1 h after CTS. CONCLUSIONS: Our results demonstrated that HA significantly suppressed mechanical stress-induced expression of catabolic proteases by inhibition of the NF-κB-IL-1ß pathway, but did not suppress mechanical stress-induced RUNX-2 signaling.

Short-term results of the PROSNAP linked elbow prosthesis with a snap-in structure and modular flange for the reconstruction of severely damaged rheumatoid elbows.

BACKGROUND: We aimed to evaluate the early clinical results of the reconstruction of problematic elbow joints due to rheumatoid arthritis (RA) using a PROSNAP linked elbow prosthesis (Kyocera Medical, Osaka, Japan) for total elbow arthroplasty. METHODS: Seventeen elbows in 14 RA patients were replaced with a PROSNAP elbow with cement fixation. The patients comprised 1 man and 13 women, with a mean age of 63.9 years (range, 52-83 years) at the time of surgery. The preoperative conditions of the elbows were arthritis mutilans (n = 10), an ankylosed or stiff elbow with a preoperative range of motion of 45° or less (n = 4), and loosening of a primary total elbow arthroplasty (n = 3). The mean follow-up period was 47.7 months (range, 32-69 months), with a 100% follow-up rate. The clinical outcome of the elbows was evaluated by the Mayo Elbow Performance Index (maximum, 100 points). RESULTS: The mean postoperative Mayo Elbow Performance Index score improved from 57.6 points to 97.1 points. Preoperatively, 3 of the 17 elbows were judged as good, 7 as fair, and 7 as poor; at final follow-up, 16 elbows were judged as excellent and 1 as good. Complications were noted in 1 elbow (6%), which had undergone a postoperative fracture. CONCLUSIONS: The PROSNAP elbow prosthesis can be safely implanted through a relatively easy procedure and provides satisfactory short-term clinical outcomes for the reconstruction of severely damaged RA elbows. LEVEL OF EVIDENCE: Level IV, case series, treatment study.