Aims. To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms. Methods. Patients with qualified synovium samples were recruited from a RA cohort. Synovium from patients diagnosed as non-inflammatory orthopaedic arthropathies was obtained as control. The expression and localization of MUC1 in synovium and fibroblast-like synoviocytes were assessed by immunohistochemistry and immunofluorescence. Small interfering RNA and MUC1 inhibitor GO-203 were adopted for inhibition of MUC1. Lysophosphatidic acid (LPA) was used as an activator of Rho-associated pathway. Expression of inflammatory cytokines, cell migration, and invasion were evaluated using quantitative real-time polymerase chain reaction (PCR) and Transwell chamber assay. Results. A total of 63 RA patients and ten controls were included. Expression of MUC1 was observed in both the synovial lining and sublining layer. The percentage of MUC1+ cells in the lining layer of synovium was significantly higher in RA than that in control, and positively correlated to joint destruction scores of RA. Meanwhile, MUC1+ cells in the sublining layer were positively correlated to the Krenn subscore of inflammatory infiltration. Knockdown of MUC1, rather than GO-203 treatment, ameliorated the expression of proinflammatory cytokines, cell migration, and invasion of rheumatoid synoviocytes. Knockdown of MUC1 decreased expression of RhoA, Cdc42, and Rac1. Treatment with LPA compromised the inhibition of migration and invasion, but not inflammation, of synoviocytes by MUC1 knockdown. Conclusion. Upregulated MUC1 promotes the aggression of rheumatoid synoviocytes via Rho guanosine triphosphatases (GTPases), thereby facilitating synovitis and joint destruction during the pathological process of RA. Cite this article: Bone Joint Res 2022;11(9):639–651

Aims. Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. Methods. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Results. A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves’ disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion. Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA. Cite this article: Bone Joint Res 2023;12(9):601–614

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps. Cite this article: Bone Joint Res 2022;11(7):426–438

Aims. To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). Methods. The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. Results. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Conclusion. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI. Cite this article: Bone Joint Res 2023;12(9):559–570

Aims. Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis. Methods. Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology. Results. Berberine inhibited proliferation and adhesion of RA-FLS cells, and significantly reduced the expression of MMP-1, MMP-3, RANKL, and TNF-α. Transcriptional results suggested that berberine intervention mainly regulated forkhead box O (FOXO) signal pathway, prolactin signal pathway, neurotrophic factor signal pathway, and hypoxia-inducible factor 1 (HIF-1) signal pathway. Conclusion. The effect of berberine on RA was related to the regulation of RAS/mitogen-activated protein kinase/FOXO/HIF-1 signal pathway in RA-FLS cells. Cite this article: Bone Joint Res 2023;12(2):91–102

Aims. There are concerns regarding complications and longevity of total elbow arthroplasty (TEA) in young patients, and the few previous publications are mainly limited to reports on linked elbow devices. We investigated the clinical outcome of unlinked TEA for patients aged less than 50 years with rheumatoid arthritis (RA). Methods. We retrospectively reviewed the records of 26 elbows of 21 patients with RA who were aged less than 50 years who underwent primary TEA with an unlinked elbow prosthesis. The mean patient age was 46 years (35 to 49), and the mean follow-up period was 13.6 years (6 to 27). Outcome measures included pain, range of motion, Mayo Elbow Performance Score (MEPS), radiological evaluation for radiolucent line and loosening, complications, and revision surgery with or without implant removal. Results. The mean MEPS significantly improved from 47 (15 to 70) points preoperatively to 95 (70 to 100) points at final follow-up (p < 0.001). Complications were noted in six elbows (23%) in six patients, and of these, four with an ulnar neuropathy and one elbow with postoperative traumatic fracture required additional surgeries. There was no revision with implant removal, and there was no radiological evidence of loosening around the components. With any revision surgery as the endpoint, the survival rates up to 25 years were 78.1% (95% confidence interval 52.8 to 90.6) as determined by Kaplan-Meier analysis. Conclusion. The clinical outcome of primary unlinked TEA for young patients with RA was satisfactory and comparable with that for elderly patients. A favourable survival rate without implant removal might support the use of unlinked devices for young patients with this disease entity, with a caution of a relatively high complication rate regarding ulnar neuropathy. Level of Evidence: Therapeutic Level IV. Cite this article: Bone Jt Open 2023;4(1):19–26

Aims. The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA). Methods. Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls. Results. We found that seven kinds of plasma proteins had genetic correlations with RA, such as Soluble Receptor for Advanced Glycation End Products (sRAGE) (correlation coefficient = 0.2582, p = 0.049), vesicle transport protein USE1 (correlation coefficient = 0.1337, p = 0.018), and spermatogenesis-associated protein 20 (correlation coefficient = 0.3706, p = 0.018). There was a significant causal relationship between sRAGE and RA. By comparing the genes encoding seven plasma proteins, we found that only USE1 was a DEG associated with RA. Conclusion. Our study identified a set of candidate plasma proteins that showed signals correlated with RA. Since the results of this study need further experimental verification, they should be interpreted with caution. However, we hope that this paper will provide new insights for the discovery of pathogenic genes and RA pathogenesis in the future. Cite this article: Bone Joint Res 2022;11(2):134–142

Aims. Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. Methods. We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets. Results. Four noteworthy RA-related modules were identified, revealing the immune- and infection-related biological processes and pathways involved in RA. HLA-DMA, HLA-DMB, HLA-DPA1, HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1, BLNK, BTK, CD3D, CD4, IL2RG, INPP5D, LCK, PTPRC, RAC2, SYK, and VAV1 were recognized as the key hub genes with high connectivity in gene regulation networks and gene pathway networks. Moreover, the long noncoding RNAs (lncRNAs) in the RA-related modules, such as FAM30A and NEAT1, were identified as the indispensable interactors with the hub genes. Finally, candidate drugs were screened by developing a cumulatively scoring approach based on the selected modules. Niclosamide and the other compounds of T-type calcium channel blocker, IKK inhibitor, and PKC activator, HIF activator, and proteasome inhibitor, which harbour the similar gene signature with niclosamide, were promising drugs with high specificity and broad coverage for the RA-related modules. Conclusion. This study provides not only the promising targets and drugs for RA but also a novel methodological insight into the target and drug screening. Cite this article: Bone Joint Res 2020;9(8):501–514

Aims. The aims of this study were to validate the outcome of total elbow arthroplasty (TEA) in patients with rheumatoid arthritis (RA), and to identify factors that affect the outcome. Methods. We searched PubMed, MEDLINE, Cochrane Reviews, and Embase from between January 2003 and March 2019. The primary aim was to determine the implant failure rate, the mode of failure, and risk factors predisposing to failure. A secondary aim was to identify the overall complication rate, associated risk factors, and clinical performance. A meta-regression analysis was completed to identify the association between each parameter with the outcome. Results. A total of 38 studies including 2,118 TEAs were included in the study. The mean follow-up was 80.9 months (8.2 to 156). The implant failure and complication rates were 16.1% (95% confidence interval (CI) 0.128 to 0.200) and 24.5% (95% CI 0.203 to 0.293), respectively. Aseptic loosening was the most common mode of failure (9.5%; 95% CI 0.071 to 0.124). The mean postoperative ranges of motion (ROMs) were: flexion 131.5° (124.2° to 138.8°), extension 29.3° (26.8° to 31.9°), pronation 74.0° (67.8° to 80.2°), and supination 72.5° (69.5° to 75.5°), and the mean postoperative Mayo Elbow Performance Score (MEPS) was 89.3 (95% CI 86.9 to 91.6). The meta-regression analysis identified that younger patients and implants with an unlinked design correlated with higher failure rates. Younger patients were associated with increased complications, while female patients and an unlinked prosthesis were associated with aseptic loosening. Conclusion. TEA continues to provide satisfactory results for patients with RA. However, it is associated with a substantially higher implant failure and complication rates compared with hip and knee arthroplasties. The patient’s age, sex, and whether cemented fixation and unlinked prosthesis were used can influence the outcome. Level of Evidence: Therapeutic Level IV. Cite this article: Bone Joint J 2020;102-B(8):967–980

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA. Cite this article: Bone Joint Res 2021;10(4):285–297

Aims. The aim of this meta-analysis was to compare the outcome of total elbow arthroplasty (TEA) undertaken for rheumatoid arthritis (RA) with TEA performed for post-traumatic conditions with regard to implant failure, functional outcome, and perioperative complications. Materials and Methods. We completed a comprehensive literature search on PubMed, Web of Science, Embase, and the Cochrane Library and conducted a systematic review and meta-analysis. Nine cohort studies investigated the outcome of TEA between RA and post-traumatic conditions. The preferred reporting items for systematic reviews and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)) guidelines and Newcastle-Ottawa scale were applied to assess the quality of the included studies. We assessed three major outcome domains: implant failures (including aseptic loosening, septic loosening, bushing wear, axle failure, component disassembly, or component fracture); functional outcomes (including arc of range of movement, Mayo Elbow Performance Score (MEPS), and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire), and perioperative complications (including deep infection, intraoperative fracture, postoperative fracture, and ulnar neuropathy). Results. This study included a total of 679 TEAs for RA (n = 482) or post-traumatic conditions (n = 197). After exclusion, all of the TEAs included in this meta-analysis were cemented with linked components. Our analysis demonstrated that the RA group was associated with a higher risk of septic loosening after TEA (odds ratio (OR) 3.96, 95% confidence interval (CI) 1.11 to 14.12), while there was an increased risk of bushing wear, axle failure, component disassembly, or component fracture in the post-traumatic group (OR 4.72, 95% CI 2.37 to 9.35). A higher MEPS (standardized mean difference 0.634, 95% CI 0.379 to 0.890) was found in the RA group. There were no significant differences in arc of range of movement, DASH questionnaire, and risk of aseptic loosening, deep infection, perioperative fracture, or ulnar neuropathy. Conclusion. The aetiology of TEA surgery appears to have an impact on the outcome in terms of specific modes of implant failures. RA patients might have a better functional outcome after TEA surgery. Cite this article: Bone Joint J 2019;101-B:1489–1497

Objectives. The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. Methods. We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs). Gene ontology (GO) enrichment analysis was conducted by DAVID. The protein association networks of gene modules were generated by STRING. Results. For RA synovium, the top-ranked gene module is HLA-A, containing TAP2, HLA-A, HLA-C, TAPBP and LILRB1 genes. For RA PBMCs, the top-ranked gene module is GRB7, consisting of HLA-DRB5, HLA-DRA, GRB7, CD63 and KIT genes. Functional enrichment analysis identified three significant GO terms for RA synovium, including antigen processing and presentation of peptide antigen via major histocompatibility complex class I (false discovery rate (FDR) = 4.86 × 10 – 4), antigen processing and presentation of peptide antigen (FDR = 2.33 × 10 – 3) and eukaryotic translation initiation factor 4F complex (FDR = 2.52 × 10 – 2). Conclusion. This study reported several RA-associated gene modules and their functional association networks. Cite this article: X. Xiao, J. Hao, Y. Wen, W. Wang, X. Guo, F. Zhang. Genome-wide association studies and gene expression profiles of rheumatoid arthritis: an analysis. Bone Joint Res 2016;5:314–319. DOI: 10.1302/2046-3758.57.2000502

Introduction. Since 1981, we have used various types of the total hip prosthesis for the reconstruction of the acetabular protrusion in rheumatoid arthritis. The cemented Charnley prosthesis was used during the initial 8 years, and we experienced loosening of the cemented acetabular socket in some cases. The bipolar femoral head prosthesis, which started to be used from 1984, was one of the cementless prosthesis. And it showed high frequency of proximal migration of outerhead. The threaded socket also showed frequent loosening. To overcome these problems, we started to utilize a new method from 1988. This method included packing morselized bone grafts into the acetabulum and fix them using a porous coated socket and screws. This study describes the results of cementless total hip arthroplasty (THA) for the acetabular protrusion in rheumatoid arthritiswith this method. Materials and methods. Sixty -one cementless THAs with use of porous coated acetabular socket were performed in 50 patients who had sever protruded acetabulum due to rheumatoid arthritis. The average follow –up period was 9 years and 5 months (range, 5 to 13 years). A Mallory/ Head prosthesis with porous coated socket was used in 43 hips and other types in 18 hips. In all operated hips, autogenous morselized bones were grafted on the thin acetabullar wall. Results. The clinical improvement in pain was the most apparent. X-ray findings of the grafted bone in the acetabulum showed a homogenous pattern in most cases (90. 2%) at 6 months after the operation. A radiolucent zone at a non-weight-bearing area between the grafted bone and socket was seen in 20 hips (32. 7%) for 3 years after the operation, and it gradually disappeared and changed to a sclerotic zone. Collapse and /or absorption of the grafted bone were noted in 3 hips of the patients with sever osteoporosis and high disease activity. Discussion. There are several technical key points to succeed THA in patients with rheumatoid arthritis. The first is the selection of the acetabular socket. The second is the method of bone grafting, and the third is the size and the shape of grafted bones. We have used various types of prosthesis for the protruded acetabulum so far, and it was considered that the bipolar and threaded types are not acceptable because of their high frequency of proximal migration and loosening. The mass and /or block bone should not be used, because they are liable to fall into collapse. It is safely recommended to use slice or morselized bones to lead the grafts to early survival and remodelling caused by tight and close contacts. Conclusion. THA with the use of morselized bone grafting into the acetabulum and a fixation with a porous coated socket-and screws is a simple and useful procedure for treating protruded acetabulum in rheumatoid arthritis

Introduction. The wrist is the ”key-stone” of hand function. Painless stability is a prerequisite for the rheumatoid wrist to perform various manual tasks. Synovectomy of the extensor tendons and the wrist joint with a Darrach procedure is offered for painful wrists, which are not controlled by conservative treatment with medication and orthosis. Radiolunate arthrodesis is performed on wrists with an unstable radiocarpal joint and preserved midcarpal joint space. This study describes the long-term (more than 10 years) follow-up of these operative procedures. Materials and methods. The follow-up study was performed on 25 wrists in 25 rheumatoid patients (22 women and 3 men), whose average age was 52 years (range, 33 to 66 years) with an average disease duration of 12 years (range, 1 to 38 years). The average follow-up period was 12. 5 years (range, 10 to 18 years). Five wrists were Larsen-Dale-Eek’s grade II, 14 were grade III, and 6 were grade IV. Depending on the severity of bone destruction, the scaphoid in 6 wrists and the triquetrum in 3 wrists were included in the fusion site. Results. Preoperative pain (88%) and swelling (96%) decreased remarkably at follow-up (12%, 4%). Average grip strength increased significantly from 100mmHg to 140mmHg (p< 0. 01). The total arc of wrist extension/ flexion decreased to two-thirds of the preoperative arc with a major loss in flexion (preop. : 26/28degrees, follow-up: 23/13degrees). The range of forearm rotation increased due to a Darrach procedure. In periodical X-ray assessments of 23 wrists, carpal collapse initially improved following the operation, however, it returned to the preoperative level after 5 years. Ulnar carpal shift improved significantly after the operation (p< 0. 01), and the position remained unchanged over 10 years. In palmar carpal subluxation, no remarkable change was noted. Bone union occurred in 87% of the operated wrists and the remaining 13% had fibrous union. Widening at the lunocapitate joint (> 2mm) was noted in 4 wrists (17%) and progressive instability at the midcarpal joint occurred in one wrist with the mutilating type of disease. Narrowing (< 1mm) was noted in 5 wrists (22%) and 3 wrists were totally fused in the functional position. Discussion. Radiolunate arthrodesis provides good stability with some motion for the moderately deteriorated rheumatoid wrist more than 10 years after the operation, in spite of some radiological progression of the disease. This operation is considered to convert the natural course of the rheumatoid wrist from the unstable form to the stable form

Introduction. The wrist is the ”key-stone” of hand function. Painless stability is a prerequisite for the rheumatoid wrist to perform various manual tasks. Synovectomy of the extensor tendons and the wrist joint with a Darrach procedure is offered for painful wrists, which are not controlled by conservative treatment with medication and orthosis. Radiolunate arthrodesis is performed on wrists with an unstable radiocarpal joint and preserved midcarpal joint space. This study describes the long-term (more than 10 years) follow-up of these operative procedures. Materials and methods. The follow-up study was performed on 25 wrists in 25 rheumatoid patients (22 women and 3 men), whose average age was 52 years (range, 33 to 66 years) with an average disease duration of 12 years (range, 1 to 38 years). The average follow-up period was 12. 5 years (range, 10 to 18 years). Five wrists were Larsen-Dale-Eek’s grade II, 14 were grade III, and 6 were grade IV. Depending on the severity of bone destruction, the scaphoid in 6 wrists and the triquetrum in 3 wrists were included in the fusion site. Results. Preoperative pain (88%) and swelling (96%) decreased remarkably at follow-up (12%, 4%). Average grip strength increased significantly from 100mmHg to 140mmHg (p< 0. 01). The total arc of wrist extension/ flexion decreased to two-thirds of the preoperative arc with a major loss in flexion (preop. : 26/28degrees, follow-up: 23/13degrees). The range of forearm rotation increased due to a Darrach procedure. In periodical X-ray assessments of 23 wrists, carpal collapse initially improved following the operation, however, it returned to the preoperative level after 5 years. Ulnar carpal shift improved significantly after the operation (p< 0. 01), and the position remained unchanged over 10 years. In palmar carpal subluxation, no remarkable change was noted. Bone union occurred in 87% of the operated wrists and the remaining 13% had fibrous union. Widening at the lunocapitate joint (> 2mm) was noted in 4 wrists (17%) and progressive instability at the midcarpal joint occurred in one wrist with the mutilating type of disease. Narrowing (< 1mm) was noted in 5 wrists (22%) and 3 wrists were totally fused in the functional position. Discussion. Radiolunate arthrodesis provides good stability with some motion for the moderately deteriorated rheumatoid wrist more than 10 years after the operation, in spite of some radiological progression of the disease. This operation is considered to convert the natural course of the rheumatoid wrist from the unstable form to the stable form

Aim. Patients with late acute periprosthetic joint infections (PJI) and treated with surgical debridement have a high failure rate. Previous studies have shown that rheumatoid arthritis (RA) is an independent risk factor for treatment failure. We conducted a case-control study to identify predictors for failure in late acute PJI treatment in RA patients. We hypothesize that patients with RA have a higher failure rate compared to controls due to the use of immunosuppressive drugs. Method. Data of an international multicenter retrospective observational study was used. Late acute PJI was defined as a sudden onset of symptoms and signs of a PJI, more than 3 months after implantation. Failure of treatment was defined as persistent signs of infection, relapse with the same or reinfection with a different micro-organism, need for prosthesis removal or death. Cases with RA were matched with cases without RA based on the affected joint. A Cox survival analyses, stratified for RA, was used to calculate hazard ratio's (HR) for failure. Subgroup analyses were used to explore other predictors for treatment failure in RA patients. Results. A total of 40 patients with RA and 80 controls without RA were included. Treatment failure occurred in 65% patients with RA compared to 45% for controls (p= .052). 68% of patients with RA used immunosuppressive drugs at time of PJI diagnosis. The use or continuation of immunosuppressive drugs in PJI was not associated with a higher failure rate; neither were the duration of symptoms and causative microorganism. The time between implantation of the prosthetic joint and diagnosis of infection was longer in RA patients: median 110 (IQR 41-171) vs 29 months (IQR 7.5–101.25). Exchange of mobile components was associated with a lower risk of treatment failure (HR 0.489, 95% CI 0.242–0.989, p-value .047). Conclusions. The use of immunosuppressive drugs does not seem to be associated with a higher failure rate in patients with RA. Mobile exchange in RA patients is associated with a lower risk of failure. This might be due to the significantly older age of the prosthesis in RA patients. Future studies are needed to explore these associations and its underlying pathogenesis

Objectives: The major objective of the present study was to investigate the risk of revision of infection after primary total knee replacements (TKR) in patients with rheumatoid arthritis (RA) during a 13-year period. We wished to compare RA patients with OA patients in order to detect differences in the risk of revision for infection, and to compare changes in the risk for the two patient groups over time. Furthermore we studied the time from primary implantation to revision for infection in the two groups. Patients and Methods: From January 1994 to June 2008, 2482 primary TKRs in patients with RA and 25189 in OA patients were identified in the Norwegian Arthroplasty Register. Kaplan-Meier survival curves, with revision for infection as the endpoint, were constructed. Cox regression analyses were performed to calculate relative risk (RR) of revision for infection according to diagnosis, age, gender, year of surgery (from 1994 through 2000 and from 2001 to June 2008) and time of revision related to the time of primary TKR. All relative risks were adjusted for the other variables. Results: The 5-year revision rate for infection of TKR was 1.1% in RA patients and 0.5% in OA patients. Rheumatoid arthritis patients had a 1.7 (95%CI 1.2–2.6) times higher risk of revision for infection compared to the control group (OA patients). The patients who had TKR surgery in the later period had a decreased risk of revision for infection (RR 0.72, 95%CI 0.53–0.98) compared to the time period 1994–2000. Furthermore, the risk of revision for late infection in RA patients, increased compared to OA from 4 years after the index operation. Conclusion: Patients with RA undergoing total knee replacement surgery were at a higher risk of revision for prosthetic joint infection and had a higher risk of late infections leading to revision, than patients with OA. These findings emphasizes the importance of preoperative management and optimizing preventive strategies, especially in this patient group

Fracture repair is a wound healing process that in young healthy patients usually proceeds to uncomplicated union. However, the healing cascade is delayed with increasing age, medication and certain diseases such as rheumatoid arthritis. Recently the important role of the immune system in fracture repair has become apparent within the emerging subject of Osteoimmunology. Patients with rheumatoid arthritis have an altered immune system and therefore we have investigated the hypothesis that patients with rheumatoid arthritis have a higher incidence of non-union after a fracture compared to patients without rheumatoid arthritis. Method: The Edinburgh Royal Infirmary computer database was searched over a 10 year period (May 1996- May 2006) to identify all patients with non-union out of the total number of patients presenting with fractures. These patients groups were then subdivided into patients that had and did not have rheumatoid arthritis. Patients were excluded if they were lost to follow up, or if the fracture either occurred before the May 1996 or management continued passed May 2006. In this study non-union was defined as failure to heal within expected timescale and lack of progression at serial x-rays (all non-union were diagnosed at least 3 months from fracture). Results: From May 1996 through to May 2006, 8,456 patients with fracture were defined. 71 of these patients with fractures had rheumatoid arthritis. Of these patients 63 had union of their fractures whilst 8 patients developed non-union of their fracture (11.3%). In a total of 8385 non rheumatoid arthritis patients 164 developed non-union of their fracture compared to 8221 patients who had union of their fractures (2%). Comparison between these two patient groups suggests rheumatoid arthritis patients are more likely to develop non-union of traumatic fractures (Chi squared test, p value < 0.001). Patients with rheumatoid arthritis who progressed to non-union were on the following medication, Gold (1), Indomethacin (1), Non steroidal anti-inflammatories (4), Combination analgesia (2), Antihypertensives (2), Omeprazole (1) and Thyroxine (1). Discussion: The results from this study suggest that patients with rheumatoid arthritis have a greater incidence of non-union after a fracture compared to patients without rheumatoid arthritis. This maybe due to the abnormal immune system in rheumatoid arthritis patients. However rheumatoid arthritis patients are often on a number of medications and these drugs rather than the innate alteration of the immune system may be responsible for the altered healthy response. However whether as a result of the rheumatoid arthritis itself or the medication, our study demonstrates a higher non-union rate in the rheumatoid arthritis patients and this needs to be taken into account when treating rheumatoid arthritis patients with fractures

Objectives. Biologic agents (BIO) drastically changed the rheumatoid arthritis (RA) therapy from starting to use biologics at 2003 in Japan. The rate of orthopaedic surgery, especially total joint arthroplasty (TJA) may reflect trends in disease severity, management and health outcomes. Methods. We surveyed the number and rate of orthopaedic surgeries and TJA in RA treatment with BIO in the last decade, so called BIO-era. Results. We had 18,701 cases of orthopaedic surgeries, including 491 rheumatoid surgeries from 2004 to 2013. They contained 382 cases of total joint arthroplasties (78%), including 258 total knee arthroplasty (TKA), 80 total hip arthroplasty (THA), 18 total elbow arthroplasty (TEA), 14 total ankle arthroplasty (TAA), 4 swanson arthroplasty for fingers. The numbers of orthopaedic surgery increased year by year. The rate of rheumatoid surgeries not changed in the last decade (r=0.8, p<0.05, Fig. 1). The numbers of TSA and TEA in 2009–2013 increased twice compared to them in 2004–2008, but TKA and THA not changed. We had 241 RA patients treated by biologics agents from 2003, including 60 rheumatoid surgeries with the biologic therapy. Over half of rheumatoid surgeries were TJA (37 cases; 61%), including 26 cases for lower joint; 11 cases for upper joint. The rate of upper TJA more increased than that of lower joint in the RA patients with BIO in this decade. Conclusion. TJA for upper joint that improve the quality of life may increase in the RA patients with biologic therapy, because their disease activity and attitudes have changed year by year in this BIO-era

Purpose. The failure rate of total ankle arthroplasty (TAA) in rheumatoid patients may be higher than in osteoarthritis patients due to the medications used to treat rheumatoid arthritis and the comorbidities associated with this disease. The purpose of this study was to prospectively look at the intermediate-term outcomes of TAA in patients with rheumatoid arthritis and to compare the results to a matched cohort of patients with ankle osteoarthritis undergoing TAA. Method. This study is a prospective, multicentre comparison study of patients two to eight years post-TAA. A cohort of 57 patients with rheumatoid arthritis was identified from the prospective national database of TAAs (RA group). Matched controls were identified in the database using age, type of prosthesis, and follow-up time as matching criteria (OA group). The following data was collected: demographic information, previous and additional surgeries at the time of TAA and major and minor complications including revisions. Generic and disease specific, validated outcome scores collected include the Short-Form 36 (SF36) and Ankle Osteoarthritis Score (AOS). Results. Each group consisted of 42 female and 15 male patients with an average follow-up of four years. The two groups were similar with an average age of 59.55 years (33–82) in the RA group and 58.13 years (36–85) in the osteoarthritis group and an average BMI of 25.77 kg/m2 in the RA group and 27.70 kg/m2 in the OA group. Preoperative AOS scores were similar in both groups: 64.42 for pain and 72.59 for disability in the RA group and 58.39 for pain and 72.37 for disability in the OA group. There was a significant improvement at latest follow-up: 16.64 for pain and 27.03 for disability in the RA group and 11.75 for pain and 22.66 for disability in the OA group. The OA group had a greater improvement in the SF-36 physical component score (29.97 to 41.29 versus 26.88 to 34.82 in the RA group) whereas the RA group had a greater improvement in the mental component score (49.71 to 56.90 versus 48.99 to 52.02 in the OA group). There was a higher rate of additional surgeries, predominantly hindfoot fusions, in the RA group than the OA group (33 versus 13). Revision rates were similar between the two groups with two revisions in the RA group and three in the OA group. There were no major wound complications in the OA group and two in the RA group. Conclusion. Total ankle arthroplasty is a good option for patients with rheumatoid arthritis. A greater number of additional surgeries were required to balance the foot and support the ankle replacement in the rheumatoid patients than in the osteoarthritis patients. Both groups showed similar improvement in a generic quality of life outcome measure (SF36) and a disease specific functional outcome measure (AOS). Revision rates were similar between the groups; however, the patients with rheumatoid arthritis had a higher rate of wound complications