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ID PMID Title PublicationDate abstract
31468238 Synovial Tissue: Cellular and Molecular Phenotyping. 2019 Aug 29 PURPOSE OF REVIEW: This review provides a summary of recent molecular findings that have refined our understanding of the cell types that constitute human synovial tissue, particularly in patients with rheumatoid arthritis (RA). RECENT FINDINGS: Recent advances in high-dimensional and single-cell assays have elucidated upwards of 20 cell subsets in the RA synovium. This includes novel fibroblast populations and lymphocyte phenotypes, which in many cases exhibit features that have not been found in other tissues thus far. Molecular profiling studies over the past several years have rapidly generated a comprehensive and detailed outline of the cellular phenotypes in synovial tissue affected by RA. Molecular features of these newly identified cell subsets immediately represent reasonable therapeutic targets and provide the opportunity to design the most clinically relevant mechanistic experiments. Broadly speaking, the ~ 20 cell types thus far identified in RA synovium seem to be fairly well conserved across patients, despite extensive heterogeneity in patient clinical features, stage of disease, and treatment responses. Thus, a next phase in molecular profiling may benefit from quantifying patient samples in terms of the ratios of cell types, with the rationale that certain cellular interactions will predominate in an individual and medications targeting these interactions may be more efficacious for that individual. Such cellular profiling in tissues combined with studies examining how the compendium of these cells interact in their three-dimensional tissue ultrastructures will be important in understanding how collectively these cells drive the disease process and ultimately how best to treat patients.
30719572 [Rare erosive arthritis and dermatitis syndrome in Whipple's disease]. 2019 Mar Whipple's disease is a rare infectious disease, which can affect various organ systems. Arthritis is a common symptom and therefore the infection is often misdiagnosed as seronegative rheumatoid arthritis. In rare cases an infection with Tropheryma whipplei can also cause skin lesions, such as subcutaneous nodules, erythema nodosum or vasculitis. This article reports the case of a 77-year-old female patient with erosive joint changes, persistently elevated serological inflammation markers and recurrent ulcerative lesions of the lower extremities, which were initially misdiagnosed as rheumatoid vasculitis. In cases of a clinically suspected infection with Tropheryma whipplei an early biopsy of the affected organ system is essential for the diagnosis.
30888472 Rheumatology practice in Japan: challenges and opportunities. 2019 Sep This article aims to and describes the characteristics of rheumatology practice in Japan, focusing on the medical environment for the treatment of rheumatoid arthritis (RA). In Japan, the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) has led to a significant paradigm shift in medical care; satisfactory safety outcomes have been demonstrated by periodic analysis, post-market surveillance and the development of guidelines via an industry-academia-government collaboration. Drug discontinuation is also considered an option, as well as medical economic analysis of any increase in the financial burden engendered by use of bDMARDs. Tocilizumab, a bDMARD established in Japan, was developed in an environment that facilitates translational research. The rheumatology community in Japan is expected to continue to develop novel therapies, while ensuring consistent quality of medical care despite limited healthcare resources.
31871338 Two Cases of High Tibial Osteotomy in Patients with Rheumatoid Arthritis Treated with Biol 2019 Dec High tibial osteotomy (HTO) procedure is generally contraindicated in rheumatoid arthritis (RA) patients because synovial inflammation may exacerbate joint damage post-surgery. The natural course of joint destruction in RA changed dramatically with new treatment strategies and the introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDs). We report the cases of two RA patients who underwent HTO and whose disease activities were well controlled by bDMARDs. Despite their short follow-up periods, they showed acceptable objective and subjective clinical results. We believe that the combination of bDMARDs and HTO can be indicated for selected RA patients before total knee arthroplasty.
27425844 Appearance of hindfoot valgus deformity and recurrence of hallux valgus in the very early 2019 Mar Control of rheumatoid arthritis (RA) disease activity is an important factor related to the development of hallux valgus (HV) deformity. Furthermore, if valgus hindfoot remains and/or appears after HV surgery, the affected foot is at risk of recurrence of HV deformity. We experienced a case suggesting the possibility that hindfoot valgus deformity appeared after HV surgery because of poor control of RA disease activity, and the HV deformity recurred in the very early period after surgery.
29409260 Resection or preservation of the metatarsal heads in rheumatoid forefoot surgery? A random 2019 Feb BACKGROUND: Despite impressive results of the pharmacological management of rheumatoid arthritis, still certain patients suffer from rheumatoid forefoot problems. Surgical treatment of these forefoot deformities can be an option. In literature no high-quality studies on this topic can be found. The goal of present study is to compare the results of a metatarsal head (MTH) resecting technique with a MTH preserving technique in the operative treatment of severe rheumatoid forefoot deformity. METHODS: Patients suffering from well-defined rheumatoid forefoot deformity were prospectively enrolled in three institutions. This non-blinded study had a randomised clinical design and eligible patients were randomly assigned to undergo either resection of preservation of the MTH. The primary outcome measure consisted of the AOFAS score. Secondary outcome measures were: the FFI, the VAS for pain and the SF-36. RESULTS: Twenty-three patients (10 in MTH preservation group) were included and analysed. After one year follow-up no significant differences in AOFAS score and additional outcome factors were found. A total of 10 complications in 23 patients were reported. CONCLUSIONS: This randomised clinical study did not show significant clinical difference between a MTH resecting and a preserving procedure in patients suffering from rheumatoid forefoot deformity. Both procedures resulted in considerable improvement of pain and activity scores.
31879000 [Increased expression of LC3 in peripheral blood mononuclear cells is related to disease s 2019 Nov Objective To detect the mRNA and protein expression of microtubule-associated protein 1 light chain 3 (LC3) in peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA), and to investigate its relationship with RA. Methods Twenty-two patients with RA and 16 healthy subjects with matching gender and age as controls were included in the study. PBMCs were isolated by density gradient centrifugation. The level of LC3 mRNA in PBMCs was detected by real-time fluorescent quantitative PCR. The protein level of LC3 in PBMCs was detected by Western blot analysis. The expression of LC3 protein in PBMCs was detected by immunofluorescence staining. Pearson analysis was used to analyze the correlation between LC3 expression and clinical parameters of RA patients. Results Compared with the normal control group, the levels of LC3 mRNA and protein in PBMCs of RA patients went up significantly, and the expression of LC3 significantly increased in PBMCs. The mRNA expression level of LC3 was obviously positively correlated with erythrocyte sedimentation rate (ESR, r=0.7480), 28 joint disease activity (DAS28, r=0.5016), C-reactive protein (CRP, r=0.6518), and rheumatoid factor (RF, r=0.7232). Conclusion The expression of LC3 is up-regulated in RA patients and is associated with ESR, DAS28, CRP and RF.
31521793 Inhibition of JAK/STAT signaling in rheumatologic disorders: The expanding spectrum. 2020 Mar Three Janus kinase (JAK) inhibitors, ruxolitinib, tofacitinib, and baricitinib, are currently approved by the FDA/EMA for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative rectocolitis. The inhibition of JAK/STAT signaling by these small molecules, downstream of several cytokine receptors, results in lower pro-inflammatory gene expression. Given the cytokine profiles observed in rheumatologic diseases, most of the recent therapeutic strategies target cytokines, either directly or through their receptors. Each cytokine receptor recruits a specific combination of JAKs to activate different programs in cells. The approved drugs are panJAK inhibitors, able to impede more than one pathway. These drugs are being tested in various rheumatologic disorders. At the same time, more specific molecules able to target one specific JAK are being developed. In this review, we describe the expanding spectrum of rheumatologic and autoimmune conditions for which JAK inhibition may represent new avenues in clinical practice.
31153827 Lipidoid-siRNA Nanoparticle-Mediated IL-1β Gene Silencing for Systemic Arthritis Therapy 2019 Aug 7 Interleukin-1 beta (IL-1β) plays a central role in the induction of rheumatoid arthritis (RA). In the present study, we demonstrated that lipidoid-polymer hybrid nanoparticle (FS14-NP) can efficiently deliver siRNA against IL-1β (siIL-1β) to macrophages and effectively suppress the pathogenesis of experimental arthritis induced by collagen antibody (CAIA mice). FS14-NP/siIL-1β achieved approximately 70% and 90% gene-silencing efficiency in the RAW 264.7 cell line and intraperitoneal macrophages, respectively. Intravenous administration of FS14-NP/siRNA led to rapid accumulation of siRNA in macrophages within the arthritic joints. Furthermore, FS14-NP/siIL-1β treatment lowered the expression of pro-inflammatory cytokines in arthritic joints and dramatically attenuated ankle swelling, bone erosion, and cartilage destruction. These results demonstrate that FS14-NP/siIL-1β may represent an effective therapy for systemic arthritis and other inflammatory disorders.
28795307 Sex, Symptom Severity, and Quality of Life in Rheumatology. 2019 Jun Inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) show a striking female predominance ranging from 3:1 in RA up to 9:1 in SLE. The background for those gender bias is not fully understood yet, but seems to be the result of a complex interaction between sex hormones, (epi-)genetics, and possibly even the composition of gut microbiota. Moreover, time of disease onset, the clinical phenotype including co-morbidities as well as the course of the diseases during life differ between genders. The patient's sex therefore plays an emerging role for individual therapy decisions and co-morbidity screening in rheumatologic care. Male lupus patients, for example, tend to show more severe features such as renal involvement, pleurisy, and serositis, when being compared to female patients. Among RA patients, women are more likely to acquire conditions like thyroid dysfunctions, fibromyalgia, and depression than their male counterparts. These examples emphasize the importance of the patient's gender for the clinical routine and the resulting implications for prevention and therapy. The present article is going to review potential causes for the female predominance of rheumatic diseases and will examine the gender's impact on the disease phenotype, symptom severity, co-morbidities, and quality of life. For reasons of scope, the focus will be on RA and SLE as two of the most important rheumatic diseases with a large socioeconomic impact on society due to their incidence as well as mortality.
31444262 Rheumatoid meningitis can present MRI findings that mimic chronic subdural haematoma. 2019 Aug 22 A 65-year-old woman with long-standing rheumatoid arthritis (RA) experienced a recurrent tingling sensation in her left arm followed by aphasia and a tingling sensation in her right arm. A subsequent imaging study showed bilateral subdural fluid accumulation and we initially diagnosed her with a transient ischaemic attack and chronic subdural haematoma (CSDH). The cerebral spinal fluid study revealed an inflammatory response without any indications of infection or malignant tumours. After a meningeal biopsy, we redefined the diagnosis to rheumatoid meningitis (RM), and the patient showed remarkable improvement with prednisolone administration. RM should be considered as an alternative diagnosis when examining central nervous system diseases in patients with RA, as RM presents a highly variable clinical picture with image findings similar to those of CSDH.
31921217 Effects of Methotrexate Alone or Combined With Arthritis-Related Biotherapies in an in vit 2019 Background: Methotrexate (MTX) at low dose is a key drug for rheumatoid arthritis (RA). MTX is widely used alone or combined with biologics or steroids. The aim was to study its effects on cytokine production using an in vitro model with synoviocytes interacting with peripheral blood mononuclear cells (PBMC) to reproduce the interactions in RA synovium. Methods: Activated-PBMC were co-cultured with RA synoviocytes during 48 h. A dose-response of MTX was tested and different biotherapies (Infliximab, Tocilizumab, Abatacept and Rituximab) were added alone or in combination with MTX. Cytokine production (IL-17, IL-6, IL-1β, IFN-γ, and IL-10) was measured by ELISA. These results were compared with those obtained with steroids. Results: MTX alone had a modest inhibitory effect on cytokine production compared to steroids. The most effective concentration was one of the lowest, 0.01 μg/ml, as for steroids. Infliximab was the most active biotherapy (p ≤ 0.05 for all cytokines) followed by Tocilizumab (p ≤ 0.05 for all cytokines except IL-6). Abatacept and Rituximab had a more restricted effect on cytokines (p ≤ 0.05 for IL-1β and IFN-γ). The combination MTX/biotherapies did not increase significantly the inhibition of cytokine production but some specific inhibitory effects were observed with Infliximab on IL-17 and IL-6, and with Abatacept and Rituximab on IL-1β. Conclusion: Low dose of MTX was at least as effective as high dose. The effects of the combination with biotherapies showed an important level of heterogeneity between the levels of some specific cytokines and the degree of inhibition with drugs.
30447739 Challenges in Implementing Treat-to-Target Strategies in Rheumatology. 2019 Feb Despite evidence that treat-to-target (TTT) approaches lead to better disease outcomes in RA, TTT is not widely implemented in rheumatology clinics in North America. This article discusses the barriers (including access to care, patient and physician factors, and systems issues) to implementing TTT in the clinic, and proposes possible solutions and future research directions.
31711542 High-quality cooperative research: studies that represent a triumph in the rheumatology co 2019 Nov 11 Over the past 20 years, the rheumatoid arthritis (RA) treatment landscape has been continuously evolving. A range of novel biologic agents, different from the conventional therapies, became available. However, some understandable concerns, such as long-term safety, accompanied their development. Over the years in rheumatology research, I aimed to broaden the knowledge of the new treatments of RA through real-word research, which proved to be valuable in providing important evidence to clinicians and enabling them to make informed treatment decisions. Nevertheless, many unanswered questions remain-it will be interesting to see how the research progresses over the next 20 years.
31797725 Radiotriquetral arthrodesis for rheumatoid wrist with flexor tendon rupture: A case report 2019 Sep Flexor tendon rupture in the wrist of patients with rheumatoid arthritis is a rare complication, and there is no standard treatment for the wrist joint. Here, we present the case of a rupture of the flexor digitorum profundus of the left index finger owing to a rheumatoid wrist. Plain radiography and computed tomography showed carpal collapse, especially lunate, and arthrosis between the capitate and lunate. For stability and mobility of the wrist and index finger, resection of the lunate and radiotriquetral (RT) arthrodesis using the distal ulna as a bone graft and arthrodesis of the distal interphalangeal joint of the index finger were performed. At 2 years postoperatively, her wrist was painless and stable on radiography without recurrence of tendon rupture, and the arc of motion of the dorsal-palmar flexion of the wrist joint was 125°. RT arthrodesis could be a surgical choice of "mobile" partial wrist arthrodesis.
31189868 [Use of Biologics and Home Visit by an Interdisciplinary Medical Care Team Led to the Impr 2019 May A woman in her 50s was diagnosed as having rheumatoid arthritis(RA)at another hospital. She refused treatment with biological therapy and had difficulty walking because of arthralgia. We formed a home-visit medical care team consisting of a physician, nurses, a physical therapist, and other medical professionals. Use of biologics, education on self-injection, and rehabilitation gradually improved her state. To support RA patients, a home-visit medical care team with the patient's cooperation and interdisciplinary professional work(IPW)would be important clinical methods.
30850234 'RA and the microbiome: do host genetic factors provide the link? 2019 May Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterised by painful synovium inflammation, bony erosions, immune activation and the circulation of autoantibodies. Despite recent advances in therapeutics enabling disease suppression, there is a considerable demand for alternative therapeutic strategies as well as optimising those available at present. The relatively low concordance rate between monozygotic twins, 20-30% contrasts with heritability estimates of ∼65%, indicating a substantive role of other risk factors in RA pathogenesis. There is established evidence that RA has an infective component to its aetiology. More recently, differences in the commensal microbiota in RA compared to controls have been identified. Studies have shown that the gut, oral and lung microbiota is different in new onset treatment naïve, and established RA patients, compared to controls. Key taxonomic associations are an increase in abundance of Porphyromonas gingivalis and Prevotella copri in RA patients, compared to healthy controls. Host genetics may provide the link between disease and the microbiome. Genetic influence may be mediated by the host immune system; a differential response to RA associated taxa is suggested. The gut microbiome contains elements which are as much as 30% heritable. A better understanding of the influence of host genetics will shed light onto the role of the microbiome in RA. Here we review the role of the microbiome in RA through the lens of host genetics, and consider future research areas addressing microbiome study design and bioinformatics approaches.
31530023 Radiographic changes in TMJ in relation to serology and disease activity in RA patients. 2020 Jan OBJECTIVES: This study was undertaken as an attempt to assess radiographic temporomandibular joint (TMJ) changes in relation to rheumatoid factor (RF), anticitrullinated protein (ACCP) antibodies and disease activity score 28 (DAS28) in rheumatoid arthritis (RA) patients to find the best predictor of rheumatoid affection of the TMJ with the ultimate goal of maintaining TMJ function and preventing joint damage. METHODS: 20 Rheumatoid Arthritis patients as well as 20 volunteers were included in this study. RA group were assessed for RF, ACCP, DAS28. Both groups were assessed by CBCT for TMJ dimensions and radiographic osteoarthritic changes. All data were statistically analyzed. RESULTS: Rheumatoid Arthritis group showed significantly less condylar height and more radiographic osteoarthritic changes than the control group. RF showed no significant correlation with either TMJ measurements or TMJ radiographic osteoarthritic changes. ACCP showed significant inverse correlation with condylar height and anteroposterior (AP) dimensions, but non-significant relation with mediolateral dimension and radiographic osteoarthritic changes. DAS28 showed significant inverse correlation with condylar AP and mediolateral dimensions. It also showed significant correlation with flattening of the TMJ condylar head and flattening of the articular fossa. Patients with high and moderate disease activity showed significantly smaller AP TMJ dimension than patients with low disease activity. Disease activity showed statistically significant direct correlation with all osteoarthritic changes except for erosions of the glenoid fossa and condyle. CONCLUSION: Disease Activity Score28 score and disease activity are strong indicators of TMJ affection in RA patients when compared to RF and ACCP. ACCP is a better indicator of changes in condylar measurements than TMJ osteoarthritic changes. While RF is the least efficient indicator of TMJ involvement in RA patients.
31443729 Investigating causal mechanisms in randomised controlled trials. 2019 Aug 23 INTRODUCTION: In some randomised trials, the primary interest is in the mechanisms by which an intervention exerts its effects on health outcomes. That is, clinicians and policy-makers may be interested in how the intervention works (or why it does not work) through hypothesised causal mechanisms. In this article, we highlight the value of understanding causal mechanisms in randomised trials by applying causal mediation analysis to two randomised trials of complex interventions. MAIN BODY: In the first example, we examine a potential mechanism by which an exercise programme for rheumatoid arthritis of the hand could improve hand function. In the second example, we explore why a rehabilitation programme for ankle fractures failed to improve lower-limb function through hypothesised mechanisms. We outline critical assumptions that are required for making valid causal inferences from these analyses, and provide results of sensitivity analyses that are used to assess the degree to which the estimated causal mediation effects could have been biased by residual confounding. CONCLUSION: This paper demonstrates how the application of causal mediation analyses to randomised trials can identify the mechanisms by which complex interventions exert their effects. We discuss methodological issues and assumptions that should be considered when mediation analyses of randomised trials are used to inform clinical practice and policy decisions.
30503725 Combined synovectomy and extensor carpi radialis longus transfer to realign and stabilise 2019 May BACKGROUND: In patients with rheumatoid arthritis, the surgical treatment of wrist lesions relies on synovectomy combined with stabilisation and realignment of the carpal bones. The objective of this study was to evaluate the outcomes and define the indications of extensor carpi radialis longus (ECRL) transfer to the extensor carpi ulnaris (ECU) as described by Clayton and Ferlic. HYPOTHESIS: ECRL-to-ECU transfer combined with synovectomy can prevent the development and/or progression of rheumatoid deformities at the wrist. MATERIAL AND METHODS: A retrospective observational study was performed in 16 wrists. The following data were collected before and after surgery: pain, synovitis, range of motion, carpal height, ulnar translocation and radial deviation of the carpal bones, and Larsen's grade of the radio-carpal and mid-carpal joints. RESULTS: After a mean follow-up of 42.5 months after surgery, pain relief was noted in 14 cases and synovitis resolution in 10 cases. Mean mobility gains were 19.7° in extension and 5.7° in flexion. The radiographs showed a decrease in carpal height, whereas radial deviation and ulnar translocation were unchanged. No change was seen in the radio-carpal and mid-carpal joint lines. In the 3 wrists that required mid-carpal arthrodesis due to advanced disease before surgery, the radio-carpal joint line was unchanged and outcomes were the same as in the overall population. DISCUSSION: ECRL-to-ECU transfer combined with synovectomy provides pain relief and prevents radio-carpal destabilisation. The main indication of ECRL transfer is reducible radial deviation and ulnar translocation. ECRL is also indicated in combination with mid-carpal arthrodesis in the small minority of patients who have predominant mid-carpal involvement with a Larsen grade greater than 2. LEVEL OF EVIDENCE: IV, retrospective observational study.