Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25483258 Demographic and clinical features of systemic sclerosis patients with anti-RNA polymerase 2015 Feb Anti-RNA polymerase III antibody (RNAP) is primarily detected in diffuse cutaneous type systemic sclerosis (dcSSc) patients and strongly associated with renal crisis. Additionally, there has been increasing evidence that cancer in SSc patients is associated with RNAP. The aim of this study was to examine the demographic and clinical features of SSc patients with RNAP. Among 246 SSc patients, 5.7% were positive for RNAP, 20.7% were positive for anti-topoisomerase I antibody (Topo I) alone and 39.4% were positive for anticentromere antibody (ACA) alone. The modified Rodnan total skin score (mRTSS) in SSc patients with RNAP (19.1 ± 2.6) was significantly higher than those in SSc patients with Topo I (11.5 ± 1.1) and patients with ACA (4.4 ± 0.4). Furthermore, among SSc patients with RNAP, the levels of RNAP were positively correlated with mRTSS. Renal crisis is also significantly more prevalent in SSc patients with RNAP than patients without RNAP. Male sex, dcSSc subtype, digital vasculopathy, including digital ulcers and acro-osteolysis, interstitial lung disease and rheumatoid arthritis complications were prevalent in SSc patients with RNAP and patients with Topo-I. Primary biliary cirrhosis and Sjögren's syndrome were more in SSc patients with RNAP and patients with ACA compared with patients with Topo 1. No significant difference in the frequency of complications, including Raynaud's phenomenon, pulmonary artery hypertension and malignancy was observed between the three groups. Thus, measurement of RNAP in SSc patients is useful for the diagnosis and risk stratification of severe manifestation, such as renal crisis and severe skin sclerosis.
26550776 Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. 2016 Feb 2 BACKGROUND: Silicone gel breast implants were removed from the U.S. market for cosmetic use in 1992 owing to safety concerns. They were reintroduced in 2006, with a call for improved surveillance of clinical outcomes. PURPOSE: To systematically review the literature regarding specific long-term health outcomes in women with silicone gel breast implants, including cancer; connective tissue, rheumatologic, and autoimmune diseases; neurologic diseases; reproductive issues, including lactation; offspring issues; and mental health issues (depression and suicide). DATA SOURCES: MEDLINE, EMBASE, and Ovid Healthstar (inception through 30 June 2015), and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the first quarter of 2015). STUDY SELECTION: 4 researchers double-screened articles for longitudinal studies that compared women with and without breast implants and reported long-term health outcomes of interest. DATA EXTRACTION: 4 researchers extracted data on participant and implant characteristics, analytic methods, and results. DATA SYNTHESIS: 32 studies (in 58 publications) met eligibility criteria. Random-effects model meta-analyses of effect sizes were conducted when feasible. For most outcomes, there was at most only a single adequately adjusted study, which usually found no significant associations. There were possible associations with decreased risk for primary breast and endometrial cancers and increased risks for lung cancer, rheumatoid arthritis, Sjögren syndrome, and Raynaud syndrome. Evidence on breast implants and other outcomes either was limited or did not exist. LIMITATION: The evidence was most frequently not specific to silicone gel implants, and studies were rarely adequately adjusted for potential confounders. CONCLUSION: The evidence remains inconclusive about any association between silicone gel implants and long-term health outcomes. Better evidence is needed from existing large studies, which can be reanalyzed to clarify the strength of associations between silicone gel implants and health outcomes. PRIMARY FUNDING SOURCE: The Plastic Surgery Foundation.
27055443 C5 nerve palsy after posterior reconstruction surgery: predictive risk factors of the inci 2016 Jul PURPOSE: It has been reported that the incidence of post-operative segmental nerve palsy, such as C5 palsy, is higher in posterior reconstruction surgery than in conventional laminoplasty. Correction of kyphosis may be related to such a complication. The aim of this study was to elucidate the risk factors of the incidence of post-operative C5 palsy, and the critical range of sagittal realignment in posterior instrumentation surgery. METHODS: Eighty-eight patients (mean age 64.0 years) were involved. The types of the disease were; 33 spondylosis with kyphosis, 27 rheumatoid arthritis, 17 athetoid cerebral palsy and 11 others. The patients were divided into two groups; Group P: patients with post-operative C5 palsy, and Group NP: patients without C5 palsy. The correction angle of kyphosis, and pre-operative diameter of C4/5 foramen on CT were evaluated between the two groups. Multivariate logistic regression analysis was used to determine the critical range of realignment and the risk factors affecting the incidence of post-operative C5 palsy. RESULTS: Seventeen (19.3 %) of the 88 patients developed C5 palsy. The correction angle of kyphosis in Group P (15.7°) was significantly larger than that in Group NP (4.5°). In Group P, pre-operative diameters of intervertebral foramen at C4/5 (3.2 mm) were significantly smaller than those in Group NP (4.1 mm). The multivariate analysis demonstrated that the risk factors were the correction angle and pre-operative diameter of the C4/5 intervertebral foramen. The logistic regression model showed a correction angle exceeding 20° was critical for developing the palsy when C4/5 foraminal diameter reaches 4.1 mm, and there is a higher risk when the C4/5 foraminal diameter is less than 2.7 mm regardless of any correction. CONCLUSIONS: This study has indicated the risk factors of post-operative C5 palsy and the critical range of realignment of the cervical spine after posterior instrumented surgery.
27255529 Could we use a lower dose of rituximab to treat rheumatoid arthritis in clinical practice: 2016 Jun 2 The CERERRA database provides evidence that low-dose rituximab performs as well as the conventional dose in the real world, thus highlighting the possible pharmacoeconomic impact. In clinical trials, it has been shown that rituximab 500 mg twice, performs as well as 1 g twice, 2 weeks apart, in terms of the American College of Rheumatology (ACR)20 and ACR50, but not the ACR70. The choice should always be made after considering that the IMAGE trial has demonstrated similar radiographic progression after the first 6 months, but with less control, with low-dose rituximab in the first 6 months. A possible alternative can be hypothesized.
25807374 Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and 2015 Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through _3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts.
27311837 TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream duri 2017 Feb OBJECTIVES: The imbalance between effector and regulatory T (Treg) cells is crucial in the pathogenesis of autoimmune arthritis. Immune responses are often investigated in the blood because of its accessibility, but circulating lymphocytes are not representative of those found in inflamed tissues. This disconnect hinders our understanding of the mechanisms underlying disease. Our goal was to identify Treg cells implicated in autoimmunity at the inflamed joints, and also readily detectable in the blood upon recirculation. METHODS: We compared Treg cells of patients with juvenile idiopathic arthritis responding or not to therapy by using: (i) T cell receptor (TCR) sequencing, to identify clonotypes shared between blood and synovial fluid; (ii) FOXP3 Treg cell-specific demethylated region DNA methylation assays, to investigate their stability and (iii) flow cytometry and suppression assays to probe their tolerogenic functions. RESULTS: We found a subset of synovial Treg cells that recirculated into the bloodstream of patients with juvenile idiopathic and adult rheumatoid arthritis. These inflammation-associated (ia)Treg cells, but not other blood Treg cells, expanded during active disease and proliferated in response to their cognate antigens. Despite the typical inflammatory-skewed balance of immune mechanisms in arthritis, iaTreg cells were stably committed to the regulatory lineage and fully suppressive. A fraction of iaTreg clonotypes were in common with pathogenic effector T cells. CONCLUSIONS: Using an innovative antigen-agnostic approach, we uncovered a population of bona fide synovial Treg cells readily accessible from the blood and selectively expanding during active disease, paving the way to non-invasive diagnostics and better understanding of the pathogenesis of autoimmunity.
26341976 Osteopontin in Immune-mediated Diseases. 2015 Dec Since its initial identification as one of the genes most highly upregulated upon T-cell activation, osteopontin (or Eta-1, as it was designated then) has been demonstrated to have many roles in the regulation of the immune response on multiple levels. It contributes to the development of immune-mediated and inflammatory diseases, and it regulates the host response to infection. In some cases, the mechanisms of these effects have been elucidated, while other mechanistic functions of the protein remain obscure. The protein itself makes these analyses complex, since it binds to a series of different integrins, and in addition to its classically secreted form, an intracellular form of osteopontin has been identified, which participates in several aspects of immune regulation. In this review, we focus on the role of osteopontin in a series of immune-related diseases, particularly those where significant advances have been made in recent years: multiple sclerosis, rheumatoid arthritis, lupus and related diseases, Sjögren's disease, colitis, and 1 area of inflammatory pathology, alcoholic and nonalcoholic liver diseases. A recurring theme in these diseases is a link between osteopontin and pathogenic T cells, particularly T helper 17 cells, where osteopontin produced by dendritic cells supports IL-17 expression, contributing to pathology. In addition, a role for osteopontin in B-cell differentiation is becoming clear. In general, osteopontin contributes to pathology in these diseases, but there are examples where it has a protective role; deciphering the mechanisms underlying these differences and the specific receptors for osteopontin will be a research challenge for the future. Aside from its newly discovered role in the development of Sjögren's disease, the role of osteopontin in inflammatory conditions in the oral cavity is still poorly understood. Elucidation of this role will be of interest.
25131613 Thoracic manifestations of connective tissue diseases. 2015 Jan Connective tissue diseases (CTDs) comprise several immunologic systemic disorders, each of which associated with a particular set of clinical manifestations and autoimmune profile. CTDs may cause numerous thoracic abnormalities, which vary in frequency and pattern according to the underlying disorder. The CTDs that most commonly involve the respiratory system are progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, polymyositis, dermatomyositis, and mixed connective tissue disease. Pulmonary abnormalities in this group of patients may result from CTD-related lung disease or treatment complications, namely drug toxicity and opportunistic infections. The most important thoracic manifestations of CTDs are interstitial lung disease and pulmonary arterial hypertension, with nonspecific interstitial pneumonia being the most common pattern of interstitial lung disease. High-resolution computed tomography is a valuable tool in the initial evaluation and follow-up of patients with CTDs. As such, general knowledge of the most common high-resolution computed tomographic features of CTD-related lung disease allows the radiologist to contribute to better patient management.
26479340 Evaluation of anti-inflammatory potential of the ethanolic extract of the Saussurea lappa 2016 Jan BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by polyarticular symmetrical arthritis. The prevalence of RA is consistent worldwide, affecting about 0.5%-1.0% of the population. The aim of this study was to investigate whether Saussurea lappa (costus) could ameliorate adjuvant arthritis (AA) in the rat for 21 days. METHODS: Animals were divided into eight groups (n=5/group). Group 1 acted as control, group 2 presented the AA rats (positive control), and groups 3, 4, and 5 were treated with different doses of S. lappa (200, 400, and 600 mg/kg, respectively), whereas groups 6, 7, and 8 were AA rats and orally administered with S. lappa (200, 400, and 600 mg/kg, respectively). The changes caused by chronic inflammation were evaluated through the measurement of ankle circumference (AC). Serum C-reactive protein (CRP), interleukins (IL-1β and IL-6), tumor necrosis factor α (TNF-α), total oxidative capacity (TOC), and total antioxidant capacity (TAC) were determined. RESULTS: Saussurea lappa dose-dependently alleviated the severity of the disease based on the reduction in AC and on the clinical scores of the histological study. Histopathological examination proved that S. lappa decreased the infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction. Saussurea lappa reduced the serum levels of CRP, TNF-α, IL-1β, and IL-6, reduced the TOC, and improved the TAC as compared with AA rats. CONCLUSIONS: The S. lappa extract has potentially useful anti-arthritic activity as well as improves the immune and antioxidant responses of adjuvant-induced monoarthritis in rats.
26026696 Functional limitations in functional somatic syndromes and well-defined medical diseases. 2015 Aug OBJECTIVE: Functional somatic syndromes (FSS), defined as physical syndromes without known underlying organic pathology, are sometimes regarded as less serious conditions than well-defined medical diseases (MD). The aims of this study were to evaluate functional limitations in FSS, and to compare the results to MD patients with the same core symptoms. METHODS: This study was performed in 89,585 participants (age: 44.4±12.4 years, 58.5% female) of the general-population cohort LifeLines. Quality of Life (QoL) and work participation were examined as indicators of functional limitations. QoL was assessed with two summary scales of the RAND-36: the physical component summary (PCS) and the mental component summary (MCS). Work participation was assessed with a self-reported questionnaire. QoL and work participation were compared between FSS and MD patients, using Chi-squared tests and ANCOVA-analyses, adjusted for age, sex, educational level, and mental disorders. RESULTS: Of the participants, 11.0% (n=9861) reported a FSS, and 2.7% (n=2395) reported a MD. Total QoL, PCS and MCS were significantly lower in all separate FSS and MD compared to controls (P≤.001). Clinically relevant differences in QoL were found between chronic fatigue syndrome and multiple sclerosis patients, and between fibromyalgia syndrome and rheumatoid arthritis patients. Compared to controls, FSS and MD patients reported a comparably reduced working percentage, increased sick absence, early retirement due to health-related reasons, and disability percentage (P≤.001). CONCLUSION: Functional limitations in FSS patients are common, and as severe as those in patients with MD when looking at QoL and work participation, emphasizing that FSS are serious health conditions.
26463246 Biologic Therapy in Inflammatory and Immunomediated Arthritis: Safety Profile. 2016 The increasing insights into the pathogenetic mechanisms of inflammatory autoimmune arthritis and the development of innovative systems of industrial production have led to discover molecules that are able to target/block other molecules that play a critical role in the immune system functioning, and that have been introduced in clinical practice alone and/or in addiction with other "old" disease-modifying anti-rheumatic drugs. For this reason, such drugs are currently known as "biological drugs" and include molecules that induce the immunosuppression acting on several immune pathways. However, though the biological drugs have been employed from more than a decade, there still exist some drawbacks of their use, in particular about the high costs of this therapy and their overall safety, including the route of administration for the intravenous use. In this review we provide an update on the correct use and current therapeutic indications of such drugs, including some of the new biologic therapies that will be soon available for the clinical use, focusing on these biological drugs: • Tumor necrosis factor-alpha (TNF-alpha) inhibitors (adalimumab, certolizumab-pegol, etanercept, golimumab and infliximab); • The T cell co-stimulation inhibitor, abatacept; • The anti-CD20 receptor monoclonal B cell agent, rituximab; • The interlukin-6 (IL-6) receptor-blocking monoclonal antibody, tocilizumab; • The interlukin-1 (IL-1) inhibitor, anakinra; • The interlukin-IL17 (IL-17) pathway inhibitors (ustekinumab, secukinumab, brodalumab).
27585690 Cardiovascular Outcomes Associated with Lowering Low-density Lipoprotein Cholesterol in Rh 2016 Nov OBJECTIVE: To examine the associations between lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular (CV) outcomes among patients with rheumatoid arthritis (RA) and patients without it. METHODS: Adult patients with RA and 2 age- and sex-matched control cohorts [RA plus general controls (RA/GN), RA plus osteoarthritis (OA) controls (RA/OA)] were identified between January 1, 2007, and December 31, 2011. Patients with a diagnosis of hyperlipidemia who initiated statin therapy without prior CV events were included. Multivariable Cox proportional hazard analyses were used. RESULTS: The study identified 1522 patients with RA with 6511 general controls (RA/GN cohort); and 1746 patients with RA with 2554 OA controls (RA/OA cohort). During followup, mean (SD) LDL-C (mg/dl) was 96.8 (32.7) for RA, 100.1 (35.1) for general controls, and 99.1 (34.3) for OA. The relationship between lowering LDL-C and CV outcomes was similar for both RA and non-RA controls (p for interaction = 0.852 in RA/GN cohort, and p = 0.610 in RA/OA cohort). After adjusting for baseline CV risk factors, lowering LDL-C was associated with a 29%-50% lower risk of CV events (HR [95% CI] = 0.71 [0.57-0.89] in RA/GN, 0.50 [0.43-0.58] in RA/OA). Subgroup analyses showed that lowering LDL-C was associated with a similar degree of reduction of CV events in RA and non-RA controls (HR of 0.67-0.68 for RA, 0.72 for general controls, 0.76 for OA controls). CONCLUSION: Lowering LDL-C levels was associated with reduced CV events. The relationship between lowering LDL-C and CV outcomes in RA was similar to the relationship found in matched general and OA controls.
25165034 Cell cycle regulation therapy combined with cytokine blockade enhances antiarthritic effec 2016 Jan OBJECTIVE: Biological disease-modifying antirheumatic drugs (DMARDs) that inhibit aberrant immune reactions in rheumatoid arthritis (RA) cannot induce complete remission in all patients. Combination therapies using two biological DMARDs have failed to exert additive effects and increased serious infections. We have found that cell cycle inhibition of synovial fibroblasts with cyclin-dependent kinase (CDK) inhibitors ameliorated the disease in animal models of RA without attenuating acquired immunity. The objective of this study was to determine whether a clinically well-tolerated selective CDK 4/6 inhibitor (CDKI), palbociclib, is effective and whether combination with cytokine blockers acts additively without enhancing immune suppression. METHODS: The effects of CDKI on haematopoiesis and physical and behavioural findings in mice were evaluated. Mice with collagen-induced arthritis (CIA) were treated with CDKI, etanercept or anti-interleukin (IL)-6 receptor antibody (MR16-1) alone or with a combination of CDKI with etanercept or MR16-1. Their clinical, histological and radiographic scores, serum anti-(type II collagen (CII)) antibody levels and proliferative responses of lymph node cells to CII were determined. RESULTS: Although CDKI induced marginal myelosuppression, it was well tolerated and ameliorated CIA dose-dependently. The combinations of low-dose CDKI and either tumour necrosis factor-α or IL-6 blocker enhanced the antiarthritic effects additively. The addition of CDKI to either cytokine blocker did not affect the levels of anti-CII antibodies and proliferative responses of lymphocytes to CII. CONCLUSIONS: A clinically well-tolerated CDK4/6 inhibitor exerted antiarthritic effects in this mouse model. By combining therapeutic agents targeting immune reaction and synovial proliferation, we have demonstrated for the first time that two molecular targeting treatments act additively and may not increase immune suppression.
25834206 Yoga in Sedentary Adults with Arthritis: Effects of a Randomized Controlled Pragmatic Tria 2015 Jul OBJECTIVE: To evaluate the effect of Integral-based hatha yoga in sedentary people with arthritis. METHODS: There were 75 sedentary adults aged 18+ years with rheumatoid arthritis (RA) or knee osteoarthritis randomly assigned to 8 weeks of yoga (two 60-min classes and 1 home practice/wk) or waitlist. Poses were modified for individual needs. The primary endpoint was physical health [Medical Outcomes Study Short Form-36 (SF-36) physical component summary (PCS)] adjusted for baseline; exploratory adjusted outcomes included fitness, mood, stress, self-efficacy, SF-36 health-related quality of life (HRQOL), and RA disease activity. In everyone completing yoga, we explored longterm effects at 9 months. RESULTS: Participants were mostly female (96%), white (55%), and college-educated (51%), with a mean (SD) age of 52 years (12 yrs). Average disease duration was 9 years and 49% had RA. At 8 weeks, yoga was associated with significantly higher PCS (6.5, 95% CI 2.0-10.7), walking capacity (125 m, 95% CI 15-235), positive affect (5.2, 95% CI 1.4-8.9), and lower Center for Epidemiologic Studies Depression Scale (-3.0, 95% CI -4.8 - -1.3). Significant improvements (p < 0.05) were evident in SF-36 role physical, pain, general health, vitality, and mental health scales. Balance, grip strength, and flexibility were similar between groups. Twenty-two out of 28 in the waitlist group completed yoga. Among all yoga participants, significant (p < 0.05) improvements were observed in mean PCS, flexibility, 6-min walk, and all psychological and most HRQOL domains at 8 weeks with most still evident 9 months later. Of 7 adverse events, none were associated with yoga. CONCLUSION: Preliminary evidence suggests yoga may help sedentary individuals with arthritis safely increase physical activity, and improve physical and psychological health and HRQOL. Clinical Trials NCT00349869.
25744772 Predictors of mortality in patients with rheumatoid arthritis in Lithuania: Data from a co 2015 BACKGROUND AND OBJECTIVE: Increased mortality and shorter survival among rheumatoid arthritis (RA) patients are recognized but not fully explained. This cohort study aimed to identify predictors of mortality among RA patients at a tertiary clinical setting. MATERIALS AND METHODS: Patients with RA were recruited during 1998-2003 and followed up until April 1, 2012, or death whichever happened first. Baseline variables included sociodemographic and disease characteristics, and comorbidities. Cox regression and hazard risk (HR) were computed to estimate risks for mortality. RESULTS: One hundred ninety-one patients were included into the study, 186 patients were eligible for the analysis and of these 131 patients (70.4%) completed the entire period of followed-up while 55 patients (29.6%) died. The average follow up period was equivalent to 9.24 year per person. A Cox regression model identified four major factors having an impact on survival. History of a stroke at baseline was identified as a major factor (HR=5.33; 95% CI, 2.13-13.32). Statistically significant risk factors were also age over 50 years (HR=4.59; 95% CI, 2.04-10.30); education less than 11 years (HR=3.3; 95% CI, 1.72-6.33) and angina pectoris (HR=1.98; 95% CI, 1.03-3.80). CONCLUSIONS: Higher age, lower education and cardiovascular comorbidities were identified as predictors of mortality in this prospective cohort study while disease-related variables were not independent predictors of mortality.
25915570 Treatment with anti-C5aR mAb leads to early-onset clinical and mechanistic effects in the 2015 Blockade of the complement cascade at the C5a/C5a receptor (C5aR)-axis is believed to be an attractive treatment avenue in rheumatoid arthritis (RA). However, the effects of such interventions during the early phases of arthritis remain to be clarified. In this study we use the murine delayed-type hypersensitivity arthritis (DTHA) model to study the very early effects of a blocking, non-depleting anti-C5aR mAb on joint inflammation with treatment synchronised with disease onset, an approach not previously described. The DTHA model is a single-paw inflammatory arthritis model characterised by synchronised and rapid disease onset driven by T-cells, immune complexes and neutrophils. We show that a reduction in paw swelling, bone erosion, cartilage destruction, synovitis and new bone formation is apparent as little as 60 h after administration of a single dose of a blocking, non-depleting anti-mouse C5aR mAb. Importantly, infiltration of neutrophils into the joint and synovium is also reduced following a single dose, demonstrating that C5aR signalling during the early stage of arthritis regulates neutrophil infiltration and activation. Furthermore, the number of T-cells in circulation and in the draining popliteal lymph node is also reduced following a single dose of anti-C5aR, suggesting that modulation of the C5a/C5aR axis results in effects on the T cell compartment in inflammatory arthritis. In summary, these data demonstrate that blockade of C5aR leads to rapid and significant effects on arthritic disease development in a DTHA model strengthening the rationale of C5aR-blockade as a treatment strategy for RA, especially during the early stages of arthritis flare.
26973329 Synovial mesenchymal stem cells from osteo- or rheumatoid arthritis joints exhibit good po 2016 Aug OBJECTIVE: To assess whether synovial mesenchymal stem cells (SMSCs) from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) can be used as an alternative cell source for cartilage repair using allogenic tissue engineered construct (TEC). METHODS: Twenty-five patients (17 female, average age 61.8 years) were divided according to their pathology (control trauma group; N = 6, OA group; N = 6) and RA patients were subdivided into two groups to evaluate the impact of biologics in accordance with whether treated with biologics [Bio(+)RA; N = 7] or not [Bio(-)RA; N = 6]. We compared the following characteristics among these groups: (1) The cell proliferation capacity of SMSCs; (2) The influence of passage number on features of SMSCs; (3) The weight and volume of TEC from the same number of SMSCs; (4) Inflammatory cytokine gene expressions levels of TEC; (5) The chondrogenic potential of TEC; and (6) Osteochondral repair using TEC in athymic nude rats. RESULTS: SMSCs from the four groups exhibited equivalent features in the above evaluation items. In in vivo studies, the TEC-treated repair tissues for all groups exhibited significantly better outcomes than those for the untreated group and no significant differences among the four TEC groups. CONCLUSION: SMSCs from OA or RA patients are no less appropriate for repairing cartilage than those from trauma patients and thus, may be an effective source for allogenic cell-based cartilage repair.
25433041 Predictors of satisfactory improvements in pain for patients with early rheumatoid arthrit 2015 Jun OBJECTIVE: The aim of this study was to identify baseline predictors of achieving patient-perceived satisfactory improvement (PPSI) in pain after 6 months of treat to target in patients with early RA. METHODS: Baseline and 6 month data were used from patients included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study. Simple and multivariable logistic regression analyses were used to identify significant predictors of achieving an absolute improvement of 30 mm or a relative improvement of 50% on a visual analogue scale for pain. RESULTS: At 6 months, 125 of 209 patients (59.8%) achieved an absolute PPSI and 130 patients (62.2%) achieved a relative PPSI in pain. Controlling for baseline pain, having symmetrical arthritis was the strongest independent predictor of achieving an absolute [odds ratio (OR) 3.17, P = 0.03] or relative (OR 3.44, P = 0.01) PPSI. Additionally, anti-CCP positivity (OR 2.04, P = 0.04) and having ≤12 tender joints (OR 0.29, P = 0.01) were predictive of achieving a relative PPSI. The total explained variance of baseline predictors was 30% for absolute and 18% for relative improvements, respectively. CONCLUSION: Symmetrical joint involvement, anti-CCP positivity and fewer tender joints at baseline are prognostic signs for achieving satisfactory improvement in pain after 6 months of treat to target in patients with early RA.
26759211 [An investigation of sleep disturbance and related factors in rheumatoid arthritis patient 2015 Nov OBJECTIVE: To explore the characteristics of sleep disturbance and its related factors in patients with rheumatoid arthritis (RA). METHODS: A total of 71 patients with RA in Department of Rheumatology Huaxi Hospital have completed the following questionnaires, including Pittsburgh sleeping quality index (PSQI), visual analogue scale (VAS), disease activity score in 28 joints (DAS28), health assessment questionnaire(HAQ), hospital anxiety and depression scale (HADS), fatigue severity scale (FSS) and a self-designed general status questionnaire. RESULTS: The prevalence of sleep disturbance was 42.3% (30/71) in rheumatoid arthritis patients (68.4%). The scores of DAS28, VAS, PSQI, HAQ, FSS and HADS in patients with sleep disturbance were significantly higher than those in patients with good sleep, which were respectively 3.90±1.12 vs 2.92±1.92, (5.03±2.63) scores vs (2.41±1.84) scores, (10.87±2.42) scores vs (4.29±1.85) scores, 3.0(0.0,7.0) scores vs 2.0 (0.5, 4.0) scores, (39.17±14.02) scores vs (29.63±16.12) scores, (14.50±7.77) scores vs (9.49±6.57) scores (P<0.05 in all scales). According to the results of Pearson correlation analysis, PSQI had significantly positive correlation with DAS28 (r=0.462, P<0.01), VAS (r=0.556, P<0.01), HAQ (r=0.360, P<0.01), FSS (r=0.420, P<0.01) and HADS (r=0.447, P<0.01) respectively. The logistic regression analysis indicated that VAS was a predictor for poor sleep quality (P<0.01). The patients receiving biological agents had significantly (P<0.05) lower scores of DAS28 (2.86±1.39 vs 3.52±1.10), PSQI [(5.90±4.24) scores vs (8.53±3.78) scores], VAS (2.15±2.30 vs 4.05±2.46), HAQ [0.0 (0.0, 2.0) scores vs 3.0 (0.0, 6.0) scores] compared to those taking oral drugs. CONCLUSION: High prevalence of sleep disturbance in patients with RA is noted, which indirectly influences the activity of disease, quality of life, depression, fatigue and other physical and mental health. Biological agents can partly improve the sleep disturbance and functional status.
26757209 Cardiovascular Comorbidities Relate More than Others with Disease Activity in Rheumatoid A 2016 OBJECTIVES: To explore the influence of comorbidities on clinical outcomes and disease activity in rheumatoid arthritis (RA). METHODS: In patients included in the cross-sectional observational multicenter international study COMORA, demographics, disease characteristics and comorbidities (hypertension, diabetes, hyperlipidemia, renal failure, ischemic heart disease, stroke, cancer, gastro-intestinal ulcers, hepatitis, depression, chronic pulmonary disease, obesity) were collected. Multivariable linear regression models explored the relationship between each comorbidity and disease activity measures: 28-swollen joint count (SJC), 28-tender joint count (TJC), erythrocyte sedimentation rate (ESR), patient's and physician's global assessment (PtGA, PhGA), patient reported fatigue and 28-Disease Activity Score (DAS28). Results are expressed as mean difference (MD) adjusted for the main confounders (age, gender, disease characteristics and treatment). RESULTS: A total of 3,920 patients were included: age (mean ±SD) 56.27 ±13.03 yrs, female 81.65%, disease duration median 7.08 yrs (IQR 2.97-13.27), DAS28 (mean ±SD) 3.74 ± 1.55. Patients with diabetes had more swollen and tender joints and worse PtGA and PhGA (MD +1.06, +0.93, +0.53 and +0.54, respectively). Patients with hyperlipidemia had a lower number of swollen and tender joints, lower ESR and better PtGA and PhGA (MD -0.77, -0.56, -3.56, -0.31 and -0.35, respectively). Patients with history of ischemic heart disease and obese patients had more tender joints (MD +1.27 and +1.07) and higher ESR levels (MD +5.64 and +5.20). DAS28 is influenced exclusively by cardiovascular comorbidities, in particular diabetes, hyperlipidemia, ischemic heart disease and obesity. CONCLUSIONS: Cardiovascular comorbidities relate more than others with disease activity in RA. Diabetes and hyperlipidemia in particular seem associated with higher and lower disease activity respectively influencing almost all considered outcomes, suggesting a special importance of this pattern of comorbidities in disease activity assessment and clinical management.