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

ID PMID Title PublicationDate abstract
29724731 Exposure to passive smoking and rheumatoid arthritis risk: results from the Swedish EIRA s 2018 Jul INTRODUCTION: Smoking has consistently been associated with increased risk of developing rheumatoid arthritis (RA). The aim of this study was to estimate the influence of passive smoking on the risk of developing anti-cyclic citrullinated peptide antibodies (ACPA)-positive and ACPA-negative RA. METHODS: A population-based case-control study using incident cases of RA was performed in Sweden, and the study population in this report was restricted to include never-smokers (589 cases, 1764 controls). The incidence of RA among never-smokers who had been exposed to passive smoking was compared with that of never-smokers who had never been exposed, by calculating the OR with a 95% CI employing logistic regression. RESULTS: No association was observed between exposure to passive smoking and RA risk (OR 1.0, 95% CI 0.8 to 1.2 for ACPA-positive RA, and OR 0.9, 95% CI 0.7 to 1.2, for ACPA-negative RA). No suggestion of a trend between duration of passive smoking and RA risk was observed. DISCUSSIONS: No association was observed between exposure to passive smoking and RA risk, which may be explained by a threshold below which no association between smoke exposure and RA occurs.
30132091 Upregulation of miR-221/222 expression in rheumatoid arthritis (RA) patients: correlation 2019 Feb miRNAs are noncoding RNA that play a critical role as fine regulators of gene expression at the posttranscriptional level within cells in numerous autoimmune diseases. miR-221/222 play a role in cancer by regulating cell proliferation, invasion and apoptosis. However, there have been insufficient studies on their role in rheumatoid arthritis (RA). This work is designed to analyze the miR-221/222 expression patterns in peripheral blood mononuclear cells (PBMCs) of patients with RA in comparison with healthy controls using quantitative RT-PCR, in a group of 30 RA patients and 20 healthy controls. The fold change of miR-221/222 expression in PBMCs was significantly elevated (p < 0.01) in RA patients compared with healthy controls. A positive correlation between expression levels of miR-221 and miR-222 was recorded (r = 0.303; p < 0.05). High miR-221/222 expression levels appeared to be elevated with high activity. miR-222 expression in high activity group of RA patients was significantly increased in relation to moderate (p < 0.01) and low (p < 0.001) activity ones with positive correlation (r = 0.363; p < 0.05) between the progress of disease activity and change in miR-222 expression level. ROC analysis showed a sensitivity of 70% and specificity of 75% for miR-221. In miR-222, the sensitivity of 80% and specificity of 70% were recorded. Our data shed some light on the role of miR-221/222 expression in RA patients, and their great potential value as new novel noninvasive biomarkers for disease detection. Therefore; further investigations are warranted to fully elucidate their role in rheumatoid.
30177313 Impact of cardiac rehabilitation on ventricular repolarization indexes in patients with rh 2018 Sep OBJECTIVE: Abnormalities in ventricular repolarization (VR) parameters have been associated with sudden cardiac death (SCD) in patients with rheumatoid arthritis (RA). The benefits of cardiac rehabilitation (CR) in patients with RA are well recognized. We aimed to assess its impact on VR indexes in patients with RA. METHODS: This study included 45 patients with RA (36 female, age 58 ± 5.5 years) and 50 age- and sex-matched otherwise healthy controls. Baseline electrocardiogram (ECG) recordings were used to compare VR parameters such as maximum and minimum QT intervals, and corrected, and dispersion (QTmax, QTmin, cQTmax, cQTmin, QTd, cQTd, respectively), JT and cJT intervals, Tp-e and cTp-e intervals, and Tp-e/QT and Tp-e/cQT ratios in patients with RA and healthy individuals. The effects of 6-week CR in patients with RA were also evaluated by comparing pre- and post-CR ECGs, exercise tolerance test (MET and VO2max) and RA characteristics (C-reactive protein (CRP), Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire(HAQ)). RESULTS: In comparison with the healthy individuals, the patients with RA had significantly higher cQTmax and QTmin intervals, QTd, cQTd, Tp-e and cTp-e intervals, and Tp-e/QT and Tp-e/cQT ratios. At the end of CR, all VR indexes (p < 005), except QTd, were significantly decreased as did the results for CRP, DAS28, and HAQ (all p < 0.05), and MET and VO2max (p < 0.05 for both) were significantly increased in patients with RA. CONCLUSIONS: CR may provide an improvement in the majority of VR indexes which are related with ventricular arrhythmia and SCD in patients with RA. Changes in ETT parameters and RA characteristics may contribute to improvement of several VR indexes such as cQTd, cJT and Tp-e intervals at the end of CR.
29680162 Baseline patient reported outcomes are more consistent predictors of long-term functional 2018 Dec OBJECTIVE: To assess baseline predictors of long-term functional disability in patients with inflammatory arthritis (IA). METHODS: We conducted a systematic review of the literature from 1990 to 2017 using MEDLINE and EMBASE. Studies were included if (i) they were prospective observational studies, (ii) all patients had IA with symptom duration ≤2 years at baseline, (iii) follow-up was at least 5 years, and (iv) baseline predictors of HAQ score at long-term follow-up (i.e., ≥5 years following baseline) were assessed. Information on the included studies and estimates of the association between baseline variables and long-term HAQ scores were extracted from the full manuscripts. RESULTS: Of 1037 abstracts identified by the search strategy, 37 met the inclusion/exclusion criteria and were included in the review. Older age at baseline and female gender were reported to be associated with higher long-term HAQ scores in the majority of studies assessing these relationships, as were higher baseline HAQ and greater pain scores (total patients included in analyses reporting significant associations/total number of patients analysed: age 9.8k/10.7k (91.6%); gender 9.9k/11.3k (87.4%); HAQ 4.0k/4.0k (99.0%); pain 2.8k/2.9k (93.6%)). Tender joint count, erythrocyte sedimentation rate (ESR) and DAS28 were also reported to predict long-term HAQ score; other disease activity measures were less consistent (tender joints 2.1k/2.5k (84.5%); erythrocyte sedimentation rate 1.6k/2.2k (72.3%); DAS28 888/1.1k (79.2%); swollen joints 684/2.6k (26.6%); C-reactive protein 279/510 (54.7%)). Rheumatoid factor (RF) and erosions were not useful predictors (RF 546/4.6k (11.9%); erosions 191/2.7k (7.0%)), whereas the results for anti-citrullinated protein antibody positivity were equivocal (ACPA 2.0k/3.8k (52.9%)). CONCLUSIONS: Baseline age, gender, HAQ and pain scores are associated with long-term disability and knowledge of these may aid the assessment of prognosis.
30402934 Performance of routine assessment of patient index data 3 (RAPID3) in monitoring disease a 2018 Nov AIM: To explore the performance of routine assessment of patient index data 3 (RAPID3) in reflecting disease activity in Chinese rheumatoid arthritis (RA) patients. METHOD: The clinical data of 189 consecutive RA patients, including RAPID3 questionnaire, Disease Activity Score based on 28-joint count (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI), and ultrasonography of hand and wrist joints were collected. The consistency between RAPID3 and DAS28, CDAI, SDAI in RA patients with different disease activities was performed by Spearman's correlations, kappa and/or weighted kappa coefficients. RESULT: RAPID3 score was significantly associated with DAS28 and erythrocyte sedimentation rate (ESR), DAS28 with C-reactive protein (CRP), CDAI, SDAI (r = 0.797, 0.786, 0.784, and 0.760 respectively, P < 0.001 for all). RAPID3 was also significantly correlated with tender joint count, swollen joint count, ESR and CRP. The agreement of RAPID3 with DAS28 scoring systems was better in patients with moderate/high disease activity than those in remission/low disease activity. Ultrasonographic subclinical synovitis was presented in 42.3%-48.6% of patients in remission/low disease activity defined by various scoring criteria including RAPID3 with no significant difference observed (P = 0.22, >0.05). CONCLUSION: RAPID3 showed good correlation with DAS28 scoring systems, especially in patients with moderate/high disease activity. RAPID3 is a reliable and convenient tool to monitor disease activity.
30139690 Fatigue in Rheumatoid Arthritis Patients: Association With Sleep Quality, Mood Status, and 2020 Sep OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by polyarthritis and systemic manifestations. RA-fatigue is a significant problem and adds on disease burden. Sleep disturbance, depression, and disease activity are suggested contributing factors to RA-fatigue; however, their combined role did not examine before among Egyptian RA patients. The objective of the study was to investigate the presence of fatigue, sleep and mood disturbances in RA patients. Also, to evaluate the possible association of poor sleep, depression, and disease activity with RA-fatigue. METHODS: This cross-sectional study included 115 RA patients diagnosed according to the 2010 ACR-EULAR criteria and 46 age and sex matched controls. Fatigue using the Multidimensional Assessment of Fatigue-Global Fatigue Index, sleep using the Pittsburgh Sleep Quality Index and mood status using Beck Depression Inventory were assessed for all participants. RA disease activity was evaluated using disease activity score-28 joints. RESULTS: RA patients had higher mean fatigue, sleep disturbance, and depression scores (27.2±8.9, 6.4±3.6, and 12.8±7.3; respectively) than controls (22.7±7, 4.8±3, 7.8±5.9; respectively) (P<.05). Poor sleep, depression and higher disease activity were significantly correlated with fatigue (r=0.4, r=0.65, r=0.55; respectively) (P<.001). The three variables may explain up to 49.1% of the variation in fatigue on multiple regression analysis. CONCLUSION: Fatigue, poor sleep, and depression are more common in Egyptian patients with RA. A remarkably higher fatigue was associated with poor sleep, depression, and high disease activity, thus monitoring these silent comorbidities in clinical practice is required.
29565675 Composite assessment of power Doppler ultrasonography and MRI in rheumatoid arthritis: a p 2018 Jun OBJECTIVE: Power Doppler ultrasonography (PDUS) and MRI are independently useful to predict structural damage in patients with rheumatoid arthritis (RA). We hypothesize that there is a complementary relationship between these modalities. The aim of this study is, therefore, to investigate the usefulness of the predictive value of composite assessment of PDUS and contrast-enhanced MRI in radiographic outcomes in patients with RA. METHODS: 20 patients (17 females and 3 males) with RA on disease-modifying antirheumatic drugs underwent PDUS and MRI of both hands at baseline. Radiography of the bilateral hands was performed at baseline and at 1 year. Articular synovitis on PDUS was evaluated according to quantitative measurement. Synovitis, bone marrow edema and bone erosion were scored according to the RA MRI scoring method. The changes of joint space narrowing and bone erosion on radiograph were assessed by the Sharp/van der Heijde method. We applied t-statistics to combine the assessment of quantitative PDUS with semiquantitative MRI. RESULTS: Structural damage progression for radiography was not correlated with any evaluations for MRI, while it showed significant correlation with synovitis on PDUS (r(s) = 0.597, p = 0.005). The composite assessment of both modalities (synovitis for PDUS and bone marrow edema for MRI) was correlated with structural damage progression on radiograph (r(s) = 0.792, p < 0.0001). CONCLUSION: Composite assessment of PDUS and MRI may have a stronger predictive value in radiographic progression than PDUS or MRI alone in RA. Advances in knowledge: Composite assessment of PDUS and MRI may be an effective predictor of structural damage in RA.
30132358 Comparison of the clinical characteristics and severity of community-acquired pneumonia be 2019 Sep Objective: To examine the clinical characteristics and severity of community-acquired pneumonia (CAP) between patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) and those treated with TNF inhibitors. Methods: We extracted RA patients treated with biological DMARDs who developed CAP between 2003 and 2015 from our hospital database. We compared the patient backgrounds, duration from the onset of symptoms to diagnosis, and the severity of CAP between patients who developed CAP after treatment with TCZ or tumor necrosis factor (TNF) inhibitor. Results: Of 98 patients who received TCZ, seven developed CAP (IL-6 inhibitor group). Of 560 patients who received TNF inhibitors, 27 developed CAP (TNF inhibitor group). Between the two groups, there was no difference in the duration from the onset of symptoms to diagnosis (7 [4-21], 7 days [1-15]). The IL-6 inhibitor group had a lower body temperature (36.5 °C [36.4-36.8], 37.8 °C [35.9-40.5]) and CRP level (0.09 mg/dL [0.02-2.5], 6.76 mg/dL [0.63-15.2]) at diagnosis than the TNF inhibitor group. The CURB-65 score did not differ significantly between groups. Conclusion: There were no delays in the diagnosis of CAP or any difference in the severity of CAP between patients with RA treated with TCZ and those treated with TNF-inhibitors.
29266813 Is Anti-Citrullinated Protein Antibody-Positive Rheumatoid Arthritis Still a More Severe D 2018 Jul OBJECTIVE: Because of its association with joint destruction, anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) is considered to be more severe than ACPA-negative RA. Clinically relevant joint destruction is now infrequent thanks to adequate disease suppression. According to patients, important outcomes are pain, fatigue, and independence. We evaluated whether ACPA-positive RA patients diagnosed during or after 2000 have more severe self-reported limitations and impairments, including restrictions at work, than ACPA-negative RA patients. METHODS: A total of 492 ACPA-positive and 450 ACPA-negative RA patients who fulfilled the 2010 criteria and were included in the Leiden Early Arthritis Clinic cohort during or after 2000 were compared for self-reported pain, fatigue, disease activity, general well-being (measured by numerical rating scales), physical function (measured by the Health Assessment Questionnaire), and work restrictions, including absenteeism at baseline and during the 4-year followup. Linear mixed models were used. RESULTS: At disease presentation, ACPA-negative patients had more severe pain, fatigue, self-reported disease activity scores, and functional disability (P < 0.05), although absolute differences were small. During followup, ACPA-negative patients remained somewhat more fatigued (P = 0.002), whereas other patient-reported impairments and limitations were similar. Thirty-eight percent of ACPA-negative and 48% of ACPA-positive patients reported absenteeism (P = 0.30), with median 4 days missed in both groups in the last 3 months. Also, restrictions at work among employed patients and restrictions with household work were not statistically different at baseline and during followup. CONCLUSION: In current rheumatology practice, ACPA-positive RA is not more severe than ACPA-negative RA in terms of patients' relevant outcomes, including physical functioning and restrictions at work. This implies that efforts to further improve the disease course should be proportional to both disease subsets.
29972778 Group 2 Innate Lymphoid Cells Attenuate Inflammatory Arthritis and Protect from Bone Destr 2018 Jul 3 Group 2 innate lymphoid cells (ILC2s) were detected in the peripheral blood and the joints of rheumatoid arthritis (RA) patients, serum-induced arthritis (SIA), and collagen-induced arthritis (CIA) using flow cytometry. Circulating ILC2s were significantly increased in RA patients compared with healthy controls and inversely correlated with disease activity. Induction of arthritis in mice led to a fast increase in ILC2 number. To elucidate the role of ILC2 in arthritis, loss- and gain-of-function mouse models for ILC2 were subjected to arthritis. Reduction of ILC2 numbers in RORα(cre)/GATA3(fl/fl) and Tie2(cre)/RORα(fl/fl) mice significantly exacerbated arthritis. Increasing ILC2 numbers in mice by IL-25/IL-33 mini-circles or IL-2/IL-2 antibody complex and the adoptive transfer of wild-type (WT) ILC2s significantly attenuated arthritis by affecting the initiation phase. In addition, adoptive transfer of IL-4/13-competent WT but not IL-4/13(-/-) ILC2s and decreased cytokine secretion by macrophages. These data show that ILC2s have immune-regulatory functions in arthritis.
29391506 Therapeutic effects of anti-CD154 antibody in cynomolgus monkeys with advanced rheumatoid 2018 Feb 1 Rheumatoid arthritis is one major chronic inflammatory systemic autoimmune disease. The CD154-CD40 interactions play a critical role in the regulation of immune responses and the maintenance of autoimmunity. Therefore, we aimed to determine whether anti-CD154 antibody treatment show positive effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in cynomolgus monkeys. Arthritis was induced using chicken type II collagen (CII) and arthritic monkey were divided into control and anti-CD154 treatment groups based on their concentrations of anti-CII antibodies on week 7 post-immunization. Blood and tissue samples were collected on week 16 post-immunization. Anti-CD154 antibody treatment improved arthritis and movement, and significantly decreased the numbers of proliferating B cells and the serum levels of anti-type II collagen antibody and sCD154 compared with non-treatment group. Further anti-CD154 antibody treatment significantly decreased the percentage of CD4+ cells and the ratio of CD4+ to CD8+ T cells and significantly increased the percentage of CD8+ cells and effector memory CD8+ cells in peripheral blood. We have shown for the first time in a nonhuman primate model of RA that CD154 blockade has beneficial effects. This study might be valuable as preclinical data of CD154 blockade in nonhuman primate models of severe rheumatoid arthritis.
29968332 MiR-146a levels in rheumatoid arthritis and their correlation with disease activity: a met 2018 Jul OBJECTIVE: To evaluate the relationship between miR-146a levels and rheumatoid arthritis (RA), and the correlation with RA activity. METHODS: For the meta-analysis, we searched the PubMed, MEDLINE, EMBASE and Cochrane databases, comparing miR-146a levels in patients with RA and controls, and correlation coefficients between miR-146a levels and Disease Activity Score for 28 joints (DAS28) and erythrocyte sedimentation rate (ESR) in patients with RA. RESULTS: Fourteen studies, totaling 683 patients with RA and 477 controls, were available. miR-146a levels were significantly higher in the RA group than in the control group (standardized mean difference [SMD] = 0.546, 95% CI = 0.033-1.059, P = 0.037). Stratification by adjustment for age and/or sex revealed significantly higher miR-146a levels in the adjusted, but not in the non-adjusted group (SMD = 0.747, 95% CI = 0.094-1.400, P = 0.025; SMD = 0.431, 95% CI = -0.430-1.291, P = 0.326, respectively). Stratification by sample size showed significantly higher miR-146a levels in RA groups of large sample sizes (N ≥ 50), but not in those of small size. miR-146a levels in synovial tissue/fluid were significantly higher in the RA group than in the OA group (SMD = 1.305, 95% CI = 1010-1.639, P < 0.001). A significant positive correlation was found between miR-146a levels and ESR (correlation coefficient = 0.534, 95% CI = 0.029-0.822, P = 0.039). CONCLUSIONS: Circulating and synovial tissue/fluid miR-146a levels are high in patients with RA, and circulating miR-146a levels positively correlate with ESR.
30064399 Measure of activity performance of the hand (MAP-Hand) questionnaire: linguistic validatio 2018 Jul 31 BACKGROUND: Developed in the Norway, the Measure of Activity Performance of the Hand (MAP-Hand) assesses 18 activities performed using the hands. It was developed for people with rheumatoid arthritis (RA) using patient generated items, which are scored on a 0-3 scale and summarised into a total score range (0 to 54). This study reports the development and psychometric testing of the British English MAP-Hand in a UK population of people with RA. METHODS: Recruitment took place in the National Health Service (NHS) through 17 Rheumatology outpatient clinics. Phase 1 (cross-cultural adaptation) involved: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews with people with RA. Phase 2 (psychometric testing) involved postal completion of the MAP-Hand, Health Assessment Questionnaire (HAQ), Upper Limb HAQ (ULHAQ), Short-Form 36 (SF-36(v2)) and Disabilities of the Arm Shoulder Hand (DASH) to measure internal consistency (Cronbach's alpha); concurrent validity (Spearman's correlations) and Minimal Detectable Difference (MDC(95)). The MAP-Hand was repeated three-weeks later to assess test-retest reliability (linear weighted kappa and Intra-Class Correlations (ICC (2,1)). Unidimensionality (internal construct validity) was assessed using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model. The RUMM2030 software was used, applying the Rasch partial credit model. RESULTS: In Phase 1, 31 participants considered all items relevant. In Phase 2, 340 people completed Test-1 and 273 (80%) completed Test-2 questionnaires. Internal consistency was excellent (α = 0.96). Test-retest reliability was good (ICC (2,1) = 0.96 (95% CI 0.94, 0.97)). The MAP-Hand correlated strongly with HAQ20 (r(s) = .88), ULHAQ (r(s) = .91), SF-36(v2) Physical Functioning (PF) Score (r(s) = -.80) and DASH (r(s) = .93), indicating strong concurrent validity. CFA failed to support unidimensionality (Chi-Square 236.0 (df 120; p < 0.001)). However, Mokken scaling suggested a probabilistic ordering. There was differential item functioning (DIF) for gender. Four testlets were formed, resulting in much improved fit and unidimensionality. Following this, testlets were further merged in pairs where opposite bias existed. This resulted in perfect fit to the model. CONCLUSIONS: The British English version of the MAP-Hand has good validity and reliability in people with RA and can be used in both research and clinical practice.
30339772 Self-Efficacy and Adherence Behaviors in Rheumatoid Arthritis Patients. 2018 Oct 18 INTRODUCTION: Rheumatoid arthritis (RA) is a common disease that requires patient self-management with chronic medications. Adherence rates for RA medications are suboptimal. This study explores medication adherence and self-efficacy behaviors among RA patients. METHODS: We conducted a qualitative study comprising focus groups and individual interviews. Nineteen participants were recruited and screened to participate in three 90-minute focus groups (n = 13) and six 60-minute individual interviews. We created and maintained a codebook to analyze data. Interviews were analyzed by using NViVo qualitative analysis software. RESULTS: Key points in participant interviews were 1) self-efficacy as influenced by the ability to establish routines, and having an understanding relationship with their healthcare provider; 2) self-efficacy to adjust medications depended on having permission from providers to adjust medications, perceptions of the effectiveness of medications, and confidence in self-knowledge to make appropriate adjustments; and 3) changes in self-efficacy over time were influenced by initial denial and later acceptance of the diagnosis. Participant interviews revealed that medication adherence is a spectrum that ranges from adherent to nonadherent. CONCLUSION: Participants' experience with RA medications revealed varied underlying reasons for adherence behaviors. Recognizing adherence as a dynamic behavior has important implications for how adherence interventions are designed. For example, participants reported adjusting medications in response to the unpredictable nature of RA. Interventions could collect information about RA symptoms and be tailored to provide adherence support at times when patients need it most. The importance of self-efficacy in influencing participants' adherence behaviors is an area for continuing research among patients and providers.
29989617 Photo Rounds: Pain in right shoulder. 2018 Jul This patient's joint pain kept her out of work for several years. While x-rays of her hands appeared normal, an x-ray of her shoulder exposed the underlying problem.
30450812 An evaluation of the Virtual Monitoring Clinic, a novel nurse-led service for monitoring p 2019 Apr OBJECTIVES: To study clinical and patient reported outcomes for the Virtual Monitoring Clinic (VMC), a remote nurse-led telemonitoring service for monitoring Rheumatoid Arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients with stable RA enrolled in the VMC were followed up prospectively. The primary outcomes evaluated at 1-year follow-up were: Disease Activity Score-28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), and patient satisfaction assessed using an 11-point Likert scale. RESULTS: Of the 251 patients enrolled, 186 completed 1-year of follow-up. There was a 2.3% (n = 450) reduction in the annual workload from the rheumatology specialist outpatient clinic as a result of the VMC. Statistically significant improvement was seen in the mean patient satisfaction score (7.70-8.16, P ≤ 0.001), with 61.5% of patients opting for the VMC alternating with rheumatology outpatient clinic visits as their preferred mode of follow-up vis-à-vis standard care. There was a marginal increase in mean DAS28 and RAPID3 scores from 2.56 to 2.78 (P < 0.05) and 5.28 to 6.03 (P < 0.05), respectively. However, given that at 1-year follow-up more than half (72.0% and 63.4% based on DAS28 and RAPID3) of the patients' disease activity had improved or remained stable, and was in remission or low activity (73.1% and 53.2% based on DAS28 and RAPID3), the VMC seemed to maintain a stable RA disease activity for the majority of patients. CONCLUSIONS: The VMC is an effective and well-accepted novel approach for the management of patients with stable RA.
30526655 TNFα expressed on the surface of microparticles modulates endothelial cell fate in rheuma 2018 Dec 7 BACKGROUND: Rheumatoid arthritis (RA) is associated with a high prevalence of atherosclerosis. Recently increased levels of microparticles (MPs) have been reported in patients with RA. MPs could represent a link between autoimmunity and endothelial dysfunction by expressing tumor necrosis factor alpha (TNFα), a key cytokine involved in the pathogenesis of RA, altering endothelial apoptosis and autophagy. The aim of this study was to investigate TNFα expression on MPs and its relationship with endothelial cell fate. METHODS: MPs were purified from peripheral blood from 20 healthy controls (HC) and from 20 patients with RA, before (time (T)0) and after (T4) 4-month treatment with etanercept (ETA). Surface expression of TNFα was performed by flow cytometry analysis. EA.hy926 cells, an immortalized endothelial cell line, were treated with RA-MPs purified at T0 and at T4 and also, with RA-MPs in vitro treated with ETA. Apoptosis and autophagy were then evaluated. RESULTS: RA-MPs purified at T0 expressed TNFα on their surface and this expression significantly decreased at T4. Moreover, at T0 RA-MPs, significantly increased both apoptosis and autophagy levels on endothelial cells, in a dose-dependent manner. RA-MPs did not significantly change these parameters after 4 months of in vivo treatment with ETA. CONCLUSIONS: Our data demonstrate that MPs isolated from patients with RA exert a pathological effect on endothelial cells by TNFα expressed on their surface. In vivo and in vitro treatment with ETA modulates this effect, suggesting anti-TNF therapy protects against endothelial damage in patients with RA.
30255412 [Hand surgery in the rheumatic hand-novel and established aspects]. 2018 Dec BACKGROUND: Hand surgery of the rheumatoid hand has undergone significant changes mostly as a result of biologicals and biosimilars. OBJECTIVE: The significance of established and innovative operative procedures in the modern treatment of the rheumatoid hand is elaborated and a subsumption of local interventional options in this context is carried out. METHODS: The analysis, evaluation and discussion of the literature and expert recommendations are presented. RESULTS: With the consistent use of modern antirheumatic drugs the destruction and deformation of the wrist and hand occur more slowly and less severely. The hand surgeon can therefore operate more selectively and focus on less pathologies at the same time. Up to the present many of the operative techniques described by the pioneers of modern hand surgery are still powerful tools. Most of the considerations about the correction of the disturbed biomechanics and about the reconstitution of stability and the range of motion are still valid. The combination of arthroscopic synovectomy and radiosynoviorthesis of the wrist seems to show promising results. CONCLUSION: Modern treatment of the rheumatoid hand is a multidisciplinary challenge. Rheumatologists, nuclear medicine physicians and hand surgeons together can achieve excellent results. A consistent medication, an early operative intervention if necessary and systematic integration of nuclear medicine physicians into the therapeutic process enable preservation of the long-term function of the hand as the main tool in daily life.
30457672 FCGR2A/FCGR3A Gene Polymorphisms and Clinical Variables as Predictors of Response to Tocil 2019 Apr We evaluated the influence of clinical, biochemical, and genetic factors on response in 142 patients diagnosed with rheumatoid arthritis, of whom 87 patients were treated with tocilizumab (61.26%) and 55 patients were treated with rituximab (38.7%;) according to the variables European League Against Rheumatism (EULAR) response, remission, low disease activity, and improvement in Disease Activity Score, 28 joints (DAS28) at 6, 12, and 18 months. A retrospective prospective cohort study was conducted. Patients carrying the FCGR3A rs396991-TT genotype treated with tocilizumab showed higher EULAR response (OR, 5.075; 95%CI, 1.20-21.33; P = .027) at 12 months, those who were naive for biological disease-modifying antirheumatic drugs (bDMARDs) at the beginning of treatment showed satisfactory EULAR response, higher remission, and greater improvement in DAS28 at 6 months. Younger age at start of tocilizumab treatment was associated with satisfactory EULAR response at 18 months and greater remission at 6 and 18 months. Subcutaneous tocilizumab administration was associated with higher remission at 6 months and improved low disease activity rate at 12 months. In patients treated with rituximab, carriers of the FCGR2A rs1801274-TT genotype had higher EULAR response at 6 months (OR, 4.861; 95%CI, 1.11-21.12; P = .035), 12 months (OR, 4.667; p = 0.066, 95%CI, 0.90-24.12; P = .066), and 18 months (OR, 2.487; 95%CI, 0.35-17.31; P = .357), higher remission (OR: 10.625; p = 0.044, CI(95%) : 1.07, 105.47) at 6 months, and greater improvement in DAS28 at 12 months (B = 0.782; 95%CI, -0.15 to 1.71; P = .098) and 18 months (B = 1.414; 95%CI, 0.19-2.63; P = .025). The FCGR3A rs396991-G allele was associated with improved low disease activity rate (OR, 4.904; 95%CI, 0.84-28.48; P = .077) and greater improvement in DAS28 (B = -1.083; 95%CI, -1.98 to -0.18; P = .021) at 18 months. Patients with a lower number of previous biological therapies had higher remission at 12 months. We suggest that the FCGR3A rs396991-TT genotype, higher baseline value of DAS28, subcutaneous tocilizumab administration, younger age at the beginning of treatment, and being bDMARD naive are associated with better response to tocilizumab. In patients treated with rituximab, we found better response in those patients with the FCGR2A rs1801274-TT genotype, the FCGR3A rs396991-G allele, and lower number of previous biological therapies.
30446927 Inhibitory effects of Clematis orientalis aqueous ethanol extract and fractions on inflamm 2019 Aug Clematis orientalis Linn has long been used as ethnopharmacy for the treatment of arthritis. This study is intended to evaluate the curative efficacy of Clematis orientalis in treating polyarthritis in rats. Aqueous ethanolic extract and fractions (hexane, butanol and aqueous) were administered orally at 200 mg/kg for 28 days after CFA immunization. Paw swelling, paw diameter, arthritic score, body weight, hematological parameters, radiographic and histological analysis of ankle joints were evaluated. Moreover, levels of various inflammatory markers through RT-PCR and ELISA were measured. DPPH and reducing power assays were used to appraise antioxidant capacity. Qualitative phytochemical analysis, determination of total phenolic and flavonoid contents were also carried out. Aqueous ethanolic extract and fractions significantly (p < 0.001) reduced paw volume, paw thickness and arthritic score and considerably prevented decrease in body weight along with anomalous alterations in hematological parameters in comparison with arthritic control. X-ray and histological examination revealed no significant structural changes in ankle joints of treated rats. Expression levels of IL-1β, TNF-α, IL-6, COX-2 and NF-Kβ were significantly (p < 0.05-0.001) suppressed as well as noteworthy increase in the levels of IL-4 and IL-10 among treated animals has been detected. Overproduction of TNF-α and PGE2 was substantially prevented in animals given different treatments. Aqueous ethanol extract and its fractions demonstrated significant and concentration-dependent antioxidant potential. In general, among fractions aqueous fraction exhibited a greater anti-arthritic effect. Phytochemical analysis of aqueous fraction confirmed the presence of flavonoids and glycosides, 215.29 mgGAE/ml phenolic content and 633.03 μgQE/ml flavonoid content. Thus, we suggest Clematis orientalis as a potent strategy for the treatment of rheumatoid arthritis.