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HLA-G is a regulatory molecule involved in immunologic tolerance. Growing evidence indicates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. This study aimed at a systematic evaluation of soluble HLA-G (sHLA-G) in plasma of rheumatoid arthritis (RA) patients with long-lasting chronic inflammation. RA patients (n=68) and healthy controls (n=26) had their plasmatic sHLA-G measured by ELISA whereas the binding capability of sHLA-G to its cognate LILRB1 receptor was measured by a Luminex-based assay. All subjects were PCR-genotyped for HLA-G 14 bp polymorphism (rs66554220). Significantly higher sHLA-G levels were observed in patients (p<0.001), however no significant differences were observed in LILRB1 binding capacity between RA patients and controls. Remarkably, the proportion of patients presenting specific binding of sHLA-G to LILRB1 was significantly decreased as compared to controls (56% vs. 81%, p=0.027). Patients without rheumatoid factor (RF-) were significantly overrepresented in the group of patients positive for LILRB1 binding as compared to patients without LILRB1 binding (31% vs 10%, p=0.033). Furthermore, methotrexate treated patients (n=58) revealed significantly lower LILRB1 binding to sHLA-G molecules than non-treated patients (medians: 12.2 vs. 67.7 units/ml, p=0.031). Unlike in controls, no significant differences in sHLA-G levels were observed among patients grouped by 14 pb genotype. Thus, in a substantial number of late RA patients, the circulating sHLA-G molecules are impaired regarding LILRB1 recognition, meaning that although increased levels are observed; these molecules are not qualified to exert their protective functions against inflammation. Our findings offer new insights into the immunopathology of RA patients with long-lasting anti-RA-treatment and highlight the importance to also measure the binding capability of sHLA-G to LILRB1.

Self-reported disability is potentially influenced by many factors in patients with rheumatoid arthritis (RA). In this sense, we evaluated the association between self-reported disability and (1) clinical features, (2) muscle strength and (3) physical performance over time among patients with RA from two distinct patient cohorts. Two independent prospective RA cohorts were analyzed. The Health Assessment Questionnaire (HAQ), Disease Activity Score in 28 Joints (DAS28), handgrip test, chair stand test, timed-up-and-go (TUG) test and Short Physical Performance Battery (SPPB) were performed at baseline and in follow-up. T test for independent samples, Mann-Whitney U test, Spearman correlation coefficients and linear regression with generalized estimating equations were performed to assess associations between individual constructs at baseline and over time. A total of 205 total RA patients were included [North American Cohort (n = 115); Brazilian Cohort (n = 90)]. At enrollment, Brazilian men had better HAQ than North American men (p<0.001). Brazilian patients overall had lower muscle strength than North American patients (p<0.05). HAQ was associated with DAS28, handgrip test, chair stand test, TUG and SPPB (p<0.001) in both cohorts. Worsening of the DAS28 and chair stand test were each associated with worsening in HAQ in longitudinal analysis over time. Worsening of handgrip was also associated in with worsening HAQ in both cohorts (p<0.05). A worse TUG test was associated with worsening in HAQ in Brazilian cohort (p<0.05) and a worse SPPB was associated with worsening in HAQ in North American cohort (p<0.05). Greater disability measured by HAQ is closely associated with disease activity, pain, muscle strength, and physical performance among RA. Worsening in self-reported disability correlate with worsening clinical factors including objectively-observed physical function.

Our goal is to study the correlations among gray-scale seven-joint ultrasound score (GS-US7), power Doppler seven-joint ultrasound score (PD-US7), disease activity score-28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in patients with and without fibromyalgia (FM). A matched case-control study included all patients consecutively seen in the Rheumatoid Arthritis (RA) Clinic. Participants were allocated into one of two groups: RA with FM and RA without FM. Ultrasound (US) and clinical scoring were blinded for the presence of FM. Medians and proportions were compared by Mann-Whitney's test and McNemar's test, respectively. Spearman's rank correlation coefficients (rs) were calculated among clinical and US scores and differences were tested by r-to-z transformation test. Seventy-two women were included, out of 247 RA patients, mostly white, with median (IQR) age of 57.5 (49.3-66.8) years, with RA symptoms for 13.0 (6.0-19.0) years and FM symptoms for 6.0 (2.0-15.0) years. Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs and prednisone use was comparable between groups. Objective activity parameters were not different between groups. RA patients with FM had greater DAS28, SDAI and CDAI but similar GS-US7 and PD-US7. GS-US7 correlated with DAS28, SDAI and CDAI in patients with and without FM (rs = 0.36-0.57), while PD-US7 correlated with clinical scores only in patients without FM (rs = 0.35-0.38). To our knowledge, this is the first study to demonstrate that ultrasound synovitis scores are not affected by FM in RA patients. PD-US7 performed better than GS-US7 in long-standing RA patients with DAS28, SDAI or CDAI allegedly overestimated due to FM. Since sonographic synovitis predicts erosion better than swollen joint count, C-reactive protein and erythrocyte sedimentation rate, US should be considered a promising treatment target in RA patients with FM.

Introduction Rheumatoid arthritis (RA) is a well-documented independent risk factor for cardiovascular disease. Obesity may provide an additional link between inflammation and accelerated atherosclerosis in RA. Objective To evaluate the association between obesity and disease parameters and cardiovascular risk factors in RA patients. Method Cross-sectional study of a cohort of RA patients from three Brazilian teaching hospitals. Information on demographics, clinical parameters and the presence of cardiovascular risk factors was collected. Blood pressure, weight, height and waist circumference (WC) were measured during the first consultation. Laboratory data were retrieved from medical records. Obesity was defined according to the NCEP/ATPIII and IDF guidelines. The prevalence of obesity was determined cross-sectionally. Disease activity was evaluated using the DAS28 system (remission < 2.6; low 2.6–3.1; moderate 3.2–5.0; high > 5.1). Results The sample consisted of 791 RA patients aged 54.7 ± 12.0 years, of whom 86.9% were women and 59.9% were Caucasian. The mean disease duration was 12.8 ± 8.9 years. Three quarters were rheumatoid factor-positive, the mean body mass index (BMI) was 27.1 ± 4.9, and the mean WC was 93.5 ± 12.5 cm. The observed risk factors included dyslipidemia (34.3%), type-2 diabetes (15%), hypertension (49.2%) and family history of premature cardiovascular disease (16.5%). BMI-defined obesity was highly prevalent (26.9%) and associated with age, hypertension and dyslipidemia. Increased WC was associated with diabetes, hypertension, dyslipidemia and disease activity. Conclusion: Obesity was highly prevalent in RA patients and associated with disease activity.

BackgroundAlthough effectively controlling inflammation, up to 50% of patients with rheumatoid arthritis (RA) experience persistent pain, associated with central sensitization and neuroinflammation. Home-based transcranial direct current stimulation (tDCS) has shown efficacy in chronic pain.ObjectiveTo investigate whether anodal tDCS (a-tDCS) is more effective than sham stimulation in reducing pain.MethodsRandomized, double-blind, sham-controlled trial with 34 women (18–70 years) with RA and VAS > 40 mm. Participants were randomized to receive a-tDCS (n = 17) or sham tDCS (n = 17). Home-based tDCS (2 mA, 20 min/day) or sham (2 mA, 90 s) for four weeks, using anodal-left M1 montage. Primary outcomes was pain (Visual Analogue Scale, VAS), Secondary outcomes included pressure pain threshold (PPT), central sensitization (CSI), physical function (HAQ-DI), fatigue (FACIT-F), CNS biomarkers, adherence, and safety.ResultsMean VAS reduction from baseline was greater in the a-tDCS group (-33.5 mm) versus s-tDCS (-14.1 mm), with a between-group difference of -19.4 mm (95% CI, -29.3 to -9.5; p = 0.003). Linear mixed-effects models showed that a-tDCS reduced VAS pain by 27.7% versus 6.0% with sham, a between-group difference of 21.7% (Cohen’s d = 1.15). HAQ-DI improved by 38.0% versus 7.2% (ES = 1.10). a-tDCS reduced analgesic use by 62% (RR = 0.38; 95% CI, 0.18–0.79). Exploratory analyses suggested that neuroplasticity mechanisms might mediate these effects.ConclusionHome-based a-tDCS effectively reduced pain, disability, and analgesic use in RA patients with persistent pain without objective inflammation.

BackgroundPatient management in rheumatoid arthritis (RA) has evolved to a “treat-to-target” (T2T) approach, which entails intensive treatment and regular follow-up with the goal of achieving low levels of disease activity or clinical remission. Even though a T2T approach is endorsed by professional organizations and yields superior outcomes, its implementation remains incomplete. EVEREST (EleVatE care in RhEumatoid arthritiS with Treat-to-target) is a quality-improvement initiative designed to improve the widespread implementation of a personalized T2T strategy and enable patients with RA to reach their full potential for remission. We describe the Brazilian results from the Global T2T Survey, first part of the EVEREST program.MethodsBetween June and September 2022, we conducted an online survey targeting rheumatologists in Brazil. Our objective was to evaluate the barriers and knowledge gaps hindering the effective implementation of T2T strategies. To achieve this, we employed a set of multiple-choice questions specifically crafted to elicit responses categorized in a structured order.Results166 rheumatologists participated in the survey, 51% of them with more than 21 years of experience in rheumatology. Regarding the perceived challenges in the management of RA in clinical practice, the highest percentage of agreement/strong agreement among the participants was related to the contradictory results of disease activity measures (60%). In terms of the main barriers to assess the disease activity in clinical practice, the lack of adherence to treatment and contradictory assessments between patient-reported outcomes and composite measures were indicated by 75% and 59% of the participants, respectively, as a moderate/serious barrier. The most frequently knowledge and skill gaps related to the management of RA pointed out by the participants were on the difficulty to assess patients’ health literacy (54% stated to have no more than intermediate knowledge on standardized methods to assess it and 43% no more than intermediate skills on determining the level of health literacy of the patients). In general, the use of tools to support the management of RA patients in clinical practice was indicated to be unusual by the participants. Self-reflection questionnaires, patient education materials and treatment consideration checklists were pointed out as the least frequently used tools (85%, 64% and 62% of the participants stated to use them never, rarely, or only sometimes, respectively).ConclusionsOur findings indicate a greater need for design, selection, and uptake of practical strategies to further improve communication between healthcare providers and patients with RA, as well as for promoting well-informed, collaborative decision-making in their care.

The treat-to-target strategy (T2T) was associated with better outcomes in psoriatic arthritis (PsA) compared to standard care in clinical trials. This study aimed to analyze factors precluding treatment optimization in a T2T strategy conducted in a real-world cohort of PsA patients. A retrospective cross-sectional study nested in a cohort was conducted. Medical records of patients ≥ 18 years old, fulfilling CASPAR criteria and with at least one visit in the PsA clinic, were reviewed. Demographic data, current medication, and minimal disease activity (MDA) criteria were recorded. Reasons for the non-escalation of therapy in patients who were not classified as MDA were reported as absolute and relative frequencies. In the 8-month period, 131 visits (corresponding to 74 patients) were conducted. The MDA criteria were available in 113 visits (86.3%) and patients were classified as MDA in 31.0% of the visits (N = 35/113). Although in 69.0% of the visits patients were not in MDA, (N = 78/113), therapy was adjusted in only 42.3% (N = 33/78). Reasons precluding treatment escalation in non-MDA subjects were physician’s impression of remission (57.7%, N = 26), non-adherence to previous prescription (17.8%, N = 8), restricted access to drugs (17.8%, N = 8), adverse events (11.1%, N = 5), poor understanding of medication instructions (6.7%, N = 3), patient’s refusal to escalate therapy (4.4%, N = 2), and recent change in therapy (2.2%, N = 1). Discordance between the physician’s clinical evaluation and the MDA criteria, non-adherence to prescription, and poor access to drugs were the main factors precluding escalation of therapy in a T2T strategy in a real-world PsA cohort.

BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disease in which achieving remission is the most effective strategy to prevent progression and optimize long-term outcomes. The performance of commonly used disease activity indices has not been well validated in the Brazilian RA population. This study aimed to evaluate the agreement between CDAI/SDAI and the revised Boolean 2.0 remission criteria, which served as the reference standard, and to identify the most accurate CDAI and SDAI remission cut-offs in this population.MethodsWe conducted a cross-sectional analysis of baseline data from a Brazilian Cohort study, which included 840 patients from 11 public hospitals in Brazil. Disease activity was assessed using DAS28-CRP, DAS28-ESR, SDAI, CDAI, and Boolean 1.0/2.0. Agreement was assessed using Cohen’s kappa, and optimal remission cut-offs were determined through ROC curve analysis.ResultsThe study population was predominantly female (89.8%), with a mean age of 57 years and a median disease duration of 12 years. DAS28-CRP showed the highest remission rate (39.2%), whereas Boolean 1.0 showed the lowest (15.1%). Strong agreement was found between Boolean 2.0, and both the SDAI (κ = 0.775) and CDAI (κ = 0.692). ROC analysis revealed that the most accurate remission cut-offs were SDAI ≤ 4.3 and CDAI ≤ 3.9, which increased remission detection by 5.9% and 6.2%, respectively.ConclusionIn our cohort, SDAI ≤ 4.3 and CDAI ≤ 3.9 were the values most closely aligned with Boolean 2.0 remission. These adjusted cut-offs may help minimize overtreatment in resource-limited settings. Prospective studies assessing function, radiographic progression, and quality of life are warranted to confirm their validity in the Brazilian population.

BackgroundPatients with rheumatologic diseases are monitored fundamentally through metric tools or index calculated from clinical data and patient exams, which allow us to assess the severity of the disease and guide the therapeutic decision. In rheumatoid arthritis (RA), for treatment to be optimized and considered effective, periodic assessment with composite disease activity index and a 'treat-to-target' approach is required. The Routine Assessment of Patient Index Data 3 (RAPID3) in the Multidimensional Health Assessment Questionnaire (MDHAQ) includes only three measures based on the central patient self-reported dataset and can be used in a 'treat-to-target' approach analogous to the Clinical Disease Activity Index (CDAI) and the Disease Activity Score 28-joints (DAS28). This tool, however, has not undergone cross-cultural or clinical validation in Brazil. In this research, we performed the MDHAQ cross-cultural and clinical validation for the Brazilian population of RA patients.MethodsThe Portuguese version of the MDHAQ was created identically in an electronic questionnaire and underwent a cross-cultural validation process with 38 participants. Test–retest was performed in 29 patients. Further, a clinical validation with 129 Rheumatoid Arthritis patients was performed. Electronic MDHAQ was answered through an online platform. We also collected socioeconomic data as well as other clinical (CDAI, SDAI, DAS28) and functional (HAQ) scores during the face-to-face assessment of patients.ResultsMDHAQ/RAPID3 maintained semantic, idiomatic, as well as conceptual and experience equivalence for the Brazilian population, with 92% acceptance of participants. It showed test–retest reliability, adequate internal consistency (Cronbach's α 0.85) and correlation of the scores obtained with adequate association with the DAS28 gold standard. RAPID3 also had high sensitivity (98%), adequate specificity (48%), high negative predictive value (92%) and negative post-test probability of 8%, attributes expected for a test tool for population screening.ConclusionThe use of MDHAQ/RAPID3 associated with traditional clinical measures can adequately allow for remote follow-up based on the 'treat-to-target' approach with performance comparable to the gold standard DAS28, being a viable tool in the sample of Brazilian patients with RA in the current context of telehealth.

Background Rheumatoid arthritis (RA) is a systemic autoimmune disease with articular and extra-articular manifestations. Chronic inflammation may contribute to sarcopenia independently of age. While cross-sectional studies report sarcopenia in 24–30% of RA patients, longitudinal data remain limited. This study aimed to assess long-term changes in sarcopenia and body composition in RA patients and explore their associations with clinical features and health outcomes. Methods In this prospective cohort study, 90 RA patients were followed for a median of 6.4 years (IQR: 5.8–7.0). Clinical features, falls, fragility fractures, and mortality were recorded. Body composition (BMI, appendicular lean mass index [ALMI], fat mass index [FMI]) was assessed using dual-energy X-ray absorptiometry; grip strength by JAMAR dynamometer; and physical performance by the Timed Up and Go test. Sarcopenia was defined using EWGSOP2 criteria. Statistical analyses included ANOVA, Kruskal–Wallis, chi-squared tests, generalized estimating equations, Kaplan–Meier curves, and regression models. Results At baseline, mean age was 56.5 ± 7.3 years, median disease duration 8.5 years (IQR:3.0–18.0), median DAS28-CRP 3.0 (IQR:1.0–3.0), and mean HAQ-DI 1.1 ± 0.9. Seven patients (7.7%) had sarcopenia, including one severe case. Most participants were overweight with elevated FMI. Sarcopenia prevalence and clinical characteristics remained stable, with no new sarcopenia cases during follow-up. ALMI increases were associated with FMI increases ( p  = 0.005). Baseline sarcopenia was not associated with falls, fractures, or mortality. Low muscle mass and poor physical performance were not linked to mortality, but low muscle strength showed a trend toward higher mortality risk (HR = 4.35, 95% CI: 0.51–37.25). After adjusting for age, disease duration, glucocorticoid dose, and DMARD use, low muscle strength was significantly associated with falls (B = 3.92,95% CI:1.03–15.02; p  = 0.046). No associations were found for low muscle mass, low physical performance, or sarcopenia with these outcomes. Conclusion In RA patients receiving regular care, sarcopenia prevalence remained high and stable. Low muscle strength was associated with falls and showed a trend toward increased mortality risk, possibly due to limited sample size, highlighting its potential prognostic value. However, the absence of a control group limits interpretation, as observed changes may reflect normal aging rather than disease-specific effects. Clinical trial number Not applicable.