Search

BACKGROUND: Outcome measures are crucial to support a treat-to-target approach to rheumatoid arthritis (RA) care, yet their integration into clinical practice remains inconsistent. We developed an Electronic Heath Record-integrated, patient-facing side-car application to display RA outcomes (disease activity, functional status, pain scores), medications, and lab results during clinical visits (RA PRO Dashboard). The study aimed to evaluate patient perceptions and attitudes towards the implementation of a novel patient-facing dashboard during clinical visits using a mixed-methods approach. METHODS: RA patients whose clinicians used the dashboard at least once during their clinical visit were invited to complete a survey regarding its usefulness in care. We also conducted semi-structured interviews with a subset of patients to assess their perceptions of the dashboard. The interviews were transcribed verbatim and analyzed thematically using deductive and inductive techniques. Emerging themes and subthemes were organized into four domains of the Ecological Model of Health. RESULTS: Out of 173 survey respondents, 79% were interested in seeing the dashboard again at a future visit, 71% felt it improved their understanding of their disease, and 65% believed it helped with decision-making about their RA care. Many patients reported that the dashboard helped them discuss their RA symptoms (76%) and medications (72%) with their clinician. Interviews with 29 RA patients revealed 10 key themes: the dashboard was perceived as a valuable visual tool that improved patients understanding of RA outcome measures, enhanced their involvement in care, and increased their trust in clinicians and the clinic. Common reported limitations included concerns about reliability of RA outcome questionnaires for some RA patients and inconsistent collection and explanation of these measures by clinicians. CONCLUSIONS: In both the quantitative and qualitative components of the study, patients reported that the dashboard improved their understanding of their RA, enhanced patient-clinician communication, supported shared decision-making, and increased patient engagement in care. These findings support the use of dashboards or similar data visualization tools in RA care and can be used in future interventions to address challenges in data collection and patient education.

BACKGROUND: Guided by the reserve capacity model, we evaluated the unique relationships between socioeconomic status (SES), reserve capacity (helplessness, self-efficacy, social support), and negative emotions on pain in patients with Rheumatoid Arthritis (RA). METHODS: The secondary analysis used baseline, cross-sectional data from 106 adults in a clinical trial comparing behavioral treatments for RA. Patients were eligible if they were ≥ 18 years old, met the ACR criteria for RA (determined by study rheumatologist), had stable disease and drug regimens for 3 months, and did not have a significant comorbid condition. Structural equation modeling evaluated the direct effects of SES, reserve capacity (helplessness- Arthritis Helplessness Index, self-efficacy -Personal Mastery Scale, social support- Social Provisions Scale) and negative emotions (stress and depressive symptoms- Perceived Stress Scale and Hamilton Depression Rating Scale) on pain (Rapid Assessment of Disease Activity in Rheumatology-RADAR & visual analog scale-VAS), and the indirect effects of SES as mediated by reserve capacity and negative emotions. The SEM model was evaluated using multiple fit criteria: χ2 goodness-of-fit statistic, the comparative fit index (CFI), the standardized root mean square residual (SRMR), and the root mean square error of approximation (RMSEA). RESULTS: Participants were mostly female (85%), 55.45 years old on average, self-identified as white (61%), Hispanic (16%), black (13%), and other (10%), and had RA for an average of 10.63 years. Results showed that low SES contributed to worse pain, through lower reserve capacity and higher negative emotions. Mediational analyses showed that reserve capacity and negative emotions partially mediated the effect of SES on pain. The final model explained 39% of the variance in pain. CONCLUSIONS: The findings indicate that lower SES was related to worse clinical pain outcomes and negative emotions and reserve capacity (helplessness, social support, and self-efficacy) mediated the effect of SES on pain. A primary limitation is the small sample size; future studies should evaluate this model further in larger, longitudinal approaches. Interventions that target negative emotions in patients with low SES may facilitate better pain control with RA. TRIAL REGISTRATION: clinicaltrials.gov NCT00072657 01/02/2004 20/03/2009.

Introduction: Tendon injuries of the hand present a diverse spectrum of challenges in emergency medicine, ranging from minor strains to catastrophic ruptures. The superficial anatomy of hand tendons predisposes them to various mechanisms of injury, leading to complex medical scenarios. Here, we present a unique case of flexor tendon exposure secondary to abscess formation and spontaneous rupture, emphasizing the importance of prompt recognition and management of such injuries in the emergency department. Case Report: A 69-year-old male with multiple comorbidities presented with diffuse pain and a pale, pulseless right lower extremity, alongside a left hand exhibiting exposed flexor tendons due to recent abscess drainage. Despite broad-spectrum antibiotics and pain management, the patient underwent above-knee amputation due to vascular compromise. Evaluation revealed a complete flexor tendon rupture likely attributable to infection, necessitating emergent hand surgery at the bedside. Conclusion: Understanding the nuances of tendon injuries is paramount for emergency physicians, given their potential for lifelong disability if inadequately addressed. Awareness of risk factors and appropriate management strategies, including early surgical intervention when indicated, is essential in optimizing patient outcomes. This case serves as a reminder of the complexities involved in hand injuries and underscores the need for vigilance and tailored care in the emergency setting.

BackgroundAutoimmune diseases have been linked to an increased risk of pregnancy-related complications. A family history of autoimmune diseases may be related to the risk of childhood cancer based on similar histocompatibility antigens. We utilized data from national registries in Denmark to examine associations between maternal autoimmune disease and cancer in their offspring.MethodsWe linked data from several national registries in Denmark to identify childhood cancer cases in children

BACKGROUND: Improving shared decision-making using a treat-to-target approach, including the use of clinical outcome measures, is important to providing high quality care for rheumatoid arthritis (RA). We developed an Electronic Health Record (EHR) integrated, patient-facing sidecar dashboard application that displays RA outcomes, medications, and lab results for use during clinical visits (RA PRO dashboard). The purpose of this study was to assess clinician perceptions and experiences using the dashboard in a university rheumatology clinic. METHODS: We conducted focus group (FG) discussions with clinicians who had access to the dashboard as part of a randomized, stepped-wedge pragmatic trial. FGs explored clinician perceptions towards the usability, acceptability, and usefulness of the dashboard. FG data were analyzed thematically using deductive and inductive techniques; generated themes were categorized into the domains of the Technology Acceptance Model (TAM). RESULTS: 3 FG discussions were conducted with a total of 13 clinicians. Overall, clinicians were enthusiastic about the dashboard and expressed the usefulness of visualizing RA outcome trajectories in a graphical format for motivating patients, enhancing patient understanding of their RA outcomes, and improving communication about medications. Major themes that emerged from the FG analysis as barriers to using the dashboard included inconsistent collection of RA outcomes leading to sparse data in the dashboard and concerns about explaining RA outcomes, especially to patients with fibromyalgia. Other challenges included time constraints and technical difficulties refreshing the dashboard to display real-time data. Methods for integrating the dashboard into the visit varied: some clinicians used the dashboard at the beginning of the visit as they documented RA outcomes; others used it at the end to justify changes to therapy; and a few shared it only with stable patients. CONCLUSIONS: The study provides valuable insights into clinicians perceptions and experiences with the RA PRO dashboard. The dashboard showed promise in enhancing patient-clinician communication, shared decision-making, and overall acceptance among clinicians. Addressing challenges related to data collection, education, and tailoring dashboard use to specific patient populations will be crucial for maximizing its potential impact on RA care. Further research and ongoing improvements in dashboard design and implementation are warranted to ensure its successful integration into routine clinical practice.

Interstitial lung disease (ILD) is a common and serious manifestation of autoimmune rheumatic diseases. While the prevalence of ILD differs among the individual autoimmune rheumatic diseases, ILD remains an important cause of morbidity and mortality in systemic sclerosis, systemic lupus erythematosus, mixed connective tissue disease, primary Sjögrens disease, rheumatoid arthritis, and idiopathic inflammatory myositis. The present review summarizes recent literature on autoimmune-associated ILD with a focus on screening and monitoring for ILD progression. Reflecting on the currently available evidence, the authors propose a guideline for monitoring for progression in patients with newly diagnosed autoimmune-associated ILD. This review also highlights clinical and biological predictors of progressive pulmonary fibrosis and describes opportunity for further study in the rapidly evolving area of rheumatology and pulmonology.

INTRODUCTION: Clinical guidelines offer little guidance for treatment selection following inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARD) in rheumatoid arthritis (RA). A molecular signature response classifier (MSRC) was validated to predict tumor necrosis factor inhibitor (TNFi) inadequate response. The decision impact of MSRC results on biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) selection was evaluated. METHODS: This is an analysis of AIMS, a longitudinal, prospective database of patients with RA tested using the MSRC. This study assessed selection of b/tsDMARDs class after MSRC testing by surveying physicians, the rate of b/tsDMARD prescriptions aligning with MSRC results, and the percentage of physicians utilizing MSRC results for decision-making. RESULTS: Of 1018 participants, 70.7% (720/1018) had treatment selected after receiving MSRC results. In this MSRC-informed cohort, 75.6% (544/720) of patients received a b/tsDMARD aligned with MSRC results, and 84.6% (609/720) of providers reported using MSRC results to guide treatment selection. The most prevalent reason reported (8.2%, 59/720) for not aligning treatment selection with MSRC results from the total cohort was health insurance coverage issues. CONCLUSION: This study showed that rheumatologists reported using the MSRC test to guide b/tsDMARD selection for patients with RA. In most cases, MSRC test results appeared to influence clinical decision-making according to physician self-report. Wider adoption of precision medicine tools like the MSRC could support rheumatologists and patients in working together to achieve optimal outcomes for RA.

INTRODUCTION: Upadacitinib (UPA) is a Janus kinase inhibitor that has demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA) with an acceptable safety profile. We investigated laboratory parameter changes in UPA RA clinical trials. METHODS: Pooled data from six randomized trials in the SELECT phase 3 program were included. Key laboratory parameters and safety data were measured for UPA 15 and 30 mg once daily (QD), adalimumab (ADA) 40 mg every other week + methotrexate (MTX), and MTX monotherapy. Exposure-adjusted event rates (EAERs) of adverse events were calculated. RESULTS: A total of 3209 patients receiving UPA 15 mg QD (10 782.7 patient-years [PY]), 1204 patients receiving UPA 30 mg QD (3162.5 PY), 579 patients receiving ADA + MTX (1573.2 PY), and 314 patients receiving MTX monotherapy (865.1 PY) were included, representing up to 6.5 years of total exposure. Decreases in mean levels of hemoglobin, neutrophils, and lymphocytes, and increases in mean levels of liver enzymes and creatinine phosphokinase were observed with UPA, with grade 3 or 4 changes observed in some patients. Mean low- and high-density lipoprotein cholesterol ratios remained stable for patients receiving UPA 15 mg QD. EAERs of anemia and neutropenia occurred at generally consistent rates between UPA and active comparators (3.1-4.3 and 1.7-5.0 events [E]/100 PY across treatment groups, respectively). Rates of hepatic disorder were higher with MTX monotherapy, UPA 15 mg and UPA 30 mg (10.8, 9.7, and 11.0 E/100 PY, respectively) versus ADA + MTX (6.4 E/100 PY). Rates of lymphopenia were highest with MTX monotherapy (3.2 E/100 PY). Treatment discontinuations due to laboratory-related events were rare, occurring in 1.1% and 2.2% of patients treated with UPA 15 and 30 mg QD, respectively. CONCLUSIONS: The results of this integrated long-term analysis of laboratory parameters continue to support an acceptable safety profile of UPA 15 mg QD for moderate-to-severe RA.

OBJECTIVE: Despite interest in optimizing the electronic health record (EHR) to facilitate chronic disease care for conditions like rheumatoid arthritis (RA), progress in this area has been slow. EHR sidecar applications offer one solution, but little guidance exists to facilitate their successful development, deployment, and maintenance in the healthcare setting. We aimed to provide a roadmap for how to develop and deploy an EHR sidecar application based on our experience building a new EHR-integrated, patient-facing visualization tool that displayed disease outcomes to RA patients during a clinical visit (the RA PRO dashboard) in a large academic health center. METHODS: We describe the technical design and implementation of the RA PRO dashboard; report clinic workflow adaptations to incorporate this new technology; and discuss the resources required and challenges encountered in maintaining this application. RESULTS: The RA PRO dashboard required extensive human-centered design work, regulatory approvals, software development, user testing, integration with Epic-based workflows, and maintenance. Key requirements were prioritized based on the anticipated effects on usefulness and ease of use. Implementation science strategies were used to improve use of the dashboard in clinic and included education for patients, staff, and clinicians; reports of actual use of the dashboard and data quality; and regular meetings between the research team and clinicians to discuss and address barriers to use. CONCLUSION: Successful development and deployment of an EHR-integrated application are resource-intensive and require technical, operational, and educational innovations. The roadmap presented in this study can serve as a resource for future developers.

Rheumatoid arthritis (RA) management leans toward achieving remission or low disease activity. In this study, we conducted single-cell RNA sequencing (scRNA-Seq) of peripheral blood mononuclear cells (PBMCs) from 36 individuals (18 patients with RA and 18 matched controls, accounting for age, sex, race, and ethnicity), to identify disease-relevant cell subsets and cell type-specific signatures associated with disease activity. Our analysis revealed 18 distinct PBMC subsets, including an IFN-induced transmembrane 3-overexpressing (IFITM3-overexpressing) IFN-activated monocyte subset. We observed an increase in CD4+ T effector memory cells in patients with moderate-high disease activity (DAS28-CRP ≥ 3.2) and a decrease in nonclassical monocytes in patients with low disease activity or remission (DAS28-CRP < 3.2). Pseudobulk analysis by cell type identified 168 differentially expressed genes between RA and matched controls, with a downregulation of proinflammatory genes in the γδ T cell subset, alteration of genes associated with RA predisposition in the IFN-activated subset, and nonclassical monocytes. Additionally, we identified a gene signature associated with moderate-high disease activity, characterized by upregulation of proinflammatory genes such as TNF, JUN, EGR1, IFIT2, MAFB, and G0S2 and downregulation of genes including HLA-DQB1, HLA-DRB5, and TNFSF13B. Notably, cell-cell communication analysis revealed an upregulation of signaling pathways, including VISTA, in both moderate-high and remission-low disease activity contexts. Our findings provide valuable insights into the systemic cellular and molecular mechanisms underlying RA disease activity.

BackgroundThere is little robust data about the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis (RA), who often have cardiovascular comorbidities. We examined the association between use of hydroxychloroquine (HCQ) in patients with RA and major adverse cardiovascular events (MACE).MethodsIn a retrospective cohort of Medicare beneficiaries aged ≥ 65 years with RA, we identified patients who initiated HCQ (users) and who did not initiate HCQ (non-users) between January 2015-June 2017. Each HCQ user was matched to 2 non-users of HCQ using propensity score derived from patient baseline characteristics. The primary outcome was the occurrence of MACE, defined as acute admissions for stroke, myocardial infarction, or heart failure. Secondary outcomes included all-cause mortality and the composite of MACE and all-cause mortality. Cox proportional hazards model was used to compare outcomes between HCQ users to non-users.ResultsThe study included 2380 RA patients with incident HCQ use and matched 4633 HCQ non-users over the study period. The mean follow-up duration was 1.67 and 1.63 years in HCQ non-users and users, respectively. In multivariable models, use of HCQ was not associated with the risk of MACE (hazard ratio 1.1; 95% CI: 0.832-1.33). However, use of HCQ was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.45-0.64) and the composite of all-cause mortality and MACE (HR 0.67; 95% CI: 0.58-0.78).ConclusionHCQ use was independently associated with a lower risk of mortality in older adults with RA but not with incidence of MACE events. Key Points • Using an incident user design (to avoid the biases of a prevalent user design) and a population-based approach, we examined the effect of hydroxychloroquine (HCQ) on the risk of major cardiovascular events (MACE) in older patients with RA. • We did not find an association between HCQ use and incident MACE. We did, however, find a significant association with the composite outcome (MACE and all-cause mortality) driven by a significant reduction in all-cause mortality with HCQ use.

BACKGROUND: The incidence of osteoporosis significantly increases in the patients with rheumatoid arthritis, and it remains unclear whether the presence of a large number of immune complexes in serum promotes the onset and development of osteoporosis. OBJECTIVE: To investigate the correlation between serum immune complexes and osteoporosis in patients with rheumatoid arthritis. METHODS: (1) Clinical trial: Serum and clinical data of 50 healthy controls and 50 patients with untreated rheumatoid arthritis were collected and retrospectively analyzed. Total immune complex level in serum was compared between two groups. Correlation of serum total immune complexes with bone mineral density, bone turnover markers and other clinical indicators in patients with rheumatoid arthritis was analyzed. (2) Cell experiment: Peripheral blood mononuclear cells from healthy volunteers were isolated and cultured, and divided into four groups: rheumatoid arthritis group was added with total immune complex suspension from rheumatoid arthritis patients; normal control group was added with total immune complex suspension from healthy medical checkups; positive control group was added with α-MEM medium containing macrophage colony-stimulating factor and receptor activator of nuclear factorkappa B ligand, and negative control group was added with α-MEM medium. Tartrate-resistant acid phosphatase staining was performed to observe the formation of osteoclasts after 7 days of treatment, RESULTS AND CONCLUSION: (1) Clinical trial: The total immune complex and serum alkaline phosphatase levels in patients with rheumatoid arthritis were significantly higher than those in health controls (P < 0.01, P < 0.05). Pearson correlation analysis showed that serum total immune complex level was positively correlated with erythrocyte sedimentation rate (r=0.330, P=0.019), serum alkaline phosphatase (r=0.545, P=0.001), anti-cyclic citrullinate peptide (r=0.377, P=0.007) and c-terminal telopeptide of type I collagen (r=0.738, P=0.001), and negatively correlated with lumbar bone mineral density (r=-0.595, P=0.001) in patients with rheumatoid arthritis. Binary Logistic regression analysis showed that age [odds ratio (OR)=1.086, 95% confidence interval (CI) (1.022,1.154), P=0.008], anti-cyclic citrullinate peptide [OR=1.002, 95% CI (0.999,1.005), P=0.035], c-terminal telopeptide of type I collagen [OR=0.141, 95% CI (0.015, 8.900), P=0.008] and serum total immune complexes [OR=2.895, 95% CI (1.228, 6.827), P=0.001] were the influencing factors for abnormal bone mass (reduced bone mass or osteoporosis) in patients with rheumatoid arthritis. (2) Cell experiment: Tartrate-resistant acid phosphatase positive osteoclasts were observed in the positive control group, normal control group and rheumatoid arthritis group, and there were more osteoclasts in the rheumatoid arthritis group than in the normal control group (P < 0.01). To conclude, serum total immune complexes can be used as a potential serologic predictor of rheumatoid arthritis complicated with osteoporosis, and removing immune complexes in serum or interfering with the binding of immune complexes to their receptors may be an effective means for the prevention and treatment of rheumatoid arthritis complicated with osteoporosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rheumatoid arthritis is a chronic autoimmune disease characterized by joint pain, swelling, and dysfunction. Acupuncture, as a traditional medical treatment, has proved its effectiveness and safety in many diseases. However, the efficacy of acupuncture in the treatment of rheumatoid arthritis remains controversial. Therefore, the purpose of this study is to evaluate and explore the effect of Tiaodu Tongmai acupuncture in the treatment of preclinical rheumatoid arthritis of different ages through the generalized estimating equation, and to provide a basis for the application of acupuncture in rheumatoid arthritis. OBJECTIVE: To investigate the effect of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis (pre-RA) patients at different ages based on generalized estimating equation. METHODS: A total of 123 patients with preclinical rheumatoid arthritis treated from January to September 2023 were selected as the study objects and divided into study group (n=64) and control group (n=59) according to different treatment methods. The study group was given Tiaodu Tongmai acupuncture treatment, and the control group was given acetaminophen tablets. The baseline balance was adjusted by propensity score matching method. The clinical efficacy and cytokine levels before and after treatment between the two groups were compared. The generalized estimating equation model was established to evaluate the efficacy of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis patients at different ages. RESULTS AND CONCLUSION: (1) After 0 days of treatment, there were significant differences in joint pain and C-reactive protein expression between study and control groups (P < 0.05). After 4 weeks of treatment, there were significant differences in visual analogue scale scores, joint pain, C-reactive protein and erythrocyte sedimentation rate between the two groups (P < 0.05). After 8 weeks of treatment, there were significant differences in visual analogue scale scores, C-reactive protein and erythrocyte sedimentation rate between the two groups (P < 0.05). After 12 weeks of treatment, there were significant differences in visual analogue scale scores, C-reactive protein and erythrocyte sedimentation rate between the two groups (P < 0.05). (2) The total effective rate of the study group was 93.75%, while that of the control group was 79.17%. The clinical efficacy of the study group was significantly better than that of the control group (P < 0.05). (3) There were significant differences in interleukin-6, interferon-γ, macrophage migration inhibitory factor, rheumatoid factor IgA, rheumatoid factor IgM, metallomatrix proteinase 3, metallomatrix proteinase 9, and anti-cyclic citrulline antibody in the study group before and after treatment (P < 0.05). The levels of interleukin-6, interferon-γ, rheumatoid factor IgA, rheumatoid factor IgM, metallomatrix proteinase 3, metallomatrix proteinase 9, and anti-cyclic citrulline antibody in the control group after treatment were significantly different from those before treatment (P < 0.05). There were significant differences in interleukin-6, interferon-γ, macrophage migration inhibitory factor, rheumatoid factor IgA, rheumatoid factor IgM, metallomatrix proteinase 3, and anti-cyclic citrulline antibody between the two groups after treatment (P < 0.05). (4) After 12 weeks of treatment, the comprehensive efficacy of patients of all ages in the study group was better than that of the control group (P < 0.05). After 8 weeks of treatment, the comprehensive efficacy of patients aged 23- 35, 36-50, and 51-60 years old in the study group was better than that of the control group (P < 0.05), and the comprehensive efficacy of patients aged 18- 22 years old was comparable between the two groups. After 4 weeks of treatment, the comprehensive efficacy of patients aged 36-50 and 51-60 years old in the study group was better than that of the control group (P < 0.05), and the comprehensive efficacy was comparable between the two groups of patients aged 18-22 and 23-35 years. Overall, Tiaodu Tongmai acupuncture therapy has advantages in treating preclinical rheumatoid arthritis patients aged 36-50 and 51- 60 years. [ABSTRACT FROM AUTHOR]

There is a potential link between rheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF). The aim of this study is to investigate the molecular processes that underlie the development of these two conditions by bioinformatics methods. The gene expression samples for RA (GSE77298) and IPF (GSE24206) were retrieved from the Gene Expression Omnibus (GEO) database. After identifying the overlapping differentially expressed genes (DEGs) for RA and IPF, we conducted functional annotation, protein–protein interaction (PPI) network analysis, and hub gene identification. Finally, we used the hub genes to predict potential medications for the treatment of both disorders. We identified 74 common DEGs for further analysis. Functional analysis demonstrated that cellular components, biological processes, and molecular functions all played a role in the emergence and progression of RA and IPF. Using the cytoHubba plugin, we identified 7 important hub genes, namely COL3A1, SDC1, CCL5, CXCL13, MMP1, THY1, and BDNF. As diagnostic indicators for RA, SDC1, CCL5, CXCL13, MMP1, and THY1 showed favorable values. For IPF, COL3A1, SDC1, CCL5, CXCL13, THY1, and BDNF were favorable diagnostic markers. Furthermore, we predicted 61 Chinese and 69 Western medications using the hub genes. Our research findings demonstrate a shared pathophysiology between RA and IPF, which may provide new insights for more mechanistic research and more effective treatments. These common pathways and hub genes identified in our study offer potential opportunities for developing more targeted therapies that can address both disorders. [ABSTRACT FROM AUTHOR]

Abnormal expression of microRNAs (miRNAs) plays a significant role in the pathogenesis of rheumatoid arthritis (RA), and thus miRNA-based therapy has emerged as a promising approach for the RA treatment. Herein, miR-30a was successfully screened and identified to be an essential mediator for the inflammation of RA. MiR-30a could directly target the Snai1 gene and further regulate the Cad11 expression to inhibit the NF-κB and MAPK signaling pathways, contributing to the anti-inflammatory effect. To enhance the therapeutic outcome of miR-30a, fluorinated polyamidoamine dendrimer (FP) was developed as the carrier to achieve the miR-30a delivery in the mice of collagen-induced arthritis. The carrier FP and miR-30a formed stable nanocomplexes and effectively mediated the transfection of miR-30a to execute the anti-inflammatory response in lipopolysaccharide-stimulated macrophages. Further, the intravenous administration of FP/miR-30a showed obvious accumulation in the inflamed joints and inhibited the inflammatory response via the Snai1/Cad11 axis, thereby contributing to the anti-arthritic efficacy. In addition, the FP/miR-30a nanocomplexes displayed favorable biocompatibility, as they did not cause the damage of organs following the systemic administration. Taken together, our study demonstrated that miR-30a is an effective anti-inflammatory oligonucleotide and the fluorinated dendrimer-mediated miR-30a delivery possesses the potential to be a promising approach for the treatment of RA and other autoimmune diseases. The intravenous administration of FP/miR-23b nanoparticles significantly mitigated the symptoms of rheumatoid arthritis through the regulation of inflammation network in macrophages. [Display omitted] • miR-30a was found to possess favorable anti-inflammatory effect in macrophages. • The Snai1 gene was identified as the target of miR-30a and further regulated the Cad11 expression. • Fluorinated polyamidoamine was used as a carrier for the miR-30a delivery. • The administration of FP/miR-30a could mitigate the symptoms of rheumatoid arthritis. • The FP/miR-30a nanocomplexes displayed favorable biocompatibility. [ABSTRACT FROM AUTHOR]

ABSTRACT Rheumatoid arthritis (RA) is a common chronic autoimmune disorder with an incompletely elucidated pathogenesis. Emerging research indicates that dietary factors may significantly influence the onset and progression of RA. Nevertheless, the causal relationship between dietary habits and RA remains ambiguous. This investigation employed a multivariable Mendelian randomization (MVMR) methodology to rigorously assess the potential causal effects of various dietary factors on RA risk. This study utilized genome‐wide association study (GWAS) summary‐level data, encompassing dietary preferences (n = 113,425–159,579), and RA data (n = 302,614) from the most recent FinnGen database. The primary causal analysis was conducted using inverse‐variance weighting (IVW), complemented by MR‐Egger, weighted median, Bayesian weighted Mendelian randomization, and Robust Adjusted Profile Score (RAPS) methodologies. Sensitivity analyses incorporated Cochran's Q test, MR‐Egger intercept test, MR‐PRESSO, and leave‐one‐out analysis. Steiger tests were employed to evaluate the identified dietary preferences. MVMR was utilized to assess the direct impact of dietary factors on RA. The study identified significant associations between RA and nine dietary preferences: F‐lentils/beans liking (Fle), chips liking (Chips), coffee difference liking (CD), coffee with sugar liking (CWS), milk chocolate liking (MC), coriander liking (Coriander), pollock liking (Pollock), soft cheese liking (SC), and blue cheese liking (BC). The MVMR analysis indicated that genetically predicted coriander and MC have a direct impact on RA, independent of other dietary factors. This study presents novel causal evidence suggesting that dietary preferences may impact the risk of RA. Specifically, a reduction in the consumption of milk chocolate and coriander may contribute to the prevention and alleviation of RA. However, additional research is required to elucidate the underlying mechanisms and to validate these findings across diverse populations. [ABSTRACT FROM AUTHOR]

There are still controversies about the efficacy of cycling to a second tumor necrosis factor inhibitor (TNFi) in patients with inflammatory arthritis. The aim of this study was to evaluate survival, persistence and effectiveness of golimumab (GLM) in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) with previous experience with other TNFi and to compare these results with TNFi naive patients. Observational cohort of consecutive patients with RA, PsA and axSpA who had started treatment with GLM according to medical indication. bDMARD naive and TNFi experienced patients were selected. A total of 147 (62.3%) bDMARD naive and 45 (19.1%) TNFi experienced patients were included. Patients were followed up for a total of 441.5 patients/year, 55 (28.6%) discontinued GLM, 42 (28.6%) and 13 (28.9%) in each group, respectively (p = 0.967). The majority (63.6%) suspended due to inefficacy, followed by lack of access (23.6%) and adverse events (9.1%). Median GLM survival was 74.0 months (95% CI 57.0, 91.0) and 71.0 months (95% CI 37.0, 105.0), in the bDMARD naive and TNFi experienced patients, respectively (p = 0.695). Drug persistence at 6, 12, 24 and 36 months was 92.8%, 88.1%, 76.1%, 65.4% and 93.1%, 77.4%, 74.2%, 68.5%, respectively. In the multivariable analysis, having public health insurance was associated with higher risk of drug discontinuation (HR 2.56, 95% CI 1.28–5.00, p = 0.008). TNFi experienced patients did not show significantly higher risk of GLM suspension (HR 1.35, 95% CI 0.70–2.57, p = 0.370). In this cohort, TNFi experienced patients had comparable survival and persistence of treatment with GLM. Having public health insurance was associated with lower drug retention rates. [ABSTRACT FROM AUTHOR]

Ultrasound (US) remission in rheumatoid arthritis (RA) targets synovitis absence. Tenosynovitis triggers flares. Despite increased ultrasound use, flare patterns among patients with low disease activity (LDA) and ultrasound remission, especially in real-world settings, are poorly understood. This study examined flare rates and predictors of US remission in patients without synovitis or tenosynovitis. In a study of 88 patients achieving US remission and LDA, the focus was on the time to the first flare over a 2-year follow-up. US remission, indicated by the absence of active synovitis and tenosynovitis based on a power Doppler (US-PD) score of 0, was assessed on various joints. Flares are defined by the need for additional medication or encountering a US-PD flare. They were monitored at the baseline, 1-year, and 2-year visits with further US evaluation at clinical flare-ups. Baseline factors linked to a shorter time to flare were analyzed. At 1 year, LDA and US remission rates were 75% and 92%, respectively, and at 2 years, 73% and 87% respectively. Over the 2 years, 40% experienced flare, occurring on average at 11.7 ± 7.0 months. Notably, 5.7% have US-PD flares without clinical signs. Analysis revealed Stage III disease and CRP as factors linked to a shorter time to flare. In patients with RA achieving LDA and US remission, frequent flares were observed with US remission over 2 years, but most maintained sustained remission. Baseline factors are essential for predicting flares, emphasizing continuous monitoring and personalized treatment to sustain remission and minimize flare risks in RA management. [ABSTRACT FROM AUTHOR]

It remains unknown whether frailty status confers an increased risk of readmission in patients with rheumatoid arthritis (RA). From the 2018 Nationwide Readmissions Database (NRD), we identified adult patients (age ≥ 18 years) admitted with a diagnosis of RA between January to June 2018. Utilizing validated Hospital Frailty Score, patients' frailty risk score was calculated at the time of index admission and categorized into frail (score ≥ 5) and non-frail (score < 5) groups. Our primary outcomes of interest were (1) 180- day readmission rate (2) inpatient mortality; secondary outcomes included prolonged length of stay, LOS (LOS ≥ 7 days), and costs of hospitalization. Multivariable Cox proportional hazard analysis was performed to evaluate the independent effect of frailty adjusting for confounding variables. 133,187 patients met inclusion criteria, with mean age 67.7 years, of whom 64,131 (48.1%) patients were categorized as frail. The rate of readmission was significantly higher in the frail (56.60%) compared to the non-frail group (30.61%). At index hospitalization, frail patients also had significantly higher inpatient mortality compared to non-frail patients (3.36% vs 0.39%, p < 0.005), longer LOS (26.24% vs 7.82%, p < 0.005). On multivariate analysis frailty was independently associated with a 9% increased risk of readmission (adjusted hazard ratio, 1.09; 95% confidence interval, 1.08 – 1.11). People with RA who are frail have higher rates of readmission than those who are not frail. These findings are crucial in identifying at-risk patients with RA and in discharge planning after hospitalization. Key Points • People with RA who are frail have higher rates of readmission than those who are not frail. • Frail RA patients are also at higher risk of hospitalization-related adverse outcomes, including inpatient mortality and longer hospital stay. • Sepsis is the most common cause for readmission identified in frail patients with RA. • These findings suggest that frailty may be a useful metric in identifying patients with RA at an increased risk of adverse health outcomes. [ABSTRACT FROM AUTHOR]

Background: The magnesium depletion score (MDS) is a scoring system developed to predict magnesium deficiency based on pathophysiological factors that affect renal reabsorption. The relationship between systemic magnesium status and arthritis is unclear. The purpose of this study was to determine the association between the MDS and rheumatoid arthritis (RA) as well as osteoarthritis (OA). Methods: This study was conducted through a cross-sectional survey of 20,513 adults aged ≥ 20 years who participated in NHANES from 2007 to 2018. The four dimensions of the MDS included diuretics, proton pump inhibitors, glomerular filtration rate, and excessive alcohol consumption. Univariate and multivariable-weighted logistic regression were used to assess the associations between MDS and RA/OA, and a test for trend was performed to analyze the presence of a dose–response relationship. Subgroup analyses and interaction tests were performed according to confounders. Results: After adjustment for all covariates, we found a graded dose–response relationship between MDS and RA or OA. When MDS was considered as a continuous variable, each onefold increase in MDS was associated with a 1.21-fold increase in the odds of having RA (OR = 1.21, 1.10, 1.33) and a 1.12-fold increase in the odds of having OA (OR = 1.12, 1.04, 1.21). There was an interaction of sex in the effect of MDS on RA (Pinteraction = 0.004) and age in the effect of MDS on OA (Pinteraction = 0.006). In addition, these associations were further confirmed in sensitivity and subgroup analyses. Conclusions: Our study identified significant dose–response associations between MDS and both RA and OA. More biological mechanisms are needed in the future to validate and clarify the results of this study. Key Points • After adjustment for all covariates, we found a graded dose-response relationship between MDS and RA and OA. • There was an interaction of sex in the effect of MDS on RA and age in the effect of MDS on OA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is widespread globally, with the emergence of metabolites derived from both the host and microbes playing a pivotal role in its pathogenesis. This study aims to elucidate the relationships between serum metabolites and the immunological and clinical features of RA. Serum samples were collected from 35 RA patients and 37 healthy controls (HC). Metabolite profiling was performed using gas chromatography-mass spectrometry (GC/MS). Principal component analysis revealed a significant distinction between the RA and HC cohorts. Employing univariate statistical analysis, we identified 36 differential metabolites. Among these, 9 metabolites, including galactose and glucose, were found to be enriched, while the remaining metabolites, such as citric acid, fumaric acid, and inosine, were depleted in RA. These diverse metabolites encompassed various metabolic processes, including the biosynthesis of fatty acids, amino acids, and glucose. The enrichment of glucose and galactose in RA exhibited a substantial correlation with elevated IgG levels, as determined through correlation analysis. Conversely, the depletion of citric acid was correlated with elevated levels of C3 and CRP. Methionine, which also declined in RA patients, displayed a negative correlation with ESR. Furthermore, galactose and glucose exhibited significant positive correlations with naïve B cells, while the decreased eicosanoic acid level in RA was significantly associated with an increase in natural killer cells. Our findings suggest that the altered serum metabolite profile in RA is closely linked to disease severity and the dysregulated immune responses observed in RA patients. Key Points • Identified nine metabolites with upregulated expression and twenty-seven metabolites with downregulated expression. • Established a correlation between alterations in serum metabolite levels and inflammatory markers in RA patients. • Discovered a significant association between changes in serum metabolites and immune cell profiles in RA patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the associations between biological aging, metabolic heterogeneity of obesity, and rheumatoid arthritis (RA). Methods: This prospective cohort study analyzed 268,184 individuals from the UK Biobank. Biological age was estimated using phenotypic age (PhenoAge), Klemera-Doubal methods (KDM-BA), and telomere length. We calculated KDM-BA acceleration and PhenoAge acceleration after subtracting the effect of chronological age by regression residual. The metabolic heterogeneity of obesity can be evaluated by four BMI metabolic phenotypes, namely metabolically unhealthy normal weight (MUNW), metabolically healthy normal weight (MHNW), metabolically unhealthy overweight/obesity (MUOO), and metabolically healthy overweight/obesity (MHOO). Cox models were employed to estimate the associations between biological aging, metabolic heterogeneity of obesity, and RA risk. Results: A total of 2842 patients experienced RA during a mean follow-up time of 12.21 years. A standard deviation (SD) increase in KDM-BA acceleration and PhenoAge acceleration was associated with an increased risk of RA by 13% (hazard ratio = 1.13; 95% CI, 1.09–1.17) and 39% (HR = 1.39; 95% CI, 1.34–1.44), respectively. A SD increase in telomere length was associated with a reduced risk of RA by 5% (HR = 0.95; 95% CI, 0.91–0.98). Compared to the MHNW group, the MUOO group was associated with a 51% increase in the risk of incident RA. In the joint effect analysis, compared to the MHNW + KDM-BA younger subgroup, the HR (95% CI) for RA was 1.68 (1.48, 1.90) in the MUOO + KDM-BA older subgroup. Conclusion: Accelerated biological aging may heighten the susceptibility to RA, particularly in individuals with obesity or metabolic dysfunction. Key Points •Accelerated biological aging increases the risk of developing RA. •Overweight/obese people with a healthy metabolism have a higher risk of RA than those with normal weight and healthy metabolism. •The BMI metabolic phenotype has a strong modifying effect on the association between KDM-BA/PhenoAge and RA risk. [ABSTRACT FROM AUTHOR]

To investigate the incidence of the discontinuation among tofacitinib and biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). This retrospective population-based cohort study included 5,008 RA patients who initiated treatment with either tofacitinib or bDMARDs (etanercept, adalimumab, golimumab, tocilizumab, or abatacept) between January 1, 2014, and December 31, 2020. We conducted Cox proportional hazards regression and subsequent time-dependent regression to assess the risk of drug discontinuation, with adjustments for potential variables. The highest drug discontinuation rate was observed with etanercept (43.27%), while the lowest was with tofacitinib (21.8%). Tofacitinib was associated with a significantly lower risk of discontinuation compared to etanercept (HR: 0.67, 95% CI: 0.57–0.80) and other bDMARDs. Higher steroid dosage and the presence of concomitant connective tissue diseases were significant risk factors for drug discontinuation. Conversely, the use of methotrexate was associated with a reduced risk of discontinuation. Tofacitinib demonstrated a lower risk of drug discontinuation compared to TNFi, with the risk factors for discontinuation including higher steroid dosage and concomitant connective tissue diseases. The study highlights the importance of considering several potential risk factors in drug discontinuation. Key Points • Non-TNFi biologic agents demonstrated better drug retention than TNFi among patients diagnosed with rheumatoid arthritis, with tofacitinib showing the lowest discontinuation rate (21.8%), underscoring its potential for superior drug retention in rheumatoid arthritis management. • Several factors were associated with drug discontinuation: higher steroid dosage and concomitant connective tissue diseases were linked to a higher discontinuation rate, whereas the concomitant use of methotrexate was associated with a lower risk of discontinuation. [ABSTRACT FROM AUTHOR]

Background: The relationship between social determinants of health (SDH) and disease outcomes in rheumatoid arthritis (RA) is not well documented. Methods: Data were extracted from the Ontario Best Practices Research Initiative (OBRI) registry for patients between January 2008 and April 2022. Adjusted mixed models analysis was used to investigate the effect of baseline SDH on disease activity (Clinical Disease Activity Index (CDAI)) and functional disability (Health Assessment Questionnaire-Disability Index (HAQ-DI)) 12 months after enrollment. The analyses were completed on multiple imputed data. Results: There were 2651 patients with a mean age of 58.1 years (SD 12.9). The majority (77.8%) were female. Greater improvements in physical function were seen in patients who were full-time employed (difference = − 0.20; 95% CI − 0.28, − 0.11), part-time employed (difference = − 0.10; 95% CI − 0.19, − 0.02), or retired (difference = − 0.17; 95% CI − 0.25, − 0.08), compared to unemployed, those with highest income ($75,000 or more) (difference = − 0.23; 95% CI − 0.37, − 0.09). Caucasian was also associated with a positive impact on functional ability (difference = − 0.09; 95% CI − 0.17, − 0.02). In contrast, smokers had smaller improvements in physical function (difference = 0.07; 95% CI 0.002, 0.14). Interestingly, women had greater improvement in CDAI (difference = − 2.40; 95% CI − 3.29, − 1.51), while they reported less improving in their physical function (difference = 0.33; 95% CI 0.27–0.39). Achieving CDAI low disease activity/remission state was also more common in females. Conclusions: Our findings suggest that disease activity and functional disability are affected by different SDH factors. The effects of SDH should be better understood and addressed by rheumatologists to provide equitable healthcare for all patients with RA. Key points • This study explored a comprehensive panel of social determinants of health and their relationship to clinical outcomes. • Previously unreported factors such as employment status and income were found to influence clinical outcomes. • Our findings can help physicians to identify high-risk patients who may benefit from additional attention to their social background. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the role of TSPAN32, a member of the tetraspanin family, in rheumatoid arthritis (RA). The objective was to assess the expression levels of TSPAN32 in experimental RA models and in RA patient immune cells, exploring its potential as a regulatory factor in RA pathogenesis. The study employed adjuvant‐induced arthritis in rats and collagen‐induced arthritis (CIA) in mice as experimental models. Ex vivo analyses included evaluating TSPAN32 expression in immune cells at different stages of the disease. In silico data analysis involved examining transcriptomic datasets from drug‐naïve and treated RA patients to correlate TSPAN32 expression with clinical parameters. TSPAN32 overexpression experiments in splenocytes from CIA mice aimed to demonstrate its functional impact on antigen‐specific immune responses. The animal models revealed a significant downregulation of TSPAN32, particularly in synovial‐infiltrating T cells. Also, TSPAN32 overexpression inhibited pro‐inflammatory cytokine production in splenocytes. In RA patients, TSPAN32 was consistently downregulated in circulating and synovial‐infiltrating T cells, as well as in CD8+ T cells, B cells and NK cells. Drug treatment did not significantly alter TSPAN32 levels. Negative correlations were observed between TSPAN32 expression and inflammatory markers (CRP, ESR) and clinical scores (SDAI) in RA patients. This study suggests that reduced TSPAN32 expression characterizes pathogenic T‐cell populations in RA, highlighting its potential as biomarker for inflammation and disease activity. TSPAN32 may play a crucial role in shaping adaptive immune responses in RA, opening avenues for novel therapeutic strategies targeting this tetraspanin family member. [ABSTRACT FROM AUTHOR]

Background: Hypocortisolemia is associated with increased expression of NR3C1 (glucocorticoid receptor, GR) in blood cells. As endogenous cortisol production is decreased in some RA patients, we tested the hypothesis that GR may be aberrantly expressed in rheumatoid synovium. Methods: We defined the cellular pattern of NR3C1 synovial expression using human and mouse single‐cell RNA‐sequencing data. Bulk synovial RNA‐sequencing data from early (n = 57) or established (n = 94) RA were compared to osteoarthritis (n = 22) and healthy synovium (n = 28). Results: GR was expressed in all synovial cell types in both human and experimental arthritis. GR synovial expression, as well as 11β‐HSD1/11β‐HSD2 enzyme ratio, were higher in RA than healthy and osteoarthritic tissue, regardless of disease duration or treatment. Given that GR expression varied across samples, we searched for differences between RA patients with higher versus lower GR expression. Indeed, the synovial transcriptome of RA patients with high versus low GR expression (1st quartile, 30,517 ± 4876 vs. 4th quartile, 19,382 ± 2523 normalized counts) was enriched for proinflammatory gene‐sets, including 'inflammatory response', 'IFN‐γ response' and 'IL6/JAK/STAT3 signalling'. High synovial GR expression was also associated with increased JAK2 and PTPRK expression, denoting activation of the proinflammatory sublining fibroblasts. In contrast, low GR expression was associated with increased COMP and COL6A2 expression, denoting a resting synovial state. Conclusions: GR is overexpressed in the synovium of some RA patients in association with proinflammatory gene expression and activated sublining fibroblast status. Further studies should examine whether GR overexpression may act as a compensatory mechanism sensitizing synovial tissue to glucocorticoid action in RA. [ABSTRACT FROM AUTHOR]

Objectives: It is not clear if or how the incidence of systemic conditions like type 2 diabetes mellitus (DM2), rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) affects dental service utilization. Using nationwide Danish register data, the aim of this study was to analyse the use of dental services 7 years before and after being diagnosed with DM2, RA or IBD between 1997 and 2011. Methods: Information about incident DM2 was obtained from the Register for Selected Chronic Diseases and Severe Mental Disorders, and incident RA and IBD were defined based on diagnosis codes of hospital contacts identified through the National Patient Register. Separately, for each of the three conditions, each individual with the incident condition was matched to one control individual based on age, gender, country of origin, municipality of residence, highest completed education, the main source of income and income using coarsened exact matching in the year of incidence. The use of dental services and treatments received within each calendar year from 7 years before to 7 years after getting the condition were analysed with generalized estimating equations. Results: People with incident DM2 were less likely (by seven percentage points) to be dental service users within a year than people without incident DM2 for a period extending from up to 7 years prior to 7 years after the diagnosis. This difference even slightly increased after the diagnosis. Those with incident IBD exhibited a consistently but modestly higher proportion of dental service use (three percentage points) than those without incident IBD before and after the diagnosis. Differences in the use of services between those with or without incident RA were minor. For all three systemic diseases, detected differences mainly mirrored differences in the provision of supragingival scaling and restorative treatment. Conclusions: The findings suggest that the impact of these three systemic conditions on dental service use was minor. [ABSTRACT FROM AUTHOR]

This commentary explores the potential cardiovascular (CV) benefits of combining methotrexate (MTX) and Janus kinase inhibitors (JAKis) in the treatment of rheumatoid arthritis (RA). While European guidelines recommend MTX as first-line treatment, concerns about the CV risks associated with JAKis have emerged. This article reviews the existing literature to assess the role of concomitant MTX in reducing CV risk when used with JAKis. Clinical trials confirm the efficacy of JAKis in combination with MTX in terms of treatment outcomes in RA. However, the number of major adverse cardiovascular events (MACEs) reported is too low to draw conclusions on adverse CV outcomes. Indirect evidence does, however, suggest potential protective effects of MTX on CV outcomes, as several mechanisms may contribute to MTX's cardioprotective effects, including reduced inflammation, adenosine monophosphate-activated protein kinase (AMPK) activation, increased cholesterol efflux, and adenosine accumulation. These mechanisms and the available data may support the case for CV benefits of concomitant MTX when JAKis are used in the treatment of patients with RA, although further research is needed. In particular, the lipid paradox associated with RA highlights the complex relationship between RA treatments (MTX, JAKis, tumor necrosis factor (TNF) inhibitors, and interleukin (IL)-6 receptor inhibitors), inflammation, different lipid profiles, and CV risk. In the absence of contraindications and when MTX is tolerated, this commentary suggests the concomitant use of MTX and JAKis as a preferred option for optimizing CV protection in patients with RA. [ABSTRACT FROM AUTHOR]

Introduction: ORAL Surveillance, a post-authorisation safety study of patients with rheumatoid arthritis (RA) enriched for cardiovascular (CV) risk, demonstrated increased risk of major adverse CV events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) for tofacitinib versus tumour necrosis factor inhibitors (TNFi). This analysis of a real-world Canadian observational study evaluated tofacitinib safety/effectiveness in patients meeting or not meeting CV risk criteria. Methods: CANTORAL included patients with moderate-to-severe RA initiating tofacitinib (10/2017–07/2020; N = 504). Interim data (data-cut: 07/2021) were stratified as CV risk-enriched (CV+ ; patients ≥ 50 years with ≥ 1 additional CV risk factor) or not CV risk-enriched (CV−; ≥ 50 years without additional CV risk factors and 18–49 years with/without CV risk factors). Safety and persistence were evaluated to month (M) 36. Effectiveness outcomes to M18 included Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA)/remission (CANTORAL co-primary endpoints) and Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]) < 3.2/ < 2.6. Results: Overall, 272/232 patients were included in CV+ /CV− cohorts (full analysis set) (435/356 patient-years [safety analysis set]). Incidence rates (events/100 patient-years) in CV+ /CV− cohorts were 138.5/112.5 for treatment-emergent adverse events (AEs); 17.0/5.6 for serious AEs; 1.2/0.3 for deaths; 5.5/1.7 for serious infections; 1.4/1.1 for herpes zoster; 1.6/0.0 for MACE; 2.1/0.3 for malignancies (excluding NMSC); 0.7/0.6 for NMSC; 0.5/0.0 for venous thromboembolic events. Persistence was generally comparable between cohorts. In CV+ /CV− cohorts, at M6, CDAI LDA and remission rates were 51.5%/54.6% and 12.0%/19.6%; DAS28-4(CRP) < 3.2/ < 2.6 rates were 44.0%/39.3% and 31.5%/28.8%, respectively; effectiveness was generally maintained to M18. Conclusions: In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit–risk assessment, including CV assessment/management, to optimise RA outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The 1-year PROspective sarilumab (preFILled syringe/pen) multinational, obsErvational (PROFILE) study evaluated the real-world effectiveness and safety of sarilumab in patients with moderate-to-severe rheumatoid arthritis (RA). Methods: Safety endpoints included adverse events (AEs) and lab abnormalities. Effectiveness endpoints included the ACR core set. The primary endpoint was the change from baseline in Clinical Disease Activity Index (CDAI). All statistics are descriptive and p values were nominal. Results: In total, 595 patients were treated, of whom 223 (37.5%) received sarilumab monotherapy and 372 (62.5%) received combination therapy. Upon initiation of sarilumab, an improvement in the mean (SD) CDAI score was observed at week 24 [11.4 (10.3)] and was maintained through week 52 [10.0 (10.5)], resulting in a mean [SD] reduction of −14.9 (12.7) and −14.4 (12.9), respectively. There were consistent improvements in disease activity that were similar for patients on monotherapy vs. combination therapy. An increase in the proportion of patients achieving remission and low disease activity was reported. By week 52, both groups had improved physical function and quality of life. There were no new safety signals. The proportions of any patients reporting a treatment-emergent adverse event (TEAE) or serious treatment-emergent AE (SAE) was 66.2% and 5.9%, respectively, and were similar between both treatment groups. Overall, 15.6% of patients discontinued sarilumab treatment due to TEAEs. The most commonly reported TEAE of interest was neutropenia (14.1%). Conclusions: In this 1-year, observational real-world study, sarilumab therapy resulted in improved clinical outcomes. The safety profile was consistent with that observed in sarilumab randomized clinical trials. This study was entered on the German website (Paul Ehrlich Institute) on January 11, 2018, with NIS No.: 423. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid meningitis (RM) is an extremely rare extra-articular complication of rheumatoid arthritis (RA), with approximately 165 cases reported world-wide. RM exhibits a broad range of symptoms, with stroke-like episodes and seizures being the most common manifestations. The primary differential diagnoses include vascular and infectious diseases. The influence of immunomodulatory medications on the pathophysiology of RM remains unclear. There are no consensus guidelines on therapeutic regimen. Methods: We present four patients with prior history of RA that developed different neurological syndromes in correlation to radiological leptomeningitis. Clinical presentations, comorbid conditions, supplementary diagnostic assessments, treatments, and prognosis are provided. A literature review of recent immunosuppressive management in RM patients was performed. Results: Three patients presented to hospital with recurrent focal seizures. Only two suffered meningism, reporting headache and fever. Magnetic resonance imaging (MRI) showed different grades of leptomeningitis across all cases. Notably, three cases demonstrated bilateral involvement extending to the pachymeninges. Two patients exhibited pronounced CSF mononuclear inflammation while extended microbiological evaluations yielded negative results. Two patients required biopsy for confirmation. The initiation of immunosuppressive therapy marked a turning point for three patients who previously exhibited progressive deterioration. Mortality was absent in all cases. Conclusions: Our experience remarks the elusive nature of RM. Rigorous exclusionary diagnostics are imperative to differentiate RM from mimicking conditions. Clinical manifestations oscillate between transient episodes and progressive neurological impairments, punctuated by frequent epileptic seizures. In scenarios where clinical worsening persists or where clinical and radiological evaluations are inconclusive, aggressive immunosuppressive therapy is recommended. [ABSTRACT FROM AUTHOR]

Among the numerous treatment options for rheumatoid arthritis (RA), the promotion of synoviocyte apoptosis and inhibition of inflammation are considered the most effective. However, the potential pro‐apoptotic effects of gross saponins of Tribulus terrestris (GSTT), which are natural saponins derived from the herb Tribulus terrestris L., on rheumatoid arthritis fibroblast‐like synoviocytes (RA‐FLSs) and their essential molecular mechanisms remain unclear. The aim of the present study was to investigate the influence of different concentrations of GSTT on RA‐FLSs using various assays, including cell counting kit‐8 (CCK‐8), reverse transcription polymerase chain reaction (RT‐PCR), enzyme‐linked immunosorbent assay (ELISA), flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot analysis. These assessments were conducted to evaluate the cell viability, changes in the levels of inflammatory cytokines, apoptosis rates and alterations in protein expression related to this process. In vivo, arthritis clinical score, haematoxylin and eosin (HE) staining and ELISA were used to assess paw inflammation, histopathology and serum inflammatory cytokine changes. Our findings demonstrated that GSTT substantially promotes the apoptosis of RA‐FLSs and reduces pro‐inflammatory cytokine levels. GSTT also reduced the Bcl‐2/Bax ratio and inhibited JNK and p38 phosphorylation. Furthermore, GSTT exhibits positive effects on RA by improving clinical scores, reducing synovial inflammatory infiltration and lowering serum pro‐inflammatory cytokine levels. Therefore, by promoting the apoptosis of RA‐FLSs and suppressing inflammation through the inhibition of the MAPK signalling pathway, GSTT is a promising therapeutic intervention for RA. [ABSTRACT FROM AUTHOR]

Background: Semaphorins are axonal guidance molecules involved in neural development and contribute to the regulation of various phases of the immune response. This study aimed to investigate the plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and the regulatory T (Treg) cell-related cytokine interleukin-10 (IL-10), as well as the gene expression levels of forkhead box P3 (FoxP3), Semaphorin-3A (Sema-3A), Neuropilin-1 (Nrp-1), Semaphorin-4A (Sema-4A), and Plexin-D1 (Plxn-D1), in the peripheral blood of newly diagnosed rheumatoid arthritis (RA) patients treated with conventional disease-modifying antirheumatic drugs (DMARDs) for 6 months compared with healthy controls. Methods: Peripheral blood samples were obtained from 40 newly diagnosed RA patients (before and after treatment) and 40 age- and sex-matched healthy subjects. The plasma concentrations of IL-6 and IL-10 were quantified via enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of FoxP3, Sema-3A, Nrp-1, Sema-4A, and Plxn-D1 were assessed via quantitative real-time PCR. Results: Compared with those in the controls, the plasma IL-6 levels in the RA patients (both pre- and post-treatment) were significantly greater (P < 0.001). Compared with the pre-treatment levels, the plasma IL-6 levels decreased significantly after DMARD therapy (P < 0.05). Moreover, plasma IL-10 levels were significantly greater in post-treatment RA patients than in controls (P < 0.05). The gene expression of FoxP3, Sema-3A, and Nrp-1 was significantly lower in pre-treated RA patients than in controls (P < 0.001). Compared with that in pre-treatment RA patients, the gene expression of FoxP3, Sema-3A, and Nrp-1 in DMARDs-treated RA patients was strongly increased (P < 0.05, P < 0.01, and P < 0.01, respectively). There was a positive correlation between Sema-3A gene expression and the gene expression of FoxP3 (r = 0.292, P < 0.01) and Nrp-1 (r = 0.569, P < 0.0001). Conclusion: Conventional DMARDs therapy effectively reduces disease activity and inflammation in newly diagnosed RA patients by increasing FoxP3, Sema-3A, and Nrp-1 gene expression. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovium and progressive joint destruction which significantly affects both quality of life and socioeconomic status. Admittedly, various treatments are available, but they are usually accompanied by various side effects, from mild to severe, and potentially with adverse events. Tumour necrosis factor‐alpha (TNF‐α) plays a crucial role in the pathophysiology of RA. It promotes inflammatory, apoptosis and necroptosis via TNF receptor‐1 (TNFR1) but elicit anti‐inflammatory effects via TNFR2. Herein, targeting TNFR2 has gained attention in RA studies. Understanding the role of nanomedicine in modulating TNFR2 signalling may be the instrument in development of RA therapies. Nanotechnology has made a significant progress in treating various conditions of diseases since its inception. Due to this, nanomedicine has emerged as a promising therapeutics approach for RA. Recent studies have demonstrated the potential of nanomedicine in RA theranostics, combining therapy and diagnostics for improved treatment outcomes. Owing to the challenges and advancements in the field of nanotechnology, nanoparticles are seen as an applicable candidate in the treatment of RA. In this review, we provide an overview of the role of nanomedicine in targeting TNFR2 for the treatment of RA and highlight the limitations of current therapies as well as the potential of nanocarriers with controlled drug release and active targeting abilities. [ABSTRACT FROM AUTHOR]

Aim: Elevated C‐reactive protein (CRP), a marker of inflammation, is common in many chronic conditions. We aimed to examine to what extent elevated CRP in chronic conditions could be explained by concurrent adiposity. Materials and Methods: This cross‐sectional study analysed UK Biobank data on 10 chronic conditions reported at baseline. Linear regression models explored the extent to which CRP concentrations were elevated in each condition, unadjusted; adjusted for sociodemographic confounders and lifestyle and body mass index (BMI) in a series of models; or adjusted for BMI and waist circumference together or for adiposity alone. Results: After exclusion of participants with a potential acute infection at baseline, we tested the association in 292 772 UK Biobank participants. Linear regression showed that elevated CRP concentration was associated with all included conditions. After adjustment for sociodemographic confounders, lifestyle and BMI, chronic kidney disease, heart failure, liver disease, psoriasis, rheumatoid arthritis and chronic obstructive pulmonary disease were still associated with elevated CRP. In contrast, the association between prevalent diabetes, prior myocardial infarction (MI), hypertension and sleep apnoea and CRP could be mostly explained by adiposity alone. For example, the 42% higher CRP concentrations in diabetes compared to those without diabetes in the unadjusted model (lnCRP β: 0.35; 95% confidence interval [CI]: 0.32–0.37, p < 0.001) were completely attenuated after adjustment for BMI (lnCRP β: −0.07; 95% CI: −0.09−0.05, p < 0.001). Conclusions/Interpretation: In diabetes, MI, hypertension and sleep apnoea and elevated CRP appears to be accounted for by the greater adiposity typically evident in these conditions. However, for the other conditions, systemic inflammation cannot be explained by excess adiposity alone. [ABSTRACT FROM AUTHOR]

Objective: to explore the effect of CD5-like molecule (CD5L) on rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) and the relative molecular mechanism of CD5L in it. Methods: Recombinant protein CD5L was used to stimulate the cultured RA-FLS cells. The inflammation-related cytokines were determined by real time-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). the signal molecules and apoptosis-related molecules were detected by western blot assay (WB), and cell counting kit-8 (CCK-8) was used to detect the proliferation. Results: CD5L can increase the production of IL-6, IL-8, AND TNF-α and this effect can be inhibited by signal pathway inhibitor. At the same time, CD5L activated ERK1/2 MaPK signal, inhibitor treatment can weaken the intensity of phosphorylation. in addition, CD5L can enhance the proliferation ability of RA-FLS. Conclusion: CD5L induces the production of inflammatory cytokines in Ra-Fls through the ERK1/2 MAPK pathway and increases cell survival. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, and understanding its genetic and molecular basis is crucial for early diagnosis, treatment, and prevention. Objective: this study aims to explore the association between IL-4 polymorphisms (rs2227284, rs2243267, rs2243270, and rs2243283) and RA risk. Methods: the four IL-4 polymorphisms were genotyped in 493 RA patients and 493 healthy controls using agena MassARRAY. Logistic regression analysis calculated odds ratio (OR) and 95% confidence interval (CI) to estimate the relationship between IL-4 polymorphisms and RA risk. Results: Overall analysis revealed that rs2243267 (GG vs. cc: OR = 0.26, FDR-p = .032; Recessive: OR = 0.27, FDR-p = .048) and rs2243270 (aa vs. GG: OR = 0.26, FDR-p = .024; Recessive: OR = 0.27, FDR-p = .024) were associated with a decreased risk of RA. stratified analysis indicated that rs2243267 and rs2243270 were correlated with reduced RA risk in female, smoking, BMI <24, and drinking population; rs2227284 was associated with a decreased RA risk in BMI <24 and drinking population. Moreover, rs2243267 and rs2243270 were significantly associated with reduced ACPA positivity. Conclusions: Our findings suggest that IL-4 polymorphisms (rs2227284, rs2243267, and rs2243270) act as protective factors for RA in the chinese han population. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is the predominant manifestation of inflammatory arthritis, distinguished by an increasing burden of morbidity and mortality. The intricate interplay of genes and signalling pathways involved in synovial inflammation in patients with RA remains inadequately comprehended. This study aimed to ascertain the role of necroptosis in RA, as along with their associations with immune cell infiltration. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify central genes for RA. In this study, identified total of 28 differentially expressed genes (DEGs) were identified in RA. Utilising WGCNA, two co-expression modules were generated, with one module demonstrating the strongest correlation with RA. Through the integration of differential gene expression analysis, a total of 5 intersecting genes were discovered. these 5 hub genes, namely fused in sarcoma (FUS), transformer 2 beta homolog (TRA2B), eukaryotic translation elongation factor 2 (EEF2), cleavage and polyadenylation specific factor 6 (CPSF6) and signal transducer and activator of transcription 3 (STAT3) were found to possess significant diagnostic value as determined by receiver operating characteristic (ROC) curve analysis. the close association between the concentrations of various immune cells is anticipated to contribute to the diagnosis and treatment of RA. Furthermore, the infiltration of immune cells mentioned earlier is likely to exert a substantial influence on the initiation of this disease. [ABSTRACT FROM AUTHOR]

Our previous study found that cullin 4B (CUL4B) inhibited rheumatoid arthritis (RA) pathology through glycogen synthase kinase-3beta (GSK3β)/canonical Wnt signalling pathway. in this work, pre-experiment and bioinformatics analysis suggested that circ_0011058 may lead to the up-regulation of CUL4B expression by inhibiting miR-335-5p. Therefore, we studied whether circ_0011058 can promote the expression of cUl4B through sponging the miR-335-5p and further promote the pathological development of RA. Bioinformatics prediction, real-time quantitative PCR (RT-qPCR), western blot (WB), double luciferase reporter gene and other relevant methods were used to study the inhibition of circ_0011058 on RA pathology and its molecular mechanism. Results showed that the expression of circ_0011058 was significantly increased in adjuvant arthritis (AA) rats and RA fibroblast-like synoviocytes (FLS). the knockout of circ_0011058 inhibited the proliferation of AA FLS and RA FLS, decreased the levels of interleukin-1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), and inhibited the expression of matrix metalloproteinase 3 (MMP3), fibronectin, which showed that circ_0011058 had a strong role in promoting RA pathology. Furthermore, miR-335-5p expression was reduced in AA rats and RA FLS. the highly expressed circ_0011058 directly sponged the miR-335-5p, which led to the increase of CUL4B expression and promoted the activation of the GSK3β/canonical signalling pathway. Finally, we confirmed that miR-335-5p mediated the roles of circ_0011058 in promoting RA pathological development, which showed that the circ_0011058/ miR-335-5p/CUL4B signal axis was involved in RA pathology. this work was of great significance for clarifying the roles of circ_0011058 in RA pathology, and further work was needed to establish whether circ_0011058 was a potential therapeutic target or diagnostic marker for RA. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of immune-mediated arthritis, which comprises rheumatoid arthritis and spondyloarthritis. This review outlines the key findings and advancements in scRNA-seq studies focused on the pathogenesis of autoimmune arthritis and its clinical application. In rheumatoid arthritis, scRNA-seq has elucidated the heterogeneity among synovial fibroblasts and immune cell subsets in inflammatory sites, offering insights into disease mechanisms and the differences in treatment responses. Various studies have identified distinct synovial fibroblast subpopulations, such as THY1+ inflammatory and THY1- destructive fibroblasts. Furthermore, scRNA-seq has revealed diverse T cell profiles in the synovium, including peripheral helper T cells and clonally expanded CD8+ T cells, shedding light on potential therapeutic targets and predictive markers of treatment response. Similarly, in spondyloarthritis, particularly psoriatic arthritis and ankylosing spondylitis, scRNA-seq studies have identified distinct cellular profiles associated with disease pathology. Challenges such as cost and sample size limitations persist, but collaborative efforts and utilization of public databases hold promise for overcoming these obstacles. Overall, scRNA-seq emerges as a powerful tool for dissecting cellular heterogeneity and driving precision medicine in immune-mediated arthritis. [ABSTRACT FROM AUTHOR]

Copyright of Rheuma Plus is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

There is an increased prevalence of atherosclerotic cardiovascular disease (ASCVD) in patients with inflammatory rheumatic diseases (IRD) including rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, and systemic sclerosis. The mechanism for the development of ASCVD in these conditions has been linked not only to a higher prevalence and undertreatment of traditional cardiovascular (CV) risk factors but importantly to chronic inflammation and a dysregulated immune system which contribute to impaired endothelial and microvascular function, factors that may contribute to accelerated atherosclerosis. Accurate ASCVD risk stratification and optimal risk management remain challenging in this population with many barriers that include lack of validated risk calculators, the remitting and relapsing nature of underlying disease, deleterious effect of medications used to manage rheumatic diseases, multimorbidity, decreased mobility due to joint pain, and lack of clarity about who bears the responsibility of performing CV risk assessment and management (rheumatologist vs. primary care provider vs. cardiologist). Despite recent advances in this field, there remain significant gaps in knowledge regarding the best diagnostic and management approach. The evolving field of Cardio-Rheumatology focuses on optimization of cardiovascular care and research in this patient population through collaboration and coordination of care between rheumatologists, cardiologists, radiologists, and primary care providers. This review aims to provide an overview of current state of knowledge about ASCVD risk stratification in patients with IRD, contributing factors including effect of medications, and review of the current recommendations for cardiovascular risk management in patients with inflammatory disease with a focus on hypertension as a key risk factor. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis (JIA) is the most prevalent pediatric rheumatic disease. While disease‐modifying antirheumatic drugs (DMARDs), especially biologics, have greatly transformed the management of JIA, there remain some unmet medical needs that require new treatment options. The objective of this work was to describe and apply a modeling and simulation approach to extrapolate upadacitinib efficacy from the adult diseases, rheumatoid arthritis (RA) and psoriatic arthritis (PsA), to their respective pediatric diseases, polyarticular course JIA (pcJIA), and juvenile PsA (JPsA). A population pharmacokinetic model characterized upadacitinib pharmacokinetics in pediatric patients using data from two phase I studies in pediatric patients with pcJIA (N = 51) or atopic dermatitis (N = 33). Efficacy simulations were conducted using previously developed exposure–response models in adults with RA and PsA. Real‐world pcJIA and JPsA patient databases were leveraged to construct representative patient profiles for the targeted population. Following administration of the proposed weight‐based dosing regimen, the model‐predicted median upadacitinib plasma exposures in pediatric patients were within 20% of those in adult RA and PsA patients receiving the approved adult regimen. Simulations demonstrate that upadacitinib efficacy in pcJIA and JPsA is predicted to be non‐inferior to that in adults with RA or PsA, respectively. The results of this work enabled recent approvals of upadacitinib for the treatment of polyarticular JIA and JPsA in the United States. Upadacitinib safety in pediatrics is being further evaluated in ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans; however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing‐Si herbal tea (JS), against H2O2‐induced inflammation and cellular damage in HIG‐82 synoviocytes. We found that JS did not show any significant alterations in cell viability at <188 μg/mL; however, a cytotoxic effect was observed at 188–1883 μg/mL concentrations tested. We found that expressions of inflammation associated extracellular matrix (ECM)‐degrading proteases MMP‐13, ADAMTS‐2, ‐8, and ‐17 were abnormally enhanced under H2O2‐induced pathological oxidative stress (ROS) in HIG‐82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose‐dependent manner. Treatment with JS showed enhanced cell viability against H2O2‐induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl‐2 were increased, whereas MMP‐13, ADAMTS‐2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H2O2, MIA, LPS, and TNF‐α treatment, respectively, in HIG‐82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H2O2‐treated HIG‐82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases. [ABSTRACT FROM AUTHOR]

Purpose: Work ability of people with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is reduced, but underexamined as a clinical treatment target. The evidence on vocational interventions indicates that delivery by a single healthcare professional (HCP) may be beneficial. Physiotherapist (PT)-led interventions have potential because PTs are most commonly consulted by RA/axSpA patients in the Netherlands. The aim was to develop a PT-led, vocational intervention for people with RA/axSpA and reduced work ability. Methods: Mixed-methods design based on the Medical Research Council (MRC) framework for developing and evaluating complex interventions, combining a rapid literature review and six group meetings with: patient representatives (n = 6 and 10), PTs (n = 12), (occupational) HCPs (n = 9), researchers (n = 6) and a feasibility test in patients (n = 4) and PTs (n = 4). Results: An intervention was developed and evaluated. Patient representatives emphasized the importance of PTs' expertise in rheumatic diseases and work ability. The potential for PTs to support patients was confirmed by PTs and HCPs. The feasibility test confirmed adequate feasibility and underlined necessity of training PTs in delivery. The final intervention comprised work-focussed modalities integrated into conventional PT treatment (10–21 sessions over 12 months), including a personalized work-roadmap to guide patients to other professionals, exercise therapy, patient education and optional modalities. Conclusion: A mixed-methods design with stakeholder involvement produced a PT-led, vocational intervention for people with RA/axSpA and reduced work ability, tested for feasibility and ready for effectiveness evaluation. [ABSTRACT FROM AUTHOR]

Purpose of review: This review focuses on the association between RA and heart failure, highlighting the role of inflammation and the prevalence of heart failure with preserved ejection fraction (HFpEF) in this population. Recent findings: The incidence of heart failure in RA patients is two to three times higher than in the general population, with inflammation playing a significant role independent of traditional cardiovascular risk factors. HFpEF accounts for about half of heart failure cases and is increasingly recognized in RA patients, although it remains underdiagnosed. Atypical presentations and non-specific symptoms further complicate diagnosis. Early control of inflammation has been shown to reduce the risk of heart failure development and progression, improving both morbidity and mortality outcomes. Summary: Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting approximately 1% of the population, with cardiovascular disease being the leading cause of premature death in these patients. [ABSTRACT FROM AUTHOR]

Background: Although normal acute phase reactants (APRs) play an important role in assessing disease activity of rheumatoid arthritis (RA), some studies pointed out the discordance between disease activity and APR level. Neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs) and lymphocyte-to-monocyte ratios (LMRs) have been reported to be sensitive measures of inflammatory reaction. This study aims to explore the value of these haematological makers in assessment of APR-negative RA patients. Methods: Out of a cohort of 418 consecutive patients with RA, we enrolled 135 patients with normal APR for this study. We performed ultrasound assessments to evaluate synovitis and bone erosion in the affected joints. Synovitis was evaluated by ultrasound grey scale (GS) and power Doppler (PD) with semi-quantitative scoring (0-3). Demographic, clinical and laboratory data were collected from the patients. Disease Activity Score-28 joints (DAS28), NLR, MLR and PLR were calculated. Results: In RA patients with normal APR, PLR exhibited a positive correlation with ultrasound-detected synovitis and bone erosion, whereas NLR, MLR showed no significant correlation with ultrasonography parameters. The area under the ROC curve (AUC) for identifying synovitis with a GS grade ≥2 based on a PLR cutoff value of ≥159.6 was 0.7868 (sensitivity: 80.95%, specificity: 74.24%). For synovitis with a PD grade ≥2, the AUC was 0.7690, using a PLR cutoff value of ≥166.1 (sensitivity: 68.0%, specificity: 83.87%). Conclusions: Our findings suggested that PLR might be a reliable and cost-effective marker for identifying moderate-to-severe synovitis in RA patients with normal APR. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disease that is primarily diagnosed and managed by rheumatologists; however, it is often primary care providers who first encounter RA-related symptoms. This study developed and validated a case definition for RA using national surveillance data in primary care settings. Methods: This cross-sectional validation study used structured electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Based on the reference set generated by EMR reviews by five experts, three machine learning steps: 'bag-of-words' approach to feature generation, feature reduction using a feature importance measure coupled with recursive feature elimination and clustering, and classification using tree-based methods (Decision Tree, Random Forest, and Extreme Gradient Boosting). The three tree-based algorithms were compared to identify the procedure that generated the optimal evaluation metrics. Nested cross-validation was used to allow evaluation and comparison and tuning of models simultaneously. Results: Of 1.3 million patients from seven Canadian provinces, 5,600 people aged 19 + were randomly selected. The optimal algorithm for selecting RA cases was generated by the XGBoost classification method. Based on feature importance scores for features in the XGBoost output, a human-readable case definition was created, where RA cases are identified when there are at least 2 occurrences of text "rheumatoid" in any billing, encounter diagnosis, or health condition table of the patient chart. The final case definition had sensitivity of 81.6% (95% CI, 75.6–86.4), specificity of 98.0% (95% CI, 97.4–98.5), positive predicted value of 76.3% (95% CI, 70.1–81.5), and negative predicted value of 98.6% (95% CI, 98.0-98.6). Conclusion: A case definition for RA in using primary care EMR data was developed based off the XGBoost algorithm. With high validity metrics, this case definition is expected to be a reliable tool for future epidemiological research and surveillance investigating the management of RA in CPCSSN dataset. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) is a complex coordinated transcriptional regulatory mechanism. It affects nearly 95% of all protein-coding genes and occurs in nearly all human organs. Aberrant alternative splicing can lead to various neurological diseases and cancers and is responsible for aging, infection, inflammation, immune and metabolic disorders, and so on. Though aberrant alternative splicing events and their regulatory mechanisms are widely recognized, the association between autoimmune disease and alternative splicing has not been extensively examined. Autoimmune diseases are characterized by the loss of tolerance of the immune system towards self-antigens and organ-specific or systemic inflammation and subsequent tissue damage. In the present review, we summarized the most recent reports on splicing events that occur in the immunopathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and attempted to clarify the role that splicing events play in regulating autoimmune disease progression. We also identified the changes that occur in splicing factor expression. The foregoing information might improve our understanding of autoimmune diseases and help develop new diagnostic and therapeutic tools for them. [ABSTRACT FROM AUTHOR]

Background: The prognostic nutritional index (PNI) is a comprehensive measure of individual immune and nutritional status. This study aimed to evaluate the role of PNI in the presence and mortality of rheumatoid arthritis (RA). Methods: This study used data of participants aged ≥ 40 years from the National Health and Nutrition Examination Survey (NHANES) 2003–2018. PNI was calculated using serum albumin and lymphocyte count. The relationship between PNI and the prevalence of RA and mortality among RA patients was assessed using logistic and Cox regression models. Nonlinear associations were explored using restricted cubic splines (RCS). Results: Of 18,245 participants (mean 55.4 years, 49% female), 1901 had RA, among whom (480/1899, 25%) died during a median follow-up period of 84 months. PNI was inversely associated with the likelihood of having RA (odds ratio = 0.97, 95% confidence interval [CI]: 0.95–0.98). Compared to participants whose PNI was in the lowest quartile, those in other quartiles had a reduced likelihood of having RA by 21-38% (Ptrend <0.01). Cox regression analysis revealed an inverse association between PNI and all-cause mortality (hazard ratio = 0.95, 95%CI: 0.91–0.99). An L-shaped association was observed between PNI and the presence and all-cause mortality of RA, with turning points occurring around the mean value of PNI. The presence and all-cause mortality of RA was significantly reduced before the turning points of PNI and plateaued afterwards. Conclusion: In middle-aged and older adults, there is an inverse association between PNI and the presence and all-cause mortality of RA. [ABSTRACT FROM AUTHOR]