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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.

Purpose: To compare characteristics of temporomandibular disorders (TMDs) in patients with rheumatoid arthritis (RA) to patients without RA. Materials and Methods: The sample included 80 patients (aged 33 to 73 years; 88% women and 22% men) with 40 in each group. An international diagnostic protocol for TMDs was followed. Results: Arthralgia was the most prevalent TMD in the RA group. Orofacial pain was more common in the RA group than in the controls (42.5% vs 15%, P = .031), with higher chronic pain grade and pain intensity (P = .005). Somatization and depression were also increased (P < .001). In multiple logistic regression analysis, arthralgia (OR: 6.4; 95% CI: 1.1 to 37.1; P = .038) and age = 55 years were predictors of RA (OR: 3.9; 95% CI: 1.4 to 10.8; P = .009) when controlling for the effects of biological sex and pain intensity. TMDs were related to 7.4 times higher odds for presence of orofacial pain, while RA was related to 3.4 times higher odds for pain. Conclusions: RA patients experienced more orofacial pain and higher pain intensity, somatization, and depression compared to healthy individuals. Pain is more influenced by TMDs than by RA. [ABSTRACT FROM AUTHOR]

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.

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: Research has shown that fatty acid metabolism genes are closely related to the development of rheumatoid arthritis. Therefore, exploring the progression of rheumatoid arthritis based on fatty acid metabolism genes is of clinical significance. OBJECTIVE: To investigate whether fatty acid metabolism genes can serve as reliable biomarkers for predicting the progression of rheumatoid arthritis. METHODS: Gene data related to synovial tissue were downloaded from the Gene Expression Comprehensive Database (GEO). STRING was used to construct the protein-protein interaction network analysis. Cytoscape was utilized for biological annotation (gene ontology) and signaling pathway enrichment analysis (Kyoto Encyclopedia of Genes and Genomes). Fatty acid metabolism related genes were screened from the molecular feature database (MSigDB). Least absolute shrinkage and selection operator and support vector machine recursive feature elimination feature were used to screen for potential biomarkers. Immune cell infiltration levels in normal individuals and rheumatoid arthritis patients were assessed using the CIBERSORT algorithm. Finally, the expression levels of fatty acid metabolism related genes were verified using the receiver operating characteristic curve in GSE77298. RESULTS AND CONCLUSION: 361 differentially expressed genes in rheumatoid arthritis were identified, of which 13 overlapped with the reported fatty acid metabolism related genes. Based on machine learning algorithms, five genes were selected, and the receiver operating characteristic curve showed that five genes (PCK1, PDK1, PTGS2, PLA2G2D, and DPEP2) could predict the development of rheumatoid arthritis. The CIBERSORT algorithm results showed that five genes were associated with activated mast cells, neutrophils, resting mast cells, and memory resting CD4+ T cells. The receiver operating characteristic curve showed that PLA2G2D and PCK1 have high diagnostic value. To conclude, the expression characteristics of fatty acid metabolism related genes can serve as potential biomarkers for predicting clinical outcomes, which can further improve the accuracy of prediction in RA patients. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations. There is little understanding of why some organs are specifically impacted in patients and the mechanisms of disease persistence remain unclear. While much work has been done characterizing the DNA methylation status in SLE, there is less information on histone modifications, a more dynamic epigenetic feature. This study identifies two histone marks of activation and the binding of p300 genome-wide in three cell types and three clinical subsets to better understand cell-specific effects and differences across clinical subsets. Results: We examined 20 patients with SLE and 8 controls and found that individual chromatin marks varied considerably across T cells, B cells, and monocytes. When pathways were examined, there was far more concordance with conservation of TNF, IL-2/STAT5, and KRAS pathways across multiple cell types and ChIP data sets. Patients with cutaneous lupus and lupus nephritis generally had less dramatically altered chromatin than the general SLE group. Signals also demonstrated significant overlap with GWAS signals in a manner that did not implicate one cell type more than the others. Conclusions: The pathways identified by altered histone modifications and p300 binding are pathways known to be important from RNA expression studies and recognized pathogenic mechanisms of disease. NFκB and classical inflammatory pathways were strongly associated with increased peak heights across all cell types but were the highest-ranking pathway for all three antibodies in monocytes according to fgsea analysis. IL-6 Jak/STAT3 signaling was the most significant pathway association in T cells marked by H3K27ac change. Therefore, each cell type experiences the disease process distinctly although in all cases there was a strong theme of classical inflammatory pathways. Importantly, this NFκB pathway, so strongly implicated in the patients with generalized SLE, was much less impacted in monocytes when cutaneous lupus was compared to the general SLE cohort and also less impacted in lupus nephritis compared to general SLE. These studies define important cell type differences and emphasize the breadth of the inflammatory effects in SLE. [ABSTRACT FROM AUTHOR]

ABSTRACT Observational studies have indicated that there is an association between rheumatoid arthritis (RA) and an elevated risk of hypertension. However, a definitive causal relationship between the two conditions has not been established. The objective of this study was to investigate the causal link between RA and hypertension, as well as the potential mediating role of circulating inflammatory proteins in this relationship. We utilized Mendelian randomization (MR) to examine the causal relationship between RA and hypertension. The study data were obtained from publicly accessible genome‐wide association study (GWAS) databases and meta‐aggregates of large GWAS studies. The primary statistical method for determining causal effects was the inverse variance weighted (IVW) method, which was supplemented by a variety of sensitivity analyses. The results of the IVW method suggest a causal relationship between RA and an increased risk of hypertension (OR = 1.03, 95% CI = 1.01–1.04, p = 3.32 × 10−5). This association remained statistically significant even after adjusting for multiple confounding factors. Furthermore, MR analyses also revealed causal links between 10 circulating inflammatory proteins and the risk of hypertension, with TNF‐related activation‐induced cytokine partially mediating RA‐induced hypertension at a mediator ratio of 11.17% (0.27%–22.08%). Our study identifies causal relationships between several genetically determined inflammatory proteins and hypertension, establishing that RA increases hypertension risk, with inflammation partially mediating this effect. These findings provide new evidence supporting the inflammatory hypothesis in the mechanism of hypertension. Inflammatory factors may serve as potential targets for antihypertensive therapy. [ABSTRACT FROM AUTHOR]

This exploratory study aimed to examine the impact of abatacept treatment on bone structure in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). RA patients initiating either abatacept or newly introduced csDMARDs were enrolled in this prospective, non-randomized, two-group study. Bone structure in the 2nd and 3rd metacarpal heads was assessed using HR-pQCT at 0, 6, and 12 months after enrollment. Synovitis was evaluated using musculoskeletal ultrasound and MRI. The adjusted mean between-group differences (abatacept–csDMARDs group) were estimated using a mixed-effect model. Thirty-five patients (abatacept group: n = 15; csDMARDs group: n = 20) were analyzed. Changes in erosion volume, depth and width were numerically smaller in the abatacept group compared to the csDMARDs group (adjusted mean between-group differences: − 1.86 mm3, − 0.02 mm, and − 0.09 mm, respectively). Over a 12-month period, 5 erosions emerged in the csDMARDs group, while only 1 erosion appeared in the abatacept group. Compared to csDMARDs, abatacept better preserved bone microarchitecture; several components of bone microarchitecture were significantly worsened at 6 months in the csDMARDs group, but were not deteriorated at 6 months in the abatacept group. Changes in synovitis scores were similar between the two treatment groups. Our results indicate that abatacept prevented the progression of bone erosion including new occurrence, and also prevented worsening of bone strength independently with synovitis compared to csDMARDs including MTX. Thus, abatacept treatment may provide benefits not only in inhibiting the progress of bone erosion but also in preventing bone microarchitectural deterioration. [ABSTRACT FROM AUTHOR]

AbstractThe primary goal of this research was to isolate and assess the bioactive compounds within Eclipta prostrata Linn’s chloroform extract, with a focus on their potential to combat arthritis, validating its traditional use. Initially, antioxidant characteristics were evaluated, followed by fractionation through column chromatography. The in-vivo safety assessment, following OECD TG 425 Guidelines, showed no mortality at doses up to 2000 mg/kg, confirming the fraction’s safety. Subsequently, the active fraction was assessed in a complete Freund’s adjuvant-induced arthritis model. It demonstrated a dose-dependent inhibitory effect on inflammation and improved various parameters, including thermal latency time, dorsal flexion, motility, and motor coordination. Active bio constituents like rutin, stigmasterol, quercetin, and beta-sitosterol were estimated in the active fraction. The findings provide validation for the traditional use of E. prostrata as a potential plant with anti-arthritic properties, suggesting its potential suitability for rheumatoid arthritis treatment. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) are widely dispersed in vivo and are isolated from several tissues, including bone marrow, heart, body fluids, skin, and perinatal tissues. Bone marrow MSCs have a multidirectional differentiation potential, which can be induced to differentiate the medium in a specific direction or by adding specific regulatory factors. MSCs repair damaged tissues through lineage differentiation, and the ex vivo transplantation of bone marrow MSCs can heal injured sites. MSCs have different propensities for lineage differentiation and pathological evolution for different diseases, which are crucial in disease progression. In this study, we describe various lineage analysis methods to explore lineage ontology in vitro and in vivo, elucidate the impact of MSC lineage differentiation on diseases, advance our understanding of the role of MSC differentiation in physiological and pathological states, and explore new targets and ideas associated with disease diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) vaccines aroused concerns about the risk of flares and adverse events in inflammatory arthritis (IA) since the vaccine clinical trials did not specifically investigate this subset of patients. Methods: A systematic literature review and meta-analysis to summarize the data on joint disease flare and adverse events following immunization (AEFI). Two researchers independently evaluated the literature on Pubmed, Scopus, and EMBASE databases from 22nd March 2020 to 30th September 2023. A random-effects model was used to pool odds ratios (OR) (with 95% CI) for the risk of joint disease flares and adverse events. Subgroup analyses were performed to evaluate the risk of disease flare between different IA and adverse events. Heterogeneity was assessed by I2 statistic. Results: A total of 9874 IA patients were included in the study: 6579 (66.6%) patients affected by RA and 3295 (33.4%) spondyloarthritis (SpA). The overall rate of flares was higher in RA vs. SpA (9.1% vs. 5.3%). However, the pooled estimated analysis showed no increased risk of joint disease flare following COVID-19 vaccination in patients affected by RA vs. SpA [OR 0.88, 95% CI: 0.77-1.00]. Furthermore, a subgroup analysis showed an increased risk of joint flares in psoriatic arthritis (PsA) patients vs. RA [OR 0.79, 95% CI: 0.68-0.93, p=0.004]. The pooled estimated analysis revealed no increased risk of AEFI in patients with RA vs. SpA [1.02, 95% CI: 0.63-1.65]. Conclusions: Our meta-analysis summarized the current evidence on joint disease flares and COVID-19 vaccine-associated AEFI in IA patients. Pooled analysis showed an increased risk of disease flares in PsA vs. RA patients. [ABSTRACT FROM AUTHOR]

Objective: Our study was conducted to explore the link between oxidative balance score (OBS) and rheumatoid arthritis (RA). Methods: A total of 21,415 participants were included in our research from five cycles (2011–2012, 2013–2014, 2015–2016, 2017–2018, and 2017–2020) of the National Health and Nutrition Examination Survey (NHANES). Moreover, 20 elements related to diet as well as lifestyle were combined to calculate OBS. The relationship between OBS and RA was assessed by employing multivariable regression analysis, and further exploration was carried out through subgroup analysis, restricted cubic spline analysis, and sensitivity analysis. Multiple covariates were selected to adjust the model for more robust results. Results: In our cross-sectional study, a higher OBS has a protective effect on the development of RA (OR = 0.98, 95% CI: 0.97 to 0.99). In contrast to individuals aged ≥60, the result is more prominent in the population aged 20–60 (OR = 0.97, 95% CI: 0.96 to 0.98). Marital status appears to introduce interference in the relationship between OBS and RA, and unmarried individuals exhibited different outcomes (OR = 1.02, 95% CI: 0.99 to 1.04) compared to others. The positive influence of OBS was more evident in patients with chronic kidney disease and cardiovascular disease, while it was stronger in individuals without diabetes and liver disease. Conclusion: A higher OBS correlates with a reduced odd of RA. Further studies are needed to shoot more sights on improving dietary habits and lifestyles to gain proper OBS and explore whether OBS can be one of the measurements utilized to measure the risk of RA. [ABSTRACT FROM AUTHOR]

Introduction and aim. Orthorexia nervosa is described as an obsession with consuming solely healthy foods accompanied by restrictive behaviors. Patients with chronic conditions frequently require dietary interventions alongside medication to manage symptoms and slow down disease progression. However, when dietary restrictions are taken to extremes, individuals may develop orthorexia nervosa, resulting in malnutrition and weight loss. This poses risks during treatment, where maintaining a balanced diet is vital. In this review we aim to display the prevalence of orthorexia nervosa in patients suffering from selected chronic diseases. Material and methods. A literature review was performed to investigate the prevalence of orthorexia nervosa among individuals with type 1 diabetes, inflammatory bowel disease, celiac disease, rheumatoid arthritis, and cancer. Description of the State of Knowledge. The occurrence of orthorexia reaches up to 7% in the general population, 72% in patients with type 1 diabetes mellitus, 77% in case of inflammatory bowel disease, 71% among individuals suffering from celiac disease, 75% in those with rheumatoid arthritis, and 50% in case of cancer. Orthorexia nervosa predominantly affects females who are younger, have higher levels of education, select organic foods, prepare their own meals, and have other concurrent chronic illnesses. The distress associated with diagnosis is considered the primary factor contributing to the development of this condition. Orthorexia ultimately leads to malnutrition, weight loss, impaired social functioning, and poses a risk of complications during the management of patients suffering from chronic diseases. Conclusion. The prevalence of orthorexia nervosa in patients suffering from the exhibited chronic illnesses is significantly higher compared to the general population. Therefore, early detection of this condition and intervention are necessary to improve patient management. Further research is needed to assess the frequency of orthorexia among individuals suffering from other chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Interstitial Lung Disease (ILD) represents the most common extra-articular manifestation of Rheumatoid Arthritis (RA) and is a major cause of mortality. This study aims to identify and evaluate biomarkers associated with Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD). Methods: We searched PubMed, Cochrane Library, EMBASE, and Web of Science databases for studies related to biomarkers of RA-ILD up until October 7, 2023. The Newcastle-Ottawa Scale (NOS) and standards recommended by the Agency for Healthcare Research and Quality (AHRQ) were used for quality assessment, and meta-analysis was conducted using Stata18.0 software. Results: A total of 98 articles were assessed for quality, 48 of which were included in the meta-analysis. 83 studies were of high quality, and 15 were of moderate quality. The meta-analysis showed significant differences in biomarkers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody, Rheumatoid Factor (RF), Krebs von den Lungen-6 (KL-6), Surfactant Protein D (SP-D), Carcinoembryonic Antigen (CEA), Carbohydrate Antigen 19-9 (CA19-9), Matrix Metalloproteinase-7 (MMP-7), C-X-C Motif Chemokine Ligand 10 (CXCL-10), and Neutrophil-to-Lymphocyte Ratio (NLR) between RA-ILD patients and RA patients. However, Platelet-to-Lymphocyte Ratio [Platelet-to-Lymphocyte Ratio (PLR)], Cancer Antigen 125 [Cancer Antigen 125 (CA-125)], and Cancer Antigen 153 [Cancer Antigen 153 (CA-153)] did not show significant differences between the two groups. KL-6, MMP-7, and Human Epididymis Protein 4 (HE4) are negatively correlated with lung function, and KL-6 is associated with the prognosis of RA-ILD. Conclusions: Biomarkers hold promising clinical value for prediction, diagnosis, severity assessment, and prognosis evaluation in RA-ILD. However, these findings need to be validated through multicenter, large-sample, prospective cohort studies. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD42023448372. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA), a chronic autoimmune condition, is characterized by persistent synovial inflammation, bone degradation, and progressive joint deterioration. Despite considerable research efforts, the precise molecular mechanism underlying RA remains elusive. This investigation aims to elucidate the potential role and molecular mechanism of N6-methyladenosine (m6A) methylation regulators in the pathogenesis of RA. Methods: In this study, we employed bioinformatics tools to elucidate the association between RA and m6A modifications, aiming to identify potential biological markers. We extracted datasets GSE12021, GSE55235, and GSE55457 from the Gene Expression Omnibus (GEO) database for comprehensive analysis. Utilizing differential expression analysis, protein-protein interaction (PPI) analysis, and single-cell sequencing techniques, we identified pivotal hub genes implicated in the pathogenesis of RA. Subsequently, we assessed the correlation between these hub genes and the pathogenesis of RA using Gene Set Enrichment Analysis (GSEA). Both in vivo and in vitro experiments were performed to confirm the expression and functional roles of the identified key hub gene in RA. Results: Differential expression analysis, PPI analysis, and single-cell analysis identified three key hub genes (YTHDC1, YTHDC2, and YTHDF2) associated with RA. GSEA results further revealed that these genes are enriched in pathways associated with inflammatory responses. Subsequent correlation analysis demonstrated a significant negative correlation between YTHDC1 expression and CD8+ T cell levels. Notably, the gene and protein expression levels of YTHDC1 and YTHDF2 were significantly reduced in the synovial tissue of RA patients. Furthermore, silencing YTHDC1 in fibroblast-like synoviocytes (FLSs) significantly inhibited their migration, invasion, proliferation, and induced apoptosis. Conclusion: YTHDC1 may potentially be involved in the pathogenesis of RA through its regulation of migration, invasion, proliferation, and apoptosis in FLSs. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a potential association between the gut microbiota and arthritis. However, the causal links between the gut microbiota and various types of arthritis, as well as the potential mediating role of inflammatory proteins, remain unclear. Mendelian randomization was used to explore the causal relationships between gut microbiota, inflammatory proteins, and various forms of arthritis (osteoarthritis, rheumatoid and psoriatic arthritis, and ankylosing spondylitis [AS]). The inverse variance-weighted method was the primary analytical approach used. Furthermore, we examined the mediating role of inflammatory proteins in the pathway linking the gut microbiota to arthritis. Sensitivity analyses were performed to verify the robustness of the findings, and enrichment analyses were conducted to investigate the biological functions and pathways involved. We identified 11 positive and 14 negative causal effects linking the genetic liability of the gut microbiota to arthritis. Similarly, 9 positive and 8 negative causal effects between inflammatory proteins and arthritis were identified. Notably, an increased abundance of the order Bacillales (odds ratio [OR] = 1.199, 95% confidence interval [CI] = 1.030–1.394, P = 0.019) and higher interleukin-7 levels (OR = 1.322, 95% CI = 1.004–1.741, P = 0.046) significantly elevated the risk of AS. Furthermore, interleukin-7 mediated 13.8% of the effect caused by the order Bacillales, with a mediation effect size of β = 0.025 (95% CI = 0.001–0.064). Sensitivity and supplementary analyses revealed no significant evidence of horizontal pleiotropy or heterogeneity. Overall, our findings demonstrate causal links between the gut microbiota, inflammatory proteins, and four arthritis types, highlighting the gut microbiota as a potential therapeutic target. Crucially, interleukin-7 not only strongly correlated with AS but also partially mediated the effect exerted by the gut microbiota on AS, suggesting that managing the gut microbiota to modulate inflammatory proteins could serve as an effective therapeutic strategy for arthritis. [ABSTRACT FROM AUTHOR]

ABSTRACT This study aims to investigate the association of rs11203366, rs11203367, rs874881, rs2240340 and rs1748033 polymorphisms of protein‐arginine deiminase type 4 (PADI4) gene with the risk of rheumatoid arthritis (RA) through a meta‐analysis that was followed with a bioinformatics approach. The data were collected from reputable articles and underwent quantitative analysis, followed by in silico analysis using some bioinformatics tools. The results showed that rs874881 polymorphism in Latino (G vs. C: OR = 1.35, 95% CI = 1.11–1.65, p = 0.003; GG + CG vs. CC: OR = 2.02, 95% CI = 1.41–2.89, p = 0.0001; CG vs. CC + GG: OR = 1.38, 95% CI = 1.04–1.83, p = 0.027; GG vs. CC: OR = 2.09, 95% CI = 1.35–3.23, p = 0.001; CG vs. CC: OR = 1.98, 95% CI = 1.36–2.87, p = 0.00033) and rs1748033 in Caucasian population (T vs. C: OR = 1.25, 95% CI = 1.07–1.45, p = 0.005; TT vs. CT + CC: OR = 1.34, 95% CI = 1.09–1.64, p = 0.005, TT + CT vs. CC: OR = 1.26, 95% CI = 1.09–1.44, p = 0.001; TT vs. CC: OR = 1.59, 95% CI = 1.13–2.23, p = 0.007; CT vs. CC: OR = 1.20, 95% CI: 1.04–1.39, p = 0.015) are associated with increased risk of RA. Moreover, rs11203366 (G vs. A: OR = 1.46, 95% CI = 1.19–1.78, p = 0.0002, GG vs. AG + AA: OR = 1.42, 95% CI = 1.01–2.01, p = 0.043; GG + AG vs. AA: OR = 2.03, 95% CI = 1.45–2.86, p = 0.00004; GG vs. AA: OR = 2.29, 95% CI = 1.49–3.51, p = 0.0002; AG vs. AA: OR = 1.93, 95% CI = 1.35–2.76, p = 0.0003) and rs11203367 (T vs. C: OR = 1.50, 95% CI = 1.23–1.83, p = 0.00007; TT vs. CT + CC: OR = 1.56, 95% CI = 1.12–2.18, p = 0.009; TT + CT vs. CC: OR = 2.02, 95% CI = 1.43–2.84, p = 0.00007, TT vs. CC: OR = 2.43, 95% CI = 1.59–3.71, p = 0.0004; CT vs. CC: OR = 1.86, 95% CI = 1.30–2.68, p = 0.0007) had an impact in the Latino population. Bioinformatics tools showed the effect of these polymorphisms on gene function. These findings suggest that rs11203366, rs11203367, rs874881 and rs1748033 polymorphisms may be genetic risk factors for RA. Moreover, differences between populations suggest that ethnicity may play an important role in the effect of these polymorphisms on RA risk. [ABSTRACT FROM AUTHOR]

The relationship between the platelet to albumin ratio (PAR) and the disease activity of early rheumatoid arthritis (ERA) remains to be elucidated. This cross-sectional study included 372 patients with ERA who were hospitalized at Xingtai People's Hospital between January 2022 and January 2024. Multiple linear regression analysis was employed to assess the correlation of PAR with Disease Activity Score 28 (DAS28) using erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and then generalized additive models were used to explore their relationship. After accounting for confounding variables, a positive correlation was observed between the PAR and DAS28-ESR and DAS28-CRP in ERA patients (β (95% CI): 0.20 (0.08, 0.32) and 0.20 (0.08, 0.33), respectively), and the general trends were consistent from the lowest tertile group (T1) to the highest tertile group (T3). Furthermore, a nonlinear relationship was identified between PAR and both DAS28-ESR and DAS28-CRP. Threshold effect analysis indicated that a value of 13.73 was a significant inflection point. In brief, PAR has a threshold effect on the disease activity of ERA. Increased PAR levels were independently positive associated with DAS28-ESR and DAS28-CRP among ERA patients with PAR < 13.73. [ABSTRACT FROM AUTHOR]

Objective: Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are the most common types of inflammatory musculoskeletal disorders that share overlapping clinical features and complications. The aim of this study was to identify shared marker genes and mechanistic similarities between PsA and RA. Methods: We utilized datasets from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) and perform functional enrichment analyses. To identify the marker genes, we applied two machine learning algorithms: the least absolute shrinkage and selection operator (LASSO) and the support vector machine recursive feature elimination (SVM-RFE). Subsequently, we assessed the diagnostic capacity of the identified marker genes using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). A transcription factor (TF) network was constructed using data from JASPAR, HumanTFDB, and GTRD. We then employed CIBERSORT to analyze the abundance of immune infiltrates in PsA and RA, assessing the relationship between marker genes and immune cells. Additionally, cellular subpopulations were identified by analyzing single-cell sequencing data from RA, with T cells examined for trajectory and cellular communication using Monocle and CellChat, thereby exploring their linkage to marker genes. Results: A total of seven overlapping DEGs were identified between PsA and RA. Gene enrichment analysis revealed that these genes were associated with mitochondrial respiratory chain complex IV, Toll-like receptors, and NF-κB signaling pathways. Both machine learning algorithms identified Ribosomal Protein L22-like 1 (RPL22L1) and Lymphocyte Antigen 96 (LY96) as potential diagnostic markers for PsA and RA. These markers were validated using test sets and experimental approaches. Furthermore, GSEA analysis indicated that gap junctions may play a crucial role in the pathogenesis of both conditions. The TF network suggested a potential association between marker genes and core enrichment genes related to gap junctions. The application of CIBERSORT and single-cell RNA sequencing provided a comprehensive understanding of the role of marker genes in immune cell function. Our results indicated that RPL22L1 and LY96 are involved in T cell development and are associated with T cell communication with NK cells and monocytes. Notably, high expression of both RPL22L1 and LY96 was linked to enhanced VEGF signaling in T cells. Conclusion: Our study identified RPL22L1 and LY96 as key biomarkers for PsA and RA. Further investigations demonstrated that these two marker genes are closely associated with gap junction function, T cell infiltration, differentiation, and VEGF signaling. Collectively, these findings provide new insights into the diagnosis and treatment of PsA and RA. [ABSTRACT FROM AUTHOR]

Chamomile, emphasized as an herbal remedy with healing potential for human health, is used in traditional medicine. In this study, the potential of compounds derived from Matricaria chamomilla L. against IL-6, JAK-1 and TNF-α target proteins associated with rheumatoid arthritis (RA) was compared with known inhibitors. The drug-likeness and ADME/T properties of these compounds were investigated using online tools, and molecular docking and molecular dynamics simulations of the selected structures were examined. IL-6, JAK-1 and TNF-α formed stable complexes with apigenin, quercetin and galaxolide, respectively, demonstrating that these compounds exhibit potential inhibitory activity against RA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint inflammation and gradual tissue destruction. New research has shown how important noncoding RNAs (ncRNAs) are for changing immune and inflammatory pathways, such as the WNT signaling pathway, which is important for activating synovial fibroblasts and osteoblasts to work. This article examines the current understanding of several ncRNAs, such as miRNAs, lncRNAs, and circRNAs, that influence NF-κB signaling in the pathogenesis of RA. We investigate how these ncRNAs impact NF-κB signaling components, altering cell proliferation, differentiation, and death in joint tissues. The paper also looks at how ncRNAs can be used as potential early detection markers and therapeutic targets in RA because they can change important pathogenic pathways. This study highlights the therapeutic potential of targeting ncRNAs in RA therapy techniques, with the goal of reducing inflammation and stopping disease progression. This thorough analysis opens up new possibilities for understanding the molecular foundations of RA and designing novel ncRNA-based treatments. [ABSTRACT FROM AUTHOR]

Background: The value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development. Methods: A 12-month "accelerator" award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research. Results: Sixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement. Conclusions: In general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted. Plain English Summary: Patient and public involvement (PPI) in the development of funding applications to deliver clinical trials is desirable, but the PPI activities and processes involved at this early, "pre-award" stage are rarely reported. In the current paper we describe such activities during a 12-month project to develop a grant proposal for a substantive, international clinical trial. Three PPI partners were co-recipients of "seed funding" to conduct the 12-month Accelerator project, an additional 22 PPI partners being subsequently recruited to co-develop the funding application for the trial, entitled the "Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial (RAPPORT)." PPI partners contributed through meetings, email discussions and the completion of feedback forms. The PPI processes used in the project were evaluated by 16 of the PPI partners using an anonymous online feedback form. The form asked about the areas covered by the UK Standards for Public Involvement. PPI partners indicated that PPI in RAPPORT was done well in relation to all areas of the UK Standards. PPI partners felt they were heard, and their input valued, and that the communication was effective. Furthermore, they appreciated online format of the PPI activities, the flexible levels of involvement offered and the support from staff with expertise in both research and PPI. Some areas for potential improvement in future initiatives were also identified, which are discussed alongside challenges to co-development of projects during the "pre-award" stage in general, and the benefit of seed funding to support effective PPI. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the methodological, reporting and evidence quality of systematic reviews or meta-analyses of Janus kinases (JAK) inhibitors for the treatment of rheumatoid arthritis (RA). Methods: Our study systematically retrieved reviews from various databases, spanning from inception to June 2024. Two evaluators independently assessed the methodological, reporting, and evidence quality of each review using the AMSTAR-2 and PRIAMA2020 tools. The evidence quality was evaluated according to GRADE criteria. Six aspects were evaluated: publication year, study type, homogeneity, risk of publication bias, AMSTAR-2 methodology, and PRIAMA2020 reporting quality. Excel 2016 facilitated conversion of scores into radar plots. Results: Following stringent selection criteria, a total of 18 relevant studies were identified. The AMSTAR-2 scores ranged from 4 to 13 points, with five studies rated as low quality and the remaining 13 as critically low quality. All studies encompassed populations, interventions, controls, and outcome measures, demonstrating commendable integrity. However, there is room for improvement in study protocol development and registration, comprehensive search strategies, inclusion and exclusion criteria, conflict of interest disclosure, and discussion of heterogeneity. PRIAMA2020 assessments ranged from 14.5 to 21 points, with two studies scoring below 15 points due to increased bias risk from data transformation and sensitivity analysis. Notably, all reviews (100%) adhered to PRIAMA2020 guidelines for certain items but none met all criteria. GRADE evaluation included 446 outcome measures, with 158 of moderate, 156 of low, and 132 of very low quality, indicating JAK inhibitors is effective in improving RA. According to radar chart, the average rank score was 13.13. One study achieved a balanced score across all dimensions, while 11 exceeded the average, five showed significant differences in PRIAMA2020 scores, and four in AMSTAR two scores. Conclusion: Despite summarizing the efficacy and safety of JAK inhibitors in treating RA, the included studies exhibited poor methodological and reporting quality, along with low-quality evidence overall. Therefore, caution is warranted among decision-makers regarding the use of JAK inhibitors in RA treatment. Urgent requirements include high-quality, multicenter studies investigating JAK inhibitors for RA. Systematic Review registration: https://www.crd.york.ac.uk/PROSPERO, identifier 413415. [ABSTRACT FROM AUTHOR]

We designed a prospective multicenter cohort study to clarify a long-term, > 10-year prevalence and aggravation of cervical spine instabilities in rheumatoid arthritis (RA). In 2001–2002, 634 outpatients were enrolled, and 233 (36.8%) were followed for > 10 years. Cervical spine instability was defined as atlantoaxial subluxation (AAS, > 3-mm atlantodental interval), vertical subluxation (VS, < 13-mm Ranawat value), and subaxial subluxation (SAS, ≥ 2-mm irreducible vertebral translation). The aggravation was determined as ≥ 2 mm decrease of the Ranawat value in VS, ≥ 2-mm increase of slippage in SAS, and these new developments. The prevalence of VS and SAS increased during both the initial and last > 5 years (all, p ≤ 0.049). While VS aggravation was associated with pre-existing AAS (p = 0.007) and VS (p = 0.002), SAS aggravation correlated with pre-existing VS (p = 0.002). Multivariable analysis found hand mutilating changes (odds ratio [OR] = 4.048, p = 0.008), RA duration ≥ 5 years (OR = 3.711, p = 0.013), C-reactive protein (CRP) level ≥ 3.8 mg/dL (OR = 2.187, p = 0.044), and previous joint surgery (OR = 2.147, p = 0.021) as predictors for VS aggravation. Pre-existing VS (OR = 2.252, p = 0.024) and CRP ≥ 1.0 mg/dL (OR = 2.139, p = 0.013) were disclosed as predictors for SAS aggravation. Low disease activity and clinical remission before the development of VS and advanced peripheral joint destruction are essential to prevent progressive cervical spine instability in RA. [ABSTRACT FROM AUTHOR]

Neutrophils (PMNs) are key players of innate immune responses through the release of cytoplasmic granule content and the formation of neutrophil extracellular traps (NETs). RNASET2 is an acidic ribonuclease, recently proposed as an alarmin signal associated with inflammatory responses. Here we show that, along the neutrophil maturation cascade, RNASET2 is expressed in segmented and mature PMNs. In human PMNs, RNASET2 colocalized with primary and tertiary granules and was found to be associated with NETs following PMA or Nigericin stimulation. Similarly, activation of PMNs by soluble immune complexes, a hallmark of several autoimmune diseases, also induced RNASET2-associated NETs. Genome-wide association studies recently identified RNASET2 among a cluster of genes associated with increased susceptibility to develop autoimmune diseases, including rheumatoid arthritis (RA). RNASET2 was found expressed by PMNs and macrophages infiltrating inflamed joints in a murine model of RA (K/BxN Serum-Transfer-Induced Arthritis, STIA), by immunostaining. Similar results were found in synovial biopsies of RA patients with active disease. In addition, we demonstrate that RNASET2 circulating levels correlated with the onset and the severity of disease in two mouse models of inflammatory arthritis, STIA and CIA (Collagen-Induced Arthritis) and in serum of RA patients. These results show that PMNs are an important source of RNASET2 and that its circulating levels are associated with RA development suggesting a role for RNASET2 in the pathogenesis of immune-mediated diseases. [ABSTRACT FROM AUTHOR]

Objective: As research into preclinical rheumatoid arthritis (pre-RA) has advanced, a growing body of evidence suggests that abnormalities in RA-affected joint cartilage precede the onset of arthritis. Thus, early prevention and treatment strategies are imperative. In this study, we aimed to explore the protective effects of mesenchymal stem cell (MSC)-derived microvesicles (MVs) on cartilage degradation in a collagen-induced arthritis (CIA) mouse model. Methods: A CIA mouse model was established to observe early pathological changes in cartilage (days 21-25) through histological and radiological examinations. On day 22, MSCs-MVs were intravenously injected into the mice with CIA. Radiological, histological, and flow cytometric examinations were conducted to observe inflammation and cartilage changes in these mice compared to the mice with CIA and the control mice. In vitro, chondrocytes were cultured with inflammatory factors such as IL-1β and TNFα to simulate inflammatory damage to cartilage. After the addition of MVs, changes in inflammatory levels and collagen expression were measured via Western blotting, immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), and quantitative PCR to determine the role of MVs in maintaining chondrocytes. Results: MSC–MVs expressed vesicular membrane proteins (CD63 and Annexin V) and surface markers characteristic of MSCs (CD44, CD73, CD90, and CD105). In the early stages of CIA in mice, a notable decrease in collagen content was observed in the joint cartilage. In mice with CIA, injection of MSCs-MVs resulted in a significant reduction in the peripheral blood levels of IL-1β, TNFα, and IL-6, along with a decrease in the ratio of proinflammatory T and B cells. Additionally, MSC-MVs downregulated the expression of IL-1β, TNFα, MMP-13, and ADAMTS-5 in cartilage while maintaining the stability of type I and type II collagen. These MVs also attenuated the destruction of cartilage, which was evident on imaging. In vitro experiments demonstrated that MSC-MVs effectively suppressed the secretion of the inflammatory factors IL-1β, TNFα, and IL-6 in stimulated peripheral blood mononuclear cells (PBMCs). Conclusions: MSCs-MVs can inhibit the decomposition of the inflammation-induced cartilage matrix by regulating immune cell inflammatory factors to attenuate cartilage destruction. MSC-MVs are promising effective treatments for the early stages of RA. [ABSTRACT FROM AUTHOR]

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease that affects about 0.1% to 2% of the population worldwide. Despite the development of several novel therapies, there is only limited benefit for many patients. Thus, there is room for new approaches to improve response to therapy, including designing better trials e.g., by identifying subpopulations that can benefit from specific classes of therapy and enabling reverse translation by analyzing completed clinical trials. We have developed an open-source, mechanistic multi-scale model of RA, which captures the interactions of key immune cells and mediators in an inflamed joint. The model consists of a treatment-naive Virtual Population (Vpop) that responds appropriately (i.e. as reported in clinical trials) to standard-of-care treatment options—Methotrexate (MTX) and Adalimumab (ADA, anti-TNF-α) and an MTX inadequate responder sub-population that responds appropriately to Tocilizumab (TCZ, anti-IL-6R) therapy. The clinical read-outs of interest are the American College of Rheumatology score (ACR score) and Disease Activity Score (DAS28-CRP), which is modeled to be dependent on the physiological variables in the model. Further, we have validated the Vpop by predicting the therapy response of TCZ on ADA Non-responders. This paper aims to share our approach, equations, and code to enable community evaluation and greater adoption of mechanistic models in drug development for autoimmune diseases. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized by inflammatory activity with distinct rhythmic fluctuations. However, the precise mechanisms governing these inflammatory rhythms remain elusive. Here, we explore the interaction between dietary patterns, gut microbiota diurnal oscillations, and the rhythmicity of RA in both collagen-induced arthritis (CIA) mice and patients with RA and highlight the significance of dietary timing in modulating RA inflammatory rhythms linked to gut microbiota. Specifically, we discovered that Parabacteroides distasonis (P. distasonis) uses β-glucosidase (β-GC) to release glycitein (GLY) from the diet in response to daily nutritional cues, influencing RA inflammatory rhythms dependent on the sirtuin 5-nuclear factor-κB (SIRT5-NF-κB) axis. Notably, we validated the daily fluctuations of P. distasonis- β-GC-GLY in patients with RA through continuous sampling across day-night cycles. These findings underscore the crucial role of dietary timing in RA rhythmicity and propose potential clinical implications for novel therapeutic strategies to alleviate arthritis. [Display omitted] • RA exhibits rhythmic inflammatory activity influenced by dietary patterns • Nutritional cues significantly modulate RA inflammatory fluctuations via gut microbiota • P. distasonis utilizes β-glucosidase to release glycitein to inhibit the SIRT5-NF-κB axis • Continuous sampling validates fluctuations of P. distasonis -β-GC-GLY in RA patients Ma et al. demonstrate that dietary timing modulates rheumatoid arthritis inflammatory rhythms by inducing diurnal oscillations in gut microbiota. Particularly, Parabacteroides distasonis utilizes β-glucosidase to release glycitein, which mitigates RA inflammation via the SIRT5-NF-κB axis. [ABSTRACT FROM AUTHOR]

Background: Thyroid dysfunction exhibits a heightened prevalence among people with diabetes compared to those without diabetes. Furthermore, TD emerges as a notable correlated risk factor for the onset of diabetic retinopathy. Methods: Using data from the FinnGen database (R9), we investigated the causal relationship between thyroid dysfunction (TD) and four stages of diabetic retinopathy (DR). A two-sample univariable Mendelian randomization (UVMR) approach was employed to estimate the total causal effect of TD on four stages of DR, while multivariable Mendelian randomization (MVMR) was used to assess the direct causal effect. The meta-analysis was conducted to summarize the collective effect of TD on four stages of DR. The inverse variance weighted (IVW) method was the primary approach for Mendelian randomization analysis, with heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analyses performed to validate the robustness of the findings. Results: In UVMR analysis, thyrotoxicosis (TOS) was significantly associated with an increased risk of diabetic retinopathy across four stages (OR, 1.10-1.19; P<0.025). However, MVMR analysis, after adjusting for Graves' disease (GD) and/or rheumatoid arthritis (RA), revealed no significant association between TOS and the four stages of diabetic retinopathy. The Meta-analysis demonstrated the collective effect of TOS on diabetic retinopathy across all stages [OR=1.11; 95% CI (1.08-1.15); P<0.01]. In UVMR analysis, the estimates for hypothyroidism (HPT) and GD were similar to those for TOS. In the MVMR analysis, after adjusting for RA, the significant effect of HPT on DR and non-proliferative diabetic retinopathy (NPDR) remained. Additionally, MVMR analysis suggested that the estimates for GD on DR were not affected by TOS, except for GD-proliferative diabetic retinopathy (PDR). However, no significant correlation persisted after adjusting for RA, including for GD-PDR. Conclusion: Our study demonstrated a significant association between thyroid dysfunction TD and DR, with the relationship being particularly pronounced in HPT-DR. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of synovial joints, with a multifactorial etiology. Collagen triple helix repeat-containing 1 protein (CTHRC1) is a biomarker produced by fibroblast-like synoviocytes, which was shown to be highly expressed in RA patients. The study aimed to measure serum CTHRC1 level in female RA patients currently on medical treatment and its influence on the clinical and sonographic severity of the disease. Results: The patients' mean age was 43.39 ± 8.55 years and median RA disease duration of 5.5 (0.33–20) years. RA patients showed significantly higher serum CTHRC1 level [89.71 ng/ml (53.95–353.45)] in comparison to controls [87.38 ng/ml (44.47–110.3)] (U = 430, P = 0.014). Furthermore, higher serum CTHRC1 levels were recorded in seropositive versus seronegative patients (U = 76, P = 0.022) and in RA patients with severe disease activity compared to those with lower disease activity (H = 9.79, P = 0.007). Furthermore, serum CTHRC1 levels were lower in RA patients receiving biological therapy compared to those receiving conventional therapy; however, this difference did not reach statistical significance. Significant positive correlations were found between CTHRC1 and disease activity, acute-phase reactants, serological markers, functional assessment, fatigue, and erosions detected by ultrasound, while a significant negative correlation was recorded between CTHRC1 and duration of biologic intake (rs = − 0.45, P = 0.036). Furthermore, on multivariate linear regression analysis, serum CTHRC1 was the only significant predictor for higher disease activity (P = 0.028, B = 0.009, 95% CI 0.001 to 0.017). Conclusion: RA patients showed higher CTHRC1 serum levels compared to healthy controls, especially those with seropositivity and highly active disease. Furthermore, it was positively associated with poor patient functional outcome, fatigability, and erosive findings by ultrasound, thus suggesting that serum CTHRC1 can be a good predictor for high RA disease activity and possibly severity. Moreover, biological therapy could influence serum CTHRC1 levels in these patients. [ABSTRACT FROM AUTHOR]

Background: Inflammation and angiogenesis are two main mechanisms that act as mutual pathways in rheumatoid arthritis (RA). This work aimed to study the efficacy of digoxin as an adjunct therapy to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in active RA patients. Methods: In a randomized, double-blinded, placebo-controlled study, 60 adult patients with active RA received a placebo or digoxin (0.25 mg every other day) combined with csDMARDs for 6 months. The American College of Rheumatology (ACR) 20, ACR50, and ACR70 response rates and the disease activity score (DAS28) were assessed for patients. Flow cytometric analysis of Th17 cells and serum concentrations of IL-17A, IL-23, HIF-1α, and VEGF were evaluated before and after three and 6 months of therapy. Results: Following three and 6 months of digoxin therapy combined with csDMARDs, significant differences were detected in laboratory and clinical parameters relative to the control group. After 6 months, 83.3% of patients in the digoxin group, compared to 56.7% in the control group, achieved an ACR20 response (p = 0.024). The digoxin group had a significantly higher percentage of patients who achieved DAS28 remission after 6 months (p = 0.024). Notable improvements in the Health Assessment Questionnaire Disability Index, ACR50, and ACR70 were detected in the digoxin group. Conclusion: Digoxin was well tolerated and exerted profound immunomodulatory and anti-inflammatory effects in RA patients, and may also exhibit anti-angiogenic properties, indicating that it might be an effective adjunct to csDMARDs in treating RA. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04834557. [ABSTRACT FROM AUTHOR]

Objectives: Large granular lymphocyte (LGL) leukemia is a rare hematologic malignancy characterized by clonal expansion of cytotoxic T-cells frequent somatic activating STAT3 mutations. Based on the disease overlap between LGL leukemia rheumatoid arthritis (RA)a putative role for CD8+ T-cells in RA we hypothesized that STAT3 mutations may be detected in RA patient CD8+ Tcells correlate with clinical characteristics. Methods: Blood samples, clinical parameters, and demographics were collected from 98 RA patients and 9 healthy controls (HCs). CD8+ cell DNA was isolated and analyzed via droplet digital (dd)PCR to detect STAT3 mutations common in LGL leukemia: Y640F, D661Y, and the S614 to G618 region. STAT3 data from 99 HCs from a public dataset supplemented our 9 HCs. Results: RA patients had significantly increased presence of STAT3 mutations compared to controls (Y640F p=0.0005, D661Y p=0.0005). The majority of these were low variant allele frequency (VAF) (0.008-0.05%) mutations detected in a higher proportion of the RA population (31/98 Y640F, 17/98 D661Y) vs. HCs (0/108 Y640F, 0/108 D661Y). In addition, 3/98 RA patients had a STAT3 mutation at a VAF >5% compared to 0/108 controls. Serological markers, RF and anti-CCP positivity, were more frequently positive in RA patients with STAT3 mutation relative to those without (88% vs 59% RF, p=0.047; 92% vs 58% anti-CCP, p=0.031, respectively). Conclusions: STAT3 activating mutations were detected in RA patient CD8+ cells and associated with seropositivity. Thus, STAT3 activating mutations may play a role in disease pathogenesis in a subset of RA patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate factors associated with frailty in rheumatoid arthritis (RA) patients. A total of 656 RA patients were evaluated using data from an observational study in 2022. Among these patients, 152 with frailty were assigned to the frailty group, and 504 without frailty were assigned to the non-frailty group. Patient characteristics were compared between the two groups by univariate analysis, and factors associated with frailty were assessed by logistic regression analysis. Patient characteristics were also compared between patients with RA-associated interstitial lung disease (RA-ILD) (n = 102) and those without RA-ILD (n = 554). The frailty group was older (mean: 73.6 vs. 66.8 years) and had a higher DAS28-ESR (3.67 vs. 2.66), a higher HAQ-DI (1.13 vs. 0.32), and a higher rate of RA-ILD (25.0 vs. 12.7 %) than the non-frailty group. Age (OR: 1.03, 95 % CI: 1.01–1.05), HAQ-DI (3.22, 2.28–4.56), DAS28-ESR (1.44, 1.19–1.75), and RA-ILD (2.21, 1.24–3.94) were associated with frailty. RA patients with RA-ILD were older (73.3 vs. 67.5 years) and had a higher DAS28-ESR (3.30 vs. 2.80), a higher HAQ-DI (1.19 vs. 0.32), a higher proportion of frail patients (37.3 vs. 20.6 %), lower MTX use (26.5 vs. 62.9 %), and higher steroid use (44.1 vs. 26.8 %) than those without RA-ILD. Maintaining reasonable control of disease activity is necessary for RA patients, including those with RA-ILD, to recover from frailty. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features include synovial inflammation, bone erosion, and joint structural damage. Our previous studies have shown that interleukin (IL)‐35 is involved in the pathogenesis of bone loss in RA patients. In this study, we are further evaluating the efficacy of IL‐35 on collagen‐induced arthritis (CIA) in the mouse model. Male DBA/1J mice (n = 10) were initially immunized, 2 μg/mouse IL‐35 was injected intraperitoneally every week for 3 weeks after the establishment of the CIA model. Clinical arthritis, histopathological analysis, and three‐dimensional micro‑computed tomography (3D micro‑CT) were determined after the mice were anesthetized on the 42th day. In vitro, RANKL/M‐CSF induced mouse preosteoclasts (RAW264.7 cells line) was subjected to antiarthritis mechanism study in the presence of IL‐35. The results of clinical arthritis, histopathological analysis, and 3D micro‑CT, the expression of RANK/RANKL/OPG axis, inflammatory cytokines, and osteoclastogenesis‐related makers demonstrated decreasing severity of synovitis and bone destruction in the ankle joints after IL‐35 treatment. Furthermore, IL‐35 attenuated inflammatory cytokine production and the expression of osteoclastogenesis‐related makers in a mouse preosteoclasts cell line RAW264.7. The osteoclastogenesis‐related makers were significantly reduced in IL‐35 treated RAW264.7 cells line after blockage with the JAK/STAT1 signaling pathway. These results demonstrated that IL‐35 protein could inhibits osteoclastogenesis and attenuates CIA in mice. We concluded that IL‐35 can exhibit anti‐osteoclastogenesis effects by reducing the expression of inflammatory cytokines and osteoclastogenesis‐related makers, thus alleviating bone destruction in the ankle joint and could be a potential therapeutic target for RA. [ABSTRACT FROM AUTHOR]

Objectives Rheumatoid arthritis (RA) seriously affects the daily life of people. The whole plant of Artemisia ordosica Krasch. (AOK) has been used in folk medicine. This study aimed to investigate the in vivo anti-RA effects of AOK extract (AOKE) on collagen-induced arthritis in rats. Methods AOKE (400, 200, or 100 mg/kg) was administered orally to animals for 30 days. Body weight, paw swelling, arthritis index, thymus, and spleen indices, and pathological changes were assessed for effects of AOKE on RA. Furthermore, the inflammatory cytokines in rat serum were detected. In addition, the expressions of STAT3, Caspase-3, Galectin-3, and S100A9 in synovial tissue were researched using immunohistochemistry. Key findings The AOKE significantly reduced the arthritis indices, paw swelling, spleen, and thymus indices. Meanwhile, AOKE (400 mg/kg) decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17A, and increased the level of IL-10 in rat serum. Histopathological examination showed that AOKE reduced inflammatory cell infiltration and cartilage erosion. Then, AOKE decreased the expressions of STAT3, Galectin-3, S100A9, and increased the expression of Caspase-3. Conclusion AOKE had interesting anti-RA activity in rats, which deserved further research for the development and clinical use of this medicinal resource. [ABSTRACT FROM AUTHOR]

Objective To investigate the predictive value of serum NLR, PTX3 and 14-3-3-η proteins in patients with rheumatoid arthritis complicated with osteoporosis. Methods A retrospective analysis was performed on 130 patients with rheumatoid arthritis admitted to our hospital from January 2019 to August 2021, who were divided into a concurrent group and a non-concurrent group according to whether they had osteoporosis, including 43 cases (33.08%) in the concurrent group and 87 cases (66.92%) in the non-concurrent group. Relevant data of the two groups of patients were collected. Risk factors were analyzed and a risk nomogram model was constructed. In addition, 55 patients with rheumatoid arthritis admitted to our hospital from September 2021 to December 2022 were selected as the verification group, and relevant data were collected to verify the risk nomogram model. Results IL-17, CRP, NLR, PTX3 and 14-3-3-η protein were independent risk factors of osteoporosis in patients with rheumatoid arthritis. Logit(P) =0.181×IL-17+0.174×CRP+2.890×NLR+3.406×PTX3+0.632×14-3-3η protein-50.616. The area under ROC curve was 0.907, 95% CI (0.975-1.000), sensitivity was 93.0%, specificity was 97.7%. Conclusion Serum NLR, PTX3 and 14-3-3η protein are significantly different in rheumatoid arthritis patients with or without osteoporosis, and IL-17, CRP, NLR, PTX3 and 14-3-3η protein have higher predictive value when combined. [ABSTRACT FROM AUTHOR]

Background: Progressive pulmonary fibrosis (PPF) has been associated with a worse prognosis, even when interstitial lung disease (ILD) is related to rheumatic diseases. Since many differences are detectable among rheumatic diseases in prevalence and features of ILD, we aimed to investigate features of PPF in different rheumatic diseases, namely rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS). Methods: In an Italian multicentre cross-sectional study, consecutive pSS or RA patients with a diagnosis of ILD from at least two years were enrolled. For each patient, demographic, clinical, and serological data, other than chest high-resolution computed tomography and lung function tests, were recorded at the enrolment and after 2 years. Results: Among 232 patients, namely 156 RA-ILD and 76 pSS-ILD, a PPF was recorded in 38.8% of cases, without differences between the two diseases. Analysing patients with a PPF, usual interstitial pneumonia was significantly more frequent in RA than pSS (71.4% and 44.4%, respectively; p = 0.019), while ILD preceded the diagnosis of the rheumatic disease in 29.1% of RA and 89.5% of pSS (p < 0.001). Finally, RA patients were significantly younger than pSS at the diagnosis of the rheumatic disease (p < 0.001). Conclusions: In conclusion, although there is a similar prevalence of PPF in RA-ILD and pSS-ILD, we demonstrated for the first time that the two conditions differ in terms of radiological patterns and demographic and clinical features, suggesting that specific factors related to such diseases might influence the lung involvement over time. Prospective studies could investigate if these specificities could induce different responses to the treatment. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the current review was to elucidate the clinical context and presentation of sexual dysfunction (SD) and gynecomastia in rheumatological patients undergoing methotrexate treatment. Moreover, we aimed also to make physicians aware of the occurrence of these side effects, to adequately inform the patient before starting treatment. Methods: Systematic review (PROSPERO id: CRD42022358275) was performed according to preferred reporting items for systematic reviews and meta-analyses. Studies (1 January 1995 to 31 May 2022) were identified by highly sensitive searches of electronic databases (Medline, Embase, Cochrane Library databases). Key terms included: (("sexual dysfunction" OR "erectile dysfunction" OR "impotence") AND ("methotrexate" OR "MTX")) and (("gynecomastia" OR "male breast") AND ("methotrexate" OR "MTX")). Results: A total of seven papers (seven case reports), involving a total of eleven patients (min one, max three), were included in the final analysis. The age of the patients ranged from 19 to 68 years (median: 50.9 years). Rheumatoid arthritis (RA) was the most frequent rheumatic disease reported (n = 8, 72.7%). No patients reported erectile dysfunction (ED) and/or gynecomastia before using MTX. Time to onset of SD and gynecomastia after MTX ranged from 2 to 104 weeks (median: 22.7 weeks). ED (n = 5, 45.4%) and gynecomastia (n = 3, 27.2%) were the most common forms of presentation. Conclusions: Future prospective controlled studies with a large sample size and long follow-up as well as randomized controlled trials are needed to confirm this association, investigate its pathophysiological basis, assess the safest dosages, evaluate the most appropriate management, and provide clear recommendations. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to examine the role of two-dimensional shear wave elastography (SWE) in the assessment of the vascular wall of the carotid arteries and atherosclerotic plaques in patients with rheumatoid arthritis with moderate and low disease activity versus healthy controls. Methods: An observational case–control study was carried out at the University Medical Hospital "Kaspela" in Plovdiv, Bulgaria, from June 2023 to August 2024. This study included 24 patients with rheumatoid arthritis (RA) and 25 healthy controls. We employed two-dimensional SWE (2D-SWE) to examine the vessels around the plaques. The potential links with the degree of stenosis, plaque type, and cardiovascular risk were analyzed. Results: In the RA group, the 2D-SWE values showed significant positive correlations with the severity of the atherosclerotic plaques (rs = 0.461; 95% CI: 0.049 to 0.739; p = 0.023) and the degree of stenosis (rs = 0.920; 95% CI: 0.793 to 0.970; p < 0.001). Based on 2D-SWE, a ROC curve analysis distinguished higher severity plaques from lower severity plaques with an AUC = 0.818, 95% CI: 0.683 to 0.913. The optimal cut-off value of 2D-SWE > 32.40 kPa was associated with a sensitivity of 96%, a specificity of 56%, a positive predictive value (PPV) of 66.70%, and a negative predictive value (NPV) of 92.90%. Conclusion: Elastography can be an effective technique for assessing and stratifying atherosclerotic plaques in patients with RA, as well as for aiding in the early detection and subsequent prevention of future complications. [ABSTRACT FROM AUTHOR]

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthritis. We aim to study subclinical PD synovitis and thermographic joint inflammation assessment in patients with RA. Methods: We compared (1) PD synovitis at clinically quiescent (non-swollen; non-tender) joints based on patients' disease activity and (2) thermography (hands/wrists) outcomes based on PD joint inflammation findings and patient's disease activity. Results: Among eighty RA patients (mean (SD) age 57.0 (12.6) years; 61 of whom (76.3%) were female), the wrists (62.7%), second metacarpophalangeal joints (MCPJs) (37.0%), third MCPJs (33.8%), fourth MCPJs (24.8%), and fifth MCPJs (20.9%) were the five joint sites most frequently displaying subclinical PD synovitis; with no statistically significance differences (p > 0.05) between patients with 28-joint disease activity score (DAS28) < 3.2 versus those with DAS28 ≥ 3.2. At these five joint sites bilaterally, (1) the total maximum (Total Tmax), total average (Total Tavg), and total minimum (Total Tmin) temperatures were significantly greater (p < 0.05) for Total PD (TPD) score >1 versus TPD score ≤ 1, while their area under the ROC curve (AUC) values in identifying TPD score >1 ranged from 0.789 to 0.810, and (2) Total Tmax, Total Tavg, Total Tmin, and TPD score were significantly greater (p < 0.05) for patients with DAS28 ≥ 3.2 versus those with DAS28 < 3.2. Conclusions: Our results would serve as useful background data in studies on RA monitoring strategies detecting subclinical PD synovitis. Thermographic temperatures were greater in patients with greater disease activity and can help discriminate ultrasound PD joint inflammation severity. [ABSTRACT FROM AUTHOR]

Background: This study investigates the clinical characteristics and differences between primary Sjögren's Syndrome (pSS) and secondary Sjögren's Syndrome (sSS) in a cohort of 50 patients. Methods: Conducted across two academic facilities in North-East Romania, the study emphasizes the importance of glandular and extraglandular manifestations, focusing on salivary flow rates, pH levels, and buffer capacity. Patients were diagnosed using the 2016 ACR-EULAR classification criteria, with a detailed examination including salivary tests, biopsies, and antibody presence. Results: The findings highlight significant differences between pSS and sSS, particularly in salivary function, with pSS patients exhibiting more severe glandular dysfunction. The study also notes a higher prevalence of inflammatory joint involvement in sSS patients, often associated with rheumatoid arthritis. Statistical analysis revealed correlations between salivary parameters and disease progression, underscoring the necessity of tailored treatment strategies. The research suggests that lower salivary flow rates and altered pH levels in pSS patients contribute to compromised oral health, including increased dental cavities and periodontal disease. Conclusions: The study's results contribute to a deeper understanding of Sjögren's Syndrome and reinforce the need for multidisciplinary management to address both systemic and oral health complications in these patients. [ABSTRACT FROM AUTHOR]

Background The prevalence and risk factors of female sexual dysfunction (FSD) in female participants with rheumatoid arthritis (RA) were reported with inconsistent results. However, no systematic review and meta-analysis of pooled data provide reliable estimates of FSD prevalence in female participants with RA. Aim To investigate the global prevalence and risk factors of FSD in female participants with RA and to analyze the association between FSD risk and RA. Methods The study search of this systematic review and meta-analysis was conducted through PubMed, Cochrane Library, Web of Science, and Embase from the inception date to December 10, 2023. Random effects meta-analysis was performed to derive the pooled prevalence. Q and I 2 tests were used to analyze heterogeneity among the studies. Subgroup analyses and meta-regression were used to detect the sources of heterogeneity. Outcomes The pooled prevalence of FSD in female participants with RA was calculated, and odds ratios (ORs) and 95% CIs were used to assess the strength of the association between FSD-related risk factors and RA. Results A total of 13 studies were included in our analysis, involving 2327 participants. The pooled prevalence of FSD in female participants with RA was 49.1% (95% CI, 38.2%-60%). The participants with RA had a higher risk of FSD than healthy controls (OR, 3.10; 95% CI, 1.74-5.53). The significant risk factors of FSD in female participants with RA were depression status (OR, 1.42; 95% CI, 0.88-2.29) and menopause (OR, 5.46; 95% CI, 2.04-14.63). Clinical Implications Female participants with RA had a significantly increased prevalence of FSD, indicating that sexual function in female participants with RA should be concerned by clinicians. Strengths and Limitations The strength of this study is that it is the first meta-analysis to assess the global prevalence and risk factors of FSD in female participants with RA. A limitation is that the results, after the articles were pooled, showed significant heterogeneity and publication bias. Conclusions The present systematic review and meta-analysis revealed that the overall prevalence of FSD in female participants with RA was 49.1%, indicating a significant association between FSD risk and RA among females. Moreover, menopause and depression status were significantly associated with FSD in female participants with RA. [ABSTRACT FROM AUTHOR]

In recent years, the scientific community has shown interest in the role of gut microbiota in the development of autoimmune diseases (AID). Although observational studies have revealed significant associations between gut microbiota and AID like rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, these connections do not necessarily imply causality. Mendelian randomization (MR) approach has been extensively employed to investigate the causal relationship. Relevant MR study findings indicate that a reduction in beneficial microbial populations, particularly Bifidobacterium and Lactobacillus, and an increase in potential pathogenic microbes, is correlated with an elevated AID risk. Given the innovative potential of MR in unraveling the etiopathogenesis of AIDs, this article offers an overview of this methodological approach and its recent applications in AID research. [ABSTRACT FROM AUTHOR]