Clinical Rheumatology最新文献

Background: Familial Mediterranean fever (FMF) is an autoinflammatory disorder associated with MEFV gene mutations. Recurrent febrile episodes associated with serosal inflammation, arthritis, and characteristic skin findings represent the classic presentation of FMF. Lifelong colchicine treatment is the standard of care. However, the feasibility of colchicine cessation in FMF remains controversial, with limited data, particularly in adults.

Methods: FMF patients diagnosed between January 2005 and December 2021 were screened, and those who voluntarily discontinued colchicine without a clinical indication were identified. After applying exclusion criteria, eligible patients were divided into two groups based on the presence of attacks in the 6 months before discontinuation. Baseline characteristics and 1-year post-discontinuation outcomes were then compared between the groups.

Results: Fifty-four FMF patients met the eligibility criteria: 17 attack-free for 6 months before colchicine discontinuation (Group 1) and 37 with attacks (Group 2). Group 1 patients were younger, started colchicine earlier, and had a milder phenotype with no M694V homozygosity. After discontinuation, Group 2 had higher attack rates, while CRP levels rose in both groups, more prominently in Group 1. Within 1 year, four patients (23.5%) in Group 1 and one (2.7%) in Group 2 remained attack-free with low CRP, and three patients in Group 2 restarted colchicine.

Conclusions: Attack frequency during discontinuation can be anticipated from pre-discontinuation patterns; however, subclinical inflammation is less predictable. FMF patients with a milder phenotype without M694V homozygosity showed higher success rates of colchicine discontinuation in the first year. These findings suggest that colchicine discontinuation may be feasible in carefully selected patients under close monitoring. Key Points • A limited subset of FMF patients with mild, attack-free disease and without M694V homozygosity may be candidates for carefully individualized consideration of colchicine discontinuation. • In the case of discontinuation of colchicine in FMF patients, the attack frequency before discontinuation, even short-term (6 months), can predict the attack frequency in the discontinuation period. • The subclinical inflammation should be evaluated independently, irrespective of the clinical phenotype of the FMF patients, if the colchicine discontinuation is considered. Therefore, close monitoring is a must after discontinuation.

Objectives: To investigate the relationship between individual urinary phytoestrogen metabolites and hyperuricemia (HUA), as well as the potential impact of a mixture of these metabolites on HUA.

Methods: This cross-sectional study included a total of 9253 participants, with data sourced from the National Health and Nutrition Examination Survey (NHANES). Urinary levels of daidzein, o-desmethylangolensin (O-DMA), equol, genistein, enterodiol, and enterolactone were measured to assess exposure to urinary phytoestrogen metabolites. HUA was defined as the study outcome. First, weighted logistic regression and smoothed curve fitting were used to analyze the relationships between individual urinary phytoestrogen metabolites and HUA. Subsequently, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) models were used to explore the comprehensive effects of the six phytoestrogen metabolites on HUA.

Results: The prevalence of HUA in this study was approximately 18.33%. Weighted logistic regression analysis indicated that urinary daidzein, O-DMA, equol, and enterolactone were associated with a reduced risk of HUA. The study further identified threshold effects of daidzein, O-DMA, and equol on the risk of HUA. WQS, qgcomp, and BKMR models revealed that mixed metabolites of urinary phytoestrogens were negatively correlated with HUA risk, with equol and enterolactone being the main contributors. A comprehensive comparison of the results from these models demonstrated high stability and consistency.

Conclusion: Mixed urinary phytoestrogen metabolites were inversely associated with the risk of HUA, with equol and enterolactone serving as the primary contributing factors. This observational study provides a basis for public health strategies but cannot establish causality. Key Points • Large-scale population studies have shown that plant estrogen metabolites (daidzein, o-desmethylangolensin, equol, and enterolactone) are significantly inversely associated with hyperuricemia (HUA) risk. Saturation effects were observed for daidzein, o-desmethylangolensin, and equol. • This study confirms that mixed exposure to these metabolites reduces HUA risk, mainly due to equol and enterolactone. • Promoting public health policies to harness plant estrogens' benefits could improve population health.

Introductions: Foot and ankle arthritis (FAA) in Rheumatoid Arthritis (RA) patients is an under-recognized clinical problem. Patients may have FAA in a disease remission state as most of the disease severity calculation consider 28 joints excluding FAA. Our objective was to estimate the prevalence of FAA, and to determine its correlation with disease activity and other clinical variables.

Methods: A cross-sectional study was conducted from 2022 to 2023 among 201 RA patients, meeting 2010 ACR/EULAR criteria. Clinical assessment, joint examination (including foot and ankle), laboratory parameters, and disease activity scores (CDAI, DAS28, SDAI) were recorded.

Results: Among the 201 RA participants, 65.0% were female, 75.1% had advanced disease, and 25.4% had comorbidity. The mean age was 44.7 ± 11.48 years. FAA was reported in 46.8% of patients, with more frequent ankle involvement (30.3%) than MTP joints (14.4%). However, 35.3% had FAA in the past. FAA was significantly associated with higher ESR (p < 0.01), pain scores (VAS) [ p = 0.001], conventional disease modifying drugs (csDMARDs) [p = 0.009] and higher swollen joint count/tender joint count (p < 0.05). FAA correlated significantly with higher disease activity scores (CDAI, SDAI, DAS28; p < 0.001). No significant association was found with age, comorbidities, BMI, disease duration, serology, or steroid use.

Conclusion: The prevalence of FAA is high in RA and strongly associated with increased disease activity despite being excluded from standard indices. These findings highlight the need to incorporate foot and ankle assessments into routine RA evaluations. Key Points •FAA is commonly affected in RA and may be considered when assessing disease activity. •FAA showed a significant association with higher disease activity, even though it is excluded from disease activity score.

Background: A high incidence of cardiovascular disease (CVD) is observed among patients with rheumatoid arthritis (RA); although the systemic inflammatory response index (SIRI) has demonstrated predictive utility across inflammatory and cardiovascular disorders, its relationship with CVD risk in RA remains underinvestigated.

Methods: The present study was partitioned into a training set, a temporal validation set, and an external validation set derived from the NHANES database and a Chinese clinical cohort. Between-group differences were characterized, and multivariable logistic regression models were fitted across SIRI tertiles within each dataset. Restricted cubic spline functions were plotted to visualize dose-response associations, and receiver operating characteristic analysis was employed to quantify discrimination and predictive probabilities. Additionally, the incremental value of augmenting the Framingham risk score with SIRI was evaluated across all three datasets. Variable importance derived from an XGBoost algorithm and SHAP summary plots were used to quantify contributor-specific risk, whereas net reclassification improvement and integrated discrimination improvement were computed to corroborate model superiority.

Results: In training set, CVD prevalence among RA patients was 23.22 % and the mean age was 65.5 years. The cohort comprised 167 male (48.55%) and 177 female (51.45%). Median SIRI values were significantly higher in participants with CVD than in those without (1.19 vs. 0.99, P < 0.001). A positive association between SIRI and CVD risk was detected (P for overall = 0.003, P for nonlinear = 0.022), participants in the highest SIRI tertile exhibited 2-fold increase in CVD risk relative to the lowest tertile (OR = 2.028, 95% CI: 1.343-3.075, P < 0.001). Incorporation of SIRI into the Framingham risk score improved the area under the receiver operating characteristic curve on training set (0.705 vs. 0.688), time validation set (0.693 vs. 0.678) and external validation set (0.793 vs. 0.761) set. Variable importance metrics and SHAP value distributions further indicated that SIRI constitutes a principal determinant of CVD risk in RA.

Conclusion: SIRI is significantly and positively associated with CVD risk in RA and effectively enhances the predictive performance of the Framingham risk score when applied to this population. Accordingly, SIRI may serve as an inflammatory biomarker for the early identification and management of CVD risk in RA, thereby informing the development of individualized therapeutic strategies. Key Points • SIRI is significantly and positively associated with CVD risk in RA. • SIRI enhances the predictive performance of the Framingham risk score when applied to RA patients.

Background: Patients with rheumatoid arthritis (RA) face significantly elevated cardiovascular risks, yet the underlying immunological mechanisms remain incompletely understood, particularly in refractory RA subgroups.

Objective: To investigate the association between Th17/Treg immune imbalance and cardiovascular complications in RA patients, with a focus on delineating the unique pathological mechanisms in refractory subgroups.

Methods: This single-center retrospective cohort study (2015-2024) included 3,464 RA patients (1,872 common RA; 1,592 refractory RA) diagnosed per 2010 ACR/EULAR criteria. Flow cytometry quantified Th17 and Treg absolute counts and ratios. Patients were stratified into four immunophenotypic subgroups: Group A (Treg-deficient/Th17-normal-or-low), Group B (Treg-normal-or-high/Th17-normal-or-low), Group C (Treg-normal-or-high/Th17-high), and Group D (Treg-deficient/Th17-high). Cardiovascular outcomes included coronary artery disease, myocardial infarction, and related events.

Results: In all RA, elevated Th17/Treg ratios correlated with increased cardiovascular risk (χ² = 8.222, P = 0.016), while individual cell counts lacked predictive value. In refractory RA, Treg counts independently predicted events (χ² = 6.050, P = 0.049), with Group A (Treg-deficient/Th17-normal-low) showing the highest event rate (9.4% vs. 4.9%, P = 0.048). Treg-deficient patients exhibited altered lipid profiles; Treg-normal-or-high refractory RA had higher smoking rates (20.0% vs. 12.6%, P = 0.008).

Conclusion: Th17/Treg imbalance serves as a central predictor of cardiovascular risk in general RA, whereas Treg deficiency dominates in refractory RA. The interplay between immune dysregulation (Treg exhaustion), pro-inflammatory HDL remodeling, and behavioral factors constructs an "immune-metabolic-environmental" axis driving cardiovascular pathogenesis. These findings provide novel biomarkers and precision intervention targets for stratified RA management. Key Points • Treg absolute count, not Th17/Treg ratio, independently predicts cardiovascular events in refractory RA. • A novel immunophenotypic stratification (Groups A-D) identifies high-risk Group A with the highest CAD incidence. • Treg deficiency drives pro-inflammatory HDL remodeling, revealing an immune-metabolic crosstalk in RA. • Distinct mechanisms exist between common and refractory RA, defining an integrated immune-metabolic-environmental axis.

Background: Current evidence indicates that high serum urate levels are associated with an increased occurrence of atrial fibrillation (AF), and urate-lowering drugs could potentially reduce this risk. Nonetheless, the processes driving this relationship remain unclear.

Objective: To identify key mediators linking urate to AF and assess the direct effects of potential drug targets on AF risk.

Methods: Genetic variants associated with serum urate levels, potential mediators, and urate-lowering drug targets were identified from genome-wide association studies (GWAS). Univariable Mendelian randomization, multivariable Mendelian randomization, and two-step-cis-MR were conducted. The Bayesian horseshoe prior MR approach was used as the primary method, and Genomic SEM was employed to support the mediation model.

Results: The study identified a genetic and causal relationship between serum urate levels and AF onset. Key mediators included systolic blood pressure (proportion mediated 56.23%), diastolic blood pressure (25.27%), hypertension (49.46%), hypercholesterolemia (4.83%), coronary atherosclerosis (12.24%), myocardial infarction (30.32%), coronary artery disease (29.74%), and heart failure (47.66%). Drug target MR analysis found strong evidence for URAT1 inhibition reducing AF risk (odds ratio [OR] = 0.91, 95% Bayesian credible interval [BCI] 0.85 to 0.97; Bayesian posterior probability [BPP] = 0.997), which persisted after mediator adjustment. Under stricter flanking regions, evidence weakened after adjustment for heart failure (OR = 0.93, 95% BCI 0.84 to 1.04; BPP = 0.907) but remained robust for other mediators.

Conclusion: This study highlights several cardiovascular conditions (hypertension, hypercholesterolemia, heart failure, coronary artery diseases) as key mediators between serum urate and AF and supports URAT1 inhibition as a potential therapeutic strategy. Key points •Elevated serum urate increases the risk of atrial fibrillation, potentially through cardiovascular mediators such as hypertension, heart failure, and coronary artery diseases. •Genetic evidence from drug-target Mendelian randomization supports URAT1 inhibition as a potential therapeutic strategy for reducing atrial fibrillation risk. •The protective effect of URAT1 inhibition against atrial fibrillation persists after adjusting for key cardiovascular mediators, suggesting additional therapeutic pathways beyond those identified.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation. Growing evidence suggests a link between insulin resistance (IR) and RA. However, the association of specific lipid-based IR indices, such as the Mffm/I index (Metabolic Score for Insulin Sensitivity), with RA prevalence remains underexplored. This study aimed to investigate the associations of the Mffm/I index and the Quantitative Insulin Sensitivity Check Index (QUICKI) with the prevalence of RA in a large, nationally representative population.

Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018. A total of 8,477 adult participants were included and categorized based on their RA status. The associations between Mffm/I, QUICKI (as both continuous variables and quartiles), and RA were evaluated using multivariable logistic regression models, adjusting for a comprehensive set of sociodemographic and clinical covariates. Results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses, interaction tests, and mediation analyses were conducted to explore the consistency of these associations and the potential mediating role of obesity.

Results: Of the 8,477 participants, 549 (6.5%) reported a diagnosis of RA. After full adjustment for potential confounders, both the Mffm/I index and QUICKI demonstrated a significant inverse association with RA. In the fully adjusted model (Model 3), participants in the highest quartile (Q4) of Mffm/I had a 40% lower odds of RA (OR = 0.60, 95% CI: 0.45-0.79) compared to the lowest quartile (Q1). Similarly, the highest quartile of QUICKI was associated with a 28% lower odds of RA (OR = 0.72, 95% CI: 0.55-0.94). These negative associations were consistent across most predefined subgroups. Mediation analysis revealed that obesity significantly mediated the relationships, accounting for 43.87% of the total effect for Mffm/I and 51.04% for QUICKI.

Conclusion: This study establishes a stable and robust inverse association between both the Mffm/I index and QUICKI and the prevalence of rheumatoid arthritis in the U.S. adult population. These findings highlight the potential role of insulin sensitivity in the pathophysiology of RA and suggest that obesity is a critical mediator in this relationship. These easily accessible indices may serve as valuable tools for risk assessment in clinical practice. Key Points • High insulin sensitivity is strongly associated with lower rheumatoid arthritis prevalence. • The novel lipid-based Mffm/I index is a robust indicator of RA prevalence. • Obesity mediates over 40% of the link between insulin resistance and RA. • Accessible insulin sensitivity indices may aid in clinical RA risk assessment.

Introduction/objectives: This study aimed to evaluate whether ultrasound-guided genicular nerve block (GNB) provides superior pain relief and functional improvement in patients with knee osteoarthritis (OA) compared to a placebo procedure. Additionally, it investigated whether the inclusion of a corticosteroid enhances the efficacy of the block.

Materials and methods: Eighty-one patients diagnosed with knee OA according to the American College of Rheumatology criteria were enrolled in this prospective, randomized, double-blind, placebo-controlled study. Participants were randomly assigned to one of three groups: GNB with local anesthetic (group 1), GNB with local anesthetic plus corticosteroid (group 2), or a placebo procedure (group 3). All patients followed a standardized daily knee exercise program. Primary outcome measure was pain severity evaluated by the Visual Analog Scale (VAS) and pressure pain threshold (PPT) measured with an algometer, secondary outcome measure was disability and function level evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the 40-m fast-paced walk test. Assessments were conducted at baseline, as well as at the 1st week and 1st month following the intervention.

Results: A total of 75 patients completed the study. All three groups demonstrated statistically significant improvements in VAS scores at both the 1st week (p-values for groups 1, 2, and 3: < 0.0001, < 0.0001, and 0.039, respectively) and the 1st month (p-values: 0.001, < 0.001, and 0.007, respectively) compared to baseline. Both treatment groups showed significantly greater improvements than the placebo group at both follow-up points (p = 0.001). Significant improvements in medial patella PPT, WOMAC scores, and the 40-m fast-paced walk test were observed in groups 1 and 2 (p < 0.05), but not in group 3. No statistically significant differences were found between groups 1 and 2 for any of the outcome measures (p > 0.05).

Conclusion: In patients with knee OA, GNB leads to reduced pain and disability and improved physical capacity, regardless of whether corticosteroids are used as an adjuvant. Key Points • Ultrasound-guided genicular nerve block appears to be an effective treatment option for reducing pain and improving function in patients with knee osteoarthritis. • Adding corticosteroids to the local anesthetic during the procedure did not provide any additional benefit in terms of pain relief or functional improvement.