Clinical Rheumatology最新文献

Background: Critically ill patients with rheumatoid arthritis (RA) have high short-term mortality. The platelet-to-lymphocyte ratio (PLR) reflects RA inflammatory activity. We evaluated whether admission PLR is associated with 28- and 90-day mortality in critically ill patients with RA.

Methods: RA patients were identified from the MIMIC-IV database. Restricted cubic spline (RCS) Cox models characterized the PLR-mortality association and defined a log PLR threshold. Patients were stratified into low, middle, and high PLR groups using this threshold with a ± 0.3 margin (δ). Cumulative incidence of death was assessed using the Kaplan-Meier method. Piecewise Cox models were constructed with incremental adjustment. Subgroup analyses tested the consistency of PLR's effect across different strata.

Results: Among 989 patients, 28- and 90-day mortality were 16.4% and 23.5%. RCS analysis showed a U-shaped association, with the lowest risk at log PLR = 4.725 and higher hazards toward both extremes. In piecewise Cox models, each + 1 log PLR was associated with lower mortality in the low PLR segment (28-day hazard ratio (HR) 0.59; 90-day HR 0.61) but higher risk in the high PLR segment (28-day HR 1.72; 90-day HR 1.67). Associations persisted after multivariable adjustment, with consistent subgroup trends.

Conclusions: Admission PLR is a significant prognostic marker in critically ill RA, demonstrating a U-shaped relationship with 28- and 90-day mortality. Both abnormally low and high PLR values were associated with higher mortality. Key Points • Admission PLR shows a U-shaped, independent association with 28- and 90-day mortality, with the lowest risk at log PLR 4.725 (~ PLR ≈112). • Threshold groups (PLR < ~ 84, 84 -153) and piecewise Cox models reveal decreasing risk below and increasing risk above the cutoff, persisting after multivariable adjustment. • Effects remain after multivariable adjustment and are consistent across clinical subgroups. • As a routine CBC metric, PLR enables simple early ICU risk stratification for RA, highlighting excess risk at both extremes.

Objective: To investigate whether benzbromarone or allopurinol use is associated with the risk of ischemic stroke among individuals aged 20-84 years with hyperuricemia or gout.

Methods: We conducted a retrospective cohort study utilizing 2006 to 2024 records from the TriNetX network. Individuals aged 20-84 years who used benzbromarone or allopurinol were included. To form the benzbromarone and allopurinol groups, individuals were matched 1:1 based on demographic and clinical comorbidities. The unadjusted risk ratio was estimated using the Compare Outcomes module in TriNetX. Additionally, a Cox proportional hazards regression model was applied to the unmatched cohort to estimate the adjusted hazard ratio, controlling for demographic and clinical comorbidities.

Results: After matching, each group included 26,510 individuals. Over a maximum 15-year follow-up period, the cumulative incidence of ischemic stroke was 1.375% in the benzbromarone group and 1.179% in the allopurinol group. The unadjusted risk ratio was 1.166 (95% CI: 1.003-1.355). The adjusted hazard ratio from the Cox model was 1.296 (95% CI: 1.129-1.488; P = 0.0002), indicating a statistically significant increased risk of ischemic stroke associated with benzbromarone use compared to allopurinol.

Conclusion: Benzbromarone use was associated with a higher long-term risk of ischemic stroke compared to allopurinol among individuals aged 20-84 years with hyperuricemia or gout. Key Points What is known: • Benzbromarone and allopurinol are two commonly prescribed urate-lowering therapies for hyperuricemia and gout. • The association between these medications and the risk of ischemic stroke remains uncertain. What is new here: • In this study, benzbromarone use was associated with a significantly higher risk of ischemic stroke compared to allopurinol use. • The adjusted hazard ratio for ischemic stroke was 1.296 (95% CI: 1.129-1.488, P = 0.0002) for benzbromarone versus allopurinol. Translational impact: • These findings suggest that benzbromarone may carry a higher long-term ischemic stroke risk than allopurinol, which could inform clinical decision-making in urate-lowering therapy selection.

Objectives: To identify echocardiographic parameters that predict prognosis in pulmonary arterial hypertension (PAH) patients with low and intermediate risk.

Methods: This single-center retrospective cohort study included PAH patients classified as low or intermediate risk according to WSPH criteria. All patients were regularly followed at the First Affiliated Hospital of Nanjing Medical University. Baseline and follow-up data were collected using standardized case report forms. Missing data were imputed using the random forest method. Statistical analyses were performed using SPSS 26.0 and R 4.3.1, with a two-sided p < 0.05 considered significant.

Results: A total of 116 PAH patients (57 low risk, 59 intermediate risk) were enrolled. During a median follow-up of 34.8 months, 28 patients (24.1%) experienced clinical failure events. The TAPSE/PASP ratio was an independent predictor of poor prognosis (HR = 0.002, 95% CI 1.09e-5-0.294, p = 0.015). Kaplan-Meier analysis showed that patients with TAPSE/PASP < 0.33 and IVC ≥ 16 mm had significantly worse event-free survival (p < 0.001).

Conclusions: The combination of TAPSE/PASP < 0.33 and IVC ≥ 16 mm identifies poor prognosis among low- and intermediate-risk PAH patients, providing a simple echocardiographic tool for early risk stratification. Key Points • TAPSE/PASP ratio combined with IVC diameter provides a simple, non-invasive index to identify poor prognosis in low- and intermediate-risk CTD-PAH patients. • This combined echocardiographic assessment may facilitate early recognition of right ventricular-pulmonary arterial uncoupling and guide timely treatment adjustment. • It refines risk evaluation beyond conventional WSPH stratification, supporting individualized long-term management in CTD-PAH.

Objectives: Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disorder causing multi-organ damage. Current diagnostic methods are hindered by inadequate sensitivity and specificity of conventional biomarkers, which frequently delay diagnosis. Therefore, identifying reliable diagnostic biomarkers for SLE remains critically needed.

Methods: SLE microarray datasets from Gene Expression Omnibus were preprocessed. Potential SLE diagnostic biomarkers were identified through differential expression analysis, weighted gene co-expression network analysis, and machine learning feature selection. Diagnostic models were constructed based on the candidate genes, optimized with nine machine learning algorithms. The expression levels of the candidate genes were further validated in clinical samples using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), with their clinical relevance assessed statistically.

Results: Four candidate genes-HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase 5 (HERC5), Interferon Alpha Inducible Protein 6 (IFI6), Interferon Inducible Protein with Tetratricopeptide Repeats 3 (IFIT3), and 2'-5'-Oligoadenylate Synthetase Like (OASL)-showed potential as SLE diagnostic biomarkers, with significantly higher expression in SLE patients versus controls. Individual receiver operating characteristic (ROC) curves for the candidate genes showed area under the curve (AUC) values exceeding 0.8 (P < 0.001), while nomogram model achieved superior accuracy (AUC = 0.905, P < 0.001). Optimized diagnostic models demonstrated robust performance in different datasets (AUC > 0.85, P < 0.001), specifically distinguishing SLE from hepatitis C, multiple sclerosis, and tuberculosis. Clinical validation confirmed these findings, with the gene combination outperforming conventional biomarkers in assessing disease activity (AUC = 0.776, P < 0.001).

Conclusions: HERC5, IFI6, IFIT3, and OASL can serve as potential diagnostic biomarkers for SLE. The combination of candidate genes demonstrates both differential diagnosis capability and quantitative assessment of disease activity. Key Points • This study integrated bioinformatics and machine learning to screen and identify four candidate genes HERC5, IFI6, IFIT3, and OASL as potential diagnostic biomarkers for SLE.. • Machine learning-optimized diagnostic models based on HERC5, IFI6, IFIT3, and OASL demonstrated excellent diagnostic performance and discriminative capability. • The expression levels and diagnostic potential of HERC5, IFI6, IFIT3, and OASL were further validated using clinical samples, and the results aligned with the findings of the bioinformatics analysis.

Introduction/objectives: This study provides a novel comparison of sleep disturbances and associated risk factors in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), and assesses the correlation between the Multidimensional Health Assessment Questionnaire (MDHAQ) and the Pittsburgh Sleep Quality Index (PSQI) in detecting poor sleep.

Method: We performed a cross-sectional study of 313 adult patients included in the PolNorRHEUMA registry. Demographics, disease activity, pain and other clinical variables were recorded. Patients completed a PSQI, with scores higher than 5 indicating poor sleep, and an MDHAQ, including queries concerning sleep, anxiety, depression, stress.

Results: This study included 129 patients with RA, 81 with PsA and 103 with axSpA. The median disease activity scores corresponded to remission or low disease activity. The prevalence of poor sleep was 61.5% in PsA, 63.7% in RA, to 66.7% in axSpA; no significant differences in PSQI total scores or sleep domains were identified. Independent risk factors for poor sleep were female sex in RA, older age and anxiety in PsA. Strong correlation coefficients between the MDHAQ sleep-related question and PSQI score were observed: 0.53 for RA, 0.65 for PsA and 0.55 for axSpA (p < 0.01). In the linear regression analysis, a significant association was maintained in RA and axSpA.

Conclusions: Our research confirms a high prevalence of sleep disturbances in RA, axSpA, and PsA, despite well-controlled disease activity, highlighting the role of non-inflammatory factors in the pathophysiology. The MDHAQ could serve as a screening tool for identifying poor sleep quality. Key Points •Poor sleep is prevalent among patients with RA, axSpA and PsA •Prevalence of sleep disturbances is high despite well-controlled disease activity. •Risk factors for poor sleep identified in this study include female sex in RA, and older age and anxiety in PsA. •The MDHAQ could serve as a screening tool for identifying patients with poor sleep quality, needing further evaluation.

Background: Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, and its molecular mechanisms remain poorly understood.

Methods: We employed a multi-faceted approach combining transcriptome-wide association studies (TWAS), chemical-genomic enrichment analysis (CGSEA), and network pharmacology to identify OA-related chemicals and construct a disease-drug interaction network. Molecular docking was performed to assess melatonin's binding affinity to ferroptosis-related proteins. Melatonin was selected as a candidate for further investigation. In vitro experiments were conducted using SW1353 chondrocytes to validate the effects of melatonin on IL-1β-induced ferroptosis, extracellular matrix degradation, and inflammatory responses.

Results: Molecular docking confirmed melatonin's strong binding affinity to ferroptosis-related proteins. In vitro experiments with IL-1β-stimulated SW1353 chondrocytes revealed that melatonin reversed IL-1β-induced ferroptosis by restoring SLC7A11/GPX4 expression, reducing ROS accumulation, and suppressing P53 activation. Melatonin also mitigated extracellular matrix degradation (via COL2A1/MMP13 modulation) and inflammatory responses (via COX-2/iNOS downregulation).

Conclusion: These findings demonstrate that melatonin alleviates OA progression by inhibiting ferroptosis and inflammation, offering a novel therapeutic strategy. This study integrates computational and experimental validation to elucidate melatonin's mechanism in OA, supporting its clinical potential. Key points • Identification of melatonin as a potential therapeutic agent for osteoarthritis (OA) by TWAS, CGSEA, and network pharmacology conjoint analysis. • Molecular docking shows strong binding capacity of melatonin to iron death-related proteins (e.g., GPX4, SLC7A11). • Experimentally confirmed that melatonin significantly reversed IL-1β-induced iron death in chondrocytes by restoring SLC7A11/GPX4 expression, inhibiting P53 activation and reducing ROS accumulation.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized by small vessel inflammation, which can lead to renal hemorrhage. Some forms of ANCA-associated vasculitis, such as microscopic polyangiitis, may lead to aneurysm formation, particularly renal aneurysm, which may resolve with appropriate immunosuppressive therapy. However, maintenance treatment should be administered cautiously to patients with ANCA-associated vasculitis and end-stage renal disease (ESRD) owing to the lower relapse rate and increased risk of infectious complications associated with immunosuppressive therapy. Herein, we describe a case involving a woman with ANCA-associated vasculitis and ESRD who did not receive maintenance immunosuppressive therapy and subsequently experienced right and left renal hemorrhages 8 and 14 years after the initiation of dialysis, respectively. Treatment choices for ANCA-associated vasculitis are based on individual factors such as disease severity and level of vasculitis activity. This case report highlights ANCA-associated vasculitis with two episodes of aneurysm-related bleeding, emphasizing that maintenance immunosuppressive therapy may be critical for patients having ANCA-associated vasculitis with ESRD, particularly those with persistently high ANCA titers.

Background: Xanthine oxidase inhibitors (XOis) are commonly used to treat gout and hyperuricemia. Beyond urate-lowering effects, XOis may influence cardiovascular outcomes via oxidative stress pathways. Prior evidence, including post hoc analyses of the CARES trial, suggests increased mortality after XOi discontinuation, raising concern for a potential "withdrawal syndrome." However, evidence from real-world outpatient populations is limited.

Objective: This study aims to evaluate whether the recent discontinuation of XOi therapy is associated with an increased risk of acute cardiovascular events in patients with gout.

Methods: We conducted a retrospective cohort study using the Merative MarketScan database. Adults with gout initiating allopurinol or febuxostat were included. Discontinuation was defined as no XOi supply in the prior 90 days during the 121- to 180-day window post-initiation. The primary outcome was hospitalization or outpatient diagnosis of acute myocardial infarction or ischemic stroke. Cox proportional hazards models with stabilized inverse probability weights were used to estimate hazard ratios (HRs), adjusting for demographic and clinical covariates.

Results: Among 508,872 patients initiating XOi therapy, 23.6% discontinued therapy within the first 121- to 180-day post-initiation timeframe. Discontinuers were younger with fewer comorbidities at baseline. After weighting, groups were well balanced. XOi discontinuation was associated with a modest but statistically significant increased risk of acute cardiovascular events (HR, 1.05; 95% CI, 1.01-1.09; p = 0.019). The magnitude of the effect increases among patients with preexisting hypertension diagnoses (HR, 1.13; 95% CI, 1.03-1.23; p = 0.006).

Conclusions: In this large real-world cohort, early discontinuation of XOi therapy was linked to a small but significant elevation in cardiovascular risk. These findings support prior signals of potential harm from XOi withdrawal, particularly among patients with cardiovascular disease, and highlight the importance of sustained therapy adherence. Key Points • Xanthine oxidase inhibitor (XOi) discontinuation was associated with a modest but significant increase in acute cardiovascular events in a large national cohort of patients with gout. • Even early discontinuation after XOi initiation may increase cardiovascular risk, underscoring the importance of treatment persistence. • Adherence to XOi therapy may be an important factor in reducing cardiovascular risk among gout patients.

Aims: To investigate the relationship between serum urate levels and gout flares and how these vary at different times of the year.

Methods: A cohort of people with incident gout was established using a large UK primary care database (Clinical Practice Research Database). Clinician-recorded gout flares and serum urate (SU) measurements were identified and described using joinpoint linear regression modelling. The relationship between SU level, flare frequency, month of the year and mean monthly temperatures was explored and correlations tested using Pearson correlation coefficients.

Results: 249,157 individuals (mean follow-up 6.7 years) experienced 417,101 flares and had 341,457 SU measurements (mean SU 437 µmol/L, standard deviation (SD) 106 µmol/L). SU levels peaked the day before a flare (487 µmol/L). Mean SU in the year preceding a flare was 474 µmol/L compared with 432 µmol/L in the year post-flare. SU levels did not near pre-flare levels in the year following a flare. Flares were most frequent, and SU was highest, in the summer months (June to August). The correlation co-efficient between flares and months of the year was 0.94, whereas the correlation with temperature was less strong (0.70).

Conclusions: SU measurement in the year following a gout flare is not indicative of the peak (pre-flare) SU levels that an individual may have experienced. Clinicians should consider this when considering SU measurements in the diagnosis of gout. Patients may find it helpful to be informed of the seasonality of gout flares and advised to take extra caution to reduce the risk of flares during summer months. Keypoints • Serum urate (SU) levels drop precipitously during gout flares and remain low for several months. • Correlations exist between flare rate and summer months, and with seasonal variation in SU levels. • Clinicians should be aware of how gout flares affect SU when interpreting SU levels.