Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious central nervous system complication of systemic lupus erythematosus (SLE) that markedly reduces patient quality of life. Despite its clinical importance, the underlying mechanisms remain incompletely defined, and effective treatments are limited. In this review, we synthesize preclinical and clinical evidence that aberrant activation of innate immunity by self-nucleic acids and consequent overproduction of Type I interferons (IFN-I) constitute a central pathogenic axis in NPSLE. IFN-I and other inflammatory mediators promote disruption of the blood-brain barrier (BBB), enabling entry of autoantibodies, cytokines, and immune cells into the brain. These factors, together with damage-associated molecular patterns, activate microglia and astrocytes, driving sustained neuroinflammation that provokes synaptic loss, neurotransmitter dysregulation, excitotoxic neuronal injury, impaired neurogenesis, and mitochondrial dysfunction-mechanisms that underlie cognitive impairment, mood disorders, and other neuropsychiatric manifestations. We review therapeutic strategies targeting each step of this cascade, including blockade of IFN-I signaling (e.g., anifrolumab), inhibition of endosomal nucleic acid sensing (TLR antagonists), cytokine and JAK inhibition, modulation of microglial function (CSF1R inhibitors), and approaches to protect or restore BBB integrity (e.g., statins). Finally, we discuss biomarker-guided patient stratification and trial designs necessary to address NPSLE heterogeneity and accelerate the development of personalized therapies. By elucidating the cellular responses of the neurovascular unit to innate immune insults, this review provides a molecular framework for developing targeted therapies for NPSLE.

Eosinophilic granulomatosis with polyangiitis (EGPA) was regarded as a heterogeneous disease with respiratory involvement manifested in various patterns. This study aimed to explore whether subtypes with different clinical features and outcomes could be identified by latent class analysis (LCA) from the perspective of the respiratory system in patients with EGPA.

Patients diagnosed with EGPA between January 2000 and December 2022 were included. The clinical data and survival of the individuals were collected. Subtypes were identified using LCA according to organ involvement and anti-neutrophil cytoplasmic antibody (ANCA) status in model 1, according to patterns of respiratory involvement, other organ involvement, ANCA status, and inflammatory markers in model 2. The characteristics and prognosis of the classes were compared.

Out of the 330 patients initially diagnosed with EGPA, 245 patients were included eventually. In model 1, 138 (56.3%) and 107 (43.7%) patients were identified in classes 1 and 2, respectively. Class 2 was older (P = .017), had less musculoskeletal, mucocutaneous, cardiovascular, gastrointestinal, and peripheral nervous involvement (all P < .001) compared to class 1. No significant difference in overall survival was found between the classes. In model 2, LCA assigned 165 (67.3%) participants to class 1 (systemic EGPA) and 80 (32.7%) to class 2 (respiratory-limited EGPA). Compared with class 1, class 2 was younger (P < .001) and had lower levels of inflammation markers (white blood cell, eosinophil, erythrocyte sedimentation rate, and C-reactive protein: P < .001). Besides, patients in class 2 were more likely to have airway involvement, including the onset of asthma (P = .041), FEV1/ FVC < 70% (P < .001), and bronchiectasis (P < .001). Moreover, class 2 exhibited better survival compared to class 1 (P = .001).

The respiratory-limited EGPA may be the relatively milder type of disease. Other organ functions, serum inflammatory markers, and ANCA should be monitored during follow-up in these patients. Cite this article as: Gu Y, Liu Y, Zhang T, Han Y, Peng M, Shi J. Latent class analysis to explore subtypes of EGPA: Focusing on respiratory involvement and inflammation markers. Arch Rheumatol. 2026;41(2):81-89.

Upper gastrointestinal bleeding is a severe postoperative complication after coronary artery bypass grafting. We aimed to identify the incidence, predictors, and outcomes of nonvariceal upper gastrointestinal bleeding (NVUGIB) readmissions within 30 days after coronary artery bypass grafting from a nationwide database.

The Nationwide Readmission Database 2016 to 2020 was queried to identify patients who had isolated coronary artery bypass grafting and were readmitted with NVUGIB in 30 days. International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) and Procedure Coding System codes were used to identify the cohort. As the Nationwide Readmission Database is an anonymous public database, the study was exempt from the institutional review board. The analysis was conducted using Stata 17 (StataCorp LLC, College Station, TX).

Of 801 221 patients who underwent isolated coronary artery bypass grafting, 784 280 were discharged alive. Within 30 days, of the 5180 patients who were readmitted with a diagnosis of NVUGIB, the mortality rate was 5.4%. Compared with nonreadmitted patients, patients with NVUGIB had a lower proportion of women (25.4% versus 31.2%, P<0.001) but higher comorbidity burdens, such as atrial fibrillation (44.4% versus 39.1%, P<0.001), and blood transfusion (39.1% versus 6.0%, P<0.001). Key predictors for 30-day readmission with NVUGIB were atrial fibrillation (hazard ratio [HR], 1.31 [95% CI, 1.20-1.44]; P<0.001) and higher age (>65 years) (HR, 1.25 [95% CI, 1.01-1.53]; P=0.04). Female sex (odds ratio, 2.01 [95% CI, 1.28-3.17]; P=0.002) was strongly associated with death. Early (≤24 hours) esophagogastroduodenoscopy had better mortality outcomes (odds ratio, 0.23 [95% CI, 0.09-0.53]; P<0.001).

NVUGIB readmissions after coronary artery bypass grafting are linked to significant morbidity and death. Early esophagogastroduodenoscopy is associated with improved outcomes, emphasizing its role in management.

Nonvalvular cardiovascular device infections, although rare in most cases, represent substantial clinical challenges due to their life-threatening potential and diagnostic complexity. Although infections associated with prosthetic valves, cardiovascular implantable electronic devices, vascular grafts, and mechanical circulatory support devices have garnered considerable attention and specific guidance, infections of other nonvalvular cardiovascular devices have not. Therefore, this Science Advisory focuses on a contemporary profile of other nonvalvular device infections and includes an algorithm for their evaluation in patients with bloodstream infection, which is common, particularly among older individuals.

Glucocorticoid withdrawal syndrome (GWS) is a frequent and clinically significant consequence of reducing chronic endogenous or exogenous glucocorticoid exposure. The syndrome presents with a range of symptoms involving musculoskeletal, gastrointestinal, neuropsychiatric, cardiovascular, and metabolic domains which can closely resemble adrenal insufficiency or recurrence of an underlying autoimmune/inflammatory disease. As a result, the true prevalence, history, and clinical burden of GWS remain poorly defined, and recognition varies widely across clinical settings. The lack of treatment options for GWS contributes to detrimental exogenous glucocorticoid exposure in patients with rheumatologic, oncologic, and endocrine diseases. The underlying biological mechanisms of GWS remain incompletely understood, which represents a major barrier to the recognition and treatment of this syndrome. This review synthesizes current evidence on the epidemiology, clinical manifestations, and management challenges of GWS. We integrate mechanistic insights from studies of chronic glucocorticoid excess, postoperative recovery of Cushing syndrome, and experimental models of glucocorticoid excess and deficiency. Glucocorticoid excess leads to central and peripheral adaptations involving the hypothalamic-pituitary-adrenal axis, glucocorticoid receptor signaling, circadian rhythms, immune and inflammatory pathways, metabolic and autonomic regulation, and glucocorticoid-sensitive neural circuits. We propose that GWS arises due to the confluence of these persisting adaptations with relative glucocorticoid deficiency and tissue- or cell-specific adaptations and recovery timelines. Thus, we provide a mechanistic framework for understanding the diverse manifestations of GWS and highlights key gaps that need to be addressed to improve mechanistic understanding, diagnosis, and clinical management.

Loeys-Dietz Syndrome (LDS) represents a clinically and genetically heterogeneous group of connective tissue disorders that share features similar to Marfan syndrome, first identified in 2005. Characterized by significant manifestations such as aortic aneurysms, arterial tortuosity, craniofacial and skeletal anomalies, LDS results from pathogenic variants in key genes of the transforming growth factor-beta (TGFβ) signaling pathway. Given its variable expressivity, a multidisciplinary approach to management is critical. The paper provides an updated overview of effective management practices since the first LDS primer in 2014. It aims to enhance clinical awareness, inform healthcare providers, and improve patient outcomes through individualized care strategies for those living with LDS.

Titin (TTN) variants have been implicated in various types of cardiomyopathy. Allelic variant heterogeneity results in variable clinical phenotypes, which remains a major barrier for effective disease management. We aim to investigate the relationship between TTN variants and their associated cardiomyopathies and clinical outcomes.

A retrospective observational study was performed to evaluate patients with cardiomyopathy and TTN variants confirmed by whole-exome sequencing (WES) from January 2015 to December 2024. Univariable Cox regression analysis was conducted to identify independent risk factors for major adverse cardiovascular events (MACEs), and receiver operating characteristic analysis was used to determine its capability. In addition, the contribution of combined pathogenic variants with the TTN gene was assessed.

A total of 53 patients were identified with TTN variants, with a median onset age of 42.3 months (IQR 18.5-76.1), while 48 of 53 (90.50%) individuals had other genetic variants. Among them, 47.17% of patients presented with recurrent heart failure, while late gadolinium enhancement (LGE) was identified in 56.67% of cases that underwent magnetic resonance imaging (MRI) assessment. The variants in the A-band of TTN were most frequently recorded among the patients. Notably, early age-onset disease (HR = 1.008; 95% CI = 1.000-1.016; p = 0.037) served as a predictor of MACE in pediatrics with TTN-associated cardiomyopathy, and the optimal cutoff value was calculated as 75.50 months (specificity 57.1% and sensitivity 75.0%). Unfortunately, the combined genetic disorders failed to establish an association with worse outcomes in the general cohort. However, the presence of multiple genetic variants was associated with more severe adverse outcomes specifically in patients with dilated cardiomyopathy (DCM), with a higher prevalence of MACE occurrence.

In our cohort, early age-onset disease was a predictor of MACE in pediatrics with TTN-associated cardiomyopathy. In addition, the early age of disease onset revealed a higher likelihood of MACE in the first year after diagnosis. Multiple genetic variants with TTN presented more severe adverse outcomes in DCM assessment.

Skeletal fluorosis patients face a markedly elevated risk of cardiovascular metabolic abnormalities, including endothelial dysfunction, excessive oxidative stress, and impaired calcium-phosphate metabolism. Current clinical interventions for this condition are limited to symptomatic analgesia and conventional anti-osteoporotic treatments, and lack targeted therapeutic strategies for the "kidney deficiency and blood stasis" pathogenesis of skeletal fluorosis that can synergistically protect both the skeletal and cardiovascular systems.

This multicenter randomized controlled trial was conducted on 1,480 skeletal fluorosis patients from the China Fluorosis Cohort (CFC), to investigate the synergistic therapeutic effects of three traditional Chinese medicine (TCM) combinations-Ginkgo biloba combined with Epimedium (Drug 1), Xianling Gubao combined with Eucommia ulmoides (Drug 2), and Gusongbao combined with Rosa roxburghii (Drug 3)-in conjunction with lifestyle modifications on cardiovascular metabolic outcomes.

Smoking and alcohol consumption were identified as independent risk factors for reduced therapeutic efficacy in skeletal fluorosis patients with comorbid cardiovascular metabolic abnormalities (OR = 2.755, 95% CI: 1.400 -5.421). Among the three TCM combinations, Drug 2 and Drug 3 significantly counteracted these adverse risk factors, reducing the risk of treatment failure by 53.9% (OR = 0.461) and 57.0% (OR = 0.430), respectively. Drug 3 exhibited superior efficacy in reducing diastolic blood pressure (β = -2.263, P = 0.010), while its systolic blood pressure-lowering effect diminished with increasing age. Drug 2 showed synergistic benefits with improved sleep quality (β = 1.596, P = 0.002) and healthy dietary habits (β = -1.180, P = 0.001), which enhanced its antihypertensive effects and led to a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels (P < 0.05). Additionally, the interaction models outperformed the main-effect models, confirming the dynamic synergistic effect between lifestyle interventions and TCM pharmacotherapy.

These findings highlight the clinical necessity of integrating behavioral interventions with pharmacotherapy to optimize cardiovascular metabolic safety in the clinical management of skeletal fluorosis. Based on these results, we propose a novel theoretical framework-Personalized Behavioral-Integrated Therapy (PBIT)-which guides the incorporation of patient-specific behavioral and demographic factors into tailored treatment strategies, thereby improving the precision and clinical outcomes of skeletal fluorosis treatment.