Background: Sleep disturbance is highly prevalent in rheumatoid arthritis (RA) and is a key determinant of patient-reported outcomes. However, the mechanistic pathways linking systemic inflammation and metabolic dysregulation, defined in this study as insulin resistance and adverse cardiometabolic indices, and sleep quality remain poorly defined. This study aimed to investigate the interplay between inflammatory/metabolic markers and sleep quality, and to determine whether sleep quality mediates the relationship between disease activity by DAS28-ESR and health-related quality of life. Methods: In this cross-sectional study, 128 patients with RA and 115 healthy controls were evaluated. Systemic inflammation and metabolic stress were characterized using ESR, CRP, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and indices including the TyG index and cardiometabolic index. Sleep was assessed via the Pittsburgh Sleep Quality Index and HRQoL via the Short Form-36. Mediation analyses (5,000 bootstrap resamples), adjusted for age, sex, smoking status, education level, and disease duration, and sensitivity analyses were performed to quantify the indirect effects of sleep quality on HRQoL domains. Results: RA patients exhibited significantly higher inflammatory and metabolic burden, markedly poorer sleep quality, and lower Vitamin D levels than controls (all p < 0.001). DAS28-ESR was the strongest independent predictor of poor sleep ( β = 0.534, p < 0.001), while Vitamin D was an independent predictor of better sleep ( β = −0.173, p = 0.002). Mediation analyses revealed that sleep quality may significantly mediate the association between disease activity and life quality, accounting for 24.4% of the effect of DAS28-ESR on Mental Health (Indirect Effect = −1.42; 95% CI − 2.38 to −0.62) and 23.6% on General Health. Sensitivity analyses confirmed these mediating effects were robust across BMI and gender subgroups. Conclusion: Sleep quality may represent a critical mechanistic link through which inflammatory disease activity translates into impaired HRQoL in RA. These findings suggest that nearly one-quarter of the disease’s psychological burden may be statistically mediated through sleep disruption. Integrating systematic sleep assessment and Vitamin D optimization into routine care may help mitigate the patient-perceived disease burden. Given the cross-sectional design, these findings should be interpreted as evidence of statistical mediation rather than confirmed causal pathways.

Background: Nociplastic-like pain features are increasingly recognized as significant contributors to chronic pain and reduced quality of life in patients with rheumatoid arthritis (RA). However, their clinical correlates and relationship with disease activity remain incompletely understood. Objective: To evaluate the prevalence of nociplastic-like pain features in patients with RA and to investigate their associations with disease activity, pain intensity, fatigue, sleep quality, and health-related quality of life. Methods: In this cross-sectional study, 160 patients with RA were enrolled. Nociplastic-like pain features were assessed using the PainDETECT questionnaire. Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28). Pain intensity, fatigue, sleep quality, and health-related quality of life were assessed using the visual analog scale (VAS), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Pittsburgh Sleep Quality Index (PSQI), and Short Form-36 (SF-36), respectively. Continuous variables were compared using t-tests or Mann–Whitney U tests according to data distribution. Stepwise multivariate linear regression analysis was performed to identify independent factors associated with PainDETECT scores. Results: Pain patterns suggestive of nociplastic-like features were identified in 22.5% of patients. These patients had significantly higher pain intensity, greater fatigue (lower FACIT-F scores), poorer sleep quality (higher PSQI scores), and lower SF-36 scores across all domains compared with patients without these features (all p < 0.001). PainDETECT scores showed a strong positive correlation with VAS pain intensity (r = 0.679, p < 0.001) and a moderate correlation with DAS28 (r = 0.536, p < 0.001). PainDETECT scores were negatively correlated with FACIT-F (r = −0.512, p < 0.001) and several SF-36 domains. In stepwise multivariate regression analysis, pain intensity, tender joint count, and education level emerged as independent predictors of nociplastic-like pain features, whereas inflammatory markers (CRP, ESR) and DAS28 were excluded from the model. Conclusions: Nociplastic-like pain features are common in RA and are independently associated with pain intensity, joint tenderness, and psychosocial factors rather than inflammatory activity alone. Routine assessment of these features is essential for personalized pain management and underscores the importance of considering potential central sensitization mechanisms in addition to traditional anti-inflammatory therapies.

Background and Objectives: Neuropathic pain is a prevalent and disabling consequence of spinal cord injury (SCI), adversely affecting physical function, psychological health, social engagement, and overall quality of life. Objectives: This study aimed to determine the prevalence of neuropathic pain in patients with spinal cord injury (SCI) and to examine its associations with clinical and demographic factors, quality of life, depression, and anxiety. Materials and Methods: Eighty-four patients with spinal cord injury (SCI) who were admitted to the Department of Physical Medicine and Rehabilitation and followed up at the rehabilitation outpatient clinic of Dicle University Faculty of Medicine (Diyarbakır, Turkey) were included in the study. Neurological status was assessed using the American Spinal Injury Association (ASIA) scale. Functional ambulation was evaluated with the Walking Index for Spinal Cord Injury (WISCI) and the Functional Ambulation Scale (FAS), while independence was measured using the Spinal Cord Independence Measure, version 3 (SCIM-III). Quality of life was assessed with the Short Form-36 (SF-36), and depression and anxiety were evaluated using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. The severity of neuropathic pain, fatigue, and paresthesia was assessed using the Visual Analog Scale (VAS) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire. Results: Neuropathic pain was observed in 41.7% of patients. No significant differences were found in age, sex, or marital status between patients with and without neuropathic pain. Patients with neuropathic pain had significantly higher Beck Anxiety Inventory (BAI) scores and lower scores in several Short Form-36 (SF-36) domains, including vitality, bodily pain, and emotional well-being. Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scores were positively correlated with Visual Analog Scale (VAS) fatigue and BAI scores, and negatively correlated with SF-36 domains such as vitality, general health, and bodily pain. Conclusions: Neuropathic pain is a common and debilitating complication following spinal cord injury (SCI). It is closely associated with reduced quality of life and heightened psychological distress, particularly anxiety. Early recognition and effective management of neuropathic pain are crucial for optimizing functional recovery and enhancing psychosocial well-being in patients with SCI.

Background: Antinuclear antibodies (ANAs) are frequently detected in patients with rheumatoid arthritis (RA); however, their prognostic relevance in predicting treatment escalation remains uncertain. Identifying biomarkers associated with earlier transition to advanced therapies may improve individualized disease management. Objectives: To evaluate the association of ANA status and titer levels with clinical characteristics, treatment trajectories, and time to biologic therapy initiation in patients with RA. Methods: In this retrospective cohort study, 223 patients with RA were stratified ac-cording to ANA status (112 ANA-positive, 111 ANA-negative). Baseline demographic data, disease activity (DAS28), and serological markers (RF, anti-CCP) were analyzed. Time to biologic therapy initiation, defined from the date of RA diagnosis to first bio-logic or targeted synthetic DMARD use, was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression. Multivariate models adjusted for relevant clinical covariates. Within the ANA-positive group, exploratory analyses compared low–moderate (1:80–1:320) and high (>1:320) ANA titers. Results: Baseline demographic and clinical characteristics were comparable between groups (all p > 0.05). ANA-positive patients more frequently initiated biologic therapy (48.2% vs. 24.3%, p < 0.001) and underwent multiple biologic switches (29.5% vs. 16.2%, p = 0.028). In multivariate analysis, ANA positivity was independently associated with earlier bi-ologic initiation (adjusted HR 2.14; 95% CI 1.32–3.46; p = 0.002), whereas RF and an-ti-CCP status were not significant predictors. In exploratory subgroup analysis, high ANA titers (>1:320) were associated with a lower hazard of biologic initiation com-pared with low–moderate titers (HR 0.24; 95% CI 0.06–0.98; p = 0.048). Conclusions: ANA positivity was independently associated with earlier initiation of biologic therapy in RA, supporting its potential incremental prognostic value beyond traditional sero-logical markers. The observed non-linear association between ANA titers and treat-ment escalation warrants cautious interpretation and validation in prospective studies.

Background: Liver involvement, particularly autoimmune hepatitis (AIH) overlap, is a rare but clinically important manifestation of systemic sclerosis (SSc). This study aimed to assess the prevalence, clinical characteristics, and diagnostic utility of laboratory parameters for identifying AIH in a cohort of patients with SSc. Methods: We retrospectively analyzed 111 patients with SSc. Clinical characteristics, autoantibody profiles, and laboratory parameters were compared between patients with and without AIH. AIH diagnosis was confirmed by liver biopsy in all cases. Given the small number of events, Firth’s penalized likelihood logistic regression was applied to identify independent risk factors. The diagnostic performance of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum IgG levels was evaluated using receiver operating characteristic (ROC) curve analysis. Prior methotrexate (MTX) exposure was recorded, and the potential confounding effect of MTX-induced liver enzyme elevations was assessed. Results: Autoimmune hepatitis (AIH) was identified in 8 of 111 patients (7.2%). All AIH-positive patients showed interface hepatitis on liver biopsy. There were no significant differences between AIH-positive and AIH-negative patients regarding age, systemic sclerosis subtype, or presence of interstitial lung disease (all p > 0.05). Firth’s penalized logistic regression indicated that diffuse cutaneous SSc, anti–Scl-70 positivity, and interstitial lung disease were not independent predictors of AIH overlap. In receiver operating characteristic analysis, alanine aminotransferase (ALT) demonstrated the highest diagnostic performance (AUC 0.88, 95% CI 0.76–0.99; p < 0.001), with a sensitivity of 87.5% and specificity of 85.4% at a cut-off > 34.5 U/L. Aspartate aminotransferase (AST) (AUC 0.86) and serum IgG (AUC 0.74) also showed significant but lower discriminatory ability. ALT retained high specificity for AIH even among patients with prior MTX exposure, supporting its utility as a non-invasive screening tool in SSc. Conclusion: Autoimmune hepatitis is a rare overlap syndrome in systemic sclerosis that occurs independently of clinical phenotype. Routine monitoring of liver transaminases, particularly ALT, provides a reliable non-invasive screening tool. Clinicians should consider ALT elevations > 34.5 U/L as a trigger for further AIH evaluation, even in patients with prior MTX exposure. Key Points • Autoimmune hepatitis (AIH) represents a clinically significant overlap in systemic sclerosis (SSc), with a prevalence of 7.2% in this cohort, indicating that it may be more common than previously reported when systematic screening is implemented. Biochemical screening rather than biopsy-only evaluation improves detection. • The development of AIH in SSc patients appears to be independent of disease subtype (limited vs. diffuse), specific autoantibody profiles (Anti-Scl70, ACA), or major organ involvement, such as interstitial lung disease. • An ALT threshold of > 34.5 U/L provides a practical “red flag” for clinicians, offering high sensitivity and specificity to prompt further diagnostic evaluation, including liver-specific autoantibody testing and liver biopsy when indicated. This threshold should be interpreted cautiously in patients with prior methotrexate (MTX) exposure, as mild ALT elevations may also reflect drug-related hepatotoxicity. • An ALT threshold of > 34.5 U/L provides a practical “red flag” for clinicians, offering high sensitivity and specificity to prompt further diagnostic evaluation, including liver-specific autoantibody testing and liver biopsy when indicated. • Because AIH can develop across the full spectrum of SSc regardless of systemic disease severity, routine monitoring of transaminases is essential for early detection and timely initiation of immunosuppressive therapy.

Background: Antinuclear antibodies (ANAs) are frequently detected in patients with rheumatoid arthritis (RA); however, their prognostic relevance for predicting treatment escalation and biologic therapy initiation remains incompletely understood. Identifying biomarkers associated with earlier transition to advanced therapies may enhance individualized, treat-to-target disease management. Objectives: We aimed to evaluate the association of ANA status and titer levels with clinical characteristics, treatment trajectories, and time to biologic therapy initiation in patients with RA. Methods: In this retrospective cohort study, 223 patients with RA were stratified according to ANA status (112 ANA-positive, 111 ANA-negative). Baseline demographic data, disease activity (DAS28), and serological markers (RF, anti-CCP) were analyzed. Time to biologic therapy initiation, defined from the date of RA diagnosis to first biologic or targeted synthetic DMARD use, was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression. Multivariate models adjusted for clinically relevant covariates (age, sex, disease duration, RF, anti-CCP). Within the ANA-positive group, exploratory analyses compared low–moderate (1:80–1:320) and high (>1:320) ANA titers, highlighting potential non-linear effects. Results: Baseline demographic and clinical characteristics were comparable between groups (all p > 0.05). ANA-positive patients more frequently initiated biologic therapy (48.2% vs. 24.3%, p < 0.001) and experienced multiple biologic switches (29.5% vs. 16.2%, p = 0.028). In multivariate analysis, ANA positivity independently predicted earlier biologic therapy initiation (adjusted HR 2.14; 95% CI 1.32–3.46; p = 0.002), whereas RF and anti-CCP status were not significant predictors. Exploratory subgroup analysis revealed the “titer paradox,” whereby high ANA titers (>1:320) were associated with a lower hazard of biologic therapy initiation compared with low–moderate titers (HR 0.24; 95% CI 0.06–0.98; p = 0.048). Conclusions: ANA positivity serves as an independent prognostic marker for earlier biologic therapy initiation in RA, providing incremental information beyond traditional serological markers. The observed non-linear association between ANA titers and treatment escalation underscores the need for cautious interpretation and validation in prospective, mechanistic studies, and highlights the potential value of integrating ANA profiling into personalized treatment strategies.