BACKGROUND:Older adults with rheumatoid arthritis (RA) frequently present with multiple comorbidities and geriatric syndromes (GS), complicating disease management and increasing vulnerability. Comprehensive geriatric assessment (CGA) is a multidimensional approach evaluating functional, physical, cognitive and psychosocial domains, providing a holistic framework for patient-centered care. AIM:To assess the utility of CGA in identifying multidomain impairments and healthcare needs in older adults with RA and to explore the relationship between comorbidity burden, GS, disease activity and functional status. METHODS:This cross-sectional observational study included 100 patients aged ≥65 years fulfilling ACR/EULAR RA criteria. Sociodemographic and clinical data were collected, including pain, fatigue, mobility, nutrition, continence, sensory function, falls, sleep, comorbidities and medication use. All participants underwent musculoskeletal examination, disease activity assessment, and a comprehensive 60-90-minute CGA. RESULTS:The mean age was 69.9 ± 3.9 years, and 52% were female. The mean Charlson Comorbidity Index (CCI) was 3.24 ± 1.58 and correlated significantly with disease activity (r = 0.207, p = 0.039). Fatigue, pain and functional disability were highly prevalent. Polypharmacy (≥5 medications) was observed in 67% of patients. Cognitive impairment (67%), depression (64%), urinary incontinence (68%) and sleep disturbance (70%) were common. Frailty status was robust in 10%, pre-frail in 57%, and frail in 33%, with 26% reporting falls. CGA identified significant multidomain deficits. CONCLUSIONS:Older adults with RA exhibit substantial hidden vulnerabilities and high comorbidity burden. Integration of CGA into routine care may improve risk stratification, optimize management, enhance medication safety and reduce functional decline within multidisciplinary care settings.
BACKGROUND:Hepatitis B and C continue to pose significant challenges to global public health, and this study is aimed at evaluating their burden. METHODS:Leveraging data from the Global Burden of Disease 2021, we analyzed age-standardized mortality rates (ASMRs) and age-standardized disability-adjusted life year rates (ASDRs) for hepatitis B and C from 1990 to 2021 using Joinpoint regression, age-period-cohort models, and decomposition analysis. Bayesian age-period-cohort models were applied to project future trends up to 2036. Additionally, we assessed the burden attributable to modifiable risk factors and its association with socioeconomic indicators. RESULTS:From 1990 to 2021, the global ASMR for hepatitis B declined from 12.19 to 7.57 per 100,000, and the ASMR for hepatitis C decreased from 8.18 to 6.10 per 100,000. Despite these decreases, the absolute numbers of deaths and DALYs continued to increase, mainly driven by population growth and aging. In 2021, males carried a disproportionately higher burden of hepatitis B and C compared to females. Moreover, countries with low socioeconomic development faced a greater burden. Notably, high alcohol consumption accounted for 16.20% of hepatitis B DALYs, while drug use was responsible for 49.49% of hepatitis C DALYs. By 2036, ASMRs are projected to decline further to 5.90 per 100,000 for hepatitis B and 5.23 per 100,000 for hepatitis C. CONCLUSIONS:Although ASMRs and ASDRs have declined, the global burden of hepatitis B and C remains considerable. Continued efforts in vaccination, antiviral treatment, and control of key risk factors are crucial, especially in populations with a high burden.
BACKGROUND:Cardiorenal syndrome (CRS), characterized by cardiac-renal interplay, imposes a substantial clinical burden. Biological aging (BA), a comprehensive indicator for evaluating the overall aging status of an organism, is linked to individual cardiac or renal diseases, while its association with mortality in the CRS population remains unclear. METHODS:We utilized data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. CRS was defined as chronic cardiorenal comorbidities, specifically the coexistence of self-reported cardiovascular disease and calculated chronic kidney disease. BA was calculated using 12 clinical biomarkers, including the Klemera-Doubal method BA (KDM-BA) and Phenotypic Age (PhenoAge). BA acceleration (BAA), quantified as residuals from linear regression of BA on chronological age, includes KDM-BAA and PhenoAge acceleration (PhenoAgeAccel). Cox proportional hazards model and restricted cubic spline were performed to investigate these associations. Results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS:1,100 CRS participants were included in the final analysis. A 10-year increase in KDM-BA and PhenoAge in CRS participants was associated with 1.14-fold and 1.63-fold higher all-cause mortality risk, respectively. CRS participants with KDM-BAA (HR: 1.40, 95% CI: 1.13-1.73) or PhenoAgeAccel (HR: 1.54, 95% CI: 1.20-1.96) had elevated all-cause mortality risk. Meanwhile, these positive associations were more pronounced in males. Moreover, KDM-BA was associated with mortality from heart disease and cerebrovascular disease in the CRS population, with a non-linear relationship observed in cerebrovascular disease. CONCLUSIONS:As composite indicators for aging, KDM-BA, PhenoAge, KDM-BAA, and PhenoAgeAccel are significantly associated with all-cause mortality among the CRS population. These measures may serve as potential prognostic biomarkers in this population.
BACKGROUND:Direct oral anticoagulants (DOACs) are preferred over VKA for stroke prevention in atrial fibrillation/flutter (AF), but concerns exist regarding their use in antiphospholipid syndrome (APS). The safety and effectiveness of DOACs in AF patients with isolated lupus anticoagulant (LA) who do not meet APS criteria remain uncertain. METHODS:Using the TriNetX global research network, we conducted a new-user, active-comparator cohort study of adults with AF/flutter (ICD-10 I48, on or after 2010) and laboratory-documented LA positivity (ICD-10 D68.62 or confirmatory ratio-based dRVVT/lupus-sensitive aPTT assays) established on or before anticoagulant initiation, excluding coded APS (D68.61) and documented positive anticardiolipin or anti-β2-glycoprotein I antibodies. The index date was the first qualifying DOAC or VKA prescription after AF diagnosis. Propensity score matching (1:1) balanced more than 100 covariates including prior stroke/TIA, prior bleeding, prior venous thromboembolism, renal function, and comorbidities. Co-primary outcomes were incident ischemic stroke and incident bleeding at 5 years, analyzed with Kaplan-Meier methods and Cox proportional hazards models. RESULTS:After matching, 1,152 patients were included (576 per group; mean follow-up ≈2.6 years). Incident ischemic stroke was similar between DOAC and VKA users (5.8% vs. 6.0%; HR 0.93, 95% CI 0.54-1.60; p=0.80). The incident bleeding composite was directionally lower with DOACs without reaching significance (18.0% vs. 22.6%; HR 0.79, 95% CI 0.57-1.10; p=0.17), as were severe intracranial bleeding (2.0% vs. 3.3%; HR 0.61, 95% CI 0.29-1.29) and the intracranial/GI hemorrhage composite (9.1% vs. 12.1%; HR 0.75, 95% CI 0.51-1.12). In a pre-specified full-cohort analysis retaining prior events, the bleeding advantage reached nominal significance (26.6% vs. 33.0%; HR 0.77, 95% CI 0.62-0.95). All-cause mortality did not differ (21.2% vs. 22.0%; HR 0.96, 95% CI 0.75-1.23; p=0.73), and there were no significant differences in myocardial infarction, venous thromboembolism, or composite arterial events. An apixaban-specific analysis was consistent. CONCLUSIONS:In this new-user cohort of AF patients with isolated lupus anticoagulant, DOAC therapy was not associated with higher rates of ischemic stroke, arterial events, venous thromboembolism, or mortality compared with VKA, and bleeding outcomes were directionally lower with DOACs without reaching statistical significance. These hypothesis-generating findings suggest DOACs may be a reasonable option in this population, pending confirmation in prospective studies.
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key immune checkpoint in Gastrointestinal system cancers (GSCs), inhibiting T-cell activation by outcompeting CD28 for B7-1/B7-2 binding on antigen-presenting cells, thereby promoting immune evasion. Its overexpression correlates with advanced stage, poor survival, and worse prognosis in gastric, colorectal, esophageal, and pancreatic cancers. CTLA-4 blockade with Ipilimumab or Tremelimumab shows promise, especially combined with PD-1/PD-L1 inhibitors, yielding enhanced antitumor immunity in microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) tumors with high immune infiltration. However, efficacy is limited by tumor heterogeneity and an immunosuppressive microenvironment enriched in CTLA-4⁺ regulatory T cells (Tregs). Inconsistent clinical responses underscore the need for predictive biomarkers, optimized combinations, and mechanistic insights into resistance. This review explores CTLA-4’s role in GSCs, highlighting microenvironment-focused strategies to improve precision and therapeutic outcomes.
BACKGROUND:Pulse oximetry is central to ICU care, yet clinically meaningful SpO₂-SaO₂ discordance is common and may reflect both racial/ethnic disparities and physiologic derangements. The independent contributions of acidemia, hyperlactatemia, and anemia to discordance have not been comprehensively evaluated in a large, diverse ICU cohort. METHODS:We performed a retrospective cohort study using the Blood-gas and Oximetry Linked Dataset (BOLD). We analyzed patient-level paired SpO₂ and SaO₂ measurements within 5 minutes, limiting to one pair per hospitalization. After exclusions and complete-case requirements for hemoglobin, pH, lactate, race/ethnicity, and prespecified covariates including SOFA (past 24 hours), MAP, and temperature, the primary analytic cohort included 10,094 adults. Outcomes were signed discrepancy (ΔSat = SpO₂ - SaO₂), clinically significant discordance (|ΔSat| ≥4%), and directional misclassification (underestimation ≤-4; overestimation ≥+4). Multivariable OLS, logistic, and multinomial regression were used; pH × lactate interaction was tested using mean-centered terms. RESULTS:Mean ΔSat was 0.93±3.74%, and 18.5% met |ΔSat| ≥4%. Lower pH, higher lactate, and lower hemoglobin were independently associated with discordance. Black race and Hispanic ethnicity were associated with greater overestimation versus White patients after adjustment. A significant pH × lactate interaction suggested attenuation of the lactate-ΔSat association at lower pH. Findings were consistent in a larger sensitivity cohort (N=18,804). CONCLUSIONS:In critically ill adults, acidemia, hyperlactatemia, and anemia are associated with clinically meaningful SpO₂-SaO₂ discordance, alongside persistent racial/ethnic differences in overestimation. Clinicians should interpret SpO₂ cautiously in metabolically stressed and anemic patients and consider confirmatory testing when clinical concern exists.
BACKGROUND:Early identification of prognostic factors in critically ill patients is essential for optimizing ICU management. Although the APACHE II score, lactate clearance rate (LCR), and central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) are each associated with outcomes, their combined predictive value remains unclear. This study evaluated their individual and combined performance in predicting 28-day mortality. METHODS:We retrospectively analyzed ICU patients admitted to Shaoxing Second Hospital from January 2021 to December 2023. Among 1188 screened patients, 634 were included. Clinical data, APACHE II score, initial Pcv-aCO2, and 24-hour LCR were collected. Patients were classified as survivors or non-survivors at 28 days. Logistic regression identified independent predictors, and receiver operating characteristic curves assessed predictive performance. The predictive performance of individual indicators and their combined models was evaluated using the area under the curve (AUC), sensitivity, and specificity. RESULTS:The 28-day mortality rate was 26.8%. Independent predictors included APACHE II score (OR=1.069), 24h LCR (OR=0.306), Pcv-aCO2 (OR=1.096), vasoactive drug use (OR=2.201), coagulation dysfunction (OR=1.781), and multiple organ dysfunction (OR=1.906) (all p<0.05). Among single indicators, 24h LCR showed the highest accuracy (AUC=0.909), followed by APACHE II score (AUC= 0.753) and Pcv-aCO2 (AUC=0.739). The combination of 24h LCR and APACHE II score achieved an AUC of 0.963, while adding Pcv-aCO2 did not further increase the AUC but improved sensitivity and specificity. CONCLUSIONS:APACHE II score, 24h LCR, and Pcv-aCO2 are independent predictors of short-term mortality. Combined assessment improves prognostic accuracy, supporting integrated evaluation for risk stratification in critically ill patients.
Simultaneous pancreas-kidney (SPK) transplantation provides durable glycemic control and survival benefit for selected patients with Type 1 diabetes and end-stage renal disease. Late-onset hyperglycemia after SPK is diagnostically challenging because pancreas graft dysfunction may reflect acute or chronic rejection, calcineurin inhibitor toxicity, vascular complications, post-transplant diabetes, or recurrent autoimmune type 1 diabetes (T1DR). Autoimmune recurrence occurs in a minority of recipients and is characterized by insulitis with selective beta-cell loss, often preceded by islet autoantibody conversion and progressive C-peptide decline. Distinguishing recurrence from rejection is clinically important because rejection may respond to intensified anti-rejection therapy, whereas established T1DR has no proven disease-modifying treatment. This case-based short review synthesizes current evidence on epidemiology, timing, maintenance immunosuppression, immunopathogenesis, genetic susceptibility, biomarkers, imaging, Banff-based histopathology, differential diagnosis, and management of recurrent autoimmune diabetes after SPK transplantation. A structured diagnostic approach integrating clinical timing, serology, metabolic testing, imaging, donor-specific antibody assessment, and pancreas biopsy with immunohistochemistry can help clinicians avoid both delayed recognition of recurrence and unnecessary escalation of immunosuppression.
BACKGROUND:Recent studies show enhanced glycolysis is linked to chronic diseases, but its relationship with hypertension is unclear. This study explores glycolysis-hypertension links and Pan-Immune Inflammation Value (PIV) and mitochondrial dysfunction chain mediation. METHODS:Data were derived from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, with 8419 participants included after excluding missing data. Weighted multivariate logistic regression was employed to analyze the independent association between glycolysis and hypertension. Restricted cubic spline curves and threshold effect analysis were used to evaluate the nonlinear relationship between LDH and hypertension. Chain mediation analysis assessed the mediating effects of PIV and mitochondrial dysfunction. Machine learning models predicted hypertension, with three interpretable methods (permutation feature importance, Partial Dependence Plots, and SHAP) embedded in the best-performing model. RESULTS:After adjusting for confounding factors, both continuous and quartile-based LDH levels showed significant positive correlations with hypertension. A U-shaped association was found, with an inflection point (ln-LDH) of 4.533. Further mediation analysis showed that PIV and mitochondrial dysfunction partially mediated the association between LDH and hypertension, with the indirect effects through PIV alone and mitochondrial dysfunction alone accounting for 2.91% and 6.09% of the total effect, respectively. In addition, the serial indirect effect through PIV and subsequently mitochondrial dysfunction accounted for 0.20% of the total effect. The XGB model had the best predictive performance for hypertension, with LDH, PIV, and MMA being important predictive variables. CONCLUSIONS:This study emphasizes the important roles of inflammation and mitochondrial dysfunction in the relationship between glycolysis and hypertension.
Background This cross-Sectional study aimed to elucidate the relationship between body fluid distribution and bone mineral density (BMD) as well as the risk of osteoporosis in men aged under 50. Methods The study included male participants aged under 50 from the National Health and Nutrition Examination Survey (NHANES). BMD was measured via dual-energy X-ray absorptiometry (DXA). Body fluid distribution was defined as extracellular fluid (ECF), intracellular fluid (ICF), and total body water (TBW) assessed by bioelectrical impedance analysis. Weighted logistic regression and weighted linear regression were adopted to unveil the associations of body fluid distribution with osteoporosis risk and BMD. Subgroup analyses were carried out. Restrictive cubic spline (RCS) models were leveraged to unravel potential non-linear relationships of body fluid distribution with osteoporosis risk and BMD. Results 1,815 participants (weighted samples: 46,823,836) were encompassed in our analysis. Among the participants, 10 cases of osteoporosis were identified (weighted samples: 319,031). The results showed significant correlations of increases in ECF, ICF, and TBW with a decrease in osteoporosis risk and an elevation in BMD. RCS analysis indicated an approximately linear relationship between body fluid components and both osteoporosis risk and BMD. Subgroup analysis revealed consistent trends between body fluid components, osteoporosis risk, and BMD across various subgroups. Conclusions Increases in ECF, ICF, and TBW were significantly linked to a lowered osteoporosis risk and enhanced BMD. These findings may aid clinicians in the early identification and intervention of patients at risk for bone loss. However, due to the cross-sectional design, causality cannot be inferred, and prospective studies are warranted.
BACKGROUND:Newer pharmacologic therapies for sickle cell disease target different clinical domains, complicating class-level comparison. Postapproval developments, including voxelotor withdrawal and regulatory reassessment of crizanlizumab, warrant a therapy-specific reassessment of benefit and risk. METHODS:We searched PubMed/MEDLINE, Scopus, Web of Science Core Collection, and CINAHL through April 4, 2026, for clinical evidence on l-glutamine, crizanlizumab, and voxelotor. Two reviewers independently screened records, assessed full texts, extracted data, and appraised methodological concerns. Core randomized evidence was distinguished from early randomized, linked follow-up, supportive secondary, and contextual evidence. Pooling was considered only for independent studies with clinically comparable outcomes and compatible follow-up. RESULTS:Of 742 records identified, 398 remained after deduplication, 52 full-text reports were assessed, and eight studies contributed to the structured synthesis. l-glutamine reduced vaso-occlusive crisis burden in the pivotal trial (rate ratio, 0.75; 95% confidence interval, 0.62-0.90). Crizanlizumab prolonged time to first vaso-occlusive crisis in SUSTAIN (hazard ratio, 0.50; 95% confidence interval, 0.33-0.75), but evidence remained dependent on one core randomized trial. Voxelotor primarily improved hemoglobin response (risk ratio, 7.84; 95% confidence interval, 3.52-17.4). No primary pooled meta-analysis was performed because comparable independent evidence was sparse, follow-up differed, linked reports overlapped, and several safety outcomes were noninformative. CONCLUSIONS:The evidence supports therapy-specific benefit signals rather than a pooled class-level conclusion. Benefit-risk interpretation should distinguish vaso-occlusive morbidity from hemoglobin-centered outcomes and account for replication, durability, and safety completeness.
