Volume 12 · Issue 02 · 2026

Obstructive sleep apnea (OSA) is a major public health crisis affecting nearly one billion people worldwide and is associated with significant cardiovascular and metabolic complications. The prevalence of OSA is rising steadily due to the obesity pandemic and is contributed by interacting anatomical, inflammatory, and neuro-respiratory mechanisms. Continuous positive airway pressure (CPAP) remains the gold standard for the management of OSA; however, it does not address underlying obesity or weight-independent pathophysiology. Obesity is an important modifiable risk factor for OSA, as weight loss is associated with resolution/improvement of the disease. Therefore, growing evidence now supports surgical and medical management of obesity as complementary strategies to improve both body weight and apnea-hypopnoea index (AHI), prompting a paradigm shift towards integrated, multimodal care. Bariatric interventions typically achieve 25%-35% total weight loss and yield significant but variable reductions in AHI with remission rates of 50%-75%, driven by mechanical unloading, improved ventilatory control, and favorable metabolic and anti-inflammatory effects. However, it is constrained by eligibility, cost, and perioperative risks. Alternatively, Incretin-based therapies, particularly Tirzepatide, achieve 10%-22% weight loss and reduce AHI to 12-30 events per hour, securing the first regulatory approval for OSA based on the largest trial-level AHI reductions. The recent introduction of several therapeutic agents with excellent weight loss potential has reshaped the management landscape of people with obesity and OSA. This review aims to analyze the literature across surgical, endoscopic, and pharmacological interventions and OSA while proposing an individualized treatment framework integrating weight-loss pharmacotherapy with device-based and structured lifestyle strategies and surgical interventions, tailored to disease phenotypes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of adults worldwide and represents a systemic cardiometabolic disorder in which cardiovascular disease is the leading cause of death. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are uniquely positioned to address this liver-heart axis by combining hepatic disease-modifying signals with proven cardiovascular risk reduction. This review synthesizes mechanistic, randomized trial, real-world, and cardiovascular outcome evidence for GLP-1RAs in MASLD and metabolic dysfunction-associated steatohepatitis (MASH). In biopsy-based trials, liraglutide (LEAN) increased steatohepatitis resolution without fibrosis worsening (39% vs. 9% with placebo), while semaglutide demonstrated dose-dependent resolution (up to 59% vs. 17% in Phase 2). More recently, semaglutide 2.4 mg weekly met both histologic endpoints at interim analysis in F2-F3 MASH (resolution without fibrosis worsening 62.9% vs. 34.3%; fibrosis improvement ≥ 1 stage 36.8% vs. 22.4%), and tirzepatide (SYNERGY-NASH) achieved high rates of MASH resolution (44%-62% vs. 10%) with concomitant fibrosis improvement signals (up to 51% vs. 30%). Cardiovascular outcome trials demonstrate consistent reductions in major adverse cardiovascular events with GLP-1RAs, including liraglutide (LEADER), semaglutide (SUSTAIN-6 and SELECT), and dulaglutide (REWIND). Mechanistically, GLP-1RAs reduce hepatic lipogenesis and lipotoxicity, attenuate inflammation, improve insulin sensitivity, and modulate gut-brain-liver signaling, with systemic benefits on weight, blood pressure, and atherogenic lipoproteins. Collectively, the evidence supports GLP-1RAs, particularly semaglutide and tirzepatide, as foundational therapies for MASLD patients with obesity, type 2 diabetes, advanced fibrosis, or heart failure phenotypes. Key gaps include treatment duration, durability of fibrosis benefit, and effectiveness in cirrhosis, requiring long-term follow-up.

Introduction: Frailty, an increasingly recognized age-related condition, appears to be associated with an increased risk of cardiovascular events. However, frailty is a heterogeneous condition with a wide metabolic spectrum and variations in body composition. Therefore, not all frail individuals have the same cardiovascular risk. This study aimed to explore the association of frailty with cardiovascular risk according to body composition and metabolic profile of frail individuals. Methods: A systematic review of English-language studies published over the past 20 years was conducted, including studies that examined the association between frailty and cardiovascular events and reported participants' body composition and metabolic profiles. Results: A total of 12 studies comprising 864,294 participants, with an average age range of 52-92 years, were included. Frailty was reported as a risk factor for cardiovascular events in 10 studies, but two studies did not show this association. The participants in all the positive studies were either overweight or obese. In addition, they had unfavorable metabolic profiles and increased prevalence of cardiovascular risk factors. Most frailty criteria predicted cardiovascular disease. However, unintentional weight loss was not associated with cardiovascular risk, especially in the very old subjects. This suggests that the sarcopenic obese, rather than the anorexic malnourished, frail individuals are at risk of cardiovascular disease. Conclusion: Frailty increases the risk of cardiovascular events only in overweight or obese individuals. Current studies are limited by defining frailty as one category, and future research is required to precisely investigate the metabolic profile of the frailty spectrum and its association with cardiovascular risk.

Although physical exercise is widely recognized for its role in glycemic control and overall health, population characteristics such as comorbidities, sedentary behavior, disease-related complications, and socioeconomic constraints hinder regular practice. The article aims to present an alternative approach to exercise prescription for the control of type 2 diabetes, considering time and space limitations that act as barriers to meeting traditional recommendations. Situations of social isolation and limited access to physical activity services may exacerbate both metabolic and psychosocial aspects, creating a negative cycle of clinical deterioration. In this context, the proposal of more flexible, simple, and accessible exercise strategies is both possible and necessary, especially for home-based settings. From this perspective, an example of an initial exercise prescription is presented, combining aerobic and strength activities using body weight or simple materials, along with progression strategies and safety considerations. This work does not provide definitive evidence, but rather to encourage feasible alternatives, greater adherence, and further research on physical exercise for individuals with T2DM in contexts of time and space restriction.

Background: Metastasis is a major driver of treatment failure and mortality for gastric cancer, and the detailed cellular and molecular patterns driving tumor cells from the primary tumor to metastatic lesions remain poorly characterized. Methods: We analyzed single-cell RNA sequencing data from 131 samples, including 27 normal gastric tissue (NC), 48 primary gastric tumors (PT), and 56 metastatic lesions (lymph node metastasis, LNM [sample number = 2]; liver metastasis, LM [sample number = 9]; ovary metastasis, OM [sample number = 3]; peritoneum metastasis, PM [sample number = 42]), and finally generated a high-resolution cellular atlas. Results: Using all cells, we identified 11 major cell types and characterized remodeling of T cell or natural killer cell, myeloid, and epithelial cells across primary and metastatic lesions. The depletion of cytotoxic CD8.Teff and NK cells in LNM, concomitant with enrichment of exhausted CD4.Tex cells, were observed. CD4.Treg cells were found enriched in PT but reduced in metastatic lesions. Comparison of gene expression between primary and metastasis for epithelial cells identified NAP1L1 as a consistently upregulated gene across all four distinct metastatic sites (LNM, LM, OM, and PM). In silico knockout of NAP1L1 in epithelial cells indicated the perturbation of focal adhesion and cell-substrate junction pathways and high expression of prometastatic genes, including Jun proto-oncogene, AP-1 transcription factor subunit, JunB proto-oncogene, AP-1 transcription factor subunit, and activating transcription factor 3. Conclusion: Our study deciphered the immune and epithelial cell dynamics of metastasis and identified NAP1L1 as a novel regulator of epithelial cell reprogramming and metastatic progression.

Background: This study aimed to investigate the associations of serum sodium and potassium levels within the normal range with cardiovascular (CV) and all-cause mortality, and to further explore the potential roles of oxidative stress and inflammatory biomarkers in these associations. Methods: We analyzed NHANES 1999-2018 data from 32,837 adults with normal baseline serum sodium (135-146 mmol/L) and potassium (3.5-5.0 mmol/L), stratified by tertiles. Weighted Cox models assessed associations with CV and all-cause mortality, and bootstrap-based causal mediation analysis assessed nine oxidative stress and inflammatory biomarkers. Results: The lowest tertile of serum sodium was associated with an increased risk of all-cause mortality (HR: 1.17; 95% CI: 1.03-1.32; p = 0.017), while the highest tertile of serum potassium was associated with an increased risk of CV (HR: 1.26; 95% CI: 1.00-1.58; p = 0.052) and all-cause mortality (HR: 1.14; 95% CI: 1.02-1.29; p = 0.025). Serum sodium and potassium showed a statistically significant interaction for all-cause mortality (p = 0.044), with the lowest risk at sodium 138-139 mmol/L and potassium 3.5-3.8 mmol/L (HR: 0.46, 95% CI: 0.31-0.68; p < 0.001). Mediation analysis showed that inflammatory biomarkers accounted for 0.8% to 1.5% of the associations between serum sodium/potassium and CV or all-cause mortality. Conclusion: In the general population, lower normal-range serum sodium was associated with higher all-cause mortality, while higher serum potassium was linked to increased cardiovascular and all-cause mortality. Inflammatory biomarkers may partially mediate these associations. Our findings provide more evidence that the "safest" sodium and potassium interval needs to be reconsidered.

Background: Type 2 diabetes mellitus (T2DM) leads to severe microvascular and macrovascular complications. Traditional single-label prediction models fail to capture their co-occurring nature. This study develops a stacked ensemble multi-label framework that integrates established machine learning techniques into a unified and clinically interpretable approach for the joint prediction of diabetes complications. Methods: In a retrospective study of 965 T2DM patients, complications were aggregated into microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (cardiovascular, cerebrovascular) categories. A class-weighted stacking ensemble integrated three base models—Random Forest, Light GBM, and Cat Boost—within Binary Relevance (BR) and Classifier Chain (CC) frameworks, with a multi-output logistic regression meta-learner. Performance was evaluated via 5-fold cross-validation (Hamming Loss, F1-score, area under the curve [AUC]). SHapley Additive exPlanations (SHAP) analysis elucidated risk factors. Results: The Stacking-CC model achieved superior performance, with an overall F1-score of 0.752 ± 0.049 and AUC of 0.857 ± 0.032. A moderate correlation (r = 0.35) between complications validated the multi-label approach. SHAP analysis revealed distinct risk profiles: macrovascular complications were strongly associated with LDL cholesterol and diastolic blood pressure, while microvascular complications were linked to drug addiction, fasting blood sugar, and HDL. Conventional factors like age and BMI showed minimal importance. Conclusion: The Stacking-CC framework effectively models co-occurring diabetic complications with high accuracy and interpretability. By delineating distinct risk hierarchies, it enables the development of targeted, complication-specific management strategies.

Background: Understanding how multimorbidity affects activities of daily living (ADL) and instrumental activities of daily living (IADL) disability in older Irish adults is essential for planning responsive health and social care systems that can support quality of daily life. This study examines how chronic noncommunicable diseases multimorbidity affects older adults' ability to live independently in Ireland. It focuses on the relationship between multimorbidity and limitations in ADL and IADL. Methods: A cross-sectional 2019 Irish Health Survey data set was used. The study analyzed data from 2114 individuals aged 65 years and older in Ireland. Descriptive, bivariate, and multivariable logistic regression analyses were used to examine the effect of multimorbidity on functional disability. Results: Difficulties in ADL and IADL were significantly higher among older adults with multimorbidity (25% and 62%) compared with single morbidity (10% and 38%; p < 0.001). Adjusted logistic regression results also revealed that multimorbidity significantly increased the odds of ADL (adjusted odds ratio [AOR] = 2.52; 95% CI: 1.80, 3.55) and IADL (AOR = 2.60; 95% CI: 2.02, 3.35) limitations. Depression and older age were strong predictors of disability, while moderate alcohol use was linked to lower ADL impairment. Gender and regional disparities were also observed. Conclusions: IADL impairments were more common, suggesting early signs of functional decline. Multimorbidity threatens older adults' independence in Ireland. Early detection of IADL limitations and integrated, person-centered care are essential. These findings support policy efforts like Sláintecare to promote aging in place.