Background and Objectives: Obstructive sleep apnea (OSA) is a prevalent disorder associated with increased cardiovascular (CV) risk. Materials and Methods: We conducted a PRISMA-compliant systematic review and meta-analysis of prospective cohort studies assessing OSA and incident CV outcomes. Results: From 2463 records, 18 studies (>25,000 participants; median follow-up 9 years) were included. OSA was associated with increased CV risk (pooled HR 1.82, 95% CI 1.45–2.28). Dose–response analysis showed a progressive risk increase: mild OSA (HR 1.21, 95% CI 0.98–1.50), moderate (HR 1.56, 95% CI 1.20–2.03), and severe (HR 2.45, 95% CI 1.85–3.25). Continuous positive airway pressure (CPAP) adherence (≥4 h/night) reduced risk (HR 0.76, 95% CI 0.60–0.96). Conclusions: OSA confers a severity-dependent CV risk, which is mitigated by adequate CPAP adherence. Systematic screening and adherence support may reduce CV morbidity and mortality. PROSPERO: CRD420251168363.

Background: SGLT2 inhibitors are key therapies in heart failure (HF), but their combined multidomain effects have not been analyzed together. Methods: We conducted a PROSPERO-registered (CRD420251235850) systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing SGLT2i (dapagliflozin, empagliflozin, canagliflozin, sotagliflozin) with placebo in adults with HF, regardless of ejection fraction or diabetes status. We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science through 1 February 2025. Outcomes were grouped into four domains: (1) clinical events, (2) symptoms/health status (Kansas City Cardiomyopathy Questionnaire, KCCQ), (3) functional capacity (6 min walk distance, peak VO₂), and (4) cardiac remodeling/energetics (cardiac MRI, 31P-MRS). We used random-effects models with Hartung–Knapp adjustment and assessed heterogeneity by I² and prediction intervals. Results: Eleven RCTs with 23,812 patients (HFrEF, HFmrEF, HFpEF, and acute or recently decompensated HF) were included. SGLT2i lowered the risk of cardiovascular death or first HF hospitalization by 23% (HR 0.77, 95% CI 0.72–0.82; p < 0.0001; I² = 28%; prediction interval 0.68–0.87), with similar effects across ejection fraction, diabetes status, and presentation type. All-cause and cardiovascular mortality dropped by 12% (HR 0.88, 95% CI 0.81–0.96) and 14% (HR 0.86, 95% CI 0.78–0.95), respectively. SGLT2i improved KCCQ—Clinical Summary Score by 4.6 points (95% CI 3.4–5.8; p < 0.0001) and increased the odds of a ≥5-point improvement (OR 1.49, 95% CI 1.32–1.68; NNT = 12). Six-minute walk distance increased by 21.8 m (95% CI 9.4–34.2; p = 0.001), and mechanistic trials showed significant reverse remodeling (ΔLVEDV −19.8 mL, ΔLVEF +6.1%; both p < 0.001). No improvement was observed in myocardial PCr/ATP ratio. Safety was favorable, with no excess ketoacidosis or severe hypoglycemia. Conclusions: This multidomain synthesis demonstrates that SGLT2 inhibitors provide consistent, robust reductions in mortality and hospitalizations, while also delivering early, clinically meaningful improvements across multiple patient-centered domains. These results establish SGLT2i as a foundational component of contemporary HF management.

Background: Endothelial and microvascular dysfunction play a central role in the pathogenesis of both cardiovascular and neurodegenerative disorders. However, whether impaired peripheral endothelial function independently predicts cognitive decline, cerebral small-vessel disease (SVD) progression, or stroke remains uncertain. Methods: We conducted a systematic review and meta-analysis of prospective cohort studies assessing the prognostic value of non-invasive peripheral endothelial tests—flow-mediated dilation (FMD), peripheral arterial tonometry (PAT/EndoPAT), and sublingual microcirculatory imaging—for cognitive or cerebrovascular outcomes. Databases (PubMed, Embase, Scopus, Web of Science) were searched from inception through 30 September 2025. Study quality was appraised using the Newcastle–Ottawa Scale (NOS), and evidence certainty was graded via GRADE. Random-effects models (DerSimonian–Laird or REML) pooled hazard ratios (HRs) using inverse-variance weighting. PROSPERO-registered (CRD42025211876). Results: Fifteen prospective cohorts (n = 13,972 participants; median follow-up 4.3 years) met inclusion criteria. Across all modalities, impaired endothelial or microvascular function predicted cognitive decline, SVD progression, or cerebrovascular events (pooled HR = 1.72, 95% CI 1.38–2.14, p < 0.001; I² = 57%). Subgroup analyses confirmed consistent associations for FMD (HR = 1.59, 95% CI 1.27–1.98) and PAT/EndoPAT (HR = 1.84, 95% CI 1.40–2.41). Evidence certainty was rated moderate-to-high according to GRADE. Conclusions: Peripheral endothelial dysfunction, measured by validated non-invasive techniques, independently predicts future cognitive and cerebrovascular events. These findings support the concept of a vascular–neural continuum, suggesting that endothelial health represents a modifiable biomarker for early neurovascular risk stratification. Routine assessment of endothelial function may help identify high-risk individuals and guide preventive interventions aimed at preserving brain and vascular health.

Background: Bloodstream infections (BSIs) complicate COVID-19 inpatients, increasing morbidity, mortality, and healthcare burden. This systematic review and meta-analysis evaluated prevalence, antimicrobial resistance (AMR), risk factors, and outcomes of BSIs in RT-PCR-confirmed COVID-19 cases. Methods: We searched PubMed, Google Scholar, ScienceDirect, and MDPI journals (January 2020–August 2025) following PRISMA 2020 guidelines. Twenty-two observational studies (~123,500 patients, ~602,000 blood cultures) were included: 10 prospective and 12 retrospective. Random-effects models estimated pooled prevalence, odds ratios (ORs), and mean differences, with subgroup analyses (ICU, non-ICU, pediatric) and meta-regression.Results: Pooled BSI prevalence was 8.2% (95% CI: 5.7–11.0; I² = 50%). Subgroup prevalence was higher in ICU (12.5%) than non-ICU (5.2%) populations. Pediatric cohorts (n = 3) showed a prevalence of 10.8%. Gram-negative pathogens predominated (61%), particularly Klebsiella pneumoniae (26%) and Acinetobacter baumannii (21%). AMR rates were 36% for MRSA and 31% for ESBL-producing Enterobacterales. Risk factors included mechanical ventilation (OR: 2.6), immunosuppression (OR: 2.3), and corticosteroid use (OR: 2.4). BSIs were associated with increased mortality (OR: 2.6), prolonged hospitalization (+6.8 days), and higher ICU admission (OR: 3.1).Conclusions: BSIs, largely driven by multidrug-resistant pathogens, substantially worsen COVID-19 outcomes. Variability in diagnostic criteria (CDC vs. ECDC) and reliance on retrospective designs are limitations, though moderate heterogeneity (I² = 50%) enhances generalizability across diverse populations. Strengthened infection prevention and antimicrobial stewardship are urgently required.

(1) Background: COVID-19 sepsis, marked by hyperinflammation and cardiac injury, poses significant challenges in high-comorbidity populations. This prospective cohort study evaluates the prognostic value of IL-6, troponin, NT-proBNP, and radiological findings for mortality and critical outcomes in a post-2022 Eastern European cohort. (2) Methods: At "Victor Babes" Hospital, Timisoara, Romania (September 2022–December 2024), 207 adults with COVID-19 sepsis (Sepsis-3 criteria) were enrolled. Baseline IL-6, troponin, NT-proBNP, CRP, PCT, D-dimers, and chest CT lung involvement were measured. Unfavorable outcomes (in-hospital death, ICU transfer, mechanical ventilation, or vasopressor use) were analyzed using logistic and linear regression. (3) Results: Among 207 patients (mean age 68.7 years, 54.1% male), 52 (25.1%) experienced unfavorable outcomes. Multivariable analysis identified IL-6 (OR 1.016, p = 0.013), troponin (OR 1.013, p = 0.017), NT-proBNP (OR 1.009, p = 0.049), >50% lung involvement (OR 1.835, p = 0.011), unvaccinated status (OR 2.312, p = 0.002), and higher BMI (OR 1.112, p = 0.005) as independent predictors of critical outcomes. Tocilizumab use (n=12) was associated with reduced mortality (p = 0.041). IL-6 (cut-off 39.0 pg/mL, AUC 0.91) and troponin (cut-off 111.3 ng/L, AUC 0.88) showed strong predictive accuracy. (4) Conclusions: Elevated IL-6, troponin, NT-proBNP, severe lung involvement, unvaccinated status, and higher BMI predict adverse outcomes in COVID-19 sepsis. Tocilizumab may offer survival benefits, warranting larger trials. These findings support targeted risk stratification in high-comorbidity populations.

(1) Background: COVID-19 sepsis, marked by hyperinflammation and cardiac injury, poses significant challenges in high-comorbidity populations. This prospective cohort study evaluates the prognostic value of IL-6, troponin, NT-proBNP, and radiological findings for mortality and unfavorable outcomes in a post-2022 Eastern European cohort. (2) Methods: At “Victor Babes” Hospital, Timisoara, Romania (September 2022–December 2024), 207 adults with COVID-19 sepsis (Sepsis-3 criteria) were enrolled. Baseline IL-6, troponin, NT-proBNP, CRP, PCT, D-dimers, and chest CT lung involvement were measured. Unfavorable outcomes (in-hospital death, ICU transfer, mechanical ventilation, or vasopressor use) were analyzed using logistic and linear regression. (3) Results: Among 207 patients (mean age: 68.7 years, 54.1% male), 52 (25.1%) experienced unfavorable outcomes. Multivariable analysis identified IL-6 (OR 1.016 per pg/mL, p = 0.013), troponin (OR 1.013 per ng/L, p = 0.017), NT-proBNP (OR 1.009 per pg/mL, p = 0.049), >50% lung involvement (OR 1.835, p = 0.011), unvaccinated status (OR 2.312, p = 0.002), and higher BMI (OR 1.112 per kg/m², p = 0.005) as independent predictors of unfavorable outcomes. Tocilizumab use (n = 12) was associated with reduced mortality (p = 0.041). IL-6 (cut-off 39.0 pg/mL, AUC = 0.91) and troponin (cut-off = 111.3 ng/L, AUC = 0.88) showed strong predictive accuracy. (4) Conclusions: Elevated IL-6, troponin, NT-proBNP, severe lung involvement, unvaccinated status, and higher BMI predict adverse outcomes in COVID-19 sepsis. Tocilizumab may offer survival benefits, warranting larger trials. These findings support targeted risk stratification in high-comorbidity populations.