Background: Percutaneous left atrial appendage occlusion (LAAO) is an established nonpharmacologic strategy for stroke prevention in atrial fibrillation (AF). Its comparative effectiveness and safety relative to contemporary medical therapy, including direct oral anticoagulants (DOACs), remain uncertain following recent large randomized controlled trials (RCTs). Methods: We performed a systematic review and meta-analysis of RCTs comparing catheter-based LAAO with medical therapy in AF patients. PubMed, CENTRAL, and ScienceDirect were searched from inception through May 2026. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models. The primary outcome was the composite primary endpoint. Secondary outcomes included all-cause death, cardiovascular death, all stroke/TIA, ischemic stroke/TIA, systemic embolism, major bleeding, and nonprocedural major bleeding. Risk of bias was assessed using ROB 2. Results: Six RCTs were included, contributing 7073 participants (3729 LAAO; 3344 medical therapy). LAAO was not associated with significant differences in the composite endpoint (RR 1.02; 95% CI 0.85–1.23), all-cause death (RR 1.02; 95% CI 0.79–1.31), cardiovascular death (RR 0.93; 95% CI 0.67–1.29), all stroke/TIA (RR 1.06; 95% CI 0.81–1.38), ischemic stroke/TIA (RR 1.24; 95% CI 0.88–1.76), systemic embolism (RR 0.76; 95% CI 0.12–4.77), or total major bleeding (RR 0.93; 95% CI 0.77–1.13). LAAO significantly reduced nonprocedural bleeding (RR 0.54; 95% CI 0.46–0.63; p < 0.0001; I² = 0.0%). Heterogeneity was low to moderate across outcomes. Conclusions: No significant differences were observed between LAAO and medical therapy for the composite endpoint, mortality, or thromboembolic outcomes; however, confidence intervals for ischemic stroke/TIA and systemic embolism remained wide and cannot exclude a clinically meaningful excess of thromboembolic events after LAAO. LAAO was associated with a substantial and consistent reduction in nonprocedural bleeding. These findings suggest LAAO may be considered an individualized alternative to oral anticoagulation for selected patients with high bleeding risk or anticoagulation intolerance, weighing upfront procedural risk against this bleeding benefit, while uncertainty for rare thromboembolic outcomes remains to be resolved.

Background and Aims: Despite a strict gluten-free diet (GFD), many patients with celiac disease (CD) continue to experience symptoms and nutrient deficiencies. Prebiotics, non-digestible substrates that foster beneficial bacteria and short-chain fatty acid (SCFA) production, may offer adjunctive benefits, though their role in CD remains unclear. We aimed to determine the clinical efficacy, safety, and nutritional outcomes of prebiotics in CD. Methods: Following PRISMA guidelines, we systematically searched PubMed, Embase, Web of Science, and CENTRAL through May 2025 for clinical studies evaluating the effects of prebiotics in CD, derived from either supplements or foods naturally abundant in prebiotics. Eligible trials and observational studies were assessed using Cochrane RoB 2.0 or Newcastle–Ottawa tools, and data were synthesized narratively. Results: Twelve studies (1,066 participants) were included. Oligofructose-enriched inulin (Synergy 1) increased fecal SCFAs by 31%, Bifidobacterium abundance, osteocalcin, and serum vitamins D and E. It also reduced hepcidin by 61% without gastrointestinal intolerance. Oats (50–70 g/day) for up to 24 months maintained histologic remission, negative serology, and improved dietary iron, fiber, thiamin, and zinc intake without worsening hemoglobin or ferritin status. Quinoa modestly lowered cholesterol, and amaranth enhanced growth and corrected trace element deficiencies in children. No study reported serious adverse events; adherence improved when prebiotics diversified the GFD. Conclusions: Prebiotics appear safe and may enhance microbiota composition, nutrient absorption, and barrier integrity without compromising mucosal healing. Larger standardized randomized trials are needed to confirm these findings.