Akriti Agrawal

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: Lymphopenia has been associated with in-hospital, early, and late mortality. We aimed to elucidate differences in baseline characteristics in patients with lymphopenia with and without acute respiratory distress syndrome (ARDS) and determine predictors of in-hospital mortality in this patient population. Methods: Patients ≥ 18 years of age with lymphopenia were identified in the National Inpatient Sample (2017–2021) and stratified according to ARDS diagnosis. Predictors of in-hospital mortality were determined using multivariate analyses with a logistic regression model. Results: From 183,185 patients with lymphopenia, 10,420 (5.7%) had ARDS, of which 92.8% had coronavirus disease 2019. The patients with ARDS suffered from more in-hospital mortality (47% versus 6.7%, p < 0.001). ARDS increased the odds of in-hospital mortality by eight-fold (odds ratio [OR]: 7.91 [7.06–8.86], p < 0.001). Age ≥ 65 years (OR: 4.88 [3.98–5.99]), moderate/severe liver disease (OR: 2.53 [1.87–3.42]), and metastatic cancer (OR: 2.18 [1.68–2.82]) were among the strongest positive predictors of in-hospital mortality (all p < 0.001). Conclusions: Patients with lymphopenia who have ARDS have higher in-hospital mortality, likely due to the condition’s clinical course. Lymphopenia may be a marker of immune dysregulation and systemic involvement in ARDS.