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Classical randomized experiments, equipped with randomization-based inference, provide assumption-free inference for treatment effects. They have been the gold standard for drawing causal inference and provide excellent internal validity. However, they have also been criticized for questionable external validity, in the sense that the conclusion may not generalize well to a larger population. The randomized survey experiment is a design tool that can help mitigate this concern, by randomly selecting the experimental units from the target population of interest. However, as pointed out by Morgan and Rubin, chance imbalances often exist in covariate distributions between different treatment groups even under completely randomized experiments. Not surprisingly, such covariate imbalances also occur in randomized survey experiments. Furthermore, the covariate imbalances happen not only between different treatment groups, but also between the sampled experimental units and the overall population of interest. In this article, we propose a two-stage rerandomization design that can actively avoid undesirable covariate imbalances at both the sampling and treatment assignment stages. We further develop asymptotic theory for rerandomized survey experiments, demonstrating that rerandomization provides better covariate balance, more precise treatment effect estimators, and shorter large-sample confidence intervals. We also propose covariate adjustment to deal with remaining covariate imbalances after rerandomization, showing that it can further improve both the sampling and estimated precision. Our work allows general relationship among covariates at the sampling, treatment assignment and analysis stages, and generalizes both rerandomization in classical randomized experiments and rejective sampling in survey sampling. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of emergent transcatheter aortic valve implantation (TAVI) in patients with decompensated aortic stenosis (AS) by comparing the clinical outcomes with the patients who had received the elective TAVI.Methods: By searching PubMed, EMBASE, and Cochrane databases, we obtained the studies comparing the clinical outcomes of emergent TAVI and elective TAVI. Finally, 14 studies were included.Results: A total of 14 eligible articles with 73,484 patients were included in this meta-analysis. Emergent TAVI was associated with a higher mortality during hospitalization (HR 2.09, 95% CI [1.39 to 3.14]), 30 days (HR 2.29, 95% CI [1.69 to 3.10]), and 1 year (HR 1.96, 95% CI [1.55 to 2.49]). Consistently, the incidence of acute kidney injury (AKI) (RR 2.48, 95% CI [1.85 to 3.32]), dialysis (RR 2.37, 95% CI [1.95 to 2.88]), bleeding (RR 1.62, 95% CI [1.27 to 2.08]), major bleeding (RR 1.05, 95% CI [1.00 to 1.10]), and 30-day rehospitalization (RR 1.30, 95% CI [1.07, 1.58]) were more common in patients receiving emergent TAVI. No statistical differences were found in the occurrence rate of vascular complications (RR 1.11, 95% CI [0.90, 1.36]), major vascular complications (RR 1.14, 95% CI [0.52, 2.52]), permanent pacemaker (PPM) placement (RR 1.05, 95% CI [0.99, 1.11]), cerebrovascular events (RR 1.11, 95% CI [0.98, 1.25]), moderate to severe paravalvular leakage (PVL) (RR 1.23, 95% [CI 0.94 to 1.61]), and device success (RR 0.99, 95% CI [0.97, 1.01]).Conclusion: Emergent TAVI is associated with some postoperative complications and increased mortality compared with elective TAVI. Emergent TAVI should be implemented cautiously and individually. [ABSTRACT FROM AUTHOR]

MARCH5 is a critical regulator of mitochondrial dynamics, apoptosis and mitophagy. However, its role in cardiovascular system remains poorly understood. This study aimed to investigate the role of MARCH5 in endothelial cell (ECs) injury and the involvement of the Akt/eNOS signalling pathway in this process. Rat models of myocardial infarction (MI) and human cardiac microvascular endothelial cells (HCMECs) exposed to hypoxia (1% O2) were used in this study. MARCH5 expression was significantly reduced in ECs of MI hearts and ECs exposed to hypoxia. Hypoxia inhibited the proliferation, migration and tube formation of ECs, and these effects were aggravated by knockdown of MARCH5 but antagonized by overexpressed MARCH5. Overexpression of MARCH5 increased nitric oxide (NO) content, p‐eNOS and p‐Akt, while MARCH5 knockdown exerted the opposite effects. The protective effects mediated by MARCH5 overexpression on ECs could be inhibited by eNOS inhibitor L‐NAME and Akt inhibitor LY294002. In conclusion, these results indicated that MARCH5 acts as a protective factor in ischaemia/hypoxia‐induced ECs injury partially through Akt/eNOS pathway. [ABSTRACT FROM AUTHOR]

A robust, sterile inflammation underlies myocardial ischemia and reperfusion injury (MIRI). Several subsets of B cells possess the immunoregulatory capacity that limits tissue damage, yet the role of B cells in MIRI remains elusive. Here, we sought to elucidate the contribution of B cells to MIRI by transient ligation of the left anterior descending coronary artery in B cell-depleted or -deficient mice. Following ischemia and reperfusion (I/R), regulatory B cells are rapidly recruited to the heart. B cell-depleted or -deficient mice exhibited exacerbated tissue damage, adverse cardiac remodeling, and an augmented inflammatory response after I/R. Rescue and chimeric experiments indicated that the cardioprotective effect of B cells was not solely dependent on IL-10. Coculture experiments demonstrated that B cells induced neutrophil apoptosis through contact-dependent interactions, subsequently promoting reparative macrophage polarization by facilitating the phagocytosis of neutrophils by macrophages. The in vivo cardioprotective effect of B cells was undetectable in the absence of neutrophils after I/R. Mechanistically, ligand-receptor imputation identified FCER2A as a potential mediator of interactions between B cells and neutrophils. Blocking FCER2A on B cells resulted in a reduction in the percentage of apoptotic neutrophils, contributing to the deterioration of cardiac remodeling. Our findings unveil a potential cardioprotective role of B cells in MIRI through mechanisms involving FCER2A, neutrophils, and macrophages.

Introduction: The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of emergent transcatheter aortic valve implantation (TAVI) in patients with decompensated aortic stenosis (AS) by comparing the clinical outcomes with the patients who had received the elective TAVI., Methods: By searching PubMed, EMBASE, and Cochrane databases, we obtained the studies comparing the clinical outcomes of emergent TAVI and elective TAVI. Finally, 14 studies were included., Results: A total of 14 eligible articles with 73,484 patients were included in this meta-analysis. Emergent TAVI was associated with a higher mortality during hospitalization (HR 2.09, 95% CI [1.39 to 3.14]), 30 days (HR 2.29, 95% CI [1.69 to 3.10]), and 1 year (HR 1.96, 95% CI [1.55 to 2.49]). Consistently, the incidence of acute kidney injury (AKI) (RR 2.48, 95% CI [1.85 to 3.32]), dialysis (RR 2.37, 95% CI [1.95 to 2.88]), bleeding (RR 1.62, 95% CI [1.27 to 2.08]), major bleeding (RR 1.05, 95% CI [1.00 to 1.10]), and 30-day rehospitalization (RR 1.30, 95% CI [1.07, 1.58]) were more common in patients receiving emergent TAVI. No statistical differences were found in the occurrence rate of vascular complications (RR 1.11, 95% CI [0.90, 1.36]), major vascular complications (RR 1.14, 95% CI [0.52, 2.52]), permanent pacemaker (PPM) placement (RR 1.05, 95% CI [0.99, 1.11]), cerebrovascular events (RR 1.11, 95% CI [0.98, 1.25]), moderate to severe paravalvular leakage (PVL) (RR 1.23, 95% [CI 0.94 to 1.61]), and device success (RR 0.99, 95% CI [0.97, 1.01])., Conclusion: Emergent TAVI is associated with some postoperative complications and increased mortality compared with elective TAVI. Emergent TAVI should be implemented cautiously and individually., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ruochen Shao et al.)