A rat liver cell atlas reveals intrahepatic myeloid heterogeneity.

The large size and vascular accessibility of the laboratory rat (Rattus norvegicus) make it an ideal hepatic animal model for diseases that require surgical manipulation. Often, the disease susceptibility and outcomes of inflammatory pathologies vary significantly between strains. This study uses single-cell transcriptomics to better understand the complex cellular network of the rat liver, as well as to unravel the cellular and molecular sources of inter-strain hepatic variation. We generated single-cell and single-nucleus transcriptomic maps of the livers of healthy Dark Agouti and Lewis rat strains and developed a factor analysis-based bioinformatics analysis pipeline to study data covariates, such as strain and batch. Using this approach, we discovered transcriptomic variation within the hepatocyte and myeloid populations that underlie distinct cell states between rat strains. This finding will help provide a reference for future investigations on strain-dependent outcomes of surgical experiment models.

Association between sex and survival after non-traumatic out of hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Existing studies have shown conflicting results regarding the relationship of sex with survival after out of hospital cardiac arrest (OHCA). This systematic review evaluates the association of female sex with survival to discharge and survival to 30 days after non-traumatic OHCA. METHODS: We searched Medline, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception through June 2021 for studies evaluating female sex as a predictor of survival in adult patients with non-traumatic cardiac arrest. Random-effects inverse variance meta-analyses were performed to calculate pooled odds ratios (ORs) with 95% confidence intervals (CI). The GRADE approach was used to assess evidence quality. RESULTS: Thirty studies including 1,068,788 patients had female proportion of 41%. There was no association for female sex with survival to discharge (OR 1.03, 95% CI 0.95-1.12; I2 = 89%). Subgroup analysis of low risk of bias studies demonstrated increased survival to discharge for female sex (OR 1.20, 95% CI 1.18-1.23; I2 = 0%) and with high certainty, the absolute increase in survival was 2.2% (95% CI 0.1-3.6%). Female sex was not associated with survival to 30 days post-OHCA (OR 1.02, 95% CI 0.92-1.14; I2 = 79%). CONCLUSIONS: In adult patients experiencing OHCA, with high certainty in the evidence from studies with low risk of bias, female sex had a small absolute difference for the outcome survival to discharge and no difference in survival at 30 days. Future models that aim to stratify risk of survival post-OHCA should focus on sex-specific factors as opposed to sex as an isolated prognostic factor.

Predictors of 1-year mortality after adult lung transplantation: Systematic review and meta-analyses.

BACKGROUND: Prognostic factors in lung transplantation are those variables that are associated with transplant outcomes. Knowledge of donor and recipient prognostic variables can aid in the optimal allocation of donor lungs to transplant recipients and can also inform post-operative discussions with patients about prognosis. Current research findings related to prognostic factors in lung transplantation are inconsistent and the relative importance of various factors is unclear. This review aims to provide the best possible estimates of the association between putative prognostic variables and 1-year all-cause mortality in adult lung transplant recipients. METHODS: We searched 5 bibliographic databases for studies assessing the associations between putative predictors (related to lung donors, recipients, or the transplant procedure) and 1-year recipient mortality. We pooled data across studies when justified and utilized GRADE methodology to assess the certainty in the evidence. RESULTS: From 72 eligible studies (2002-2020), there were 34 recipient variables, 4 donor variables, 10 procedural variables, and 7 post-transplant complication variables that were amenable to a meta-analysis. With a high degree of certainty in the evidence only post-transplant need for extra-corporeal membrane oxygenation (ECMO) (HR 1.91, 95% CI 1.79-2.04) predicted 1-year mortality. No donor variables appeared to predict transplant outcome with high or even moderate certainty. CONCLUSION: Across the range of contemporary donors and recipients that clinicians accept for lung transplantation, this review, with high certainty, found 1 prognostic factor that predicted 1-year mortality, and 37 additional factors with a moderate degree of certainty. The lack of prognostic significance for some widely accepted factors (e.g., donor smoking, age) likely relates to existing limits in the range of these variables at the time of donor and recipient selection.