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Background and Aims: NASH, characterized by inflammation and fibrosis, is emerging as a leading etiology of HCC. Lipidomics analyses in the liver have shown that the levels of polyunsaturated phosphatidylcholine (PC) are decreased in patients with NASH, but the roles of membrane PC composition in the pathogenesis of NASH have not been investigated. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), a phospholipid (PL) remodeling enzyme that produces polyunsaturated PLs, is a major determinant of membrane PC content in the liver., Approach and Results: The expression of LPCAT3 and the correlation between its expression and NASH severity were analyzed in human patient samples. We examined the effect of Lpcat3 deficiency on NASH progression using Lpcat3 liver-specific knockout (LKO) mice. RNA sequencing, lipidomics, and metabolomics were performed in liver samples. Primary hepatocytes and hepatic cell lines were used for in vitro analyses. We showed that LPCAT3 was dramatically suppressed in human NASH livers, and its expression was inversely correlated with NAFLD activity score and fibrosis stage. Loss of Lpcat3 in mouse liver promotes both spontaneous and diet-induced NASH/HCC. Mechanistically, Lpcat3 deficiency enhances reactive oxygen species production due to impaired mitochondrial homeostasis. Loss of Lpcat3 increases inner mitochondrial membrane PL saturation and elevates stress-induced autophagy, resulting in reduced mitochondrial content and increased fragmentation. Furthermore, overexpression of Lpcat3 in the liver ameliorates inflammation and fibrosis of NASH., Conclusions: These results demonstrate that membrane PL composition modulates the progression of NASH and that manipulating LPCAT3 expression could be an effective therapeutic for NASH., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Anastomotic leak after esophagectomy carries important short- and long-term sequelae. The authors conducted a systematic review and meta-analysis to determine its association with surgical volume., Materials and Methods: A systematic literature review was performed to identify all studies reporting on anastomotic leak after esophagectomy. Studies with less than 100 cases were excluded. The primary outcome was postesophagectomy anastomotic leak, while secondary outcomes were operative mortality overall and after anastomotic leak. Pooled event rates (PER) were calculated, and the association with annual esophagectomy volume by center was investigated., Results: Of the 3932 retrieved articles, 472 were included ( n =177 566 patients). The PER of anastomotic leak was 8.91% [95% CI=8.32; 9.53%]. The PER of early mortality overall and after an anastomotic leak was 2.49% [95% CI=2.27; 2.74] and 11.39% [95% CI=9.66; 13.39], respectively. Centers with less than 37 annual esophagectomies had a higher leak rate compared to those with greater than or equal to 37 annual esophagectomies (9.58% vs. 8.34%; P =0.040). On meta-regression, surgical volume was inversely associated with the PER of esophageal leak and of early mortality., Conclusions: The frequency of anastomotic leaks after esophagectomy, perioperative, and leak associated mortality are inversely associated with esophagectomy volume., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Cardiac tumors and their associated outcomes are poorly characterized. This study sought to comprehensively assess the epidemiology and natural history of primary and secondary malignant cardiac tumors (PMCT and SMCT), a well as establish predictors of mortality., Methods: A comprehensive literature review was performed to identify articles reporting on PMCTs and SMCTs. The prevalence of important cardiac tumor (CT) subtypes was evaluated and further stratified based on the continental region. Outcomes of interest included short- and long-term mortality and utilization of heart transplantation (HTX). A random effect model was adopted, and a meta-regression was performed to determine predictors of the prevalence of CTs as well as predictors of operative mortality., Results: Of the 1,226 retrieved articles, 74 were included in our study (n = 8,849 patients). The mean follow-up was 2.27 years, mean age was 42.9 years, and 55% of the patients were females. There was a total number of 7,484 benign primary cardiac tumors (PCTs) (5,140 were myxoma), 862 (9.7%) malignant PCTs, and 355 secondary cardiac tumors. The prevalence of PMCTs among PCTs was 10.83% [95%CI = 09.11; 12.83%] with a trend towards being lower in South America compared to other continents (Prevalence = 5.80%). The prevalence of HTX among all patients was 2.45% [1.36; 4.38%]. The pooled short-term mortality was 5.90% [4.70; 7.39%] and the incidence of late mortality in all CTs, benign CT and PMCTs was 2.55% [1.76; 3.72%], 0.79% [0.46; 1.37%] and 14.77% [9.32; 23.40%], respectively. On meta-regression, the annual volume of cardiac tumor cases per center was the only predictor of lower early mortality (Beta = -0.14 ± 0.03, P < 0.0001)., Conclusions: PMCTs represent the minority of PCT (~10%) and have a higher prevalence in Europe and North America. Survival is higher in benign pathology and is significantly improved by treatment in specialized high-volume centers. Approximately 2% of patients with CTs undergo heart transplantation., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)