The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Drug overdose is an escalating public health crisis in the United States (U.S.). This study evaluated the temporal trend of drug overdose-related deaths in the U.S., with an emphasis on identifying disparities across subpopulations and the contributing drugs. Using the nationwide death dataset from the National Vital Statistics System (NVSS), we estimated the drug overdose-related age-standardized mortality rate (ASMR) and temporal trends for individuals aged 12 and older from 2012 to 2022. Excess mortality during the Coronavirus disease 2019 (COVID-19) pandemic was evaluated based on the pre-pandemic trends using predictive modeling analysis. Among 809,967 overdose-related deaths during 2012-2022, ASMR increased by 8.9% [95% confidence interval (CI): 6.0%-11.9%] per year from 2012 to 2019 and increased to 12.9% (95% CI: 2.1%-24.8%) from 2019 to 2022, with the excess ASMR of 16.9% in 2020, increased to 26.4% in 2021 and then decreased to 19.3% in 2022. Significant age, sex, racial/ethnic and geographic disparities were demonstrated, with adolescents (annual percentage change [APC]:21.6%) and males (APC:13.6%) having the most pronounced increase during the pandemic. Ethnic minorities especially the non-Hispanic American Indian/Alaska Native experienced the highest excess ASMR (33.1% in 2020). Illicit fentanyl and synthetics starting with the lowest ASMR in 2012 (1.0 per 100,000), marked the most dramatic increase and became the leading cause of overdose-related death since 2016 (7.5 per 100,000), leading to the highest ASMR by 2022 (27.4 per 100,000). All drug types except heroin experienced varying degrees of excess ASMRs, with prescription opioid pain relievers (23.5%-55.1%), benzodiazepines (27.4%-40.9%) and antidepressants (10.4%-17.8%) exhibiting consistent increases from 2020 to 2022, while the excess ASMRs for illicit fentanyl and synthetics (25.3%-10.0%), psychostimulants (32.8%-14.6%) and methadone (35.0%-33.3%) decreased between 2021 and 2022. Overdose-related mortality is increasing at an alarming rate, and the stark differences point to the need for targeted interventions to reduce the burden of drug overdose deaths. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acute-on-chronic liver failure is a complex condition with varied definitions, complicating risk stratification and targeted management. We apply unsupervised clustering to data from 1,256 patients with acute-on-chronic liver failure as defined by the North American Association for the Study of End-Stage Liver Disease. We systematically evaluate multiple algorithmic models to enable unbiased cohort stratification and to determine key clustering factors and clinical impacts across clusters. The optimal number of clusters is determined using the Partitioning Around Medoids with Ambiguous Clustering algorithm. The clusters from the best-performing nonnegative matrix factorization algorithm are selected, with the Lee’s algorithm demonstrating the best performance. Two distinct clusters are identified, showing markedly different 30-day mortality rates (70.35% vs 26.06%). Importantly, acid-base balance-related variables, including bicarbonate, pH, base excess, lactate, and anion gap, are among the primary clustering drivers. An external validation cohort, a decompensated cirrhosis cohort, and a European Association for the Study of the Liver-Chronic Liver Failure Consortium defined Acute-on-chronic liver failure patients cohort confirm consistent distributions of key clustering variables and divergence in 30-day mortality rates, supporting the role of acid-base balance variables. In summary, we show that the unbiased clustering approach successfully identifies distinct acute-on-chronic liver failure clusters with different mortality risks and emphasizes the critical role of metabolic regulation in acute-on-chronic liver failure outcomes, as well as consistent validation.