IDENTIFICATION OF SUBPHENOTYPES OF SEPSIS-ASSOCIATED LIVER DYSFUNCTION USING CLUSTER ANALYSIS.

ABSTRACT: Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. Patients: We included adult patients (age ≥18 years) who developed SALD within the first 48 hours of intensive care unit (ICU) admission. We excluded patients who died or were discharged from the ICU within the first 48 hours of admission. Patients with abnormal liver function before ICU admission were also excluded. Measurements and Main Results: Patients in the MIMIC-IV 1.0 database served as a derivation cohort. Patients in the eICU database were used as validation cohort. We identified four subphenotypes of SALD (subphenotype α, ß, γ, δ) using K-means cluster analysis in 5234 patients in derivation cohort. The baseline characteristics and clinical outcomes were compared between the phenotypes using one-way analysis of variance/Kruskal-Wallis test and the χ 2 test. Moreover, we used line charts to illustrate the trend of liver function parameters over 14 days after ICU admission. Subphenotype α (n = 1,055) was the most severe cluster, characterized by shock with multiple organ dysfunction (MODS) group. Subphenotype ß (n = 1,179) had the highest median bilirubin level and the highest proportion of patients with underlying liver disease and coexisting coagulopathy (increased bilirubin group). Subphenotype γ (n = 1,661) was the cluster with the highest mean age and had the highest proportion of patients with chronic kidney disease (aged group). Subphenotype δ (n = 1,683) had the lowest 28-day and in-hospital mortality (mild group). The characteristics of clusters in the validation cohort were similar to those in the derivation cohort. In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.

Comparison of anticoagulation monitoring strategies for adults supported on extracorporeal membrane oxygenation: A systematic review.

BACKGROUND: Anticoagulation is critical in patients supported on extracorporeal membrane oxygenation (ECMO). The appropriate monitoring strategies for heparin remain unclear. OBJECTIVES: This systematic review aimed to compare the accuracy and safety of various monitoring strategies for patients supported on ECMO. METHODS: The PubMed and Web of Science databases were searched for articles in March 2023 without restrictions on publication date. Anticoagulation monitoring strategies for adults supported on ECMO were compared across all included studies. The incidence of bleeding, thrombosis, mortality, blood transfusion, correlation between tests and heparin dose, and the discordance between different tests were discussed in the included studies. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane Collaboration's tool. RESULTS: Twenty-six studies, including a total of 1,684 patients, met the inclusion criteria. The monitoring of anticoagulation by activated partial thromboplastin time (aPTT) resulted in less blood product transfusion than that by activated clotting time (ACT). Moreover, the monitoring of anticoagulation by anti-factor Xa (Anti-Xa) resulted in a more stable anticoagulation than that by aPTT. Anti-Xa and aPTT correlated with heparin dose better than ACT, and the discordance between different monitoring tests was common. Finally, combined monitoring showed some advantages in reducing mortality and blood product transfusion. CONCLUSION: Anti-Xa and aPTT are more suitable for anticoagulation monitoring for patients supported on ECMO than ACT. Thromboelastography and combination strategies are less applied. Most of the studies were retrospective, and their sample sizes were relatively small; thus, more appropriate monitoring strategies and higher quality research are needed.

Associations between the use of aspirin or other antiplatelet drugs and all-cause mortality among patients with COVID-19: A meta-analysis.

Introduction: Whether aspirin or other antiplatelet drugs can reduce mortality among patients with coronavirus disease (COVID-19) remains controversial. Methods: We identified randomized controlled trials, prospective cohort studies, and retrospective studies on associations between aspirin or other antiplatelet drug use and all-cause mortality among patients with COVID-19 in the PubMed database between March 2019 and September 2021. Newcastle-Ottawa Scale and Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias. The I2 statistic was used to assess inconsistency among trial results. The summary risk ratio (RR) and odds ratio (OR) were obtained through the meta-analysis. Results: The 34 included studies comprised three randomized controlled trials, 27 retrospective studies, and 4 prospective cohort studies. The retrospective and prospective cohort studies showed low-to-moderate risks of bias per the Newcastle-Ottawa Scale score, while the randomized controlled trials showed low-to-high risks of bias per the Cochrane Risk of Bias Assessment Tool. The randomized controlled trials showed no significant effect of aspirin use on all-cause mortality in patients with COVID-19 {risk ratio (RR), 0.96 [95% confidence interval (CI) 0.90-1.03]}. In retrospective studies, aspirin reduced all-cause mortality in patients with COVID-19 by 20% [odds ratio (OR), 0.80 (95% CI 0.70-0.93)], while other antiplatelet drugs had no significant effects. In prospective cohort studies, aspirin decreased all-cause mortality in patients with COVID-19 by 15% [OR, 0.85 (95% CI 0.80-0.90)]. Conclusion: The administration of aspirin may reduce all-cause mortality in patients with COVID-19.