Background. There were controversies over the relationship between Anion gap (AG) and mortality in critically ill patients. Therefore, a large multicenter cohort study was conducted to evaluate the association of AG and mortality in large-scale intensive care units (ICUs) patients. Methods. This retrospective cohort study included adult ICU patients enrolled from eICU Collaborative Research Database. According to initial serum AG upon ICU admission, patients were divided into three groups: AG < 8 mmol / L , 8 ≤ AG ≤ 16 mmol / L , and AG > 16 mmol / L . Logistic regression models were built to investigate the association between serum AG and ICU and hospital mortalities. Serum AG was added into Acute Physiology and Chronic Health Evaluation (APACHE) IV score and the model discrimination was assessed by the area under the curve (AUC) of receiver operating characteristic curves. The relationship between serum AG and mortalities in patients with different acid-base status and serum lactate were also evaluated. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People’s Hospital. Results. A total of 8520 patients entered the final cohort. There are 42 patients with serum AG < 8 mmol / L , 3238 patients with 8 ≤ AG ≤ 16 mmol / L , and 5240 patients with AG > 16 mmol / L . Serum AG > 16 mmol / L is related with increased ICU mortality (odds ratio [OR], 1.530; 95% confidence interval [CI], 1.305–1.794) and hospital mortality (OR, 1.618; 95% CI, 1.415–1.849), compared with 8 ≤ AG ≤ 16 mmol / L . Adding Serum AG to APACHE IV score could statistically improve the prediction of ICU (0.770 [0.761–0.779] to 0.774 [0.765–0.783], P = 0.001 ) and hospital mortalities (0.756 [0.747–0.765] to 0.761 [0.751–0.770], P = 0.012 ). The associations between serum AG and mortalities remain robust in patients with different acid-base statuses and serum lactate. The findings are validated in the external cohort. Conclusions. Initial serum AG > 16 mmol / L after ICU admission is associated with increased mortality in critically ill patients.
Background: Several clinical trials have demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) reduce the incidence of non-fatal myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. In this study, we applied a network pharmacology method to investigate the mechanisms by which GLP-1RAs reduce MI occurrence in patients with T2DM.Methods: Targets of three GLP-1RAs (liraglutide, semaglutide, and albiglutide), T2DM, and MI were retrieved from online databases. The intersection process and associated targets retrieval were employed to obtain the related targets of GLP-1RAs against T2DM and MI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analyses were performed. The STRING database was used to obtain the protein-protein interaction (PPI) network, and Cytoscape was used to identify core targets, transcription factors, and modules.Results: A total of 198 targets were retrieved for the three drugs and 511 targets for T2DM with MI. Finally, 51 related targets, including 31 intersection targets and 20 associated targets, were predicted to interfere with the progression of T2DM and MI on using GLP-1RAs. The STRING database was used to establish a PPI network comprising 46 nodes and 175 edges. The PPI network was analyzed using Cytoscape, and seven core targets were screened: AGT, TGFB1, STAT3, TIMP1, MMP9, MMP1, and MMP2. The transcription factor MAFB regulates all seven core targets. The cluster analysis generated three modules. The GO analysis for 51 targets indicated that the terms were mainly enriched in the extracellular matrix, angiotensin, platelets, and endopeptidase. The results of KEGG analysis revealed that the 51 targets primarily participated in the renin-angiotensin system, complement and coagulation cascades, hypertrophic cardiomyopathy, and AGE-RAGE signaling pathway in diabetic complications.Conclusion: GLP-1RAs exert multi-dimensional effects on reducing the occurrence of MI in T2DM patients by interfering with targets, biological processes, and cellular signaling pathways related to atheromatous plaque, myocardial remodeling, and thrombosis.
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