Relationship of the Endothelial Activation and Stress Index with 28-day mortality in urosepsis patients: a retrospective two-cohort investigation

Background The Endothelial Activation and Stress Index (EASIX) is a novel biomarker for assessing endothelial dysfunction. This study aimed to evaluate its prognostic value for 28-day mortality in patients with urosepsis. Materials and methods We conducted a retrospective study of patients with urosepsis admitted to the ICU using data from the MIMIC-IV database and West China Hospital. Restricted cubic spline (RCS) regression, multivariable Cox regression, and Kaplan–Meier analysis were used to assess the association between EASIX and short-term mortality. Four machine learning feature selection methods (LASSO-COX, Boruta, random forest, and gradient boosting) were applied to identify key prognostic features and develop a predictive model, which was evaluated using ROC curve analysis and validated in an external cohort. Result A total of 2,593 patients were included. The 28-day ICU and in-hospital mortality rates were 16.0 and 17.2%, respectively. Higher EASIX scores were significantly associated with increased mortality across quartiles (ICU mortality: 10.5% in Q1 to 30.4% in Q4, p < 0.001). In the fully adjusted model, each unit increase in EASIX was associated with a 7% higher risk of ICU mortality (HR 1.07, 95% CI 1.05–1.11, p < 0.001), and patients in Q4 had a 57% higher risk than those in Q1 (HR 1.57, 95% CI 1.09–2.26, p = 0.016). RCS analysis revealed a non-linear relationship between EASIX and mortality. The predictive model incorporating EASIX, Charlson Comorbidity Index, RDW, and SAPS II achieved AUC values of 0.70–0.73 across training, internal validation, and external validation cohorts, demonstrating improved performance compared to traditional severity scores. Conclusion EASIX is independently associated with short-term mortality in patients with urosepsis and may serve as a valuable tool for risk stratification following further validation.