The Prognostic Value of the CALLY Index in Sepsis: A Composite Biomarker Reflecting Inflammation, Nutrition, and Immunity

<b>Background/Objectives</b>: Sepsis remains a leading cause of mortality worldwide, necessitating the development of effective prognostic markers for early risk stratification. The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel biomarker that integrates inflammatory, nutritional, and immunological parameters. This study aimed to evaluate the association between the CALLY index and 30-day all-cause mortality in sepsis patients. <b>Methods</b>: This retrospective cohort study included adult patients diagnosed with sepsis in the emergency department between 1 January 2022, and 1 January 2025. The CALLY index was calculated as (CRP × absolute lymphocyte count)/albumin. The primary outcome was 30-day all-cause mortality. Five machine learning models-extreme gradient boosting (XGBoost), multilayer perceptron, random forest, support vector machine, and generalized linear model-were developed for mortality prediction. Four feature selection strategies (gain score, SHAP values, Boruta, and LASSO regression) were used to evaluate predictor consistency. The clinical utility of the CALLY index was assessed using decision curve analysis (DCA). <b>Results</b>: A total of 1644 patients were included, of whom 345 (21.0%) died within 30 days. Among the five machine learning models, the XGBoost model achieved the highest performance (AUC: 0.995, R²: 0.867, MAE: 0.063, RMSE: 0.145). In gain-based feature selection, the CALLY index emerged as the top predictor (gain: 0.187), followed by serum lactate (0.185) and white blood cell count (0.117). The CALLY index also ranked second in SHAP analysis (mean value: 0.317) and first in Boruta importance (mean importance: 37.54). DCA showed the highest net clinical benefit of the CALLY index within the 0.10-0.15 risk threshold range. <b>Conclusions</b>: This study demonstrates that the CALLY index is a significant predictor of 30-day mortality in sepsis patients. Machine learning analysis further reinforced the prognostic value of the CALLY index.