Development and validation of an interpretable machine learning model for predicting sepsis risk in pleural effusion patients.

Background: Intensive care unit (ICU)-acquired sepsis in patients with pleural effusion presents a formidable clinical challenge with high mortality. We aimed to develop and externally validate an interpretable machine learning (ML) framework for early risk prediction. Methods: This multicenter retrospective study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU databases). A robust tri-algorithm intersection strategy [Boruta, least absolute shrinkage and selection operator (LASSO), and recursive feature elimination (RFE)] was employed to extract core predictors. Nine supervised ML algorithms were systematically evaluated. SHapley Additive exPlanations (SHAP) and restricted cubic spline (RCS) analyses were integrated to demystify the "black-box" decision-making process. The optimal model was deployed as a dynamic nomogram and validated via decision curve analysis (DCA). Results: We identified a parsimonious subset of 10 critical predictors. During comprehensive algorithmic competition, the logistic regression (LR) model demonstrated superior discriminative performance and external generalizability. Global SHAP analysis identified baseline Sequential Organ Failure Assessment (SOFA) score, pneumonia, and preemptive sedative use as top-tier risk drivers, while highlighting the prognostic value of metabolic markers (anion gap and albumin). Crucially, RCS analysis revealed a distinct non-linear, "U-shaped" dose-response relationship between baseline white blood cell (WBC) counts and sepsis risk, cautioning against the deceptive reassurance of sepsis-associated leukopenia. DCA confirmed that the nomogram provided substantial net clinical benefit. Conclusions: We successfully developed a highly transparent, data-driven ML framework to predict ICU-acquired sepsis risk in pleural effusion patients. The resulting web-based nomogram offers intensive care physicians an actionable bedside tool for personalized risk stratification and timely intervention.