PLoS One. 2026 Jun 2;21(6):e0348676. doi: 10.1371/journal.pone.0348676. eCollection 2026.
ABSTRACT
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has shown inconsistent prognostic value in individuals with sepsis. This study aimed to clarify its ability to predict 28-day mortality via a machine learning-based analysis of a large ICU database.
METHODS: This retrospective analysis employed data from the MIMIC-IV database (v3.1). The Boruta algorithm combined with XGBoost was used for two-stage feature selection. Patients were stratified by NLR quartiles into three groups (low: <4.34, intermediate: 4.34-14.70, and high: >14.70). This study defined 28-day mortality as the primary outcome. Associations between the NLR and mortality were evaluated by using multivariable logistic regression (progressively adjusted for demographic, clinical, and machine learning-derived features), along with restricted cubic splines. Sensitivity analyses included quantifying NLR feature importance via machine learning and performing subgroup analyses across clinical strata.
RESULTS: This cohort study included 4,376 patients with a 28-day mortality rate of 18.4%. Compared with the SOFA and SAPS II scores, the prediction performance of XGBoost was superior (ROC-AUC 0.875; 95% CI 0.854-0.896; PR-AUC 0.603). Although the NLR ranked 14th in SHAP-based feature importance, multivariable analysis confirmed its independent association with elevated mortality risk: 28-day (OR 1.16; 95% CI 1.06-1.27; p < 0.001), in-hospital (OR 1.13; 95% CI 1.03-1.24; p < 0.001), and ICU (OR 1.14; 95% CI 1.03-1.25; p = 0.008). Stratified analyses indicated consistent mortality associations for the NLR, with enhanced predictive value being observed in patients aged >45 years and those with SOFA scores ≤4 or SAPS II scores >29. Specifically, patients ≥65 years of age demonstrated a 17% increase in 28-day mortality risk (p = 0.019), and patients with a SOFA score ≤4 exhibited a greater than 20% elevated risk across all of the endpoints (p < 0.001), whereas no significant association was observed in the SOFA ≥9 subgroup (p = 0.369).
CONCLUSIONS: The NLR effectively identifies inflammation-driven mortality risk for early sepsis patients but fails to predict outcomes for patients with terminal organ failure. This biphasic predictive pattern highlights the unique value of the NLR in moderate sepsis risk stratification but cautions against its use in cases of advanced disease. Its value lies in dynamic monitoring rather than static risk assessment.
PMID:42228737 | DOI:10.1371/journal.pone.0348676