Background: Systemic inflammation and the resulting hypercatabolism in sepsis critically drive malnutrition and metabolic dysregulation, significantly worsening clinical outcomes. However, existing nutritional assessment tools are not sepsis-specific, and their comparative prognostic performance in this population remains unclear. This study aimed to compare current tools and develop a novel, sepsis-specific biomarker that integrates inflammatory, nutritional, and metabolic dimensions to optimise risk stratification. Methods: In this retrospective cohort study, data from 1915 sepsis patients admitted to a tertiary ICU between January 2021 and May 2025 were analysed. Nutritional risk was assessed using the modified nutrition risk in critically ill (mNUTRIC) score, prognostic nutritional index (PNI), nutritional risk index (NRI), and controlling nutritional status (CONUT) score. Prognostic performance for ICU mortality was evaluated using receiver operating characteristic (ROC) curves, Kaplan–Meier survival analysis, and Cox regression. Leveraging machine learning (LASSO regression), key variables were screened to modify the PNI, resulting in the development of the Lactate-Modified Prognostic Nutritional Index (LPNI). Results: Among conventional indices, mNUTRIC demonstrated the highest prognostic accuracy (AUC = 0.725, 95% CI 0.699– 0.751), followed by PNI (AUC = 0.687, 95% CI 0.660– 0.713). The novel LPNI, superior discriminative ability (AUC = 0.754, 95% CI 0.729– 0.780) and served as a robust independent risk factor for ICU mortality in the total cohort (HR = 3.25, 95% CI 2.36– 4.48, p < 0.001), as well as in septic shock (HR = 2.40, 95% CI 1.85– 3.10, p < 0.001) and non-shock subgroups (HR = 2.60, 95% CI 1.49– 4.51, p < 0.001). Distinct from the broad risk classification of traditional tools, the LPNI identified a specific high-risk inflammatory-metabolic-nutritional phenotype in 18.8% of patients. This severe phenotype was significantly more prevalent in patients with septic shock compared to those without (24.3% vs 9.0%, p < 0.001). Sensitivity analysis and internal validation confirmed the stability of these findings. Conclusion: The LPNI is an objective composite biomarker that integrates inflammatory, nutritional, and metabolic dimensions. It is independently associated with ICU mortality in sepsis patients, including those with or without septic shock. A newly developed online calculator based on the LPNI is provided to facilitate its potential bedside application; however, further prospective validation of its clinical utility is warranted. Keywords: sepsis, systemic inflammation, inflammatory-metabolic-nutritional phenotype, lactate-modified prognostic nutritional index, risk stratification, biomarker
Li et al. (Fri,) studied this question.