Integrating serum ferritin and neutrophil-to-lymphocyte ratio with Sequential Organ Failure Assessment score improves mortality prediction in sepsis

BACKGROUND Sepsis causes significant mortality in patients. Typically, the Sequential Organ Failure Assessment (SOFA) score is used; however, recent studies have demonstrated improved predictive accuracy by using inflammatory biomarkers such as serum ferritin and the neutrophil-to-lymphocyte ratio (NLR). Serum ferritin, although traditionally associated with iron metabolism, also acts as an acute-phase reactant reflecting systemic inflammation. AIM To assess the prognostic value of integrating ferritin and NLR with SOFA in predicting mortality in critically ill patients with sepsis. METHODS Medical Information Mart for Intensive Care database-IV database was used to conduct this retrospective cohort study. Patients were divided into quartiles based on values of serum ferritin and NLR. Cox proportional hazards regression assessed the association with 30-day mortality, adjusted for age, sex, and the Charlson comorbidity index. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), calibration plot, and net reclassification index (NRI). Bootstrapped internal validation was performed using 1000 resamples. RESULTS Patients in the ferritin Q1 quartile (lowest ferritin quartile) had 30% lower adjusted mortality risk (hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.57-0.9; P = 0.005) compared to Q3 (highest ferritin quartile). Similarly, NLR Q1 (lowest NLR quartile) had 27% lower adjusted mortality risk (HR: 0.73, 95%CI: 0.59-0.91; P = 0.006). Moreover, patients with both serum ferritin and NLR in the Q1 (lowest) quartile had the lowest risk of mortality (HR: 0.56, 95%CI: 0.42-0.74; P < 0.001). With biomarker integration, the AUROC improved from 0.602 (95%CI: 0.574-0.630) for SOFA alone to 0.656 (0.629-0.683; P < 0.001), primarily driven by ferritin. NRI demonstrated a modest but significant improvement in reclassification. Old age was also found to be associated with a higher risk of mortality. CONCLUSION Lower ferritin and NLR are associated with reduced 30-day mortality, with ferritin markedly improving SOFA-based prediction and NLR offering minimal added benefit. Accessible biomarkers enhance early risk assessment in low-resource intensive care units.