Serial Assessment of Serum HMGB1 and △SOFA for Predicting 28-Day Mortality in Sepsis Patients: A Prospective Cohort Study in the Emergency Department

Background : Prognostic assessment in sepsis relies on evaluating the dynamic progression of organ dysfunction and the inflammatory response. This study compared the predictive value of serially measured serum HMGB1, a key late mediator of sepsis, with the △SOFA score for 28-day mortality. Methods : This prospective cohort study enrolled 250 sepsis patients admitted to the emergency department of a tertiary hospital from January 2022 to August 2024. Serum HMGB1 levels and SOFA scores were dynamically assessed on days 1, 4, and 7. Receiver operating characteristic (ROC) curve analysis and Kaplan-Meier survival analysis were employed to evaluate their prognostic performance. The primary endpoint was 28-day all-cause mortality. Results : A total of 232 patients (median age 71.5 years, 56% male) with a 28-day mortality rate of 13.8% (32/232) were included. Non-survivors had a higher prevalence of autoimmune diseases (43.8% vs. 11.5%) and lung infections (81.3% vs. 47.0%). Serum HMGB1 levels peaked on day 4 and were significantly higher in non-survivors and septic shock patients (P < 0.05). D1-HMGB1 levels showed significant positive correlations with SOFA scores and inflammatory cytokines (IL-6, IL-8, IL-10, IL-17a, TNF-α). The area under the ROC curve (AUC) for predicting 28-day mortality was 0.856 (95% CI: 0.751-0.921) for day 4 HMGB1 (D4-HMGB1) and 0.893 (95% CI: 0.845-0.941) for D7-△SOFA. The optimal cut-off value for D4-HMGB1 was 6.4 ng/mL. Kaplan-Meier analysis confirmed that patients with D4-HMGB1 ≥ 6.4 ng/mL had significantly higher mortality (log-rank, P = 0.001). This prognostic value remained consistent across key patient subgroups, including those with acute kidney injury, autoimmune diseases, or respiratory comorbidities. Conclusion : Dynamic monitoring of serum HMGB1 provides valuable prognostic information. Specifically, the day 4 HMGB1 level demonstrates excellent and earlier predictive performance for 28-day mortality, even comparable to the D7-△SOFA score, highlighting its potential as a prognostic biomarker in sepsis. Clinical trial number : Not applicable.