Abstract
BACKGROUND: The prognostic nutritional index (PNI), reflecting nutritional and immune-inflammatory status, has been linked to outcomes across a range of disorders. Its prognostic value in acute pancreatitis (AP) and the potential mediating role of systemic inflammatory response syndrome (SIRS) remain unclear. OBJECTIVE: To investigate whether systemic inflammatory response syndrome (SIRS) mediates the linkage between the prognostic nutritional index (PNI) and risk of death from any cause during hospitalization, as well as short- and long-term outcomes, in patients with acute pancreatitis (AP). METHODS: This was an international retrospective cohort study utilizing the U.S. MIMIC-IV dataset (v2.2) and a hospital-based dataset in China, encompassing 2,574 patients diagnosed with AP (MIMIC cohort: 941; Chinese cohort: 1,633). Analyses included multivariable Cox regression, receiver operating characteristic (ROC) curves, Kaplan-Meier survival curves, restricted cubic spline (RCS) modeling, subgroup analysis, and mediation analysis. RESULTS: After adjustment for age, sex, comorbidities, and BISAP scores, PNI remained to serve as a standalone protective factor among AP patients (all HR < 1, P < 0.05). PNI exhibited strong predictive performance, particularly for long-term mortality. The low PNI exhibited markedly greater mortality compared with those with high PNI at all time points (log-rank P < 0.01). PNI demonstrated a significant nonlinear negative correlation with mortality, with more pronounced protective effects in certain subgroups. SIRS partially mediated the PNI-mortality association. CONCLUSION: PNI is an independent determinant of mortality in AP, offering complementary prognostic value to BISAP. SIRS partially mediates this association but is not the primary pathway.