Assessment of S100A8/A9 and resistin as predictive biomarkers for mortality in critically ill patients with sepsis.

INTRODUCTION

Sepsis is associated with high mortality. Early intervention is crucial to reducing sepsis-related mortality. This study aims to assess the clinical potential of S100A8/A9 and resistin as novel biomarkers for predicting mortality risk in sepsis patients.

METHOD

Serum samples were collected and analyzed from 141 adult sepsis patients (discovery cohort), 43 non-sepsis intensive care units (ICU) patients, 15 healthy volunteers, and 55 sepsis patients along with 17 non-sepsis ICU patients (validation cohort). The 28-day mortality and sequential organ failure assessment (SOFA) scores of the participants were compared. Additionally, the predictive ability of S100A8/A9 and resistin for sepsis mortality was evaluated using the area under the receiver operating characteristic curve at ICU admission.

RESULTS

The concentrations of S100A8/A9 and resistin in sepsis patients were noticeably increased relative to non-sepsis patients and healthy controls. Serum S100A8/A9 concentrations in surviving sepsis patients were significantly higher than in non-surviving patients. On the day of admission, serum resistin concentrations in Gram-negative (G-) sepsis patients were considerably elevated relative to Gram-positive (G+) infected sepsis patients. Among sepsis patients admitted to the ICU, the AUC for S100A8/A9 in predicting 28-day mortality was 0.617 ( = 0.032; 95% confidence bounds 0.513-0.721), and for SOFA was 0.750 ( < 0.0001; 95% confidence bounds 0.660-0.840). Sepsis patients with high serum S100A8/A9 concentrations (≥ 377.53 ng/mL) had a higher survival rate relative to those with low concentrations (<377.53 ng/mL). In the validation cohort, the AUC for S100A8/A9 and 28-day mortality was 0.708 ( = 0.032; 95% confidence bounds 0.563-0.854), and for SOFA was 0.698 ( = 0.025; 95% confidence bounds 0.550-0.845). Additionally, sepsis patients with high serum S100A8/A9 concentrations (≥ 377.53 ng/mL) also had a higher survival rate relative to those with lower concentrations (< 377.53 ng/mL). Furthermore, serum resistin levels in patients with a normal phenotype and mixed phenotype with hyperinflammation were predictive of mortality, with an AUC of 0.810 ( = 0.034; 95% confidence bounds 0.605-1.00) and 0.708 ( = 0.015; 95% confidence bounds 0.571-0.846). In patients with a normal sepsis phenotype, those with high serum resistin levels (≥ 63.695 ng/mL) had a lower survival rate compared to those with low resistin levels (< 63.695 ng/mL). In contrast, in patients with a mixed phenotype with hyperinflammation, those with high serum resistin levels (≥ 107.64 ng/mL) had a higher survival rate compared to those with lower resistin levels (< 107.64 ng/mL).

DISCUSSION

Sepsis, the leading cause of death in intensive care unit patients. Identifying reliable biomarkers is essential for improving both the diagnosis and treatment of sepsis. We found that serum S100A8/A9 concentration at ICU admission is a significant predictor of 28-day mortality risk in sepsis patients. Additionally, resistin levels at ICU admission play an important role in predicting 28-day mortality risk in patients with both normal and mixed phenotypes with hyperinflammation. These findings suggest that S100A8/A9 and resistin could serve as effective biomarkers. Moreover, these findings could guide early clinical decisions in the treatment of sepsis patients.