{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:53:11Z","timestamp":1792000391773,"version":"4.4.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (<jats:italic>P<\/jats:italic> = 0.032; 95% confidence bounds 0.513\u20130.721), and for SOFA was 0.750 (<jats:italic>P<\/jats:italic> &amp;lt; 0.0001; 95% confidence bounds 0.660\u20130.840). Sepsis patients with high serum S100A8\/A9 concentrations (\u2265 377.53 ng\/mL) had a higher survival rate relative to those with low concentrations (&amp;lt;377.53 ng\/mL). In the validation cohort, the AUC for S100A8\/A9 and 28-day mortality was 0.708 (<jats:italic>P<\/jats:italic> = 0.032; 95% confidence bounds 0.563\u20130.854), and for SOFA was 0.698 (<jats:italic>P<\/jats:italic> = 0.025; 95% confidence bounds 0.550\u20130.845). Additionally, sepsis patients with high serum S100A8\/A9 concentrations (\u2265 377.53 ng\/mL) also had a higher survival rate relative to those with lower concentrations (&amp;lt; 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 (<jats:italic>P<\/jats:italic> = 0.034; 95% confidence bounds 0.605\u20131.00) and 0.708 (<jats:italic>P<\/jats:italic> = 0.015; 95% confidence bounds 0.571\u20130.846). In patients with a normal sepsis phenotype, those with high serum resistin levels (\u2265 63.695 ng\/mL) had a lower survival rate compared to those with low resistin levels (&amp;lt; 63.695 ng\/mL). In contrast, in patients with a mixed phenotype with hyperinflammation, those with high serum resistin levels (\u2265 107.64 ng\/mL) had a higher survival rate compared to those with lower resistin levels (&amp;lt; 107.64 ng\/mL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1555307","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:11:41Z","timestamp":1749640301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Assessment of S100A8\/A9 and resistin as predictive biomarkers for mortality in critically ill patients with sepsis"],"prefix":"10.3389","volume":"15","author":[{"given":"Jing","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengquan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyou","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingsen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13054-021-03862-5","article-title":"Biomarkers for sepsis: more than just fever and leukocytosis-a narrative review","volume":"26","author":"Barichello","year":"2022","journal-title":"Crit. 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