{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:11:18Z","timestamp":1789017078312,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Early changes in innate immune responsiveness precede overt organ dysfunction in sepsis. In emergency department (ED) patients with suspected infection and physiological deterioration, we estimated the prevalence of reduced LPS-induced TNF-\u03b1 responsiveness, characterized the associated clinical outcomes, and assessed the diagnostic accuracy of a point-of-care LPS-induced TNF-\u03b1 release assay (TARA) for Sepsis-3 adjudicated at 24\u00a0h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective observational cohort, adults with suspected infection and NEWS2 \u22653 were consecutively enrolled. Whole-blood samples collected at ED arrival (0\u00a0h) and 4\u00a0h later were stimulated\n                      <jats:italic>ex vivo<\/jats:italic>\n                      with LPS, and TNF-\u03b1 release was measured using the TARA assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 203 enrolled patients, 180 had valid paired TARA results and 142 fulfilled Sepsis-3 criteria within 24\u00a0h. Reduced LPS-induced TNF-\u03b1 responsiveness, defined by a negative TARA result, was frequent (75%) and was associated with higher Sepsis-3 adjudication (83.0% vs. 66.7%). Using a parallel rule (0 or 4\u00a0h), negative TARA identified Sepsis-3 with 78.9% sensitivity (95% CI 71.4 to 84.8), 39.5% specificity (95% CI 25.6 to 55.3), 83.0% PPV, 33.3% NPV, LR+ of 1.30, LR- of 0.54, and 70.6% accuracy. Predictive values are prevalence-dependent and not transportable to unselected ED populations, whereas the likelihood ratios are. In prespecified low-risk subsets, sensitivity was 87.0% (95% CI 75.6 to 93.6) with NEWS2 &amp;lt;5 and 79.1% (70.8 to 85.6) with qSOFA \u22641. Using a composite endpoint (Sepsis-2\/Sepsis-3), accuracy improved to 77.0% with maintained sensitivity (78.8%). In a parsimonious model adjusted for age and qSOFA, TARA remained independently associated with Sepsis-3 (adjusted OR 2.94, 95% CI 1.28 to 6.75;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.011), with an optimism-corrected AUC of 0.729 after bootstrap internal validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In ED patients with suspected infection and NEWS2 \u22653, point-of-care TARA identified a prevalent phenotype of reduced LPS-induced TNF-\u03b1 responsiveness, with high sensitivity and low specificity for Sepsis-3, including in patients with low severity scores. This profile is consistent with an adjunctive rather than a stand-alone diagnostic role, requiring further confirmation in multicenter cohorts with broader ED case-mix.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1897997","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:31:55Z","timestamp":1789014715000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Point-of-care LPS-induced TNF-\u03b1 release testing for early sepsis risk stratification in the emergency department"],"prefix":"10.3389","volume":"17","author":[{"given":"Berta","family":"Cister\u00f3","sequence":"first","affiliation":[{"name":"Emergency Department, Hospital Universitari Parc Taul\u00ed, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA)","place":["Sabadell, Spain"]},{"name":"Medicine Department, Universitat Aut\u00f2noma de 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