Observational studyFrontiers in immunology2026
Point-of-care LPS-induced TNF-α release testing for early sepsis risk stratification in the emergency department.
Observational study in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
21 authors.
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Abstract
Background and objective: 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-α responsiveness, characterized the associated clinical outcomes, and assessed the diagnostic accuracy of a point-of-care LPS-induced TNF-α release assay (TARA) for Sepsis-3 adjudicated at 24 h. Methods: In this prospective observational cohort, adults with suspected infection and NEWS2 ≥3 were consecutively enrolled. Whole-blood samples collected at ED arrival (0 h) and 4 h later were stimulated Results: Of the 203 enrolled patients, 180 had valid paired TARA results and 142 fulfilled Sepsis-3 criteria within 24 h. Reduced LPS-induced TNF-α 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 h), 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 <5 and 79.1% (70.8 to 85.6) with qSOFA ≤1. 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; Conclusions: In ED patients with suspected infection and NEWS2 ≥3, point-of-care TARA identified a prevalent phenotype of reduced LPS-induced TNF-α 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.
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