ArticleAnnals of intensive care2026
Longitudinal measurements of inflammatory mediators in patients at risk of sepsis in the Emergency Department.
Article in Annals of intensive care, 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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Abstract
Sepsis is a complex condition with time‑dependent evolution, and longitudinal biomarker dynamics may improve its characterisation. We hypothesised that biomarker kinetics are associated with sepsis, the intensity of organ dysfunction, and patient survival. This single‑centre, prospective, observational study included adult patients presenting to the Emergency Department with suspected infection and a National Early Warning Score 2 (NEWS2) ≥3. Blood samples were collected at baseline, 4 and 24 h and pro-inflammatory and anti-inflammatory cytokines, chemokines, as well as other inflammatory mediators or acute-phase reactants, were analysed. Linear and nonlinear mixed-effects models assessed associations between biomarker trajectories over time, sepsis diagnosis, and organ dysfunction severity. Joint models evaluated the predictive value of biomarker kinetics during the first 24 h for in‑hospital mortality. Of 214 screened patients, 173 were analysed and 137(79%) developed sepsis. Linear and nonlinear mixed models showed significant time‑dependent decreases in IL10 (β -0.016, 95%CI -0.028 to -0.004), IL1RN (β -0.014, 95%CI -0.024 to -0.004), and IL6 (β -1.021, 95%CI -1.609 to -0.433 for the first spline 0-4 h). Sepsis diagnosis was associated with higher IL1RN (β 0.378, 95%CI 0.153-0.603) and TNFRSF1A (β 0.40, 95%CI 0.21-0.58); a significant interaction between sepsis and time was observed only for IL6 (β -0.33, CI95% -0.653 to-0.007) for the second spline 4-24 h. Increasing SOFA scores correlated with elevated IL10 (β 0.048), IL1RN (β 0.044), CCL2 (β 0.046), TNFRSF1A (β 0.050), and procalcitonin (PCT; β 2.15), all p < 0.01. The SOFA score-time interaction was significant only for IL6 (β 0.122, 95%CI 0.006 to 0.238 during the first spline 0-4 h followed by β -0.080, 95%CI -0.133 to -0.027 for the second spline 4-24 h). Joint survival models adjusted identified associations between longitudinal IL8 (HR 0.655, 95%CrI 0.582-0.728), TNFRSF1A (HR 0.505, 95%CrI 0.419-0.682), and PCT (HR 1.004, 95%CrI 1.001-1.008) concentrations and survival outcome. However, IL8 and TNFRSF1A showed an unexpected inverse association with survival, and the overall discriminatory performance was modest. In conclusion, Sepsis status and organ dysfunction severity were associated with distinct inflammatory biomarker levels and kinetics. IL6 showed a unique time‑dependent relationship, whereas the dynamics of TNFRSF1A, IL8 and PCT showed exploratory associations with survival. Further studies are warranted to confirm our results.
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