Vanessa Stein

Background: Acute infections and sepsis are a leading cause of death. These patients are primarily encountered at the emergency department (ED), where early assessment for sepsis is necessary to improve outcome. In sepsis, the inflammatory response causes several characteristic pathophysiological changes, including a dysregulated and generalized activation of the endothelium. This study aimed to analyze endothelial markers released to the blood as diagnostic biomarkers for acute infection and sepsis in the ED, as smaller studies have previously shown promising results in other settings. Methods: Serum samples from n = 312 adult patients with suspected acute infections at presentation to the ED were utilized. Patients’ courses of disease and outcomes were assessed by clinical adjudication. E-selectin, P-selectin, ICAM-1, and VCAM-1 were measured by ELISAs. The accuracy of each marker for predicting bacterial infection, sepsis, and in-hospital mortality was evaluated. Results: For sepsis, E-selectin and ICAM-1 both showed an area under the receiver operating characteristic (AUROC) of 0.62, lower than procalcitonin with 0.77 (both P < 0.01) and lactate with 0.73 (P = 0.030 and 0.046, respectively), but similar to CRP with 0.60 (P = 0.758 and 0.876, respectively). For 28-day in-hospital mortality among patients with infection, ICAM-1 performed best with an AUROC of 0.75. Conclusions: Despite promising results in small studies and specific cohorts, particularly in intensive care units, this large-scale evaluation of four endothelial biomarkers highlights their limited diagnostic utility in a broader inclusion setup design at the earliest possible time point of evaluation.