Diagnostic potential of extended inflammation parameters for sepsis identification: a retrospective case-control study

A prediction model combining three different EIPs demonstrated high discrimination in a case-control setting, however this design of comparing ICU sepsis patients to healthy outpatient controls introduces severe spectrum bias characteristic of two-gate studies, which can inflate discrimination metrics significantly when compared with single-gate Emergency Department populations where diagnostic uncertainty is genuine. These results should be considered preliminary exploratory findings only. The extreme spectrum bias inherent to our case-control design means reported performance reflects statistical discrimination in an artificial scenario rather than real-world diagnostic accuracy, with expected ED performance substantially lower (estimated AUC 0.70-0.79). Rigorous prospective validation in consecutive ED patients with suspected infection, including head-to-head comparison with established biomarkers procalcitonin and C-reactive protein, is essential before any clinical consideration.