Clinical Comparator Dependence of Inflammatory and Hematologic Biomarker Discrimination for Sepsis: A Matched Retrospective Study Using MIMIC-IV Emergency Department Data
- 1Departamento de Patología Clínica, Facultad de Medicinay Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey 64460, Nuevo León, Mexico
Abstract
Background: The diagnostic performance of sepsis biomarkers may vary according to the clinical comparator population. We evaluated 11 routinely available inflammatory and hematologic biomarkers in two matched diagnostic settings. Methods: We conducted a retrospective observational study using linked MIMIC-IV, MIMIC-IV-ED, and MIMIC-IV-Note data. Adult emergency department episodes were classified as sepsis, suspected infection without sepsis, or controls without suspected infection. Comparison-specific profile matching retained the same 525 sepsis episodes in both analyses, together with 214 controls without suspected infection and 315 episodes with suspected infection without sepsis. Biomarker discrimination was assessed using area under the receiver operating characteristic curve (AUROC) with DeLong inference. Results: Against controls without suspected infection, C-reactive protein (CRP) had the highest AUROC (0.786; 95% CI, 0.748–0.823), followed by absolute lymphocyte count (0.654; 0.613–0.696) and the neutrophil-to-lymphocyte ratio (NLR; 0.636; 0.594–0.677). Against suspected infection without sepsis, absolute lymphocyte count had the highest AUROC (0.677; 0.641–0.714), followed by NLR (0.626; 0.588–0.664), whereas CRP discrimination decreased to 0.555 (0.514–0.595). The cross-setting difference for CRP was 0.231 (95% CI, 0.183–0.278; Holm-adjusted p <0.001). Sensitivity analyses produced similar qualitative findings. Conclusions: Biomarker discrimination for sepsis varied according to the clinical comparator population, with the magnitude of cross-setting change differing across biomarkers. CRP showed the largest change, whereas absolute lymphocyte count retained modest discrimination in both settings. These findings emphasize the importance of interpreting biomarker performance within clinically relevant diagnostic contrasts.
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BibTeX
@article{sanchezvela2026clinical,
title = {{Clinical Comparator Dependence of Inflammatory and Hematologic Biomarker Discrimination for Sepsis: A Matched Retrospective Study Using MIMIC-IV Emergency Department Data}},
author = {Salvador Sánchez-Vela and Jorge Martín Llaca-Díaz and Erik Alejandro Díaz-Chuc and Erik Alejandro San Miguel-Garay and Sergio Ayala-De la Cruz},
journal = {Journal of Clinical Medicine},
year = {2026},
month = nov,
doi = {10.3390/jcm15218489},
url = {https://www.mdpi.com/2077-0383/15/21/8489},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical Comparator Dependence of Inflammatory and Hematologic Biomarker Discrimination for Sepsis: A Matched Retrospective Study Using MIMIC-IV Emergency Department Data
AU - Salvador Sánchez-Vela
AU - Jorge Martín Llaca-Díaz
AU - Erik Alejandro Díaz-Chuc
AU - Erik Alejandro San Miguel-Garay
AU - Sergio Ayala-De la Cruz
PY - 2026
DA - 2026/11/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15218489
UR - https://www.mdpi.com/2077-0383/15/21/8489
AB - Background: The diagnostic performance of sepsis biomarkers may vary according to the clinical comparator population. We evaluated 11 routinely available inflammatory and hematologic biomarkers in two matched diagnostic settings. Methods: We conducted a retrospective observational study using linked MIMIC-IV, MIMIC-IV-ED, and MIMIC-IV-Note data. Adult emergency department episodes were classified as sepsis, suspected infection without sepsis, or controls without suspected infection. Comparison-specific profile matching retained the same 525 sepsis episodes in both analyses, together with 214 controls without suspected infection and 315 episodes with suspected infection without sepsis. Biomarker discrimination was assessed using area under the receiver operating characteristic curve (AUROC) with DeLong inference. Results: Against controls without suspected infection, C-reactive protein (CRP) had the highest AUROC (0.786; 95% CI, 0.748–0.823), followed by absolute lymphocyte count (0.654; 0.613–0.696) and the neutrophil-to-lymphocyte ratio (NLR; 0.636; 0.594–0.677). Against suspected infection without sepsis, absolute lymphocyte count had the highest AUROC (0.677; 0.641–0.714), followed by NLR (0.626; 0.588–0.664), whereas CRP discrimination decreased to 0.555 (0.514–0.595). The cross-setting difference for CRP was 0.231 (95% CI, 0.183–0.278; Holm-adjusted p <0.001). Sensitivity analyses produced similar qualitative findings. Conclusions: Biomarker discrimination for sepsis varied according to the clinical comparator population, with the magnitude of cross-setting change differing across biomarkers. CRP showed the largest change, whereas absolute lymphocyte count retained modest discrimination in both settings. These findings emphasize the importance of interpreting biomarker performance within clinically relevant diagnostic contrasts.
SN - 2077-0383
ER -