Admission immune-inflammatory biomarker profiles for trauma severity stratification: an externally validated machine learning study

Traumatic injury induces rapid systemic immune-inflammatory alterations, but whether routinely measurable admission biomarkers can provide an early biological estimate of anatomical injury burden remains uncertain. This study aimed to characterize trauma-associated immune-inflammatory profiles across trauma severity levels defined by injury severity score (ISS) and evaluate their combined value for early severity stratification.

This two-center retrospective study included healthy participants as a physiological reference group, non-trauma acute-care patients as a clinically relevant comparator, and trauma patients classified as mild (ISS <16), moderate (ISS 16-25), or severe (ISS >25). Nineteen admission laboratory biomarkers and demographic variables were evaluated in a development cohort of 775 participants and an independent external validation cohort of 349 participants. Multinomial least absolute shrinkage and selection operator regression was used to identify severity-associated biomarkers. Ten classifiers were compared on the same predefined trauma-only development split, and the selected model was evaluated in an independent external trauma cohort.

A 10-feature panel was retained following feature selection and collectively defined an immune-inflammatory profile associated with increasing trauma severity. Increasing injury burden was associated with heterogeneous and partly nonlinear inflammatory and hematologic alterations, including changes in neutrophil-related indices, lymphocyte-related measures, and albumin. The multinomial logistic regression model achieved the best overall performance, with an accuracy of 0.941 and 0.973 in the internal holdout and external validation cohorts, respectively, with an external macro-AUC of 0.993. Model interpretation consistently identified neutrophil count and RDW-CV as major contributors to severity stratification.

Admission-stage blood biomarkers capture reproducible immune-inflammatory alterations associated with increasing anatomical injury severity. Their combined analysis may provide a complementary approach for early biological assessment of injury burden and supports further investigation of clinically accessible biomarkers of trauma-associated immune-inflammatory dysregulation.