Prediction of Multiple Infections After Severe Burn Trauma

In Brief Objective: To develop predictive models for early triage of burn patients based on hypersusceptibility to repeated infections. Background: Infection remains a major cause of mortality and morbidity after severe trauma, demanding new strategies to combat infections. Models for infection prediction are lacking. Methods: Secondary analysis of 459 burn patients (≥16 years old) with 20% or more total body surface area burns recruited from 6 US burn centers. We compared blood transcriptomes with a 180-hour cutoff on the injury-to-transcriptome interval of 47 patients (≤1 infection episode) to those of 66 hypersusceptible patients [multiple (≥2) infection episodes (MIE)]. We used LASSO regression to select biomarkers and multivariate logistic regression to built models, accuracy of which were assessed by area under receiver operating characteristic curve (AUROC) and cross-validation. Results: Three predictive models were developed using covariates of (1) clinical characteristics; (2) expression profiles of 14 genomic probes; (3) combining (1) and (2). The genomic and clinical models were highly predictive of MIE status [AUROCGenomic = 0.946 (95% CI: 0.906–0.986); AUROCClinical = 0.864 (CI: 0.794–0.933); AUROCGenomic/AUROCClinicalP = 0.044]. Combined model has an increased AUROCCombined of 0.967 (CI: 0.940–0.993) compared with the individual models (AUROCCombined/AUROCClinicalP = 0.0069). Hypersusceptible patients show early alterations in immune-related signaling pathways, epigenetic modulation, and chromatin remodeling. Conclusions: Early triage of burn patients more susceptible to infections can be made using clinical characteristics and/or genomic signatures. Genomic signature suggests new insights into the pathophysiology of hypersusceptibility to infection may lead to novel potential therapeutic or prophylactic targets. Early genomic signature and clinical characteristics of 113 burn patients were used paradigmatically to build 3 novel predictive models of multiple, repeated infections in burn trauma, which could facilitate early triage of traumatically injured burn patients to prevent or treat sepsis. Genomic signature suggests new mechanistic aspects of hypersusceptibility to infections.