Journal Article

Development of clinical phenotypes and biological profiles via proteomic analysis of trauma patients

Tachino, Jotaro, Togami, Yuki, Ogura, Hiroshi, Matsumoto, Hisatake, Nakagawa, Yuko, Kojima, Takashi, Seno, Shigeto, Sugihara, Fuminori, Okuzaki, Daisuke, Kitamura, Tetsuhisa, Komukai, Sho, Katayama, Yusuke, Kido, Yoshiyuki

2022

Overview

Background Trauma is a heterogeneous condition, and specific clinical phenotypes may identify target populations that could benefit from certain treatment strategies. In this retrospective study, we determined clinical phenotypes and identified new target populations of trauma patients and their treatment strategies. Methods We retrospectively analyzed datasets from the Japan Trauma Data Bank and determined trauma death clinical phenotypes using statistical machine learning techniques and evaluation of biological profiles. Results The analysis included 71,038 blunt trauma patients [median age, 63 (interquartile range [IQR], 40–78) years; 45,479 (64.0%) males; median Injury Severity Score, 13 (IQR, 9–20)], and the derivation and validation cohorts included 42,780 (60.2%) and 28,258 (39.8%) patients, respectively. Of eight derived phenotypes (D-1–D-8), D-8 ( n  = 2178) had the highest mortality (48.6%) with characteristic severely disturbed consciousness and was further divided into four phenotypes: D-8α, multiple trauma in the young ( n  = 464); D-8β, head trauma with lower body temperature ( n  = 178); D-8γ, severe head injury in the elderly ( n  = 957); and D-8δ, multiple trauma, with higher predicted mortality than actual mortality ( n  = 579). Phenotype distributions were comparable in the validation cohort. Biological profile analysis of 90 trauma patients revealed that D-8 exhibited excessive inflammation, including enhanced acute inflammatory response, dysregulated complement activation pathways, and impaired coagulation, including downregulated coagulation and platelet degranulation pathways, compared with other phenotypes. Conclusions We identified clinical phenotypes with high mortality, and the evaluation of the molecular pathogenesis underlying these clinical phenotypes suggests that lethal trauma may involve excessive inflammation and coagulation disorders.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Blood clotting disorders / Care and treatment / Causes of / Clustering / Critical care / Critical Care Medicine / Datasets / Diagnosis / Emergency Medicine / Genotype & phenotype / Inflammation / Inflammatory response / Intensive / Machine learning / Mass spectrometry / Medicine / Medicine & Public Health / Methods / Mortality / Pathology / Pathophysiology / Patients / Personalized medicine / Personalized medicine in the ICU / Phenotype / Precision medicine / Reproducibility / Risk factors / Scientific imaging / Services / Supercomputers / Trauma / Trauma care / Trauma centers