Life science
Medicine & healthcare, Bioinformatics

Development of approaches to promote personalized
medicine in trauma care
Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine
Specially Appointed Assistant Professor Jotaro Tachino

https://researchmap.jp/jotarotachino?lang=en

Specially Appointed Assistant Professor Hisatake Matsumotohttps://researchmap.jp/38283828?lang=en

Life science

Abstract
This research aims to provide personalized medicine of trauma care byidentifying potential subgroups in multiple trauma, which are complicatedby factors such as age, sex and pre-existing medical conditions. Traditional studies have not accounted for the heterogeneity of trauma patients.
This research used machine learning on the Japan Trauma Data Bank
to create a model that identifies individualized trauma patterns (traumaphenotypes) and performed proteomic profiles to evaluate the biologicalcharacteristics of high-mortality phenotypes.

▍ Background & Results
Despite the standardization of trauma care globally, there are still approximately 4.5 million trauma-related deaths annually, posing a significant
challenge. The pathophysiological importance of coagulation-fibrinolysis
and immune responses in trauma is well-known, but their clinical application as treatment targets remains limited. This complexity arises from thecombination of patient background and the nature and extent of injuries.
Previous studies have indicated that the combination of injured organs inpolytrauma can affect patient outcomes and potentially indicate a risk oftrauma death (J. Tachino et al. J Trauma Acute Care Surg. 2021).
Our research aimed to develop novel approaches to trauma care byidentifying potential subgroups (phenotypes) in heterogeneous trauma
patients using machine learning, followed by pathophysiological analysis.
Proteomic analysis using patient serum (mass spectrometry) was performed for this purpose.

The study analyzed data from 71,038 blunt trauma patients in the JTDB,
identifying eight trauma phenotypes. One phenotype exhibited a highmortality rate of about 50%. Latent class analysis further subdivided thisphenotype into four subtypes (α to δ): “α represented younger patientswith polytrauma”, “β involved head injuries with low body temperature”,“γ was seen in elderly patients with severe head injuries” and “δ characterized polytrauma patients with a higher actual mortality rate thanpredicted”. Subsequently, this phenotyping was applied to 90 patients at
the Osaka University Advanced Critical Care Center, and serum proteomic
profile was performed. The high-mortality phenotype showed enhanced
acute inflammatory response, dysregulation in the complement activation
pathway, and reduced regulation in coagulation and platelet degranulation
pathways, indicating coagulopathy.

▍ Significance of the research and Future perspective
This research is significant in two main points. First, it utilizes early trauma care data to identify clinical states with high mortality, allowing for theidentification of populations for early intervention, leading to potential revisions and development of new treatment strategies. Second, the molecularpathology of phenotypes derived from proteomic analysis identifies coagulation disorders and excessive inflammation in high-mortality phenotypes.
These findings may lead to breakthroughs in new trauma care strategies
and drug development. Currently, an application is being developed toidentify trauma phenotypes in real-time. Future developments aim to integrate this system with electronic health records and diagnostic imaging,facilitating natural identification of phenotypes during clinical care.

P a t e n t Japanese Patent Application No.2022-009695, No.2023-120246
Tachino, Jotaro; Matsumoto, Hisatake et al. Development of clinical phenotypes and biological profiles via proteomic analysis of trauma patients. CriticalCare. 2022, 26, 241. doi: 10.1186/s13054-022-04103-z
Tr e a t i s e
Tachino, Jotaro; Katayama, Yusuke et al. Assessment of the interaction effect between injury regions in multiple injuries: A nationwide cohort study inJapan. J. Trauma Acute Care Surg. 2021, 90(1), 185-190. doi: 10.1097/TA.0000000000002969
UR
L https://www.med.osaka-u.ac.jp/eng/activities/results/2022year/matsumoto2022-08-10
K e y w o r d trauma, phenotype, inflammatory response, personalized medicine