Metabolomics and Precision Medicine in Trauma: The State of the Field

Abstract

Trauma is a major problem in the United States. Mortality from trauma is the number one cause of death under the age of 45 in the United States and is the third leading cause of death for all age groups. There are approximately 200,000 deaths per year due to trauma in the United States at a cost of over $671 billion in combined healthcare costs and lost productivity. Unsurprisingly, trauma accounts for approximately 30% of all life-years lost in the United States. Due to immense development of trauma systems, a large majority of trauma patients survive the injury, but then go on to die from complications arising from the injury. These complications are marked by early and significant metabolic changes accompanied by inflammatory responses that lead to progressive organ failure and, ultimately, death. Early resuscitative and surgical interventions followed by close monitoring to identify and rescue treatment failures are key to successful outcomes. Currently, the adequacy of resuscitation is measured using vital signs, noninvasive methods such as bedside echocardiography or stroke volume variation, and other laboratory endpoints of resuscitation, such as lactate and base deficit. However, these methods may be too crude to understand cellular and subcellular changes that may be occurring in trauma patients. Better diagnostic and therapeutic markers are needed to assess the adequacy of interventions and monitor responses at a cellular and subcellular level and inform clinical decision-making before complications are clinically apparent. The developing field of metabolomics holds great promise in the identification and application of biochemical markers toward the clinical decision-making process.

A prospective pilot study using metabolomics discloses specific fatty acid, catecholamine and tryptophan metabolic pathways as possible predictors for a negative outcome after severe trauma

“…The presented results highlight the usefulness of metabolomic approaches in the characterization of pathophysiological events after severe trauma, as suggested by previous reviews [11]. To the best of our knowledge, this is one the first reports using untargeted liquid chromatography coupled to mass spectrometry (LC-MS) in plasma for a non-favorable outcome in a severe trauma population.…”

“…Globally, despite there have been previous reports on the use of metabolomics in acute trauma care in the intensive care unit, these have been often restricted to the TBI context and/or non-chromatographic techniques (reviewed in [11]). To overcome these limitations, in the present work we have analyzed the metabolomic profiles of severe trauma patients admitted to an ICU, by comparing the early metabolomicprofiles of those patients who survived the trauma versus the ones belonging to non-survivors.…”

Metabolic Syndrome: Major Risk Factor for Morbidity and Mortality in Severely Injured Trauma Patients

“…By identifying unique molecular characteristics of a person with MetS at the time of initial trauma, clinicians at the point of care may eventually be able to predict an individual's clinical course, facilitating more timely, individualized treatment, ultimately improving outcomes. 21 Our study has several limitations. Because many patients in our registry did not have triglyceride or cholesterol levels drawn routinely, waist-to-hip ratios measured, or complete urinalyses collected, we identified MetS by selecting patients with known type 2 diabetes, BMI 30 kg/m 2 , and a history of hypertension requiring medication.…”

Risk stratification of allogeneic stem cell recipients with respect to the potential for development of GVHD via their pre-transplant plasma lipid and metabolic signature

“…The strategy used in our study to enable this goal investigated the plasma metabolome and lipidome to profile SCT patients. This approach resulted in the generation of complex and multidimensional data that required the use of multivariate statistical approaches to decrease dimensional space, a common approach in metabolomic and lipidomic studies 34,35 . The predictors and potential biomarkers of GVHD found in the plasma of patients pre-transplant indicate that the metabolic profile prior to bone marrow transplant is a major influence in their clinical course following transplantation and can be used to correlate immune and metabolic phenotype.…”