Two patients arrive at the R Adams Cowley Shock Trauma Center on a busy Saturday night. The men, both in their 20s, were injured in the same high-speed car crash and have similar severe traumatic brain injuries (TBI).
The patients receive comparable treatment, but one eventually recovers enough to go home, while the other develops sepsis — a common TBI complication — that leads to his death.
Groundbreaking TBI Study
Researchers at the University of Maryland School of Medicine (UMSOM) and the University of Maryland School of Nursing (UMSON) recently were awarded a three-year, $3.5 million grant from the U.S. Army and Air Force to study why some TBI patients recover and others develop organ failure and sepsis.
TBI is a leading cause of death in the United States, accounting for 50,000 deaths and 235,000 hospitalizations each year. The numbers are especially stark for members of the military. It has been called the “signature injury” of the conflicts in Iraq and Afghanistan, with more than 380,000 diagnoses since 2000, according to the Defense and Veterans Brain Injury Center.
The researchers’ groundbreaking study, titled “Genomics, Microbiomics, and Bioenergetics-Based Personalized Treatment for Head Trauma Patients at Risk for Sepsis,” and soon to be underway at Shock Trauma, aims to identify patients at risk for sepsis using biomarkers that would allow medical staff to intervene early to prevent sepsis and organ failure.
“The gist of the problem is that people come in with severe traumatic brain injury and seem to dichotomize,” explains study co-primary investigator Jennifer Klinedinst, PhD, MPH, MSN, RN, FAHA, associate professor, Organizational Systems and Adult Health, UMSON. “Some of them go down the path of ending up with organ failure and sepsis and some of them don’t, even though on admission they look sort of equivalent. We’re trying to predict who’s going to go down those paths and who’s not by using a lot of different data.”
Researchers will be looking at changes in three biomarkers as potential prognosticators of sepsis development: blood cell gene expression, blood cell energy metabolism, and the gut microbiome.
“This study will put us in a much better position to give personalized critical care,” says co-primary investigator Gary Fiskum, PhD, the M. Jane Matjasko Professor for Research and vice chair for research, Department of Anesthesiology, UMSOM. “Not all people are the same, and by using these biomarkers, we’ll be able to say we need this particular drug that will improve the energy metabolism in cells, or we’re going to use this particular yogurt probiotic that may make the gut microbiome change from an unhealthy one to a healthy one.”
In addition to Fiskum and Klinedinst, co-investigators include Claire M. Fraser, PhD, Dean’s Endowed Professor and director, Institute for Genome Sciences, UMSOM; Rosemary A. Kozar, MD, PhD, professor and director of translational research, Shock Trauma; and Catriona Miller, PhD, director of research initiatives, Center for the Sustainment of Trauma and Readiness Skills (C-STARS), Shock Trauma; and Deborah Stein, MD, MPH, FACS, FCCM, former chief of trauma, Shock Trauma.
Klinedinst says the scope of the study would be impossible without the expertise of the co-investigators. “This is a very team-based effort,” she says. “There is no way to make this happen without these key players.”
Fiskum agrees. “By using the Institute for Genome Sciences, by using the School of Medicine, by using clinical input from Dr. Kozar at the Shock Trauma Center, it’s a much stronger study than if we used just one,” he says. “It wouldn’t give us nearly as much information.”
Fiskum also noted the importance of Shock Trauma. “There would be no study whatsoever if Shock Trauma wasn’t on board,” he adds. The research will be conducted within C-STARS and administered by the Center for Shock, Trauma and Anesthesiology Research (STAR).
Shock Trauma is an ideal facility to conduct the study because of the large number of TBI patients admitted per year — more than 500, according to Fiskum.
Beginning this fall, patients between the ages of 18 and 65 who are admitted to Shock Trauma and diagnosed with TBI will be recruited by nurses and research staff to participate in the study. Stool and blood samples will be taken on admission and at regular intervals for seven days.
The information gathered from the samples, as well as the clinical data from the patient, ultimately will be used to determine which patients are more likely to develop sepsis. “The goal is to intervene early,” Klinedinst explains.
She continues, “For example, if it’s a microbiome diversity issue, we could potentially give them a fecal transplant to stop them from getting septic. If it’s a bioenergetics issue, we can give them antioxidants. If it’s a genomic issue, we’ll look at those pathways and see what it is and that will determine a potential intervention. Is it an immune pathway? Is it an inflammation pathway? Is it an energy crisis?”
The first-of-its-kind study has the potential to improve outcomes for thousands of patients suffering from severe TBI. “If we can figure out why some patients transition to sepsis and others don’t, we can dramatically improve treatments and lives,” Fiskum says.