Genetic examinations of trauma, burn victims produce consistent results

Mar 7 2005

A genetic tool with the potential to identify which trauma and burn patients are most likely to become seriously ill has worked consistently in a wide range of experimental clinical settings - an important hurdle to overcome before the method is routinely used in emergency rooms and intensive care units.

In a report published today (March 7) in the Proceedings of the National Academy of Sciences, researchers from eight institutions, including the University of Florida, describe how they were able to consistently analyze which genes are active in patients with serious infections or traumatic injuries.

Researchers want to understand the genetic features that enhance a patient's recovery as well as the elements that cause people to die sometimes weeks after an injury occurs. Identifying those factors could help physicians choose the best treatment, a decision that could mean the difference between life and death, scientists say.

"The vast majority of patients who experience severe trauma or burn injuries actually do well," said Lyle Moldawer, a surgery professor in UF's College of Medicine. "They're resuscitated at the scene, taken to the hospital, have an uneventful recovery and they're discharged. But there's a certain fraction who go on to develop complications that lead to organ failure and death, which is the most common cause of death after traumatic injury - sepsis and multisystem organ failure. So the goal is to use functional genomics as a tool to identify those patients who, after severe trauma and burn injury, will go on to manifest this multisystem organ failure. It's a way to better characterize the nature of the immuno-inflammatory response to trauma."

Ronald G. Tompkins, M.D., a surgeon and biomedical engineer at Massachusetts General Hospital, is leading the effort to develop standard operating procedures for the care of burn and trauma patients and increase understanding of the body's molecular reactions to injury, including inflammation. The lead research author is J. Perren Cobb, M.D., an associate professor of surgery at Washington University in St. Louis.

Traumatic injuries claim hundreds of thousands of lives each year in the United States. In addition, millions of patients are hospitalized, at an annual cost to society of more than $200 billion. Patients may face a long and difficult recovery period riddled with many potentially fatal complications along the way.

"What we have shown is medical professionals can collect blood and tissue samples from patients, process them at different institutions and get consistent results," said Henry Baker, associate director of the UF Genetics Institute and interim chairman of molecular genetics and microbiology. "For any tool used in clinical medicine, it's important that people are able to get the same answers wherever the tool is being used."

Genomic analyses took place at UF, the Stanford Genome Technology Center and Washington University in St. Louis. Overall data analysis was based at Massachusetts General Hospital at Harvard Medical School.

Specially trained clinical personnel sampled whole blood and other available tissues from more than 200 severely traumatized or burned patients and 23 healthy individuals in an effort to correlate molecular markers with white blood cell behavior, and ultimately, with patient outcome. Studies in healthy patients were conducted at UF, Washington University in St. Louis, the University of Rochester School of Medicine and the University of Medicine and Dentistry of New Jersey. Patients with severe traumatic injuries were studied at the University of Washington at Seattle and the University of Rochester.

In the end, scientists could see dramatic changes in genes turning on and off in trauma victims compared with healthy people. Among the trauma patients, researchers say "analytical noise" - differences attributable to the testing method - was not significant, suggesting that profiling gene reactions may provide meaningful information to doctors.

The next step is for scientists to continue the experimental procedures in larger multicenter trials, following hundreds of patients over time to describe the molecular profile of healing in response to burns and traumatic injury, researchers say.