Transforming research to improve therapies for trauma in the twenty-first century

Abstract

Improvements have been made in optimizing initial care of trauma patients, both in prehospital systems as well as in the emergency department, and these have also favorably affected longer term outcomes. However, as specific treatments for bleeding are largely lacking, many patients continue to die from hemorrhage. Also, major knowledge gaps remain on the impact of tissue injury on the host immune and coagulation response, which hampers the development of interventions to treat or prevent organ failure, thrombosis, infections or other complications of trauma. Thereby, trauma remains a challenge for intensivists. This review describes the most pressing research questions in trauma, as well as new approaches to trauma research, with the aim to bring improved therapies to the bedside within the twenty-first century.

Transforming research to improve therapies for trauma in the twenty-first century: an alternative perspective

“…Instead of looking into the future from where we stand today, we move the needle into the future and reflect backwards. We agree with Juffermans and colleagues that specific treatments for bleeding are largely lacking [ 1 ], however, they fail to delve deeper. Why are there so few safe and effective drugs to treat hemorrhage, traumatic brain injury or burn trauma?…”

“…We read with interest the perspective of Juffermans and colleagues on transforming research to improve therapies for trauma care in the twenty-first century [ 1 ]. We would like to offer a different perspective.…”

“…Candidate therapies listed in Table 3 in Juffermans’ manuscript [ 1 ] are largely single-nodal target therapies. Single-nodal or branch-point targets fail to appreciate the complexity of the system.…”

“…A second major reason for lack of trauma drug breakthroughs is the choice of animal model and its suitability for future clinical translation. Although animal models were discussed in Juffermans’ review [ 1 ] there was no discussion on specific-pathogen free (SPF) animals. If the research goal is to examine a particular mechanism or pathway, the use of SPF animals may be the right choice.…”

“…Similarly, Rosshart and colleagues showed SPF-type mice reconstituted with natural microbiota exhibited reduced inflammation and increased survival following influenza virus infection, and they showed improved resistance against colorectal tumorigenesis [ 13 , 14 ]. Finally, as discussed by Juffermans and colleagues, there are other reasons for why so few drugs translate from animals to humans, including poor clinical trial design, patient selection, and many other factors [ 1 ].…”