M. Bishawi1,2, B. Johnston1,2, C. Almond1,2, L. Stempora1,2, D. Bowles1, A. T. Limkakeng1,2, J. Cheeseman1,2, E. Elster2,3,4, A. Kirk1,2 1Duke University Medical Center,Surgery,Durham, NC, USA 2Uniformed Services University (USU) Surgical Critical Care Initiative (SC2i),Bethesda, MD, USA 3Walter Reed National Military Medical Center,Bethesda, MD, USA 4Uniformed Services University of the Health Sciences,Bethesda, MD, USA
Introduction: The caspase family of cysteine proteases play an essential role in the signaling pathways associated with apoptosis and inflammation. Circulating caspase activity levels may be an early indicator of overall cell death and inflammatory system activation in injured military personnel. We hypothesized that circulating caspase activity levels may correlate with injury severity in trauma patients, and early changes in these levels may predict short term patient outcomes.
Methods: This was an exploratory pilot sub study from the SC2i initiative. Longitudinal plasma samples derived from 11 trauma patients were used. The patients were divided into two groups based on their short term outcomes. Group A had an overall benign hospital stay, and group B were patients having a prolonged hospital stay with significant post injury morbidity and mortality. Caspase activities in all available plasma samples were measured using a commercially available bioluminescent assay kit (Promega Corporation Maddison WI). Caspase activity level data were then merged with and compared to clinical data obtained in a prospectively maintained study database.
Results:Group A patients (n=5) trended to be younger (36.2±21 vs. 58.7±18, p=0.117), had a trend of a higher presenting GCS score (14.6±0.9 vs. 10.2±5.7, p=0.113), and had a lower expanded ISS score (25.2±11 vs. 43.5±14 p=0.03) as compared to Group B patients (n=6). Overall hospital length of stay was also shorter for Group A patients (4.5±1.9 vs. 33.7±23.7, p=0.03), as well as ICU length of stay (0.5±1 vs. 24.6±19, p=0.03). All group A patients were discharged home compared to none of group B patients (p<0.01). In-hospital mortality was significantly higher for Group B patients (67% vs. 0%, p<0.01). Caspase activity levels were similar between the groups early after injury, but significantly increased in group B patients over time while remining unchanged for group A patients. (Figure)
Conclusion:In this pilot study, circulating caspase activity levels significantly increased in severely injured patients that experienced substantial midterm morbidity and mortality. A larger study including more patients to further explore the utility of caspase activity measurements in risk stratification for injured personnel is warranted. If confirmed, caspase activity measurements may become an important biomarker that will help in post injury patient care and resource utilization to further improve outcomes.
