Abstract
IntroductionWe wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.MethodsWe performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients.ResultsWe found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts. However, aged patients had more comorbidities. Advanced age was associated with more severe organ failure, infectious complications, ventilator days, and intensive care unit length of stay, as well as, an increased likelihood of being discharged to skilled nursing or long-term care facilities. Additionally, advanced age was an independent predictor of a complicated recovery and 28-day mortality. Acutely after trauma, blood neutrophil genome-wide expression analysis revealed an attenuated transcriptomic response as compared to the young; this attenuated response was supported by the patients’ plasma cytokine and chemokine concentrations. Later, these patients demonstrated gene expression changes consistent with simultaneous, persistent pro-inflammatory and immunosuppressive states.ConclusionsWe concluded that advanced age is one of the strongest non-injury related risk factors for poor outcomes after severe trauma with hemorrhagic shock and is associated with an altered and unique peripheral leukocyte genomic response. As the general population’s age increases, it will be important to individualize prediction models and therapeutic targets to this high risk cohort.
Highlights
We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock
When comparing clinical outcomes among other risk factors, age >55 years was associated with significantly higher multiple organ failure (MOF) scores, longer ICU length of stay (LOS), increased ventilator days, and higher rates of both noninfectious and infectious complications (Table 1)
We have found that advanced age is one of the greatest predictors of poor clinical outcomes after severe blunt traumatic injury with hemorrhagic shock, and that advanced aging is associated with a unique genomic expression pattern in circulating neutrophils (Figure 6)
Summary
We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock. The Inflammation and the Host Response to Injury Collaborative Program Trauma Glue Grant (GG) was a prospective, multi-institutional observational study with the primary aims of describing the epidemiology, proteomic, and leukocyte genomic response in severely injured burn and trauma patients [5]. The latter consisted of patients who had suffered blunt trauma and who were in hemorrhagic shock without evidence of severe traumatic brain injury (TBI). Patients who exhibited a complicated clinical trajectory, defined as greater than fourteen days of persistent organ dysfunction or death, had exacerbation and prolongation of their transcriptomic response, and failure to return to baseline expression patterns [6]. A rapid genomic composite score was developed, using 63 select genes, which determine within 12 to 24 hours of injury those patients who are destined to have a complicated clinical trajectory [8,9]
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