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Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.

ABSTRACT: We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients.We 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.We 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.

SUBMITTER: Vanzant EL

PROVIDER: S-EPMC4404112 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.

Vanzant Erin L EL Hilton Rachael E RE Lopez Cecilia M CM Zhang Jianyi J Ungaro Ricardo F RF Gentile Lori F LF Szpila Benjamin E BE Maier Ronald V RV Cuschieri Joseph J Bihorac Azra A Leeuwenburgh Christiaan C Moore Frederick A FA Baker Henry V HV Moldawer Lyle L LL Brakenridge Scott C SC Efron Philip A PA

Critical care (London, England) 20150304

<h4>Introduction</h4>We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.<h4>Methods</h4>We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients.<h4>Results</h4>We found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts. How ...[more]

PMID: 25880307

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Project description:BackgroundChoosing the appropriate endpoint for a trauma hemorrhage control trial can determine the likelihood of its success. Recent Phase 3 trials and observational studies have used 24-h and/or 30-day all-cause mortality as the primary endpoint and some have not used exception from informed consent (EFIC), resulting in multiple failed trials. Five recent high-quality prospective studies among 4,064 hemorrhaging trauma patients provide new evidence to support earlier primary endpoints.MethodsThe goal of this project was to determine the optimal endpoint for hemorrhage control trials using existing literature and new analyses of previously published data.ResultsRecent studies among bleeding trauma patients show that hemorrhagic deaths occur rapidly, at a high rate, and in a consistent pattern. Early preventable deaths among trauma patients are largely due to hemorrhage and the median time to hemorrhagic death from admission is 2.0 to 2.6 h. Approximately 85% of hemorrhagic deaths occur within 6 h. The hourly mortality rate due to traumatic injury decreases rapidly after enrollment from 4.6% per hour at 1 hour postenrollment to 1% per hour at 6 h to <0.1% per hour by 9 h and thereafter. Early primary endpoints (within 6 h) have critically important benefits for hemorrhage control trials, including being congruent with the median time to hemorrhagic death, biologic plausibility, and enabling the use of all-cause mortality, which is definitive and objective.ConclusionsPrimary endpoints should be congruent with the timing of the disease process. Therefore, if a resuscitation/hemorrhage control intervention is under study, a primary endpoint of all-cause mortality evaluated within the first 6 h is appropriate. Before choosing the timing of the primary endpoint for a large multicenter trial, we recommend performing a Phase 2 trial under EFIC to better understand the effects of the hemorrhage control intervention and distribution of time to death. When early primary endpoints are used, patients should be monitored for multiple subsequent secondary safety endpoints, including 24 h and 30-day all-cause mortality as well as the customary safety endpoints.

Project description:BackgroundThe presence of in-house attending trauma surgeons has improved efficiency of processes in the treatment of polytrauma patients. However, literature remains equivocal regarding the influence of the presence of in-house attendings on mortality. In our hospital there is a double trauma surgeon on-call system. In this system an in-house trauma surgeon is 24/7 backed up by a second trauma surgeon to assist with urgent surgery or multiple casualties. The aim of this study was to evaluate outcome in severely injured patients in this unique trauma system.MethodsFrom 2014 to 2021, a prospective population-based cohort consisting of consecutive polytrauma patients aged ≥ 15 years requiring both urgent surgery (≤ 24h) and admission to Intensive Care Unit (ICU) was investigated. Demographics, treatment, outcome parameters and pre- and in-hospital transfer times were analyzed.ResultsThree hundred thirteen patients with a median age of 44 years (71% male), and median Injury Severity Score (ISS) of 33 were included. Mortality rate was 19% (68% due to traumatic brain injury). All patients stayed ≤ 32 min in ED before transport to either CT or OR. Fifty-one percent of patients who needed damage control surgery (DCS) had a more deranged physiology, needed more blood products, were more quickly in OR with shorter time in OR, than patients with early definitive care (EDC). There was no difference in mortality rate between DCS and EDC patients. Fifty-six percent of patients had surgery during off-hours. There was no difference in outcome between patients who had surgery during daytime and during off-hours. Death could possibly have been prevented in 1 exsanguinating patient (1.7%).ConclusionIn this cohort of severely injured patients in need of urgent surgery and ICU support it was demonstrated that surgical decision making was swift and accurate with low preventable death rates. 24/7 Physical presence of a dedicated trauma team has likely contributed to these good outcomes.

Project description:The effect of sex on posttraumatic pathophysiology and outcomes after severe traumatic injury remains debated. We sought to determine the relationship of sex to the genomic and inflammatory responses, and clinical outcomes after hemorrhagic shock.We analyzed blunt trauma patients in hemorrhagic shock from a prospective multi-institutional cohort study to assess for sex-based differences in the genomic response and clinical outcomes. Serially drawn blood samples were analyzed to evaluate peripheral leukocyte genomewide expression and circulating inflammatory mediators at intervals between 0.5 and 28 days after injury. Multivariate logistic regression models were developed to assess the effect of sex on outcomes after controlling for age, injury and shock severity, blood transfusion, and comorbidities.The cohort consisted of 1,285 (67%) male and 643 (33%) female blunt trauma patients. Injury and shock severity were similar between the two groups. There were small but statistically significant differences between males and females regarding their age, body mass index, and 12-hour blood and crystalloid administration. Organ failure was more severe in males, with slower recovery (9.0 vs. 6.5 days) in males compared to females (p < 0.01). However, there were no differences between males and females in plasma levels of IL-6, IL-8, IL-10, IL-1?, tumor necrosis factor alpha, and monocyte chemoattractant protein 1. Multivariate analysis revealed that sex was not a significant independent risk factor for complicated recovery or 28-day mortality. Transcriptomic analysis revealed 333 genes with significant differential expression patterns between males and females (FDR, <0.001), including genes associated with general inflammation, innate immunity, cell adhesion, and cell signaling. None of the former genes were directly associated with sex hormones or X/Y chromosomes.There are sex-specific differences in the leukocyte genomic response to severe injury that are associated with more robust and longer-duration organ dysfunction. However, these expression patterns do not seem to be associated with sex-linked genes or circulating cytokine level differences, and do not translate to worsened sex-specific organ failure outcomes or inpatient mortality.Prognostic/epidemiologic study, level III.

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Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.

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Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.

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