Introduction The effect of gender on post-traumatic pathophysiology and outcomes after severe traumatic injury remains debated. We sought to determine the relationship of gender to the genomic and inflammatory responses, and clinical outcomes after hemorrhagic shock. Methods We analyzed blunt trauma patients in hemorrhagic shock from a prospective, multi-institutional cohort study to assess for gender based differences in the genomic response and clinical outcomes. Serially drawn blood samples were analyzed to evaluate peripheral leukocyte genome-wide 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 gender on outcomes after controlling for age, injury and shock severity, blood transfusion, and comorbidities. Results 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, BMI, 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-1β, TNF-α and MCP-1. Multivariate analysis revealed that gender 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. Conclusion There are gender-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 appear to be associated with sex-linked genes or circulating cytokine level differences, and do not translate to worsened gender-specific organ failure outcomes or inpatient mortality.
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