High rates of long-term PTSD persist after major trauma in adolescents. Injury events such as perceived threat to life and control over the event are strongly associated with PTSD risk. Prolonged PTSD severely impacts QoL outcomes. Early identification and treatment of risk factors for long-term PTSD will be important to improve outcomes in injured adolescents.
We identified fresh human leukocytes as an abundant source of the candidate epithelial tumor suppressor gene, Ecrg4, an epigenetically regulated gene, which unlike other tumor suppressor genes, encodes an orphan-secreted, ligand-like protein. In human cell lines, Ecrg4 gene expression was low, Ecrg4 protein undetectable, and Ecrg4 promoter hypermethylation high (45-90%) and reversible by the methylation inhibitor 5-AzaC. In contrast, Ecrg4 gene expression in fresh, normal human PBMCs and PMNs was 600-800 times higher than in cultured cell lines, methylation of the Ecrg4 promoter was low (<3%), and protein levels were readily detectable in lysates and on the cell surface. Flow cytometry, immunofluorescent staining, and cell surface biotinylation established that full-length, 14-kDa Ecrg4 was localized on PMN and monocyte cell surfaces, establishing that Ecrg4 is a membrane-anchored protein. LPS treatment induced processing and release of Ecrg4, as detected by flow and immunoblotting, whereas an effect of fMLF treatment on Ecrg4 on the PMN cell surface was detected on the polarized R2 subpopulation of cells. This loss of cell surface Ecrg4 was associated with the detection of intact and processed Ecrg4 in the conditioned media of fresh leukocytes and was shown to be associated with the inflammatory response that follows severe, cutaneous burn injury. Furthermore, incubation of macrophages with a soluble Ecrg4-derived peptide increased the P-p65, suggesting that processing of an intact sentinel Ecrg4 on quiescent circulating leukocytes leads to processing from the cell surface following injury and macrophage activation.
This study demonstrates that US can be obtained rapidly, integrated into the resuscitation, and completed quickly. US provides a highly accurate, noninvasive method to evaluate the abdomen in the blunt trauma patient, and has supplanted the previously used methods at this institution.
Major trauma in adolescents is associated with significant and marked deficits in long-term QoL outcomes, compared with U.S. norms for healthy adolescents. Early identification and treatment of risk factors for poor long-term QoL outcomes must become an integral component of trauma care in mature trauma care systems.
A combination of three independent injury data sources generated a composite data set of serious and fatal injury. This regional injury analysis was the most comprehensive overview of injury in our region. Important observations included the following: there has been no change in the overall incidence of severe injury within our county; the incidence of fatal traumatic injury has significantly decreased; the leading causes of nonfatal injury do not correlate with the rank order of fatal injury; intentional injury was the leading cause of injury deaths; and scene fatalities represent a poorly studied group of patients who may benefit from primary prevention and injury control research.
Adolescent trauma survivors have high rates of ASD. ASD severely impacts QoL outcomes and is associated with female sex and mechanism of injury in adolescents. Early recognition and treatment of ASD in seriously injured adolescents will improve QoL outcomes.
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