Histone deactylase gene expression profiles are associated with outcomes in blunt @entity130 XXXX .

@entity1 @entity34268 @entity295 @entity46015 @entity3262 @entity1092 @entity3997 @entity15152 @entity17029 @entity204 @entity130
INTRODUCTION: Treatment with @entity15152 ( @entity15152 ) inhibitors, such as @entity1092 ( @entity3262 ), increase survival in animal models of @entity130 and @entity295 . @entity3262 is a pan-inhibitor that blocks most of the known @entity15152 isoforms. Targeting individual @entity15152 isoforms may increase survival and reduce complications, but little is known of the natural history of @entity15152 gene expression following @entity130 . We hypothesized that distinct @entity15152 isoform gene expression patterns would be associated with differences in outcomes following @entity130 . METHODS: 28 day longitudinal @entity15152 leukocyte gene expression profiles in 172 blunt @entity130 @entity1 were extracted from the Inflammation And Host Response to Injury (Glue Grant) dataset. Outcome was classified as complicated ( @entity204 or no recovery by day 28, n=51) or uncomplicated (n=121). Mixed modeling was used to compare the @entity15152 expression trajectories between the groups, corrected for Injury Severity Score, base deficit, and volume of blood products transfused over the initial 12 hours following admission. Weighted gene correlation network analysis (WGCNA) identified modules of genes with significant co-expression, and @entity15152 genes were mapped to these modules. Biological function of these modules was investigated using the Gene Ontology database. RESULTS: Elevated longitudinal @entity15152 expression trajectories for @entity17029 ,3,6 and 11 were associated with complicated outcomes. In contrast, suppressed expression of Sirtuin (SIRT) 3 was associated with adverse outcome (p<0.01). WGCNA analysis identified significant co-expression of @entity15152 and SIRT genes with genes involved in ribosomal function and downregulation of protein translation in response to stress ( @entity17029 ), T-cell signaling and T-cell selection ( @entity3997 ), as well as coagulation and hemostasis ( @entity34268 ). No co-expression of @entity46015 was identified. CONCLUSION: Expression trajectories of @entity15152 1,3,6,11 and @entity34268 correlate with outcomes following @entity130 , and may potentially serve as biomarkers. They may also be promising targets for pharmacological intervention. The effects of @entity15152 and SIRT gene expression in @entity130 may be mediated through pathways involved in ribosomal and T-cell function as well as coagulation and hemostasis. LEVEL OF EVIDENCE: III STUDY TYPE: Prognostic.
