title: Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma.
abstract: BACKGROUND
  We recently proffered that a new syndrome persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has replaced late multiple-organ failure as a predominant phenotype of chronic critical illness. Our goal was to validate this by determining whether severely injured trauma patients with complicated outcomes have evidence of PICS at the genomic level.
  
  
  METHODS
  We performed a secondary analysis of the Inflammation and Host Response to Injury database of adults with severe blunt trauma. Patients were classified into complicated, intermediate, and uncomplicated clinical trajectories. Existing genomic microarray data were compared between cohorts using Ingenuity Pathways Analysis. Epidemiologic data and outcomes were also analyzed between cohorts on admission, Day 7, and Day 14.
  
  
  RESULTS
  Complicated patients were older, were sicker, and required increased ventilator days compared with the intermediate/uncomplicated patients. They also had persistent leukocytosis as well as low lymphocyte and albumin levels compared with uncomplicated patients. Total white blood cell leukocyte analysis in complicated patients showed that overall genome-wide expression patterns and those patterns on Days 7 and 14 were more aberrant from control subjects than were patterns from uncomplicated patients. Complicated patients also had significant down-regulation of adaptive immunity and up-regulation of inflammatory genes on Days 7 and 14 (vs. magnitude in fold change compared with control and in magnitude compared with uncomplicated patients). On Day 7, complicated patients had significant changes in functional pathways involved in the suppression of myeloid cell differentiation, increased inflammation, decreased chemotaxis, and defective innate immunity compared with uncomplicated patients and controls. Subset analysis of monocyte, neutrophil, and T-cells supported these findings.
  
  
  CONCLUSIONS
  Genomic analysis of patients with complicated clinical outcomes exhibit persistent genomic expression changes consistent with defects in the adaptive immune response and increased inflammation. Clinical data showed persistent inflammation, immunosuppression, and protein depletion. Overall, the data support the hypothesis that patients with complicated clinical outcomes are exhibiting PICS.
  
  
  METHODS
  Epidemiologic study, level III.
authors.affiliation: From the Departments of Surgery (E.L.V., R.U., R.D., A.G.C., L.F.G., D.C.N., A.L.C., J.L., B.M., L.L.M., F.A.M., P.A.E.), Molecular Genetics and Microbiology (C.M.L., H.V.B.), and Anesthesia (T.O-B., A.B.), and Institute on Aging (C.L.), University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Vanzant
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lopez
authors.forename: Tezcan
authors.initials: T
authors.lastname: Ozrazgat-Baslanti
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ungaro
authors.forename: Ruth
authors.initials: R
authors.lastname: Davis
authors.forename: Alex G
authors.initials: AG
authors.lastname: Cuenca
authors.forename: Lori F
authors.initials: LF
authors.lastname: Gentile
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Angela L
authors.initials: AL
authors.lastname: Cuenca
authors.forename: Azra
authors.initials: A
authors.lastname: Bihorac
authors.forename: Christiaan
authors.initials: C
authors.lastname: Leeuwenburgh
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lanz
authors.forename: Henry V
authors.initials: HV
authors.lastname: Baker
authors.forename: Bruce
authors.initials: B
authors.lastname: McKinley
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Moore
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D015601:Injury Severity Score; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D014949:Wounds, Nonpenetrating / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult