title: Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.
abstract: BACKGROUND
  We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.
  
  
  METHODS
  We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. erin.vanzant@surgery.ufl.edu.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Vanzant
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. rhilton@ufl.edu.
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Hilton
authors.affiliation: Department of Surgery, Anesthesia, University of Florida, PO Box 100254, Gainesville, FL, 32610-0254, USA. mclopez@ufl.edu.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lopez
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. jianyi.zhang@surgery.ufl.edu.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. ricardo.ungaro@surgery.ufl.edu.
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Ungaro
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. lori.gentile@surgery.ufl.edu.
authors.forename: Lori F
authors.initials: LF
authors.lastname: Gentile
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. benjamin.szpila@surgery.ufl.edu.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Szpila
authors.affiliation: Department of Surgery, Harborview Medical Center, University of Washington, PO Box 356410, Seattle, WA, 98195-6410, USA. ronmaier@uw.edu.
authors.forename: Ronald V
authors.initials: RV
authors.lastname: Maier
authors.affiliation: Department of Surgery, Harborview Medical Center, University of Washington, PO Box 356410, Seattle, WA, 98195-6410, USA. jcushchie@uw.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cuschieri
authors.affiliation: Department of Surgery, Aging and Geriatrics, University of Florida, PO Box 100107, Gainesville, FL, 32610, USA. abihorac@anest.ufl.edu.
authors.forename: Azra
authors.initials: A
authors.lastname: Bihorac
authors.affiliation: Department of Surgery, University of Florida College of Medicine, PO Box 10019, Gainesville, FL, 32610-0019, USA. cleeuwen@ufl.edu.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Leeuwenburgh
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. frederick.moore@surgery.ufl.edu.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Moore
authors.affiliation: Department of Surgery, Anesthesia, University of Florida, PO Box 100254, Gainesville, FL, 32610-0254, USA. hvbaker@ufl.edu.
authors.forename: Henry V
authors.initials: HV
authors.lastname: Baker
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. lyle.moldawer@surgery.ufl.edu.
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. scott.brakenridge@surgery.ufl.edu.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Brakenridge
authors.affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. philip.efron@surgery.ufl.edu.|Department of Surgery, University of Florida College of Medicine, PO Box 10019, Gainesville, FL, 32610-0019, USA. philip.efron@surgery.ufl.edu.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D015331:Cohort Studies; D015897:Comorbidity; D016207:Cytokines / Q000097:blood; D005431:Florida / Q000453:epidemiology; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D007239:Infections / Q000453:epidemiology; D007362:Intensive Care Units; D007902:Length of Stay / Q000706:statistics & numerical data; D008134:Long-Term Care; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000453:epidemiology; D015999:Multivariate Analysis; D009504:Neutrophils / Q000378:metabolism; D010351:Patient Discharge; D063868:Patient Outcome Assessment; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012771:Shock, Hemorrhagic / Q000453:epidemiology*; D012866:Skilled Nursing Facilities; D014949:Wounds, Nonpenetrating / Q000453:epidemiology*
chemical_list: D018925:Chemokines; D016207:Cytokines