title: Temporal Patterns of Circulating Inflammation Biomarker Networks Differentiate Susceptibility to Nosocomial Infection Following Blunt Trauma in Humans.
abstract: BACKGROUND
  Severe traumatic injury can lead to immune dysfunction that renders trauma patients susceptible to nosocomial infections (NI) and prolonged intensive care unit (ICU) stays. We hypothesized that early circulating biomarker patterns following trauma would correlate with sustained immune dysregulation associated with NI and remote organ failure.
  
  
  METHODS
  In a cohort of 472 blunt trauma survivors studied over an 8-year period, 127 patients (27%) were diagnosed with NI versus 345 trauma patients without NI. To perform a pairwise, case-control study with 1:1 matching, 44 of the NI patients were compared with 44 no-NI trauma patients selected by matching patient demographics and injury characteristics. Plasma obtained upon admission and over time were assayed for 26 inflammatory mediators and analyzed for the presence of dynamic networks.
  
  
  RESULTS
  Significant differences in ICU length of stay (LOS), hospital LOS, and days on mechanical ventilation were observed in the NI patients versus no-NI patients. Although NI was not detected until day 7, multiple mediators were significantly elevated within the first 24 hours in patients who developed NI. Circulating inflammation biomarkers exhibited 4 distinct dynamic patterns, of which 2 clearly distinguish patients destined to develop NI from those who did not. Mediator network connectivity analysis revealed a higher, coordinated degree of activation of both innate and lymphoid pathways in the NI patients over the initial 24 hours.
  
  
  CONCLUSIONS
  These studies implicate unique dynamic immune responses, reflected in circulating biomarkers that differentiate patients prone to persistent critical illness and infections following injury, independent of mechanism of injury, injury severity, age, or sex.
authors.affiliation: *Department of Surgery, University of Pittsburgh, Pittsburgh, PA †Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA ‡Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA §Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA ¶Department of Internal Medicine, Division of Rheumatology, Wayne State University, Detroit, MI ||Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Rami A
authors.initials: RA
authors.lastname: Namas
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Khalid
authors.initials: K
authors.lastname: Almahmoud
authors.forename: Othman
authors.initials: O
authors.lastname: Abdul-Malak
authors.forename: Akram
authors.initials: A
authors.lastname: Zaaqoq
authors.forename: Rajaie
authors.initials: R
authors.lastname: Namas
authors.forename: Qi
authors.initials: Q
authors.lastname: Mi
authors.forename: Derek
authors.initials: D
authors.lastname: Barclay
authors.forename: Brian
authors.initials: B
authors.lastname: Zuckerbraun
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Peitzman
authors.forename: Jason
authors.initials: J
authors.lastname: Sperry
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003428:Cross Infection / Q000209:etiology*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D014949:Wounds, Nonpenetrating / Q000097:blood* / Q000150:complications*
chemical_list: D015415:Biomarkers