title: Inflammatory cytokine and chemokine expression is associated with heterotopic ossification in high-energy penetrating war injuries.
abstract: OBJECTIVE
  Heterotopic ossification (HO) develops frequently after modern high-energy penetrating war injuries. The purpose of this prospective study was to identify and characterize the unique cytokine and chemokine profile associated with the development of HO as it pertained to the systemic inflammatory response after penetrating combat-related trauma.
  
  
  METHODS
  Patients with high-energy penetrating extremity wounds were prospectively enrolled. Surgical debridement along with the use of a pulse lavage and vacuum-assisted-closure device was performed every 48-72 hours until definitive wound closure. Wound bed tissue biopsy, wound effluent, and serum were collected before each debridement. Effluent and serum were analyzed for 22 relevant cytokines and chemokines. Tissue was analyzed quantitatively for bacterial colonization. Correlations between specific wound and patient characteristics were also analyzed. The primary clinical outcome measure was the formation of HO as confirmed by radiographs at a minimum of 2 months of follow-up.
  
  
  RESULTS
  Thirty-six penetrating extremity war wounds in 24 patients were investigated. The observed rate of HO in the study population was 38%. Of the 36 wounds, 13 (36%) demonstrated HO at a minimum follow-up of 2 months. An elevated injury severity score was associated with the development of HO (P = 0.006). Wound characteristics that correlated with the development of HO included impaired healing (P = 0.005) and bacterial colonization (P < 0.001). Both serum (interleukin-6, interleukin-10, and MCP-1) and wound effluent (IP-10 and MIP-1α) cytokine and chemokine bioprofiles were individually associated and suggestive of the development of HO (P < 0.05).
  
  
  CONCLUSIONS
  A severe systemic and wound-specific inflammatory state as evident by elevated levels of inflammatory cytokines, elevated injury severity score, and bacterial wound colonization is associated with the development of HO. These findings suggest that the development of HO in traumatic combat-related wounds is associated with a hyper-inflammatory systemic response to injury.
  
  
  METHODS
  Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: Integrated Department of Orthopedics and Rehabilitation, Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: Korboi N
authors.initials: KN
authors.lastname: Evans
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Forsberg
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Potter
authors.forename: Jason S
authors.initials: JS
authors.lastname: Hawksworth
authors.forename: Trevor S
authors.initials: TS
authors.lastname: Brown
authors.forename: Romney
authors.initials: R
authors.lastname: Andersen
authors.forename: James R
authors.initials: JR
authors.lastname: Dunne
authors.forename: Douglas
authors.initials: D
authors.lastname: Tadaki
authors.forename: Eric A
authors.initials: EA
authors.lastname: Elster
mesh_terms: D001753:Blast Injuries / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D008297:Male; D009999:Ossification, Heterotopic / Q000097:blood / Q000276:immunology*; D014857:Warfare; D014950:Wounds, Penetrating / Q000097:blood / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines