Inflammatory biomarkers in combat wound healing.
BACKGROUND
Modern war ballistics and blast injuries inflict devastating extremity injuries, violating soft tissue, bone, and neurovascular structures. Despite advances in complex wound management, appropriate timing of war wound closure remains subjective. In addition, the pathophysiology of acute wound failure is poorly defined.


METHODS
Patients with penetrating extremity wounds sustained during combat were prospectively studied and followed for 30 days after definitive wound closure. The primary outcome was wound healing. Wound dehiscence was defined as spontaneous partial or complete wound disruption after closure. Serum, wound effluent, and wound bed tissue biopsy were collected at each surgical wound debridement. Serum and wound effluent were analyzed with a multiplex array of 22 cytokines and chemokines, and wound tissue for corresponding gene transcript expression.


RESULTS
Fifty-two penetrating extremity war wounds in 33 male patients were investigated. Nine (17%) wounds dehisced. Concomitant vascular injury, increased wound size, and higher injury severity score correlated with wound dehiscence. Both serum and wound effluent cytokine and chemokine protein profiles were statistically associated with healing outcome at various time points. Wound biopsy gene transcript expression demonstrated increased tissue inflammation associated with wound failure. Multiple protein and gene transcript biomarkers predictive of wound healing were identified.


CONCLUSIONS
The cytokine and chemokine protein and gene transcript expression patterns demonstrate a condition of inflammatory dysregulation associated with war wound failure. A molecular biomarker panel may predict combat wound healing outcome and warrants prospective validation.
Hawksworth
Jason S
JS
Department of Regenerative Medicine, Combat Casualty Care, Naval Medical Research Center, Silver Spring, MD 20910, USA.
Stojadinovic
Alexander
A
Gage
Frederick A
FA
Tadaki
Doug K
DK
Perdue
Philip W
PW
Forsberg
Jonathan
J
Davis
Thomas A
TA
Dunne
James R
JR
Denobile
John W
JW
Brown
Trevor S
TS
Elster
Eric A
EA
D055826:Afghan Campaign 2001-; D015415:Biomarkers / Q000097:blood*; D018925:Chemokines / Q000097:blood / Q000235:genetics; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006230:Hand Injuries / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000235:genetics / Q000473:pathology; D054542:Iraq War, 2003-2011; D007869:Leg Injuries / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008889:Military Personnel; D011379:Prognosis; D011446:Prospective Studies; D012313:RNA / Q000235:genetics; D012372:ROC Curve; D015599:Trauma Severity Indices; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*; D014950:Wounds, Penetrating / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D012313:RNA