Correlation of procalcitonin and cytokine expression with dehiscence of wartime extremity wounds.
BACKGROUND
Despite technological advances in the treatment of severe extremity trauma, the timing of wound closure remains the subjective clinical decision of the treating surgeon. Traditional serum markers are poor predictors of wound-healing. The objective of this study was to evaluate the cytokine and chemokine profiles of severe extremity wounds prior to closure to determine if wound effluent markers can be used to predict healing.


METHODS
Serum and effluent (exudate) samples were collected prospectively from adult volunteers with multiple high-energy penetrating extremity wounds sustained during military combat. Samples were collected prior to definitive wound closure or flap coverage. Wounds were followed clinically for six weeks. The primary clinical outcome measures were wound-healing and dehiscence. Control serum samples were collected from normal age and sex-matched adult volunteers. All samples were analyzed for the following cytokines and chemokines: procalcitonin; eotaxin; granulocyte macrophage colony stimulating factor; interferon (IFN)-gamma; interleukin (IL)-1 through 8, 10, 12, 13, and 15; IFN-gamma inducible protein-10; monocyte chemotactic protein-1; macrophage inflammatory protein-1alpha; the protein regulated on activation, normal T expressed and secreted (RANTES); and tumor necrosis factor (TNF)-alpha.


RESULTS
Fifty wounds were analyzed in twenty patients. Four of the fifty wounds dehisced. An increased rate of wound dehiscence was observed in patients with a concomitant closed head injury as well as in those with an associated arterial injury of the affected limb (p < 0.05). Among the serum chemokines and cytokines, only serum procalcitonin levels correlated with wound dehiscence (p < 0.05). Effluent analysis showed that, compared with wounds that healed, wounds that dehisced were associated with elevated procalcitonin, decreased RANTES protein, and decreased IL-13 concentrations (p < 0.05). No wound with an effluent procalcitonin concentration of <220 pg/mL, an IL-13 concentration of >12 pg/mL, or a RANTES protein concentration of >1000 pg/mL failed to heal.


CONCLUSIONS
Effluent procalcitonin, IL-13, and RANTES protein levels as well as serum procalcitonin levels correlate with wound dehiscence following closure of severe open extremity wounds. These preliminary results indicate that effluent biomarker analysis may be an objective means of determining the timing of traumatic wound closure.
Forsberg
Jonathan Agner
JA
Department of Orthopaedic Surgery, National Naval Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA. jonathan.forsberg@med.navy.mil
Elster
Eric A
EA
Andersen
Romney C
RC
Nylen
Eric
E
Brown
Trevor S
TS
Rose
Matthew W
MW
Stojadinovic
Alexander
A
Becker
Kenneth L
KL
McGuigan
Francis Xavier
FX
D000328:Adult; D000346:Afghanistan; D001753:Blast Injuries / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D054542:Iraq War, 2003-2011; D035002:Lower Extremity / Q000293:injuries*; D008297:Male; D008889:Military Personnel; D010865:Pilot Projects; D011446:Prospective Studies; D011498:Protein Precursors / Q000378:metabolism*; D013529:Surgical Wound Dehiscence / Q000378:metabolism*; D014481:United States; D034941:Upper Extremity / Q000293:injuries*; D014945:Wound Healing / Q000502:physiology*; D014948:Wounds, Gunshot / Q000378:metabolism; D014950:Wounds, Penetrating / Q000378:metabolism*
C000606589:CALCA protein, human; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D018793:Interleukin-13; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide