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Correlation of Procalcitonin and Cytokine Expression with Dehiscence of Wartime Extremity Wounds

Forsberg, Jonathan Agner MD; Elster, Eric A. MD, FACS; Andersen, Romney C. MD; Nylen, Eric MD; Brown, Trevor S. PhD; Rose, Matthew W. MD; Stojadinovic, Alexander MD, FACS; Becker, Kenneth L. MD, PhD; McGuigan, Francis Xavier MD

Journal of Bone & Joint Surgery - American Volume: 01 March 2008 - Volume 90 - Issue 3 - p 580–588
doi: 10.2106/JBJS.G.00265
Scientific Articles

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)-γ; interleukin (IL)-1 through 8, 10, 12, 13, and 15; IFN-γ inducible protein-10; monocyte chemotactic protein-1; macrophage inflammatory protein-1α; the protein regulated on activation, normal T expressed and secreted (RANTES); and tumor necrosis factor (TNF)-α.

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.

Level of Evidence: Prognostic Level I. See Instructions to Authors for a complete description of levels of evidence.

1Departments of Orthopaedic Surgery (J.A.F. and R.C.A.) and Surgery (E.A.E. and M.W.R.), National Naval Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889. E-mail address for J.A. Forsberg:

2Section of Endocrinology, Department of Medicine, Veterans Affairs Medical Center, 50 Irving Street N.W., Room GE247, Washington, DC 20422

3Combat Casualty Care Directorate, Department of Regenerative Medicine, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910

4Department of Surgery, Walter Reed Army Medical Center, 6900 Georgia Avenue N.W., Suite 5C27A, Washington, DC 20307

5Department of Orthopaedic Surgery, Georgetown University Hospital, 3800 Reservoir Road N.W. (G-PHC), Washington, DC 20007

Copyright 2008 by The Journal of Bone and Joint Surgery, Incorporated
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