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Correlation of Procalcitonin and Cytokine Expression with Dehiscence of Wartime Extremity Wounds
Jonathan Agner Forsberg, MD1; Eric A. Elster, MD, FACS1; Romney C. Andersen, MD1; Eric Nylen, MD2; Trevor S. Brown, PhD3; Matthew W. Rose, MD1; Alexander Stojadinovic, MD, FACS4; Kenneth L. Becker, MD, PhD2; Francis Xavier McGuigan, MD5
1 Departments 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: jonathan.forsberg@med.navy.mil
2 Section of Endocrinology, Department of Medicine, Veterans Affairs Medical Center, 50 Irving Street N.W., Room GE247, Washington, DC 20422
3 Combat Casualty Care Directorate, Department of Regenerative Medicine, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910
4 Department of Surgery, Walter Reed Army Medical Center, 6900 Georgia Avenue N.W., Suite 5C27A, Washington, DC 20307
5 Department of Orthopaedic Surgery, Georgetown University Hospital, 3800 Reservoir Road N.W. (G-PHC), Washington, DC 20007
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the U.S. Navy Bureau of Medicine Advanced Development Program as well as the Orthopaedic Trauma Research Program (#06131004). No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.
Disclaimer: The views expressed in this article are those of the authors and do not reflect the official policy of the Department of the Army, the Department of the Navy, the Department of Defense, or the United States Government.
Investigation performed at the National Naval Medical Center, Bethesda, Maryland

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2008 Mar 01;90(3):580-588. doi: 10.2106/JBJS.G.00265
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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)-?; interleukin (IL)-1 through 8, 10, 12, 13, and 15; IFN-? inducible protein-10; monocyte chemotactic protein-1; macrophage inflammatory protein-1a; the protein regulated on activation, normal T expressed and secreted (RANTES); and tumor necrosis factor (TNF)-a.

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.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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