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Early Detection of Pressure Ulcer Development Following Traumatic Spinal Cord Injury Using Inflammatory Mediators

  • Shilpa Krishnan
    Correspondence
    Corresponding author Shilpa Krishnan, PT, PhD, Postdoctoral Fellow, Division of Rehabilitation Sciences, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1137.
    Affiliations
    Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Science, University of Pittsburgh, Pittsburgh, PA
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  • Patricia E. Karg
    Affiliations
    Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Science, University of Pittsburgh, Pittsburgh, PA
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  • Michael L. Boninger
    Affiliations
    Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Science, University of Pittsburgh, Pittsburgh, PA

    Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, PA

    Human Engineering Research Laboratories, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA

    McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA

    Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
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  • Yoram Vodovotz
    Affiliations
    McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA

    Department of Surgery, University of Pittsburgh, Pittsburgh, PA
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  • Greg Constantine
    Affiliations
    McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA

    Department of Mathematics, University of Pittsburgh, Pittsburgh, PA
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  • Gwendolyn A. Sowa
    Affiliations
    Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, PA

    Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
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  • David M. Brienza
    Affiliations
    Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Science, University of Pittsburgh, Pittsburgh, PA

    Human Engineering Research Laboratories, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA

    Department of Mathematics, University of Pittsburgh, Pittsburgh, PA
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Published:January 25, 2016DOI:https://doi.org/10.1016/j.apmr.2016.01.003

      Abstract

      Objective

      To identify changes in concentrations of inflammatory mediators in plasma and urine after traumatic spinal cord injury (SCI) and before the occurrence of a first pressure ulcer.

      Design

      Retrospective; secondary analysis of existing data.

      Setting

      Acute hospitalization and inpatient rehabilitation sites at a university medical center.

      Participants

      Individuals with a pressure ulcer and plasma samples (n=17) and individuals with a pressure ulcer and urine samples (n=15) were matched by age and plasma/urine sample days to individuals with SCI and no pressure ulcer (N=35).

      Interventions

      Not applicable.

      Main Outcome Measures

      Plasma and urine samples were assayed in patients with SCI, capturing samples within 4 days after the SCI to a week before the formation of the first pressure ulcer. The Wilcoxon signed-rank test was performed to identify changes in the inflammatory mediators between the 2 time points.

      Results

      An increase in concentration of the chemokine interferon-γ–induced protein of 10kd/CXCL10 in plasma (P<.01) and a decrease in concentration of the cytokine interferon-α in urine (P=.01) were observed before occurrence of a first pressure ulcer (∼4d) compared with matched controls.

      Conclusions

      Altered levels of inflammatory mediators in plasma and urine may be associated with pressure ulcer development after traumatic SCI. These inflammatory mediators should be explored as possible biomarkers for identifying individuals at risk for pressure ulcer formation.

      Keywords

      List of abbreviations:

      GM-CSF (granulocyte-macrophage colony-stimulating factor), IFN (interferon), IL (interleukin), IL-1RA (interleukin-1 receptor antagonist), IP-10 (interferon-γ–induced protein of 10kd), MIP (macrophage inflammatory protein), PU (pressure ulcer), SCI (spinal cord injury)
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      References

        • DeVivo M.J.
        Epidemiology of traumatic spinal cord injury: trends and future implications.
        Spinal Cord. 2012; 50: 365-372
        • Krause J.S.
        • Zhai Y.
        • Saunders L.L.
        • Carter R.E.
        Risk of mortality after spinal cord injury: an 8-year prospective study.
        Arch Phys Med Rehabil. 2009; 90: 1708-1715
        • Hopkins A.
        • Dealey C.
        • Bale S.
        • Defloor T.
        • Worboys F.
        Patient stories of living with a pressure ulcer.
        J Adv Nurs. 2006; 56: 345-353
        • Henzel M.K.
        • Bogie K.
        • Guihan M.
        • Ho C.H.
        Pressure ulcer management and research priorities for patients with spinal cord injury: consensus opinion from SCI QUERI Expert Panel on Pressure Ulcer Research Implementation.
        J Rehabil Res Dev. 2011; 48: xi-xxxii
        • Pan W.
        • Zhang L.
        • Liao J.
        • Csernus B.
        • Kastin A.J.
        Selective increase in TNFα permeation across the blood–spinal cord barrier after SCI.
        J Neuroimmunol. 2003; 134: 111-117
        • Zaaqoq A.M.
        • Namas R.
        • Almahmoud K.
        • et al.
        Inducible protein-10, a potential driver of neurally-controlled IL-10 and morbidity in human blunt trauma.
        Crit Care Med. 2014; 42: 1487-1497
        • Yang L.
        • Blumbergs P.C.
        • Jones N.R.
        • Manavis J.
        • Sarvestani G.T.
        • Ghabriel M.N.
        Early expression and cellular localization of proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in human traumatic spinal cord injury.
        Spine (Phila Pa 1976). 2004; 29: 966-971
        • Loerakker S.
        • Huisman E.S.
        • Seelen H.A.
        • et al.
        Plasma variations of biomarkers for muscle damage in male nondisabled and spinal cord injured subjects.
        J Rehabil Res Dev. 2012; 49: 361-372
        • Hausmann O.
        Post-traumatic inflammation following spinal cord injury.
        Spinal Cord. 2003; 41: 369-378
        • Shuman S.L.
        • Bresnahan J.C.
        • Beattie M.S.
        Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats.
        J Neurosci Res. 1998; 50: 798-808
        • Zhou Z.
        • Peng X.
        • Insolera R.
        • Fink D.J.
        • Mata M.
        IL-10 promotes neuronal survival following spinal cord injury.
        Exp Neurol. 2009; 220: 183-190
        • Genovese T.
        • Esposito E.
        • Mazzon E.
        • et al.
        Absence of endogenous interleukin-10 enhances secondary inflammatory process after spinal cord compression injury in mice.
        J Neurochem. 2009; 108: 1360-1372
        • Makhsous M.
        • Lin F.
        • Pandya A.
        • Pandya M.S.
        • Chadwick C.C.
        Elevation in the serum and urine concentration of injury-related molecules after the formation of deep tissue injury in a rat spinal cord injury pressure ulcer model.
        PM R. 2010; 2: 1063-1065
        • Bronneberg D.
        • Bouten C.V.
        • Oomens C.W.
        • van Kemenade P.M.
        • Baaijens F.P.
        An in vitro model system to study the damaging effects of prolonged mechanical loading of the epidermis.
        Ann Biomed Eng. 2006; 34: 506-514
        • Frost F.
        • Roach M.J.
        • Kushner I.
        • Schreiber P.
        Inflammatory C-reactive protein and cytokine levels in asymptomatic people with chronic spinal cord injury.
        Arch Phys Med Rehabil. 2005; 86: 312-317
        • Iocono J.A.
        • Colleran K.R.
        • Remick D.G.
        • Gillespie B.W.
        • Ehrlich H.P.
        • Garner W.L.
        Interleukin-8 levels and activity in delayed-healing human thermal wounds.
        Wound Repair Regen. 2000; 8: 216-225
        • Scivoletto G.
        • Fuoco U.
        • Morganti B.
        • Cosentino E.
        • Molinari M.
        Pressure sores and blood and serum dysmetabolism in spinal cord injury patients.
        Spinal Cord. 2004; 42: 473-476
        • Segal J.L.
        • Gonzales E.
        • Yousefi S.
        • Jamshidipour L.
        • Brunnemann S.R.
        Circulating levels of IL-2R, ICAM-1, and IL-6 in spinal cord injuries.
        Arch Phys Med Rehabil. 1997; 78: 44-47
        • Stechmiller J.K.
        • Kilpadi D.V.
        • Childress B.
        • Schultz G.S.
        Effect of vacuum-assisted closure therapy on the expression of cytokines and proteases in wound fluid of adults with pressure ulcers.
        Wound Repair Regen. 2006; 14: 371-374
        • Black J.
        • Baharestani M.M.
        • Cuddigan J.
        • et al.
        National Pressure Ulcer Advisory Panel's updated pressure ulcer staging system.
        Adv Skin Wound Care. 2007; 20: 269-274
        • Marino R.J.
        • Ditunno Jr., J.F.
        • Donovan W.H.
        • Maynard Jr., F.
        Neurologic recovery after traumatic spinal cord injury: data from the Model Spinal Cord Injury Systems.
        Arch Phys Med Rehabil. 1999; 80: 1391-1396
        • Margolis D.J.
        • Knauss J.
        • Bilker W.
        • Baumgarten M.
        Medical conditions as risk factors for pressure ulcers in an outpatient setting.
        Age Ageing. 2003; 32: 259-264
        • Guihan M.
        • Bombardier C.H.
        Potentially modifiable risk factors among veterans with spinal cord injury hospitalized for severe pressure ulcers: a descriptive study.
        J Spinal Cord Med. 2012; 35: 240-250
        • Diegelmann R.F.
        Excessive neutrophils characterize chronic pressure ulcers.
        Wound Repair Regen. 2003; 11: 490-495
        • Payne W.G.
        • Ochs D.E.
        • Meltzer D.D.
        • et al.
        Long-term outcome study of growth factor-treated pressure ulcers.
        Am J Surg. 2001; 181: 81-86
        • Neville L.F.
        • Mathiak G.
        • Bagasra O.
        The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily.
        Cytokine Growth Factor Rev. 1997; 8: 207-219
        • Lee Y.
        • Shih K.
        • Bao P.
        • Ghirnikar R.
        • Eng L.
        Cytokine chemokine expression in contused rat spinal cord.
        Neurochem Int. 2000; 36: 417-425
        • Schmohl M.
        • Beckert S.
        • Joos T.O.
        • Konigsrainer A.
        • Schneiderhan-Marra N.
        • Loffler M.W.
        Superficial wound swabbing: a novel method of sampling and processing wound fluid for subsequent immunoassay analysis in diabetic foot ulcerations.
        Diabetes Care. 2012; 35: 2113-2120
        • Löffler M.
        • Schmohl M.
        • Schneiderhan-Marra N.
        • Beckert S.
        Wound fluid diagnostics in diabetic foot ulcers.
        in: Dinh T. Global perspective on diabetic foot ulcerations. INTECH Open Access Publisher, Croatia2011
        • Henry G.
        • Garner W.L.
        Inflammatory mediators in wound healing.
        Surg Clin North Am. 2003; 83: 483-507
        • Gotsch F.
        • Romero R.
        • Friel L.
        • et al.
        CXCL10/IP-10: a missing link between inflammation and anti-angiogenesis in preeclampsia?.
        J Maternal Fetal Neonatal Med. 2007; 20: 777-792
        • Gonzalez R.
        • Hickey M.J.
        • Espinosa J.M.
        • Nistor G.
        • Lane T.E.
        • Keirstead H.S.
        Therapeutic neutralization of CXCL10 decreases secondary degeneration and functional deficit after spinal cord injury in mice.
        Regen Med. 2007; 2: 771-783
        • Mantovani A.
        • Cassatella M.A.
        • Costantini C.
        • Jaillon S.
        Neutrophils in the activation and regulation of innate and adaptive immunity.
        Nat Rev Immunol. 2011; 11: 519-531
        • Lim J.Y.
        • Choi B.H.
        • Lee S.
        • Jang Y.H.
        • Choi J.S.
        • Kim Y.M.
        Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury.
        PLoS One. 2013; 8: e54256
        • Chung J.
        • Kim M.H.
        • Yoon Y.J.
        • Kim K.H.
        • Park S.R.
        • Choi B.H.
        Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on glial scar formation after spinal cord injury in rats.
        J Neurosurg Spine. 2014; 21: 966-973
        • Barrientos S.
        • Brem H.
        • Stojadinovic O.
        • Tomic-Canic M.
        Clinical application of growth factors and cytokines in wound healing.
        Wound Repair Regen. 2014; 22: 569-578
        • Groves R.W.
        • Schmidt-Lucke J.A.
        Recombinant human GM-CSF in the treatment of poorly healing wounds.
        Adv Skin Wound Care. 2000; 13: 107-112
        • Tompkins W.A.
        Immunomodulation and therapeutic effects of the oral use of interferon-alpha: mechanism of action.
        J Interferon Cytokine Res. 1999; 19: 817-828
        • Ito M.
        • Natsume A.
        • Takeuchi H.
        • et al.
        Type I interferon inhibits astrocytic gliosis and promotes functional recovery after spinal cord injury by deactivation of the MEK/ERK pathway.
        J Neurotrauma. 2009; 26: 41-53