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Erschienen in: European Journal of Trauma and Emergency Surgery 6/2010

01.12.2010 | Original Article

Neutrophil-derived circulating free DNA (cf-DNA/NETs), a potential prognostic marker for mortality in patients with severe burn injury

verfasst von: Jens Altrichter, Siegfried Zedler, Robert Kraft, Eugen Faist, Steffen R. Mitzner, Martin Sauer, Joachim Windolf, Martin Scholz, Tim Lögters

Erschienen in: European Journal of Trauma and Emergency Surgery | Ausgabe 6/2010

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Abstract

The predictive value of circulating free DNA/neutrophil extracellular traps (cf-DNA/NETs) has recently been shown in patients with major trauma for sepsis, multiple organ failure, and mortality. Here we report on the predictive potential of cf-DNA/NETs for mortality in patients with severe burn injury. In a prospective study 32 patients with severe burn injury were included. Blood samples were sequentially obtained on day 1, 3, 5, and 7 after admission. cf-DNA/NETs was directly quantified from plasma by means of rapid fluorescence assay. Time kinetics of cf-DNA/NETs were correlated with clinical data, C-reactive protein (CRP), procalcitonin (PCT), and interleukin (IL)-6. Furthermore sensitivity, specificity, and positive and negative predictive value, as well as receiver operation characteristic (ROC) curves were calculated. Seven patients died within the first month after burn injury. cf-DNA/NETs values from these patients were significantly increased already on day 1 and 3 after admission compared with patients who survived (p < 0.01). In contrast, PCT levels of nonsurvivors were significantly elevated on day 3 and 5 (p < 0.01), while CRP and IL-6 did not show any significant difference between survivors and nonsurvivors. At a cutoff of 255 ng/ml, cf-DNA/NETs had sensitivity of 0.8 and specificity of 0.74. ROC revealed largest areas under the curve (AUC) for cf-DNA/NETs on day 1 (0.851) and 3 (0.883) after admission. For all values between day 1 and 7, AUC was 0.815. cf-DNA/NETs seems to be a rapid, valuable marker for prediction of mortality in burn patients. A larger confirmation trial ought to be carried out.
Literatur
1.
Zurück zum Zitat Pham TN, Kramer CB, Wang J, Rivara FP, Heimbach DM, Gibran NS, et al. Epidemiology and outcomes of older adults with burn injury: an analysis of the National Burn Repository. J Burn Care Res. 2009;30:30–6.CrossRefPubMed Pham TN, Kramer CB, Wang J, Rivara FP, Heimbach DM, Gibran NS, et al. Epidemiology and outcomes of older adults with burn injury: an analysis of the National Burn Repository. J Burn Care Res. 2009;30:30–6.CrossRefPubMed
2.
Zurück zum Zitat Gomez M, Cartotto R, Knighton J, Smith K, Fish JS. Improved survival following thermal injury in adult patients treated at a regional burn center. J Burn Care Res. 2008;29:130–7.PubMed Gomez M, Cartotto R, Knighton J, Smith K, Fish JS. Improved survival following thermal injury in adult patients treated at a regional burn center. J Burn Care Res. 2008;29:130–7.PubMed
3.
Zurück zum Zitat Farrell RT, Gamelli RL, Aleem RF, Sinacore JM. The relationship of body mass index and functional outcomes in patients with acute burns. J Burn Care Res. 2008;29:102–8.PubMed Farrell RT, Gamelli RL, Aleem RF, Sinacore JM. The relationship of body mass index and functional outcomes in patients with acute burns. J Burn Care Res. 2008;29:102–8.PubMed
4.
Zurück zum Zitat Belgian Outcome in Burn Injury Study Group. Development and validation of a model for prediction of mortality in patients with acute burn injury. Br J Surg. 2009;96:111–7.CrossRef Belgian Outcome in Burn Injury Study Group. Development and validation of a model for prediction of mortality in patients with acute burn injury. Br J Surg. 2009;96:111–7.CrossRef
5.
Zurück zum Zitat Lorente JA, Vallejo A, Galeiras R, Tomicic V, Zamora J, Cerda E, et al. Organ dysfunction as estimated by the sequential organ failure assessment score is related to outcome in critically ill burn patients. Shock. 2009;31:125–31.CrossRefPubMed Lorente JA, Vallejo A, Galeiras R, Tomicic V, Zamora J, Cerda E, et al. Organ dysfunction as estimated by the sequential organ failure assessment score is related to outcome in critically ill burn patients. Shock. 2009;31:125–31.CrossRefPubMed
6.
Zurück zum Zitat Tobiasen J, Hiebert JM, Edlich RF. The abbreviated burn severity index. Ann Emerg Med. 1982;11:260–2.CrossRefPubMed Tobiasen J, Hiebert JM, Edlich RF. The abbreviated burn severity index. Ann Emerg Med. 1982;11:260–2.CrossRefPubMed
7.
Zurück zum Zitat Barati M, Alinejad F, Bahar MA, Tabrisi MS, Shamshiri AR, Bodouhi NO, et al. Comparison of WBC, ESR, CRP and PCT serum levels in septic and non-septic burn cases. Burns. 2008;34:770–4.CrossRefPubMed Barati M, Alinejad F, Bahar MA, Tabrisi MS, Shamshiri AR, Bodouhi NO, et al. Comparison of WBC, ESR, CRP and PCT serum levels in septic and non-septic burn cases. Burns. 2008;34:770–4.CrossRefPubMed
8.
Zurück zum Zitat Carsin H, Assicot M, Feger F, Roy O, Pennacino I, Le Bever H, et al. Evolution and significance of circulating procalcitonin levels compared with IL-6, TNF alpha and endotoxin levels early after thermal injury. Burns. 1997;23:218–24.CrossRefPubMed Carsin H, Assicot M, Feger F, Roy O, Pennacino I, Le Bever H, et al. Evolution and significance of circulating procalcitonin levels compared with IL-6, TNF alpha and endotoxin levels early after thermal injury. Burns. 1997;23:218–24.CrossRefPubMed
9.
Zurück zum Zitat Gauglitz GG, Finnerty CC, Herndon DN, Mlcak RP, Jeschke MG. Are serum cytokines early predictors for the outcome of burn patients with inhalation injuries who do not survive? Crit Care. 2008;12:R81.CrossRefPubMed Gauglitz GG, Finnerty CC, Herndon DN, Mlcak RP, Jeschke MG. Are serum cytokines early predictors for the outcome of burn patients with inhalation injuries who do not survive? Crit Care. 2008;12:R81.CrossRefPubMed
10.
Zurück zum Zitat Lavrentieva A, Kontakiotis T, Lazaridis L, Tsotsolis N, Koumis J, Kyriazis G, et al. Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis? Burns. 2007;33:189–94.CrossRefPubMed Lavrentieva A, Kontakiotis T, Lazaridis L, Tsotsolis N, Koumis J, Kyriazis G, et al. Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis? Burns. 2007;33:189–94.CrossRefPubMed
11.
Zurück zum Zitat Scheller J, Rose-John S. Interleukin-6 and its receptor: from bench to bedside. Med Microbiol Immunol. 2006;195(4):173–83.CrossRefPubMed Scheller J, Rose-John S. Interleukin-6 and its receptor: from bench to bedside. Med Microbiol Immunol. 2006;195(4):173–83.CrossRefPubMed
12.
Zurück zum Zitat Chiu TW, Young R, Chan LY, Burd A, Lo DY. Plasma cell-free DNA as an indicator of severity of injury in burn patients. Clin Chem Lab Med. 2006;44:13–7.CrossRefPubMed Chiu TW, Young R, Chan LY, Burd A, Lo DY. Plasma cell-free DNA as an indicator of severity of injury in burn patients. Clin Chem Lab Med. 2006;44:13–7.CrossRefPubMed
13.
Zurück zum Zitat Fox A, Gal S, Fisher N, Smythe J, Wainscoat J, Tyler MP, et al. Quantification of circulating cell-free plasma DNA and endothelial gene RNA in patients with burns and relation to acute thermal injury. Burns. 2008;34:809–16.CrossRefPubMed Fox A, Gal S, Fisher N, Smythe J, Wainscoat J, Tyler MP, et al. Quantification of circulating cell-free plasma DNA and endothelial gene RNA in patients with burns and relation to acute thermal injury. Burns. 2008;34:809–16.CrossRefPubMed
14.
Zurück zum Zitat Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–5.CrossRefPubMed Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–5.CrossRefPubMed
15.
Zurück zum Zitat Brinkmann V, Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol. 2007;5:577–82.CrossRefPubMed Brinkmann V, Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol. 2007;5:577–82.CrossRefPubMed
16.
Zurück zum Zitat Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176:231–41.CrossRefPubMed Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176:231–41.CrossRefPubMed
17.
Zurück zum Zitat Lögters T, Margraf S, Altrichter J, Cinatl J, Mitzner S, Windolf J, et al. The clinical value of neutrophil extracellular traps. Med Microbiol Immunol. 2009;198:211–9.CrossRefPubMed Lögters T, Margraf S, Altrichter J, Cinatl J, Mitzner S, Windolf J, et al. The clinical value of neutrophil extracellular traps. Med Microbiol Immunol. 2009;198:211–9.CrossRefPubMed
18.
Zurück zum Zitat Medina E. Neutrophil extracellular traps: a strategic tactic to defeat pathogens with potential consequences for the host. J Innate Immun. 2009;1:176–80.CrossRefPubMed Medina E. Neutrophil extracellular traps: a strategic tactic to defeat pathogens with potential consequences for the host. J Innate Immun. 2009;1:176–80.CrossRefPubMed
20.
Zurück zum Zitat Margraf S, Lögters T, Reipen J, Altrichter J, Scholz M, Windolf J. Neutrophil-derived circulating free DNA (cf-DNA/NETs): a potential prognostic marker for posttraumatic development of inflammatory second hit and sepsis. Shock. 2008;30:352–8.CrossRefPubMed Margraf S, Lögters T, Reipen J, Altrichter J, Scholz M, Windolf J. Neutrophil-derived circulating free DNA (cf-DNA/NETs): a potential prognostic marker for posttraumatic development of inflammatory second hit and sepsis. Shock. 2008;30:352–8.CrossRefPubMed
21.
Zurück zum Zitat Lögters T, Paunel-Görgülü A, Zilkens C, Altrichter J, Scholz M, Thelen S, et al. Diagnostic accuracy of Neutrophil-derived circulating free DNA (cf-DNA/NETs) for septic arthritis. J Orthop Res. 2009;27:1401–7.CrossRefPubMed Lögters T, Paunel-Görgülü A, Zilkens C, Altrichter J, Scholz M, Thelen S, et al. Diagnostic accuracy of Neutrophil-derived circulating free DNA (cf-DNA/NETs) for septic arthritis. J Orthop Res. 2009;27:1401–7.CrossRefPubMed
22.
Zurück zum Zitat Gauglitz GG, Song J, Herndon DN, Finnerty CC, Boehning D, Barral JM, et al. Characterization of the inflammatory response during acute and post-acute phases after severe burn. Shock. 2008;30:503–7.CrossRefPubMed Gauglitz GG, Song J, Herndon DN, Finnerty CC, Boehning D, Barral JM, et al. Characterization of the inflammatory response during acute and post-acute phases after severe burn. Shock. 2008;30:503–7.CrossRefPubMed
23.
Zurück zum Zitat Schinkel C, Zimmer S, Kremer JP, Wlaz A, Rordorf-Adam C, Henckel von Donnersmarck G, et al. Comparative analysis of transcription and protein release of the inflammatory cytokines interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) following major burn and mechanical trauma. Shock. 1995;4:241–6.CrossRefPubMed Schinkel C, Zimmer S, Kremer JP, Wlaz A, Rordorf-Adam C, Henckel von Donnersmarck G, et al. Comparative analysis of transcription and protein release of the inflammatory cytokines interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) following major burn and mechanical trauma. Shock. 1995;4:241–6.CrossRefPubMed
24.
Zurück zum Zitat Tschöp J, Martignoni A, Reid MD, Adediran SG, Gardner J, Noel GJ, et al. Differential immunological phenotypes are exhibited after scald and flame burns. Shock. 2009;31:157–63.CrossRefPubMed Tschöp J, Martignoni A, Reid MD, Adediran SG, Gardner J, Noel GJ, et al. Differential immunological phenotypes are exhibited after scald and flame burns. Shock. 2009;31:157–63.CrossRefPubMed
25.
Zurück zum Zitat Kitz R, Rose MA, Placzek K, Schulze J, Zielen S, Schubert R. LPS inhalation challenge: a new tool to characterize the inflammatory response in humans. Med Microbiol Immunol. 2008;197(1):13–9.CrossRefPubMed Kitz R, Rose MA, Placzek K, Schulze J, Zielen S, Schubert R. LPS inhalation challenge: a new tool to characterize the inflammatory response in humans. Med Microbiol Immunol. 2008;197(1):13–9.CrossRefPubMed
26.
Zurück zum Zitat von Müller L, Mertens T. Human cytomegalovirus infection and antiviral immunity in septic patients without canonical immunosuppression. Med Microbiol Immunol. 2008;197(2):75–82.CrossRef von Müller L, Mertens T. Human cytomegalovirus infection and antiviral immunity in septic patients without canonical immunosuppression. Med Microbiol Immunol. 2008;197(2):75–82.CrossRef
27.
Zurück zum Zitat Neely AN, Fowler LA, Kagan RJ, Warden GD. Procalcitonin in pediatric burn patients: an early indicator of sepsis? J Burn Care Rehabil. 2004;25:76–80.CrossRefPubMed Neely AN, Fowler LA, Kagan RJ, Warden GD. Procalcitonin in pediatric burn patients: an early indicator of sepsis? J Burn Care Rehabil. 2004;25:76–80.CrossRefPubMed
28.
Zurück zum Zitat Gomez CR, Nomellini V, Baila H, Oshima K, Kovacs EJ. Comparison of the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: scald injury versus i.p. LPS administration. Shock. 2009;31:178–84.CrossRefPubMed Gomez CR, Nomellini V, Baila H, Oshima K, Kovacs EJ. Comparison of the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: scald injury versus i.p. LPS administration. Shock. 2009;31:178–84.CrossRefPubMed
29.
Zurück zum Zitat Xie GS, Hou AR, Li LY, Gao YN, Cheng SJ. Quantification of plasma DNA as a screening tool for lung cancer. Chin Med J. 2004;117:1485–8.PubMed Xie GS, Hou AR, Li LY, Gao YN, Cheng SJ. Quantification of plasma DNA as a screening tool for lung cancer. Chin Med J. 2004;117:1485–8.PubMed
30.
Zurück zum Zitat Swaminathan R, Butt AN. Circulating nucleic acids in plasma and serum: recent developments. Ann N Y Acad Sci. 2006;1075:1–9.CrossRefPubMed Swaminathan R, Butt AN. Circulating nucleic acids in plasma and serum: recent developments. Ann N Y Acad Sci. 2006;1075:1–9.CrossRefPubMed
31.
Zurück zum Zitat Swarup V, Rajeswari MR. Circulating (cell-free) nucleic acids—a promising, non invasive tool for early detection of several human diseases. FEBS lett. 2007;581:795–9.CrossRefPubMed Swarup V, Rajeswari MR. Circulating (cell-free) nucleic acids—a promising, non invasive tool for early detection of several human diseases. FEBS lett. 2007;581:795–9.CrossRefPubMed
32.
Zurück zum Zitat Tong YK, Lo YM. Diagnostic developments involving cell-free (circulating) nucleic acids. Clin Chim Acta. 2006;363:187–96.CrossRefPubMed Tong YK, Lo YM. Diagnostic developments involving cell-free (circulating) nucleic acids. Clin Chim Acta. 2006;363:187–96.CrossRefPubMed
33.
Zurück zum Zitat Taback B, Hoon DS. Circulating nucleic acids in plasma and serum: past, present and future. Curr Opin Mol Ther. 2004;6:273–8.PubMed Taback B, Hoon DS. Circulating nucleic acids in plasma and serum: past, present and future. Curr Opin Mol Ther. 2004;6:273–8.PubMed
34.
Zurück zum Zitat Kessenbrock K, Krumbholz M, Schönermarck U, Back W, Gross WL, Werb C, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009;15:623–5.CrossRefPubMed Kessenbrock K, Krumbholz M, Schönermarck U, Back W, Gross WL, Werb C, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009;15:623–5.CrossRefPubMed
35.
Zurück zum Zitat Osterloh A, Breloer M. Heat shock proteins: linking danger and pathogen recognition. Med Microbiol Immunol. 2008;197:1–8.CrossRefPubMed Osterloh A, Breloer M. Heat shock proteins: linking danger and pathogen recognition. Med Microbiol Immunol. 2008;197:1–8.CrossRefPubMed
36.
Zurück zum Zitat Valeva A, Walev I, Weis S, Boukhallouk F, Wassenaar TM, Bhakdi S. Pro-inflammatory feedback activation cycle evoked by attack of Vibrio cholerae cytolysin on human neutrophil granulocytes. Med Microbiol Immunol. 2008;197:285–93.CrossRefPubMed Valeva A, Walev I, Weis S, Boukhallouk F, Wassenaar TM, Bhakdi S. Pro-inflammatory feedback activation cycle evoked by attack of Vibrio cholerae cytolysin on human neutrophil granulocytes. Med Microbiol Immunol. 2008;197:285–93.CrossRefPubMed
37.
Zurück zum Zitat Li X, Schwacha MG, Chaudry IH, Choudhry MA. Heme oxygenase-1 protects against neutrophil-mediated intestinal damage by down-regulation of neutrophil p47phox and p67phox activity and O2- production in a two-hit model of alcohol intoxication and burn injury. J Immunol. 2008;180:6933–40.PubMed Li X, Schwacha MG, Chaudry IH, Choudhry MA. Heme oxygenase-1 protects against neutrophil-mediated intestinal damage by down-regulation of neutrophil p47phox and p67phox activity and O2- production in a two-hit model of alcohol intoxication and burn injury. J Immunol. 2008;180:6933–40.PubMed
Metadaten
Titel
Neutrophil-derived circulating free DNA (cf-DNA/NETs), a potential prognostic marker for mortality in patients with severe burn injury
verfasst von
Jens Altrichter
Siegfried Zedler
Robert Kraft
Eugen Faist
Steffen R. Mitzner
Martin Sauer
Joachim Windolf
Martin Scholz
Tim Lögters
Publikationsdatum
01.12.2010
Verlag
Urban and Vogel
Erschienen in
European Journal of Trauma and Emergency Surgery / Ausgabe 6/2010
Print ISSN: 1863-9933
Elektronische ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-010-0013-1

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