Plasma cell-free DNA as an indicator of severity of injury in burn patients
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Tor W. Chiu
Abstract
Background: Raised levels of plasma cell-free DNA have been detected in various patient groups, including trauma patients. We hypothesized that plasma DNA is increased in burn patients and may represent an objective indicator of burn severity and have predictive as well as prognostic significance.
Methods: This was a prospective clinical study with full ethical approval. With informed consent, blood samples were collected from 28 burn patients within 24h of injury and from 12 control subjects. Plasma cell-free DNA was measured by real-time quantitative polymerase chain reaction (PCR) assay for the β-globin gene. Descriptive analysis, non-parametric data comparison tests (Mann-Whitney) and correlation tests (Spearman rank) were performed on the data.
Results: Samples were taken at a mean time of 5.7h after injury from 13 patients with flame/flash burns and 15 patients with scalds. Median plasma DNA levels in the control, scald and flame/flash burn patient groups were 287, 648 and 2685 kilogenome-equivalents/L, respectively. Plasma DNA levels correlated with the length of hospital stay, but not with admission to the intensive care unit (ICU) nor the length of ICU stay. DNA levels correlated with the burn surface area (Spearman rank r=0.54, p=0.04) and the number of operations needed (Spearman rank r=0.55, p=0.03) for scalds, but not for flame/flash burns.
Conclusions: Plasma DNA is increased after burn injury and is significantly correlated with some outcome measures, including the length of hospital stay. DNA levels are higher in flame/flash patients than in scald patients; the difference may provide an objective indication of burn depth and inhalation injury.
References
1. Young AE, Manara AR, Burd DA. Intensive care management of the child with severe burns. Care of the Critically III 1995; 11:93–7.Suche in Google Scholar
2. Sheridan RL, Schnitzer JJ. Management of the high-risk pediatric burn patient. J Pediatr Surg 2001; 36:1308–12.10.1053/jpsu.2001.25805Suche in Google Scholar
3. Meyers-Paal R, Blakeney P, Robert R, Murphy L, Chinkes D, Meyer W, et al. Physical and psychologic rehabilitation outcomes for pediatric patients who suffer 80% or more TBSA, 70% or more third degree burns. J Burn Care Rehabil 2000; 21:43–9.10.1097/00004630-200021010-00009Suche in Google Scholar
4. Bull JP. Revised analysis of mortality due to burns. Lancet 1971; 2:1133–4.10.1016/S0140-6736(71)91286-4Suche in Google Scholar
5. Baux S, Mimoun M, Saade H. Burns in the elderly. Burns 1989; 15:239–40.10.1016/0305-4179(89)90039-9Suche in Google Scholar
6. Tompkins RG, Burke JF, Schoenfeld D, Bondoc CC, Quinby WC Jr, Behringer GC, et al. Prompt eschar excision: a treatment system contributing to reduced burn mortality. A statistical evaluation of burn care at Massachusetts General Hospital (1974–1984). Ann Surg 1986; 204:272–81.10.1097/00000658-198609000-00006Suche in Google Scholar PubMed PubMed Central
7. Thompson P, Herndon DN, Abston S, Rutan T. Effect of early excision of patients with major thermal injury. J Trauma 1987; 27:205–7.10.1097/00005373-198702000-00019Suche in Google Scholar PubMed
8. Herndon DN, Barrow RE, Rutan RL, Rutan TC, Desai MH, Abston S. A comparison of conservative versus early excision. Therapies in severely burned patients. Ann Surg 1989; 209:547–53.10.1097/00000658-198905000-00006Suche in Google Scholar PubMed PubMed Central
9. Engrav LH, Heimbach DM, Reus JL, Harnar TJ, Marvin JA. Early excision and grafting vs. nonoperative treatment of burns of indeterminant depth: a randomized prospective study. J Trauma 1983; 23:1001–4.10.1097/00005373-198311000-00007Suche in Google Scholar PubMed
10. Hildreth MA, Herndon DN, Desai MH, Duke MA. Reassessing caloric requirements in pediatric burn patients. J Burn Care Rehabil 1988; 9:616–8.10.1097/00004630-198811000-00009Suche in Google Scholar PubMed
11. Mochizuki H, Trocki O, Dominioni L, Alexander JW. Reduction of postburn hypermetabolism by early enteral feeding. Curr Surg 1985; 42:121–5.Suche in Google Scholar
12. Wolf SE, Rose JK, Desai MH, Mileski JP, Barrow RE, Herndon DN. Mortality determinants in massive pediatric burns. An analysis of 103 children with ≥80% TBSA burns (≥70% full-thickness). Ann Surg 1997; 225:554–65.10.1097/00000658-199705000-00012Suche in Google Scholar PubMed PubMed Central
13. Ryan CM, Schoenfeld DA, Thorpe WP, Sheridan RL, Cassem EH, Tompkins RG. Objective estimates of the probability of death from burn injuries. N Engl J Med 1998; 338:362–6.10.1056/NEJM199802053380604Suche in Google Scholar
14. Pape SA, Skouras CA, Byrne PO. An audit of the use of laser Doppler imaging (LDI) in the assessment of burns of intermediate depth. Burns 2001; 27:233–9.10.1016/S0305-4179(00)00118-2Suche in Google Scholar
15. Clark JC, Reid WH, Gilmour WH, Campbell D. Mortality probability in victims of fire trauma: revised equation to include inhalation injury. Br Med J 1986; 292:1303–5.10.1136/bmj.292.6531.1303Suche in Google Scholar
16. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum. Lancet 1997; 350:485–7.10.1016/S0140-6736(97)02174-0Suche in Google Scholar
17. Bianchi DW. Fetal DNA in maternal plasma: the plot thickens and the placental barrier thins. Am J Hum Genet 1998; 62:763–4.10.1086/301809Suche in Google Scholar
18. Bischoff FZ, Lewis DE, Simpson JL. Cell-free fetal DNA in maternal blood: kinetics, source and structure. Hum Reprod Update 2005; 11:59–67.10.1093/humupd/dmh053Suche in Google Scholar
19. Lo YM, Tein MS, Pang CC, Yeung CK, Tong KL, Hjeim NM. Presence of donor-specific DNA in plasma of kidney and liver transplant recipients. Lancet 1998; 351:1329–30.10.1016/S0140-6736(05)79055-3Suche in Google Scholar
20. Chen XQ, Stroun M, Magnenat JL, Nicod LP, Kurt AM, Lyautey J, et al. Microsatellite alterations in plasma DNA of small cell lung cancer patients. Nat Med 1996; 2:1033–35.10.1038/nm0996-1033Suche in Google Scholar PubMed
21. Lei LI, Chan LY, Chan WY, Johnson PJ, Lo YM. Quantitative analysis of circulating cell-free Epstein-Barr virus (EBV) levels in patients with EBV-associated lymphoid malignancies. Br J Haematol 2000; 111:239–46.Suche in Google Scholar
22. Jen J, Wu L, Sidransky D. An overview on the isolation and analysis of circulating tumor DNA in plasma and serum. Ann NY Acad Sci 2000; 906:8–12.10.1111/j.1749-6632.2000.tb06581.xSuche in Google Scholar PubMed
23. Papadopoulou E, Davilas E, Sotiriou V, Koliopanos A, Aggelaki F, Dardoufas K, et al. Cell-free DNA and RNA in plasma as a new molecular marker for prostate cancer. Oncol Res 2004; 14:439–45.10.3727/0965040041791473Suche in Google Scholar PubMed
24. Gautschi O, Bigosch C, Huegli B, Jermann M, Marx A, Chasse B, et al. Circulating deoxyribonucleic acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy. J Clin Oncol 2004; 22:4157–64.10.1200/JCO.2004.11.123Suche in Google Scholar PubMed
25. Xie GS, Hou AR, Li LY, Gao YN, Cheng S. Quantification of plasma DNA as a screening tool for lung cancer. Chin Med J 2004; 117:1485–8.Suche in Google Scholar
26. Johnson PJ, Lo YM. Plasma nucleic acids in the diagnosis and management of malignant disease. Clin Chem 2002; 48:1186–93.10.1093/clinchem/48.8.1186Suche in Google Scholar
27. Sozzi G, Conte D, Leon ME, Cirincione R, Roz L, Ratcliffe C, et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol 2003; 21:3902–8.10.1200/JCO.2003.02.006Suche in Google Scholar PubMed
28. Lo YM, Rainer TH, Chan LY, Hjelm NM, Cocks RA. Plasma DNA as a prognostic marker in trauma patients. Clin Chem 2000; 46:319–23.10.1093/clinchem/46.3.319Suche in Google Scholar
29. Laktionov PP, Tamkovich SN, Rykova EY, Bryzgunova OE, Starikov AV, Kuznetsova NP, et al. Extracellular circulating nucleic acids in human plasma in health and disease. Nucleosides Nucleotides Nucleic Acids 2004; 23:879–83.10.1081/NCN-200026035Suche in Google Scholar PubMed
30. Lam NY, Rainer TH, Chan LY, Joynt GM, Lo DY. Time course of early and late changes in plasma DNA in trauma patients. Clin Chem 2003; 49:1286–91.10.1373/49.8.1286Suche in Google Scholar PubMed
31. Rainer TH, Wong LK, Lam W, Yuen E, Lam NY, Metrewelli C, et al. Prognostic use of circulating plasma nucleic acid concentrations with acute stroke. Clin Chem 2003; 49:562–9.10.1373/49.4.562Suche in Google Scholar PubMed
32. Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998; 62:768–75.10.1086/301800Suche in Google Scholar PubMed PubMed Central
33. Holland PM, Abramson RD, Watson R, Gelfand DH. Detection of specific polymerase chain reaction product by utilizing the 5′-3′ exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci USA 1991; 88:7272–80.10.1073/pnas.88.16.7276Suche in Google Scholar PubMed PubMed Central
34. Tobiasen J, Hiebert J, Edlich R. Prediction of burn mortality. Surg Gynecol Obst 1982; 154:711–4.Suche in Google Scholar
35. Grad S, Ertel W, Keel M, Infanger M, Vonderschmitt DJ, Maly FE. Strongly enhanced serum levels of vascular endothelial growth factor (VEGF) after polytrauma and burn. Clin Chem Lab Med 1998; 36:379–83.10.1515/CCLM.1998.064Suche in Google Scholar PubMed
©2006 by Walter de Gruyter Berlin New York
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- Where does the evidence come from?
- NASBA: a novel approach to assess hormonal receptors and ERBB2 status in breast cancer
- Plasma cell-free DNA as an indicator of severity of injury in burn patients
- Bivariate statistical approach to evaluate laboratory performance by analysis of standard curves in an External Quality Assurance program for quantitative assays based on real-time PCR with Taq-Man™ probes
- Erythrocyte membrane acetylcholinesterase activity in subjects with MTHFR 677C→T genotype
- Plasma levels of tumor M2-pyruvate kinase should not be used as a tumor marker for hematological malignancies and solid tumors
- APO A-V–1131T→C polymorphism frequency and its association with morbidity in a Brazilian elderly population
- Association study between fibronectin and coronary heart disease
- Serum calcium and phosphorus associate with the occurrence and severity of angiographically documented coronary heart disease, possibly through correlation with atherogenic (apo)lipoproteins
- Urinary calcium excretion in severe preeclampsia and eclampsia
- In vitro re-mineralization of demineralized bone matrix in human serum
- Measurement of serum amyloid A1 (SAA1), a major isotype of acute phase SAA
- Disturbed lipoprotein composition in non-dialyzed, hemodialysis, continuous ambulatory peritoneal dialysis and post-transplant patients with chronic renal failure
- Measurement of serum testosterone using high-performance liquid chromatography/tandem mass spectrometry
- Quantitative bacterial micro-assay for rapid detection of serum phenylalanine on dry blood-spots: application in phenylketonuria screening
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