Trauma and its severe complications are major health problems and leading causes of mortality and morbidity among young people in the world. The increasing ability to keep most trauma patients alive has resulted in an increased incidence of complications in this population. The pathophysiology of trauma complications is tremendously complex. Biomarkers have traditionally been considered as important area of medical research: the measurement of certain biomarkers has led to a better understanding of pathophysiology, while others have been used either to assess the effectiveness of specific treatments or for prognostic purposes. If with early diagnosis and early intervention, trauma complications can be prevented and cured. The aim of the review is to discuss new biomarkers which can be used in the prediction of severe trauma complications, mainly sepsis and Multiple Organ Dysfunction Syndrome (MODS). We also discuss to which degree currently available trauma complications biomarkers may help to overcome the present diagnostic uncertainty. We address how new insights into the pathogenesis of trauma complications may help in the development of specific biomarkers and how this may also impact the identification and development of new therapeutic targets. Research into biomarkers may help to predict the prognosis of patients with severe trauma.
Published in | Journal of Surgery (Volume 5, Issue 1) |
DOI | 10.11648/j.js.20170501.12 |
Page(s) | 8-14 |
Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
Copyright |
Copyright © The Author(s), 2017. Published by Science Publishing Group |
Trauma Complications, Biomarkers, Sepsis, Multiple Organ Dysfunction Syndrome, Acute Phase Proteins, Immunocyte, Organ Damage, Cytokine, Single Nucleotide Polymorphism
[1] | Mondello S, Cantrell A, Italiano D, Fodale V, Mondello P, Ang D. Complications of trauma patients admitted to the ICU in level I academic trauma centers in the United States. Biomed Res Int. 2014; 473419. |
[2] | Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001; 69: 89-95. |
[3] | Werner M. Serum protein changes during the acute phase reaction. Clin Chim Acta. 1969; 25: 299-305. |
[4] | Markanday A. Acute phase reactants in infections: Evidence-based review and a guide for clinicians. Open Forum Infect Dis. 2015; 2: ofv098. |
[5] | Cray C, Zaias J, Altman NH. Acute phase response in animals: a review. Comp Med. 2009; 59: 517-26. |
[6] | Miglietta F, Faneschi ML, Lobreglio G, Palumbo C, Rizzo A, Cucurachi M et al. Procalcitonin, C-reactive protein and serum lactate dehydrogenase in the diagnosis of bacterial sepsis, SIRS and systemic candidiasis. Infez Med. 2015; 23: 230-7. |
[7] | Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med. 2006; 34: 1996-2003. |
[8] | Tang BMP, Eslick GD, Craig JC, Mclean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. 2007; 7: 210-7. |
[9] | Mohsen AH, Kamel BA. Predictive values for procalcitonin in the diagnosis of neonatal sepsis. Electron Physician. 2015; 7: 1190-5. |
[10] | Neunhoeffer F, Plinke S, Renk H, Hofbeck M, Fuchs J, Kumpf M, et al. Serum Concentrations of Interleukin-6, Procalcitonin, and C-Reactive Protein: Discrimination of Septical Complications and Systemic Inflammatory Response Syndrome after Pediatric Surgery. Eur J Pediatr Surg. 2016; 26: 180-5. |
[11] | Bauer PR, Kashyap R, League SC, Park JG, Block DR, Baumann NA, et al. Diagnostic accuracy and clinical relevance of an inflammatory biomarker panel for sepsis in adult critically ill patients. Diagn Microbiol Infect Dis. 2016; 84: 175-80. |
[12] | Hofer N, Zacharias E, Muller W, Resch B. An update on the use of C-reactive protein in early-onset neonatal sepsis: current insights and new tasks. Neonatology. 2012; 102: 25-36. |
[13] | Vreugdenhil AC, Dentener MA, Snoek AM, Greve JW, Buurman WA. Lipopolysaccharide binding protein and serum amyloid A secretion by human intestinal epithelial cells during the acute phase response. J Immunol. 1999; 163: 2792-8. |
[14] | Gasanov U, Hughes D, Hansbro PM. Methods for the isolation and identification of Listeria spp. and Listeria monocytogenes: a review. FEMS Microbiol Rev. 2005; 29: 851-75. |
[15] | Augsburger M, Iglesias K, Bardy D, Mangin P, Palmiere C. Diagnostic value of lipopolysaccharide-binding protein and procalcitonin for sepsis diagnosis in forensic pathology. Int J Legal Med. 2013; 127: 427-35. |
[16] | Vincent JL, Opal SM, Marshall JC, Tracey KJ. Sepsis definitions: time for change. Lancet 2013; 381: 774-5. |
[17] | Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis. 2013; 13: 260-8. |
[18] | van der Poll T, Opal SM. Host-pathogen interactions in sepsis. Lancet Infect Dis. 2008; 8: 32-43. |
[19] | Vanzant EL, Lopez CM, Ozrazgat-Baslanti T, Ungaro R, Davis R, Cuenca AG. Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma. J Trauma Acute Care Surg. 2014; 76: 21-9. |
[20] | Nauseef WM, Borregaard N. Neutrophils at work. Nat Immunol. 2014; 15: 602-11. |
[21] | Pynn JM, Parravicini E, Saiman L, Bateman DA, Barasch JM, Lorenz JM. Urinary neutrophil gelatinase-associated lipocalin: potential biomarker for late-onset sepsis. Pediatr Res. 2015; 78: 76-81. |
[22] | Hong DY, Kim JW, Paik JH, Jung HM, Baek KJ, Park SO, et al. Value of plasma neutrophil gelatinase-associated lipocalin in predicting the mortality of patients with sepsis at the emergency department. Clin Chim Acta. 2016; 452: 177-81. |
[23] | Muzlovic I, Ihan A, Stubljar D. CD64 index on neutrophils can diagnose sepsis and predict 30-day survival in subjects after ventilator-associated pneumonia. J Infect Dev Ctries. 2016; 10 (3): 260-8. |
[24] | Papadimitriou-Olivgeris M, Lekka K, Zisimopoulos K, Spiliopoulou I, Logothetis D, Theodorou G, et al. Role of CD64 expression on neutrophils in the diagnosis of sepsis and the prediction of mortality in adult critically ill patients. Diagn Microbiol Infect Dis. 2015; 82: 234-9. |
[25] | Du J, Li L, Dou Y, Li P, Chen R, Liu H. Diagnostic utility of neutrophil CD64 as a marker for early-onset sepsis in preterm neonates. PLoS One. 2014; 9: e102647. |
[26] | Nahm CH, Choi JW, Lee J. Delta neutrophil index in automated immature granulocyte counts for assessing disease severity of patients with sepsis. Ann Clin Lab Sci. 2008; 38: 241-6. |
[27] | Seok Y, Choi JR, Kim J, KimYK, Lee J, Song J, et al. Delta neutrophil index: a promising diagnostic and prognostic marker for sepsis. Shock. 2012; 37: 242-6. |
[28] | Lewis SM, Treacher DF, Edgeworth J, Mahalingam G, Brown CS, Mare TA, et al. Expression of CD11c and EMR2 on neutrophils: potential diagnostic biomarkers for sepsis and systemic inflammation. Clin Exp Immunol. 2015; 182: 184-94. |
[29] | Heffernan DS, Monaghan SF, Thakkar RK, Machan JT, Cioffi WG, Ayala A. Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern. Crit Care. 2012; 16: R12. |
[30] | Zahorec R. Ratio of neutrophil to lymphocyte counts: rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001; 102: 5-14. |
[31] | Liu X, Shen Y, Wang H, Ge Q, Fei A, Pan S. Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Patients with Sepsis: A Prospective Observational Study. Mediators Inflamm. 2016; 8191254. |
[32] | Riché F, Gayat E, Barthélémy R, Le Dorze M, Matéo J, Payen D. Reversal of neutrophil-to-lymphocyte count ratio in early versus late death from septic shock. Crit Care. 2015; 19: 439. |
[33] | Salciccioli JD, Marshall DC, Pimentel MA, Santos MD, Pollard D, Celi LA, et al. The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study. Crit Care. 2015; 19: 13. |
[34] | Stieglitz D, Schmid T, Chhabra NF, Echtenacher B, Mannel DN, Mostbock S. TNF and regulatory T cells are critical for sepsis-induced suppression of T cells. Immun Inflamm Dis. 2015; 3: 374-85. |
[35] | Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011; 306: 2594-605. |
[36] | Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, et al. Increased circulating regulatory T cells (CD4 (+) CD25 (+) CD127 (-)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 2009; 35: 678-86. |
[37] | Andaluz-Ojeda D, Iglesias V, Bobillo F, Almansa R, Rico L, Gandia F, et al. Early natural killer cell counts in blood predict mortality in severe sepsis. Crit Care. 2011; 15: R243. |
[38] | Duong S, Condotta SA, Rai D, Martin MD, Griffith TS, Badovinac VP. Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions. J Immunol. 2014; 192: 3618-25. |
[39] | Patschan SA, Patschan D, Temme J, Korsten P, Wessels JT, Koziolek M, et al. Endothelial progenitor cells (EPC) in sepsis with acute renal dysfunction (ARD). Crit Care. 2011; 15: R94. |
[40] | Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995; 23: 1638-52. |
[41] | Guild CS, deShazo M, Geraci SA. Negative predictive value of cardiac troponin for predicting adverse cardiac events following blunt chest trauma. South Med J. 2014; 107: 52-6. |
[42] | Schmidt AM, Yan SD, Yan SF, Stern DM. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest. 2001; 108: 949-55. |
[43] | Doyle IR, Hermans C, Bernard A, Nicholas TE, Bersten AD. Clearance of clara cell secretory protein 16 (CC16) and surfactant proteins A and B from blood in acute respiratory failure. Am J of Resp Crit Care Med. 1998; 158: 1528-35. |
[44] | Determann RM, Royakkers AA, Haitsma JJ, Zhang H, Slutsky AS, Ranieri VM, Schultz MJ. Plasma levels of surfactant protein D and KL-6 for evaluation f lung injury in critically ill mechanically ventilated patients. BMC Pulm Med. 2010; 10: 6. |
[45] | Grigoryev DN, Cheranova DI, Chaudhary S, Heruth DP, Zhang LQ, Ye SQ. Identification Identification of new biomarkers for Acute Respiratory Distress Syndrome by expression-based genome-wide association study. BMC Pulm Med. 2015; 15: 95. |
[46] | Lorente L, Martin MM, Almeida T, Hernandez M, Ramos L, Ar¬gueso M, et al. Serum substance P levels are associated with se¬verity and mortality in patients with severe traumatic brain in¬jury. Crit Care. 2015; 19: 192. |
[47] | Lorente L, Martin MM, Gonzalez-Rivero AF, Ramos L, Argueso M, Caceres JJ, et al. Serum soluble CD40 Ligand levels are as¬sociated with severity and mortality of brain trauma in¬jury patients. Thromb Res. 2014; 134: 832-6. |
[48] | Terzi I, Papaioannou V, Papanas N, Dragoumanis C, Petala A, Theodorou V, et al. Alpha1-microglobulin as an early biomarker of sepsis-associated acute kidney injury: a prospective cohort study. Hippokratia 2014; 18: 262-8. |
[49] | Nakamura Y, Ishikura H, Nishida T, Kawano Y, Yuge R, Ichiki R, et al. Usefulness of presepsin in the diagnosis of sepsis in patients with or without acute kidney injury. BMC Anesthesiol 2014; 14: 88. |
[50] | Bojic S, Kotur-Stevuljevic J, Kalezic N, Stevanovic P, Jelic-Ivanovic Z, Bilanovic D, et al. Diagnostic value of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in sepsis-associated acute kidney. Tohoku J Exp Med. 2015; 237: 103-9. |
[51] | David F, Farley J, Huang H, Lavoie JP, Laverty S. Cytokine and chemokine gene expression of IL-1beta stimulated equine articular chondrocytes. Vet Surg. 2007; 36: 221-7. |
[52] | Aziz M, Jacob A, Yang WL, Matsuda A, Wang P. Current trends in inflammatory and immunomodulatory mediators in sepsis. J Leukoc Biol. 2013; 93: 329-42. |
[53] | Gentile LF, Cuenca AG, Vanzant EL, Efron PA, McKinley B, Moore F, et al. Is there value in plasma cytokine measurements in patients with severe trauma and sepsis? Methods. 2013; 6: 3-9. |
[54] | Surbatovic M, Radakovic S. Tumor necrosis factor-alpha levels early in severe acute pancreatitis: is there predictive value regarding severity and outcome? J Clin Gastroenterol. 2013; 47: 637-43. |
[55] | Shen Y, Cui N, Miao B, Zhao E. Immune dysregulation in patients with severe acute pancreatitis. Inflammation. 2011; 34: 36-42. |
[56] | Riché F, Panis Y, Laisné MJ, Briard C, Cholley B, Bernard-Poenaru O, et al. High tumor necrosis factor serum level is associated with increased survival in patients with abdominal septic shock: a prospective study in 59 patients. Surgery. 1996; 120: 801-7. |
[57] | Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990; 8: 253–78. |
[58] | Ventetuolo CE, Levy MM. Biomarkers: diagnosis and risk assessment in sepsis. Clin Chest Med. 2008; 29: 591-603. |
[59] | Oberholzer A, Souza SM, Tschoeke SK, Oberholzer C, Abouhamze A, Pribble JP, et al. Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis. Shock. 2005; 23: 488-93. |
[60] | Zeng L, Gu W, Zhang AQ, Zhang M, Zhang LY, Du DY, et al. A Functional Variant of Lipopolysaccharide Binding Protein Predisposes to Sepsis and Organ Dysfunction in Patients with Major Trauma. Ann Surg 2012; 255: 147-57. |
[61] | Zeng L, Du J, Gu W, Zhang AQ, Wang HY, Wen DL, et al. Rs1800625 in the receptor for advanced glycation end products gene predisposes to sepsis and multiple organ dysfunction syndrome in patients with major trauma. Crit Care. 2015; 19: 6. |
[62] | Landmann R, Zimmerli W, Sansano S, Link S, Hahn A, Glauser MP, et al. Increased circulating soluble CD14 is associated with high mortality in Gram-negative septic shock. J Infect Dis. 1995; 171: 639-44. |
[63] | Hubacek JA, Stüber F, Fröhlich D, Book M, Wetegrove S, Rothe G, et al. The common functional C (-159) T polymorphism within the promoter region of the lipopolysaccharide receptor CD14 is not associated with sepsis development or mortality. Genes Immun. 2000; 1: 405-7. |
[64] | Sutherland AM, Walley KR, Russell JA. Polymorphisms in CD14, mannose binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults. Crit Care Med. 2005; 33: 638-44. |
[65] | Feng B, Mao ZR, Pang K, Zhang SL, Li L. Association of tumor necrosis factor α -308G/A and interleukin-6 -174G/C gene polymorphism with pneumonia-induced sepsis. J Crit Care 2015; 30: 920-3. |
[66] | Baghel K, Srivastava RN, Chandra A, Goel SK, Agrawal J, Kazmi HR, et al. TNF-α, IL-6, and IL-8 cytokines and their association with TNF-α-308 G/A polymorphism and postoperative sepsis. J Gastrointest Surg. 2014; 18: 1486-94. |
[67] | Kothari N, Bogra J, Abbas H, Kohli M, Malik A, Kothari D, et al. Tumor necrosis factor gene polymorphism results in high TNF level in sepsis and septic shock. Cytokine. 2013; 61: 676-81. |
[68] | Ma P, Chen D, Pan J, Du B. Genomic polymorphism within interleukin-1 family cytokines influences the outcome of septic patients. Crit Care Med. 2002; 30: 1046-50. |
[69] | Wen AQ, Gu W, Wang J, Feng K, Qin L, Ying C et al. Clinical relevance of IL-1β promoter polymorphisms (-1470, -511, and -31) in patients with major trauma. Shock. 2010; 33: 576-82. |
[70] | Chen KH, Gu W, Zeng L, Jiang DP, Zhang LY, Zhou J et al. Identification of haplotype tag snps within the entire TLR2 gene and their clinical relevance in patients with major trauma. Shock. 2011; 35: 35-41. |
[71] | Chen K, Wang YT, Gu W, Zeng L, Jiang DP, Du DY et al. Functional significance of the toll-like receptor 4 promoter gene polymorphisms in the Chinese Han population. Crit Care Med. 2010; 38: 1292-9. |
[72] | Zeng L, Zhang AQ, Gu W, Zhou J, Zhang LY, Du DY, et al. Identification of haplotype tag SNPs within the whole myeloid differentiation 2 gene and their clinical relevance in patients with major trauma. Shock; 2012: 37: 366-72. |
APA Style
Ling Zeng, Jian-xin Jiang. (2017). Severe Trauma Complications Prediction by Biomarkers. Journal of Surgery, 5(1), 8-14. https://doi.org/10.11648/j.js.20170501.12
ACS Style
Ling Zeng; Jian-xin Jiang. Severe Trauma Complications Prediction by Biomarkers. J. Surg. 2017, 5(1), 8-14. doi: 10.11648/j.js.20170501.12
AMA Style
Ling Zeng, Jian-xin Jiang. Severe Trauma Complications Prediction by Biomarkers. J Surg. 2017;5(1):8-14. doi: 10.11648/j.js.20170501.12
@article{10.11648/j.js.20170501.12, author = {Ling Zeng and Jian-xin Jiang}, title = {Severe Trauma Complications Prediction by Biomarkers}, journal = {Journal of Surgery}, volume = {5}, number = {1}, pages = {8-14}, doi = {10.11648/j.js.20170501.12}, url = {https://doi.org/10.11648/j.js.20170501.12}, eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.js.20170501.12}, abstract = {Trauma and its severe complications are major health problems and leading causes of mortality and morbidity among young people in the world. The increasing ability to keep most trauma patients alive has resulted in an increased incidence of complications in this population. The pathophysiology of trauma complications is tremendously complex. Biomarkers have traditionally been considered as important area of medical research: the measurement of certain biomarkers has led to a better understanding of pathophysiology, while others have been used either to assess the effectiveness of specific treatments or for prognostic purposes. If with early diagnosis and early intervention, trauma complications can be prevented and cured. The aim of the review is to discuss new biomarkers which can be used in the prediction of severe trauma complications, mainly sepsis and Multiple Organ Dysfunction Syndrome (MODS). We also discuss to which degree currently available trauma complications biomarkers may help to overcome the present diagnostic uncertainty. We address how new insights into the pathogenesis of trauma complications may help in the development of specific biomarkers and how this may also impact the identification and development of new therapeutic targets. Research into biomarkers may help to predict the prognosis of patients with severe trauma.}, year = {2017} }
TY - JOUR T1 - Severe Trauma Complications Prediction by Biomarkers AU - Ling Zeng AU - Jian-xin Jiang Y1 - 2017/03/20 PY - 2017 N1 - https://doi.org/10.11648/j.js.20170501.12 DO - 10.11648/j.js.20170501.12 T2 - Journal of Surgery JF - Journal of Surgery JO - Journal of Surgery SP - 8 EP - 14 PB - Science Publishing Group SN - 2330-0930 UR - https://doi.org/10.11648/j.js.20170501.12 AB - Trauma and its severe complications are major health problems and leading causes of mortality and morbidity among young people in the world. The increasing ability to keep most trauma patients alive has resulted in an increased incidence of complications in this population. The pathophysiology of trauma complications is tremendously complex. Biomarkers have traditionally been considered as important area of medical research: the measurement of certain biomarkers has led to a better understanding of pathophysiology, while others have been used either to assess the effectiveness of specific treatments or for prognostic purposes. If with early diagnosis and early intervention, trauma complications can be prevented and cured. The aim of the review is to discuss new biomarkers which can be used in the prediction of severe trauma complications, mainly sepsis and Multiple Organ Dysfunction Syndrome (MODS). We also discuss to which degree currently available trauma complications biomarkers may help to overcome the present diagnostic uncertainty. We address how new insights into the pathogenesis of trauma complications may help in the development of specific biomarkers and how this may also impact the identification and development of new therapeutic targets. Research into biomarkers may help to predict the prognosis of patients with severe trauma. VL - 5 IS - 1 ER -