title: Predictive value of neuron-specific enolase for prognosis in patients with moderate or severe traumatic brain injury: a systematic review and meta-analysis.
abstract: BACKGROUND
  Prognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury.
  
  
  METHODS
  We searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses.
  
  
  RESULTS
  We screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies,n= 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L;I2 = 83%) and a Glasgow Outcome Scale ≤ 3 (14 studies,n= 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L;I2 = 82%). We were unable to determine a clinical threshold value using the available patient data.
  
  
  CONCLUSIONS
  In patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available.
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Eric
authors.initials: E
authors.lastname: Mercier
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Amélie
authors.initials: A
authors.lastname: Boutin
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Michèle
authors.initials: M
authors.lastname: Shemilt
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: François
authors.initials: F
authors.lastname: Lauzier
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Ryan
authors.initials: R
authors.lastname: Zarychanski
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fergusson
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Lynne
authors.initials: L
authors.lastname: Moore
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Lauralyn A
authors.initials: LA
authors.lastname: McIntyre
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Patrick
authors.initials: P
authors.lastname: Archambault
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: France
authors.initials: F
authors.lastname: Légaré
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: François
authors.initials: F
authors.lastname: Rousseau
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: François
authors.initials: F
authors.lastname: Lamontagne
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Linda
authors.initials: L
authors.lastname: Nadeau
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval (Mercier, Boutin, Shemilt, Lauzier, Moore, Archambault, Légaré, Turgeon), Population Health and Optimal Health Practices Research Unit; Department of Social and Preventive Medicine (Boutin, Moore); Department of Anesthesiology and Critical Care Medicine (Lauzier, Archambault, Turgeon), Division of Critical Care Medicine; Department of Family Medicine and Emergency Medicine (Archambault, Légaré), Faculty of Medicine (Lauzier); Department of Molecular Biology (Rousseau, Nadeau), Medical Biochemistry and Pathology, Université Laval, Québec City, Que.; Department of Haematology and Medical Oncology (Zarychanski), University of Manitoba, Winnipeg, Man.; Center for Transfusion and Critical Care Research (Fergusson, McIntyre, Turgeon), Clinical Epidemiology Unit, Ottawa Health Research Institute, University of Ottawa; Department of Critical Care Medicine (Fergusson, McIntyre), Ottawa Hospital, University of Ottawa, Ottawa, Ont.; Centre de Recherche Étienne Lebel (Lamontagne), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Que.; Department of Medicine (Lamontagne), Université de Sherbrooke, Sherbrooke, Que.
authors.forename: Alexis F
authors.initials: AF
authors.lastname: Turgeon