Ethics approval and consent to participate
The Medical Ethics Committees of all participating centers approved the CENTER-TBI study, and informed consent was obtained according to local regulations
Consent for publication
Not applicable
Availability of data and materials
The data supporting the findings in the study are available upon reasonable request from the corresponding Author (EvV) and are stored at https://center-tbi.incf.org/
Conflicts of Interest
GC is Editor-in-Chief of Intensive Care Medicine. GC reports grants, personal fees as Speakers’ Bureau Member and Advisory Board Member from Integra and Neuroptics; personal fees from Nestle and UCB Pharma, all outside of the submitted work.
DKM reports grants from the European Union and UK National Institute for Health Research, during the conduct of the study; grants, personal fees, and non-financial support from GlaxoSmithKline; personal fees from Neurotrauma Sciences, Lantmaanen AB, Pressura, and Pfizer, outside of the submitted work. The other authors declare that they have no competing interests.
Funding
Data used in preparation of this manuscript were obtained in the context of CENTER-TBI, a large collaborative project, supported by the Framework 7 program of the European Union (602150). The funder had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript.
David K. Menon was supported by a Senior Investigator Award from the National Institute for Health Research (UK). The funder had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript.
Authors’ contributions
EvV analyzed the data and drafted the manuscript, and the supplementary tables and figures. All coauthors gave feedback on the manuscript. MvdJ supervised the project. All coauthors gave feedback on (and approved) the final version of the manuscript.
CENTER-TBI INVESTIGATORS AND PARTICIPANTS
Cecilia Åkerlund1, Krisztina Amrein2, Nada Andelic3, Lasse Andreassen4, Audny Anke5, Anna Antoni6, Gérard Audibert7, Philippe Azouvi8, Maria Luisa Azzolini9, Ronald Bartels10, Pál Barzó11, Romuald Beauvais12, Ronny Beer13, Bo-Michael Bellander14, Antonio Belli15, Habib Benali16, Maurizio Berardino17, Luigi Beretta9, Morten Blaabjerg18, Peter Bragge19, Alexandra Brazinova20, Vibeke Brinck21, Joanne Brooker22, Camilla Brorsson23, Andras Buki24, Monika Bullinger25, Manuel Cabeleira26, Alessio Caccioppola27, Emiliana Calappi 27, Maria Rosa Calvi9, Peter Cameron28, Guillermo Carbayo Lozano29, Marco Carbonara27, Simona Cavallo17, Giorgio Chevallard30, Arturo Chieregato30, Giuseppe Citerio31, 32, Hans Clusmann33, Mark Coburn34, Jonathan Coles35, Jamie D. Cooper36, Marta Correia37, Amra Čović 38, Nicola Curry39, Endre Czeiter24, Marek Czosnyka26, Claire Dahyot Fizelier40, Paul Dark41, Helen Dawes42, Véronique De Keyser43, Vincent Degos16, Francesco Della Corte44, Hugo den Boogert10, Bart Depreitere45, Đula Đilvesi 46, Abhishek Dixit47, Emma Donoghue22, Jens Dreier48, Guy Loup Dulière49, Ari Ercole47, Patrick Esser42, Erzsébet Ezer50, Martin Fabricius51, Valery L. Feigin52, Kelly Foks53, Shirin Frisvold54, Alex Furmanov55, Pablo Gagliardo56, Damien Galanaud16, Dashiell Gantner28, Guoyi Gao57, Pradeep George58, Alexandre Ghuysen59, Lelde Giga60, Ben Glocker61, Jagoš Golubovic46, Pedro A. Gomez 62, Johannes Gratz63, Benjamin Gravesteijn64, Francesca Grossi44, Russell L. Gruen65, Deepak Gupta66, Juanita A. Haagsma64, Iain Haitsma67, Raimund Helbok13, Eirik Helseth68, Lindsay Horton 69, Jilske Huijben64, Peter J. Hutchinson70, Bram Jacobs71, Stefan Jankowski72, Mike Jarrett21, Ji yao Jiang58, Faye Johnson73, Kelly Jones52, Mladen Karan46, Angelos G. Kolias70, Erwin Kompanje74, Daniel Kondziella51, Evgenios Kornaropoulos47, Lars Owe Koskinen75, Noémi Kovács76, Ana Kowark77, Alfonso Lagares62, Linda Lanyon58, Steven Laureys78, Fiona Lecky79, 80, Didier Ledoux78, Rolf Lefering81, Valerie Legrand82, Aurelie Lejeune83, Leon Levi84, Roger Lightfoot85, Hester Lingsma64, Andrew I.R. Maas43, Ana M. Castaño León62, Marc Maegele86, Marek Majdan20, Alex Manara87, Geoffrey Manley88, Costanza Martino89, Hugues Maréchal49, Julia Mattern90, Catherine McMahon91, Béla Melegh92, David Menon47, Tomas Menovsky43, Ana Mikolic64, Benoit Misset78, Visakh Muraleedharan58, Lynnette Murray28, Ancuta Negru93, David Nelson1, Virginia Newcombe47, Daan Nieboer64, József Nyirádi2, Otesile Olubukola79, Matej Oresic94, Fabrizio Ortolano27, Aarno Palotie95, 96, 97, Paul M. Parizel98, Jean François Payen99, Natascha Perera12, Vincent Perlbarg16, Paolo Persona100, Wilco Peul101, Anna Piippo-Karjalainen102, Matti Pirinen95, Dana Pisica64, Horia Ples93, Suzanne Polinder64, Inigo Pomposo29, Jussi P. Posti 103, Louis Puybasset104, Andreea Radoi 105, Arminas Ragauskas106, Rahul Raj102, Malinka Rambadagalla107, Isabel Retel Helmrich64, Jonathan Rhodes108, Sylvia Richardson109, Sophie Richter47, Samuli Ripatti95, Saulius Rocka106, Cecilie Roe110, Olav Roise111,112, Jonathan Rosand113, Jeffrey V. Rosenfeld114, Christina Rosenlund115, Guy Rosenthal55, Rolf Rossaint77, Sandra Rossi100, Daniel Rueckert61 Martin Rusnák116, Juan Sahuquillo105, Oliver Sakowitz90, 117, Renan Sanchez Porras117, Janos Sandor118, Nadine Schäfer81, Silke Schmidt119, Herbert Schoechl120, Guus Schoonman121, Rico Frederik Schou122, Elisabeth Schwendenwein6, Charlie Sewalt64, Toril Skandsen123, 124 , Peter Smielewski26, Abayomi Sorinola125, Emmanuel Stamatakis47, Simon Stanworth39, Robert Stevens126, William Stewart127, Ewout W. Steyerberg64, 128, Nino Stocchetti129, Nina Sundström130, Riikka Takala131, Viktória Tamás125, Tomas Tamosuitis132, Mark Steven Taylor20, Braden Te Ao52, Olli Tenovuo103, Alice Theadom52, Matt Thomas87, Dick Tibboel133, Marjolein Timmers74, Christos Tolias134, Tony Trapani28, Cristina Maria Tudora93, Andreas Unterberg90, Peter Vajkoczy 135, Shirley Vallance28, Egils Valeinis60, Zoltán Vámos50, Mathieu van der Jagt136, Gregory Van der Steen43, Joukje van der Naalt71, Jeroen T.J.M. van Dijck 101, Thomas A. van Essen101, Wim Van Hecke137, Caroline van Heugten138, Dominique Van Praag139, Ernest van Veen64, Thijs Vande Vyvere137, Roel P. J. van Wijk101, Alessia Vargiolu32, Emmanuel Vega83, Kimberley Velt64, Jan Verheyden137, Paul M. Vespa140, Anne Vik123, 141, Rimantas Vilcinis132, Victor Volovici67, Nicole von Steinbüchel38, Daphne Voormolen64, Petar Vulekovic46, Kevin K.W. Wang142, Eveline Wiegers64, Guy Williams47, Lindsay Wilson69, Stefan Winzeck47, Stefan Wolf143, Zhihui Yang113, Peter Ylén144, Alexander Younsi90, Frederick A. Zeiler47,145, Veronika Zelinkova20, Agate Ziverte60 , Tommaso Zoerle27
1 Department of Physiology and Pharmacology, Section of Perioperative Medicine and Intensive Care, Karolinska Institutet, Stockholm, Sweden
2 János Szentágothai Research Centre, University of Pécs, Pécs, Hungary
3 Division of Surgery and Clinical Neuroscience, Department of Physical Medicine and Rehabilitation, Oslo University Hospital and University of Oslo, Oslo, Norway
4 Department of Neurosurgery, University Hospital Northern Norway, Tromso, Norway
5 Department of Physical Medicine and Rehabilitation, University Hospital Northern Norway, Tromso, Norway
6 Trauma Surgery, Medical University Vienna, Vienna, Austria
7 Department of Anesthesiology & Intensive Care, University Hospital Nancy, Nancy, France
8 Raymond Poincare hospital, Assistance Publique – Hopitaux de Paris, Paris, France
9 Department of Anesthesiology & Intensive Care, S Raffaele University Hospital, Milan, Italy
10 Department of Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands
11 Department of Neurosurgery, University of Szeged, Szeged, Hungary
12 International Projects Management, ARTTIC, Munchen, Germany
13 Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria
14 Department of Neurosurgery & Anesthesia & intensive care medicine, Karolinska University Hospital, Stockholm, Sweden
15 NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham, UK
16 Anesthesie-Réanimation, Assistance Publique – Hopitaux de Paris, Paris, France
17 Department of Anesthesia & ICU, AOU Città della Salute e della Scienza di Torino - Orthopedic and Trauma Center, Torino, Italy
18 Department of Neurology, Odense University Hospital, Odense, Denmark
19 BehaviourWorks Australia, Monash Sustainability Institute, Monash University, Victoria, Australia
20 Department of Public Health, Faculty of Health Sciences and Social Work, Trnava University, Trnava, Slovakia
21 Quesgen Systems Inc., Burlingame, California, USA
22 Australian & New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
23 Department of Surgery and Perioperative Science, Umeå University, Umeå, Sweden
24 Department of Neurosurgery, Medical School, University of Pécs, Hungary and Neurotrauma Research Group, János Szentágothai Research Centre, University of Pécs, Hungary
25 Department of Medical Psychology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
26 Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
27 Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
28 ANZIC Research Centre, Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Victoria, Australia
29 Department of Neurosurgery, Hospital of Cruces, Bilbao, Spain
30 NeuroIntensive Care, Niguarda Hospital, Milan, Italy
31 School of Medicine and Surgery, Università Milano Bicocca, Milano, Italy
32 NeuroIntensive Care, ASST di Monza, Monza, Italy
33Department of Neurosurgery, Medical Faculty RWTH Aachen University, Aachen, Germany
34 Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
35 Department of Anesthesia & Neurointensive Care, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
36 School of Public Health & PM, Monash University and The Alfred Hospital, Melbourne, Victoria, Australia
37 Radiology/MRI department, MRC Cognition and Brain Sciences Unit, Cambridge, UK
38 Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany
39 Oxford University Hospitals NHS Trust, Oxford, UK
40 Intensive Care Unit, CHU Poitiers, Potiers, France
41 University of Manchester NIHR Biomedical Research Centre, Critical Care Directorate, Salford Royal Hospital NHS Foundation Trust, Salford, UK
42 Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK
43 Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium
44 Department of Anesthesia & Intensive Care, Maggiore Della Carità Hospital, Novara, Italy
45 Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium
46 Department of Neurosurgery, Clinical centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
47 Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
48 Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
49 Intensive Care Unit, CHR Citadelle, Liège, Belgium
50 Department of Anaesthesiology and Intensive Therapy, University of Pécs, Pécs, Hungary
51 Departments of Neurology, Clinical Neurophysiology and Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark
52 National Institute for Stroke and Applied Neurosciences, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland, New Zealand
53 Department of Neurology, Erasmus MC, Rotterdam, the Netherlands
54 Department of Anesthesiology and Intensive care, University Hospital Northern Norway, Tromso, Norway
55 Department of Neurosurgery, Hadassah-hebrew University Medical center, Jerusalem, Israel
56 Fundación Instituto Valenciano de Neurorrehabilitación (FIVAN), Valencia, Spain
57 Department of Neurosurgery, Shanghai Renji hospital, Shanghai Jiaotong University/school of medicine, Shanghai, China
58 Karolinska Institutet, INCF International Neuroinformatics Coordinating Facility, Stockholm, Sweden
59 Emergency Department, CHU, Liège, Belgium
60 Neurosurgery clinic, Pauls Stradins Clinical University Hospital, Riga, Latvia
61 Department of Computing, Imperial College London, London, UK
62 Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Spain
63 Department of Anesthesia, Critical Care and Pain Medicine, Medical University of Vienna, Austria
64 Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands
65 College of Health and Medicine, Australian National University, Canberra, Australia
66 Department of Neurosurgery, Neurosciences Centre & JPN Apex trauma centre, All India Institute of Medical Sciences, New Delhi-110029, India
67 Department of Neurosurgery, Erasmus MC, Rotterdam, the Netherlands
68 Department of Neurosurgery, Oslo University Hospital, Oslo, Norway
69 Division of Psychology, University of Stirling, Stirling, UK
70 Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital & University of Cambridge, Cambridge, UK
71 Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
72 Neurointensive Care , Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
73 Salford Royal Hospital NHS Foundation Trust Acute Research Delivery Team, Salford, UK
74 Department of Intensive Care and Department of Ethics and Philosophy of Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
75 Department of Clinical Neuroscience, Neurosurgery, Umeå University, Umeå, Sweden
76 Hungarian Brain Research Program - Grant No. KTIA_13_NAP-A-II/8, University of Pécs, Pécs, Hungary
77 Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany
78 Cyclotron Research Center , University of Liège, Liège, Belgium
79 Centre for Urgent and Emergency Care Research (CURE), Health Services Research Section, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
80 Emergency Department, Salford Royal Hospital, Salford UK
81 Institute of Research in Operative Medicine (IFOM), Witten/Herdecke University, Cologne, Germany
82 VP Global Project Management CNS, ICON, Paris, France
83 Department of Anesthesiology-Intensive Care, Lille University Hospital, Lille, France
84 Department of Neurosurgery, Rambam Medical Center, Haifa, Israel
85 Department of Anesthesiology & Intensive Care, University Hospitals Southhampton NHS Trust, Southhampton, UK
86 Cologne-Merheim Medical Center (CMMC), Department of Traumatology, Orthopedic Surgery and Sportmedicine, Witten/Herdecke University, Cologne, Germany
87 Intensive Care Unit, Southmead Hospital, Bristol, Bristol, UK
88 Department of Neurological Surgery, University of California, San Francisco, California, USA
89 Department of Anesthesia & Intensive Care,M. Bufalini Hospital, Cesena, Italy
90 Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany
91 Department of Neurosurgery, The Walton centre NHS Foundation Trust, Liverpool, UK
92 Department of Medical Genetics, University of Pécs, Pécs, Hungary
93 Department of Neurosurgery, Emergency County Hospital Timisoara , Timisoara, Romania
94 School of Medical Sciences, Örebro University, Örebro, Sweden
95 Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
96 Analytic and Translational Genetics Unit, Department of Medicine; Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
97 Program in Medical and Population Genetics; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA
98 Department of Radiology, University of Antwerp, Edegem, Belgium
99 Department of Anesthesiology & Intensive Care, University Hospital of Grenoble, Grenoble, France
100 Department of Anesthesia & Intensive Care, Azienda Ospedaliera Università di Padova, Padova, Italy
101 Dept. of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands and Dept. of Neurosurgery, Medical Center Haaglanden, The Hague, The Netherlands
102 Department of Neurosurgery, Helsinki University Central Hospital
103 Division of Clinical Neurosciences, Department of Neurosurgery and Turku Brain Injury Centre, Turku University Hospital and University of Turku, Turku, Finland
104 Department of Anesthesiology and Critical Care, Pitié -Salpêtrière Teaching Hospital, Assistance Publique, Hôpitaux de Paris and University Pierre et Marie Curie, Paris, France
105 Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Barcelona, Spain
106 Department of Neurosurgery, Kaunas University of technology and Vilnius University, Vilnius, Lithuania
107 Department of Neurosurgery, Rezekne Hospital, Latvia
108 Department of Anaesthesia, Critical Care & Pain Medicine NHS Lothian & University of Edinburg, Edinburgh, UK
109 Director, MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK
110 Department of Physical Medicine and Rehabilitation, Oslo University Hospital/University of Oslo, Oslo, Norway
111 Division of Orthopedics, Oslo University Hospital, Oslo, Norway
112 Institue of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
113 Broad Institute, Cambridge MA Harvard Medical School, Boston MA, Massachusetts General Hospital, Boston MA, USA
114 National Trauma Research Institute, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia
115 Department of Neurosurgery, Odense University Hospital, Odense, Denmark
116 International Neurotrauma Research Organisation, Vienna, Austria
117 Klinik für Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg, Germany
118 Division of Biostatistics and Epidemiology, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary
119 Department Health and Prevention, University Greifswald, Greifswald, Germany
120 Department of Anaesthesiology and Intensive Care, AUVA Trauma Hospital, Salzburg, Austria
121 Department of Neurology, Elisabeth-TweeSteden Ziekenhuis, Tilburg, the Netherlands
122 Department of Neuroanesthesia and Neurointensive Care, Odense University Hospital, Odense, Denmark
123 Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
124 Department of Physical Medicine and Rehabilitation, St.Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
125 Department of Neurosurgery, University of Pécs, Pécs, Hungary
126 Division of Neuroscience Critical Care, John Hopkins University School of Medicine, Baltimore, USA
127 Department of Neuropathology, Queen Elizabeth University Hospital and University of Glasgow, Glasgow, UK
128 Dept. of Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
129 Department of Pathophysiology and Transplantation, Milan University, and Neuroscience ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy
130 Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden
131 Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku, Turku, Finland
132 Department of Neurosurgery, Kaunas University of Health Sciences, Kaunas, Lithuania
133 Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands
134 Department of Neurosurgery, Kings college London, London, UK
135 Neurologie, Neurochirurgie und Psychiatrie, Charité – Universitätsmedizin Berlin, Berlin, Germany
136 Department of Intensive Care Adults, Erasmus MC– University Medical Center Rotterdam, Rotterdam, the Netherlands
137 icoMetrix NV, Leuven, Belgium
138 Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK
139 Psychology Department, Antwerp University Hospital, Edegem, Belgium
140 Director of Neurocritical Care, University of California, Los Angeles, USA
141 Department of Neurosurgery, St.Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
142 Department of Emergency Medicine, University of Florida, Gainesville, Florida, USA
143 Department of Neurosurgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
144 VTT Technical Research Centre, Tampere, Finland
145 Section of Neurosurgery, Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada