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1. Prognostic models for depression and post-traumatic stress disorder symptoms following traumatic brain injury: a CENTER-TBI study

Author: Kelly Jones, Antonio Belli, Suzanne Polinder, Emmanuel Stamatakis, Hester F Lingsma, Dick Tibboel, Ronny Beer, Raimund Helbok, Horia Ples, Ari Ercole, Peter Cameron, Marek Czosnyka, Catherine McMahon, Peter Vajkoczy, Paul Dark, Alexandra Brazinova, Marek Majdan, Rahul Raj, William Stewart, Ewout W Steyerberg, Giuseppe Citerio, Nino Stocchetti, Alessia Vargiolu, Hester Lingsma, Helen Dawes, Benoit Misset, Faye Johnson, David van Klaveren, Simon Stanworth, Fiona Lecky, Peter Smielewski, Alice Theadom, Peter Bragge, David Nelson, János Sándor, Paul M Vespa, Olli Tenovuo, Olav Røise, Wim Van Hecke, Vincent Degos, David Menon, Bart Depreitere, Audny Anke, Rolf Rossaint, Mark Coburn, Victor Volovici, Daan Nieboer, Jonathan Rosand, Nada Andelic, Hans Clusmann, Emma Donoghue, Jonathan Coles, stefan jankowski, Jonathan Rhodes, Guy Williams, Rolf Lefering, Mathieu van der Jagt, Daniel Kondziella, Noah D Silverberg, Arturo Chieregato, Sophie Richter, Endre Czeiter, Stefan Winzeck, Jan Verheyden, András Büki, Benjamin Gravesteijn, Evgenios Kornaropoulos, Virginia Newcombe, Lindsay Wilson, Lindsay Horton, Amra Covic, Dominique Van Praag, Cecilia Åkerlund, Krisztina Amrein, Lasse Andreassen, Anna Antoni, Gérard Audibert, Philippe Azouvi, Ronald Bartels, Pál Barzó, Romuald Beauvais, Bo-Michael Bellander, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Marta Correia, Nicola Curry, Véronique De Keyser, Hugo den Boogert, Đula Đilvesi, Abhishek Dixit, Jens Dreier, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Jagoš Golubovic Ben Glocker, Johannes Gratz, Francesca Grossi, Deepak Gupta, Iain Haitsma, Eirik Helseth, Jilske Huijben, Bram Jacobs, Mike Jarrett, Mladen Karan, Erwin Kompanje, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Didier Ledoux, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Marc Maegele, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Béla Melegh, Tomas Menovsky, Ana Mikolic, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M Parizel, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Matti Pirinen, Inigo Pomposo, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Malinka Rambadagalla, Sylvia Richardson, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Christina Rosenlund, Guy Rosenthal, Sandra Rossi, Juan Sahuquillo, Oliver Sakowitz, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Abayomi Sorinola, Robert Stevens, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Matt Thomas, Marjolein Timmers, Christos Tolias, Tony Trapani, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Emmanuel Vega, Kimberley Velt, Anne Vik, Rimantas Vilcinis, Daphne Voormolen, Petar Vulekovic, Kevin K W Wang, Eveline Wiegers, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Joukje van der Naalt, Braden Te Ao, Caroline van Heugten, Francesco Della Corte, Ernest Van Veen, Andrew IR Maas, Andreas Unterberg, Thomas A van Essen, Mathilde Jost, Shuyuan Shi, Maria Luisa Azzolini, Maria Rosa Calvi, Jamie D Cooper, Claire Dahyot Fizelier, Guy Loup Dulière, Valery L Feigin, Pedro A Gomez, Russell L Gruen, Juanita A Haagsma, Peter J Hutchinson, Ji yao Jiang, Angelos G Kolias, Lars Owe Koskinen, Andrew I Z Maas, Ana M Castaño León, Jean François Payen, Anna Piippo Karjalainen, Dana Pisica, Jussi PPosti, Isabel Retel Helmrich, Jeffrey VRosenfeld, Daniel Rueckert Martin Rusnák, Renan SanchezPorras, Rico Frederik Schou, Cristina Maria Tudora, Gregory Van der Steen, Jeroen T J M van Dijck, Thijs Vande Vyvere, Roel P J van Wijk, and Nicole von Steinbüchel
Subjects: Psychiatry, RC435-571
Abstract: Background Traumatic brain injury (TBI) is associated with an increased risk of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). We aimed to identify predictors and develop models for the prediction of depression and PTSD symptoms at 6 months post-TBI.Methods We analysed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study. We used linear regression to model the relationship between predictors and depression (Patient Health Questionnaire-9) and PTSD symptoms (PTSD Checklist for Diagnostic and Statistical Manual for Mental Health Disorders Fifth Edition). Predictors were selected based on Akaike’s Information Criterion. Additionally, we fitted logistic models for the endpoints ‘probable MDD’ and ‘probable PTSD’. We also examined the incremental prognostic value of 2–3 weeks of symptoms.Results We included 2163 adults (76% Glasgow Coma Scale=13–15). Depending on the scoring criteria, 7–18% screened positive for probable MDD and about 10% for probable PTSD. For both outcomes, the selected models included psychiatric history, employment status, sex, injury cause, alcohol intoxication and total injury severity; and for depression symptoms also preinjury health and education. The performance of the models was modest (proportion of explained variance=R2 8% and 7% for depression and PTSD, respectively). Symptoms assessed at 2–3 weeks had a large incremental prognostic value (delta R2=0.25, 95% CI 0.24 to 0.26 for depression symptoms; delta R2=0.30, 95% CI 0.29 to 0.31 for PTSD).Conclusion Preinjury characteristics, such as psychiatric history and unemployment, and injury characteristics, such as violent injury cause, can increase the risk of mental health problems after TBI. The identification of patients at risk should be guided by early screening of mental health.
Published: 2025
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2. Diagnostic and prognostic performance of urine ubiquitin carboxy-terminal hydrolase L1 across multiple acute brain injury types – A longitudinal prospective cohort study

Author: Santtu Hellström, Antti Sajanti, Aditya Jhaveri, Abhinav Srinath, Carolyn Bennett, Ying Cao, Fredrika Koskimäki, Johannes Falter, Janek Frantzén, Seán B. Lyne, Tomi Rantamäki, Riikka Takala, Jussi P. Posti, Susanna Roine, Sulo Kolehmainen, Miro Jänkälä, Jukka Puolitaival, Romuald Girard, Melissa Rahi, Jaakko Rinne, Eero Castrén, and Janne Koskimäki
Subjects: Brain injury, UCHL1, Urine, Outcome, Stroke, Traumatic brain injury, Neurology. Diseases of the nervous system, RC346-429
Abstract: Introduction: Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is recognized as a diagnostic and prognostic blood biomarker for traumatic brain injury (TBI). This study aimed to evaluate whether UCH-L1 concentrations measured in patients' urine post-injury could serve as a diagnostic or prognostic biomarker for outcomes in various types of acute brain injuries (ABI). Material and methods: This pilot study included 46 ABI patients: aneurysmal subarachnoid hemorrhage (n = 22), ischemic stroke (n = 16), and traumatic brain injury (n = 8), along with three healthy controls. Urine samples were collected at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) periods post-admission. UCH-L1 and creatinine levels were quantified using ELISA. UCH-L1 concentrations were compared to functional outcomes (modified Rankin Scale, mRS) and dichotomized into favorable (mRS 0–3) and unfavorable (mRS 4–6) groups. Non-parametric statistical tests and ROC analysis was performed. Results: UCH-L1 concentrations in healthy controls were significantly lower compared to both early and late samples after ABI (p ≤ 0.001). The diagnostic performance of urine UCH-L1 at early timepoint showed excellent discriminatory ability, with AUC of 97.6% (95% CI: 93.0–100, p = 0.006 (sensitivity 98%, specificity 100%). Urine UCH-L1 concentrations, both with and without creatinine normalization, did not distinguish between favorable and unfavorable outcomes in either early (p = 0.88 and p = 0.36) or late samples (p = 0.98 and p = 0.30) in any types of ABI. Discussion and conclusions: Although UCH-L1 concentrations in urine did not differentiate between favorable and unfavorable outcomes, a significant difference was observed between healthy subjects and ABI patients. This finding underscores the significant diagnostic utility of urine UCH-L1 concentrations, regardless of the type of acute brain injury.
Published: 2025
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3. Common lipidomic signatures across distinct acute brain injuries in patient outcome prediction

Author: Santtu Hellström, Antti Sajanti, Abhinav Srinath, Carolyn Bennett, Romuald Girard, Aditya Jhaveri, Ying Cao, Johannes Falter, Janek Frantzén, Fredrika Koskimäki, Seán B. Lyne, Tomi Rantamäki, Riikka Takala, Jussi P. Posti, Susanna Roine, Sulo Kolehmainen, Kenneth Nazir, Miro Jänkälä, Jukka Puolitaival, Melissa Rahi, Jaakko Rinne, Anni I. Nieminen, Eero Castrén, and Janne Koskimäki
Subjects: Brain injury, Lipidomics, Neurotrophins, Outcome, Prognosis, Stroke, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Lipidomic alterations have been associated with various neurological diseases. Examining temporal changes in serum lipidomic profiles, irrespective of injury type, reveals promising prognostic indicators. In this longitudinal prospective observational study, serum samples were collected early (46 ± 24 h) and late (142 ± 52 h) post-injury from 70 patients with ischemic stroke, aneurysmal subarachnoid hemorrhage, and traumatic brain injury that had outcomes dichotomized as favorable (modified Rankin Scores (mRS) 0–3) and unfavorable (mRS 4–6) three months post-injury. Lipidomic profiling of 1153 lipids, analyzed using statistical and machine learning methods, identified 153 lipids with late-stage significant outcome differences. Supervised machine learning pinpointed 12 key lipids, forming a combinatory prognostic equation with high discriminatory power (AUC 94.7 %, sensitivity 89 %, specificity 92 %; p
Published: 2025
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4. Genetic vulnerability and adverse mental health outcomes following mild traumatic brain injury: a meta-analysis of CENTER-TBI and TRACK-TBI cohortsResearch in context

Author: Mart Kals, Lindsay Wilson, Daniel F. Levey, Livia Parodi, Ewout W. Steyerberg, Sylvia Richardson, Feng He, Xiaoying Sun, Sonia Jain, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, Geoff T. Manley, Andrew I.R. Maas, Murray B. Stein, David K. Menon, Cecilia Ackerlund, Hadie Adams, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Marc Maegele, Marek Majdan, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Veronika Rehorčíková, Isabel Retel Helmrich, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Ranjit D. Singh, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Aurore Thibaut, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Mathieu van der Jagt, Joukje van der Naalt, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Inge A. van Erp, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Roel van Wijk, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Peter Vulekovic, Daniel Whitehouse, Eveline Wiegers, Guy Williams, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Agate Ziverte, Tommaso Zoerle, Opeolu Adeoye, Neeraj Badjatia, Jason Barber, Michael Bergin, Kim Boase, Yelena Bodien, Randall Chesnut, John Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Venkata Feeser, Adam R. Ferguson, Brandon Foreman, Etienne Gaudette, Joseph Giacino, Luis Gonzalez, Shankar Gopinath, Ramesh Grandhi, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Russell Huie, Ruchira Jha, Dirk C. Keene, Ryan Kitagawa, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Richard Ben Rodgers, Eric Rosenthal, Angelle Sander, Danielle Sandsmark, Andrea Schneider, David Schnyer, Seth Seabury, Mark Sherer, Gabriella Sugar, Nancy Temkin, Arthur Toga, Abel Torres-Espin, Alex Valadka, Mary Vassar, Kevin Wang, Vincent Wang, John K. Yue, Esther Yuh, and Ross Zafonte
Subjects: Traumatic brain injury, Mental health, Post-traumatic stress disorder, Depression, Polygenic risk score, Medicine (General), R5-920
Abstract: Summary: Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings: Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p
Published: 2024
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5. Parsimonious immune-response endotypes and global outcome in patients with traumatic brain injuryResearch in context

Author: Romit J. Samanta, Anne-Cécile Chiollaz, Edward Needham, John K. Yue, Adel Helmy, Elisa R. Zanier, Kevin K.W. Wang, Firas Kobeissy, Jussi P. Posti, Charlotte Summers, Geoffrey T. Manley, Andrew IR. Maas, Olli Tenovuo, Jean-Charles Sanchez, David K. Menon, Neeraj Badjatia, Ramon Diaz-Arrastia, Ann-Christine Duhaime, V Ramana Feeser, Shankar Gopinath, Ramesh Grandhi, Ruchira J. Ha, Dirk Keene, Christopher Madden, Michael McCrea, Randall Merchant, Laura B. Ngwenya, Richard B. Rodgers, David Schnyer, Sabrina R. Taylor, Ross Zafonte, Cecilia Ackerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Ronny Beer, Bo-Michael Bellander, Habib Benali, Maurizio Berardino, Luigi Beretta, Erta Beqiri, Morten Blaabjerg, Stine Borgen Lund, Camilla Brorsson, Andras Buki, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Erzsébet Ezer, Martin Fabricius, Kelly Foks, Shirin Frisvold, Alex Furmanov, Damien Galanaud, Dashiell Gantner, Alexandre Ghuysen, Lelde Giga, Jagoš Golubović, Pedro A. Gomez, Benjamin Gravesteijn, Francesca Grossi, Deepak Gupta, Iain Haitsma, Raimund Helbok, Eirik Helseth, Jilske Huijben, Peter J. Hutchinson, Stefan Jankowski, Faye Johnson, Mladen Karan, Angelos G. Kolias, Daniel Kondziella, Evgenios Kornaropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Steven Laureys, Fiona Lecky, Didier Ledoux, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, David Menon, Tomas Menovsky, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, József Nyirádi, Fabrizio Ortolano, Jean-François Payen, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Horia Ples, Inigo Pomposo, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Oddrun Sandrød, Kari Schirmer-Mikalsen, Rico Frederik Schou, Charlie Sewalt, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Matt Thomas, Dick Tibboel, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Roel van Wijk, Alessia Vargiolu, Emmanuel Vega, Anne Vik, Rimantas Vilcinis, Victor Volovici, Peter Vulekovic, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Alexander Younsi, Frederick A. Zeiler, Agate Ziverte, and Tommaso Zoerle
Subjects: Traumatic brain injury, Stratified medicine, Inflammation, Clustering, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.
Published: 2024
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6. Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injuryResearch in context

Author: Lindsay Wilson, Virginia F.J. Newcombe, Daniel P. Whitehouse, Stefania Mondello, Andrew I.R. Maas, David K. Menon, Cecilia Ackerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, David Nelson, Daan Nieboer, József Nyirádi, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Isabel Retel Helmrich, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Ranjit D. Singh, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Aurore Thibaut, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Mathieu van der Jagt, Joukje van der Naalt, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Inge A. van Erp, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Roel P.J. van Wijk, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Peter Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, and Tommaso Zoerle
Subjects: Traumatic brain injury, Blood biomarkers, GFAP, NFL, UCH-L1, Outcomes, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.
Published: 2024
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7. The prevalence of cardiac complications and their impact on outcomes in patients with non-traumatic subarachnoid hemorrhage

Author: Maarit Lång, Stephan M. Jakob, Riikka Takala, Magnus N. Lyngbakken, Anu Turpeinen, Torbjørn Omland, Tobias M. Merz, Jan Wiegand, Juha Grönlund, Melissa Rahi, Mika Valtonen, Timo Koivisto, Helge Røsjø, and Stepani Bendel
Subjects: Medicine, Science
Abstract: Abstract Subarachnoid hemorrhage (SAH) is a serious condition, and a myocardial injury or dysfunction could contribute to the outcome. We assessed the prevalence and prognostic impact of cardiac involvement in a cohort with SAH. This is a prospective observational multicenter study. We included 192 patients treated for non-traumatic subarachnoid hemorrhage. We performed ECG recordings, echocardiographic examinations, and blood sampling within 24 h of admission and on days 3 and 7 and at 90 days. The primary endpoint was the evidence of cardiac involvement at 90 days, and the secondary endpoint was to examine the prevalence of a myocardial injury or dysfunction. The median age was 54.5 (interquartile range [IQR] 48.0–64.0) years, 44.3% were male and the median World Federation of Neurological Surgeons (WFNS) score was 2 (IQR 1–4). At day 90, 22/125 patients (17.6%) had left ventricular ejection fractions ≤ 50%, and 2/121 patients (1.7%) had evidence of a diastolic dysfunction as defined by mitral peak E-wave velocity by peak eʹ velocity (E/eʹ) > 14. There was no prognostic impact from echocardiographic evidence of cardiac complications on neurological outcomes. The overall prevalence of cardiac dysfunction was modest. We found no demographic or SAH-related factors associated with 90 days cardiac dysfunction.
Published: 2022
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8. Comparative effectiveness of decompressive craniectomy versus craniotomy for traumatic acute subdural hematoma (CENTER-TBI): an observational cohort studyResearch in context

Author: Thomas A. van Essen, Inge A.M. van Erp, Hester F. Lingsma, Dana Pisică, John K. Yue, Ranjit D. Singh, Jeroen T.J.M. van Dijck, Victor Volovici, Alexander Younsi, Angelos Kolias, Lianne D. Peppel, Majanka Heijenbrok-Kal, Gerard M. Ribbers, David K. Menon, Peter J.A. Hutchinson, Geoffrey T. Manley, Bart Depreitere, Ewout W. Steyerberg, Andrew I.R. Maas, Godard C.W. de Ruiter, Wilco C. Peul, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, Lars-Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Veronika Rehorčíková, Isabel Retel Helmrich, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Ana Kowark, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Mathieu Van der Jagt, Joukje van der Naalt, Gregory Van der Steen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest Van Veen, Roel van Wijk, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Frederick A. Zeiler, Agate Ziverte, and Tommaso Zoerle
Subjects: Acute subdural hematoma, Decompressive craniectomy, Craniotomy, Comparative effectiveness research, Instrumental variable analysis, Practice variation, Medicine (General), R5-920
Abstract: Summary: Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p
Published: 2023
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9. Dynamic prediction of mortality after traumatic brain injury using a machine learning algorithm

Author: Rahul Raj, Jenni M. Wennervirta, Jonathan Tjerkaski, Teemu M. Luoto, Jussi P. Posti, David W. Nelson, Riikka Takala, Stepani Bendel, Eric P. Thelin, Teemu Luostarinen, and Miikka Korja
Subjects: Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Abstract Intensive care for patients with traumatic brain injury (TBI) aims to optimize intracranial pressure (ICP) and cerebral perfusion pressure (CPP). The transformation of ICP and CPP time-series data into a dynamic prediction model could aid clinicians to make more data-driven treatment decisions. We retrained and externally validated a machine learning model to dynamically predict the risk of mortality in patients with TBI. Retraining was done in 686 patients with 62,000 h of data and validation was done in two international cohorts including 638 patients with 60,000 h of data. The area under the receiver operating characteristic curve increased with time to 0.79 and 0.73 and the precision recall curve increased with time to 0.57 and 0.64 in the Swedish and American validation cohorts, respectively. The rate of false positives decreased to ≤2.5%. The algorithm provides dynamic mortality predictions during intensive care that improved with increasing data and may have a role as a clinical decision support tool.
Published: 2022
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10. Brain Plasticity Modulator p75 Neurotrophin Receptor in Human Urine after Different Acute Brain Injuries—A Prospective Cohort Study

Author: Santtu Hellström, Antti Sajanti, Abhinav Srinath, Carolyn Bennett, Romuald Girard, Ying Cao, Janek Frantzén, Fredrika Koskimäki, Johannes Falter, Seán B. Lyne, Tomi Rantamäki, Riikka Takala, Jussi P. Posti, Susanna Roine, Jukka Puolitaival, Miro Jänkälä, Sulo Kolehmainen, Melissa Rahi, Jaakko Rinne, Eero Castrén, and Janne Koskimäki
Subjects: neurotrophins, brain injury, stroke, trauma, outcome, recovery, Biology (General), QH301-705.5
Abstract: Acute brain injuries (ABIs) pose a substantial global burden, demanding effective prognostic indicators for outcomes. This study explores the potential of urinary p75 neurotrophin receptor (p75NTR) concentration as a prognostic biomarker, particularly in relation to unfavorable outcomes. The study involved 46 ABI patients, comprising sub-cohorts of aneurysmal subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. Furthermore, we had four healthy controls. Samples were systematically collected from patients treated at the University Hospital of Turku between 2017 and 2019, at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) post-admission time points. Urinary p75NTR levels, measured by ELISA and normalized to creatinine, were compared against patients’ outcomes using the modified Rankin Scale (mRS). Early urine samples showed no significant p75NTR concentration difference between favorable and unfavorable mRS groups. In contrast, late samples exhibited a statistically significant increase in p75NTR concentrations in the unfavorable group (p = 0.033), demonstrating good prognostic accuracy (AUC = 70.9%, 95% CI = 53–89%, p = 0.03). Assessment of p75NTR concentration changes over time revealed no significant variation in the favorable group (p = 0.992) but a significant increase in the unfavorable group (p = 0.009). Moreover, p75NTR concentration was significantly higher in ABI patients (mean ± SD 40.49 ± 28.83–65.85 ± 35.04 ng/mg) compared to healthy controls (mean ± SD 0.54 ± 0.44 ng/mg), irrespective of sampling time or outcome (p < 0.0001). In conclusion, late urinary p75NTR concentrations emerged as a potential prognostic biomarker for ABIs, showing increased levels associated with unfavorable outcomes regardless of the specific type of brain injury. While early samples exhibited no significant differences, the observed late increases emphasize the time-dependent nature of this potential biomarker. Further validation in larger patient cohorts is crucial, highlighting the need for additional research to establish p75NTR as a reliable prognostic biomarker across various ABIs. Additionally, its potential role as a diagnostic biomarker warrants exploration.
Published: 2024
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11. Concomitant spine trauma in patients with traumatic brain injury: Patient characteristics and outcomes

Author: Lennart Riemann, Obada T. Alhalabi, Andreas W. Unterberg, Alexander Younsi, The CENTER-TBI investigators and participants, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Cović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Ðula Ðilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Ana M. Castaño-León, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Isabel Retel Helmrich, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Ranjit D. Singh, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Inge A. van Erp, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Thijs Vande Vyvere, Roel P. J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Daniel Whitehouse, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, and Tommaso Zoerle
Subjects: traumatic brain injury, traumatic spine injury, outcome, CENTER-TBI, spine trauma, Neurology. Diseases of the nervous system, RC346-429
Abstract: ObjectiveSpine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).MethodsData from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7–8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.ResultsA total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37–66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.ConclusionRates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.
Published: 2022
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12. Cerebral Microbleeds and Structural White Matter Integrity in Patients With Traumatic Brain Injury—A Diffusion Tensor Imaging Study

Author: Juho Dahl, Olli Tenovuo, Jussi P. Posti, Jussi Hirvonen, Ari J. Katila, Janek Frantzén, Henna-Riikka Maanpää, Riikka Takala, Eliisa Löyttyniemi, Jussi Tallus, Virginia Newcombe, David K. Menon, Peter J. Hutchinson, and Mehrbod Mohammadian
Subjects: traumatic brain injury, white matter, cerebral microbleeds, diffuse axonal injury, diffusion tensor imaging, Neurology. Diseases of the nervous system, RC346-429
Abstract: Diffuse axonal injury (DAI) is a common neuropathological manifestation of traumatic brain injury (TBI), presenting as traumatic alterations in the cerebral white matter (WM) microstructure and often leading to long-term neurocognitive impairment. These WM alterations can be assessed using diffusion tensor imaging (DTI). Cerebral microbleeds (CMBs) are a common finding on head imaging in TBI and are often considered a visible sign of DAI, although they represent diffuse vascular injury. It is poorly known how they associate with long-term white matter integrity. This study included 20 patients with TBI and CMBs, 34 patients with TBI without CMBs, and 11 controls with orthopedic injuries. DTI was used to assess microstructural WM alterations. CMBs were detected using susceptibility-weighted imaging (SWI) and graded according to their location in the WM and total lesion load was counted. Patients underwent SWI within 2 months after injury. DTI and clinical outcome assessment were performed at an average of eight months after injury. Outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The Glasgow Coma Scale (GCS) and length of post-traumatic amnesia (PTA) were used to assess clinical severity of the injury. We found that CMB grading and total lesion load were negatively associated with fractional anisotropy (FA) and positively associated with mean diffusivity (MD). Patients with TBI and CMBs had decreased FA and increased MD compared with patients with TBI without CMBs. CMBs were also associated with worse clinical outcome. When adjusting for the clinical severity of the injury, none of the mentioned associations were found. Thus, the difference in FA and MD is explained by patients with TBI and CMBs having more severe injuries. Our results suggest that CMBs are not associated with greater WM alterations when adjusting for the clinical severity of TBI. Thus, CMBs and WM alterations may not be strongly associated pathologies in TBI.
Published: 2022
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13. Neurocognitive correlates of probable posttraumatic stress disorder following traumatic brain injury

Author: Dominique L.G. Van Praag, Kristien Wouters, Filip Van Den Eede, Lindsay Wilson, Andrew I.R. Maas, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Iris Ceyisakar, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Ana M. Castaño-León, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P.J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, and Tommaso Zoerle
Subjects: Cognition, Head injury, Neuropsychology, Posttraumatic stress disorder, Stress, Neurology. Diseases of the nervous system, RC346-429
Abstract: Introduction: Neurocognitive problems associated with posttraumatic stress disorder (PTSD) can interact with impairment resulting from traumatic brain injury (TBI). Research question: We aimed to identify neurocognitive problems associated with probable PTSD following TBI in a civilian sample. Material and methods: The study is part of the CENTER-TBI project (Collaborative European Neurotrauma Effectiveness Research) that aims to better characterize TBI. For this cross-sectional study, we included patients of all severities aged over 15, and a Glasgow Outcome Score Extended (GOSE) above 3. Participants were assessed at six months post-injury on the PTSD Checklist-5 (PCL-5), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Primary analysis was a complete case analysis. Regression analyses were performed to investigate the association between the PCL-5 and cognition. Results: Of the 1134 participants included in the complete case analysis, 13.5% screened positive for PTSD. Probable PTSD was significantly associated with higher TMT-(B-A) (OR = 1.35, 95% CI: 1.14–1.60, p
Published: 2022
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14. The influence of dexmedetomidine and propofol on circulating cytokine levels in healthy subjects

Author: Minna Kallioinen, Annalotta Scheinin, Mikael Maksimow, Jaakko Långsjö, Kaike Kaisti, Riikka Takala, Tero Vahlberg, Katja Valli, Marko Salmi, Harry Scheinin, and Anu Maksimow
Subjects: Dexmedetomidine, Propofol, Immunology, Immunosuppression, Cytokines, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background Surgery and diseases modify inflammatory responses and the immune system. Anesthetic agents also have effects on the human immune system but the responses they induce may be altered or masked by the surgical procedures or underlying illnesses. The aim of this study was to assess how single-drug dexmedetomidine and propofol anesthesia without any surgical intervention alter acute immunological biomarkers in healthy subjects. Methods Thirty-five healthy, young male subjects were anesthetized using increasing concentrations of dexmedetomidine (n = 18) or propofol (n = 17) until loss of responsiveness (LOR) was detected. The treatment allocation was randomized. Multi-parametric immunoassays for the detection of 48 cytokines, chemokines and growth factors were used. Concentrations were determined at baseline and at the highest drug concentration for each subject. Results The changes in the concentration of eotaxin (decrease after dexmedetomidine) and platelet-derived growth factor (PDGF, increase after propofol) were statistically significantly different between the groups. Significant changes were detected within both groups; the concentrations of monocyte chemotactic protein 1, chemokine ligand 27 and macrophage migration inhibitory factor were lower in both groups after the drug administration. Dexmedetomidine decreased the concentration of eotaxin, interleukin-18, interleukin-2Rα, stem cell factor, stem cell growth factor and vascular endothelial growth factor, and propofol decreased significantly the levels of hepatocyte growth factor, IFN-γ-induced protein 10 and monokine induced by IFN-γ, and increased the levels of interleukin-17, interleukin-5, interleukin-7 and PDGF. Conclusions Dexmedetomidine seemed to have an immunosuppressive effect on the immune system whereas propofol seemed to induce mixed pro- and anti-inflammatory effects on the immune system. The choice of anesthetic agent could be relevant when treating patients with compromised immunological defense mechanisms. Trial registration Before subject enrollment, the study was registered in the European Clinical Trials database (EudraCT number 2013–001496-21, The Neural Mechanisms of Anesthesia and Human Consciousness) and in ClinicalTrials.gov (Principal Investigator: Harry Scheinin, number NCT01889004, The Neural Mechanisms of Anesthesia and Human Consciousness, Part 2, on the 23rd of June 2013).
Published: 2019
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15. Volume Change in Frontal Cholinergic Structures After Traumatic Brain Injury and Cognitive Outcome

Author: Anna Östberg, Christian Ledig, Ari Katila, Henna-Riikka Maanpää, Jussi P. Posti, Riikka Takala, Jussi Tallus, Ben Glocker, Daniel Rueckert, and Olli Tenovuo
Subjects: cholinergic system, traumatic brain injury, atlas based volumetric MRI analysis, structural MRI, cognitive testing, Neurology. Diseases of the nervous system, RC346-429
Abstract: The cholinergic nuclei in the basal forebrain innervate frontal cortical structures regulating attention. Our aim was to investigate if cognitive test results measuring attention relate to the longitudinal volume change of cholinergically innervated structures following traumatic brain injury (TBI). During the prospective, observational TBIcare project patients with all severities of TBI (n = 114) and controls with acute orthopedic injuries (n = 17) were recruited. Head MRI was obtained in both acute (mean 2 weeks post-injury) and late (mean 8 months) time points. T1-weighted 3D MR images were analyzed with an automatic segmentation method to evaluate longitudinal, structural brain volume change. The cognitive outcome was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses included 16 frontal cortical structures, of which four showed a significant correlation between post-traumatic volume change and the CANTAB test results. The strongest correlation was found between the volume loss of the supplementary motor cortex and motor screening task results (R-sq 0.16, p < 0.0001), where poorer test results correlated with greater atrophy. Of the measured sum structures, greater cortical gray matter atrophy rate showed a significant correlation with the poorer CANTAB test results. TBI caused volume loss of frontal cortical structures that are heavily innervated by cholinergic neurons is associated with neuropsychological test results measuring attention.
Published: 2020
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16. High angular resolution diffusion-weighted imaging in mild traumatic brain injury

Author: Mehrbod Mohammadian, Timo Roine, Jussi Hirvonen, Timo Kurki, Henna Ala-Seppälä, Janek Frantzén, Ari Katila, Anna Kyllönen, Henna-Riikka Maanpää, Jussi Posti, Riikka Takala, Jussi Tallus, and Olli Tenovuo
Subjects: Traumatic brain injury, Magnetic resonance imaging, Diffusion-weighted magnetic resonance imaging, Probabilistic tractography, Global approach, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: We sought to investigate white matter abnormalities in mild traumatic brain injury (mTBI) using diffusion-weighted magnetic resonance imaging (DW-MRI). We applied a global approach based on tract-based spatial statistics skeleton as well as constrained spherical deconvolution tractography. DW-MRI was performed on 102 patients with mTBI within two months post-injury and 30 control subjects. A robust global approach considering only the voxels with a single-fiber configuration was used in addition to global analysis of the tract skeleton and probabilistic whole-brain tractography. In addition, we assessed whether the microstructural parameters correlated with age, time from injury, patient's outcome and white matter MRI hyperintensities. We found that whole-brain global approach restricted to single-fiber voxels showed significantly decreased fractional anisotropy (FA) (p = 0.002) and increased radial diffusivity (p = 0.011) in patients with mTBI compared with controls. The results restricted to single-fiber voxels were more significant and reproducible than those with the complete tract skeleton or the whole-brain tractography. FA correlated with patient outcomes, white matter hyperintensities and age. No correlation was observed between FA and time of scan post-injury. In conclusion, the global approach could be a promising imaging biomarker to detect white matter abnormalities following traumatic brain injury.
Published: 2017
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17. Analysis of intracranial pressure pulse waveform in traumatic brain injury patients: a CENTER-TBI study

Author: Agnieszka Uryga, Arkadiusz Ziółkowski, Agnieszka Kazimierska, Agata Pudełko, Cyprian Mataczyński, Erhard W. Lang, Marek Czosnyka, Magdalena Kasprowicz, Audny Anke, Ronny Beer, Bo-Michael Bellander, Erta Beqiri, Andras Buki, Manuel Cabeleira, Marco Carbonara, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Endre Czeiter, Bart Depreitere, Ari Ercole, Shirin Frisvold, Raimund Helbok, Stefan Jankowski, Danile Kondziella, Lars-Owe Koskinen, Ana Kowark, David K. Menon, Geert Meyfroidt, Kirsten Moeller, David Nelson, Anna Piippo-Karjalainen, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Jonathan Rhodes, Saulius Rocka, Rolf Rossaint, Juan Sahuquillo, Oliver Sakowitz, Peter Smielewski, Nino Stocchetti, Nina Sundström, Riikka Takala, Tomas Tamosuitis, Olli Tenovuo, Andreas Unterberg, Peter Vajkoczy, Alessia Vargiolu, Rimantas Vilcinis, Stefan Wolf, Alexander Younsi, Frederick A. Zeiler, Ragauskas, Arminas, Rocka, Saulius, Tamosuitis, Tomas, Vilcinis, Rimantas, American asssociation of neurological ssurgeons, Uryga, A, Ziółkowski, A, Kazimierska, A, Pudełko, A, Mataczyński, C, Lang, E, Czosnyka, M, Kasprowicz, M, Citerio, G, Ročka, Saulius, and Tamošuitis, Tomas
Subjects: intracranial pressure, pulse amplitude, pulse shape index, clinical outcome, spectral analysis, morphological analysis, traumatic brain injury, spectral analysi, morphological analysi, General Medicine
Abstract: OBJECTIVE Intracranial pressure (ICP) pulse waveform analysis may provide valuable information about cerebrospinal pressure-volume compensation in patients with traumatic brain injury (TBI). The authors applied spectral methods to analyze ICP waveforms in terms of the pulse amplitude of ICP (AMP), high frequency centroid (HFC), and higher harmonics centroid (HHC) and also used a morphological classification approach to assess changes in the shape of ICP pulse waveforms using the pulse shape index (PSI). METHODS The authors included 184 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Sub-Study in the analysis. HFC was calculated as the average power-weighted frequency within the 4- to 15-Hz frequency range of the ICP power density spectrum. HHC was defined as the center of mass of the ICP pulse waveform harmonics from the 2nd to the 10th. PSI was defined as the weighted sum of artificial intelligence–based ICP pulse class numbers from 1 (normal pulse waveform) to 4 (pathological waveform). RESULTS AMP and PSI increased linearly with mean ICP. HFC increased proportionally to ICP until the upper breakpoint (average ICP of 31 mm Hg), whereas HHC slightly increased with ICP and then decreased significantly when ICP exceeded 25 mm Hg. AMP (p < 0.001), HFC (p = 0.003), and PSI (p < 0.001) were significantly greater in patients who died than in patients who survived. Among those patients with low ICP (< 15 mm Hg), AMP, PSI, and HFC were greater in those with poor outcome than in those with good outcome (all p < 0.001). CONCLUSIONS Whereas HFC, AMP, and PSI could be used as predictors of mortality, HHC may potentially serve as an early warning sign of intracranial hypertension. Elevated HFC, AMP, and PSI were associated with poor outcome in TBI patients with low ICP.
Published: 2022
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18. Casemix, management, and mortality of patients receiving emergency neurosurgery for traumatic brain injury in the Global Neurotrauma Outcomes Study: a prospective observational cohort study

Author: David Clark, Alexis Joannides, Amos Olufemi Adeleye, Abdul Hafid Bajamal, Tom Bashford, Hagos Biluts, Karol Budohoski, Ari Ercole, Rocío Fernández-Méndez, Anthony Figaji, Deepak Kumar Gupta, Roger Härtl, Corrado Iaccarino, Tariq Khan, Tsegazeab Laeke, Andrés Rubiano, Hamisi K Shabani, Kachinga Sichizya, Manoj Tewari, Abenezer Tirsit, Myat Thu, Manjul Tripathi, Rikin Trivedi, Bhagavatula Indira Devi, Franco Servadei, David Menon, Angelos Kolias, Peter Hutchinson, Ghayur Abbas, Omar Ibrahim Abdallah, Ahmed Abdel-Lateef, Khalif Abdifatah, Awfa Abdullateef, Ruvini Abeygunaratne, Mostafa Aboellil, Abass Adam, Robert Adams, Amos Adeleye, Augustine Adeolu, Novan Krisno Adji, Nur Afianti, Sudarsan Agarwal, Ifeanyi Kene Aghadi, Paúl Martín Méndez Aguilar, Syeda Rida Ahmad, Daniyal Ahmed, Nafees Ahmed, Haider Aizaz, Yunus Kuntawi Aji, Alex Alamri, Augusto Jacinto Mussindo Alberto, Luis Alcocer Alcocer, Lesly Gonzales Alfaro, Amro Al-Habib, Ahmad Alhourani, Syed Muhammad Rafay Ali, Fahad Alkherayf, Ahmed AlMenabbawy, Aliyah Alshareef, Muhammad Adil s/o Aminullah, Madeha Amjad, Robson Luis Oliveira de Amorim, Sathiaprabhu Anbazhagan, Almir Andrade, Waleed Antar, Theophilus T.K. Anyomih, Salah Aoun, Tedy Apriawan, Daniele Armocida, Paul Arnold, Miguel Arraez, Temesgen Assefa, Andres Asser, S.P. Athiththan, Deepal Attanayake, Maung Maung Aung, Allan Avi, Victor Enrique Antolinez Ayala, Mohammed Azab, Gaousul Azam, Mohd Azharuddin, Olukemi Badejo, Mohamed Badran, Azam Ali Baig, Rehman Ali Baig, Ankur Bajaj, Paul Baker, Renu Bala, Artur Balasa, Ross Balchin, James Balogun, Vin Shen Ban, Bharath Kumar Reddy Bandi, Soham Bandyopadhyay, Matthew Bank, Ernest Barthelemy, Mohammed Talha Bashir, Luciano Silveira Basso, Surajit Basu, Auricelio Batista, Marlies Bauer, Devi Bavishi, Abi Beane, Shmuel Bejell, Anteneh Belachew, Antonio Belli, Amani Belouaer, Najia El Abbadi Bendahane, Okanga Benjamin, Youssef Benslimane, Chaymae Benyaiche, Claudio Bernucci, Luigi Valentino Berra, Arnold Bhebe, Alexios Bimpis, Diana Blanaru, Jean Claude Bonfim, Luis A B Borba, Alp Ozgun Borcek, Erika Borotto, Ahmad Elmabri Mohammad Bouhuwaish, Facundo Bourilhon, Gioia Brachini, Joshua Breedon, Maximilian Broger, Giacoma Maria Floriana Brunetto, Placido Bruzzaniti, Natalia Budohoska, Hira Burhan, Maximiliano Luis Calatroni, Catherine Camargo, Pier Francesco Cappai, Salvatore Massimiliano Cardali, Ana M Castaño-Leon, David Cederberg, Mikel Celaya, Marco Cenzato, Lakshmi Madhavi Challa, Dhanny Charest, Bipin Chaurasia, Rabah Chenna, Iype Cherian, Juliana Henry Ching'o, Tejas Chotai, Ajay Choudhary, Nabeel Choudhary, Florence Choumin, Tomislav Cigic, Juan Ciro, Carlo Conti, Antônio Carlos de Souza Corrêa, Giulia Cossu, Maíra Piani Couto, Aurora Cruz, Divya D'Silva, Giuseppe Antonio D'Aliberti, Lamin Dampha, Roy Thomas Daniel, Andrew Dapaah, Aneela Darbar, Gabriel Dascalu, Happy Amos Dauda, Owain Davies, Andrea Delgado-Babiano, Markus Dengl, Marko Despotovic, Indira Devi, Celeste Dias, Mohamed Dirar, Melina Dissanayake, Hananiah Djimbaye, Simon Dockrell, Ali Dolachee, Julija Dolgopolova, Muge Dolgun, Abdalrouf Dow, Davide Drusiani, Artjom Dugan, Dinh Tuan Duong, Trung Kien Duong, Tomasz Dziedzic, Ali Ebrahim, Nizar El Fatemi, Antonios El El Helou, Rachid El El Maaqili, Brahim El El Mostarchid, Abdessamad El El Ouahabi, Mohammad Elbaroody, Ahmed El-Fiki, Ahmed El-Garci, Nasser M.F. El-Ghandour, Muhammed Elhadi, Vanessa Elleder, Safa Elrais, Mohamed El-shazly, Mohamed Elshenawy, Hesham Elshitany, Omar El-Sobky, Marwa Emhamed, Basil Enicker, Onur Erdogan, Sebastian Ertl, Ignatius Esene, Omar Ocampo Espinosa, Tarig Fadalla, Mohammed Fadelalla, Rodrigo Moreira Faleiro, Nida Fatima, Charbel Fawaz, Assefa Fentaw, Carla Eiriz Fernandez, Ana Ferreira, Francesco Ferri, Tony Figaji, Emerson L B Filho, Loic Fin, Benjamin Fisher, Fitra Fitra, Alexis Palpan Flores, Ioan Stefan Florian, Vincenzo Fontana, Lauren Ford, Daniel Fountain, Jose Maria Roda Frade, Antonio Fratto, Christian Freyschlag, Aranzazu Sánchez Gabin, Clare Gallagher, Mario Ganau, Maria Luisa Gandia-Gonzalez, Andoni Garcia, Borja Hernandez Garcia, Sanjeewa Garusinghe, Biniam Gebreegziabher, Adrian Gelb, Jerome St George, Antonino Francesco Germanò, Ilaria Ghetti, Prajwal Ghimire, Alessandro Giammarusti, Jose Luis Gil, Panagiota Gkolia, Yoseph Godebo, Prakash Rao Gollapudi, Jagos Golubovic, Jeremias Fernando Gomes, Javier Gonzales, William Gormley, Alexander Gots, Giulia Letizia Gribaudi, Dylan Griswold, Paolo Gritti, Ruan Grobler, Rudy Gunawan, Birhanu Hailemichael, Elmehdi Hakkou, Mark Haley, Alhafidz Hamdan, Ali Hammed, Waeel Hamouda, Nurul Ashikin Hamzah, Nyein Latt Han, Sahin Hanalioglu, Rashan Haniffa, Martin Hanko, John Hanrahan, Timothy Hardcastle, Fahd Derkaoui Hassani, Volkmar Heidecke, Eirik Helseth, Miguel Ángel Hernández-Hernández, Zachary Hickman, Le Minh Chau Hoang, Alexa Hollinger, Lenka Horakova, Kismet Hossain-Ibrahim, Boru Hou, Samer Hoz, Janine Hsu, Martin Hunn, Madiha Hussain, Giorgia Iacopino, Mylena Miki Lopes Ideta, Irene Iglesias, Ali Ilunga, Nafiz Imtiaz, Rafiza Islam, Serge Ivashchenko, Karim Izirouel, Mohamed Sobhi Jabal, Soubhi Jabal, John Nute Jabang, Aimun Jamjoom, Irfan Jan, Landing BM Jarju, Saad Javed, Bojan Jelaca, Sukhdeep Singh Jhawar, Ting Ting Jiang, Fernando Jimenez, Jorge Jiris, Ron Jithoo, Walt Johnson, Mathew Joseph, Rameshman Joshi, Eija Junttila, Mubashir Jusabani, Stephen Akau Kache, Satyavara Prasad Kadali, Gabriela F Kalkmann, Usman Kamboh, Hitham Kandel, Ahmet Kamil Karakus, Mengistu Kassa, Ari Katila, Yoko Kato, Martin Keba, Kristy Kehoe, Huseyin Hayri Kertmen, Soha Khafaji, Monty Khajanchi, Mohammed Khan, Muhammad Mukhtar Khan, Sohail Daud Khan, Ahtesham Khizar, Amir Khriesh, Sara Kierońska, Paul Kisanga, Boniface Kivevele, Kacper Koczyk, Anna-Lucia Koerling, Danielle Koffenberger, Kennet Kõiv, Leho Kõiv, Branislav Kolarovszki, Marton König, Dilek Könü-Leblebicioglu, Santhoshi Devi Koppala, Tommi Korhonen, Boguslaw Kostkiewicz, Kacper Kostyra, Srinivas Kotakadira, Arjun Reddy Kotha, Madhu Narayana Rao Kottakki, Nenad Krajcinovic, Michal Krakowiak, Andreas Kramer, Selvamuthukumaran Krishnamoorthy, Ashok Kumar, Pankaj Kumar, Pradhumna Kumar, Nilaksha Kumarasinghe, Gowtham Kuncha, Raja K. Kutty, Ghazwan Lafta, Simon Lammy, Pierfrancesco Lapolla, Jacopo Lardani, Nebojsa Lasica, Giancarlo Lastrucci, Yoann Launey, Laura Lavalle, Tim Lawrence, Albert Lazaro, Vitalii Lebed, Ville Leinonen, Lawrence Lemeri, Leon Levi, Jia Yi Lim, Xiao Yi Lim, Jorge Linares-Torres, Laura Lippa, Lurdes Lisboa, Jinfang Liu, Ziyuan Liu, William B Lo, Jan Lodin, Federico Loi, Daniella Londono, Pedro Antonio Gomez Lopez, Cristina Barceló López, Madeleine De Lotbiniere-Bassett, Rihards Lulens, Facundo Hector Luna, Teemu Luoto, Vijaya Sekhar M.V., Ndyebo Mabovula, Matthew MacAllister, Alcina Americo Macie, Rodolfo Maduri, Moufid Mahfoud, Ashraf Mahmood, Fathia Mahmoud, Dominic Mahoney, Wissam Makhlouf, George Malcolm, Adefolarin Malomo, Toluyemi Malomo, Manoranjitha Kumari Mani, Tomás Gazzinelli Marçal, Jacopo Marchello, Nicolò Marchesini, Franz Marhold, Niklas Marklund, Rubén Martín-Láez, Vickneswaran Mathaneswaran, David José Mato-Mañas, Helen Maye, Aaron Lawson McLean, Catherine McMahon, Saniya Mediratta, Mehreen Mehboob, Alisson Meneses, Nesrine Mentri, Hagos Mersha, Ana Milena Mesa, Cristy Meyer, Christopher Millward, Salomao Amone Mimbir, Andrea Mingoli, Parashruram Mishra, Tejesh Mishra, Basant Misra, Siddharth Mittal, Imran Mohammed, Ioana Moldovan, Masechaba Molefe, Alexis Moles, Preston Moodley, Mario Augusto Narváez Morales, Lucy Morgan, German Del Castillo Morillo, Wahab Moustafa, Nikolaos Moustakis, Salma Mrichi, Satya Shiva Munjal, Abdul-Jalilu Mohammed Muntaka, Denver Naicker, Paulo E H Nakashima, Pratap Kumar Nandigama, Samantha Nash, Ionut Negoi, Valetina Negoita, Samundra Neupane, Manh Hung Nguyen, Fajar Herbowo Niantiarno, Abbi Noble, Mohd Arman Muhamad Nor, Blazej Nowak, Andrei Oancea, Frazer O'Brien, Oghenekevwe Okere, Sandra Olaya, Leandro Oliveira, Louise Makarem Oliveira, Fatma Omar, Okezi Ononeme, René Opšenák, Simone Orlandini, Alrobah Osama, Dorcas Osei-Poku, Haytham Osman, Alvaro Otero, Malte Ottenhausen, Shuli Otzri, Oumaima Outani, Emmanuel Abem Owusu, Kevin Owusu-Agyemang, Ahmad Ozair, Baris Ozoner, Elli Paal, Mauro Sérgio Paiva, Wellingson Paiva, Sharad Pandey, Gastone Pansini, Luigi Pansini, Tobias Pantel, Nikolaos Pantelas, Konstantinos Papadopoulos, Vladimir Papic, Kee Park, Nick Park, Eric Homero Albuquerque Paschoal, Mylla Christie de Oliveira Paschoalino, Rajesh Pathi, Anilkumar Peethambaran, Thiago Andrade Pereira, Irene Panero Perez, Claudio José Piqueras Pérez, Tamilanandh Periyasamy, Stefano Peron, Michael Phillips, Sofía Sotos Picazo, Ertugrul Pinar, Daniel Pinggera, Rory Piper, Pathmanesan Pirakash, Branko Popadic, Jussi P. Posti, Rajmohan Bhanu Prabhakar, Sivanesalingam Pradeepan, Manjunath Prasad, Paola Calvachi Prieto, Ron Prince, Andrea Prontera, Eva Provaznikova, Danilo Quadros, Nezly Jadid Romero Quintero, Mahmood Qureshi, Happiness Rabiel, Gabriel Rada, Sivagnanam Ragavan, Jueria Rahman, Omar Ramadhan, Padma Ramaswamy, Sakina Rashid, Jagath Rathugamage, Tõnu Rätsep, Minna Rauhala, Asif Raza, Naga Raju Reddycherla, Linus Reen, Mohamed Refaat, Luca Regli, Haijun Ren, Antonio Ria, Thales Francisco Ribeiro, Alessandro Ricci, Romana Richterová, Florian Ringel, Faith Robertson, Catarina Mayrink Siqueira Cabral Rocha, Juvenal de Souza Rogério, Adan Anibal Romano, Sally Rothemeyer, Gail Rousseau Gail Rousseau, Ranette Roza, Kevin David Farelo Rueda, Raiza Ruiz, Malin Rundgren, Radoslaw Rzeplinski, Raj S.Chandran, Ramesh Andi Sadayandi, William Sage, André Norbert Josef Sagerer, Mustafa Sakar, Mohcine Salami, Danjuma Sale, Youssuf Saleh, Cristina Sánchez-Viguera, Saning'o Sandila, Ahmet Metin Sanli, Laura Santi, Antonio Santoro, Aieska Kellen Dantas Dos Santos, Samir Cezimbra dos Santos, Borja Sanz, Shabal Sapkota, Gopalakrishnan Sasidharan, Ibrahim Sasillo, Rajeev Satoskar, Ali Caner Sayar, Vignesh Sayee, Florian Scheichel, Felipe Lourenzon Schiavo, Alexander Schupper, Andreas Schwarz, Teresa Scott, Esther Seeberger, Claudionor Nogueira Costa Segundo, Anwar Sadat Seidu, Antonio Selfa, Nazan Has Selmi, Claudiya Selvarajah, Necmiye Şengel, Martin Seule, Luiz Severo, Purva Shah, Muhammad Shahzad, Thobekile Shangase, Mayur Sharma, Ehab Shiban, Emnet Shimber, Temitayo Shokunbi, Kaynat Siddiqui, Emily Sieg, Martin Siegemund, Shahidur Rahman Sikder, Ana Cristina Veiga Silva, Ana Silva, Pedro Alberto Silva, Deepinder Singh, Carly Skadden, Josef Skola, Eirini Skouteli, Pawel Słoniewski, Brandon Smith, Guirish Solanki, Davi Fontoura Solla, Davi Solla, Ozcan Sonmez, Müge Sönmez, Wai Cheong Soon, Roberto Stefini, Martin Nikolaus Stienen, Bogdan Stoica, Matthew Stovell, Maria Natalia Suarez, Alaa Sulaiman, Mazin Suliman, Adi Sulistyanto, Şeniz Sulubulut, Sandra Sungailaite, Madlen Surbeck, Tomasz Szmuda, Graziano Taddei, Abraham Tadele, Ahmed Saleh Ahmed Taher, Riikka Takala, Krishna Murthy Talari, Bih Huei Tan, Leonardo Tariciotti, Murad Tarmohamed, Oumayma Taroua, Emiliano Tatti, Olli Tenovuo, Sami Tetri, Poojan Thakkar, Nqobile Thango, Satish Kumar Thatikonda, Tuomo Thesleff, Claudius Thomé, Owen Thornton, Shelly Timmons, Eva Ercilio Timoteo, Campbell Tingate, Souhil Tliba, Christos Tolias, Emma Toman, Ivan Torres, Luis Torres, Youness Touissi, Musa Touray, Maria Pia Tropeano, Georgios Tsermoulas, Christos Tsitsipanis, Mehmet Erhan Turkoglu, Özhan Merzuk Uçkun, Jamie Ullman, Gheorghe Ungureanu, Sarah Urasa, Obaid Ur-Rehman, Muhammed Uysal, Antonios Vakis, Egils Valeinis, Vaishali Valluru, Debby Vannoy, Pablo Vargas, Phillipos Varotsis, Rahul Varshney, Atul Vats, Damjan Veljanoski, Sara Venturini, Abhijit Verma, Clara Villa, Genaro Villa, Sofia Villar, Erin Villard, Antonio Viruez, Stefanos Voglis, Petar Vulekovic, Saman Wadanamby, Katherine Wagner, Rebecca Walshe, Jan Walter, Marriam Waseem, Tony Whitworth, Ruwani Wijeyekoon, Adam Williams, Mark Wilson, Sein Win, Achmad Wahib Wahju Winarso, Abraão Wagner Pessoa Ximenes, Anurag Yadav, Dipak Yadav, Kamal Makram Yakoub, Ali Yalcinkaya, Guizhong Yan, Eesha Yaqoob, Carlos Yepes, Ayfer Nazmiye Yılmaz, Betelehem Yishak, Farhat Basheer Yousuf, Muhammad Zamzuri Zahari, Hussein Zakaria, Diego Zambonin, Luca Zavatto, Bassel Zebian, Anna Maria Zeitlberger, Furong Zhang, Fengwei Zheng, and Michal Ziga
Subjects: casemix, management, mortality, emergency neurosurgery, traumatic brain injury, prospective observational cohort study, Neurology (clinical)
Abstract: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.
Published: 2022
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19. Abstract TP234: Different Type Of Acute Brain Injuries Share Similar Pattern Of Lipidomic Profile Changes In Human Serum

Author: Antti Sajanti, Santtu Hellström, Romuald Girard, Janek Frantzen, Juzoh Umemori, Fredrika Koskimäki, Sean B. Lyne, Johannes Falter, Tomi Rantamäki, Kenneth Nazir, Bajera Gharat, Jussi Posti, Susanna Roine, Riikka Takala, Sulo Kolehmainen, Ying Cao, Yan Li, Iiro Heino, Melissa Rahi, Jaakko Rinne, Anni I Nieminen, Eero Castren, and Janne Koskimaki
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Background: Neuronal recovering processes after acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI) are complex including brain plasticity and synaptic regeneration mechanisms. Temporal changes in lipidomic profile after different acute brain injuries may reveal new insights about brain plasticity, recovery and biomarker development after acute injury. Hypotheses: Measurable temporal changes in serum lipidomic profile may be similar irrespective of the type of the brain injury and may reveal conserved molecular aberrations after different types of acute brain injuries. These common changes may also be associated to outcome and serve as possible biomarkers. Methods: Prospective cohort (n=74) consisted of IS (n=30), aSAH (n=31) and TBI (n=13) patients. Serum samples were collected in two time points after the insult (early 24-48h and late 120-192h). Lipidomic profiling of 1153 lipids was performed using Lipidyzer Platform. The lipidomics data was analyzed with Metaboanalyst for ANOVA, PCA, heatmap, box plots with following settings: missing values were imputated with KNN using 20% cutoff, log-transformed and auto-scaled. Results: We identified four diacylglycerols (DAG), one cholesterol ester (CE), seven triacylglycerols (TAG) and one sphingomyelin (SM) which showed increased levels in late serum samples across all types of brain injuries (p Conclusion: Changes in lipidomic profiles across time were identified. This suggests common lipidomic characteristics irrespective of the type of brain insult and encourage further studies. Interestingly, lipidomic profiles may be associated to recovery after acute brain injury and further analyses of this data will follow.
Published: 2023
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20. Abstract TP236: Temporal Metabolomic Profiling Exposed Affiliated Metabolites Altered And Associations To Outcome After Different Acute Brain Injuries

Author: Santtu Hellström, Antti Sajanti, Romuald Girard, Janek Frantzen, Juzoh Umemori, Fredrika Koskimaki, Sean B. Lyne, Johannes Falter, Tomi Rantamäki, Kenneth Nazir, Bharat Gajera, Jussi Posti, Susanna Roine, Riikka Takala, Sulo Kolehmainen, Ying Cao, Yan Li, Iiro Heino, Melissa Rahi, Jaakko Rinne, Anni Nieminen, Eero Castren, and Janne Koskimaki
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Background: Neuronal recovering processes after acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI) are complex including brain plasticity and synaptic regeneration mechanisms. Hypotheses: Transient changes in metabolome after different acute brain injuries may reveal affiliated metabolites, metabolic pathways and associations that can also reflect important biological mechanisms. Measurable temporal changes in serum metabolomic profile may be similar irrespective of the type of the brain injury. These metabolomic commonalities may be associated to outcome. Methods: Prospective cohort (n=74) consisted of IS (n=30), aSAH (n=31) and TBI (n=13) patients. Serum samples were collected in two time points after the insult (early 24-48h and late 120-192h). Orbitrap Profiling of 462 metabolites was used to measure metabolites. Outcome was measured 90 days after injury (mRS favorable 0-3, unfavorable 4-6). The metabolomics data was imputed for missing value using KNN with 20% cut off for missing value, log-transformed and autoscaled. For statistics, t-test and ANOVA was performed and FDR-corrected p-value 0.05 was considered to be statistically significant. Results: We identified four similarly temporally increased metabolite levels across all acute brain injury types (p Conclusion: Similar metabolic changes across time were identified with apparent associations to outcome. This suggests important common metabolic characteristics irrespective of the type of brain insult and encourage further studies and validation. Identified metabolites may be further developed as a prognostic biomarker and may indicate new metabolic pathways active irrespective the type of brain injury reflecting biological mechanisms.
Published: 2023
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21. Abstract WP222: Temporally Differentially Expressed MikroRNAs In Serum Predict Recovery In Different Acute Brain Injuries

Author: Antti Sajanti, Santtu Hellström, Yan Li, Ying Cao, Romuald Girard, Janek Frantzen, Juzoh Umemori, Fredrika Koskimaki, Sean B. Lyne, Johannes Falter, Tomi Rantamäki, Kenneth Nazir, Bharat Gajera, Jussi Posti, Susanna Roine, Riikka Takala, Sulo Kolehmainen, Iiro Heino, Melissa Rahi, Jaakko Rinne, Anni Nieminen, Eero Castren, and Janne Koskimaki
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Background: Brain plasticity is important processes in recovering after different types of acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI). Knowledge gaps still exist which miRNAs contribute to recovery of the acute brain injuries. Hypotheses: Temporally differentially expressed (DE) miRNAs after acute brain injuries may have association to outcome irrespective the type of the acute brain injury. MiRNAs that are DE across different type of brain injuries may reveal important conserved associations that can reflect important biological mechanisms and serve as a biomarker. Methods: Prospective cohort (n=24) consisted of IS (n=8), aSAH (n=8) and TBI (n=8) patients. Two serum samples were collected per patient (early 24-48h and late 120-192h after injury). Outcome was measured 90 days after injury (mRS favorable 0-3 (n=15), unfavorable 4-6 (n=9). MiRNAs were extracted from the samples (total n = 48 samples). Sequencing was performed and DESeq2 was used to identify DE miRNAs. The miRNA putative target genes were predicted with miRWalk. Normalized expression values of identified DE miRNAs were used and linear canonical discriminant analysis (LDA) was performed. Canonical scores were used to build combinatory biomarker with logistic modelling predicting outcome. Results: We identified 22 temporally DE miRNAs (p Conclusions: Results show that combinatory biomarker of identified miRNAs perform well across different type of brain injuries. Validation in larger cohort is justified. Identified common miRNAs also provide new targets for mechanistical validation in disease models of TBI and stroke.
Published: 2023
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22. Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI)

Author: Eveline Janine Anna Wiegers, Hester Floor Lingsma, Jilske Antonia Huijben, David James Cooper, Giuseppe Citerio, Shirin Frisvold, Raimund Helbok, Andrew Ian Ramsay Maas, David Krishna Menon, Elizabeth Madeleine Moore, Nino Stocchetti, Diederik Willem Dippel, Ewout Willem Steyerberg, Mathieu van der Jagt, Joanne Brooker, Peter Bragge, Jeffrey Rosenfeld, Jamie D. Cooper, Ronny Beer, Herbert Schoechl, Martin Rusnák, Elisabeth Schwendenwein, Anna Antoni, Véronique De Keyser, Tomas Menovsky, Dominique Van Praag, Andrew I.R. Maas, Gregory Van der Steen, Paul M. Parizel, Thijs Vande Vyvere, Bart Depreitere, Wim Van Hecke, Jan Verheyden, Benoit Misset, Didier Ledoux, Steven Laureys, Alexandre Ghuysen, Hugues Maréchal, Guy-Loup Dulière, Guoyi Gao, Ji-yao Jiang, Daniel Kondziella, Martin Fabricius, Rico Frederik Schou, Morten Blaabjerg, Christina Rosenlund, Anna Piippo-Karjalainen, Rahul Raj, Matti Pirinen, Samuli Ripatti, Aarno Palotie, Peter Ylén, Jussi P. Posti, Olli Tenovuo, Riikka Takala, Jean-François Payen, Emmanuel Vega, Aurelie Lejeune, Gérard Audibert, Vincent Degos, Habib Benali, Damien Galanaud, Vincent Perlbarg, Louis Puybasset, Philippe Azouvi, Valerie Legrand, Claire Dahyot-Fizelier, Rolf Rossaint, Mark Steven Coburn, Ana Kowark, Hans Clusmann, Jens Dreier, Stefan Wolf, Peter Vajkoczy, Marc Maegele, Johannes Gratz, Nadine Schäfer, Rolf Lefering, Amra Covic, Nicole von Steinbüchel, Silke Schmidt, Monika Bullinger, Alexander Younsi, Andreas Unterberg, Julia Mattern, Oliver Sakowitz, Renan Sanchez-Porras, Natascha Perera, Romuald Beauvais, Janos Sandor, Endre Czeiter, Andras Buki, Erzsébet Ezer, Zoltán Vámos, Béla Melegh, Viktória Tamás, Abayomi Sorinola, Noémi Kovács, József Nyirádi, Krisztina Amrein, Pál Barzó, Deepak Gupta, Leon Levi, Guy Rosenthal, Alex Furmanov, Costanza Martino, Luigi Beretta, Maria Rosa Calvi, Maria Luisa Azzolini, Emiliana Calappi, Tommaso Zoerle, Fabrizio Ortolano, Marco Carbonara, Alessio Caccioppola, Alessia Vargiolu, Arturo Chieregato, Giorgio Chevallard, Francesco Della Corte, Francesca Grossi, Sandra Rossi, Paolo Persona, Maurizio Berardino, Simona Cavallo, Malinka Rambadagalla, Agate Ziverte, Lelde Giga, Egils Valeinis, Rimantas Vilcinis, Tomas Tamosuitis, Saulius Rocka, Arminas Ragauskas, Joukje van der Naalt, Bram Jacobs, Ewout W. Steyerberg, Ronald Bartels, Hugo den Boogert, Erwin Kompanje, Marjolijn Timmers, Kelly Foks, Iain Haitsma, Victor Volovici, Juanita A. Haagsma, Ana Mikolic, Hester Lingsma, Kimberley Velt, Jilske Huijben, Daphne Voormolen, Daan Nieboer, Eveline Wiegers, Charlie Sewalt, Benjamin Gravesteijn, Suzanne Polinder, Dick Tibboel, Roel van Wijk, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wilco Peul, Guus Schoonman, Kelly Jones, Valery L. Feigin, Braden Te Ao, Alice Theadom, Eirik Helseth, Cecilie Roe, Olav Roise, Nada Andelic, Lasse Andreassen, Audny Anke, Anne Vik, Toril Skandsen, Horia Ples, Cristina Maria Tudora, Ancuta Negru, Peter Vulekovic, Đula Đilvesi, Mladen Karan, Jagoš Golubovic, Veronika Rehorcíková, Mark Steven Taylor, Alexandra Brazinova, Marek Majdan, Juan Sahuquillo, Andreea Radoi, Guillermo Carbayo Lozano, Inigo Pomposo, Alfonso Lagares, Pedro A. Gomez, Ana M. Castaño-León, Pablo Gagliardo, Matej Oresic, Bo-Michael Bellander, Linda Lanyon, Pradeep George, Visakh Muraleedharan, David Nelson, Cecilia Ackerlund, Lars-Owe Koskinen, Nina Sundström, Camilla Brorsson, Antonio Belli, Alex Manara, Matt Thomas, Marek Czosnyka, Peter Smielewski, Manuel Cabeleira, Jonathan Coles, Sylvia Richardson, Frederick A. Zeiler, Emmanuel Stamatakis, Guy Williams, David Menon, Ari Ercole, Abhishek Dixit, Virginia Newcombe, Sophie Richter, Charles McFadyen, Peter J. Hutchinson, Angelos G. Kolias, Hadie Adams, Marta Correia, Jonathan Rhodes, William Stewart, Catherine McMahon, Daniel Rueckert, Ben Glocker, Christos Tolias, Helen Dawes, Patrick Esser, Caroline van Heugten, Nicola Curry, Simon Stanworth, Fiona Lecky, Olubukola Otesile, Faye Johnson, Paul Dark, Stefan Jankowski, Roger Lightfoot, Lindsay Wilson, Lindsay Horton, Robert Stevens, Jonathan Rosand, Geoffrey Manley, Mike Jarrett, Vibeke Brinck, Kevin K.W. Wang, Zhihui Yang, Paul M. Vespa, Russell L. Gruen, Peter Cameron, Emma Donoghue, Dashiell Gantner, Russel Gruen, Lynette Murray, Jeffrey V. Rosenfeld, Dinesh Varma, Tony Trapani, Shirley Vallance, Cristopher MacIsaac, Andrea Jordan, Wiegers, E. J. A., Lingsma, H. F., Huijben, J. A., Cooper, D. J., Citerio, G., Frisvold, S., Helbok, R., Maas, A. I. R., Menon, D. K., Moore, E. M., Stocchetti, N., Dippel, D. W., Steyerberg, E. W., van der Jagt, M., Brooker, J., Bragge, P., Rosenfeld, J., Cooper, J. D., Beer, R., Schoechl, H., Rusnak, M., Schwendenwein, E., Antoni, A., De Keyser, V., Menovsky, T., Van Praag, D., Van der Steen, G., Parizel, P. M., Vande Vyvere, T., Depreitere, B., Van Hecke, W., Verheyden, J., Misset, B., Ledoux, D., Laureys, S., Ghuysen, A., Marechal, H., Duliere, G. -L., Gao, G., Jiang, J. -Y., Kondziella, D., Fabricius, M., Schou, R. F., Blaabjerg, M., Rosenlund, C., Piippo-Karjalainen, A., Raj, R., Pirinen, M., Ripatti, S., Palotie, A., Ylen, P., Posti, J. P., Tenovuo, O., Takala, R., Payen, J. -F., Vega, E., Lejeune, A., Audibert, G., Degos, V., Benali, H., Galanaud, D., Perlbarg, V., Puybasset, L., Azouvi, P., Legrand, V., Dahyot-Fizelier, C., Rossaint, R., Coburn, M. S., Kowark, A., Clusmann, H., Dreier, J., Wolf, S., Vajkoczy, P., Maegele, M., Gratz, J., Schafer, N., Lefering, R., Covic, A., von Steinbuchel, N., Schmidt, S., Bullinger, M., Younsi, A., Unterberg, A., Mattern, J., Sakowitz, O., Sanchez-Porras, R., Perera, N., Beauvais, R., Sandor, J., Czeiter, E., Buki, A., Ezer, E., Vamos, Z., Melegh, B., Tamas, V., Sorinola, A., Kovacs, N., Nyiradi, J., Amrein, K., Barzo, P., Gupta, D., Levi, L., Rosenthal, G., Furmanov, A., Martino, C., Beretta, L., Calvi, M. R., Azzolini, M. L., Calappi, E., Zoerle, T., Ortolano, F., Carbonara, M., Caccioppola, A., Vargiolu, A., Chieregato, A., Chevallard, G., Della Corte, F., Grossi, F., Rossi, S., Persona, P., Berardino, M., Cavallo, S., Rambadagalla, M., Ziverte, A., Giga, L., Valeinis, E., Vilcinis, R., Tamosuitis, T., Rocka, S., Ragauskas, A., van der Naalt, J., Jacobs, B., Bartels, R., den Boogert, H., Kompanje, E., Timmers, M., Foks, K., Haitsma, I., Volovici, V., Haagsma, J. A., Mikolic, A., Lingsma, H., Velt, K., Huijben, J., Voormolen, D., Nieboer, D., Wiegers, E., Sewalt, C., Gravesteijn, B., Polinder, S., Tibboel, D., van Wijk, R., van Dijck, J. T. J. M., van Essen, T. A., Peul, W., Schoonman, G., Jones, K., Feigin, V. L., Te Ao, B., Theadom, A., Helseth, E., Roe, C., Roise, O., Andelic, N., Andreassen, L., Anke, A., Vik, A., Skandsen, T., Ples, H., Tudora, C. M., Negru, A., Vulekovic, P., Dilvesi, D., Karan, M., Golubovic, J., Rehorcikova, V., Taylor, M. S., Brazinova, A., Majdan, M., Sahuquillo, J., Radoi, A., Carbayo Lozano, G., Pomposo, I., Lagares, A., Gomez, P. A., Castano-Leon, A. M., Gagliardo, P., Oresic, M., Bellander, B. -M., Lanyon, L., George, P., Muraleedharan, V., Nelson, D., Ackerlund, C., Koskinen, L. -O., Sundstrom, N., Brorsson, C., Belli, A., Manara, A., Thomas, M., Czosnyka, M., Smielewski, P., Cabeleira, M., Coles, J., Richardson, S., Zeiler, F. A., Stamatakis, E., Williams, G., Menon, D., Ercole, A., Dixit, A., Newcombe, V., Richter, S., Mcfadyen, C., Hutchinson, P. J., Kolias, A. G., Adams, H., Correia, M., Rhodes, J., Stewart, W., Mcmahon, C., Rueckert, D., Glocker, B., Tolias, C., Dawes, H., Esser, P., van Heugten, C., Curry, N., Stanworth, S., Lecky, F., Otesile, O., Johnson, F., Dark, P., Jankowski, S., Lightfoot, R., Wilson, L., Horton, L., Stevens, R., Rosand, J., Manley, G., Jarrett, M., Brinck, V., Wang, K. K. W., Yang, Z., Vespa, P. M., Gruen, R. L., Cameron, P., Donoghue, E., Gantner, D., Gruen, R., Murray, L., Rosenfeld, J. V., Varma, D., Trapani, T., Vallance, S., Macisaac, C., Jordan, A., Public Health, Neurology, Intensive Care, Neurosurgery, Erasmus MC other, Pediatric Surgery, CENTER-TBI Collaboration Group, OzENTER-TBI Collaboration Group, Molecular Neuroscience and Ageing Research (MOLAR), Psychology 3, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Wiegers, E, Lingsma, H, Huijben, J, Cooper, D, Citerio, G, Frisvold, S, Helbok, R, Maas, A, Menon, D, Moore, E, Stocchetti, N, Dippel, D, Steyerberg, E, van der Jagt, M, Brooker, J, Bragge, P, Rosenfeld, J, Cooper, J, Beer, R, Schoechl, H, Rusnák, M, Schwendenwein, E, Antoni, A, De Keyser, V, Menovsky, T, Van Praag, D, Van der Steen, G, Parizel, P, Vande Vyvere, T, Depreitere, B, Van Hecke, W, Verheyden, J, Misset, B, Ledoux, D, Laureys, S, Ghuysen, A, Maréchal, H, Dulière, G, Gao, G, Jiang, J, Kondziella, D, Fabricius, M, Schou, R, Blaabjerg, M, Rosenlund, C, Piippo-Karjalainen, A, Raj, R, Pirinen, M, Ripatti, S, Palotie, A, Ylén, P, Posti, J, Tenovuo, O, Takala, R, Payen, J, Vega, E, Lejeune, A, Audibert, G, Degos, V, Benali, H, Galanaud, D, Perlbarg, V, Puybasset, L, Azouvi, P, Legrand, V, Dahyot-Fizelier, C, Rossaint, R, Coburn, M, Kowark, A, Clusmann, H, Dreier, J, Wolf, S, Vajkoczy, P, Maegele, M, Gratz, J, Schäfer, N, Lefering, R, Covic, A, von Steinbüchel, N, Schmidt, S, Bullinger, M, Younsi, A, Unterberg, A, Mattern, J, Sakowitz, O, Sanchez-Porras, R, Perera, N, Beauvais, R, Sandor, J, Czeiter, E, Buki, A, Ezer, E, Vámos, Z, Melegh, B, Tamás, V, Sorinola, A, Kovács, N, Nyirádi, J, Amrein, K, Barzó, P, Gupta, D, Levi, L, Rosenthal, G, Furmanov, A, Martino, C, Beretta, L, Calvi, M, Azzolini, M, Calappi, E, Zoerle, T, Ortolano, F, Carbonara, M, Caccioppola, A, Vargiolu, A, Chieregato, A, Chevallard, G, Della Corte, F, Grossi, F, Rossi, S, Persona, P, Berardino, M, Cavallo, S, Rambadagalla, M, Ziverte, A, Giga, L, Valeinis, E, Vilcinis, R, Tamosuitis, T, Rocka, S, Ragauskas, A, van der Naalt, J, Jacobs, B, Bartels, R, den Boogert, H, Kompanje, E, Timmers, M, Foks, K, Haitsma, I, Volovici, V, Haagsma, J, Mikolic, A, Velt, K, Voormolen, D, Nieboer, D, Sewalt, C, Gravesteijn, B, Polinder, S, Tibboel, D, van Wijk, R, van Dijck, J, van Essen, T, Peul, W, Schoonman, G, Jones, K, Feigin, V, Te Ao, B, Theadom, A, Helseth, E, Roe, C, Roise, O, Andelic, N, Andreassen, L, Anke, A, Vik, A, Skandsen, T, Ples, H, Tudora, C, Negru, A, Vulekovic, P, Đilvesi, Đ, Karan, M, Golubovic, J, Rehorcíková, V, Taylor, M, Brazinova, A, Majdan, M, Sahuquillo, J, Radoi, A, Carbayo Lozano, G, Pomposo, I, Lagares, A, Gomez, P, Castaño-León, A, Gagliardo, P, Oresic, M, Bellander, B, Lanyon, L, George, P, Muraleedharan, V, Nelson, D, Ackerlund, C, Koskinen, L, Sundström, N, Brorsson, C, Belli, A, Manara, A, Thomas, M, Czosnyka, M, Smielewski, P, Cabeleira, M, Coles, J, Richardson, S, Zeiler, F, Stamatakis, E, Williams, G, Ercole, A, Dixit, A, Newcombe, V, Richter, S, Mcfadyen, C, Hutchinson, P, Kolias, A, Adams, H, Correia, M, Rhodes, J, Stewart, W, Mcmahon, C, Rueckert, D, Glocker, B, Tolias, C, Dawes, H, Esser, P, van Heugten, C, Curry, N, Stanworth, S, Lecky, F, Otesile, O, Johnson, F, Dark, P, Jankowski, S, Lightfoot, R, Wilson, L, Horton, L, Stevens, R, Rosand, J, Manley, G, Jarrett, M, Brinck, V, Wang, K, Yang, Z, Vespa, P, Gruen, R, Cameron, P, Donoghue, E, Gantner, D, Murray, L, Varma, D, Trapani, T, Vallance, S, Macisaac, C, and Jordan, A
Subjects: medicine.medical_specialty, Fluid balance and outcome in critically ill patients traumatic brain injury, Icu mortality, Traumatic brain injury, Critically ill, business.industry, INTRACRANIAL-PRESSURE, Glasgow Outcome Scale, Odds ratio, medicine.disease, GUIDELINES, Intensive care unit, law.invention, law, Emergency medicine, medicine, MANAGEMENT, Observational study, Neurology (clinical), Human medicine, business, Balance (ability)
Abstract: Background Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in fluid management policies in patients with traumatic brain injury and to study the effect of this variability on patients' outcomes.Methods We did a prospective, multicentre, comparative effectiveness study of two observational cohorts: CENTER-TBI in Europe and OzENTER-TBI in Australia. Patients from 55 hospitals in 18 countries, aged 16 years or older with traumatic brain injury requiring a head CT, and admitted to the ICU were included in this analysis. We extracted data on demographics, injury, and clinical and treatment characteristics, and calculated the mean daily fluid balance (difference between fluid input and loss) and mean daily fluid input during ICU stay per patient. We analysed the association of fluid balance and input with ICU mortality and functional outcome at 6 months, measured by the Glasgow Outcome Scale Extended (GOSE). Patient-level analyses relied on adjustment for key characteristics per patient, whereas centre-level analyses used the centre as the instrumental variable.Findings 2125 patients enrolled in CENTER-TBI and OzENTER-TBI between Dec 19, 2014, and Dec 17, 2017, were eligible for inclusion in this analysis. The median age was 50 years (IQR 31 to 66) and 1566 (74%) of patients were male. The median of the mean daily fluid input ranged from 1middot48 L (IQR 1middot12 to 2middot09) to 4middot23 L (3middot78 to 4middot94) across centres. The median of the mean daily fluid balance ranged from -0middot85 L (IQR -1middot51 to -0middot49) to 1middot13 L (0middot99 to 1middot37) across centres. In patient-level analyses, a mean positive daily fluid balance was associated with higher ICU mortality (odds ratio [OR] 1middot10 [95% CI 1middot07 to 1middot12] per 0middot1 L increase) and worse functional outcome (1middot04 [1middot02 to 1middot05] per 0middot1 L increase); higher mean daily fluid input was also associated with higher ICU mortality (1middot05 [1middot03 to 1middot06] per 0middot1 L increase) and worse functional outcome (1middot04 [1middot03 to 1middot04] per 1-point decrease of the GOSE per 0middot1 L increase). Centre-level analyses showed similar associations of higher fluid balance with ICU mortality (OR 1middot17 [95% CI 1middot05 to 1middot29]) and worse functional outcome (1middot07 [1middot02 to 1middot13]), but higher fluid input was not associated with ICU mortality (OR 0middot95 [0middot90 to 1middot00]) or worse functional outcome (1middot01 [0middot98 to 1middot03]).Interpretation In critically ill patients with traumatic brain injury, there is significant variability in fluid management, with more positive fluid balances being associated with worse outcomes. These results, when added to previous evidence, suggest that aiming for neutral fluid balances, indicating a state of normovolaemia, contributes to improved outcome. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
Published: 2021
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23. Surgery versus conservative treatment for traumatic acute subdural haematoma: a prospective, multicentre, observational, comparative effectiveness study

Author: Thomas A van Essen, Hester F Lingsma, Dana Pisică, Ranjit D Singh, Victor Volovici, Hugo F den Boogert, Alexander Younsi, Lianne D Peppel, Majanka H Heijenbrok-Kal, Gerard M Ribbers, Robert Walchenbach, David K Menon, Peter Hutchinson, Bart Depreitere, Ewout W Steyerberg, Andrew I R Maas, Godard C W de Ruiter, Wilco C Peul, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, Lars-Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Veronika Rehorčíková, Isabel Retel Helmrich, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Ana Kowark, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Mathieu Van der Jagt, Joukje van der Naalt, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest Van Veen, Roel van Wijk, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Frederick A. Zeiler, Agate Ziverte, Tommaso Zoerle, CENTER-TBI Collaboration Group, Molecular Neuroscience and Ageing Research (MOLAR), Public Health, Neurosurgery, Rehabilitation Medicine, van Essen, T, Lingsma, H, Pisică, D, Singh, R, Volovici, V, den Boogert, H, Younsi, A, Peppel, L, Heijenbrok-Kal, M, Ribbers, G, Walchenbach, R, and Citerio, G
Subjects: Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Brain Injuries, Traumatic, traumatic acute subdural haematoma, Glasgow Outcome Scale, Hematoma, Subdural, Acute, Humans, Surgery, Prospective Studies, Neurology (clinical), Human medicine, Conservative Treatment
Abstract: Contains fulltext : 251563.pdf (Publisher’s version ) (Closed access) BACKGROUND: Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute surgical evacuation with one preferring initial conservative treatment in acute subdural haematoma. METHODS: We did a prospective, observational, comparative effectiveness study using data from participants enrolled in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We included patients with no pre-existing severe neurological disorders who presented with acute subdural haematoma within 24 h of traumatic brain injury. Using an instrumental variable analysis, we compared outcomes between centres according to treatment preference for acute subdural haematoma (acute surgical evacuation or initial conservative treatment), measured by the case-mix-adjusted percentage of acute surgery per centre. The primary endpoint was functional outcome at 6 months as rated with the Glasgow Outcome Scale Extended, which was estimated with ordinal regression as a common odds ratio (OR) and adjusted for prespecified confounders. Variation in centre preference was quantified with the median OR (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). FINDINGS: Between Dec 19, 2014 and Dec 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI, of whom 1407 (31%) presented with acute subdural haematoma and were included in our study. Acute surgical evacuation was done in 336 (24%) patients, by craniotomy in 245 (73%) of those patients and by decompressive craniectomy in 91 (27%). Delayed decompressive craniectomy or craniotomy after initial conservative treatment (n=982) occurred in 107 (11%) patients. The percentage of patients who underwent acute surgery ranged from 5·6% to 51·5% (IQR 12·3-35·9) between centres, with a two-times higher probability of receiving acute surgery for an identical patient in one centre versus another centre at random (adjusted MOR for acute surgery 1·8; p
Published: 2022
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24. Incidence, Risk Factors, and Effects on Outcome of Ventilator-Associated Pneumonia in Patients With Traumatic Brain Injury

Author: Chiara Robba, Paola Rebora, Erika Banzato, Eveline J.A. Wiegers, Nino Stocchetti, David K. Menon, Giuseppe Citerio, Cecilia Åkerlund, David Nelson, Krisztina Amrein, József Nyirádi, Nada Andelic, Lasse Andreassen, Audny Anke, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Luigi Beretta, Maria Rosa Calvi, Ronald Bartels, Hugo den Boogert, Ronny Beer, Raimund Helbok, Bo-Michael Bellander, Habib Benali, Vincent Degos, Damien Galanaud, Vincent Perlbarg, Audrey Vanhaudenhuyse, Maurizio Berardino, Morten Blaabjerg, Stine Borgen Lund, Camilla Brorsson, Andras Buki, Endre Czeiter, Manuel Cabeleira, Marek Czosnyka, Peter Smielewski, Alessio Caccioppola, Emiliana Calappi, Marco Carbonara, Davide Mulazzi, Fabrizio Ortolano, Tommaso Zoerle, Peter Cameron, Dashiell Gantner, Lynnette Murray, Tony Trapani, Shirley Vallance, Guillermo Carbayo Lozano, Inigo Pomposo, Ana M. Castaño-León, Pedro A. Gomez, Alfonso Lagares, Giorgio Chevallard, Arturo Chieregato, Mark Coburn, Ana Kowark, Rolf Rossaint, Jonathan Coles, Jamie D. Cooper, Marta Correia, Claire Dahyot-Fizelier, Véronique De Keyser, Andrew I.R. Maas, Tomas Menovsky, Nandesh Nair, Gregory Van der Steen, Francesco Della Corte, Francesca Grossi, Bart Depreitere, Dula Dilvesi, Jagos Golubovic, Mladen Karan, Petar Vulekovic, Abhishek Dixit, Ari Ercole, Evgenios Koraropoulos, David Menon, Virginia Newcombe, Sophie Richter, Emmanuel Stamatakis, Guy Williams, Stefan Winzeck, Frederik A. Zeiler, Jens Dreier, Guy-Loup Dulière, Hugues Maréchal, Erzsébet Ezer, Zoltán Vámos, Martin Fabricius, Daniel Kondziella, Kelly Foks, Shirin Frisvold, Alex Furmanov, Guy Rosenthal, Alexandre Ghuysen, Lelde Giga, Egils Valeinis, Agate Ziverte, Deepak Gupta, Iain Haitsma, Victor Volovici, Eirik Helseth, Peter J. Hutchinson, Angelos G. Kolias, Stefan Jankowski, Lars-Owe Koskinen, Noémi Kovács, Steven Laureys, Quentin Noirhomme, Aurelie Lejeune, Emmanuel Vega, Roger Lightfoot, Ewout W. Steyerberg, Hester Lingsma, Daphne Voormolen, Alex Manara, Matt Thomas, Costanza Martino, Julia Mattern, Oliver Sakowitz, Alexander Younsi, Catherine McMahon, Visakh Muraleedharan, Ancuta Negru, Horia Ples, Cristina Maria Tudora, Jean-François Payen, Paolo Persona, Sandra Rossi, Wilco Peul, Jeroen T.J. M. van Dijck, Thomas A. van Essen, Roel P.J. van Wijk, Anna Piippo-Karjalainen, Rahul Raj, Jussi P. Posti, Olli Tenovuo, Louis Puybasset, Andreea Radoi, Juan Sahuquillo, Arminas Ragauskas, Saulius Rocka, Jonathan Rhodes, Cecilie Roe, Olav Roise, Jeffrey V. Rosenfeld, Christina Rosenlund, Oddrun Sandro, Kari Schirmer-Mikalsen, Renan Sanchez-Porras, Anne Vik, Rico Frederik Schou, Abayomi Sorinola, Viktória Tamás, Nina Sundström, Riikka Takala, Tomas Tamosuitis, Dick Tibboel, Christos Tolias, Peter Vajkoczy, Alessia Vargiolu, Rimantas Vilcinis, and Stefan Wolf
Subjects: Pulmonary and Respiratory Medicine, Mechanical ventilation, medicine.medical_specialty, Longitudinal study, Traumatic brain injury, business.industry, medicine.medical_treatment, Incidence (epidemiology), Glasgow Outcome Scale, Ventilator-associated pneumonia, Critical Care and Intensive Care Medicine, medicine.disease, respiratory tract diseases, Clinical trial, Interquartile range, Emergency medicine, medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Background No large prospective data, to our knowledge, are available on ventilator-associated pneumonia (VAP) in patients with traumatic brain injury (TBI). Research Question To evaluate the incidence, timing, and risk factors of VAP after TBI and its effect on patient outcome. Study Design and Methods This analysis is of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury data set, from a large, multicenter, prospective, observational study including patients with TBI admitted to European ICUs, receiving mechanical ventilation for ≥ 48 hours and with an ICU length of stay (LOS) ≥ 72 hours. Characteristics of patients with VAP vs characteristics of patients without VAP were compared, and outcome was assessed at 6 months after injury by using the Glasgow Outcome Scale Extended. Results The study included 962 patients: 196 (20.4%) developed a VAP at a median interval of 5 days (interquartile range [IQR], 3-7 days) after intubation. Patients who developed VAP were younger (median age, 39.5 [IQR, 25-55] years vs 51 [IQR, 30-66] years; P Interpretation VAP occurs less often than previously described in patients after TBI and has a detrimental effect on ICU LOS but not on mortality and neurological outcome. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT02210221; URL: www.clinicaltrials.gov
Published: 2020
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25. Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury

Author: Louis Jacob, Mélanie Cogné, Olli Tenovuo, Cecilie Røe, Nada Andelic, Marek Majdan, Jukka Ranta, Peter Ylen, Helen Dawes, Philippe Azouvi, Cecilia Åkerlund, Krisztina Amrein, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó9, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Iris Ceyisakar, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Ana M. Castaño-León, Marc Maegele, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P. J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Molecular Neuroscience and Ageing Research (MOLAR), Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Neurokirurgian yksikkö, Helsinki Institute for Information Technology, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Clinicum, Helsinki University Hospital Area, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Jacob, L., Cogne, M., Tenovuo, O., Roe, C., Andelic, N., Majdan, M., Ranta, J., Ylen, P., Dawes, H., Azouvi P., (CENTER-TBI Participants and Investigators), Beretta, Luigi, Jacob, L, Cogne, M, Tenovuo, O, Roe, C, Andelic, N, Majdan, M, Ranta, J, Ylen, P, Dawes, H, Azouvi, P, Akerlund, C, Amrein, K, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azzolini, M, Bartels, R, Barzo9, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Ceyisakar, I, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dilvesi, D, Dixit, A, Donoghue, E, Dreier, J, Duliere, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovacs, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lingsma, H, Maas, A, Castano-Leon, A, Maegele, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menon, D, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyiradi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnak, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Sewalt, C, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Synnot, A, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te Ao, B, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Vallance, S, Valeinis, E, Vamos, Z, van der Jagt, M, Van der Steen, G, van der Naalt, J, van Dijck, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, Vande Vyvere, T, van Wijk, R, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, von Steinbuchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Oslo University Hospital [Oslo], Oxford Brookes University, European Commission, EC: 602150, The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Data used in preparation of this article were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC Grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA), and from Integra LifeSciences Corporation (USA). Data for the CENTER-TBI study were collected through the Quesgen e-CRF (Quesgen Systems Inc, USA), hosted on the INCF platform and extracted via the INCF Neurobot tool (INCF, Sweden). The funder had no role in the study design, collection, analysis, and interpretation of the data, writing of the report, and the decision to submit the article for publication., European Project: 602150,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,CENTER-TBI(2013), Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, and Psychiatrie & Neuropsychologie
Subjects: Male, 030506 rehabilitation, Neurology, predictive factors, IMPACT, medicine.medical_treatment, CENTER-TBI, Health Services Accessibility, 3124 Neurology and psychiatry, predictive factor, Injury Severity Score, 0302 clinical medicine, Brain Injuries, Traumatic, Epidemiology, EPIDEMIOLOGY, Prospective Studies, rehabilitation, OUTCOMES, Rehabilitation, traumatic brain injury, Neurological Rehabilitation, General Medicine, Middle Aged, RECOVERY, Prognosis, 3. Good health, Hospitalization, Europe, Educational Status, international prospective study, Female, HEALTH, 0305 other medical science, Adult, Employment, medicine.medical_specialty, Traumatic brain injury, 03 medical and health sciences, Sex Factors, medicine, Humans, Glasgow Coma Scale, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, MORTALITY, 3112 Neurosciences, PATHWAYS, CARE, medicine.disease, Multicenter study, Emergency medicine, MODERATE, business, 030217 neurology & neurosurgery
Abstract: BackgroundAlthough rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care.ObjectiveTherefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI.MethodsData from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge.ResultsIn the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24).ConclusionsBased on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.
Published: 2020
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26. A genome-wide association study of outcome from traumatic brain injury

Author: Mart Kals, Kevin Kunzmann, Livia Parodi, Farid Radmanesh, Lindsay Wilson, Saef Izzy, Christopher D. Anderson, Ava M. Puccio, David O. Okonkwo, Nancy Temkin, Ewout W. Steyerberg, Murray B. Stein, Geoff T. Manley, Andrew I.R. Maas, Sylvia Richardson, Ramon Diaz-Arrastia, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, David K. Menon, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan P. Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire DahyotFizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, GuyLoup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J.A. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Jiyao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, LarsOwe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Ana M. CastañoLeón, Marc Maegele, Marek Majdan, Alex Manara, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia F.J. Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Paul M. Parizel, JeanFrançois Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Isabel Retel Helmrich, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan SanchezPorras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Thijs Vande Vyvere, Roel P.J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Janek Frantzén, Ari Katila, Henna-Rikka Maanpää, Jussi Tallus, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Sonia Jain, Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Geoffrey T. 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A., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Jiyao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, LarsOwe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., CastañoLeón, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David K., Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia F. J., Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, JeanFrançois, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, SanchezPorras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Åkerlund, Cecilia, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Amrein, Krisztina, Ziverte, Agate, Zoerle, Tommaso, Izzy, Saef, Radmanesh, Farid, Frantzén, Janek, Katila, Ari, Maanpää, Henna-Rikka, Tallus, Jussi, Adeoye, Opeolu, Badjatia, Neeraj, Andelic, Nada, Boase, Kim, Barber, Jason, Bodien, Yelena, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Andreassen, Lasse, Feeser, Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Anke, Audny, Hemphill, Claude, Hotz, Gillian, Jain, Sonia, Keene, Dirk, Korley, Frederick K., Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Antoni, Anna, Madden, Christopher, Manley, Geoffrey T., Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B., Noel, Florence, Audibert, Gérard, Nolan, Amber, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Azouvi, Philippe, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Yue, John K., Azzolini, Maria Luisa, Yuh, Esther, Zafonte, Ross, Carroll, Ellen, Chatfield, Doris A., Coles, Jonathan P., Helmy, Adel, Manktelow, Anne, Outtrim, Joanne G., Bartels, Ronald, Takala, Rikka, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, DahyotFizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, GuyLoup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Molecular Neuroscience and Ageing Research (MOLAR), Kals, M, Kunzmann, K, Parodi, L, Radmanesh, F, Wilson, L, Izzy, S, Anderson, C, Puccio, A, Okonkwo, D, Temkin, N, Steyerberg, E, Stein, M, Manley, G, Citerio, G, Genetic Associations In Neurotrauma (GAIN) Consortium, CENTER-TBI, CABI, MGB, TBIcare Studies, TRACK-TBI, „Elsevier Science' grupė, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Institute for Molecular Medicine Finland, Complex Disease Genetics, Research Programs Unit, Centre of Excellence in Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, and Biostatistics Helsinki
Subjects: Traumatic, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, LOCI, SUSCEPTIBILITY, Traumatic Brain Injury (TBI), Mannose-Binding Lectin, DISEASE, General Biochemistry, Genetics and Molecular Biology, Traumatic brain injury, Consortia, Recovery, Brain Injuries, Traumatic, Genetics, 2.1 Biological and endogenous factors, Humans, Prospective Studies, Aetiology, Traumatic Head and Spine Injury, Outcome, Human Genome, 3112 Neurosciences, Neurosciences, General Medicine, LECTIN, Brain Disorders, Good Health and Well Being, consortia, genome-wide association study, outcome, recovery, traumatic brain injury, Brain Injuries, Genetic Associations In Neurotrauma (GAIN) Consortium, Public Health and Health Services, Human medicine, Transcriptome, Genome-Wide association study
Abstract: EBioMedicine 77, 103933 (2022). doi:10.1016/j.ebiom.2022.103933, Published by Elsevier, Amsterdam [u.a.]
Published: 2022
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27. Abstract TMP120: Brain Plasticity Modulator P75 Neurotrophin Receptor And Its Mechanistically Linked Signaling Molecules Predict Clinical Outcome Across Different Acute Brain Injuries

Author: Antti Sajanti, Yan Li, Ying Cao, Romuald Girard, Juzoh Umemori, Janek Frantzen, Fredrika Koskimaki, Séan Lyne, Johannes Falter, Tomi Rantamaki, Iiro Heino, Riikka Takala, Jussi Posti, Susanna Roine, Ilkka Saarenpää, Sulo Kolehmainen, Melissa Rahi, Jaakko Rinne, Eero Castren, and Janne Koskimaki
Subjects: Advanced and Specialized Nursing, nervous system, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: Brain plasticity and synaptic regeneration are important processes in recovering after acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI). p75 neurotrophic receptor (p75NTR) is a consequential receptor modulating brain plasticity and apoptosis. Hypotheses: Measurable changes in serum levels of p75NTR mechanistically linked proteins are associated to recovery of acute brain injuries. Differentially expressed (DE) miRNAs after acute brain injuries target to p75NTR pathway and have association to outcome. Methods: Concentrations of p75NTR, NGF, sortilin, IL1β, TNFα and cyclophilin were measured from serum using ELISA. Prospective cohort (n=75) consisted of IS (n=30), aSAH (n=31) and TBI (n=14) patients. Serum samples were collected 24-48h after insults. Late samples (120-192h) were also taken from 12 aSAH patients. Outcome was measured 90 days after injury (mRS favorable 0-4, unfavorable 5-6). We generated characteristic curves and area under the curve (AUC) for weighted linear combination of the biomarkers with a linear discriminant analysis. MiRNAs were extracted from the cohort (early and late samples, n=53). Results: In the whole cohort (n=75) combination of cyclophilin, IL1β, sortilin, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.69, p=0.01). In IS group combination of cyclophilin, sortilin, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.84, p=0.02). In aSAH group combination of IL1β, p75NTR and NGF predicted unfavorable mRS (AUC 0.77, p=0.07). In 12 aSAH patient sub-group (late samples included) combination of cyclophilin, IL1β, sortilin, p75NTR and TNFα predicted unfavorable mRS (AUC 1.0, p=0.07). In TBI group combination of cyclophilin, IL1β, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.79, p=0.08). In the aSAH group 2 DE miRNAs were detected, 4 in the IS group and 7 in the TBI group (pp75NTR , NGF , IL1 β , cyclophilin ( PPIA ), and sortilin ( SORT1 ). Conclusions: p75NTR and mechanistically linked proteins predict outcome across different types of brain injuries suggesting a common mechanism irrespective of the type of brain insult. Identified DE miRNAs targeted studied molecules.
Published: 2022
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28. Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation

Author: Stefania Galimberti, Francesca Graziano, Andrew I R Maas, Giulia Isernia, Fiona Lecky, Sonia Jain, Xiaoying Sun, Raquel C Gardner, Sabrina R Taylor, Amy J Markowitz, Geoffrey T Manley, Maria Grazia Valsecchi, Giuseppe Bellelli, Giuseppe Citerio, Cecilia Ackerlund, Hadie Adams, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Marc Maegele, Marek Majdan, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Veronika Rehorčíková, Isabel Retel Helmrich, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Ranjit D. Singh, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Mathieu van der Jagt, Joukje van der Naalt, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Inge A. van Erp, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Roel van Wijk, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Peter Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Agate Ziverte, Tommaso Zoerle, Opeolu Adeoye, Neeraj Badjatia, Jason Barber, Michael Bergin, Kim Boase, Yelena Bodien, Randall Chesnut, John Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Venkata Feeser, Adam R Ferguson, Brandon Foreman, Etienne Gaudette, Joseph Giacino, Luis Gonzalez, Shankar Gopinath, Ramesh Grandhi, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Russell Huie, Ruchira Jha, C. Dirk Keene, Ryan Kitagawa, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Richard Ben Rodgers, Jonathan Rosand, Eric Rosenthal, Angelle Sander, Danielle Sandsmark, Gabriella Sugar, Andrea Schneider, David Schnyer, Seth Seabury, Mark Sherer, Murray Stein, Nancy Temkin, Arthur Toga, Abel Torres-Espin, Alex Valadka, Mary Vassar, Kevin Wang, Vincent Wang, John K. 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I. R., Isernia, G., Lecky, F., Jain, S., Sun, X., Gardner, R. C., Taylor, S. R., Markowitz, A. J., Manley, G. T., Valsecchi, M. G., Bellelli, G., Citerio, G., Ackerlund, C., Adams, H., Amrein, K., Andelic, N., Andreassen, L., Anke, A., Antoni, A., Audibert, G., Azouvi, P., Azzolini, M. L., Bartels, R., Barzo, P., Beauvais, R., Beer, R., Bellander, B. -M., Belli, A., Benali, H., Berardino, M., Beretta, L., Blaabjerg, M., Bragge, P., Brazinova, A., Brinck, V., Brooker, J., Brorsson, C., Buki, A., Bullinger, M., Cabeleira, M., Caccioppola, A., Calappi, E., Calvi, M. R., Cameron, P., Carbayo Lozano, G., Carbonara, M., Castano-Leon, A. M., Cavallo, S., Chevallard, G., Chieregato, A., Clusmann, H., Coburn, M. S., Coles, J., Cooper, J. D., Correia, M., Covic, A., Curry, N., Czeiter, E., Czosnyka, M., Dahyot-Fizelier, C., Dark, P., Dawes, H., De Keyser, V., Degos, V., Della Corte, F., den Boogert, H., Depreitere, B., Dilvesi, D., Dixit, A., Donoghue, E., Dreier, J., Duliere, G. -L., Ercole, A., Esser, P., Ezer, E., Fabricius, M., Feigin, V. L., Foks, K., Frisvold, S., Furmanov, A., Gagliardo, P., Galanaud, D., Gantner, D., Gao, G., George, P., Ghuysen, A., Giga, L., Glocker, B., Golubovic, J., Gomez, P. A., Gratz, J., Gravesteijn, B., Grossi, F., Gruen, R. L., Gupta, D., Haagsma, J. A., Haitsma, I., Helbok, R., Helseth, E., Horton, L., Huijben, J., Hutchinson, P. J., Jacobs, B., Jankowski, S., Jarrett, M., Jiang, J. -Y., Johnson, F., Jones, K., Karan, M., Kolias, A. G., Kompanje, E., Kondziella, D., Koskinen, L. -O., Kovacs, N., Kowark, A., Lagares, A., Lanyon, L., Laureys, S., Ledoux, D., Lefering, R., Legrand, V., Lejeune, A., Levi, L., Lightfoot, R., Lingsma, H., Maegele, M., Majdan, M., Manara, A., Marechal, H., Martino, C., Mattern, J., Mcfadyen, C., Mcmahon, C., Melegh, B., Menon, D., Menovsky, T., Mikolic, A., Misset, B., Muraleedharan, V., Murray, L., Negru, A., Nelson, D., Newcombe, V., Nieboer, D., Nyiradi, J., Oresic, M., Ortolano, F., Otesile, O., Palotie, A., Parizel, P. M., Payen, J. -F., Perera, N., Perlbarg, V., Persona, P., Peul, W., Piippo-Karjalainen, A., Pirinen, M., Pisica, D., Ples, H., Polinder, S., Pomposo, I., Posti, J. P., Puybasset, L., Radoi, A., Ragauskas, A., Raj, R., Rambadagalla, M., Rehorcikova, V., Retel Helmrich, I., Rhodes, J., Richardson, S., Richter, S., Ripatti, S., Rocka, S., Roe, C., Roise, O., Rosenfeld, J., Rosenlund, C., Rosenthal, G., Rossaint, R., Rossi, S., Rueckert, D., Rusnak, M., Sahuquillo, J., Sakowitz, O., Sanchez-Porras, R., Sandor, J., Schafer, N., Schmidt, S., Schoechl, H., Schoonman, G., Schou, R. F., Schwendenwein, E., Sewalt, C., Singh, R. D., Skandsen, T., Smielewski, P., Sorinola, A., Stamatakis, E., Stanworth, S., Stevens, R., Stewart, W., Steyerberg, E. W., Stocchetti, N., Sundstrom, N., Takala, R., Tamas, V., Tamosuitis, T., Taylor, M. S., Te Ao, B., Tenovuo, O., Theadom, A., Thomas, M., Tibboel, D., Timmers, M., Tolias, C., Trapani, T., Tudora, C. M., Unterberg, A., Vajkoczy, P., Valeinis, E., Vallance, S., Vamos, Z., van der Jagt, M., van der Naalt, J., Van der Steen, G., van Dijck, J. T. J. M., van Erp, I. A., van Essen, T. A., Van Hecke, W., van Heugten, C., Van Praag, D., van Veen, E., van Wijk, R., Vande Vyvere, T., Vargiolu, A., Vega, E., Velt, K., Verheyden, J., Vespa, P. M., Vik, A., Vilcinis, R., Volovici, V., von Steinbuchel, N., Voormolen, D., Vulekovic, P., Wang, K. K. W., Wiegers, E., Williams, G., Wilson, L., Wolf, S., Yang, Z., Ylen, P., Younsi, A., Zeiler, F. A., Ziverte, A., Zoerle, T., Adeoye, O., Badjatia, N., Barber, J., Bergin, M., Boase, K., Bodien, Y., Chesnut, R., Corrigan, J., Crawford, K., Diaz-Arrastia, R., Dikmen, S., Duhaime, A. -C., Ellenbogen, R., Feeser, V., Ferguson, A. R., Foreman, B., Gaudette, E., Giacino, J., Gonzalez, L., Gopinath, S., Grandhi, R., Gullapalli, R., Hemphill, C., Hotz, G., Huie, R., Jha, R., Keene, C. D., Kitagawa, R., Korley, F., Kramer, J., Kreitzer, N., Levin, H., Lindsell, C., Machamer, J., Madden, C., Martin, A., Mcallister, T., Mccrea, M., Merchant, R., Mukherjee, P., Nelson, L., Ngwenya, L. B., Noel, F., Nolan, A., Okonkwo, D., Palacios, E., Perl, D., Puccio, A., Rabinowitz, M., Robertson, C., Rodgers, R. B., Rosand, J., Rosenthal, E., Sander, A., Sandsmark, D., Sugar, G., Schneider, A., Schnyer, D., Seabury, S., Sherer, M., Stein, M., Temkin, N., Toga, A., Torres-Espin, A., Valadka, A., Vassar, M., Wang, K., Wang, V., Yue, J. K., Yuh, E., and Zafonte, R.
Subjects: Male, Traumatic/therapy, Frailty, Brain Injuries, Traumatic/therapy, traumatic brain injury, Reproducibility of Results, Middle Aged, Cohort Studies, Brain Injuries, Brain Injuries, Traumatic, outcome, Humans, Glasgow Coma Scale, Neurology (clinical), Human medicine, Prospective Studies, Aged
Abstract: Background: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury. Methods: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0–30), we obtained a standardised value (range 0–1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182. Findings: 2993 participants (median age was 51 years [IQR 30–67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03–0·15), with a median score of 0·17 (0·08–0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02–1·04; p
Published: 2022
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29. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI

Author: Ewout W Steyerberg, Eveline Wiegers, Charlie Sewalt, Andras Buki, Giuseppe Citerio, Véronique De Keyser, Ari Ercole, Kevin Kunzmann, Linda Lanyon, Fiona Lecky, Hester Lingsma, Geoffrey Manley, David Nelson, Wilco Peul, Nino Stocchetti, Nicole von Steinbüchel, Thijs Vande Vyvere, Jan Verheyden, Lindsay Wilson, Andrew I R Maas, David K Menon, Cecilia Ackerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Rafael Badenes, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M Castaño-León, Giorgio Chevallard, Arturo Chieregato, Maryse Cnossen, Mark Coburn, Jonathan Coles, Jamie D Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Helen Dawes, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Simone Dijkland, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Kelly Jones, Mladen Karan, Angelos G Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Alfonso Lagares, Steven Laureys, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Angels Lozano, Marc Maegele, Marek Majdan, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Davide Mulazzi, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, Virginia Newcombe, Daan Nieboer, Quentin Noirhomme, József Nyirádi, Mauro Oddo, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Anna Piippo-Karjalainen, Sébastien Pili Floury, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Ana Stevanovic, Robert Stevens, William Stewart, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Joukje van der Naalt, Gregory Van der Steen, Jeroen T J M van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Roel P J van Wijk, Audrey Vanhaudenhuyse, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Paul M Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Daphne Voormolen, Petar Vulekovic, Kevin K W Wang, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Molecular Neuroscience and Ageing Research (MOLAR), Steyerberg, Ew, Wiegers, E, Sewalt, C, Buki, A, Citerio, G, De Keyser, V, Ercole, A, Kunzmann, K, Lanyon, L, Lecky, F, Lingsma, H, Manley, G, Nelson, D, Peul, W, Stocchetti, N, von Steinbuchel, N, Vande, Vyvere T, Verheyden, J, Wilson, L, Maas, Air, Menon, DK (CENTER-TBI Participants and Investigator), Beretta, L, Public Health, Ercole, Ari [0000-0001-8350-8093], Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, CENTER-TBI Participants Investigators, Steyerberg, E, von Steinbüchel, N, Vande Vyvere, T, Maas, A, Menon, D, Ackerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Auslands, K, Azouvi, P, Azzolini, M, Badenes, R, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Carbayo Lozano, G, Carbonara, M, Castaño-León, A, Chevallard, G, Chieregato, A, Cnossen, M, Coburn, M, Coles, J, Cooper, J, Correia, M, Čović, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dawes, H, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dijkland, S, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubović, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovács, N, Lagares, A, Laureys, S, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lozano, A, Maegele, M, Majdan, M, Manara, A, Maréchal, H, Martino, C, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Mulazzi, D, Muraleedharan, V, Murray, L, Nair, N, Negru, A, Newcombe, V, Nieboer, D, Noirhomme, Q, Nyirádi, J, Oddo, M, Oresic, M, Ortolano, F, Otesile, O, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Piippo-Karjalainen, A, Pili Floury, S, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Rădoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Real, R, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnák, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schäfer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevanovic, A, Stevens, R, Stewart, W, Sundström, N, Synnot, A, Takala, R, Tamás, V, Tamosuitis, T, Taylor, M, Te Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Valeinis, E, Vallance, S, Vámos, Z, van der Naalt, J, Van der Steen, G, van Dijck, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, van Wijk, R, Vanhaudenhuyse, A, Vargiolu, A, Vega, E, Velt, K, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, Voormolen, D, Vulekovic, P, Wang, K, Williams, G, Winzeck, S, Wolf, S, Yang, Z, Ylén, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Section Neuropsychology, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and RS: FPN NPPP I
Subjects: Male, NEUROTRAUMA EFFECTIVENESS RESEARCH, Glasgow Outcome Scale, ALCOHOL, Cohort Studies, Traumatic brain injury, 0302 clinical medicine, Patient Admission, Quality of life, QUALITY-OF-LIFE, Brain Injuries, Traumatic/classification, Brain Injuries, Traumatic, Longitudinal Studies, Prospective Studies, Registries, Israel, Prospective cohort study, SCALE, Middle Aged, Prognosis, 3. Good health, Europe, Intensive Care Units, Critical Pathways, Female, Cohort study, Adult, medicine.medical_specialty, 03 medical and health sciences, Case mix index, SDG 3 - Good Health and Well-being, medicine, Humans, Glasgow Coma Scale, Traumatic/classification, Psychiatry, Critical Care Outcomes, Diagnosis-Related Groups, Aged, business.industry, MORTALITY, 030208 emergency & critical care medicine, El Niño, Brain Injuries, Human medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. Methods: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). Findings: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13–15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30–66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE
Published: 2019
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30. Association between Physiological Signal Complexity and Outcomes in Moderate and Severe Traumatic Brain Injury: A CENTER-TBI Exploratory Analysis of Multi-Scale Entropy

Author: Daniel Kondziella, Juan Sahuquillo, Oliver Sakowitz, Riikka Takala, Ari Ercole, Giuseppe Citerio, Rahul Raj, Andreea Rădoi, Kirsten Moller, Frederick Zeiler, Arminas Ragauskas, Zeiler, F, Ercole, A, Placek, M, Hutchinson, P, Stocchetti, N, Czosnyka, M, Smielewski, P, and Citerio, G
Subjects: Adult, Male, 030506 rehabilitation, medicine.medical_specialty, Intracranial Pressure, Traumatic brain injury, Cbf autoregulation, Glasgow Outcome Scale, Blood Pressure, Multi scale entropy, 03 medical and health sciences, Vascular reactivity, multi-scale entropy, 0302 clinical medicine, Physical medicine and rehabilitation, Heart Rate, Brain Injuries, Traumatic, medicine, Humans, Autoregulation, Monitoring, Physiologic, Retrospective Studies, business.industry, autoregulation, Exploratory analysis, Middle Aged, medicine.disease, cerebral physiology, humanities, Cerebrovascular Circulation, Intensive Care Units, outcome, Female, Neurology (clinical), 0305 other medical science, business, complexity, 030217 neurology & neurosurgery
Abstract: In traumatic brain injury (TBI), preliminary retrospective work on signal entropy suggests an association with global outcome. The goal of this study was to provide multi-center validation of the association between multi-scale entropy (MSE) of cardiovascular and cerebral physiological signals, with six-month outcome. Using the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we selected patients with a minimum of 72 h of physiological recordings and a documented six-month Glasgow Outcome Scale Extended (GOSE) score. The 10-sec summary data for heart rate (HR), mean arterial pressure (MAP), intracranial pressure (ICP), and pulse amplitude of ICP (AMP) were derived across the first 72 h of data. The MSE complexity index (MSE-Ci) was determined for HR, MAP, ICP, and AMP, with the association between MSE and dichotomized six-month outcomes assessed using Mann-Whitney U testing and logistic regression analysis. A total of 160 patients had a minimum of 72 h of recording and a documented outcome. Decreased HR MSE-Ci (7.3 [interquartile range (IQR) 5.4 to 10.2] vs. 5.1 [IQR 3.1 to 7.0]; p = 0.002), lower ICP MSE-Ci (11.2 [IQR 7.5 to 14.2] vs. 7.3 [IQR 6.1 to 11.0]; p = 0.009), and lower AMP MSE-Ci (10.9 [IQR 8.0 to 13.7] vs. 8.7 [IQR 6.6 to 11.0]; p = 0.022), were associated with death. Similarly, lower HR MSE-Ci (8.0 [IQR 6.2 to 10.9] vs. 6.2 [IQR 3.9 to 8.7]; p = 0.003) and lower ICP MSE-Ci (11.4 [IQR 8.6 to 14.4)] vs. 9.2 [IQR 6.0 to 13.5]), were associated with unfavorable outcome. Logistic regression analysis confirmed that lower HR MSE-Ci and ICP MSE-Ci were associated with death and unfavorable outcome at six months. These findings suggest that a reduction in cardiovascular and cerebrovascular system entropy is associated with worse outcomes. Further work in the field of signal complexity in TBI multi-modal monitoring is required.
Published: 2021

31. Acute Kidney Injury in Traumatic Brain Injury Patients: Results From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study

Author: Daniel Kondziella, Juan Sahuquillo, Riikka Takala, Chao-Yuan Huang, Geert Meyfroidt, Giuseppe Citerio, Rahul Raj, Jussi Posti, Renán Sánchez-Porras, Peter Hutchinson, Virginia Newcombe, Frederick Zeiler, Public Health, Robba, C, Banzato, E, Rebora, P, Iaquaniello, C, Huang, C, Wiegers, E, Meyfroidt, G, and Citerio, G
Subjects: medicine.medical_specialty, Traumatic brain injury, business.industry, medicine.medical_treatment, Glasgow Outcome Scale, Osmotic diuretic, Hazard ratio, Acute kidney injury, Kidney failure, Poison control, 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, medicine.disease, Polytrauma, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Renal replacement therapy, business, Kidney disease
Abstract: OBJECTIVES: Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients. DESIGN: The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study. SETTING: Sixty-five ICUs across Europe. PATIENTS: For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay. MEASUREMENTS AND MAIN RESULTS: We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5-1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours; acute kidney injury stage 2 equals to serum creatinine × 2-2.9 times baseline; acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% (n = 100), acute kidney injury stage 2 equals to 1% (n = 14), and acute kidney injury stage 3 equals to 3% (n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1-4 d). Renal history (hazard ratio = 2.48; 95% CI, 1.39-4.43; p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52; 95% CI, 1.22-5.197; p = 0.012), hypernatremia (hazard ratio = 1.88; 95% CI, 1.31-2.71; p = 0.001), and osmotic therapy administration (hazard ratio = 2.08; 95% CI, 1.45-2.99; p < 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality. CONCLUSIONS: Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.
Published: 2021

32. Persistent postconcussive symptoms in children and adolescents with mild traumatic brain injury receiving initial head computed tomography

Author: Lennart Riemann, Daphne C. Voormolen, Katrin Rauen, Klaus Zweckberger, Andreas Unterberg, Alexander Younsi, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Iris Ceyisakar, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Ðula Ðilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Andrew I. R. Maas, Ana M. Castaño-León, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T. J. M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P. J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K. W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Riemann, L, Voormolen, D, Rauen, K, Zweckberger, K, Unterberg, A, Younsi, A, Citerio, G, Public Health, Riemann, L., Voormolen, D. C., Rauen, K., Zweckberger, K., Unterberg, A., Younsi A., (CENTER-TBI Investigators and Participants), Beretta, Luigi, University of Zurich, Younsi, Alexander, and Molecular Neuroscience and Ageing Research (MOLAR)
Subjects: Male, Pediatrics, Neurologi, Health-related quality of life, Computed tomography, law.invention, 0302 clinical medicine, Quality of life, law, Prevalence, Child, Pediatric, medicine.diagnostic_test, Post-Concussion Syndrome, 11359 Institute for Regenerative Medicine (IREM), General Medicine, Rivermead post-concussion symptoms questionnaire, Intensive care unit, 2746 Surgery, health-related quality of life, HRQOL, 2728 Neurology (clinical), trauma, Post concussion, Neurology, Postconcussive symptom, Child, Preschool, 030220 oncology & carcinogenesis, CT imaging, Postconcussive symptoms, Female, medicine.medical_specialty, Adolescent, Traumatic brain injury, 610 Medicine & health, Neuroimaging, Trauma, RPQ, Young Adult, 03 medical and health sciences, mild traumatic brain injury, medicine, Humans, In patient, 2735 Pediatrics, Perinatology and Child Health, Mild traumatic brain injury, Brain Concussion, business.industry, postconcussive symptoms, Glasgow Coma Scale, medicine.disease, pediatric, Quality of Life, Rivermead Post Concussion Symptoms Questionnaire, Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract: OBJECTIVE: The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment. METHODS: Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13-15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. RESULTS: A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001). CONCLUSIONS: Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL., Funding Agencies: OneMind (USA) Hannelore Kohl Stiftung (Germany)
Published: 2021

33. Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations

Author: J. Russell Huie, Stefania Mondello, Christopher J. Lindsell, Luca Antiga, Esther L. Yuh, Elisa R. Zanier, Serge Masson, Bedda L. Rosario, Adam R. Ferguson, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Sonia Jain, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, David Okonkwo, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, David Schnyer, Seth Seabury, Murray Stein, Sabrina Taylor, Nancy Temkin, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, Ross Zafonte, Cecilia Ackerlund, Hadie Adams, Vanni Agnoletti, Judith Allanson, Krisztina Amrein, Norberto Andaluz, Nada Andelic, Lasse Andreassen, Audny Anke, Azasevac Antun, Anna Antoni, Hilko Ardon, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Camelia Baciu, Rafael Badenes, Ronald Bartels, Pál Barzó, Ursula Bauerfeind, Romuald Beauvais, Ronny Beer, Francisco Javier Belda, Bo Michael Bellander, Antonio Belli, Rémy Bellier, Habib Benali, Thierry Benard, Maurizio Berardino, Luigi Beretta, Christopher Beynon, Federico Bilotta, Harald Binder, Erta Biqiri, Morten Blaabjerg, Hugo den Boogert, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Lozano Guillermo Carbayo, Marco Carbonara, Elsa Carise, K. Carpenter, Ana M. Castaño León, Francesco Causin, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Maryse Cnossen, Mark Coburn, Jonathan Coles, Lizzie Coles-Kemp, Johnny Collett, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot Fizelier, François Damas, Pierre Damas, Helen Dawes, Véronique De Keyser, Francesco Della Corte, Bart Depreitere, Godard C.W. de Ruiter, Dula Dilvesi, Shenghao Ding, Diederik Dippel, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy Loup Dulière, Heiko Engemann, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Junfeng Feng, Kelly Foks, Francesca Fossi, Gilles Francony, Ulderico Freo, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Karin Geleijns, Pradeep George, Alexandre Ghuysen, Lelde Giga, Benoit Giraud, Ben Glocker, Jagos Golubovic, Pedro A. Gomez, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Asta Kristine Håberg, Bram Jacobs, Iain Haitsma, Jed A. Hartings, Raimund Helbok, Eirik Helseth, Daniel Hertle, Astrid Hoedemaekers, Stefan Hoefer, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Stefan Jankowski, Mike Jarrett, Bojan Jelaca, Ji yao Jiang, Kelly Jones, Konstantinos Kamnitsas, Mladen Karan, Ari Katila, Maija Kaukonen, Thomas Kerforne, Riku Kivisaari, Angelos G. Kolias, Bálint Kolumbán, Erwin Kompanje, Ksenija Kolundzija, Daniel Kondziella, Lars Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Christian Ledig, Rolf Lefering, Valerie Legrand, Jin Lei, Leon Levi, Roger Lightfoot, Hester Lingsma, Dirk Loeckx, Angels Lozano, Andrew I.R. Maas, Stephen MacDonald, Marc Maegele, Majdan Marek, Sebastian Major, Alex Manara, Geoffrey Manley, Didier Martin, Leon Francisco Martin, Costanza Martino, Hugues Maréchal, Armando Maruenda, Alessandro Masala, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Cristina Morganti Kossmann, Davide Mulazzi, Holger Mühlan, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, Quentin Noirhomme, József Nyirádi, Mauro Oddo, Annemarie Oldenbeuving, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Adriana Patruno, Jean François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Floury Sébastien Pili, Matti Pirinen, Horia Ples, Maria Antonia Poca, Suzanne Polinder, Inigo Pomposo, Jussi Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Veronika Rehorčíková, Jonathan Rhodes, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Gerwin Roks, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Marco Sacchi, Barbara Sahakian, Juan Sahuquillo, Oliver Sakowitz, Francesca Sala, Renan Sanchez Porras, Janos Sandor, Edgar Santos, Luminita Sasu, Davide Savo, Nadine Schäffer, Inger Schipper, Barbara Schlößer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Michael Schöll, Charlie Sewalt, Özcan Sir, Toril Skandsen, Lidwien Smakman, Dirk Smeets, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Nicole Steinbüchel, Ana Stevanovic, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Fabio Silvio Taccone, Riikka Takala, Viktória Tamás, Päivi Tanskanen, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Ralph Telgmann, Guido Teodorani, Alice Theadom, Matt Thomas, Dick Tibboel, Christos Tolias, Jean Flory Luaba Tshibanda, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Gregory Van der Steen, Mathieu van der Jagt, JV de Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Julia Van Waesberghe, Audrey Vanhaudenhuyse, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Giacinta Vizzino, Carmen Vleggeert Lankamp, Victor Volovici, Daphne Voormolen, Peter Vulekovic, Zoltán Vámos, Derick Wade, Kevin K.W. Wang, Lei Wang, Lars Wessels, Eveline Wiegers, Eno Wildschut, Guy Williams, Lindsay Wilson, Maren K.L. Winkler, Stefan Wolf, Peter Ylén, Alexander Younsi, Menashe Zaaroor, Frederik Zeiler, Yang Zhihui, Agate Ziverte, Fabrizio Zumbo, Huie, J Russell, Mondello, Stefania, Lindsell, Christopher J, Antiga, Luca, Yuh, Esther L, Zanier, Elisa R, Masson, Serge, Rosario, Bedda L, Ferguson, Adam R (Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators), Beretta, Luigi, Huie, J, Mondello, S, Lindsell, C, Antiga, L, Yuh, E, Zanier, E, Masson, S, Rosario, B, Ferguson, A, Citerio, G, and Molecular Neuroscience and Ageing Research (MOLAR)
Subjects: Traumatic, 030506 rehabilitation, Data Interpretation, Data management, data sharing, TERMINAL HYDROLASE-L1, Big data, Poison control, 0302 clinical medicine, Brain Injuries, Traumatic, TBI, Medicine, Biomarker discovery, Common Data Elements, traumatic brain injury, Injuries and accidents, Statistical, Reference Standards, NET RECLASSIFICATION INDEX, Data Interpretation, Statistical, Biomarker (medicine), biomarker, 0305 other medical science, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, CT, The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, medicine.medical_specialty, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, Context (language use), Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Traumatic Brain Injury (TBI), Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators, 03 medical and health sciences, MICROARRAY, Special Section: Statistical Methods in Tbi Research, Humans, biomarkers, Intensive care medicine, Traumatic Head and Spine Injury, Neurology & Neurosurgery, business.industry, Information Dissemination, OUTCOME PREDICTION, Neurosciences, COMMON DATA ELEMENTS, Precision medicine, Brain Disorders, DIFFUSE AXONAL INJURY, Data sharing, Good Health and Well Being, Brain Injuries, DISCOVERY, TRACK, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 238746.pdf (Publisher’s version ) (Closed access) Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.
Published: 2021

34. Missing Data in Prediction Research: A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study

Author: Marek Majdan, Thomas Van Essen, Daniel Kondziella, Juan Sahuquillo, Oliver Sakowitz, Joukje Van der Naalt, Benjamin Gravesteijn, Ana M Castaño-Leon, Riikka Takala, Ari Ercole, Thijs Vande Vyvere, Giuseppe Citerio, Rahul Raj, Jussi Posti, Renán Sánchez-Porras, Andreea Rădoi, Sandra Rossi, Pedro Gomez, Virginia Newcombe, William Stewart, Jonathan Coles, Frederick Zeiler, Arminas Ragauskas, Gravesteijn, Benjamin Yaël, Sewalt, Charlie Aletta, Venema, Esmee, Nieboer, Daan, Steyerberg, Ewout W (CENTER-TBI Collaborators), Beretta, Luigi, Molecular Neuroscience and Ageing Research (MOLAR), Gravesteijn, B, Sewalt, C, Venema, E, Nieboer, D, Steyerberg, E, Citerio, G, Public Health, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and RS: FPN NPPP I
Subjects: 030506 rehabilitation, EXTERNAL VALIDATION, EFFICIENCY, Biomedical Research, Databases, Factual, Computer science, IMPACT, MODELS, MULTICENTER, Poison control, TRAUMATIC BRAIN-INJURY, imputation, Analysis of clinical trials, Machine learning, computer.software_genre, Cohort Studies, 03 medical and health sciences, missing data, tutorial, 0302 clinical medicine, Injury prevention, REGRESSION, Brain Injuries, Traumatic, Humans, Imputation (statistics), Prospective Studies, Estimation, business.industry, traumatic brain injury, Statistical model, prediction, Missing data, Prognosis, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Europe, BIAS, Data Interpretation, Statistical, Cohort, MODERATE, Neurology (clinical), Artificial intelligence, 0305 other medical science, business, computer, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 234957.pdf (Publisher’s version ) (Closed access) In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modeling. We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns; 2) choose a method of imputation; 3) perform imputation; 4) assess diagnostics of the imputation; and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data.
Published: 2021

35. Outcome prediction after moderate and severe traumatic brain injury

Author: Marek Majdan, Thomas Van Essen, Daniel Kondziella, Juan Sahuquillo, Oliver Sakowitz, Joukje Van der Naalt, Mathieu Van der Jagt, Ana M Castaño-Leon, Riikka Takala, Matti Pirinen, Thijs Vande Vyvere, Giuseppe Citerio, Rahul Raj, Jussi Posti, Renán Sánchez-Porras, Andreea Rădoi, Peter Hutchinson, Sandra Rossi, Pedro Gomez, Virginia Newcombe, William Stewart, Jonathan Coles, Frederick Zeiler, Aarno Palotie, Diederik Dippel, Arminas Ragauskas, Dijkland, S. A., Helmrich, I. R. A. R., Nieboer, D., Van Der Jagt, M., Dippel, D. W. J., Menon, D. K., Stocchetti, N., Maas, A. I. R., Lingsma, H. F., Steyerberg E. W., (CENTER-TBI Participants and Investigators), Beretta, Luigi, Dijkland, S, Helmrich, I, Nieboer, D, Van Der Jagt, M, Dippel, D, Menon, D, Stocchetti, N, Maas, A, Lingsma, H, Steyerberg, E, Citerio, G, Public Health, Intensive Care, Neurology, Molecular Neuroscience and Ageing Research (MOLAR), and CENTER-TBI Participants Investigators
Subjects: 030506 rehabilitation, medicine.medical_specialty, Neurologi, Traumatic brain injury, Crash, Context (language use), Analysis of clinical trials, 03 medical and health sciences, 0302 clinical medicine, external validation, Brain Injuries, Traumatic, clinical prediction model, Medicine, Humans, Models, Statistical, Receiver operating characteristic, business.industry, traumatic brain injury, Head injury, Recovery of Function, medicine.disease, 3. Good health, Europe, Neurology, Emergency medicine, Cohort, outcome, Human medicine, Neurology (clinical), prognosis, 0305 other medical science, business, 030217 neurology & neurosurgery, prognosi, Cohort study
Abstract: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS = 14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS = 16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (n = 1742). For CRASH, AUCs ranged between 0.82 and 0.88 in 1742 patients and between 0.66 and 0.80 in the stricter IMPACT selection (n = 1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02 and 0.61 and between 0.48 and 1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality-of-care assessment.
Published: 2020

36. Informed consent procedures in patients with an acute inability to provide informed consent: Policy and practice in the CENTER-TBI study

Author: Roel P.J. van Wijk, Jeroen T.J.M. van Dijck, Marjolein Timmers, Ernest van Veen, Giuseppe Citerio, Hester F. Lingsma, Andrew I.R. Maas, David K. Menon, Wilco C. Peul, Nino Stocchetti, Erwin J.O. Kompanje, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Iris Ceyisakar, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-Yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Ana M. Castaño-León, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Benoit Misset, Davide Mulazzi, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Gregory Van der Steen, Joukje van der Naalt, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Molecular Neuroscience and Ageing Research (MOLAR), CENTER-TB1 Investigators, Intensive Care, Public Health, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, HUS Neurocenter, Neurokirurgian yksikkö, Helsinki University Hospital Area, Statistical and population genetics, Biostatistics Helsinki, Staff Services, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, van Wijk, R, van Dijck, J, Timmers, M, van Veen, E, Citerio, G, Lingsma, H, Maas, A, Menon, D, Peul, W, Stocchetti, N, Kompanje, E, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Ceyisakar, I, Coburn, M, Coles, J, Cooper, J, Correia, M, Čović, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Corte, F, den Boogert, H, Depreitere, B, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kolias, A, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovács, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Castaño-León, A, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Maréchal, H, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Misset, B, Mulazzi, D, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyirádi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnák, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schäfer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Sewalt, C, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Sundström, N, Synnot, A, Takala, R, Tamás, V, Tamosuitis, T, Taylor, M, Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Vallance, S, Valeinis, E, Vámos, Z, Van der Steen, G, van der Naalt, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, Vyvere, T, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, von Steinbüchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylén, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, van Wijk, R. P. J., van Dijck, J. T. J. M., Timmers, M., van Veen, E., Citerio, G., Lingsma, H. F., Maas, A. I. R., Menon, D. K., Peul, W. C., Stocchetti, N., Kompanje, E. J. O., Akerlund, C., Amrein, K., Andelic, N., Andreassen, L., Anke, A., Antoni, A., Audibert, G., Azouvi, P., Azzolini, M. L., Bartels, R., Barzo, P., Beauvais, R., Beer, R., Bellander, B. -M., Belli, A., Benali, H., Berardino, M., Beretta, L., Blaabjerg, M., Bragge, P., Brazinova, A., Brinck, V., Brooker, J., Brorsson, C., Buki, A., Bullinger, M., Cabeleira, M., Caccioppola, A., Calappi, E., Calvi, M. R., Cameron, P., Lozano, G. C., Carbonara, M., Cavallo, S., Chevallard, G., Chieregato, A., Ceyisakar, I., Coburn, M., Coles, J., Cooper, J. D., Correia, M., Covic, A., Curry, N., Czeiter, E., Czosnyka, M., Dahyot-Fizelier, C., Dark, P., Dawes, H., De Keyser, V., Degos, V., Corte, F. D., den Boogert, H., Depreitere, B., Dilvesi, D., Dixit, A., Donoghue, E., Dreier, J., Duliere, G. -L., Ercole, A., Esser, P., Ezer, E., Fabricius, M., Feigin, V. L., Foks, K., Frisvold, S., Furmanov, A., Gagliardo, P., Galanaud, D., Gantner, D., Gao, G., George, P., Ghuysen, A., Giga, L., Glocker, B., Golubovic, J., Gomez, P. A., Gratz, J., Gravesteijn, B., Grossi, F., Gruen, R. L., Gupta, D., Haagsma, J. A., Haitsma, I., Helbok, R., Helseth, E., Horton, L., Huijben, J., Hutchinson, P. J., Jacobs, B., Jankowski, S., Jarrett, M., Jiang, J. -Y., Johnson, F., Jones, K., Karan, M., Kolias, A. G., Kompanje, E., Kondziella, D., Koraropoulos, E., Koskinen, L. -O., Kovacs, N., Kowark, A., Lagares, A., Lanyon, L., Laureys, S., Lecky, F., Ledoux, D., Lefering, R., Legrand, V., Lejeune, A., Levi, L., Lightfoot, R., Lingsma, H., Castano-Leon, A. M., Maegele, M., Majdan, M., Manara, A., Manley, G., Martino, C., Marechal, H., Mattern, J., Mcmahon, C., Melegh, B., Menon, D., Menovsky, T., Misset, B., Mulazzi, D., Muraleedharan, V., Murray, L., Negru, A., Nelson, D., Newcombe, V., Nieboer, D., Nyiradi, J., Olubukola, O., Oresic, M., Ortolano, F., Palotie, A., Parizel, P. M., Payen, J. -F., Perera, N., Perlbarg, V., Persona, P., Peul, W., Piippo-Karjalainen, A., Pirinen, M., Ples, H., Polinder, S., Pomposo, I., Posti, J. P., Puybasset, L., Radoi, A., Ragauskas, A., Raj, R., Rambadagalla, M., Rhodes, J., Richardson, S., Richter, S., Ripatti, S., Rocka, S., Roe, C., Roise, O., Rosand, J., Rosenfeld, J. V., Rosenlund, C., Rosenthal, G., Rossaint, R., Rossi, S., Rueckert, D., Rusnak, M., Sahuquillo, J., Sakowitz, O., Sanchez-Porras, R., Sandor, J., Schafer, N., Schmidt, S., Schoechl, H., Schoonman, G., Schou, R. F., Schwendenwein, E., Sewalt, C., Skandsen, T., Smielewski, P., Sorinola, A., Stamatakis, E., Stanworth, S., Stevens, R., Stewart, W., Steyerberg, E. W., Sundstrom, N., Synnot, A., Takala, R., Tamas, V., Tamosuitis, T., Taylor, M. S., Ao, B. T., Tenovuo, O., Theadom, A., Thomas, M., Tibboel, D., Tolias, C., Trapani, T., Tudora, C. M., Vajkoczy, P., Vallance, S., Valeinis, E., Vamos, Z., Van der Steen, G., van der Naalt, J., van Essen, T. A., Van Hecke, W., van Heugten, C., Van Praag, D., Vyvere, T. V., Vargiolu, A., Vega, E., Velt, K., Verheyden, J., Vespa, P. M., Vik, A., Vilcinis, R., Volovici, V., von Steinbuchel, N., Voormolen, D., Vulekovic, P., Wang, K. K. W., Wiegers, E., Williams, G., Wilson, L., Winzeck, S., Wolf, S., Yang, Z., Ylen, P., Younsi, A., Zeiler, F. A., Zelinkova, V., Ziverte, A., and Zoerle, T.
Subjects: Patient Consent, MULTICENTER, Critical Care and Intensive Care Medicine, Patient Admission, 0302 clinical medicine, Traumatic brain injury, Informed consent, Surveys and Questionnaires, Brain Injuries, Traumatic, Prospective Studies, Israel, media_common, CAPACITY ASSESSMENT, OUTCOMES, RESUSCITATION RESEARCH, PROXY CONSENT, Member states, Research Personnel, humanities, 3. Good health, Europe, Intensive Care Units, Policy, medicine.medical_specialty, Concordance, TRAUMATIC BRAIN-INJURY, Legislation, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, medicine, Humans, media_common.cataloged_instance, In patient, European Union, European union, Ethics, SURROGATE DECISION-MAKERS, business.industry, 030208 emergency & critical care medicine, 3126 Surgery, anesthesiology, intensive care, radiology, Proxy, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Human Experimentation, 030228 respiratory system, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, DEFERRED CONSENT, Observational study, Human medicine, business, Follow-Up Studies
Abstract: PurposeEnrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice.MethodsVariation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries.ResultsVariation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N=1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N=426;20%) and deferred consent (N=334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%).ConclusionsAlternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers.
Published: 2020
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37. Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Author: Benjamin Y. Gravesteijn, Daan Nieboer, Ari Ercole, Hester F. Lingsma, David Nelson, Ben van Calster, Ewout W. Steyerberg, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Maryse Cnossen, Mark Coburn, Jonathan Coles, D. Jamie Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier Guy-Loup Dulière, Patrick Esser, Erzsébet Ezer Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett Ji-yao Jiang, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Ana M. Castaño-León, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Davide Mulazzi, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, Virginia Newcombe, Quentin Noirhomme, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Ana Kowark, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Audrey Vanhaudenhuyse, Roel P.J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederik A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Gravesteijn, B. Y., Nieboer, D., Ercole, A., Lingsma, H. F., Nelson, D., van Calster, B., Steyerberg E. W., (CENTER-TBI collaborators), Beretta, L., Ercole, Ari [0000-0001-8350-8093], Apollo - University of Cambridge Repository, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Psychiatrie & Neuropsychologie, Molecular Neuroscience and Ageing Research (MOLAR), Gravesteijn, B, Nieboer, D, Ercole, A, Lingsma, H, Nelson, D, van Calster, B, Steyerberg, E, Akerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzo, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Chevallard, G, Chieregato, A, Citerio, G, Cnossen, M, Coburn, M, Coles, J, Cooper, D, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dawes, Ragauskas, Arminas, Ročka, Saulius, Tamošuitis, Tomas, Vilcinis, Rimantas, Public Health, Tamosuitis, Tomas, „Elsevier Science' grupė, Academic Medical Center, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Clinicum, Helsinki University Hospital Area, Neurokirurgian yksikkö, Samuli Olli Ripatti / Principal Investigator, and Complex Disease Genetics
Subjects: Male, Epidemiology, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), Logistic regression, computer.software_genre, Data science, Machine Learning, 0302 clinical medicine, Traumatic brain injury, Brain Injuries, Traumatic, Medicine, 030212 general & internal medicine, Decision Making, Computer-Assisted, Glasgow Outcome Scale, Regression analysis, Middle Aged, Prognosis, 3142 Public health care science, environmental and occupational health, Regression, Random forest, Female, TUTORIAL, Cohort study, Algorithm, Algorithms, Adult, BIG DATA, Prognosi, cohort study, data science, machine learning, prediction, prognosis, traumatic brain injury, Machine learning, VALIDATION, 03 medical and health sciences, VDP::Teknologi: 500::Medisinsk teknologi: 620, Humans, VDP::Medisinske Fag: 700, Glasgow Coma Scale, Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci), Models, Statistical, business.industry, CARE, 3141 Health care science, VDP::Medical disciplines: 700, Logistic Models, Cohort study, Data science, Machine learning, Prediction, Prognosis, Traumatic brain injury, Artificial intelligence, Gradient boosting, business, Prediction, computer, 030217 neurology & neurosurgery, Predictive modelling, VDP::Technology: 500::Medical technology: 620
Abstract: OBJECTIVE: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. STUDY DESIGN AND SETTING: We performed logistic (LR), lasso, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n=11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks, and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with GCS, Data used in preparation of this manuscript were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), the OneMind (USA) and the Integra LifeSciences Corporation (USA). The funder had no role in the study design, enrollment, collection of data, writing, or publication decisions.
Published: 2020
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38. Tracheal intubation in traumatic brain injury: a multicentre prospective observational study

Author: Benjamin Yael Gravesteijn, Charlie Aletta Sewalt, Daan Nieboer, David Krishna Menon, Andrew Maas, Fiona Lecky, Markus Klimek, Hester Floor Lingsma, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Iris Ceyisakar, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Ana M. Castaño-León, Marc Maegele, Marek Majdan, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P.J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, CENTER-TBI Collaborators, Gravesteijn, B, Sewalt, C, Nieboer, D, Menon, D, Maas, A, Lecky, F, Klimek, M, Lingsma, H, Akerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzo, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Ceyisakar, I, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, Boogert, H, Depreitere, B, Dilvesi, D, Dixit, A, Donoghue, E, Dreier, J, Duliere, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovacs, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Castano-Leon, A, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nyiradi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnak, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Synnot, A, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Vallance, S, Valeinis, E, Vamos, Z, van der Jagt, M, Van der Steen, G, van der Naalt, J, van Dijck, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, Vyvere, T, van Wijk, R, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, von Steinbuchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Gravesteijn, Benjamin Yael, Sewalt, Charlie Aletta, Nieboer, Daan, Menon, David Krishna, Maas, Andrew, Lecky, Fiona, Klimek, Marku, Lingsma, Hester Floor (Center TBI Collaborators), Beretta, Luigi, Molecular Neuroscience and Ageing Research (MOLAR), Ragauskas, Arminas, Ročka, Saulius, Tamošuitis, Tomas, Vilcinis, Rimantas, Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Neurokirurgian yksikkö, Helsinki Institute for Information Technology, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Clinicum, Helsinki University Hospital Area, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Anesthesiology, Public Health, Neurology, Neurosurgery, Intensive Care, Pediatric Surgery, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Psychiatrie & Neuropsychologie, Tamosuitis, Tomas, and „Elsevier Science' grupė
Subjects: Male, Medicin och hälsovetenskap, Neurologi, medicine.medical_treatment, CENTER-TBI, GUIDELINES, Medical and Health Sciences, DECREASED SURVIVAL, 0302 clinical medicine, Neuroscience and Neuroanaesthesia, HYPOTENSION, Brain Injuries, Traumatic, Medicine, Intubation, RAPID-SEQUENCE INTUBATION, 030212 general & internal medicine, Prospective Studies, tracheal intubation, Prospective cohort study, neurological outcome, OUTCOMES, Trauma Severity Indices, Abbreviated Injury Scale, traumatic brain injury, Head injury, Middle Aged, prehospital, PREHOSPITAL ENDOTRACHEAL INTUBATION, 3. Good health, Europe, Neurology, Anesthesia, effectiveness, Europe, neurological outcome, prehospital, tracheal intubation, traumatic brain injury, Female, Adult, Anestesi och intensivvård, Traumatic brain injury, effectiveness, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, MANAGEMENT, Intubation, Intratracheal, Humans, Aged, POSITIVE-PRESSURE VENTILATION, Anesthesiology and Intensive Care, business.industry, Tracheal intubation, Glasgow Coma Scale, HEAD-INJURY, 030208 emergency & critical care medicine, Odds ratio, medicine.disease, 3126 Surgery, anesthesiology, intensive care, radiology, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Anesthesiology and Pain Medicine, Human medicine, business
Abstract: Contains fulltext : 226032.pdf (Publisher’s version ) (Open Access) BACKGROUND: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. METHODS: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. RESULTS: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79-1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65-1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. CONCLUSION: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. CLINICAL TRIAL REGISTRATION: NCT02210221.
Published: 2020
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39. Prehospital Guidelines

Author: Riikka Takala
Published: 2020
Full Text: View/download PDF

40. Diffuse Intracranial Injury Patterns Are Associated with Impaired Cerebrovascular Reactivity in Adult Traumatic Brain Injury: A CENTER-TBI Validation Study

Author: Frederick A. Zeiler, François Mathieu, Miguel Monteiro, Ben Glocker, Ari Ercole, Erta Beqiri, Manuel Cabeleira, Nino Stocchetti, Peter Smielewski, Marek Czosnyka, Virginia Newcombe, David K. Menon, Audny Anke, Bo-Michael Bellander, Andras Buki, Marco Carbonara, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Endre Czeiter, Bart Depreitere, Shirin Frisvold, Raimund Helbok, Stefan Jankowski, Danile Kondziella, Lars-Owe Koskinen, Ana Kowark, Geert Meyfroidt, Kirsten Moeller, David Nelson, Anna Piippo-Karjalainen, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Jonathan Rhodes, Saulius Rocka, Rolf Rossaint, Juan Sahuquillo, Oliver Sakowitz, Nina Sundström, Riikka Takala, Tomas Tamosuitis, Olli Tenovuo, Peter Vajkoczy, Alessia Vargiolu, Rimantas Vilcinis, Stefan Wolf, Alexander Younsi, Zeiler, F, Mathieu, F, Monteiro, M, Glocker, B, Ercole, A, Beqiri, E, Cabeleira, M, Stocchetti, N, Smielewski, P, Czosnyka, M, Newcombe, V, Menon, D, and Citerio, G
Subjects: Adult, Male, 030506 rehabilitation, medicine.medical_specialty, Validation study, Traumatic brain injury, injury pattern, Computed tomography, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Cerebrovascular reactivity, Brain Injuries, Traumatic, medicine, Retrospective analysis, Humans, Autoregulation, Prospective Studies, image segmentation, medicine.diagnostic_test, business.industry, autoregulation, computed tomography, PRx, Original Articles, Middle Aged, medicine.disease, humanities, Cerebrovascular Circulation, Female, Neurology (clinical), Radiology, 0305 other medical science, business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, CT
Abstract: Recent single-center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intracranial injury and worse cerebrovascular reactivity. The goal of this study was to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high-resolution intensive care unit (HR ICU) data set. Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher) and the presence of a digital admission CT scan. Physiological signals were processed for pressure reactivity index (PRx) and both the percent (%) time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH), and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteristics and PRx metrics was conducted using Mann-U, Jonckheere-Terpstra testing, with a combination of univariate linear and logistic regression techniques. A total of 165 patients were included. Cisternal compression and high admission Rotterdam and Helsinki CT scores, and Marshall CT diffuse injury sub-scores were associated with increased percent (%) time and hourly dose above PRx threshold of 0, +0.25, and +0.35 (p
Published: 2020

41. Variation in neurosurgical management of traumatic brain injury: a survey in 68 centers participating in the CENTER-TBI study

Author: van Essen, Thomas A., den Boogert, Hugo F., Cnossen, Maryse C., de Ruiter, Godard C. W., Haitsma, Iain, Polinder, Suzanne, Steyerberg, Ewout W., Menon, David, Maas, Andrew I. R., Lingsma, Hester F., Peul, Wilco C., Cecilia, Ackerlund, Hadie, Adams, Vanni, Agnoletti, Judith, Allanson, Krisztina, Amrein, Norberto, Andaluz, Nada, Andelic, Lasse, Andreassen, Azasevac, Antun, Audny, Anke, Anna, Antoni, Hilko, Ardon, Gerard, Audibert, Kaspars, Auslands, Philippe, Azouvi, Luisa, Azzolini Maria, Camelia, Baciu, Rafael, Badenes, Ronald, Bartels, Pal, Barzo, Ursula, Bauerfeind, Romuald, Beauvais, Ronny, Beer, Francisco Javier, Belda, Bo-Michael, Bellander, Antonio, Belli, Remy, Bellier, Habib, Benali, Thierry, Benard, Maurizio, Berardino, Luigi, Beretta, Christopher, Beynon, Federico, Bilotta, Harald, Binder, Erta, Biqiri, Morten, Blaabjerg, Hugo, den Boogert, Pierre, Bouzat, Peter, Bragge, Alexandra, Brazinova, Vibeke, Brinck, Joanne, Brooker, Camilla, Brorsson, Andras, Buki, Monika, Bullinger, Emiliana, Calappi, Rosa, Calvi Maria, Peter, Cameron, Lozano Guillermo, Carbayo, Marco, Carbonara, Elsa, Carise, Carpenter, K., Ana M, Castano-Leon, Francesco, Causin, Giorgio, Chevallard, Arturo, Chieregato, Giuseppe, Citerio, Maryse, Cnossen, Mark, Coburn, Jonathan, Coles, Lizzie, Coles-Kemp, Johnny, Collett, Jamie, Cooper D., Marta, Correia, Amra, Covic, Nicola, Curry, Endre, Czeiter, Marek, Czosnyka, Claire, Dahyot-Fizelier, Francois, Damas, Pierre, Damas, Helen, Dawes, Veronique, De Keyser, Francesco, Della Corte, Bart, Depreitere, Godard, de Ruiter C. W., Dula, Dilvesi, Diederik, Dippel, Abhishek, Dixit, Emma, Donoghue, Jens, Dreier, Guy-Loup, Duliere, George, Eapen, Heiko, Engemann, Ari, Ercole, Patrick, Esser, Erzsebet, Ezer, Martin, Fabricius, Valery, Feigin L., Kelly, Foks, Francesca, Fossi, Gilles, Francony, Ulderico, Freo, Shirin, Frisvold, Alex, Furmanov, Pablo, Gagliardo, Damien, Galanaud, Dashiell, Gantner, Karin, Geleijns, Pradeep, George, Alexandre, Ghuysen, Lelde, Giga, Benoit, Giraud, Ben, Glocker, Jagos, Golubovic, Pedro, Gomez A., Francesca, Grossi, Russell, Gruen L., Deepak, Gupta, Juanita, Haagsma A., Iain, Haitsma, Jed, Hartings A., Raimund, Helbok, Eirik, Helseth, Daniel, Hertle, Astrid, Hoedemaekers, Stefan, Hoefer, Lindsay, Horton, Jilske, Huijben, Peter, Hutchinson J., Kristine, Haberg Asta, Bram, Jacobs, Stefan, Jankowski, Mike, Jarrett, Bojan, Jelaca, Kelly, Jones, Konstantinos, Kamnitsas, Mladen, Karan, Ari, Katila, Maija, Kaukonen, Thomas, Kerforne, Riku, Kivisaari, Angelos, Kolias G., Balint, Kolumban, Erwin, Kompanje, Ksenija, Kolundzija, Daniel, Kondziella, Lars-Owe, Koskinen, Noemi, Kovacs, Alfonso, Lagares, Linda, Lanyon, Steven, Laureys, Fiona, Lecky, Christian, Ledig, Rolf, Lefering, Valerie, Legrand, Jin, Lei, Leon, Levi, Roger, Lightfoot, Hester, Lingsma, Dirk, Loeckx, Angels, Lozano, Andrew, Maas I. R., Stephen, MacDonald, Marc, Maegele, Marek, Majdan, Sebastian, Major, Alex, Manara, Geoffrey, Manley, Didier, Martin, Francisco, Martin Leon, Costanza, Martino, Armando, Maruenda, Hugues, Marechal, Alessandro, Masala, Julia, Mattern, Charles, McFadyen, Catherine, McMahon, Bela, Melegh, David, Menon, Tomas, Menovsky, Cristina, Morganti-Kossmann, Davide, Mulazzi, Visakh, Muraleedharan, Lynnette, Murray, Holger, Muehlan, Nandesh, Nair, Ancuta, Negru, David, Nelson, Virginia, Newcombe, Daan, Nieboer, Quentin, Noirhomme, Jozsef, Nyiradi, Mauro, Oddo, Annemarie, Oldenbeuving, Matej, Oresic, Fabrizio, Ortolano, Aarno, Palotie, Paul, Parizel M., Adriana, Patruno, Jean-Francois, Payen, Natascha, Perera, Vincent, Perlbarg, Paolo, Persona, Anna, Piippo-Karjalainen, Sebastien, Pili Floury, Matti, Pirinen, Horia, Ples, Maria Antonia, Poca, Suzanne, Polinder, Inigo, Pomposo, Jussi, Posti, Louis, Puybasset, Andreea, Radoi, Arminas, Ragauskas, Rahul, Raj, Malinka, Rambadagalla, Ruben, Real, Veronika, Rehorcikova, Jonathan, Rhodes, Samuli, Ripatti, Saulius, Rocka, Cecilie, Roe, Olav, Roise, Gerwin, Roks, Jonathan, Rosand, Jeffrey, Rosenfeld, Christina, Rosenlund, Guy, Rosenthal, Rolf, Rossaint, Sandra, Rossi, Daniel, Rueckert, Martin, Rusnak, Marco, Sacchi, Barbara, Sahakian, Juan, Sahuquillo, Oliver, Sakowitz, Francesca, Sala, Renan, Sanchez-Porras, Janos, Sandor, Edgar, Santos, Luminita, Sasu, Davide, Savo, Nadine, Schaeffer, Inger, Schipper, Barbara, Schloesser, Silke, Schmidt, Herbert, Schoechl, Guus, Schoonman, Frederik, Schou Rico, Elisabeth, Schwendenwein, Michael, Schoell, Ozcan, Sir, Toril, Skandsen, Lidwien, Smakman, Dirk, Smeets, Peter, Smielewski, Abayomi, Sorinola, Emmanuel, Stamatakis, Simon, Stanworth, Nicole, Steinbuechel, Ana, Stevanovic, Robert, Stevens, William, Stewart, Ewout, Steyerberg W., Nino, Stocchetti, Nina, Sundstrom, Anneliese, Synnot, Fabio Silvio, Taccone, Riikka, Takala, Viktoria, Tamas, Paivi, Tanskanen, Steven, Taylor Mark, Braden, Te Ao, Olli, Tenovuo, Ralph, Telgmann, Guido, Teodorani, Alice, Theadom, Matt, Thomas, Dick, Tibboel, Christos, Tolias, Luaba, Tshibanda Jean-Flory, Tony, Trapani, Maria, Tudora Cristina, Peter, Vajkoczy, Shirley, Vallance, Egils, Valeinis, Gregory, Van der Steen, Mathieu, Van der Jagt, Joukje, Van der Naalt, Jeroen, van Dijck T. J. M., Thomas, Van Essen A., Wim, Van Hecke, Caroline, van Heugten, Dominique, Van Praag, Thijs, Vande Vyvere, Julia, Van Waesberghe, Audrey, Vanhaudenhuyse, Alessia, Vargiolu, Emmanuel, Vega, Kimberley, Velt, Jan, Verheyden, Paul, Vespa M., Anne, Vik, Rimantas, Vilcinis, Giacinta, Vizzino, Carmen, Vleggeert-Lankamp, Victor, Volovici, Daphne, Voormolen, Peter, Vulekovic, Zoltan, Vamos, Derick, Wade, Kevin, Wang K. W., Lei, Wang, Lars, Wessels, Eno, Wildschut, Guy, Williams, Lindsay, Wilson, Maren, Winkler K. L., Stefan, Wolf, Peter, Ylen, Alexander, Younsi, Menashe, Zaaroor, Yang, Zhihui, Agate, Ziverte, Fabrizio, Zumbo, van Essen, Thomas A., den Boogert, Hugo F., Cnossen, Maryse C., de Ruiter, Godard C. W., Haitsma, Iain, Polinder, Suzanne, Steyerberg, Ewout W., Menon, David, Maas, Andrew I. R., Lingsma, Hester F., Peul, Wilco C., Cecilia, Ackerlund, Hadie, Adams, Vanni, Agnoletti, Judith, Allanson, Krisztina, Amrein, Norberto, Andaluz, Nada, Andelic, Lasse, Andreassen, Azasevac, Antun, Audny, Anke, Anna, Antoni, Hilko, Ardon, Gerard, Audibert, Kaspars, Auslands, Philippe, Azouvi, Luisa, Azzolini Maria, Camelia, Baciu, Rafael, Badenes, Ronald, Bartels, Pal, Barzo, Ursula, Bauerfeind, Romuald, Beauvais, Ronny, Beer, Francisco Javier, Belda, Bo-Michael, Bellander, Antonio, Belli, Remy, Bellier, Habib, Benali, Thierry, Benard, Maurizio, Berardino, Luigi, Beretta, Christopher, Beynon, Federico, Bilotta, Harald, Binder, Erta, Biqiri, Morten, Blaabjerg, Hugo, den Boogert, Pierre, Bouzat, Peter, Bragge, Alexandra, Brazinova, Vibeke, Brinck, Joanne, Brooker, Camilla, Brorsson, Andras, Buki, Monika, Bullinger, Emiliana, Calappi, Rosa, Calvi Maria, Peter, Cameron, Lozano Guillermo, Carbayo, Marco, Carbonara, Elsa, Carise, Carpenter, K., Ana M, Castano-Leon, Francesco, Causin, Giorgio, Chevallard, Arturo, Chieregato, Giuseppe, Citerio, Maryse, Cnossen, Mark, Coburn, Jonathan, Coles, Lizzie, Coles-Kemp, Johnny, Collett, Jamie, Cooper D., Marta, Correia, Amra, Covic, Nicola, Curry, Endre, Czeiter, Marek, Czosnyka, Claire, Dahyot-Fizelier, Francois, Damas, Pierre, Damas, Helen, Dawes, Veronique, De Keyser, Francesco, Della Corte, Bart, Depreitere, Godard, de Ruiter C. 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J. M., Thomas, Van Essen A., Wim, Van Hecke, Caroline, van Heugten, Dominique, Van Praag, Thijs, Vande Vyvere, Julia, Van Waesberghe, Audrey, Vanhaudenhuyse, Alessia, Vargiolu, Emmanuel, Vega, Kimberley, Velt, Jan, Verheyden, Paul, Vespa M., Anne, Vik, Rimantas, Vilcinis, Giacinta, Vizzino, Carmen, Vleggeert-Lankamp, Victor, Volovici, Daphne, Voormolen, Peter, Vulekovic, Zoltan, Vamos, Derick, Wade, Kevin, Wang K. W., Lei, Wang, Lars, Wessels, Eno, Wildschut, Guy, Williams, Lindsay, Wilson, Maren, Winkler K. L., Stefan, Wolf, Peter, Ylen, Alexander, Younsi, Menashe, Zaaroor, Yang, Zhihui, Agate, Ziverte, and Fabrizio, Zumbo
Abstract: BackgroundNeurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe.MethodsA survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP).ResultsThe survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25mmHg, 18% 30mmHg, and 17% 20mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions.ConclusionDespite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care.
Published: 2019

42. Dexmedetomidine and Subarachnoid Haemorrhage

Author: Orion Corporation, Orion Pharma and Riikka Takala, MD, PhD Senior Staff Anaesthesiologist
Published: 2017

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