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1. 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

2. Traumatic brain injury : progress and challenges in prevention, clinical care, and research

Author

Andrew I R Maas, David K Menon, Geoffrey T Manley, Mathew Abrams, Cecilia Åkerlund, Nada Andelic, Marcel Aries, Tom Bashford, Michael J Bell, Yelena G Bodien, Benjamin L Brett, András Büki, Randall M Chesnut, Giuseppe Citerio, David Clark, Betony Clasby, D Jamie Cooper, Endre Czeiter, Marek Czosnyka, Kristen Dams-O'Connor, Véronique De Keyser, Ramon Diaz-Arrastia, Ari Ercole, Thomas A van Essen, Éanna Falvey, Adam R Ferguson, Anthony Figaji, Melinda Fitzgerald, Brandon Foreman, Dashiell Gantner, Guoyi Gao, Joseph Giacino, Benjamin Gravesteijn, Fabian Guiza, Deepak Gupta, Mark Gurnell, Juanita A Haagsma, Flora M Hammond, Gregory Hawryluk, Peter Hutchinson, Mathieu van der Jagt, Sonia Jain, Swati Jain, Ji-yao Jiang, Hope Kent, Angelos Kolias, Erwin J O Kompanje, Fiona Lecky, Hester F Lingsma, Marc Maegele, Marek Majdan, Amy Markowitz, Michael McCrea, Geert Meyfroidt, Ana Mikolić, Stefania Mondello, Pratik Mukherjee, David Nelson, Lindsay D Nelson, Virginia Newcombe, David Okonkwo, Matej Orešič, Wilco Peul, Dana Pisică, Suzanne Polinder, Jennie Ponsford, Louis Puybasset, Rahul Raj, Chiara Robba, Cecilie Røe, Jonathan Rosand, Peter Schueler, David J Sharp, Peter Smielewski, Murray B Stein, Nicole von Steinbüchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Nancy Temkin, Olli Tenovuo, Alice Theadom, Ilias Thomas, Abel Torres Espin, Alexis F Turgeon, Andreas Unterberg, Dominique Van Praag, Ernest van Veen, Jan Verheyden, Thijs Vande Vyvere, Kevin K W Wang, Eveline J A Wiegers, W Huw Williams, Lindsay Wilson, Stephen R Wisniewski, Alexander Younsi, John K Yue, Esther L Yuh, Frederick A Zeiler, Marina Zeldovich, Roger Zemek, InTBIR Participants and Investigators, Maas, A, Menon, D, Manley, G, Abrams, M, Åkerlund, C, Andelic, N, Aries, M, Bashford, T, Bell, M, Bodien, Y, Brett, B, Büki, A, Chesnut, R, Citerio, G, Clark, D, Clasby, B, Cooper, D, Czeiter, E, Czosnyka, M, Dams-O'Connor, K, De Keyser, V, Diaz-Arrastia, R, Ercole, A, van Essen, T, Falvey, É, Ferguson, A, Figaji, A, Fitzgerald, M, Foreman, B, Gantner, D, Gao, G, Giacino, J, Gravesteijn, B, Guiza, F, Gupta, D, Gurnell, M, Haagsma, J, Hammond, F, Hawryluk, G, Hutchinson, P, van der Jagt, M, Jain, S, Jiang, J, Kent, H, Kolias, A, Kompanje, E, Lecky, F, Lingsma, H, Maegele, M, Majdan, M, Markowitz, A, Mccrea, M, Meyfroidt, G, Mikolić, A, Mondello, S, Mukherjee, P, Nelson, D, Nelson, L, Newcombe, V, Okonkwo, D, Orešič, M, Peul, W, Pisică, D, Polinder, S, Ponsford, J, Puybasset, L, Raj, R, Robba, C, Røe, C, Rosand, J, Schueler, P, Sharp, D, Smielewski, P, Stein, M, von Steinbüchel, N, Stewart, W, Steyerberg, E, Stocchetti, N, Temkin, N, Tenovuo, O, Theadom, A, Thomas, I, Espin, A, Turgeon, A, Unterberg, A, Van Praag, D, van Veen, E, Verheyden, J, Vyvere, T, Wang, K, Wiegers, E, Williams, W, Wilson, L, Wisniewski, S, Younsi, A, Yue, J, Yuh, E, Zeiler, F, Zeldovich, M, Zemek, R, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Intensive Care, and MUMC+: MA Medische Staf IC (9)

Subjects
NEUROTRAUMA EFFECTIVENESS RESEARCH, OUTCOME PREDICTION, PREHOSPITAL TRIAGE TOOLS, COMMON DATA ELEMENTS, Violence, INTENSIVE-CARE, CEREBRAL PERFUSION-PRESSURE, POSTTRAUMATIC-STRESS-DISORDER, Cost of Illness, LIFE-SUSTAINING THERAPY, CT HEAD RULE, Brain Injuries, Traumatic, Humans, Neurology (clinical), MAJOR TRAUMA, Human medicine, Sports
Abstract

Traumatic brain injury (TBI) has the highest incidence of all common neurological disorders, and poses a substantial public health burden. TBI is increasingly documented not only as an acute condition but also as a chronic disease with long-term consequences, including an increased risk of late-onset neurodegeneration. The first Lancet Neurology Commission on TBI, published in 2017, called for a concerted effort to tackle the global health problem posed by TBI. Since then, funding agencies have supported research both in high-income countries (HICs) and in low-income and middle-income countries (LMICs). In November 2020, the World Health Assembly, the decision-making body of WHO, passed resolution WHA73.10 for global actions on epilepsy and other neurological disorders, and WHO launched the Decade for Action on Road Safety plan in 2021. New knowledge has been generated by large observational studies, including those conducted under the umbrella of the International Traumatic Brain Injury Research (InTBIR) initiative, established as a collaboration of funding agencies in 2011. InTBIR has also provided a huge stimulus to collaborative research in TBI and has facilitated participation of global partners. The return on investment has been high, but many needs of patients with TBI remain unaddressed. This update to the 2017 Commission presents advances and discusses persisting and new challenges in prevention, clinical care, and research.

Published
2022

4. Cortical atrophy in patients with cerebral amyloid angiopathy: a case-control study

Author

Panagiotis Fotiadis, Eitan Auriel, Marieke J.H. Wermer, Jeroen van der Grond, Jonathan Rosand, Reisa A. Sperling, Yael D. Reijmer, Mark A. van Buchem, Alison M. Ayres, Keith A. Johnson, Kristin Schwab, Jonathan R. Polimeni, Gisela M. Terwindt, Aaron P. Schultz, Anand Viswanathan, Alzheimer’s Disease Neuroimaging Initiative, Steven M. Greenberg, Anna M. van Opstal, Trey Hedden, M. Edip Gurol, Sanneke van Rooden, and Sergi Martinez-Ramirez

Subjects
Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Clinical Neurology, Disease, Statistics, Nonparametric, Article, 03 medical and health sciences, 0302 clinical medicine, Atrophy, mental disorders, Image Processing, Computer-Assisted, medicine, Humans, Dementia, Aged, Cerebral Hemorrhage, Retrospective Studies, Cerebral Cortex, Amyloid beta-Peptides, business.industry, Amyloidosis, Case-control study, Retrospective cohort study, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Cerebral Amyloid Angiopathy, 030104 developmental biology, medicine.anatomical_structure, Cerebral cortex, Case-Control Studies, Linear Models, Female, Neurology (clinical), Cerebral amyloid angiopathy, business, 030217 neurology & neurosurgery
Abstract

SummaryBackgroundLoss of cortical grey matter is a diagnostic marker of many neurodegenerative diseases, and is a key mediator of cognitive impairment. We postulated that cerebral amyloid angiopathy (CAA), characterised by cortical vascular amyloid deposits, is associated with cortical tissue loss independent of parenchymal Alzheimer's disease pathology. We tested this hypothesis in patients with hereditary cerebral haemorrhage with amyloidosis–Dutch type (HCHWA-D), a monogenetic disease with minimal or no concomitant Alzheimer's disease pathology, as well as in patients with sporadic CAA and healthy and Alzheimer's disease controls.MethodsIn this observational case-control study, we included six groups of participants: patients diagnosed with HCHWA-D using genetic testing; healthy controls age-matched to the HCHWA-D group; patients with probable sporadic CAA without dementia; two independent cohorts of healthy controls age-matched to the CAA group; and patients with Alzheimer's disease age-matched to the CAA group. De-identified (but unmasked) demographic, clinical, radiological, and genetic data were collected at Massachusetts General Hospital (Boston, MA, USA), at Leiden University (Leiden, Netherlands), and at sites contributing to Alzheimer's Disease Neuroimaging Initiative (ADNI). The primary outcome measure was cortical thickness. The correlations between cortical thickness and structural lesions, and blood-oxygen-level-dependent time-to-peak (BOLD-TTP; a physiological measure of vascular dysfunction) were analysed to understand the potential mechanistic link between vascular amyloid and cortical thickness. The radiological variables of interest were quantified using previously validated computer-assisted tools, and all results were visually reviewed to ensure their accuracy.ResultsBetween March 15, 2006, and Dec 1, 2014, we recruited 369 individuals (26 patients with HCHWA-D and 28 age-matched, healthy controls; 63 patients with sporadic CAA without dementia; two healthy control cohorts with 63 and 126 individuals; and 63 patients with Alzheimer's disease). The 26 patients with HCHWA-D had thinner cortices (2·31 mm [SD 0·18]) than the 28 healthy controls (mean difference −0·112 mm, 95% CI −0·190 to −0·034, p=0·006). The 63 patients with sporadic CAA without dementia had thinner cortices (2·17 mm [SD 0·11]) than the two healthy control cohorts (n=63, mean difference −0·14 mm, 95% CI −0·17 to −0·10, p

Published
2016

5. Identification of additional risk loci for stroke and small vessel disease

Author

Matthew Traylor, Vilmundur Gudnason, Kerri L. Wiggins, Christophe Tzourio, Reinhold E. Schmidt, Hugo J. Aparicio, Tamara B. Harris, Audrey Y. Chu, Oscar R. Benavente, Anton J. M. de Craen, Nancy L. Pedersen, Lars Lannfelt, Didier Leys, Erkki Vartiainen, Myriam Fornage, Marileen L.P. Portegies, Nicholas L. Smith, Daniel Woo, Martin Dichgans, John W. Cole, Christina Jern, Christopher R Levi, Kenneth Rice, André G. Uitterlinden, Rebecca F. Gottesman, M. Arfan Ikram, Ralph L. Sacco, Cornelia M. van Duijn, Samuli Ripatti, Anita L. DeStefano, Donna K. Arnett, Curtis R. French, Tobias Kurth, Tomi Pastinen, Raji P. Grewal, Susan R. Heckbert, Jordi Jimenez-Conde, Jemma C. Hopewell, Cecilia M. Lindgren, Azadeh Reyahi, Michèle M. Sale, Marcello Ricardo Paulista Markus, Albert Hofman, Seung Hoan Choi, Peter J. Koudstaal, Veikko Salomaa, Robert Clarke, Arne Lindgren, B. Gwen Windham, Farid Radmanesh, Peter M. Rothwell, Carsten Oliver Schmidt, Xueqiu Jian, David S. Knopman, Yongmei Liu, Joan Montaner, Jean-François Dartigues, Paul M. Ridker, Julie A. Johnson, Stefan Gustafsson, Jerome I. Rotter, Manja Kloss, Tatjana Rundek, David J. Stott, Ganesh Chauhan, Ordan J. Lehmann, Ali Moussavi Nik, Marcel den Hoed, Alessandro Pezzini, Jin-Moo Lee, Hans J. Grabe, Sylvia Wassertheil-Smoller, Anders Hamsten, Thomas H. Mosley, Muralidharan Sargurupremraj, Lenore J. Launer, Kathryn M. Rexrode, Quenna Wong, Jonathan Rosand, David A. Bennett, Philip L. De Jager, James F. Meschia, Alexa S. Beiser, J. Wouter Jukema, Traci M. Bartz, Mike A. Nalls, Cathie Sudlow, Erik Ingelsson, Yoichiro Kamatani, Ulf Schminke, Joris Deelen, Stéphanie Debette, Andrew P. Morris, Aki S. Havulinna, Sudha Seshadri, Bradford B. Worrall, Stephen S. Rich, Lars Lindgren, Hieab H.H. Adams, Ani Manichaikul, Jean-Sébastien Vidal, Bruce M. Psaty, Julie E. Buring, Jean Dallongeville, Oscar L. Lopez, Corey R. Arnold, Olle Melander, Olafur Kjartansson, Alexander Teumer, Sarah J. Childs, William T. Longstreth, Charles C. White, Stefan T. Engelter, Daniel I. Chasman, Norrina B. Allen, Rainer Malik, Vincent Thijs, Stella Trompet, Joshua C. Bis, Ian Ford, Peter Carlsson, Céline Bellenguez, Sara L. Pulit, Pankaj Sharma, Patrik K. E. Magnusson, Flora Xue, Giorgio B. Boncoraglio, Mark Lathrop, Melissa E. Garcia, Andrew D. Johnson, Steve Bevan, Albert V. Smith, Claudia L. Satizabal, Agnieszka Slowik, Michael Griswold, Claudine Berr, and Hugh S. Markus

Subjects
Adult, Male, 0301 basic medicine, Adolescent, Population, Genome-wide association study, Biology, Bioinformatics, Article, Brain ischemia, Mice, Young Adult, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, medicine, Animals, Humans, Child, education, Allele frequency, Stroke, Aged, Aged, 80 and over, education.field_of_study, Cerebral infarction, Forkhead Transcription Factors, Odds ratio, Middle Aged, 16. Peace & justice, medicine.disease, R1, 3. Good health, Minor allele frequency, 030104 developmental biology, Genetic Loci, Cerebral Small Vessel Diseases, Child, Preschool, Female, Neurology (clinical), 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Background Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. Methods For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p−6) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-wide significant findings (at p−8), we explored associations with additional cerebrovascular phenotypes and did functional experiments using conditional (inducible) deletion of the probable causal gene in mice. We also studied the expression of orthologs of this probable causal gene and its effects on cerebral vasculature in zebrafish mutants. Findings We replicated seven of eight known loci associated with risk for ischaemic stroke, and identified a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with risk of all-stroke (odds ratio [OR] 1·08, 95% CI 1·05–1·12, p=1·48 × 10−8; minor allele frequency 21%). The rs12204590 stroke risk allele was also associated with increased MRI-defined burden of white matter hyperintensity—a marker of cerebral small vessel disease—in stroke-free adults (n=21 079; p=0·0025). Consistently, young patients (aged 2–32 years) with segmental deletions of FOXF2 showed an extensive burden of white matter hyperintensity. Deletion of Foxf2 in adult mice resulted in cerebral infarction, reactive gliosis, and microhaemorrhage. The orthologs of FOXF2 in zebrafish (foxf2b and foxf2a) are expressed in brain pericytes and mutant foxf2b−/− cerebral vessels show decreased smooth muscle cell and pericyte coverage. Interpretation We identified common variants near FOXF2 that are associated with increased stroke susceptibility. Epidemiological and experimental data suggest that FOXF2 mediates this association, potentially via differentiation defects of cerebral vascular mural cells. Further expression studies in appropriate human tissues, and further functional experiments with long follow-up periods are needed to fully understand the underlying mechanisms. Funding NIH, NINDS, NHMRC, CIHR, European national research institutions, Fondation Leducq.

Published
2016

6. Recovery from brain injury: a surprising new drug target

Author

Jin-Moo Lee, Pooja Khatri, and Jonathan Rosand

Subjects
medicine.medical_specialty, Injury control, business.industry, Drug target, MEDLINE, Human factors and ergonomics, Poison control, Recovery of Function, Suicide prevention, Occupational safety and health, Brain Injuries, Injury prevention, Humans, Medicine, Neurology (clinical), business, Intensive care medicine
Published
2019

7. In search of genes for stroke

Author

Paul I.W. de Bakker and Jonathan Rosand

Subjects
business.industry, medicine, Neurology (clinical), medicine.disease, Bioinformatics, business, Stroke, Gene
Published
2007

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