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1. Clinical profile of patients with acute traumatic brain injury undergoing cranial surgery in the United States: report from the 18-centre TRACK-TBI cohort studyResearch in context

Author

John K. Yue, John H. Kanter, Jason K. Barber, Michael C. Huang, Thomas A. van Essen, Mahmoud M. Elguindy, Brandon Foreman, Frederick K. Korley, Patrick J. Belton, Dana Pisică, Young M. Lee, Ryan S. Kitagawa, Mary J. Vassar, Xiaoying Sun, Gabriela G. Satris, Justin C. Wong, Adam R. Ferguson, J. Russell Huie, Kevin K.W. Wang, Hansen Deng, Vincent Y. Wang, Yelena G. Bodien, Sabrina R. Taylor, Debbie Y. Madhok, Michael A. McCrea, Laura B. Ngwenya, Anthony M. DiGiorgio, Phiroz E. Tarapore, Murray B. Stein, Ava M. Puccio, Joseph T. Giacino, Ramon Diaz-Arrastia, Hester F. Lingsma, Pratik Mukherjee, Esther L. Yuh, Claudia S. Robertson, David K. Menon, Andrew I.R. Maas, Amy J. Markowitz, Sonia Jain, David O. Okonkwo, Nancy R. Temkin, Geoffrey T. Manley, Jason E. Chung, Bukre Coskun, Shawn R. Eagle, Leila L. Etemad, Brian Fabian, Feeser V. Ramana, Shankar Gopinath, Christine J. Gotthardt, Ramesh Grandhi, Sabah Hamidi, Ruchira M. Jha, Christopher Madden, Randall Merchant, Lindsay D. Nelson, Richard B. Rodgers, Andrea L.C. Schneider, David M. Schnyer, Abel Torres-Espin, Joye X. Tracey, Alex B. Valadka, and Ross D. Zafonte

Subjects
Decompressive craniectomy, Craniotomy, Glasgow outcome scale, Medical decisionmaking, Neuroimaging, Triage, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery. Methods: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014–2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported. Findings: Of 2032 subjects (age: mean = 41.4-years, range = 17–89-years; male = 71% female = 29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale = 6 vs. 15; midline shift ≥5 mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p

Published
2024
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2. 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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3. Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study

Author

Hester F Lingsma, Ramesh Grandhi, Amy J Markowitz, Debbie Y Madhok, Geoffrey T Manley, Jason Barber, Xiaoying Sun, Michael A McCrea, Kevin K W Wang, Lindsay D Nelson, Pratik Mukherjee, Neeraj Badjatia, Ava M Puccio, David O Okonkwo, Patrick J Belton, Sonia Jain, Nancy R Temkin, Cathra Halabi, Richard B Rodgers, Andrea L C Schneider, Shawn R Eagle, Shankar Gopinath, Randall Merchant, Ross D Zafonte, Raquel C Gardner, John K Yue, Leila L Etemad, Mahmoud M Elguindy, Thomas A van Essen, Rick J G Vreeburg, Christine J Gotthardt, Joye X Tracey, Bukre C Coskun, Nishanth Krishnan, Frederick K Korley, Claudia S Robertson, Ann-Christine Duhaime, Gabriela G Satris, Phiroz E Tarapore, Michael C Huang, Joseph T Giacino, Esther L Yuh, Alex B Valadka, Anthony M DiGiorgio, Yelena G Bodien, Brian Fabian, Adam R Ferguson, Brandon Foreman, J Russell Huie, C Dirk Keene, Christine L MacDonald, Laura B Ngwenya, David M Schnyer, Sabrina R Taylor, Abel Torres-Espin, Mary J Vassar, and Justin C Wong

Subjects
Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Objectives An estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort.Methods Data from hospitalized subjects with Glasgow Coma Scale score of 3–12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014–2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1–3 (vs. 4–8)) at 3, 6, and 12 months after injury.Results Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01–4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months.Conclusions After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed.Level of evidence IV.Trial registration number NCT02119182.

Published
2024
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4. Neuroinflammatory Biomarkers for Traumatic Brain Injury Diagnosis and Prognosis: A TRACK-TBI Pilot Study

Author

John K. Yue, Firas H. Kobeissy, Sonia Jain, Xiaoying Sun, Ryan R.L. Phelps, Frederick K. Korley, Raquel C. Gardner, Adam R. Ferguson, J. Russell Huie, Andrea L.C. Schneider, Zhihui Yang, Haiyan Xu, Cillian E. Lynch, Hansen Deng, Miri Rabinowitz, Mary J. Vassar, Sabrina R. Taylor, Pratik Mukherjee, Esther L. Yuh, Amy J. Markowitz, Ava M. Puccio, David O. Okonkwo, Ramon Diaz-Arrastia, Geoffrey T. Manley, Kevin K.W. Wang, Collaboration group, Neeraj Badjatia, Brandon Foreman, Shankar Gopinath, Ramesh Grandhi, Ruchira M. Jha, Hester F. Lingsma, Christopher Madden, Debbie Y. Madhok, Michael A. McCrea, Randall Merchant, Lindsay D. Nelson, Laura B. Ngwenya, Claudia S. Robertson, Richard B. Rodgers, Gabriela G. Satris, David M. Schnyer, Alex B. Valadka, Thomas A. van Essen, and Ross Zafonte

Subjects
acute phase reactant, alarmin, cytokine, neuroinflammation, prognosis, traumatic brain injury, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24?h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1?4/5?8); and incomplete versus full recovery (GOSE

Published
2023
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5. Diagnostic performance of point-of-care ubiquitin carboxy-terminal Hydrolase-L1 assay in distinguishing imaging abnormalities in traumatic brain injury: A TRACK-TBI cohort study

Author

Kevin K. Wang, Jennifer C. Munoz-Pareja, Lauren A. Lautenslager, J. Adrian Tyndall, Zhihui Yang, Maria R. Kerrigan, Ramon Diaz-Arrastia, Frederick K. Korley, David Okonkwo, Ava M. Puccio, John K. Yue, Sabrina R. Taylor, Pratik Mukherjee, Esther L. Yuh, Nancy R. Temkin, Claudia S. Robertson, Xiaoying Sun, Sonia Jain, Amy J. Markowitz, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J Claude Hemphill, Gillian Hotz, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Lindsay Nelson, Laura Ngwenya, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, and Ross Zafonte

Subjects
TBI, Biomarkers, UCH-L1, Point of care, Mild TBI, NSE, Toxicology. Poisons, RA1190-1270, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5
Abstract

The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Phase 1 Cohort, enrolled 1375 TBI patients (GCS 3–15) presenting to one of 18 US Level I trauma centers within 24 h of injury who had an admission head CT; blood samples were collected, along with 122 orthopedic and 209 healthy controls. The TBI cohort consisted of 810 CT-negative (CT-) and 549 CT-positive (CT+) subjects. Of the CT- subjects who had MRIs, 121 were MRI-positive (MRI+) and 333 were MRI-negative (MRI-). UCH-L1 POC showed best diagnostic performance for CT + versus CT-, 0–8 h post-injury with an AUC of 0·779 [0·708–0.850] when compared to the 0–25 h interval, with an AUC of 0.684 [0.655–0.712]. NSE assay has an AUC of 0.695 [0.619–0.770] for the 0–8 h interval and 0.634 [0.603–0.665] for the 0–25 h interval. During the first 8 after injury, POC UCH-L1 outperforms NSE in identifying TBI patients with structural abnormalities on neuroimaging.

Published
2023
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6. Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study

Author

Margot Kelly-Hedrick, MBE, Sunny Yang Liu, BA, Nancy Temkin, PhD, Jason Barber, MS, Jordan Komisarow, MD, Geoffrey Manley, MD, PhD, Tetsu Ohnuma, MD, MPH, PhD, Katharine Colton, MD, Miriam M. Treggiari, MD, MPH, PhD, Eric E. Monson, PhD, Monica S. Vavilala, MD, Ramesh Grandhi, MD, MS, Daniel T. Laskowitz, MD, MHS, Joseph P. Mathew, MD, MHS, MBA, Adrian Hernandez, MD, MHS, Michael L. James, MD, Karthik Raghunathan, MD, MPH, Ben Goldstein, PhD, Amy J. Markowitz, JD, Vijay Krishnamoorthy, MD, MPH, PhD, the Transforming Clinical Research and Knowledge in Traumatic Brain Injury Investigators, Neeraj Badjatia, MD, Adam R. Ferguson, PhD, Brandon Foreman, MD, Michael McCrea, PhD, Randall Merchant, PhD, Laura B. Ngwenya, MD, PhD, David Okonkwo, MD, PhD, David Schnyer, PhD, John K. Yue, MD, and Ross Zafonte, DO

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate–severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN:. Retrospective cohort study. SETTING:. ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS:. Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate–severe TBI (Glasgow Coma Scale of

Published
2023
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7. MaPPeRTrac: A Massively Parallel, Portable, and Reproducible Tractography Pipeline.

Author

Lanya T. Cai, Joseph Y. Moon, Paul B. Camacho, Aaron T. Anderson, Won Jong Chwa, Bradley P. Sutton, Amy J. Markowitz, Eva M. Palacios, Alexis A. Rodriguez, Geoffrey T. Manley, Shivsundaram Shankar, Peer-Timo Bremer, Pratik Mukherjee, Ravi K. Madduri, Shankar Gopinath, Ramesh Grandhi, C. Dirk Keene, Michael A. McCrea, Randall Merchant, Laura B. Ngwenya, Ava M. Puccio, David Schnyer, Sabrina R. Taylor, John K. Yue, Esther L. Yuh, and Ross Zafonte

Published
2024
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8. Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: an observational cohort study

Author

Frederick K Korley, Sonia Jain, Xiaoying Sun, Ava M Puccio, John K Yue, Raquel C Gardner, Kevin K W Wang, David O Okonkwo, Esther L Yuh, Pratik Mukherjee, Lindsay D Nelson, Sabrina R Taylor, Amy J Markowitz, Ramon Diaz-Arrastia, Geoffrey T Manley, Opeolu Adeoye, Neeraj Badatjia, Ann-Christine Duhaime, Adam Ferguson, Brandon Foreman, Joseph T Giacino, Shankar Gopinath, Ramesh Grandhi, Ryan Kitagawa, Christopher Madden, Randall Merchant, Mike McCrea, Laura Ngwenya, Miri Rabinowitz, Claudia Robertson, David Schnyer, Murray Stein, Mary Vassar, Vincent Wang, Alex Valadka, and Ross Zafonte

Subjects
Neurology (clinical)
Published
2022
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9. Emotional Resilience Predicts Preserved White Matter Microstructure Following Mild Traumatic Brain Injury

Author

Lanya T. Cai, Benjamin L. Brett, Eva M. Palacios, Esther L. Yuh, Ioanna Bourla, Jamie Wren-Jarvis, Yang Wang, Christine Mac Donald, Ramon Diaz-Arrastia, Joseph T. Giacino, David O. Okonkwo, Harvey S. Levin, Claudia S. Robertson, Nancy Temkin, Amy J. Markowitz, Geoffrey T. Manley, Murray B. Stein, Michael A. McCrea, Ross D. Zafonte, Lindsay D. Nelson, Pratik Mukherjee, Adam R. Ferguson, Sabrina R. Taylor, John K. Yue, Ruchira Jha, Shankar Gopinath, Sonia Jain, Laura B. Ngwenya, Neeraj Badjatia, Rao Gullapalli, Frederick K. Korley, Ava M. Puccio, David Schnyer, Christopher Madden, Ramesh Grandhi, C. Dirk Keene, and Randall Merchant

Subjects
Cognitive Neuroscience, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Biological Psychiatry
Abstract

Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient (ER) mTBI phenotype compared with a neuropsychiatrically distressed (ND) mTBI phenotype.The present study used diffusion MRI to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. Diffusion MR images from 172 mTBI patients were analyzed to compute individual diffusion tensor imaging (DTI) maps at 2 weeks and 6 months postinjury.By comparing the DTI parameters between the two phenotypes at global, regional, and voxel levels, the present study showed that the ER patients have higher axial diffusivity (AD) compared to their ND counterparts early after mTBI. Longitudinal analysis revealed greater compromise of WM microstructure in ND patients, with greater decrease of global AD and more widespread decrease of regional AD during the first 6 months after injury compared to their ER counterparts.These results provide neuroimaging evidence of WM microstructural differences underpinning mTBI phenotypes identified from neuropsychological assessments and show differing longitudinal trajectories of these biological effects. These findings suggest diffusion MRI can provide short- and long-term imaging biomarkers of resilience.

Published
2022
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10. 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. Manley, 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, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Mark Sherer, Murray Stein, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, John K. Yue, Esther Yuh, Ross Zafonte, Public Health, Cell biology, Ragauskas, Arminas, Ročka, Saulius, Tamošuitis, Tomas, Vilcinis, Rimantas, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J. 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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11. Life After Mild Traumatic Brain Injury: Widespread Structural Brain Changes Associated With Psychological Distress Revealed With Multimodal Magnetic Resonance Imaging

Author

Francesca Sibilia, Rachel M. Custer, Andrei Irimia, Farshid Sepehrband, Arthur W. Toga, Ryan P. Cabeen, Opeolu Adeoye, Neeraj Badjatia, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Laura B. Ngwenya, Florence Noel, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, and Ross Zafonte

Subjects
General Medicine
Published
2022
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12. 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. Yue, Esther Yuh, Ross Zafonte, Galimberti, S, Graziano, F, Maas, A, Isernia, G, Lecky, F, Jain, S, Sun, X, Gardner, R, Taylor, S, Markowitz, A, Manley, G, Valsecchi, M, Bellelli, G, Citerio, G, Ackerlund, C, Adams, H, 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, Carbayo Lozano, G, Carbonara, M, Castano-Leon, A, Cavallo, S, Chevallard, G, Chieregato, A, 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, 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, Koskinen, L, 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, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, 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, Schwendenwein, E, Sewalt, C, Singh, R, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, 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, van Erp, I, van Essen, T, 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, Vik, A, Vilcinis, R, Volovici, V, von Steinbuchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, 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, Ellenbogen, R, Feeser, V, Ferguson, A, Foreman, B, Gaudette, E, Giacino, J, Gonzalez, L, Gopinath, S, Grandhi, R, Gullapalli, R, Hemphill, C, Hotz, G, Huie, R, Jha, R, Keene, C, 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, Noel, F, Nolan, A, Okonkwo, D, Palacios, E, Perl, D, Puccio, A, Rabinowitz, M, Robertson, C, Rodgers, R, 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, V, Yue, J, Yuh, E, Zafonte, R, Molecular Neuroscience and Ageing Research (MOLAR), CENTER-TBI TRACK-TBI Participants and Investigators, Galimberti, S., Graziano, F., Maas, A. 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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13. Association of Posttraumatic Epilepsy With 1-Year Outcomes After Traumatic Brain Injury

Author

John, Burke, James, Gugger, Kan, Ding, Jennifer A, Kim, Brandon, Foreman, John K, Yue, Ava M, Puccio, Esther L, Yuh, Xiaoying, Sun, Miri, Rabinowitz, Mary J, Vassar, Sabrina R, Taylor, Ethan A, Winkler, Hansen, Deng, Michael, McCrea, Murray B, Stein, Claudia S, Robertson, Harvey S, Levin, Sureyya, Dikmen, Nancy R, Temkin, Jason, Barber, Joseph T, Giacino, Pratik, Mukherjee, Kevin K W, Wang, David O, Okonkwo, Amy J, Markowitz, Sonia, Jain, Daniel, Lowenstein, Geoffrey T, Manley, Ramon, Diaz-Arrastia, Neeraj, Badjatia, Ann-Christine, Duhaime, V Ramana, Feeser, Etienne, Gaudette, Shankar, Gopinath, C Dirk, Keene, Frederick K, Korley, Christopher, Madden, Randall, Merchant, David, Schnyer, and Ross, Zafonte

Subjects
Adult, Male, Incidence, Research, General Medicine, Epilepsy, Post-Traumatic, United States, Cohort Studies, Online Only, Trauma Centers, Neurology, Risk Factors, Surveys and Questionnaires, Brain Injuries, Traumatic, Humans, Female, Glasgow Coma Scale, Prospective Studies, Self Report, Original Investigation
Abstract

Key Points Question Is posttraumatic epilepsy (PTE) associated with unfavorable functional outcomes after traumatic brain injury (TBI)? Findings In this cohort study that included 3296 individuals, the incidence of self-reported diagnosis of PTE at 1 year after injury among individuals who had experienced TBI was 2.8%. Patients with PTE had worse outcome scores at 1 year after injury compared with those without PTE, even after accounting for injury severity and neuroimaging findings on cranial computed tomography. Meaning These findings suggest that PTE is a significant sequela of TBI with adverse associations with recovery., This cohort study assesses the incidence, risk factors, and functional outcomes associated with self-reported posttraumatic epilepsy in patients with traumatic brain injury., Importance Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known. Objective To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort. Design, Setting, and Participants This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018. Patients with TBI, extracranial orthopedic injuries (orthopedic controls), and individuals without reported injuries (eg, friends and family of participants; hereafter friend controls) were prospectively followed for 12 months. Data were analyzed from January 2020 to April 2021. Exposure Demographic, imaging, and clinical information was collected according to TBI Common Data Elements. Incidence of self-reported PTE was assessed using the National Institute of Neurological Disorders and Stroke Epilepsy Screening Questionnaire (NINDS-ESQ). Main Outcomes and Measures Primary outcomes included Glasgow Outcome Scale Extended, Rivermead Cognitive Metric (RCM; derived from the Rivermead Post Concussion Symptoms Questionnaire), and the Brief Symptom Inventory-18 (BSI). Results Of 3296 participants identified as part of the study, 3044 met inclusion criteria, and 1885 participants (mean [SD] age, 41.3 [17.1] years; 1241 [65.8%] men and 644 [34.2%] women) had follow-up information at 12 months, including 1493 patients with TBI; 182 orthopedic controls, 210 uninjured friend controls; 41 patients with TBI (2.8%) and no controls had positive screening results for PTE. Compared with a negative screening result for PTE, having a positive screening result for PTE was associated with presenting Glasgow Coma Scale score (8.1 [4.8] vs.13.5 [3.3]; P

Published
2021

14. Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury: A TRACK-TBI Study With External Validation in CENTER-TBI

Author

Ramon Diaz-Arrastia, Thomas W. McAllister, Joel H. Kramer, Brandon Foreman, Alex B. Valadka, Dana Pisică, Sureyya Dikmen, Randall Merchant, Adam R. Ferguson, C. Dirk Keene, Raquel C. Gardner, Xiaoying Sun, Geoffrey T. Manley, Arthur W. Toga, Yelena G. Bodien, John D. Corrigan, Andrew I R Maas, Joseph T. Giacino, Christopher J. Madden, Pratik Mukherjee, Florence Noel, Claudia S. Robertson, Amber Nolan, Ross Zafonte, Murray B. Stein, Hester F. Lingsma, Nancy R. Temkin, Natalie Kreitzer, Opeolu Adeoye, J. Claude Hemphill, Rao P. Gullapalli, Kim Boase, Jan Verheyden, Luis Gonzalez, Laura B. Ngwenya, Christopher J. Lindsell, Miri Rabinowitz, Michael McCrea, Gillian Hotz, Jonathan Rosand, Shankar P. Gopinath, Harvey S. Levin, David M. Schnyer, Neeraj Badjatia, Ann-Christine Duhaime, Esther L. Yuh, Angelle M. Sander, Sabrina R Taylor, Étienne Gaudette, Eva M. Palacios, Gabriella Satris, Alastair J. Martin, David O. Okonkwo, Seth A. Seabury, Joan Machamer, Karen Crawford, Amy J. Markowitz, Richard G. Ellenbogen, V. Ramana Feeser, Lindsay D. Nelson, Mark Harris, Daniel P. Perl, Mary J. Vassar, Sonia Jain, Ragauskas, Arminas, Rocka, Saulius, Tamosuitis, Tomas, Vilcinis, Rimantas, American Medical Association, Yuh, E. L., Jain, S., Sun, X., Pisica, D., Harris, M. H., Taylor, S. R., Markowitz, A. J., Mukherjee, P., Verheyden, J., Giacino, J. T., Levin, H. S., Mccrea, M., Stein, M. B., Temkin, N. R., Diaz-Arrastia, R., Robertson, C. S., Lingsma, H. F., Okonkwo, D. O., Maas, A. I. R., Manley, G. T., Adeoye, O., Badjatia, N., Boase, K., Bodien, Y., Corrigan, J. D., Crawford, K., Dikmen, S., Duhaime, A. -C., Ellenbogen, R., Feeser, V. R., Ferguson, A. R., Foreman, B., Gardner, R., Gaudette, E., Gonzalez, L., Gopinath, S., Gullapalli, R., Hemphill, J. C., Hotz, G., Keene, C. D., Kramer, J., Kreitzer, N., Lindsell, C., Machamer, J., Madden, C., Martin, A., Mcallister, T., Merchant, R., Nelson, L., Ngwenya, L. B., Noel, F., Nolan, A., Palacios, E., Perl, D., Rabinowitz, M., Rosand, J., Sander, A., Satris, G., Schnyer, D., Seabury, S., Toga, A., Valadka, A., Vassar, M., Zafonte R., (TRACK-TBI Investigators for the CENTER-TBI Investigators), Beretta, L., Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Yuh, E, Jain, S, Sun, X, Pisica, D, Harris, M, Taylor, S, Markowitz, A, Mukherjee, P, Verheyden, J, Giacino, J, Levin, H, Mccrea, M, Stein, M, Temkin, N, Diaz-Arrastia, R, Robertson, C, Lingsma, H, Okonkwo, D, Maas, A, Manley, G, Adeoye, O, Badjatia, N, Boase, K, Bodien, Y, Corrigan, J, Crawford, K, Dikmen, S, Duhaime, A, Ellenbogen, R, Feeser, V, Ferguson, A, Foreman, B, Gardner, R, Gaudette, E, Gonzalez, L, Gopinath, S, Gullapalli, R, Hemphill, J, Hotz, G, Keene, C, Kramer, J, Kreitzer, N, Lindsell, C, Machamer, J, Madden, C, Martin, A, Mcallister, T, Merchant, R, Nelson, L, Ngwenya, L, Noel, F, Nolan, A, Palacios, E, Perl, D, Rabinowitz, M, Rosand, J, Sander, A, Satris, G, Schnyer, D, Seabury, S, Toga, A, Valadka, A, Vassar, M, Zafonte, R, Citerio, G, Public Health, Neurosurgery, Molecular Neuroscience and Ageing Research (MOLAR), and TRACK-TBI Investigators for the CENTER-TBI Investigators

Subjects
Male, validity, Neurology, Neurologi, common data elements, ethnic disparities, Cohort Studies, 0302 clinical medicine, Tomography, Original Investigation, screening and diagnosis, nrecovery, Injuries and accidents, RECOVERY, Middle Aged, Prognosis, 3. Good health, X-Ray Computed, Detection, classification, 030220 oncology & carcinogenesis, TRACK-TBI Investigators for the CENTER-TBI Investigators, Biomedical Imaging, Female, Cognitive Sciences, Radiology, Intracranial Hemorrhages, Comments, Human, 4.2 Evaluation of markers and technologies, Adult, concussio, medicine.medical_specialty, Subarachnoid hemorrhage, Physical Injury - Accidents and Adverse Effects, Prognosi, Traumatic brain injury, Clinical Sciences, Traumatic Brain Injury (TBI), CONCUSSION, Head trauma, scale, models, 03 medical and health sciences, Epidural hematoma, Hematoma, Clinical Research, medicine, Online First, Humans, Brain Concussion, Traumatic Head and Spine Injury, Intracranial Hemorrhage, Aged, Neurology & Neurosurgery, business.industry, Research, Glasgow Coma Scale, Neurosciences, prediction, Petechial rash, Recovery of Function, medicine.disease, Brain Disorders, Good Health and Well Being, identification, Human medicine, Neurology (clinical), Cohort Studie, Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract

Key Points Question Are different patterns of intracranial injury on head computed tomography associated with prognosis after mild traumatic brain injury (mTBI)? Findings In this cohort study, subarachnoid hemorrhage, subdural hematoma, and contusion often co-occurred and were associated with both incomplete recovery and more severe impairment out to 12 months after injury, while intraventricular and/or petechial hemorrhage co-occurred and were associated with more severe impairment up to 12 months after injury; epidural hematoma was associated with incomplete recovery at some points but not with more severe impairment. Some intracranial hemorrhage patterns were more strongly associated with outcomes than previously validated demographic and clinical variables. Meaning In this study, different pathological features on head computed tomography carried different implications for mild traumatic brain injury prognosis to 1 year., The longitudinal, observational study aims to identify pathological computed tomography features associated with adverse outcomes after mild traumatic brain injury., Importance A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale–Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures Acute nonpenetrating head trauma. Main Outcomes and Measures Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores

Published
2021
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15. Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study

Author

Opeolu Adeoye, Neeraj Badjatia, Amber Nolan, Dana P. Goldman, Christopher J. Lindsell, Thomas W. McAllister, Seth A. Seabury, Alex B. Valadka, Joel H. Kramer, Joan Machamer, Raquel C. Gardner, Gabriella Satris, Brandon Foreman, Geoffrey T. Manley, Arthur W. Toga, David O. Okonkwo, Ann-Christine Duhaime, Randall Merchant, C. Dirk Keene, Gillian Hotz, Alastair J. Martin, Jonathan Rosand, David M. Schnyer, Michael McCrea, Murray B. Stein, John K. Yue, Sabrina R Taylor, Claudia S. Robertson, Étienne Gaudette, Kevin K.W. Wang, Laura B. Ngwenya, Natalie Kreitzer, M. Ross Bullock, Rao P. Gullapalli, Shankar P. Gopinath, Lindsay D. Nelson, Yelena G. Bodien, J. Claude Hemphill, Karen Crawford, John D. Corrigan, Amy J. Markowitz, Joseph T. Giacino, Mark Sherer, Richard G. Ellenbogen, Christopher J. Madden, Daniel P. Perl, Ross Zafonte, Miri Rabinowitz, V. Ramana Feeser, Mary J. Vassar, Track-Tbi Investigators, Esther L. Yuh, Sureyya Dikmen, Florence Noel, Nancy R. Temkin, Kim Boase, Jason Barber, Angelle M. Sander, Harvey S. Levin, Frederick K. Korley, Luis Gonzalez, Randall M. Chesnut, Eva M. Palacios, Pratik Mukherjee, Adam R. Ferguson, Ava M. Puccio, Ramon Diaz-Arrastia, and Sonia Jain

Subjects
Moderate to severe, Adult, Male, Pediatrics, medicine.medical_specialty, Traumatic brain injury, Glasgow Outcome Scale, Neuropsychological Tests, Cohort Studies, Disability Evaluation, Interquartile range, Activities of Daily Living, Brain Injuries, Traumatic, Medicine, Humans, In patient, Glasgow Coma Scale, Longitudinal Studies, Prospective Studies, Cause of death, Original Investigation, business.industry, Persistent Vegetative State, Disability Rating Scale, Recovery of Function, Middle Aged, medicine.disease, Prognosis, Treatment Outcome, Withholding Treatment, Female, Neurology (clinical), business, Cohort study
Abstract

Importance Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. Objective To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. Design, Setting, and Participants This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. Exposures Moderate or severe TBI. Main Outcomes and Measures The Glasgow Outcome Scale–Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. Results A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. Conclusions and Relevance In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.

Published
2021

16. 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

17. Pathological Computed Tomography Features Associated with Adverse Outcomes after Mild Traumatic Brain Injury

Author

Esther L. Yuh, Sonia Jain, Xiaoying Sun, Dana Pisicǎ, Mark H. Harris, Sabrina R. Taylor, Amy J. Markowitz, Pratik Mukherjee, Jan Verheyden, Joseph T. Giacino, Harvey S. Levin, Michael McCrea, Murray B. Stein, Nancy R. Temkin, Ramon Diaz-Arrastia, Claudia S. Robertson, H.F. (Hester) Lingsma, David O. Okonkwo, Andrew I.R. Maas, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan MacHamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur W. Toga, Alex Valadka, Mary Vassar, Ross Zafonte, Esther L. Yuh, Sonia Jain, Xiaoying Sun, Dana Pisicǎ, Mark H. Harris, Sabrina R. Taylor, Amy J. Markowitz, Pratik Mukherjee, Jan Verheyden, Joseph T. Giacino, Harvey S. Levin, Michael McCrea, Murray B. Stein, Nancy R. Temkin, Ramon Diaz-Arrastia, Claudia S. Robertson, H.F. (Hester) Lingsma, David O. Okonkwo, Andrew I.R. Maas, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan MacHamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur W. Toga, Alex Valadka, Mary Vassar, and Ross Zafonte

Abstract

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; int

Published
2021
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18. Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months after Mild Traumatic Brain Injury

Author

Murray B. Stein, Esther Yuh, Sonia Jain, David O. Okonkwo, Christine L. Mac Donald, Harvey Levin, Joseph T. Giacino, Sureyya Dikmen, Mary J. Vassar, Ramon Diaz-Arrastia, Claudia S. Robertson, Lindsay D. Nelson, Michael McCrea, Xiaoying Sun, Nancy Temkin, Sabrina R. Taylor, Amy J. Markowitz, Geoffrey T. Manley, Pratik Mukherjee, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur Toga, Alex Valadka, Paul Vespa, Kevin Wang, John K. Yue, and Ross Zafonte

Subjects
Traumatic brain injury, Cognitive Neuroscience, Hippocampus, behavioral disciplines and activities, Amygdala, 050105 experimental psychology, Article, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Biological Psychiatry, Brain Concussion, Cognitive reserve, medicine.diagnostic_test, business.industry, 05 social sciences, Glasgow Coma Scale, Brain, Magnetic resonance imaging, Emergency department, medicine.disease, medicine.anatomical_structure, Anesthesia, Neurology (clinical), business, Insula, 030217 neurology & neurosurgery
Abstract

Background Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. Methods Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13–15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. Results Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. Conclusions Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.

Published
2020

19. Predicting Long-Term Global Outcome after Traumatic Brain Injury: Development of a Practical Prognostic Tool Using the Traumatic Brain Injury Model Systems National Database

Author

Allen W. Brown, Jeanne M. Hoffman, Katharine A. Stromberg, Adam Sima, Cynthia Harrison-Felix, Randall Merchant, Amma A. Agyemang, Kristin M. Graham, William C. Walker, Jennifer H. Marwitz, and Jeffrey S. Kreutzer

Subjects
030506 rehabilitation, medicine.medical_specialty, Traumatic brain injury, Glasgow Outcome Scale, Amnesia, functional outcome, 03 medical and health sciences, 0302 clinical medicine, Medicine, Predictability, classification tree, traumatic brain injury classification tree, business.industry, Original Articles, medicine.disease, Confidence interval, Outcome (probability), Term (time), Sample size determination, Emergency medicine, prognosis, Neurology (clinical), medicine.symptom, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

For patients surviving serious traumatic brain injury (TBI), families and other stakeholders often desire information on long-term functional prognosis, but accurate and easy-to-use clinical tools are lacking. We aimed to build utilitarian decision trees from commonly collected clinical variables to predict Glasgow Outcome Scale (GOS) functional levels at 1, 2, and 5 years after moderate-to-severe closed TBI. Flexible classification tree statistical modeling was used on prospectively collected data from the TBI-Model Systems (TBIMS) inception cohort study. Enrollments occurred at 17 designated, or previously designated, TBIMS inpatient rehabilitation facilities. Analysis included all participants with nonpenetrating TBI injured between January 1997 and January 2017. Sample sizes were 10,125 (year-1), 8,821 (year-2), and 6,165 (year-5) after cross-sectional exclusions (death, vegetative state, insufficient post-injury time, and unavailable outcome). In our final models, post-traumatic amnesia (PTA) duration consistently dominated branching hierarchy and was the lone injury characteristic significantly contributing to GOS predictability. Lower-order variables that added predictability were age, pre-morbid education, productivity, and occupational category. Generally, patient outcomes improved with shorter PTA, younger age, greater pre-morbid productivity, and higher pre-morbid vocational or educational achievement. Across all prognostic groups, the best and worst good recovery rates were 65.7% and 10.9%, respectively, and the best and worst severe disability rates were 3.9% and 64.1%. Predictability in test data sets ranged from C-statistic of 0.691 (year-1; confidence interval [CI], 0.675, 0.711) to 0.731 (year-2; CI, 0.724, 0.738). In conclusion, we developed a clinically useful tool to provide prognostic information on long-term functional outcomes for adult survivors of moderate and severe closed TBI. Predictive accuracy for GOS level was demonstrated in an independent test sample. Length of PTA, a clinical marker of injury severity, was by far the most critical outcome determinant.

Published
2018
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20. Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study

Author

John K. Yue, Arthur W. Toga, Joan Machamer, M. Ross Bullock, Pratik Mukherjee, Sureyya Dikmen, Michael McCrea, Murray B. Stein, Brandon Foreman, Paul M. Vespa, Esther L. Yuh, Randall Merchant, David O. Okonkwo, Gillian Hotz, Neeraj Badjatia, Jonathan Rosand, Alex B. Valadka, Joseph T. Giacino, Thomas W. McAllister, David M. Schnyer, Ava M. Puccio, Adam R. Ferguson, Seth A. Seabury, Luis Alonso González, Claudia S. Robertson, Natalie Kreitzer, John D. Corrigan, J. Claude Hemphill, Ann-Christine Duhaime, Christopher J. Madden, Yelena G. Bodien, Karen Crawford, Harvey S. Levin, Ramon Diaz-Arrastia, Shankar P. Gopinath, Rao P. Gullapalli, Joel H. Kramer, Frederick K. Korley, Richard G. Ellenbogen, Alastair J. Martin, Sonia Jain, Raquel C. Gardner, V. Ramana Feeser, Jason Barber, Gabriella Satris, Opeolu Adeoye, Eva M. Palacios, Mark Sherer, Angelle M. Sander, Sabrina R Taylor, Geoffrey T. Manley, Christopher J. Lindsell, Étienne Gaudette, Kevin K.W. Wang, Florence Noel, Nancy R. Temkin, Kim Boase, Ross Zafonte, Miri Rabinowitz, Daniel P. Perl, Mary J. Vassar, Lindsay D. Nelson, and Randall M. Chesnut

Subjects
medicine.medical_specialty, business.industry, Traumatic brain injury, Glasgow Outcome Scale, Trauma center, Glasgow Coma Scale, medicine.disease, Natural history, 03 medical and health sciences, 0302 clinical medicine, Traumatic injury, Orthopedic surgery, Physical therapy, Medicine, 030212 general & internal medicine, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract

Most traumatic brain injuries (TBIs) are classified as mild (mTBI) based on admission Glasgow Coma Scale (GCS) scores of 13 to 15. The prevalence of persistent functional limitations for these patients is unclear.To characterize the natural history of recovery of daily function following mTBI vs peripheral orthopedic traumatic injury in the first 12 months postinjury using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, and, using clinical computed tomographic (CT) scans, examine whether the presence (CT+) or absence (CT-) of acute intracranial findings in the mTBI group was associated with outcomes.TRACK-TBI, a cohort study of patients with mTBI presenting to US level I trauma centers, enrolled patients from February 26, 2014, to August 8, 2018, and followed up for 12 months. A total of 1453 patients at 11 level I trauma center emergency departments or inpatient units met inclusion criteria (ie, mTBI [n = 1154] or peripheral orthopedic traumatic injury [n = 299]) and were enrolled within 24 hours of injury; mTBI participants had admission GCS scores of 13 to 15 and clinical head CT scans. Patients with peripheral orthopedic trauma injury served as the control (OTC) group.Participants with mTBI or OTC.The Glasgow Outcome Scale Extended (GOSE) scale score, reflecting injury-related functional limitations across broad life domains at 2 weeks and 3, 6, and 12 months postinjury was the primary outcome. The possible score range of the GOSE score is 1 (dead) to 8 (upper good recovery), with a score less than 8 indicating some degree of functional impairment.Of the 1453 participants, 953 (65.6%) were men; mean (SD) age was 40.9 (17.1) years in the mTBI group and 40.9 (15.4) years in the OTC group. Most participants (mTBI, 87%; OTC, 93%) reported functional limitations (GOSE8) at 2 weeks postinjury. At 12 months, the percentage of mTBI participants reporting functional limitations was 53% (95% CI, 49%-56%) vs 38% (95% CI, 30%-45%) for OTCs. A higher percentage of CT+ patients reported impairment (61%) compared with the mTBI CT- group (49%; relative risk [RR], 1.24; 95% CI, 1.08-1.43) and a higher percentage in the mTBI CT-group compared with the OTC group (RR, 1.28; 95% CI, 1.02-1.60).Most patients with mTBI presenting to US level I trauma centers report persistent, injury-related life difficulties at 1 year postinjury, suggesting the need for more systematic follow-up of patients with mTBI to provide treatments and reduce the risk of chronic problems after mTBI.

Published
2019

21. Risk of Posttraumatic Stress Disorder and Major Depression in Civilian Patients After Mild Traumatic Brain Injury: A TRACK-TBI Study

Author

Murray B, Stein, Sonia, Jain, Joseph T, Giacino, Harvey, Levin, Sureyya, Dikmen, Lindsay D, Nelson, Mary J, Vassar, David O, Okonkwo, Ramon, Diaz-Arrastia, Claudia S, Robertson, Pratik, Mukherjee, Michael, McCrea, Christine L, Mac Donald, John K, Yue, Esther, Yuh, Xiaoying, Sun, Laura, Campbell-Sills, Nancy, Temkin, Geoffrey T, Manley, Opeolu, Adeoye, Neeraj, Badjatia, Kim, Boase, Yelena, Bodien, M Ross, Bullock, Randall, Chesnut, John D, Corrigan, Karen, Crawford, Ann-Christine, Duhaime, Richard, Ellenbogen, V Ramana, Feeser, Adam, Ferguson, Brandon, Foreman, Raquel, Gardner, Etienne, Gaudette, Luis, Gonzalez, Shankar, Gopinath, Rao, Gullapalli, J Claude, Hemphill, Gillian, Hotz, Frederick, Korley, Joel, Kramer, Natalie, Kreitzer, Chris, Lindsell, Joan, Machamer, Christopher, Madden, Alastair, Martin, Thomas, McAllister, Randall, Merchant, Florence, Noel, Eva, Palacios, Daniel, Perl, Ava, Puccio, Miri, Rabinowitz, Jonathan, Rosand, Angelle, Sander, Gabriela, Satris, David, Schnyer, Seth, Seabury, Mark, Sherer, Sabrina, Taylor, Arthur, Toga, Alex, Valadka, Paul, Vespa, Kevin, Wang, and Ross, Zafonte

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Traumatic brain injury, Comorbidity, behavioral disciplines and activities, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, mental disorders, Brain Injuries, Traumatic, Prevalence, Medicine, Humans, Glasgow Coma Scale, Longitudinal Studies, Prospective Studies, Young adult, Psychiatry, Prospective cohort study, Depression (differential diagnoses), Original Investigation, Depressive Disorder, Major, business.industry, Emergency department, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Case-Control Studies, Major depressive disorder, Female, business, Emergency Service, Hospital, 030217 neurology & neurosurgery
Abstract

IMPORTANCE: Traumatic brain injury (TBI) has been associated with adverse mental health outcomes, such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), but little is known about factors that modify risk for these psychiatric sequelae, particularly in the civilian sector. OBJECTIVE: To ascertain prevalence of and risk factors for PTSD and MDD among patients evaluated in the emergency department for mild TBI (mTBI). DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal cohort study (February 2014 to May 2018). Posttraumatic stress disorder and MDD symptoms were assessed using the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9 Item. Risk factors evaluated included preinjury and injury characteristics. Propensity score weights-adjusted multivariable logistic regression models were performed to assess associations with PTSD and MDD. A total of 1155 patients with mTBI (Glasgow Coma Scale score, 13-15) and 230 patients with nonhead orthopedic trauma injuries 17 years and older seen in 11 US hospitals with level 1 trauma centers were included in this study. MAIN OUTCOMES AND MEASURES: Probable PTSD (PTSD Checklist for DSM-5 score, ≥33) and MDD (Patient Health Questionnaire-9 Item score, ≥15) at 3, 6, and 12 months postinjury. RESULTS: Participants were 1155 patients (752 men [65.1%]; mean [SD] age, 40.5 [17.2] years) with mTBI and 230 patients (155 men [67.4%]; mean [SD] age, 40.4 [15.6] years) with nonhead orthopedic trauma injuries. Weights-adjusted prevalence of PTSD and/or MDD in the mTBI vs orthopedic trauma comparison groups at 3 months was 20.0% (SE, 1.4%) vs 8.7% (SE, 2.2%) (P

Published
2019

22. Association of Sex and Age With Mild Traumatic Brain Injury–Related Symptoms: A TRACK-TBI Study

Author

Adam R. Ferguson, Yelena G. Bodien, Pratik Mukherjee, Ramon Diaz-Arrastia, Ann-Christine Duhaime, Murray B. Stein, Jeffrey Brennan, John K. Yue, Karen Crawford, Amy J. Markowitz, Ross Zafonte, Alastair J. Martin, Gillian Hotz, Claudia S. Robertson, Michael McCrea, Esther L. Yuh, Jonathan Rosand, David M. Schnyer, Randall Merchant, Brandon Foreman, Opeolu Adeoye, Miri Rabinowitz, Laura B. Ngwenya, Amber Nolan, Richard G. Ellenbogen, Joel H. Kramer, M. Ross Bullock, C. Dirk Keene, Christopher J. Lindsell, Track-Tbi Investigators, Jason Barber, Angelle M. Sander, Shankar P. Gopinath, Xiaoying Sun, V. Ramana Feeser, Arthur W. Toga, Seth A. Seabury, Alex B. Valadka, Neeraj Badjatia, Natalie Kreitzer, Florence Noel, J. Claude Hemphill, Nancy R. Temkin, Joan Machamer, Kim Boase, Harvey S. Levin, Luis Gonzalez, Sonia Jain, Randall M. Chesnut, Thomas W. McAllister, Ava M. Puccio, Gabriella Satris, John D. Corrigan, Raquel C. Gardner, Geoffrey T. Manley, Rao P. Gullapalli, Joseph T. Giacino, Christopher J. Madden, Frederick K. Korley, Eva M. Palacios, Sabrina R Taylor, Étienne Gaudette, Kevin K.W. Wang, David O. Okonkwo, Mary J. Vassar, Sureyya Dikmen, and Lindsay D. Nelson

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Traumatic brain injury, Risk Assessment, Severity of Illness Index, Brain Injuries, Traumatic, Severity of illness, medicine, Humans, Cognitive Dysfunction, Glasgow Coma Scale, Prospective Studies, Sex Distribution, Prospective cohort study, Brain Concussion, Depression (differential diagnoses), Original Investigation, Aged, Post-Concussion Syndrome, business.industry, Research, General Medicine, Middle Aged, Rivermead post-concussion symptoms questionnaire, medicine.disease, Online Only, Neurology, Orthopedic surgery, Anxiety, Female, medicine.symptom, business
Abstract

Key Points Question Do postacute mild traumatic brain injury (mTBI) symptoms differ between men and women? Findings In this cohort study of 2000 patients with mTBI, the severity of cognitive and somatic symptoms on the Rivermead Post Concussion Symptoms Questionnaire at 12 months after injury was significantly worse in women than in men, whereas this difference was not significant in an orthopedic trauma control group. The association between mTBI and somatic symptoms was greater in women aged 35 to 49 years than those aged 17 to 34 years or older than 50 years. Meaning Sex and age may be important factors in the individualized, postacute treatment of patients with mTBI., This cohort study uses data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study to assess whether patient sex and age are associated with mild traumatic brain injury symptoms., Importance Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. Objective To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. Design, Setting, and Participants The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. Exposures Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. Main Outcomes and Measures Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). Results A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate–corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate–corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02). Conclusions and Relevance This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

Published
2021
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23. Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury

Author

Joel H. Kramer, Joan Machamer, Raquel C. Gardner, Michael McCrea, Rao P. Gullapalli, Harvey S. Levin, Frederick K. Korley, Benjamin L. Brett, Mary J. Vassar, Thomas W. McAllister, Geoffrey T. Manley, Ava M. Puccio, Eva M. Palacios, Mark D. Kramer, Joseph T. Giacino, Luis Gonzalez, Karen Crawford, Amy J. Markowitz, Mark Sherer, Jason Barber, Lindsay D. Nelson, Randall M. Chesnut, Angelle M. Sander, M. Ross Bullock, Christopher J. Madden, Richard G. Ellenbogen, Murray B. Stein, John K. Yue, Shankar P. Gopinath, John D. Corrigan, Alex B. Valadka, Natalie Kreitzer, V. Ramana Feeser, J. Claude Hemphill, Pratik Mukherjee, Yelena G. Bodien, Laura B. Ngwenya, Neeraj Badjatia, John Whyte, Sabrina R Taylor, Sonia Jain, Ann-Christine Duhaime, Gillian Hotz, Étienne Gaudette, Gabriella Satris, Jonathan Rosand, Kevin K.W. Wang, David M. Schnyer, Alastair J. Martin, Claudia S. Robertson, Adam R. Ferguson, Esther L. Yuh, Florence Noel, Ramon Diaz-Arrastia, Sureyya Dikmen, Nancy R. Temkin, Kim Boase, Arthur W. Toga, Track-Tbi Investigators, David O. Okonkwo, Randall Merchant, Ross Zafonte, Opeolu Adeoye, Miri Rabinowitz, Seth A. Seabury, Christopher J. Lindsell, Brandon Foreman, and C. Dirk Keene

Subjects
Traumatic brain injury, business.industry, Trail Making Test, Glasgow Coma Scale, Wechsler Adult Intelligence Scale, General Medicine, NIH Toolbox, Rivermead post-concussion symptoms questionnaire, medicine.disease, medicine, business, Prospective cohort study, Cohort study, Clinical psychology
Abstract

Importance Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. Objective To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. Design, setting, and participants This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. Exposures TBI. Main outcomes and measures Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Results Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34). Conclusions and relevance In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.

Published
2021
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24. Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study

Author

John K Yue, Esther L Yuh, Frederick K Korley, Ethan A Winkler, Xiaoying Sun, Ross C Puffer, Hansen Deng, Winward Choy, Ankush Chandra, Sabrina R Taylor, Adam R Ferguson, J Russell Huie, Miri Rabinowitz, Ava M Puccio, Pratik Mukherjee, Mary J Vassar, Kevin K W Wang, Ramon Diaz-Arrastia, David O Okonkwo, Sonia Jain, Geoffrey T Manley, Opeolu M Adeoye, Neeraj Badjatia, Kim Boase, Yelena G Bodien, Malcom R Bullock, Randall M Chesnut, John D Corrigan, Karen Crawford, Sureyya S Dikmen, Ann-Christine Duhaime, Richard G Ellenbogen, Venkata Feeser, Brandon Foreman, Raquel C Gardner, Etienne Gaudette, Joseph T Giacino, Dana P Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J C Hemphill, Gillian Hotz, Joel H Kramer, Natalie P Kreitzer, Harvey S Levin, Christopher J Lindsell, Joan Machamer, Christopher J Madden, Alastair J Martin, Thomas W McAllister, Michael McCrea, Randall Merchant, Lindsay D Nelson, Florence Noel, Eva M Palacios, Daniel P Perl, Claudia S Robertson, Jonathan Rosand, Angelle M Sander, Gabriela G Satris, David M Schnyer, Seth A Seabury, Mark Sherer, Murray B Stein, Nancy R Temkin, Arthur W Toga, Alex B Valadka, Paul M Vespa, and Ross Zafonte

Subjects
Adult, Male, Traumatic brain injury, Sensitivity and Specificity, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Brain Injuries, Traumatic, Glial Fibrillary Acidic Protein, Medicine, Humans, Glasgow Coma Scale, Prospective Studies, Prospective cohort study, Stroke, 030304 developmental biology, 0303 health sciences, Venipuncture, Receiver operating characteristic, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Female, Neurology (clinical), business, Nuclear medicine, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Cohort study
Abstract

Summary Background After traumatic brain injury (TBI), plasma concentration of glial fibrillary acidic protein (GFAP) correlates with intracranial injury visible on CT scan. Some patients with suspected TBI with normal CT findings show pathology on MRI. We assessed the discriminative ability of GFAP to identify MRI abnormalities in patients with normal CT findings. Methods TRACK-TBI is a prospective cohort study that enrolled patients with TBI who had a clinically indicated head CT scan within 24 h of injury at 18 level 1 trauma centres in the USA. For this analysis, we included patients with normal CT findings (Glasgow Coma Scale score 13–15) who consented to venepuncture within 24 h post injury and who had an MRI scan 7–18 days post injury. We compared MRI findings in these patients with those of orthopaedic trauma controls and healthy controls recruited from the study sites. Plasma GFAP concentrations (pg/mL) were measured using a prototype assay on a point-of-care platform. We used receiver operating characteristic (ROC) analysis to evaluate the discriminative ability of GFAP for positive MRI scans in patients with negative CT scans over 24 h (time between injury and venepuncture). The primary outcome was the area under the ROC curve (AUC) for GFAP in patients with CT-negative and MRI-positive findings versus patients with CT-negative and MRI-negative findings within 24 h of injury. The Dunn Kruskal–Wallis test was used to compare GFAP concentrations between MRI lesion types with Benjamini–Hochberg correction for multiple comparisons. This study is registered with ClinicalTrials.gov , number NCT02119182 . Findings Between Feb 26, 2014, and June 15, 2018, we recruited 450 patients with normal head CT scans (of whom 330 had negative MRI scans and 120 had positive MRI scans), 122 orthopaedic trauma controls, and 209 healthy controls. AUC for GFAP in patients with CT-negative and MRI-positive findings versus patients with CT-negative and MRI-negative findings was 0·777 (95% CI 0·726–0·829) over 24 h. Median plasma GFAP concentration was highest in patients with CT-negative and MRI-positive findings (414·4 pg/mL, 25–75th percentile 139·3–813·4), followed by patients with CT-negative and MRI-negative findings (74·0 pg/mL, 17·5–214·4), orthopaedic trauma controls (13·1 pg/mL, 6·9–20·0), and healthy controls (8·0 pg/mL, 3·0–14·0; all comparisons between patients with CT-negative MRI-positive findings and other groups p Interpretation Analysis of blood GFAP concentrations using prototype assays on a point-of-care platform within 24 h of injury might improve detection of TBI and identify patients who might need subsequent MRI and follow-up. Funding National Institute of Neurological Disorders and Stroke and US Department of Defense.

Published
2018

25. Using Decision Tree Methodology to Predict Employment After Moderate to Severe Traumatic Brain Injury

Author

Cynthia Harrison-Felix, Jennifer H. Marwitz, Randall Merchant, Amma A. Agyemang, Adam Sima, William C. Walker, Allen W. Brown, Kristin M. Graham, Jeffrey S. Kreutzer, Katharine A. Stromberg, and Jeanne M. Hoffman

Subjects
Moderate to severe, Adult, Employment, Male, 030506 rehabilitation, medicine.medical_specialty, Time Factors, Traumatic brain injury, Cross-sectional study, Decision tree, MEDLINE, Physical Therapy, Sports Therapy and Rehabilitation, 03 medical and health sciences, 0302 clinical medicine, Brain Injuries, Traumatic, medicine, Humans, business.industry, Decision tree learning, Rehabilitation, Decision Trees, Recovery of Function, Middle Aged, medicine.disease, Confidence interval, Cross-Sectional Studies, Sample size determination, Physical therapy, Educational Status, Female, Neurology (clinical), Erratum, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

Objective To build decision tree prediction models for long-term employment outcomes of individuals after moderate to severe closed traumatic brain injury (TBI) and assess model accuracy in an independent sample. Setting TBI Model Systems Centers. Participants TBI Model Systems National Database participants injured between January 1997 and January 2017 with moderate to severe closed TBI. Sample sizes were 7867 (year 1 postinjury), 6783 (year 2 postinjury), and 4927 (year 5 postinjury). Design Cross-sectional analyses using flexible classification tree methodology and validation using an independent subset of TBI Model Systems National Database participants. Main measures Competitive employment at 1, 2, and 5 years postinjury. Results In the final employment prediction models, posttraumatic amnesia duration was the most important predictor of employment in each outcome year. Additional variables consistently contributing were age, preinjury education, productivity, and occupational category. Generally, individuals spending fewer days in posttraumatic amnesia, who were competitively employed preinjury, and more highly educated had better outcomes. Predictability in test data sets ranged from a C-statistic of 0.72 (year 5; confidence interval: 0.68-0.76) to 0.77 (year 1; confidence interval: 0.74-0.80). Conclusion An easy-to-use decision tree tool was created to provide prognostic information on long-term competitive employment outcomes in individuals with moderate to severe closed TBI. Length of posttraumatic amnesia, a clinical marker of injury severity, and preinjury education and employment status were the most important predictors.

Published
2018

26. Making Football Safer: Assessing the Current National Football League Policy on the Type of Helmets Allowed on the Playing Field

Author

Ethan Beckett, Kellen Garrison Cresswell, Raymond J. Colello, Randall Merchant, Ian Alexander Colello, and Duaa AbdelHameid

Subjects
education, 0206 medical engineering, Applied psychology, Football, Poison control, 02 engineering and technology, League, Suicide prevention, Occupational safety and health, 03 medical and health sciences, 0302 clinical medicine, Injury prevention, Concussion, medicine, Humans, Policy Making, Brain Concussion, technology, industry, and agriculture, Human factors and ergonomics, 030229 sport sciences, equipment and supplies, medicine.disease, 020601 biomedical engineering, Head Protective Devices, Neurology (clinical), Psychology, human activities
Abstract

In an effort to reduce concussions in football, a helmet safety-rating system was developed in 2011 that rated helmets based on their ability to reduce g-forces experienced by the head across a range of impact forces measured on the playing field. Although this was considered a major step in making the game safer, the National Football League (NFL) continues to allow players the right to choose what helmet to wear during play. This prompted us to ask: What helmets do NFL players wear and does this helmet policy make the game safer? Accordingly, we identified the helmets worn by nearly 1000 players on Week 13 of the 2015-2016 season and Week 1 of the 2016-2017 season. Using stop-motion footage, we found that players wore a wide range of helmets with varying safety ratings influenced in part by the player's position and age. Moreover, players wearing lower safety-rated helmets were more likely to receive a concussion than those wearing higher safety-rated helmets. Interestingly, many players suffering a concussion in 2015 did not switch to a higher safety-rated helmet in 2016. Using a helmet-to-helmet impactor, we found that the g-forces experienced in the highest safety-rated helmets were roughly 30% less than that for the lowest safety-rated helmets. These results suggest that the current NFL helmet policy puts players at increased risk of receiving a concussion as many players are wearing low safety-rated helmets, which transmits more energy to the brain than higher safety-rated helmets, following collision. Thus, to reduce concussions, the NFL should mandate that players only wear helmets that receive the highest safety rating.

Published
2018

27. Response to Foks et al. (doi: 10.1089/neu.2018.5979): Why Our Long-Term Functional Prognosis Tools are a Valuable Contribution to the Traumatic Brain Injury Outcome Literature

Author

Katharine A. Stromberg, Kristin M. Graham, Randall Merchant, Allen W. Brown, Adam Sima, Jeanne M. Hoffman, Cynthia Harrison-Felix, Jeffrey S. Kreutzer, Amma A. Agyemang, William C. Walker, and Jennifer H. Marwitz

Subjects
medicine.medical_specialty, Text mining, business.industry, Traumatic brain injury, medicine, Neurology (clinical), Letters to the Editor, Intensive care medicine, business, medicine.disease, Outcome (game theory), Term (time)
Published
2019
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28. Nutritional Supplementation withChlorella pyrenoidosaLowers Serum Methylmalonic Acid in Vegans and Vegetarians with a Suspected Vitamin B12Deficiency

Author

Randall Merchant, Todd W Phillips, and Jay Udani

Subjects
Vitamin, medicine.medical_specialty, Nutrition and Dietetics, Nutritional Supplementation, medicine.diagnostic_test, Methylmalonic acid, Medicine (miscellaneous), Vegetarian nutrition, Biology, Hematocrit, biology.organism_classification, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, medicine, Chlorella pyrenoidosa, Vitamin B12, Mean corpuscular volume
Abstract

Since vitamin B12 occurs in substantial amounts only in foods derived from animals, vegetarians and particularly vegans are at risk of developing deficiencies of this essential vitamin. The chlorella used for this study is a commercially available whole-food supplement, which is believed to contain the physiologically active form of the vitamin. This exploratory open-label study was performed to determine if adding 9 g of Chlorella pyrenoidosa daily could help mitigate a vitamin B12 deficiency in vegetarians and vegans. Seventeen vegan or vegetarian adults (26-57 years of age) with a known vitamin B12 deficiency, as evidenced by a baseline serum methylmalonic acid (MMA) level above 270 nmol/L at screening, but who otherwise appeared healthy were enrolled in the study. Each participant added 9 g of C. pyrenoidosa to their daily diet for 60 ± 5 days and their serum MMA, vitamin B12, homocysteine (Hcy) levels as well as mean corpuscular volume (MCV), hemoglobin (Hgb), and hematocrit (Hct) were measured at 30 and 60 days from baseline. After 30 and 60 days, the serum MMA level fell significantly (P

Published
2015
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31. Assessment of Follow-up Care After Emergency Department Presentation for Mild Traumatic Brain Injury and Concussion

Author

Murray B. Stein, Joan Machamer, John K. Yue, Esther L. Yuh, Luis Gonzalez, Yelena G. Bodien, Randall M. Chesnut, Daniel P. Perl, Mary J. Vassar, Mark Sherer, Adam R. Ferguson, Neeraj Badjatia, Gabriella Satris, Ramon Diaz-Arrastia, Lindsay D. Nelson, Harvey S. Levin, Ross Zafonte, Sabrina R Taylor, Paul M. Vespa, John D. Corrigan, Seth A. Seabury, Gillian Hotz, Claudia S. Robertson, Opeolu Adeoye, Randall Merchant, Miri Rabinowitz, Étienne Gaudette, Kevin K.W. Wang, M. Ross Bullock, Jordan Brooks, Shankar P. Gopinath, Christopher J. Lindsell, Ann-Christine Duhaime, Jonathan Rosand, David M. Schnyer, Karen Crawford, Amy J. Markowitz, Dana P. Goldman, Pratik Mukherjee, Alex B. Valadka, Joseph T. Giacino, Arthur W. Toga, Ava M. Puccio, Christopher J. Madden, Thomas W. McAllister, Richard G. Ellenbogen, Natalie Kreitzer, Raquel C. Gardner, David O. Okonkwo, J. Claude Hemphill, Angelle M. Sander, Frederick K. Korley, Michael McCrea, V. Ramana Feeser, Sureyya Dikmen, Joel H. Kramer, A. Martin, Geoffrey T. Manley, Eva M. Palacios, Sonia Jain, Florence Noel, Nancy R. Temkin, Kim Boase, Rao P. Gullapalli, and Brandon Foreman

Subjects
Adult, Male, medicine.medical_specialty, Traumatic brain injury, Aftercare, 01 natural sciences, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Trauma Centers, law, Brain Injuries, Traumatic, Concussion, Health care, Humans, Medicine, Glasgow Coma Scale, Prospective Studies, 030212 general & internal medicine, 0101 mathematics, Brain Concussion, Original Investigation, Post-concussion syndrome, Post-Concussion Syndrome, business.industry, Research, 010102 general mathematics, General Medicine, Emergency department, Middle Aged, Rivermead post-concussion symptoms questionnaire, medicine.disease, Intensive care unit, United States, Featured, 3. Good health, Online Only, Brain Injuries, Emergency medicine, Emergency Medicine, Female, Pamphlets, Emergency Service, Hospital, business
Abstract

Key Points Question Do patients with mild traumatic brain injury (mTBI) receive adequate levels of follow-up care? Findings In a cohort study using data on 831 patients with mTBI presenting to the emergency department at 1 of 11 level I trauma centers across the United States, 42% of patients reported receiving educational material at discharge and 44% reported seeing a physician or other medical practitioner within 3 months after injury. Among patients with 3 or more moderate to severe postconcussive symptoms, only 52% reported having seen a practitioner within 3 months following the injury. Meaning A large proportion of patients with mTBI do not receive follow-up care after injury even when they experience ongoing postconcussive symptoms., This cohort study describes follow-up care for patients within 3 months of receiving treatment for mild traumatic brain injury (TBI) or concussion at US emergency departments of level I trauma centers., Importance Mild traumatic brain injury (mTBI) affects millions of Americans each year. Lack of consistent clinical practice raises concern that many patients with mTBI may not receive adequate follow-up care. Objective To characterize the provision of follow-up care to patients with mTBI during the first 3 months after injury. Design, Setting, and Participants This cohort study used data on patients with mTBI enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study between February 26, 2014, and August 25, 2016. We examined site-specific variations in follow-up care, the types of clinicians seen by patients receiving follow-up care, and patient and injury characteristics associated with a higher likelihood of receiving follow-up care. The TRACK-TBI study is a prospective, multicenter, longitudinal observational study of patients with TBI presenting to the emergency department of 1 of 11 level I US trauma centers. Study data included patients with head trauma who underwent a computed tomography (CT) scan within 24 hours of injury, had a Glasgow Coma Scale score of 13 to 15, were aged 17 years or older, and completed follow-up care surveys at 2 weeks and 3 months after injury (N = 831). Main Outcomes and Measures Follow-up care was defined as hospitals providing TBI educational material at discharge, hospitals calling patients to follow up, and patients seeing a physician or other medical practitioner within 3 months after the injury. Unfavorable outcomes were assessed with the Rivermead Post Concussion Symptoms Questionnaire. Results Of 831 patients (289 [35%] female; 483 [58%] non-Hispanic white; mean [SD] age, 40.3 [16.9] years), less than half self-reported receiving TBI educational material at discharge (353 patients [42%]) or seeing a physician or other health care practitioner within 3 months after injury (367 patients [44%]). Follow-up care varied by study site; adjusting for patient characteristics, the provision of educational material varied from 19% to 72% across sites. Of 236 patients with a positive finding on a CT scan, 92 (39%) had not seen a medical practitioner 3 months after the injury. Adjusting for injury severity and demographics, patient admission to the hospital ward or intensive care unit, patient income, and insurance status were not associated with the probability of seeing a medical practitioner. Among the patients with 3 or more moderate to severe postconcussive symptoms, only 145 of 279 (52%) reported having seen a medical practitioner by 3 months. Conclusions and Relevance There are gaps in follow-up care for patients with mTBI after hospital discharge, even those with a positive finding on CT or who continue to experience postconcussive symptoms.

Published
2018
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32. The Citicoline Brain Injury Treatment (COBRIT) Trial: Design and Methods

Author

Randall Merchant, Ramon Diaz-Arrastia, Shelly D. Timmons, Beth M. Ansel, Joseph H. Ricker, Thomas A. Novack, Shing M. Lee, Howard M. Eisenberg, Bruce Levin, Ross Zafonte, William T. Friedewald, Jack Jallo, and Nancy R. Temkin

Subjects
Adult, Male, medicine.medical_specialty, Cytidine Diphosphate Choline, Adolescent, Traumatic brain injury, Neuropsychological Tests, Placebo, Severity of Illness Index, Drug Administration Schedule, law.invention, Placebos, Disability Evaluation, Young Adult, Clinical Protocols, Double-Blind Method, Randomized controlled trial, law, Outcome Assessment, Health Care, Severity of illness, medicine, Humans, Stroke, Nootropic Agents, Aged, Cause of death, business.industry, Brain, Original Articles, Middle Aged, medicine.disease, Clinical trial, Neuroprotective Agents, Research Design, Brain Injuries, Anesthesia, Physical therapy, Female, Neurology (clinical), business, Citicoline, medicine.drug
Abstract

Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established. Citicoline, a naturally occurring endogenous compound, offers the potential of neuroprotection, neurorecovery, and neurofacilitation to enhance recovery after TBI. Citicoline has a favorable side-effect profile in humans and several meta-analyses suggest a benefit of citicoline treatment in stroke and dementia. COBRIT is a randomized, double-blind, placebo-controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate, and severe TBI. In all, 1292 patients will be recruited over an estimated 32 months from eight clinical sites with random assignment to citicoline (1000 mg twice a day) or placebo (twice a day), administered enterally or orally. Functional outcomes are assessed at 30, 90, and 180 days after the day of randomization. The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global test procedure at 90 days. The measures comprise the following core battery: the California Verbal Learning Test II; the Controlled Oral Word Association Test; Digit Span; Extended Glasgow Outcome Scale; the Processing Speed Index; Stroop Test part 1 and Stroop Test part 2; and Trail Making Test parts A and B. Secondary outcomes include survival, toxicity, and rate of recovery.

Published
2009
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33. Outcome measures for clinical trials in neurotrauma

Author

Jeffrey S. Kreutzer, Charlotte Gilman, M. Ross Bullock, Randall Merchant, Graham M. Teasdale, Sung C. Choi, and Anthony Marmarou

Subjects
medicine.medical_specialty, Traumatic brain injury, Population, Neurosurgical Procedures, Physical medicine and rehabilitation, Quality of life, Outcome Assessment, Health Care, medicine, Humans, Glasgow Coma Scale, education, Randomized Controlled Trials as Topic, education.field_of_study, business.industry, Surrogate endpoint, Glasgow Outcome Scale, Neuropsychology, Outcome measures, General Medicine, medicine.disease, Clinical trial, Brain Injuries, Physical therapy, Surgery, Neurology (clinical), business
Abstract

Under the auspices of the American Brain Injury Consortium and the Joint Section of Neurotrauma and Critical Care of the American Association of Neurological Surgeons, the authors have reviewed and formulated opinions based on the evidence on protocol design and the outcome measures used for clinical trials in patients with a severe or moderate traumatic brain injury (TBI). First, in view of the heterogeneity of the population under study, the authors suggest that block randomization and stratification should always be used in the design of neurotrauma trials. Second, although the Glasgow Outcome Scale (GOS) remains the most widely used and accepted instrument for TBI trials, the authors believe the eight-point expanded scale that has recently been designed will ultimately provide greater discrimination, and narrower categories and will ultimately prove superior for detecting more subtle changes in outcome. Furthermore, the authors recommend, in view of the profound cognitive impairment in survivors of TBI, that neuropsychological tests be explored further as an adjunct to the GOS. Future research should focus on the development of more sensitive and specific surrogate outcome measures such as magnetic resonance imaging, neurochemical, neuropsychological, and quality of life measures in order to detect a neuroprotective effect in patients with TBI.

Published
2002
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34. Predicting Long-Term Global Outcome After TBI: Development of a Practical Prognostic Tool

Author

Katharine A. Stromberg, Kristin M. Graham, William C. Walker, Amma A. Agyemang, Jeffrey S. Kreutzer, Adam Sima, Randall Merchant, and Jennifer H. Marwitz

Subjects
medicine.medical_specialty, business.industry, Rehabilitation, medicine, Physical Therapy, Sports Therapy and Rehabilitation, Intensive care medicine, business, Outcome (game theory), Term (time)
Published
2017
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35. The effect of oral care on intracranial pressure in critically ill adults

Author

Cindy L. Munro, Christina M. Szabo, Angela Starkweather, Randall Merchant, and Mary Jo Grap

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Intracranial Pressure, Critical Care Nursing, Oral hygiene, Nursing care, Young Adult, Neuroscience Nursing, Intensive care, Critical care nursing, Nursing Interventions Classification, Medicine, Humans, Intensive care medicine, Intracranial pressure, Aged, Monitoring, Physiologic, integumentary system, Endocrine and Autonomic Systems, business.industry, musculoskeletal, neural, and ocular physiology, Repeated measures design, Actigraphy, Middle Aged, Oral Hygiene, humanities, nervous system diseases, Medical–Surgical Nursing, Surgery, Female, Neurology (clinical), Intracranial Hypertension, business
Abstract

A major goal in the care of patients with neurological problems is to prevent or minimize episodes of increased intracranial pressure (ICP). Elevations in ICP in response to nursing interventions have been acknowledged since the 1960s when ICP monitoring was first introduced in the clinical setting. Until recently, few studies have specifically examined the effect of oral care on ICP, and oral care and other hygiene measures were combined or not specified, prohibiting a direct interpretation of the influence of oral care alone on ICP. The purpose of this study was to describe the relationship between routine oral care interventions and the changes in ICP specifically focusing on the effect of intensity and duration of this intervention. Twenty-three patients with a clinical condition requiring ICP monitoring were enrolled over a 12-month period. Oral care provided by neuroscience intensive care nurses was observed and videotaped. Characteristics of the intervention were documented including products used, patient positioning, and duration of the intervention. A 1-5 subjective scale was used to score intensity of oral care. Wrist actigraphy data were collected from the nurses to provide an objective measure of intensity. Patient physiologic data were collected at 12-second epochs 5 minutes before, during, and 5 minutes after oral care. The mixed-effect repeated measures analysis of variance model indicated that there was a statistically significant increase in ICP in response to oral care (p = .0031). There was, however, no clinically significant effect on ICP. This study provides evidence that oral care is safe to perform in patients in the absence of preexisting elevated ICP.

Published
2014

36. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT)

Author

Ramon Diaz-Arrastia, Sureyya Dikmen, Emilia Bagiella, Nancy R. Temkin, Dale C. Hesdorffer, Howard M. Eisenberg, Jack Jallo, Randall Merchant, Ross Zafonte, Tessa Hart, Sherry M. Melton, Joseph H. Ricker, William T. Friedewald, Beth M. Ansel, Thomas A. Novack, and Shelly D. Timmons

Subjects
Adult, Male, Cytidine Diphosphate Choline, Adolescent, Traumatic brain injury, Placebo, Placebo group, Severity of Illness Index, Young Adult, Primary outcome, Double-Blind Method, Trauma Centers, medicine, Cognitive status, Humans, Glasgow Coma Scale, Nootropic Agents, business.industry, General Medicine, Odds ratio, Middle Aged, medicine.disease, Treatment Outcome, Anesthesia, Brain Injuries, Female, Injury treatment, business, Cognition Disorders, Citicoline, medicine.drug
Abstract

Traumatic brain injury (TBI) is a serious public health problem in the United States, yet no treatment is currently available to improve outcome after TBI. Approved for use in TBI in 59 countries, citicoline is an endogenous substance offering potential neuroprotective properties as well as facilitated neurorepair post injury.To determine the ability of citicoline to positively affect functional and cognitive status in persons with complicated mild, moderate, and severe TBI.The Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind randomized clinical trial conducted between July 20, 2007, and February 4, 2011, among 1213 patients at 8 US level 1 trauma centers to investigate effects of citicoline vs placebo in patients with TBI classified as complicated mild, moderate, or severe.Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo.Functional and cognitive status, assessed at 90 days using the TBI-Clinical Trials Network Core Battery. A global statistical test was used to analyze the 9 scales of the core battery. Secondary outcomes were functional and cognitive improvement, assessed at 30, 90, and 180 days, and examination of the long-term maintenance of treatment effects.Rates of favorable improvement for the Glasgow Outcome Scale-Extended were 35.4% in the citicoline group and 35.6% in the placebo group. For all other scales the rate of improvement ranged from 37.3% to 86.5% in the citicoline group and from 42.7% to 84.0% in the placebo group. The citicoline and placebo groups did not differ significantly at the 90-day evaluation (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]).Among patients with traumatic brain injury, the use of citicoline compared with placebo for 90 days did not result in improvement in functional and cognitive status.clinicaltrials.gov Identifier: NCT00545662.

Published
2012

37. In vitro lymphocyte proliferation induced by radio-frequency electromagnetic radiation under isothermal conditions

Author

Stephen F. Cleary, Li-Ming Liu, and Randall Merchant

Subjects
Physiology, Radio Waves, Lymphocyte, Biophysics, Ficoll, Lymphocyte proliferation, Absorption (skin), In Vitro Techniques, Lymphocyte Activation, Peripheral blood mononuclear cell, Electromagnetic Fields, medicine, Humans, Radiology, Nuclear Medicine and imaging, Centrifugation, Microwaves, Chemistry, Temperature, Dose-Response Relationship, Radiation, General Medicine, Molecular biology, In vitro, Dose–response relationship, medicine.anatomical_structure, Biochemistry, Electromagnetic Phenomena
Abstract

Whole human blood was exposed or sham-exposed in vitro for 2 h to 27 or 2,450 MHz radio-frequency electromagnetic (RF) radiation under isothermal conditions (i.e., 37 +/- 0.2 degrees C). Immediately after exposure, mononuclear cells were separated from blood by Ficoll density-gradient centrifugation and cultured for 3 days at 37 degrees C with or without mitogenic stimulation by phytohemagglutinin (PHA). Lymphocyte proliferation was assayed at the end of the culture period by 6 h of pulse labeling with 3H-thymidine (3H-TdR). Exposure to radiation at either frequency at specific absorption rates (SARs) below 50 W/kg resulted in a dose-dependent, statistically significant increase of 3H-TdR uptake in PHA-activated or unstimulated lymphocytes. Exposure at 50 W/kg or higher suppressed 3H-TdR uptake relative to that of sham-exposed cells. There were no detectable effects of RF radiation on lymphocyte morphology or viability. Notwithstanding the characteristic temperature dependence of lymphocyte activation in vitro, the isothermal exposure conditions of this study warrant the conclusion that the biphasic, dose-dependent effects of the radiation on lymphocyte proliferation were not dependent on heating.

Published
1990

39. Tumor infiltration by myeloid suppressor cells in response to T cell activation in rat gliomas.

Author

Martin Graf, Jeremy Sauer, and Randall Merchant

Abstract

We have recently reported that activation of tumor-specific T cells by subcutaneous vaccination with irradiated T9 glioma cells of syngeneic rats with a pre-existing, intracranial (i.c.) T9 glioma (T9+vaccination) promotes the mobilization of myeloid suppressor cells (MSC) which inhibit T cell function resulting in unregulated tumor progression. The current study investigated if this immunological paradigm could be recapitulated in T cell deficient rats, in other rat glioma models or using a dendritic cell (DC) vaccine. When nude rats were used in the T9+vaccination model, the level of MSC tumor infiltration remained low in vaccinated and control groups and there was no significant difference in tumor size between the groups. Increased tumor infiltration by MSC after vaccination with respective irradiated tumor cells was observed in the 9L, F98 and D74 gliomas. RT-2 tumors were markedly infiltrated with MSC regardless of vaccination. Enhanced tumor progression in response to immunization and T cell activation was observed in rats bearing F98 and D74 gliomas, although less pronounced than in the T9 model, and there was a trend for increased tumor size in the 9L glioma model. Increased MSC infiltrate and augmented T9 glioma growth were observed when DC pulsed with T9 cell lysate was used as a vaccine. These results suggest that MSC infiltration and unregulated tumor growth in response to vaccination is T cell-dependent; is not unique to the T9 glioma; and can be recapitulated with an alternate immunization approach. [ABSTRACT FROM AUTHOR]

Published
2005

40. Glioma Proliferation Modulated in Vitro by Isothermal Radiofrequency Radiation Exposure

Author

Randall Merchant, Li-Ming Liu, and Stephen F. Cleary

Subjects
Radiation, Radiobiology, DNA synthesis, Cell growth, Cell, Biophysics, Biology, medicine.disease, Molecular biology, Uridine, chemistry.chemical_compound, medicine.anatomical_structure, Biochemistry, chemistry, Cell culture, Glioma, medicine, Radiology, Nuclear Medicine and imaging, Thymidine
Abstract

Isothermal (37 +/- 0.2 degrees C) exposure of glioma cells (LN71) for 2 h to 27 or 2450 MHz continuous-wave radiofrequency (RF) radiation in vitro modulated the rates of DNA and RNA synthesis 1, 3, and 5 days after exposure. The alterations indicate effects on cell proliferation and were not caused by RF-induced cell heating. The dose response for either frequency of the radiation was biphasic. Exposure to specific absorption rates (SARs) of 50 W/kg or less stimulated incorporation rates of tritiated thymidine (3H-TdR) and tritiated uridine (3H-UdR), whereas higher SARs suppressed DNA and RNA synthesis. Statistically significant time-dependent alterations were detected for up to 5 days postexposure, suggesting a kinetic cellular response to RF radiation and the possibility of cumulative effects on cell proliferation. General mechanisms of effects are discussed.

Published
1990
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