426 results on '"Okonkwo, P. O."'
Search Results
2. Insights into epileptogenesis from post-traumatic epilepsy
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Pease, Matthew, Gupta, Kunal, Moshé, Solomon L., Correa, Daniel J., Galanopoulou, Aristea S., Okonkwo, David O., Gonzalez-Martinez, Jorge, Shutter, Lori, Diaz-Arrastia, Ramon, and Castellano, James F.
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- 2024
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3. Interaction of obesity and proteins associated with the NLRP3 inflammasome following mild traumatic brain injury
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Eagle, Shawn R., Basantani, Mahesh K., Preszler, Jonathan, Sherry, Natalie, McIntyre, Peyton, Kershaw, Erin E., Puccio, Ava M., and Okonkwo, David O.
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- 2024
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4. Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS)
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Picetti, Edoardo, Demetriades, Andreas K., Catena, Fausto, Aarabi, Bizhan, Abu-Zidan, Fikri M., Alves, Oscar L., Ansaloni, Luca, Armonda, Rocco A., Badenes, Rafael, Bala, Miklosh, Balogh, Zsolt J., Barbanera, Andrea, Bertuccio, Alessandro, Biffl, Walter L., Bouzat, Pierre, Buki, Andras, Castano-Leon, Ana Maria, Cerasti, Davide, Citerio, Giuseppe, Coccolini, Federico, Coimbra, Raul, Coniglio, Carlo, Costa, Francesco, De Iure, Federico, Depreitere, Bart, Fainardi, Enrico, Fehlings, Michael J., Gabrovsky, Nikolay, Godoy, Daniel Agustin, Gruen, Peter, Gupta, Deepak, Hawryluk, Gregory W. J., Helbok, Raimund, Hossain, Iftakher, Hutchinson, Peter J., Iaccarino, Corrado, Inaba, Kenji, Ivanov, Marcel, Kaprovoy, Stanislav, Kirkpatrick, Andrew W., Klein, Sam, Kolias, Angelos, Konovalov, Nikolay A., Lagares, Alfonso, Lippa, Laura, Loza-Gomez, Angelica, Luoto, Teemu M., Maas, Andrew I. R., Maciejczak, Andrzej, Maier, Ronald V., Marklund, Niklas, Martin, Matthew J., Melloni, Ilaria, Mendoza-Lattes, Sergio, Meyfroidt, Geert, Munari, Marina, Napolitano, Lena M., Okonkwo, David O., Otomo, Yasuhiro, Papadopoulos, Marios C., Petr, Ondra, Peul, Wilco C., Pudkrong, Aichholz K., Qasim, Zaffer, Rasulo, Frank, Reizinho, Carla, Ringel, Florian, Rizoli, Sandro, Rostami, Elham, Rubiano, Andres M., Russo, Emanuele, Sarwal, Aarti, Schwab, Jan M., Servadei, Franco, Sharma, Deepak, Sharif, Salman, Shiban, Ehab, Shutter, Lori, Stahel, Philip F., Taccone, Fabio S., Terpolilli, Nicole A., Thomé, Claudius, Toth, Peter, Tsitsopoulos, Parmenion P., Udy, Andrew, Vaccaro, Alexander R., Varon, Albert J., Vavilala, Monica S., Younsi, Alexander, Zackova, Monika, Zoerle, Tommaso, and Robba, Chiara
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- 2024
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5. Topical tranexamic acid (TXA) is non-inferior to intravenous TXA in adult spine surgery: a meta-analysis
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Mitha, Rida, Colan, Jhair Alejandro, Hernandez-Rovira, Miguel A., Jawad-Makki, Mohamed-Ali H., Patel, Rujvee P., Elsayed, Galal A., Shaw, Jeremy D., Okonkwo, David O., Buell, Thomas J., Hamilton, D. Kojo, and Agarwal, Nitin
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- 2024
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6. Interaction of Medical Conditions and Football Exposures Associated with Premortem Chronic Traumatic Encephalopathy Diagnosis in Former Professional American Football Players
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Eagle, Shawn R., Grashow, Rachel, DiGregorio, Heather, Terry, Douglas P., Baggish, Aaron, Weisskopf, Marc G., Okonkwo, David O., and Zafonte, Ross
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- 2024
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7. Robust Functional Magnetoencephalographic Brain Measures with 1.0 Millimeter Spatial Separation
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Krieger, Don, Shepard, Paul, and Okonkwo, David O.
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Quantitative Biology - Neurons and Cognition - Abstract
Neuroelectric currents were extracted from free-running magnetoencephalographic (MEG) rest and task recordings from 617 normative subjects (ages: 18-87). State-dependent neuroelectric differential activation (DA) with spatial resolution comparable to that of local field potentials was detected in the majority of this cohort. Rest-high (rest greater than task) or task-high DA was found in the majority of individual subjects in more than 13,000 1 mm^3 voxels per subject. On average, 6% of the DA voxels bordered a second voxel whose DA was opposite, i.e., one was rest-high and the other was task-high. 516 subjects showed more than 100 such opposite voxel pairs 1 mm apart; 226 subjects showed more than 1000. The number of bordering voxel pairs with the same DA was consistently higher for almost all subjects and averaged 20%, ruling out the possibility that opposite bordering voxels occur simply by chance. For 65 brain regions, more than 10% of the cohort showed significantly more same than opposite pairs. These findings taken together support the conclusion that neuroelectric DA is consistently distinguishable at single 1 mm^3 brain voxels with 1-mm spatial separation. When restricted to voxels with near-zero rest or task counts, significantly more rest-high than task-high voxels were found in 35 regions for at least 10 percent of the subjects. This inequality was not found when all DA-voxels were included. This supports the conclusion that the DA found in many rest-high voxels with near-zero task counts is due in part to task-dependent inhibition., Comment: 14 pages, 4 figures
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- 2022
8. Neuroinflammatory Biomarkers for Traumatic Brain Injury Diagnosis and Prognosis: A TRACK-TBI Pilot Study
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Yue, John K, Kobeissy, Firas H, Jain, Sonia, Sun, Xiaoying, Phelps, Ryan RL, Korley, Frederick K, Gardner, Raquel C, Ferguson, Adam R, Huie, J Russell, Schneider, Andrea LC, Yang, Zhihui, Xu, Haiyan, Lynch, Cillian E, Deng, Hansen, Rabinowitz, Miri, Vassar, Mary J, Taylor, Sabrina R, Mukherjee, Pratik, Yuh, Esther L, Markowitz, Amy J, Puccio, Ava M, Okonkwo, David O, Diaz-Arrastia, Ramon, Manley, Geoffrey T, Wang, Kevin KW, Badjatia, Neeraj, Foreman, Brandon, Gopinath, Shankar, Grandhi, Ramesh, Jha, Ruchira M, Lingsma, Hester F, Madden, Christopher, Madhok, Debbie Y, McCrea, Michael A, Merchant, Randall, Nelson, Lindsay D, Ngwenya, Laura B, Robertson, Claudia S, Rodgers, Richard B, Satris, Gabriela G, Schnyer, David M, Valadka, Alex B, van Essen, Thomas A, and Zafonte, Ross
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Clinical Research ,Brain Disorders ,Traumatic Brain Injury (TBI) ,Traumatic Head and Spine Injury ,Physical Injury - Accidents and Adverse Effects ,Neurosciences ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,acute phase reactant ,alarmin ,cytokine ,neuroinflammation ,prognosis ,traumatic brain injury - 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
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- 2023
9. Neuroworsening in the Emergency Department Is a Predictor of Traumatic Brain Injury Intervention and Outcome: A TRACK-TBI Pilot Study.
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Yue, John K, Krishnan, Nishanth, Kanter, John H, Deng, Hansen, Okonkwo, David O, Puccio, Ava M, Madhok, Debbie Y, Belton, Patrick J, Lindquist, Britta E, Satris, Gabriela G, Lee, Young M, Umbach, Gray, Duhaime, Ann-Christine, Mukherjee, Pratik, Yuh, Esther L, Valadka, Alex B, DiGiorgio, Anthony M, Tarapore, Phiroz E, Huang, Michael C, Manley, Geoffrey T, and TRACK-TBI Investigators
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TRACK-TBI Investigators ,Glasgow Coma Scale ,emergency department ,mortality ,neurological examination ,neuroworsening ,patient outcome assessment ,traumatic brain injury ,Prevention ,Physical Injury - Accidents and Adverse Effects ,Clinical Research ,Traumatic Head and Spine Injury ,Brain Disorders ,Traumatic Brain Injury (TBI) ,Neurosciences ,Injuries and accidents ,Good Health and Well Being ,Clinical Sciences - Abstract
IntroductionNeuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization.MethodsAdult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan
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- 2023
10. Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury.
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Stein, Murray B, Jain, Sonia, Parodi, Livia, Choi, Karmel W, Maihofer, Adam X, Nelson, Lindsay D, Mukherjee, Pratik, Sun, Xiaoying, He, Feng, Okonkwo, David O, Giacino, Joseph T, Korley, Frederick K, Vassar, Mary J, Robertson, Claudia S, McCrea, Michael A, Temkin, Nancy, Markowitz, Amy J, Diaz-Arrastia, Ramon, Rosand, Jonathan, Manley, Geoffrey T, and TRACK-TBI Investigators
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TRACK-TBI Investigators ,Humans ,Brain Concussion ,Longitudinal Studies ,Prospective Studies ,Stress Disorders ,Post-Traumatic ,Depressive Disorder ,Major ,Traumatic Head and Spine Injury ,Mental Health ,Post-Traumatic Stress Disorder (PTSD) ,Neurosciences ,Brain Disorders ,Physical Injury - Accidents and Adverse Effects ,Anxiety Disorders ,Clinical Research ,Traumatic Brain Injury (TBI) ,Serious Mental Illness ,Mental health ,Good Health and Well Being ,Clinical Sciences ,Public Health and Health Services ,Psychology - Abstract
Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80-7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual's PRS could be clinically actionable if used-possibly with other non-genetic predictors-to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.
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- 2023
11. Durability of stand-alone anterolateral interbody fusion in staged minimally invasive circumferential scoliosis surgery with delayed posterior instrumentation due to medical necessity
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Agarwal, Nitin, Roy, Souvik, Lavadi, Raj Swaroop, Alan, Nima, Ozpinar, Alp, Buell, Thomas J., Hamilton, D. Kojo, Kanter, Adam S., and Okonkwo, David O.
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- 2023
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12. Effects of age and time since injury on traumatic brain injury blood biomarkers: a TRACK-TBI study
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Gardner, Raquel C, Puccio, Ava M, Korley, Frederick K, Wang, Kevin KW, Diaz-Arrastia, Ramon, Okonkwo, David O, Puffer, Ross C, Yuh, Esther L, Yue, John K, Sun, Xiaoying, Taylor, Sabrina R, Mukherjee, Pratik, Jain, Sonia, Manley, Geoffrey T, Feeser, Venkata R, Ferguson, Adam R, Gaudette, Etienne, Gopinath, Shankar, Keene, C Dirk, Madden, Christopher, Martin, Alastair, McCrea, Michael, Merchant, Randall, Ngwenya, Laura B, Robertson, Claudia, Temkin, Nancy, Vassar, Mary, and Zafonte, Ross
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Aging ,Traumatic Brain Injury (TBI) ,Clinical Research ,Brain Disorders ,Neurosciences ,Physical Injury - Accidents and Adverse Effects ,Traumatic Head and Spine Injury ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Neurological ,Injuries and accidents ,traumatic brain injury ,aging ,head CT ,biomarkers ,diagnostic ,TRACK-TBI Investigators - Abstract
Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury. Our aims were to investigate age-related differences in diagnostic accuracy and 2-week evolution of four leading candidate blood-based traumatic brain injury biomarkers-plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, S100 calcium binding protein B and neuron-specific enolase-among participants in the 18-site prospective cohort study Transforming Research And Clinical Knowledge in Traumatic Brain Injury. Day-1 biomarker data were available for 2602 participants including 2151 patients with traumatic brain injury, 242 orthopedic trauma controls and 209 healthy controls. Participants were stratified into 3 age categories (young: 17-39 years, middle-aged: 40-64 years, older: 65-90 years). We investigated age-stratified biomarker levels and biomarker discriminative abilities across three diagnostic groups: head CT-positive/negative; traumatic brain injury/orthopedic controls; and traumatic brain injury/healthy controls. The difference in day-1 glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and neuron-specific enolase levels across most diagnostic groups was significantly smaller for older versus younger adults, resulting in a narrower range within which a traumatic brain injury diagnosis may be discriminated in older adults. Despite this, day-1 glial fibrillary acidic protein had good to excellent performance across all age-categories for discriminating all three diagnostic groups (area under the curve 0.84-0.96; lower limit of 95% confidence intervals all >0.78). Day-1 S100 calcium-binding protein B and ubiquitin carboxy-terminal hydrolase L1 showed good discrimination of CT-positive versus negative only among adults under age 40 years within 6 hours of injury. Longitudinal blood-based biomarker data were available for 522 hospitalized patients with traumatic brain injury and 24 hospitalized orthopaedic controls. Glial fibrillary acidic protein levels maintained good to excellent discrimination across diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients only. In conclusion, the blood-based glial fibrillary acidic protein assay tested here has good to excellent performance across all age-categories for discriminating key traumatic brain injury diagnostic groups to at least 3 days post-injury in this trauma centre cohort. The addition of a blood-based diagnostic to the evaluation of traumatic brain injury, including geriatric traumatic brain injury, has potential to streamline diagnosis.
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- 2022
13. Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury
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Kulbe, Jacqueline R, Jain, Sonia, Nelson, Lindsay D, Korley, Frederick K, Mukherjee, Pratik, Sun, Xiaoying, Okonkwo, David O, Giacino, Joseph T, Vassar, Mary J, Robertson, Claudia S, McCrea, Michael A, Wang, Kevin KW, Temkin, Nancy, Mac Donald, Christine L, Taylor, Sabrina R, Ferguson, Adam R, Markowitz, Amy J, Diaz-Arrastia, Ramon, Manley, Geoffrey T, and Stein, Murray B
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Brain Disorders ,Clinical Research ,Physical Injury - Accidents and Adverse Effects ,Neurosciences ,Traumatic Brain Injury (TBI) ,Post-Traumatic Stress Disorder (PTSD) ,Traumatic Head and Spine Injury ,Humans ,Glial Fibrillary Acidic Protein ,Brain Concussion ,Stress Disorders ,Post-Traumatic ,Prospective Studies ,Longitudinal Studies ,C-Reactive Protein ,Brain Injuries ,Traumatic ,Biomarkers ,TRACK-TBI Investigators ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale [GCS] score 13-15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and serum high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. GFAP levels were positively associated (Spearman's rho = 0.35, p
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- 2022
14. Diffusion Tensor Imaging Reveals Elevated Diffusivity of White Matter Microstructure that Is Independently Associated with Long-Term Outcome after Mild Traumatic Brain Injury: A TRACK-TBI Study
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Palacios, Eva M, Yuh, Esther L, Donald, Christine L Mac, Bourla, Ioanna, Wren-Jarvis, Jamie, Sun, Xiaoying, Vassar, Mary J, Diaz-Arrastia, Ramon, Giacino, Joseph T, Okonkwo, David O, Robertson, Claudia S, Stein, Murray B, Temkin, Nancy, McCrea, Michael A, Levin, Harvey S, Markowitz, Amy J, Jain, Sonia, Manley, Geoffrey T, Mukherjee, Pratik, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Barber, Jason, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Keene, C Dirk, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Nolan, Amber, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Sherer, Mark, Taylor, Sabrina, Toga, Arthur, Valadka, Alex, Vespa, Paul, Wang, Kevin, Yue, John K, and Zafonte, Ross
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Traumatic Head and Spine Injury ,Neurosciences ,Clinical Research ,Traumatic Brain Injury (TBI) ,Physical Injury - Accidents and Adverse Effects ,Brain Disorders ,Biomedical Imaging ,Injuries and accidents ,Neurological ,Adolescent ,Adult ,Brain ,Brain Concussion ,Brain Injuries ,Traumatic ,Cohort Studies ,Diffusion Magnetic Resonance Imaging ,Diffusion Tensor Imaging ,Humans ,Middle Aged ,White Matter ,Young Adult ,concussion ,diffusion tensor imaging ,Glasgow Outcome Scale ,MRI ,traumatic brain injury ,TRACK-TBI Investigators ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE
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- 2022
15. Correction: Early management of isolated severe traumatic brain injury patients in a hospital without neurosurgical capabilities: a consensus and clinical recommendations of the World Society of Emergency Surgery (WSES)
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Picetti, Edoardo, Catena, Fausto, Abu-Zidan, Fikri, Ansaloni, Luca, Armonda, Rocco A., Bala, Miklosh, Balogh, Zsolt J., Bertuccio, Alessandro, Biffl, Walt L., Bouzat, Pierre, Buki, Andras, Cerasti, Davide, Chesnut, Randall M., Citerio, Giuseppe, Coccolini, Federico, Coimbra, Raul, Coniglio, Carlo, Fainardi, Enrico, Gupta, Deepak, Gurney, Jennifer M., Hawryluk, Gregory W. J., Helbok, Raimund, Hutchinson, Peter J. A., Iaccarino, Corrado, Kolias, Angelos, Maier, Ronald W., Martin, Matthew J., Meyfroidt, Geert, Okonkwo, David O., Rasulo, Frank, Rizoli, Sandro, Rubiano, Andres, Sahuquillo, Juan, Sams, Valerie G., Servadei, Franco, Sharma, Deepak, Shutter, Lori, Stahel, Philip F., Taccone, Fabio S., Udy, Andrew, Zoerle, Tommaso, Agnoletti, Vanni, Bravi, Francesca, De Simone, Belinda, Kluger, Yoram, Martino, Costanza, Moore, Ernest E., Sartelli, Massimo, Weber, Dieter, and Robba, Chiara
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- 2023
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16. Early management of isolated severe traumatic brain injury patients in a hospital without neurosurgical capabilities: a consensus and clinical recommendations of the World Society of Emergency Surgery (WSES)
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Picetti, Edoardo, Catena, Fausto, Abu-Zidan, Fikri, Ansaloni, Luca, Armonda, Rocco A., Bala, Miklosh, Balogh, Zsolt J., Bertuccio, Alessandro, Biffl, Walt L., Bouzat, Pierre, Buki, Andras, Cerasti, Davide, Chesnut, Randall M., Citerio, Giuseppe, Coccolini, Federico, Coimbra, Raul, Coniglio, Carlo, Fainardi, Enrico, Gupta, Deepak, Gurney, Jennifer M., Hawryluk, Gregory W. J., Helbok, Raimund, Hutchinson, Peter J. A., Iaccarino, Corrado, Kolias, Angelos, Maier, Ronald W., Martin, Matthew J., Meyfroidt, Geert, Okonkwo, David O., Rasulo, Frank, Rizoli, Sandro, Rubiano, Andres, Sahuquillo, Juan, Sams, Valerie G., Servadei, Franco, Sharma, Deepak, Shutter, Lori, Stahel, Philip F., Taccone, Fabio S., Udy, Andrew, Zoerle, Tommaso, Agnoletti, Vanni, Bravi, Francesca, De Simone, Belinda, Kluger, Yoram, Martino, Costanza, Moore, Ernest E., Sartelli, Massimo, Weber, Dieter, and Robba, Chiara
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- 2023
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17. A genome-wide association study of outcome from traumatic brain injury
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Kals, Mart, Kunzmann, Kevin, Parodi, Livia, Radmanesh, Farid, Wilson, Lindsay, Izzy, Saef, Anderson, Christopher D, Puccio, Ava M, Okonkwo, David O, Temkin, Nancy, Steyerberg, Ewout W, Stein, Murray B, Manley, Geoff T, Maas, Andrew IR, Richardson, Sylvia, Diaz-Arrastia, Ramon, Palotie, Aarno, Ripatti, Samuli, Rosand, Jonathan, Menon, David K, Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, 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, Coles, Jonathan P, 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, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A, Gratz, Johannes, Gravesteijn, Benjamin, and Grossi, Francesca
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Epidemiology ,Health Sciences ,Traumatic Head and Spine Injury ,Genetics ,Physical Injury - Accidents and Adverse Effects ,Neurosciences ,Brain Disorders ,Human Genome ,Traumatic Brain Injury (TBI) ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Brain Injuries ,Traumatic ,Genome-Wide Association Study ,Humans ,Mannose-Binding Lectin ,Prospective Studies ,Transcriptome ,Traumatic brain injury ,Genome-Wide association study ,Outcome ,Recovery ,Consortia ,Genetic Associations In Neurotrauma (GAIN) Consortium ,Clinical Sciences ,Public Health and Health Services ,Clinical sciences - Abstract
BackgroundFactors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.MethodsWe performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.FindingsThe estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10-8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10-5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10-4).InterpretationWhile multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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- 2022
18. Critical care for concomitant severe traumatic brain injury and acute spinal cord injury in the polytrauma patient: illustrative case
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Deng, Hansen, Luy, Diego D, Abou-Al-Shaar, Hussam, Yue, John K, Zinn, Pascal O, Puccio, Ava M, and Okonkwo, David O
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Biomedical and Clinical Sciences ,Clinical Sciences ,Spinal Cord Injury ,Clinical Research ,Traumatic Brain Injury (TBI) ,Brain Disorders ,Neurosciences ,Physical Injury - Accidents and Adverse Effects ,Traumatic Head and Spine Injury ,Rehabilitation ,Neurodegenerative ,Injuries and accidents ,Neurological ,Good Health and Well Being ,decompressive hemicraniectomy ,polytrauma ,spinal cord injury ,traumatic brain injury - Abstract
BackgroundThe occurrence of traumatic brain injury with spinal cord injury (SCI) in polytrauma patients is associated with significant morbidity. Clinicians face challenges from a decision-making and rehabilitative perspective. Management is complex and understudied. Treatment should be systematic beginning at the scene, focusing on airway resuscitation and hemodynamic stabilization, immobilization, and timely transport. Early operative interventions should be provided, followed by minimizing secondary pathophysiology. The authors present a case to delineate decision-making in the treatment of combined cranial and spinal trauma.ObservationsA 19-year-old man presented as a level I trauma patient after falling 30 feet as the result of scaffolding collapse. The patient was unresponsive and was intubated; he had an initial Glasgow Coma Scale score of 4. Computed tomography revealed multicompartmental bleeding and herniation, for which supra- and infratentorial decompressive craniectomies were performed. The patient also suffered from thoracic SCI that resulted in complete paraplegia. Multimodality monitoring was used. After stabilization and lengthy rehabilitation, the patient obtained significant functional improvement.LessonsThe approach to initial management of concomitant head and spine trauma is to establish intracranial stability followed by intraspinal stability. Patients can make considerable recovery, particularly younger patients, who are more likely to benefit from early aggressive interventions and medical treatment.
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- 2022
19. Microbiologically Influenced Corrosion: A Concern for Oil and Gas Sector in Africa
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Etim, Ini-Ibehe N., Njoku, Demian I., Uzoma, Paul C., Kolawole, Sharafadeen K., Olanrele, Olajire S., Ekarenem, Okpo O., Okonkwo, Bright O., Ikeuba, Alexander I., Udoh, Inime I., Njoku, Chigoziri N., Etim, Iniobong P., and Emori, Wilfred
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- 2023
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20. Prognostic Value of Hemorrhagic Brainstem Injury on Early Computed Tomography: A TRACK-TBI Study.
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Williams, John R, Nieblas-Bedolla, Edwin, Feroze, Abdullah, Young, Christopher, Temkin, Nancy R, Giacino, Joseph T, Okonkwo, David O, Manley, Geoffrey T, Barber, Jason, Durfy, Sharon, Markowitz, Amy J, Yuh, Esther L, Mukherjee, Pratik, Mac Donald, Christine L, and and The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators
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and The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators ,Brain Stem ,Humans ,Tomography ,X-Ray Computed ,Prognosis ,Glasgow Coma Scale ,Retrospective Studies ,Prospective Studies ,Brain Injuries ,Traumatic ,Brainstem injury ,Computed tomography ,Outcomes ,Traumatic axonal injury ,Traumatic brain injury ,Biomedical Imaging ,Neurosciences ,Physical Injury - Accidents and Adverse Effects ,Traumatic Head and Spine Injury ,Brain Disorders ,Traumatic Brain Injury (TBI) ,Injuries and accidents ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
BackgroundTraumatic brainstem injury has yet to be incorporated into widely used imaging classification systems for traumatic brain injury (TBI), and questions remain regarding prognostic implications for this TBI subgroup. To address this, retrospective data on patients from the multicenter prospective Transforming Research and Clinical Knowledge in TBI study were studied.MethodsPatients with brainstem and cerebrum injury (BSI+) were matched by age, sex, and admission Glasgow Coma Scale (GCS) score to patients with cerebrum injuries only. All patients had an interpretable head computed tomography (CT) scan from the first 48 hours after injury and a 6-month Glasgow Outcome Scale Extended (GOSE) score. CT scans were reviewed for brainstem lesions and, when present, characterized by location, size, and type (traumatic axonal injury, contusion, or Duret hemorrhage). Clinical, demographic, and outcome data were then compared between the two groups.ResultsMann-Whitney U-tests showed no significant difference in 6-month GOSE scores in patients with BSI+ (mean 2.7) compared with patients with similar but only cerebrum injuries (mean 3.9), although there is a trend (p = 0.10). However, subclassification by brainstem lesion type, traumatic axonal injury (mean 4.0) versus Duret hemorrhage or contusion (mean 1.4), did identify a proportion of BSI+ with significantly less favorable outcome (p = 0.002). The incorporation of brainstem lesion type (traumatic axonal injury vs. contusion/Duret), along with GCS into a multivariate logistic regression model of favorable outcome (GOSE score 4-8) did show a significant contribution to the prognostication of this brainstem injury subgroup (odds ratio 0.08, 95% confidence interval 0.00-0.67, p = 0.01).ConclusionsThese findings suggest two groups of patients with brainstem injuries may exist with divergent recovery potential after TBI. These data support the notion that newer CT imaging classification systems may augment traditional clinical measures, such as GCS in identifying those patients with TBI and brainstem injuries that stand a higher chance of favorable outcome.
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- 2021
21. Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury: A TRACK-TBI Study With External Validation in CENTER-TBI.
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Yuh, Esther L, Jain, Sonia, Sun, Xiaoying, Pisica, Dana, Harris, Mark H, Taylor, Sabrina R, Markowitz, Amy J, Mukherjee, Pratik, Verheyden, Jan, Giacino, Joseph T, Levin, Harvey S, McCrea, Michael, Stein, Murray B, Temkin, Nancy R, Diaz-Arrastia, Ramon, Robertson, Claudia S, Lingsma, Hester F, Okonkwo, David O, Maas, Andrew IR, Manley, Geoffrey T, TRACK-TBI Investigators for the CENTER-TBI Investigators, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Corrigan, John D, Crawford, Karen, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Keene, C Dirk, Kramer, Joel, Kreitzer, Natalie, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Nolan, Amber, Palacios, Eva, Perl, Daniel, Rabinowitz, Miri, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Toga, Arthur, Valadka, Alex, Vassar, Mary, and Zafonte, Ross
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TRACK-TBI Investigators for the CENTER-TBI Investigators - Abstract
ImportanceA 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.ObjectiveTo identify pathological CT features associated with adverse outcomes after mTBI.Design, setting, and participantsThe 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.ExposuresAcute nonpenetrating head trauma.Main outcomes and measuresFrequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores
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- 2021
22. Impact of Coronavirus Disease 2019 Shutdown on Neurotrauma Volume in Pennsylvania
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Algattas, Hanna N, McCarthy, David, Kujawski, Brandon, Agarwal, Nitin, Brown, Joshua, Forsythe, Raquel M, Leonardo, Jody, Walsh, Kevin, Gross, Bradley A, Friedlander, Robert M, Okonkwo, David O, Whiting, Donald, and Miele, Vincent J
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Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Brain Disorders ,Physical Injury - Accidents and Adverse Effects ,Injuries and accidents ,Good Health and Well Being ,Accidental Falls ,Accidents ,Traffic ,Adolescent ,Adult ,Aged ,Brain Injuries ,Traumatic ,COVID-19 ,Female ,Humans ,Male ,Middle Aged ,Nervous System Diseases ,Pennsylvania ,Quarantine ,Registries ,Trauma Centers ,Wounds and Injuries ,Wounds ,Gunshot ,Young Adult ,Neurotrauma ,Clinical sciences - Abstract
ObjectiveThe 2020 coronavirus disease 2019 (COVID-19) pandemic resulted in state-specific quarantine protocols and introduced the concept of social distancing into modern parlance. We assess the impact of the COVID-19 pandemic on neurotrauma presentations in the first 3 months after shutdown throughout Pennsylvania.MethodsThe Pennsylvania Trauma Systems Foundation was queried for registry data from the Pennsylvania Trauma Outcomes Study between March 12 and June 5 in each year from 2017 to 2020.ResultsAfter the COVID-19 shutdown, there was a 27% reduction in neurotrauma volume, from 2680 cases in 2017 to 2018 cases in 2020, and a 28.8% reduction in traumatic brain injury volume. There was no significant difference in neurotrauma phenotype incurred relative to total cases. Injury mechanism was less likely to be motor vehicle collision and more likely caused by falls, gunshot wound, and recreational vehicle accidents (P < 0.05). Location of injury was less likely on roads and public locations and more likely at indoor private locations (P < 0.05). The proportion of patients with neurotrauma with blood alcohol concentration >0.08 g/dL was reduced in 2020 (11.4% vs. 9.0%; P < 0.05). Mortality was higher during 2020 compared with pre-COVID years (7.7% vs. 6.4%; P < 0.05).ConclusionsDuring statewide shutdown, neurotrauma volume and alcohol-related trauma decreased and low-impact traumas and gunshot wounds increased, with a shift toward injuries occurring in private, indoor locations. These changes increased mortality. However, there was not a change in the types of injuries sustained.
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- 2021
23. High-Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study
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Xu, Linda B, Yue, John K, Korley, Frederick, Puccio, Ava M, Yuh, Esther L, Sun, Xiaoying, Rabinowitz, Miri, Vassar, Mary J, Taylor, Sabrina R, Winkler, Ethan A, Puffer, Ross C, Deng, Hansen, McCrea, Michael, Stein, Murray B, Robertson, Claudia S, Levin, Harvey S, Dikmen, Sureyya, Temkin, Nancy R, Giacino, Joseph T, Mukherjee, Pratik, Wang, Kevin KW, Okonkwo, David O, Markowitz, Amy J, Jain, Sonia, Manley, Geoffrey T, Diaz-Arrastia, Ramon, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Kramer, Joel, Kreitzer, Natalie, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Okonkwo, David, Palacios, Eva, Perl, Daniel, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Toga, Arthur, and Adeoye, Alex VaOpeolu
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Traumatic Brain Injury (TBI) ,Clinical Research ,Neurosciences ,Brain Disorders ,Traumatic Head and Spine Injury ,Physical Injury - Accidents and Adverse Effects ,Injuries and accidents ,Adult ,Biomarkers ,Biomedical Research ,Brain Injuries ,Traumatic ,C-Reactive Protein ,Disabled Persons ,Female ,Humans ,Male ,Middle Aged ,Prognosis ,Prospective Studies ,Time Factors ,Young Adult ,biomarkers ,head trauma ,traumatic brain injury ,TRACK-TBI Investigators ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
Systemic inflammation impacts outcome after traumatic brain injury (TBI), but most TBI biomarker studies have focused on brain-specific proteins. C-reactive protein (CRP) is a widely used biomarker of inflammation with potential as a prognostic biomarker after TBI. The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study prospectively enrolled TBI patients within 24 h of injury, as well as orthopedic injury and uninjured controls; biospecimens were collected at enrollment. A subset of hospitalized participants had blood collected on day 3, day 5, and 2 weeks. High-sensitivity CRP (hsCRP) and glial fibrillary acidic protein (GFAP) were measured. Receiver operating characteristic analysis was used to evaluate the prognostic ability of hsCRP for 6-month outcome, using the Glasgow Outcome Scale-Extended (GOSE). We included 1206 TBI subjects, 122 orthopedic trauma controls (OTCs), and 209 healthy controls (HCs). Longitudinal biomarker sampling was performed in 254 hospitalized TBI subjects and 19 OTCs. hsCRP rose between days 1 and 5 for TBI and OTC subjects, and fell by 2 weeks, but remained elevated compared with HCs (p
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- 2021
24. Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months After Mild Traumatic Brain Injury
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Stein, Murray B, Yuh, Esther, Jain, Sonia, Okonkwo, David O, Donald, Christine L Mac, Levin, Harvey, Giacino, Joseph T, Dikmen, Sureyya, Vassar, Mary J, Diaz-Arrastia, Ramon, Robertson, Claudia S, Nelson, Lindsay D, McCrea, Michael, Sun, Xiaoying, Temkin, Nancy, Taylor, Sabrina R, Markowitz, Amy J, Manley, Geoffrey T, Mukherjee, Pratik, Investigators, TRACK-TBI, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Barber, Jason, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Keene, C Dirk, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Ngwenya, Laura B, Noel, Florence, Nolan, Amber, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Toga, Arthur, Valadka, Alex, Vespa, Paul, Wang, Kevin, Yue, John K, and Zafonte, Ross
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Neurosciences ,Mental Health ,Post-Traumatic Stress Disorder (PTSD) ,Prevention ,Behavioral and Social Science ,Anxiety Disorders ,Physical Injury - Accidents and Adverse Effects ,Traumatic Head and Spine Injury ,Brain Disorders ,Traumatic Brain Injury (TBI) ,Clinical Research ,Biomedical Imaging ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Mental health ,Neurological ,Amygdala ,Brain ,Brain Concussion ,Hippocampus ,Humans ,Stress Disorders ,Post-Traumatic ,TRACK-TBI Investigators ,Cingulate ,Insula ,PTSD ,Posttraumatic stress disorder ,TBI ,Traumatic brain injury - Abstract
BackgroundBrain 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.MethodsUsing 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.ResultsOverall, 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.ConclusionsResults, 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.
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- 2021
25. COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI).
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Smith, Douglas H, Dollé, Jean-Pierre, Ameen-Ali, Kamar E, Bretzin, Abigail, Cortes, Etty, Crary, John F, Dams-O'Connor, Kristen, Diaz-Arrastia, Ramon, Edlow, Brian L, Folkerth, Rebecca, Hazrati, Lili-Naz, Hinds, Sidney R, Iacono, Diego, Johnson, Victoria E, Keene, C Dirk, Kofler, Julia, Kovacs, Gabor G, Lee, Edward B, Manley, Geoffrey, Meaney, David, Montine, Thomas, Okonkwo, David O, Perl, Daniel P, Trojanowski, John Q, Wiebe, Douglas J, Yaffe, Kristine, McCabe, Thomas, and Stewart, William
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Chronic traumatic encephalopathy ,Concussion ,Dementia ,Neurodegenerative disease ,Traumatic brain injury ,Brain Disorders ,Acquired Cognitive Impairment ,Injury - Traumatic brain injury ,Injury (total) Accidents/Adverse Effects ,Neurodegenerative ,Neurosciences ,Injury - Trauma - (Head and Spine) ,Neurological ,Biochemistry and Cell Biology ,Clinical Sciences - Abstract
Efforts to characterize the late effects of traumatic brain injury (TBI) have been in progress for some time. In recent years much of this activity has been directed towards reporting of chronic traumatic encephalopathy (CTE) in former contact sports athletes and others exposed to repetitive head impacts. However, the association between TBI and dementia risk has long been acknowledged outside of contact sports. Further, growing experience suggests a complex of neurodegenerative pathologies in those surviving TBI, which extends beyond CTE. Nevertheless, despite extensive research, we have scant knowledge of the mechanisms underlying TBI-related neurodegeneration (TReND) and its link to dementia. In part, this is due to the limited number of human brain samples linked to robust demographic and clinical information available for research. Here we detail a National Institutes for Neurological Disease and Stroke Center Without Walls project, the COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI), designed to address current limitations in tissue and research access and to advance understanding of the neuropathologies of TReND. As an international, multidisciplinary collaboration CONNECT-TBI brings together multiple experts across 13 institutions. In so doing, CONNECT-TBI unites the existing, comprehensive clinical and neuropathological datasets of multiple established research brain archives in TBI, with survivals ranging minutes to many decades and spanning diverse injury exposures. These existing tissue specimens will be supplemented by prospective brain banking and contribute to a centralized route of access to human tissue for research for investigators. Importantly, each new case will be subject to consensus neuropathology review by the CONNECT-TBI Expert Pathology Group. Herein we set out the CONNECT-TBI program structure and aims and, by way of an illustrative case, the approach to consensus evaluation of new case donations.
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- 2021
26. B-Cell Lymphoma 2 (Bcl-2) Gene Is Associated with Intracranial Hypertension after Severe Traumatic Brain Injury
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Deng, Hansen, Zusman, Benjamin E, Nwachuku, Enyinna L, Yue, John K, Chang, Yue-Fang, Conley, Yvette P, Okonkwo, David O, and Puccio, Ava M
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Genetics ,Brain Disorders ,Traumatic Brain Injury (TBI) ,Clinical Research ,Traumatic Head and Spine Injury ,Physical Injury - Accidents and Adverse Effects ,Rare Diseases ,Neurosciences ,Neurological ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Apoptosis ,Brain Injuries ,Traumatic ,Cerebrovascular Circulation ,Female ,Genotype ,Humans ,Intracranial Hypertension ,Intracranial Pressure ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Prospective Studies ,Proto-Oncogene Proteins c-bcl-2 ,Young Adult ,apoptosis ,Bcl-2 ,genotype ,intracranial hypertension ,traumatic brain injury ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
Severe traumatic brain injury (TBI) activates the apoptotic cascade in neurons and glia as part of secondary cellular injury. B-cell lymphoma 2 (Bcl-2) gene encodes a pro-survival protein to suppress programmed cell death, and variation in this gene has potential to affect intracranial pressure (ICP). Participants were recruited from a single clinical center using a prospective observational study design. Inclusion criteria were: age 16-80 years; Glasgow Coma Scale (GCS) score 4-8; and at least 24 h of ICP monitoring treated between 2000-2014. Outcomes were mean ICP, spikes >20 and >25 mm Hg, edema, and surgical intervention. Odds ratios (OR), mean increases/decreases (B), and 95% confidence intervals (CIs) were reported. In 264 patients, average age was 39.2 years old and 78% of patients were male. Mean ICPs were 11.4 ± 0.4 mm Hg for patients with homozygous wild-type (AA), 12.8 ± 0.6 mm Hg for heterozygous (AG), and 14.3 ± 1.2 mm Hg for homozygous variant (GG; p = 0.023). Rs17759659 GG genotype was associated with more ICP spikes >20 mm Hg (p = 0.017) and >25 mm Hg (p = 0.048). Multi-variate analysis showed that GG relative to AA genotype had higher ICP (B = 2.7 mm Hg, 95% CI [0.5,4.9], p = 0.015), edema (OR = 2.5 [1.0, 6.0], p = 0.049) and need for decompression (OR = 3.7 [1.5-9.3], p = 0.004). In this prospective severe TBI cohort, Bcl-2 rs17759659 was associated with increased risk of intracranial hypertension, cerebral edema, and need for surgical intervention. The variant allele may impact programmed cell death of injured neurons, resulting in elevated ICP and post-traumatic secondary insults. Further risk stratification and targeted genotype-based therapies could improve outcomes after severe TBI.
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- 2021
27. Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial.
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Kawabori, Masahito, Weintraub, Alan H, Imai, Hideaki, Zinkevych, Laroslav, McAllister, Peter, Steinberg, Gary K, Frishberg, Benjamin M, Yasuhara, Takao, Chen, Jefferson W, Cramer, Steven C, Achrol, Achal S, Schwartz, Neil E, Suenaga, Jun, Lu, Daniel C, Semeniv, Ihor, Nakamura, Hajime, Kondziolka, Douglas, Chida, Dai, Kaneko, Takehiko, Karasawa, Yasuaki, Paadre, Susan, Nejadnik, Bijan, Bates, Damien, Stonehouse, Anthony H, Richardson, R Mark, and Okonkwo, David O
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Injury (total) Accidents/Adverse Effects ,Injury - Trauma - (Head and Spine) ,Clinical Research ,Brain Disorders ,Injury - Traumatic brain injury ,Clinical Trials and Supportive Activities ,Neurosciences ,Patient Safety ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveTo determine if chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623).MethodsThis 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 STEMTRA trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multi-center trial (N = 63) underwent randomization in a 1:1:1:1 ratio to 2.5 × 106, 5.0 × 106, 10 × 106 SB623 cells or control. Safety was assessed in patients who underwent surgery (N = 61), and efficacy in the modified intent-to-treat population of randomized patients who underwent surgery (N = 61; SB623 = 46, control = 15).ResultsThe primary efficacy endpoint of significant improvement from baseline of Fugl-Meyer Motor Scale score at 6 months for SB623-treated patients was achieved. SB623-treated patients improved by (LS mean [SE]) +8.3 (1.4) vs +2.3 (2.5) for control at 6 months, the LS mean difference was 6.0 (95% CI: 0.3-11.8); p = 0.040. Secondary efficacy endpoints improved from baseline, but were not statistically significant vs control at 6 months. There were no dose-limiting toxicities or deaths, and 100% of SB623-treated patients experienced treatment-emergent adverse events vs 93.3% of control patients (p = 0.25).ConclusionsSB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls.Classification of evidenceThis study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.
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- 2021
28. Comparison of GFAP and UCH-L1 Measurements from Two Prototype Assays: The Abbott i-STAT and ARCHITECT Assays
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Korley, Frederick K, Datwyler, Saul A, Jain, Sonia, Sun, Xiaoying, Beligere, Gangamani, Chandran, Raj, Marino, Jaime A, McQuiston, Beth, Zhang, Hongwei, Caudle, Krista L, Wang, Kevin KW, Puccio, Ava M, Okonkwo, David O, Yue, John K, Taylor, Sabrina R, Markowitz, Amy, Manley, Geoffrey T, and Diaz-Arrastia, Ramon
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Neurosciences ,Bioengineering ,assay ,biomarkers ,glial fibrillary acidic protein ,traumatic brain injury ,ubiquitin carboxyl-terminal hydrolase L1 - Abstract
Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) may aid in the evaluation of traumatic brain injury (TBI). The objective of this analysis was to compare GFAP and UCH-L1 values measured using a handheld device compared with a core laboratory platform. We analyzed plasma samples from patients with TBI and healthy controls enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) cohort study. GFAP and UCH-L1 were measured twice in each subject using prototype assays, first with the Abbott i-STAT™ handheld device, and second with the Abbott ARCHITECT® platform. We then quantified the agreement in biomarker values obtained using these two methods. GFAP and UCH-L1 were measured twice in 570 and 572 samples, respectively. GFAP values measured by the ARCHITECT platform (median 143.3 [interquartile range (IQR): 19.8-925.8] pg/mL) were higher than values measured by the i-STAT (median 116.0 [IQR: 9.2-856.5] pg/mL). GFAP values from the two platforms were strongly correlated (p = 0.985). Similarly, UCH-L1 values measured by the ARCHITECT platform (median 163.9 [IQR: 82.5-412.4] pg/mL) were higher than values measured by the i-STAT (median 122.5 [IQR: 63.0-297.3] pg/mL). UCH-L1 values from the two platforms were strongly correlated (p = 0.933). Passing-Bablok regression equations were developed to estimate the relationship between the two platforms, specifically to predict i-STAT values from the ARCHITECT platform. GFAP and UCH-L1 values measured using the prototype assays on the Abbott i-STAT and ARCHITECT platforms are strongly correlated and values from either platform may be converted to the other.
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- 2021
29. Hydrocephalus and Cerebrospinal Fluid Analysis Following Severe Traumatic Brain Injury: Evaluation of a Prospective Cohort
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Deng, Hansen, Goldschmidt, Ezequiel, Nwachuku, Enyinna, Yue, John K, Angriman, Federico, Wei, Zhishuo, Agarwal, Nitin, Puccio, Ava M, and Okonkwo, David O
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Biomedical and Clinical Sciences ,Clinical Sciences ,Assistive Technology ,Traumatic Head and Spine Injury ,Brain Disorders ,Physical Injury - Accidents and Adverse Effects ,Traumatic Brain Injury (TBI) ,Neurosciences ,Clinical Research ,Bioengineering ,Hydrocephalus ,Injuries and accidents ,Good Health and Well Being ,post-traumatic hydrocephalus ,traumatic brain injury ,ventriculoperitoneal shunt ,decompressive hemicraniectomy ,shunt failure ,cerebrospinal fluid - Abstract
The development of hydrocephalus after severe traumatic brain injury (TBI) is an under-recognized healthcare phenomenon and can increase morbidity. The current study aims to characterize post-traumatic hydrocephalus (PTH) in a large cohort. Patients were prospectively enrolled age 16-80 years old with Glasgow Coma Scale (GCS) score ≤8. Demographics, GCS, Injury Severity Score (ISS), surgery, and cerebrospinal fluid (CSF) were analyzed. Outcomes were shunt failure and Glasgow Outcome Scale (GOS) at 6 and 12-months. Statistical significance was assessed at p < 0.05. In 402 patients, mean age was 38.0 ± 16.7 years and 315 (78.4%) were male. Forty (10.0%) patients developed PTH, with predominant injuries being subdural hemorrhage (36.4%) and diffuse axonal injury (36.4%). Decompressive hemicraniectomy (DHC) was associated with hydrocephalus (OR 3.62, 95% CI (1.62-8.07), p < 0.01). Eighteen (4.5%) patients had shunt failure and proximal obstruction was most common. Differences in baseline CSF cell count were associated with increased shunt failure. PTH was not associated with worse outcomes at 6 (p = 0.55) or 12 (p = 0.47) months. Hydrocephalus is a frequent sequela in 10.0% of patients, particularly after DHC. Shunt placement and revision procedures are common after severe TBI, within the first 4 months of injury and necessitates early recognition by the clinician.
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- 2021
30. Predictors of six-month inability to return to work in previously employed subjects after mild traumatic brain injury: A TRACK-TBI pilot study.
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Yue, John K, Phelps, Ryan Rl, Hemmerle, Debra D, Upadhyayula, Pavan S, Winkler, Ethan A, Deng, Hansen, Chang, Diana, Vassar, Mary J, Taylor, Sabrina R, Schnyer, David M, Lingsma, Hester F, Puccio, Ava M, Yuh, Esther L, Mukherjee, Pratik, Huang, Michael C, Ngwenya, Laura B, Valadka, Alex B, Markowitz, Amy J, Okonkwo, David O, Manley, Geoffrey T, and TRACK-TBI Investigators
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TRACK-TBI Investigators ,Concussion ,disability ,mild traumatic brain injury ,post-concussion syndrome ,return to work ,Clinical Research ,Traumatic Head and Spine Injury ,Behavioral and Social Science ,Traumatic Brain Injury (TBI) ,Brain Disorders ,Physical Injury - Accidents and Adverse Effects ,Neurosciences - Abstract
Return to work (RTW) is an important milestone of mild traumatic brain injury (mTBI) recovery. The objective of this study was to evaluate whether baseline clinical variables, three-month RTW, and three-month postconcussional symptoms (PCS) were associated with six-month RTW after mTBI. Adult subjects from the prospective multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with mTBI (Glasgow Coma Scale 13-15) who were employed at baseline, with completed three-and six-month RTW status, and three-month Acute Concussion Evaluation (ACE), were extracted. Univariate and multivariable analyses were performed for six-month RTW, with focus on baseline employment, three-month RTW, and three-month ACE domains (physical, cognitive, sleep, and/or emotional postconcussional symptoms (PCS)). Odds ratios (OR) and 95% confidence intervals [CI] were reported. Significance was assessed at p < 0.05. In 152 patients aged 40.7 ± 15.0years, 72% were employed full-time at baseline. Three- and six-month RTW were 77.6% and 78.9%, respectively. At three months, 59.2%, 47.4%, 46.1% and 31.6% scored positive for ACE physical, cognitive, sleep, and emotional PCS domains, respectively. Three-month RTW predicted six-month RTW (OR = 19.80, 95% CI [7.61-51.52]). On univariate analysis, scoring positive in any three-month ACE domain predicted inability for six-month RTW (OR = 0.10-0.11). On multivariable analysis, emotional symptoms predicted inability to six-month RTW (OR = 0.19 [0.04-0.85]). Subjects who scored positive in all four ACE domains were more likely to be unable to RTW at six months (4 domains: 58.3%, vs. 0-to-3 domains: 9.5%; multivariable OR = 0.09 [0.02-0.33]). Three-month post-injury is an important time point at which RTW status and PCS should be assessed, as both are prognostic markers for six-month RTW. Clinicians should be particularly vigilant of patients who present with emotional symptoms, and patients with symptoms across multiple PCS categories, as these patients are at further risk of inability to RTW and may benefit from targeted evaluation and support.
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- 2021
31. Point-of-Care Platform Blood Biomarker Testing of Glial Fibrillary Acidic Protein versus S100 Calcium-Binding Protein B for Prediction of Traumatic Brain Injuries: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study
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Okonkwo, David O, Puffer, Ross C, Puccio, Ava M, Yuh, Esther L, Yue, John K, Diaz-Arrastia, Ramon, Korley, Frederick K, Wang, Kevin KW, Sun, Xiaoying, Taylor, Sabrina R, Mukherjee, Pratik, Markowitz, Amy J, Jain, Sonia, Manley, Geoffrey T, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, Ross, Chesnut, Randall, Corrigan, John, Crawford, Karen, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, Venkata, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, Claude, Hotz, Gillian, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Palacios, Eva, Perl, Daniel, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, and Zafonte, Ross
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Brain Disorders ,Clinical Research ,Physical Injury - Accidents and Adverse Effects ,Traumatic Brain Injury (TBI) ,Traumatic Head and Spine Injury ,Neurosciences ,Injuries and accidents ,Good Health and Well Being ,Adult ,Aged ,Biomarkers ,Brain Injuries ,Traumatic ,Cohort Studies ,Female ,Glial Fibrillary Acidic Protein ,Humans ,Male ,Middle Aged ,Point-of-Care Systems ,S100 Calcium Binding Protein beta Subunit ,Sensitivity and Specificity ,biomarkers ,glial fibrillary acidic protein ,S100 calcium-binding protein B ,traumatic brain injury ,Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
Glial fibrillary acidic protein (GFAP) is cleared by the Food and Drug Administration (FDA) to determine need for head computed tomography (CT) within 12 h after mild traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 13-15); S100 calcium-binding protein B (S100B) serves this function in Europe. This phase 1 biomarker cohort analysis of the multi-center, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study compares GFAP's diagnostic performance, measured on a rapid point-of-care platform, against protein S100B to predict intracranial abnormalities on CT within 24 h post-injury across the spectrum of TBI (GCS 3-15). Head CT scan performed in TBI subjects and blood was collected for all consenting subjects presenting to 18 United States level 1 trauma centers. Plasma was analyzed on a point-of-care device prototype assay for GFAP and serum was analyzed for S100B. In 1359 patients with TBI (GCS 3-15), mean (standard deviation [SD]) age = 40.1 (17.0) years; 68% were male. Plasma GFAP levels were significantly higher in CT+ TBI subjects (median = 1358 pg/mL, interquartile range [IQR]: 472-3803) than in CT- TBI subjects (median = 116 pg/mL, IQR: 26-397) or orthopedic trauma controls (n = 122; median = 13 pg/mL, IQR: 7-20), p
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- 2020
32. Magnetic Resonance Imaging Pilot Study of Intravenous Glyburide in Traumatic Brain Injury
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Eisenberg, Howard M, Shenton, Martha E, Pasternak, Ofer, Simard, J Marc, Okonkwo, David O, Aldrich, Christina, He, Feng, Jain, Sonia, and Hayman, Erik G
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Biomedical and Clinical Sciences ,Clinical Sciences ,Brain Disorders ,Traumatic Brain Injury (TBI) ,Biomedical Imaging ,Traumatic Head and Spine Injury ,Neurosciences ,Clinical Trials and Supportive Activities ,Clinical Research ,Physical Injury - Accidents and Adverse Effects ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Brain Edema ,Brain Injuries ,Traumatic ,Cerebral Hemorrhage ,Double-Blind Method ,Female ,Glyburide ,Humans ,Image Interpretation ,Computer-Assisted ,Infusions ,Intravenous ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Neuroprotective Agents ,Pilot Projects ,Young Adult ,contusion ,edema ,glyburide ,MRI ,SUR1 ,TBI ,Neurology & Neurosurgery ,Clinical sciences ,Biological psychology - Abstract
Pre-clinical studies of traumatic brain injury (TBI) show that glyburide reduces edema and hemorrhagic progression of contusions. We conducted a small Phase II, three-institution, randomized placebo-controlled trial of subjects with TBI to assess the safety and efficacy of intravenous (IV) glyburide. Twenty-eight subjects were randomized and underwent a 72-h infusion of IV glyburide or placebo, beginning within 10 h of trauma. Of the 28 subjects, 25 had Glasgow Coma Scale (GCS) scores of 6-10, and 14 had contusions. There were no differences in adverse events (AEs) or severe adverse events (ASEs) between groups. The magnetic resonance imaging (MRI) percent change at 72-168 h from screening/baseline was compared between the glyburide and placebo groups. Analysis of contusions (7 per group) showed that lesion volumes (hemorrhage plus edema) increased 1036% with placebo versus 136% with glyburide (p = 0.15), and that hemorrhage volumes increased 11.6% with placebo but decreased 29.6% with glyburide (p = 0.62). Three diffusion MRI measures of edema were quantified: mean diffusivity (MD), free water (FW), and tissue MD (MDt), corresponding to overall, extracellular, and intracellular water, respectively. The percent change with time for each measure was compared in lesions (n = 14) versus uninjured white matter (n = 24) in subjects receiving placebo (n = 20) or glyburide (n = 18). For placebo, the percent change in lesions for all three measures was significantly different compared with uninjured white matter (analysis of variance [ANOVA], p
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- 2020
33. B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective
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Deng, Hansen, Yue, John K, Zusman, Benjamin E, Nwachuku, Enyinna L, Abou-Al-Shaar, Hussam, Upadhyayula, Pavan S, Okonkwo, David O, and Puccio, Ava M
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Pediatric ,Brain Disorders ,Traumatic Head and Spine Injury ,Childhood Injury ,Traumatic Brain Injury (TBI) ,Neurosciences ,Hematology ,Clinical Research ,Rare Diseases ,Lymphoma ,Cancer ,Physical Injury - Accidents and Adverse Effects ,Injuries and accidents ,Good Health and Well Being ,Apoptosis ,Biomarkers ,Brain Injuries ,Traumatic ,Humans ,Lymphoma ,B-Cell ,Proto-Oncogene Proteins c-bcl-2 ,Bcl-2 ,Bax ,Bcl-x(L) ,apoptosis ,programmed cell death ,traumatic brain injury ,Bcl-xL ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
Background and Objectives: The injury burden after head trauma is exacerbated by secondary sequelae, which leads to further neuronal loss. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein and a key modulator of the programmed cell death (PCD) pathways. The current study evaluates the clinical evidence on Bcl-2 and neurological recovery in patients after traumatic brain injury (TBI). Materials and Methods: All studies in English were queried from the National Library of Medicine PubMed database using the following search terms: (B-cell lymphoma 2/Bcl-2/Bcl2) AND (brain injury/head injury/head trauma/traumatic brain injury) AND (human/patient/subject). There were 10 investigations conducted on Bcl-2 and apoptosis in TBI patients, of which 5 analyzed the pericontutional brain tissue obtained from surgical decompression, 4 studied Bcl-2 expression as a biomarker in the cerebrospinal fluid (CSF), and 1 was a prospective randomized trial. Results: Immunohistochemistry (IHC) in 94 adults with severe TBI showed upregulation of Bcl-2 in the pericontusional tissue. Bcl-2 was detected in 36-75% of TBI patients, while it was generally absent in the non-TBI controls, with Bcl-2 expression increased 2.9- to 17-fold in TBI patients. Terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick-end labeling (TUNEL) positivity for cell death was detected in 33-73% of TBI patients. CSF analysis in 113 TBI subjects (90 adults, 23 pediatric patients) showed upregulation of Bcl-2 that peaked on post-injury day 3 and subsequently declined after day 5. Increased Bcl-2 in the peritraumatic tissue, rising CSF Bcl-2 levels, and the variant allele of rs17759659 are associated with improved mortality and better outcomes on the Glasgow Outcome Score (GOS). Conclusions: Bcl-2 is upregulated in the pericontusional brain and CSF in the acute period after TBI. Bcl-2 has a neuroprotective role as a pro-survival protein in experimental models, and increased expression in patients can contribute to improvement in clinical outcomes. Its utility as a biomarker and therapeutic target to block neuronal apoptosis after TBI warrants further evaluation.
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- 2020
34. Polytrauma Is Associated with Increased Three- and Six-Month Disability after Traumatic Brain Injury: A TRACK-TBI Pilot Study.
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Yue, John K, Satris, Gabriela G, Dalle Ore, Cecilia L, Huie, J Russell, Deng, Hansen, Winkler, Ethan A, Lee, Young M, Vassar, Mary J, Taylor, Sabrina R, Schnyer, David M, Lingsma, Hester F, Puccio, Ava M, Yuh, Esther L, Mukherjee, Pratik, Valadka, Alex B, Ferguson, Adam R, Markowitz, Amy J, Okonkwo, David O, and Manley, Geoffrey T
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disability ,functional outcome ,outcome measure ,polytrauma ,traumatic brain injury ,Neurosciences ,Injury - Traumatic brain injury ,Clinical Research ,Injury - Trauma - (Head and Spine) ,Injury (total) Accidents/Adverse Effects ,Brain Disorders ,Rehabilitation ,Injuries and accidents - Abstract
Polytrauma and traumatic brain injury (TBI) frequently co-occur and outcomes are routinely measured by the Glasgow Outcome Scale-Extended (GOSE). Polytrauma may confound GOSE measurement of TBI-specific outcomes. Adult patients with TBI from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study had presented to a Level 1 trauma center after injury, received head computed tomography (CT) within 24 h, and completed the GOSE at 3 months and 6 months post-injury. Polytrauma was defined as an Abbreviated Injury Score (AIS) ≥3 in any extracranial region. Univariate regressions were performed using known GOSE clinical cutoffs. Multi-variable regressions were performed for the 3- and 6-month GOSE, controlling for known demographic and injury predictors. Of 361 subjects (age 44.9 ± 18.9 years, 69.8% male), 69 (19.1%) suffered polytrauma. By Glasgow Coma Scale (GCS) assessment, 80.1% had mild, 5.8% moderate, and 14.1% severe TBI. On univariate logistic regression, polytrauma was associated with increased odds of moderate disability or worse (GOSE ≤6; 3 month odds ratio [OR] = 2.57 [95% confidence interval (CI): 1.50-4.41; 6 month OR = 1.70 [95% CI: 1.01-2.88]) and death/severe disability (GOSE ≤4; 3 month OR = 3.80 [95% CI: 2.03-7.11]; 6 month OR = 3.33 [95% CI: 1.71-6.46]). Compared with patients with isolated TBI, more polytrauma patients experienced a decline in GOSE from 3 to 6 months (37.7 vs. 24.7%), and fewer improved (11.6 vs. 22.6%). Polytrauma was associated with greater univariate ordinal odds for poorer GOSE (3 month OR = 2.79 [95% CI: 1.73-4.49]; 6 month OR = 1.73 [95% CI: 1.07-2.79]), which was conserved on multi-variable ordinal regression (3 month OR = 3.05 [95% CI: 1.76-5.26]; 6 month OR = 2.04 [95% CI: 1.18-3.42]). Patients with TBI with polytrauma are at greater risk for 3- and 6-month disability compared with those with isolated TBI. Methodological improvements in assessing TBI-specific disability, versus disability attributable to all systemic injuries, will generate better TBI outcomes assessment tools.
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- 2020
35. Decreased DNA Methylation of RGMA is Associated with Intracranial Hypertension After Severe Traumatic Brain Injury: An Exploratory Epigenome-Wide Association Study
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Liu, Dongjing, Zusman, Benjamin E., Shaffer, John R., Li, Yunqi, Arockiaraj, Annie I., Liu, Shuwei, Weeks, Daniel E., Desai, Shashvat M., Kochanek, Patrick M., Puccio, Ava M., Okonkwo, David O., Conley, Yvette P., and Jha, Ruchira M.
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- 2022
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36. In Vivo Changes in Dynamic Adjacent Segment Motion 1 Year After One and Two-Level Cervical Arthrodesis
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LeVasseur, Clarissa M., Pitcairn, Samuel W., Okonkwo, David O., Kanter, Adam S., Shaw, Jeremy D., Donaldson, William F., Lee, Joon Y., and Anderst, William J.
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- 2022
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37. The Relationship Between Seizures and Spreading Depolarizations in Patients with Severe Traumatic Brain Injury
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Foreman, Brandon, Lee, Hyunjo, Okonkwo, David O., Strong, Anthony J., Pahl, Clemens, Shutter, Lori A., Dreier, Jens P., Ngwenya, Laura B., and Hartings, Jed A.
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- 2022
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38. Kickstand rods and correction of coronal malalignment in patients with adult spinal deformity
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Mundis, Jr., Gregory M., Walker, Corey T., Smith, Justin S., Buell, Thomas J., Lafage, Renaud, Shaffrey, Christopher I., Eastlack, Robert K., Okonkwo, David O., Bess, Shay, Lafage, Virginie, Uribe, Juan S., Lenke, Lawrence G., and Ames, Christopher P.
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- 2022
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39. Transport and retention of polybrominated diphenyl ether in landfill and e-waste contaminated soils: a laboratory-scale soil flushing approach
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Akortia, E. and Okonkwo, J. O.
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- 2022
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40. Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial
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Hergenroeder, Georgene W., Yokobori, Shoji, Choi, Huimahn Alex, Schmitt, Karl, Detry, Michelle A., Schmitt, Lisa H., McGlothlin, Anna, Puccio, Ava M., Jagid, Jonathan, Kuroda, Yasuhiro, Nakamura, Yukihiko, Suehiro, Eiichi, Ahmad, Faiz, Viele, Kert, Wilde, Elisabeth A., McCauley, Stephen R., Kitagawa, Ryan S., Temkin, Nancy R., Timmons, Shelly D., Diringer, Michael N., Dash, Pramod K., Bullock, Ross, Okonkwo, David O., Berry, Donald A., and Kim, Dong H.
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- 2022
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41. MEG-Derived Functional Tractography, Results for Normal and Concussed Cohorts
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Krieger, Don, Shepard, Paul, Schneider, Walter, Beers, Sue, Kontos, Anthony, Collins, Michael, and Okonkwo, David O.
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Quantitative Biology - Neurons and Cognition - Abstract
Measures of neuroelectric activity from each of 18 automatically identified white matter tracts were extracted from resting MEG recordings from a normative, n=588, and a chronic TBI, traumatic brain injury, n=63, cohort, 60 of whose TBIs were mild. Activity in the TBI cohort was significantly reduced compared with the norms for ten of the tracts, p < 10-6 for each. Significantly reduced activity (p < 10-3) was seen in more than one tract in seven mTBI individuals and one member of the normative cohort., Comment: 3 pages, 2 figures
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- 2018
42. Normative atlases of neuroelectric brain activity and connectivity from a large human cohort
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Krieger, Don, Shepard, Paul, and Okonkwo, David O.
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Quantitative Biology - Neurons and Cognition - Abstract
Magnetoencephalographic (MEG) recordings from a large normative cohort (n = 619) were processed to extract measures of regional neuroelectric activity. The overall objective of the effort was to use these measures to identify normative human neuroelectric brain function. The aims were (a) to identify and measure the values and range of those neuroelectric properties which are common to the cohort, (b) to identify and measure the values and range of those neuroelectric properties which distinguish one individual from another, and (c) to identify relationships of the measures to properties of the individual, e.g. sex, biological age, and sleep symptoms. It is hoped that comparison of the resultant established norms to measures from recordings of symptomatic individuals will enable advances is our understanding of pathology. MEG recordings during resting and task conditions were provided by The Cambridge (UK) Centre for Ageing and Neuroscience Stage 2 cohort study. Referee consensus processing was used to localize and validate neuroelectric currents, p < 10-12 for each, p < 10-4 for each when corrected for multiple comparisons. Comparisons of regional activity and connectivity within-subjects produced profuse reliable measures detailing differences between individuals, p < 10-8 for each comparison, p < 0.005 for each when corrected for a total of 5 x 105 comparisons. Cohort-wide regional comparisons (p < 10-8 for each) produced profuse measures which were common to the preponderance of individuals, detailing normative commonalities in brain function. Comparisons of regional gray matter (cellular) vs white matter (communication fibers) activity produced robust differences both cohort-wide and for each individual. These results validate the high spatial resolution of the results and establish the unprecedented ability to obtain neuroelectric measures from the white matter., Comment: 37 pages, 13 figures, 13 tables
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- 2018
43. Seemless Utilization of Heterogeneous XSede Resources to Accelerate Processing of a High Value Functional Neuroimaging Dataset
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Krieger, Don, Shepard, Paul, Zusman, Ben, Jana, Anirban, and Okonkwo, David O.
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Quantitative Biology - Neurons and Cognition - Abstract
We describe the technical effort used to process a voluminous high value human neuroimaging dataset on the Open Science Grid with opportunistic use of idle HPC resources to boost computing capacity more than 5-fold. With minimal software development effort and no discernable competitive interference with other HPC users, this effort delivered 15,000,000 core hours over 7 months., Comment: 8 pages, 10 figures, supplementary materials. Proceedings of the 2018 PEARC Conference, Practice & Experience in Advanced Research Computing, Pittsburgh, PA, July, 2018. arXiv admin note: substantial text overlap with arXiv:1710.05246. author note: The overlap with arXiv:1710.05246 is primarily in "background" material which includes a description of the solver and sample scientific findings
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- 2018
44. Shared High Value Research Resources: The CamCAN Human Lifespan Neuroimaging Dataset Processed on the Open Science Grid
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Krieger, Don, Shepard, Paul, Zusman, Ben, Jana, Anirban, and Okonkwo, David O.
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Quantitative Biology - Neurons and Cognition ,Computer Science - Distributed, Parallel, and Cluster Computing - Abstract
The CamCAN Lifespan Neuroimaging Dataset, Cambridge (UK) Centre for Ageing and Neuroscience, was acquired and processed beginning in December, 2016. The referee consensus solver deployed to the Open Science Grid was used for this task. The dataset includes demographic and screening measures, a high-resolution MRI scan of the brain, and whole-head magnetoencephalographic (MEG) recordings during eyes closed rest (560 sec), a simple task (540 sec), and passive listening/viewing (140 sec). The data were collected from 619 neurologically normal individuals, ages 18-87. The processed results from the resting recordings are completed and available online. These constitute 1.7 TBytes of data including the location within the brain (1 mm resolution), time stamp (1 msec resolution), and 80 msec time course for each of 3.7 billion validated neuroelectric events, i.e. mean 6.1 million events for each of the 619 participants. The referee consensus solver provides high yield (mean 11,000 neuroelectric currents/sec; standard deviation (sd): 3500/sec) high confidence (p < 10-12 for each identified current) measures of the neuroelectric currents whose magnetic fields are detected in the MEG recordings. We describe the solver, the implementation of the solver deployed on the Open Science Grid, the workflow management system, the opportunistic use of high performance computing (HPC) resources to add computing capacity to the Open Science Grid reserved for this project, and our initial findings from the recently completed processing of the resting recordings. This required 14 million core hours, i.e. 40 core hours per second of data., Comment: 8 pages, 7 figures; Proceedings of the 2017 IEEE International Conference on Bioinformatics and Biomedicine; Keynote to The International Workshop on High Throughput Computing in Bioinformatics and Biomedicine using the Open Science Grid
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- 2017
45. Diagnosing the GOSE: Structural and Psychometric Properties Using Item Response Theory, a TRACK-TBI Pilot Study
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Ranson, Jana, Magnus, Brooke E, Temkin, Nancy, Dikmen, Sureyya, Giacino, Joseph T, Okonkwo, David O, Valadka, Alex B, Manley, Geoffrey T, Nelson, Lindsay D, Cooper, Shelly R, Dams-O’Connor, Kristen, Gordon, Wayne A, Maas, Andrew IR, Menon, David K, Mukherjee, Pratik, Puccio, Ava M, Vassar, Mary J, Yue, John K, and Yuh, Esther L
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Brain Disorders ,Clinical Research ,Physical Injury - Accidents and Adverse Effects ,Traumatic Brain Injury (TBI) ,Traumatic Head and Spine Injury ,Neurosciences ,Mental health ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Brain Injuries ,Traumatic ,Female ,Glasgow Outcome Scale ,Humans ,Male ,Middle Aged ,Outcome Assessment ,Health Care ,Pilot Projects ,Psychometrics ,Young Adult ,Glasgow Outcome Scale-Extended ,item response theory ,outcome assessment ,psychometrics ,traumatic brain injury ,TRACK-TBI Investigators ,Glasgow Outcome Scale–Extended ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
The Glasgow Outcome Scale-Extended (GOSE) was designed to assess global outcome after traumatic brain injury (TBI). Since its introduction, several empirically founded criticisms of the GOSE have been raised, including poor reliability; an insensitivity to small, but potentially meaningful, changes; a tendency to produce ceiling effects; inconsistent associations with neurocognitive, psychological, and quality-of-life measures; and an inability to assess the multi-dimensional nature of TBI outcome. The current project took a diagnostic approach to identifying the underlying causes of reported limitations by exploring the internal construct validity of the GOSE at 3 and 6 months post-injury using item response theory (IRT) techniques. Data were from the TRACK-TBI Pilot Study, a large (N = 586), prospective, multi-site project that included TBI cases of all injury severity levels. To assess the level of latent functional "impairment" captured by GOSE items independent of the assigned outcome category or GOSE total score, items were modified so that higher scores reflected greater impairment. Results showed that although the GOSE's items capture varying levels of impairment across a broad disability spectrum at 3 and 6 months, there was also evidence at each time point of item redundancy (multiple items capturing similar levels of impairment), item deficiency (lack of items capturing lower levels of impairment), and item inefficiency (items only capturing minimal impairment information). The findings illustrate the value of IRT to illuminate strengths and weaknesses of clinical outcome assessment measures and provide a framework for future measure refinement.
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- 2019
46. Sleep disturbances precede depressive symptomatology following traumatic brain injury.
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Wickwire, Emerson M, Albrecht, Jennifer S, Griffin, Nicholas R, Schnyer, David M, Yue, John K, Markowitz, Amy J, Okonkwo, David O, Valadka, Alex B, Badjatia, Neeraj, and Manley, Geoffrey T
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Clinical and Health Psychology ,Biomedical and Clinical Sciences ,Psychology ,Behavioral and Social Science ,Depression ,Physical Injury - Accidents and Adverse Effects ,Neurosciences ,Clinical Research ,Traumatic Head and Spine Injury ,Traumatic Brain Injury (TBI) ,Brain Disorders ,Sleep Research ,Mental Health ,6.6 Psychological and behavioural ,Evaluation of treatments and therapeutic interventions ,Mental health ,Injuries and accidents ,TRACK-TBI Investigators - Abstract
The purpose of the present study was to evaluate the impact of sleep disturbances on subsequent depressive symptomatology among a representative sample of patients following traumatic brain injury (TBI). Within a retrospective cohort design, our sample included 305 individuals from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot; NINDS-OD09-004) database. At 3-months post-TBI, symptoms of insomnia were reported by 34% of patients, and symptoms of hypersomnia were reported by 39% of patients. For the vast majority of individuals, sleep complaints were likely to persist through 6-month follow-up. Symptoms of hypersomnia but not insomnia at three months were associated with worsened depressive symptomatology at six months. These results highlight the importance of sleep disturbances in recovery from TBI and suggest targeted sleep treatments as a pathway to improve outcomes and quality of life following TBI.
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- 2019
47. Consensus statement from the International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury
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Hutchinson, Peter J, Kolias, Angelos G, Tajsic, Tamara, Adeleye, Amos, Aklilu, Abenezer Tirsit, Apriawan, Tedy, Bajamal, Abdul Hafid, Barthélemy, Ernest J, Devi, B Indira, Bhat, Dhananjaya, Bulters, Diederik, Chesnut, Randall, Citerio, Giuseppe, Cooper, D Jamie, Czosnyka, Marek, Edem, Idara, El-Ghandour, Nasser MF, Figaji, Anthony, Fountas, Kostas N, Gallagher, Clare, Hawryluk, Gregory WJ, Iaccarino, Corrado, Joseph, Mathew, Khan, Tariq, Laeke, Tsegazeab, Levchenko, Oleg, Liu, Baiyun, Liu, Weiming, Maas, Andrew, Manley, Geoffrey T, Manson, Paul, Mazzeo, Anna T, Menon, David K, Michael, Daniel B, Muehlschlegel, Susanne, Okonkwo, David O, Park, Kee B, Rosenfeld, Jeffrey V, Rosseau, Gail, Rubiano, Andres M, Shabani, Hamisi K, Stocchetti, Nino, Timmons, Shelly D, Timofeev, Ivan, Uff, Chris, Ullman, Jamie S, Valadka, Alex, Waran, Vicknes, Wells, Adam, Wilson, Mark H, and Servadei, Franco
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Biomedical and Clinical Sciences ,Clinical Sciences ,Traumatic Brain Injury (TBI) ,Traumatic Head and Spine Injury ,Neurosciences ,Brain Disorders ,Physical Injury - Accidents and Adverse Effects ,Injuries and accidents ,Good Health and Well Being ,Brain Injuries ,Traumatic ,Consensus ,Decompressive Craniectomy ,Humans ,Intracranial Hypertension ,Neurosurgery ,Neurotrauma ,Decompression ,Cranioplasty ,Neurology & Neurosurgery ,Clinical sciences - Abstract
BackgroundTwo randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach.MethodsThe International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries.ResultsThe invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval.ConclusionsIn this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.
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- 2019
48. Age and sex-mediated differences in six-month outcomes after mild traumatic brain injury in young adults: a TRACK-TBI study.
- Author
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Yue, John K, Levin, Harvey S, Suen, Catherine G, Morrissey, Molly Rose, Runyon, Sarah J, Winkler, Ethan A, Puffer, Ross C, Deng, Hansen, Robinson, Caitlin K, Rick, Jonathan W, Phelps, Ryan RL, Sharma, Sourabh, Taylor, Sabrina R, Vassar, Mary J, Cnossen, Maryse C, Lingsma, Hester F, Gardner, Raquel C, Temkin, Nancy R, Barber, Jason, Dikmen, Sureyya S, Yuh, Esther L, Mukherjee, Pratik, Stein, Murray B, Cage, Tene A, Valadka, Alex B, Okonkwo, David O, Manley, Geoffrey T, and TRACK-TBI Investigators
- Subjects
TRACK-TBI Investigators ,Humans ,Brain Concussion ,Glasgow Outcome Scale ,Prospective Studies ,Pilot Projects ,Stress Disorders ,Post-Traumatic ,Wechsler Scales ,Age Factors ,Sex Characteristics ,Adolescent ,Adult ,Female ,Male ,Young Adult ,Age factors ,common data elements ,functional disability ,mild traumatic brain injury ,post-traumatic stress disorder ,risk factors ,sex ,young adults ,Behavioral and Social Science ,Traumatic Head and Spine Injury ,Physical Injury - Accidents and Adverse Effects ,Brain Disorders ,Traumatic Brain Injury (TBI) ,Mental Health ,Post-Traumatic Stress Disorder (PTSD) ,Prevention ,Clinical Research ,Neurosciences ,2.3 Psychological ,social and economic factors ,Aetiology ,Mental health ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
Introduction: Risk factors for young adults with mTBI are not well understood. Improved understanding of age and sex as risk factors for impaired six-month outcomes in young adults is needed. Methods: Young adult mTBI subjects aged 18-39 years (18-29y; 30-39y) with six-month outcomes were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Multivariable regressions were performed for outcomes with age, sex, and the interaction factor age-group*sex as variables of interest, controlling for demographic and injury variables. Mean-differences (B) and 95% CIs are reported. Results: One hundred mTBI subjects (18-29y, 70%; 30-39y, 30%; male, 71%; female, 29%) met inclusion criteria. On multivariable analysis, age-group*sex was associated with six-month post-traumatic stress disorder (PTSD; PTSD Checklist-Civilian version); compared with female 30-39y, female 18-29y (B= -19.55 [-26.54, -4.45]), male 18-29y (B= -19.70 [-30.07, -9.33]), and male 30-39y (B= -15.49 [-26.54, -4.45]) were associated with decreased PTSD symptomatology. Female sex was associated with decreased six-month functional outcome (Glasgow Outcome Scale-Extended (GOSE): B= -0.6 [1.0, -0.1]). Comparatively, 30-39y scored higher on six-month nonverbal processing speed (Wechsler Adult Intelligence Scale-Processing Speed Index (WAIS-PSI); B= 11.88, 95% CI [1.66, 22.09]). Conclusions: Following mTBI, young adults aged 18-29y and 30-39y may have different risks for impairment. Sex may interact with age for PTSD symptomatology, with females 30-39y at highest risk. These results may be attributable to cortical maturation, biological response, social modifiers, and/or differential self-report. Confirmation in larger samples is needed; however, prevention and rehabilitation/counseling strategies after mTBI should likely be tailored for age and sex.
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- 2019
49. Early and Late Reoperation Rates With Various MIS Techniques for Adult Spinal Deformity Correction
- Author
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Eastlack, Robert K, Srinivas, Ravi, Mundis, Gregory M, Nguyen, Stacie, Mummaneni, Praveen V, Okonkwo, David O, Kanter, Adam S, Anand, Neel, Park, Paul, Nunley, Pierce, Uribe, Juan S, Akbarnia, Behrooz A, Chou, Dean, and Deviren, Vedat
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Neurosciences ,reoperation ,minimally invasive surgery ,adult spinal deformity ,International Spine Study Group ,Clinical sciences - Abstract
Study designA multicenter retrospective review of an adult spinal deformity database.ObjectiveWe aimed to characterize reoperation rates and etiologies of adult spinal deformity surgery with circumferential minimally invasive surgery (cMIS) and hybrid (HYB) techniques.MethodsInclusion criteria were age ≥18 years, and one of the following: coronal Cobb >20°, sagittal vertical axis >5 cm, pelvic tilt >20°, and pelvic incidence-lumbar lordosis >10°. Patients with either cMIS or HYB surgery, ≥3 spinal levels treated with 2-year minimum follow-up were included.ResultsA total of 133 patients met inclusion for this study (65 HYB and 68 cMIS). Junctional failure (13.8%) was the most common reason for reoperation in the HYB group, while fixation failure was the most common reason in the cMIS group (14.7%). There was a higher incidence of proximal junctional failure (PJF) than distal junctional failure (DJF) within HYB (12.3% vs 3.1%), but no significant differences in PJF or DJF rates when compared to cMIS. Early (30 days) reoperations (cMIS = 26.5%; HYB = 27.7%), but early reoperations were more common in the HYB group after propensity matching, largely due to infection rates (10.8% vs 0%, P = .04).ConclusionsAdult spinal deformity correction with cMIS and HYB techniques result in overall reoperation rates of 27.9% and 33.8%, respectively, at minimum 2-year follow-up. Junctional failures are more common after HYB approaches, while pseudarthrosis/fixation failures happen more often with cMIS techniques. Early reoperations were less common than later returns to the operating room in both groups, but cMIS demonstrated less risk of infection and early reoperation when compared with the HYB group.
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- 2019
50. Testing a Multivariate Proteomic Panel for Traumatic Brain Injury Biomarker Discovery: A TRACK-TBI Pilot Study.
- Author
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Huie, J Russell, Diaz-Arrastia, Ramon, Yue, John K, Sorani, Marco D, Puccio, Ava M, Okonkwo, David O, Manley, Geoffrey T, Ferguson, Adam R, and TRACK-TBI Investigators
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TRACK-TBI Investigators ,Humans ,Inflammation ,Pilot Projects ,Proteomics ,Adolescent ,Adult ,Aged ,Middle Aged ,Female ,Male ,Young Adult ,Biomarkers ,Brain Injuries ,Traumatic ,TBI ,biomarkers ,proteomics ,Traumatic Brain Injury (TBI) ,Brain Disorders ,Physical Injury - Accidents and Adverse Effects ,Neurosciences ,Clinical Research ,Traumatic Head and Spine Injury ,4.1 Discovery and preclinical testing of markers and technologies ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Injuries and accidents ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
The complex and heterogeneous nature of traumatic brain injury (TBI) has rendered the identification of diagnostic and prognostic biomarkers elusive. A single acute biomarker may not be sufficient to categorize injury severity and/or predict outcome. Using multivariate dimension reduction analyses, we tested the sensitivity and specificity of a multi-analyte panel of proteins as an ensemble biomarker for TBI. Serum was collected within 24 h of injury in a cohort of 130 patients enrolled in the multi-center prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study and run on an array that measured 72 proteins. Using unsupervised principal components analysis, we first identified the subset of protein changes accounting for the most variance across patients. This yielded a group of 21 proteins that reflected an inverse relationship between inflammatory cytokines and regulators of anti-inflammation, and generated an individual inflammatory profile score for each patient. We then tested the association between these scores and computed tomography (CT) findings at hospital admission, as well as their prognostic association with functional recovery at 3 and 6 months (Glasgow Outcome Scale-Extended), and cognitive recovery at 6 months (California Verbal Learning Test, Second Edition) after injury. Inflammatory signatures were significantly increased in patients with positive CT findings, as well as in those who showed poor or incomplete recovery. Inflammation biomarker scores also showed significant sensitivity and specificity as a discriminator of these outcome measures (all areas under the curve [AUCs] >0.62). This proof of concept for the feasibility of multivariate biomarker identification demonstrates the prognostic validity of using a proteomic panel as a potential biomarker for TBI.
- Published
- 2019
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