204 results on '"M. Ross Bullock"'
Search Results
2. Diagnostic performance of point-of-care ubiquitin carboxy-terminal Hydrolase-L1 assay in distinguishing imaging abnormalities in traumatic brain injury: A TRACK-TBI cohort study
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Kevin K. Wang, Jennifer C. Munoz-Pareja, Lauren A. Lautenslager, J. Adrian Tyndall, Zhihui Yang, Maria R. Kerrigan, Ramon Diaz-Arrastia, Frederick K. Korley, David Okonkwo, Ava M. Puccio, John K. Yue, Sabrina R. Taylor, Pratik Mukherjee, Esther L. Yuh, Nancy R. Temkin, Claudia S. Robertson, Xiaoying Sun, Sonia Jain, Amy J. Markowitz, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J Claude Hemphill, Gillian Hotz, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Lindsay Nelson, Laura Ngwenya, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, and Ross Zafonte
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TBI ,Biomarkers ,UCH-L1 ,Point of care ,Mild TBI ,NSE ,Toxicology. Poisons ,RA1190-1270 ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 - Abstract
The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Phase 1 Cohort, enrolled 1375 TBI patients (GCS 3–15) presenting to one of 18 US Level I trauma centers within 24 h of injury who had an admission head CT; blood samples were collected, along with 122 orthopedic and 209 healthy controls. The TBI cohort consisted of 810 CT-negative (CT-) and 549 CT-positive (CT+) subjects. Of the CT- subjects who had MRIs, 121 were MRI-positive (MRI+) and 333 were MRI-negative (MRI-). UCH-L1 POC showed best diagnostic performance for CT + versus CT-, 0–8 h post-injury with an AUC of 0·779 [0·708–0.850] when compared to the 0–25 h interval, with an AUC of 0.684 [0.655–0.712]. NSE assay has an AUC of 0.695 [0.619–0.770] for the 0–8 h interval and 0.634 [0.603–0.665] for the 0–25 h interval. During the first 8 after injury, POC UCH-L1 outperforms NSE in identifying TBI patients with structural abnormalities on neuroimaging.
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- 2023
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3. Association between Cerebrospinal Fluid and Serum Biomarker Levels and Diagnosis, Injury Severity, and Short-Term Outcomes in Patients with Acute Traumatic Spinal Cord Injury
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Zhihui Yang, Seza Apiliogullari, Yueqiang Fu, Ayah Istanbouli, Sehajpreet Kaur, Iktej Singh Jabbal, Ahmed Moghieb, Zoha Irfan, Robert Logan Patterson, Milin Kurup, Lindsey Morrow, Michael Cohn, Zhiqun Zhang, Jiepei Zhu, Ronald L. Hayes, Helen M. Bramlett, M. Ross Bullock, W. Dalton Dietrich, Michael Y. Wang, Firas Kobeissy, and Kevin W. Wang
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spinal cord injury ,ASIA impairment scale ,American Spinal Injury Association ,biomarker ,injury severity ,diagnostic and prognostic markers ,Medicine (General) ,R5-920 - Abstract
Acute traumatic spinal cord injury (SCI) is recognized as a global problem that can lead to a range of acute and secondary complications impacting morbidity and mortality. There is still a lack of reliable diagnostic and prognostic biomarkers in patients with SCI that could help guide clinical care and identify novel therapeutic targets for future drug discovery. The aim of this prospective controlled study was to determine the cerebral spinal fluid (CSF) and serum profiles of 10 biomarkers as indicators of SCI diagnosis, severity, and prognosis to aid in assessing appropriate treatment modalities. CSF and serum samples of 15 SCI and ten healthy participants were included in the study. The neurological assessments were scored on admission and at discharge from the hospital using the American Spinal Injury Association Impairment Score (AIS) grades. The CSF and serum concentrations of SBDP150, S100B, GFAP, NF-L, UCHL-1, Tau, and IL-6 were significantly higher in SCI patients when compared with the control group. The CSF GBDP 38/44K, UCHL-L1, S100B, GFAP, and Tau levels were significantly higher in the AIS A patients. This study demonstrated a strong correlation between biomarker levels in the diagnosis and injury severity of SCI but no association with short-term outcomes. Future prospective controlled studies need to be done to support the results of this study.
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- 2023
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4. Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury
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Ashley K. Pringle, Elshadaie Solomon, Benjamin J. Coles, Brandon R. Desousa, Anan Shtaya, Shyam Gajavelli, Nedal Dabab, Malik J. Zaben, Diederik O. Bulters, M. Ross Bullock, and Aminul I. Ahmed
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cerebral cortex ,endogenous stem cells ,motor recovery ,sonic hedgehog ,traumatic brain injury ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability globally. No drug treatments are available, so interest has turned to endogenous neural stem cells (NSCs) as alternative strategies for treatment. We hypothesized that regulation of cell proliferation through modulation of the sonic hedgehog pathway, a key NSC regulatory pathway, could lead to functional improvement. We assessed sonic hedgehog (Shh) protein levels in the cerebrospinal fluid (CSF) of patients with TBI. Using the cortical contusion injury (CCI) model in rodents, we used pharmacological modulators of Shh signaling to assess cell proliferation within the injured cortex using the marker 5-Ethynyl-2?-deoxyuridine (EdU); 50mg/mL. The phenotype of proliferating cells was determined and quantified. Motor function was assessed using the rotarod test. In patients with TBI there is a reduction of Shh protein in CSF compared with control patients. In rodents, following a severe CCI, quiescent cells become activated. Pharmacologically modulating the Shh signaling pathway leads to changes in the number of newly proliferating injury-induced cells. Upregulation of Shh signaling with Smoothened agonist (SAG) results in an increase of newly proliferating cells expressing glial fibrillary acidic protein (GFAP), whereas the Shh signaling inhibitor cyclopamine leads to a reduction. Some cells expressed doublecortin (DCX) but did not mature into neurons. The SAG-induced increase in proliferation is associated with improved recovery of motor function. Localized restoration of Shh in the injured rodent brain, via increased Shh signaling, has the potential to sustain endogenous cell proliferation and the mitigation of TBI-induced motor deficits albeit without the neuronal differentiation.
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- 2021
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5. Feasibility of Human Neural Stem Cell Transplantation for the Treatment of Acute Subdural Hematoma in a Rat Model: A Pilot Study
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Shoji Yokobori, Kazuma Sasaki, Takahiro Kanaya, Yutaka Igarashi, Ryuta Nakae, Hidetaka Onda, Tomohiko Masuno, Satoshi Suda, Kota Sowa, Masataka Nakajima, Markus S. Spurlock, Lee Onn Chieng, Tom G. Hazel, Karl Johe, Shyam Gajavelli, Akira Fuse, M. Ross Bullock, and Hiroyuki Yokota
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traumatic brain injury ,acute subdural hematoma ,transplantation ,neural stem cell ,treatment ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Human neural stem cells (hNSCs) transplantation in several brain injury models has established their therapeutic potential. However, the feasibility of hNSCs transplantation is still not clear for acute subdural hematoma (ASDH) brain injury that needs external decompression. Thus, the aim of this pilot study was to test feasibility using a rat ASDH decompression model with two clinically relevant transplantation methods. Two different methods, in situ stereotactic injection and hNSC-embedded matrix seating on the brain surface, were attempted. Athymic rats were randomized to uninjured or ASDH groups (F344/NJcl-rnu/rnu, n = 7–10/group). Animals in injury group were subjected to ASDH, and received decompressive craniectomy and 1-week after decompression surgery were transplanted with green fluorescent protein (GFP)-transduced hNSCs using one of two approaches. Histopathological examinations at 4 and 8 weeks showed that the GFP-positive hNSCs survived in injured brain tissue, extended neurite-like projections resembling neural dendrites. The in situ transplantation group had greater engraftment of hNSCs than matrix embedding approach. Immunohistochemistry with doublecortin, NeuN, and GFAP at 8 weeks after transplantation showed that transplanted hNSCs remained as immature neurons and did not differentiate toward to glial cell lines. Motor function was assessed with rotarod, compared to control group (n = 10). The latency to fall from the rotarod in hNSC in situ transplanted rats was significantly higher than in control rats (median, 113 s in hNSC vs. 69 s in control, P = 0.02). This study first demonstrates the robust engraftment of in situ transplanted hNSCs in a clinically-relevant ASDH decompression rat model. Further preclinical studies with longer study duration are warranted to verify the effectiveness of hNSC transplantation in amelioration of TBI induced deficits.
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- 2019
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6. The Cost of Gun Shot Wounds to the Head: An unevenly distributed burden
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Nathan Schoen, David Matichak, Valerie Armstrong, Shaina Sedighim, Emma Lew, Jonathan Jagid, M. Ross Bullock, and Angela Richardson
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Surgery ,Neurology (clinical) - Abstract
Despite the significant clinical consequences and socioeconomic costs of gun-shot wounds to the head (GSWH), studies examining pre-hospital risk factors, geo-spatial patterns, and economic cost are lacking.A retrospective analysis was performed for GSWH patients (single or multiple injuries) presenting to the level one Ryder Trauma Center (hospital patients) as well as the Miami Dade County Medical Examiner (ME) Department, from October 2013 to October 2015. Additionally, ME data was queried from the previous decade (2008-2017) to analyze longitudinal trends.402 consecutive cases met inclusion criteria: 297 (74%) presented to the ME and 105 (26%) presented to the hospital. GSWH in our cohort had a case fatality rate of 89%, predominantly afflicting males, Caucasians, and victims of suicide, with a mean age of 41.9 ± 20.6 years. Hospital patients were more likely to be Black males from low socioeconomic (SES) regions involved in assault. Older, Caucasian males were overrepresented in patients attempting and completing suicide, thus comprised a higher percentage of ME cases. Geo-spatial analysis of hospital patient injury zip-codes illustrates GSWH are significantly clustered in low-income urban centers with greater poverty rates. In Miami-Dade County, the economic burden of GSWH, as measured by total healthcare costs and lifetime productivity losses, was estimated to be $11,867,415 and $246,179,498 respectively.In the first analysis of GSWH with the inclusion of both hospital and ME data in a representative urban setting, our findings demonstrate pre-hospital risk factors and the unequal distribution of the significant economic costs of GSWH.
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- 2022
7. Life After Mild Traumatic Brain Injury: Widespread Structural Brain Changes Associated With Psychological Distress Revealed With Multimodal Magnetic Resonance Imaging
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Francesca Sibilia, Rachel M. Custer, Andrei Irimia, Farshid Sepehrband, Arthur W. Toga, Ryan P. Cabeen, Opeolu Adeoye, Neeraj Badjatia, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Laura B. Ngwenya, Florence Noel, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, and Ross Zafonte
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General Medicine - Published
- 2022
8. A Panel of CSF and Serum Biomarkers Reflecting Injury Severity and Outcome in a Human Spinal Cord Injury Study
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Lindsey Morrow, Milin Kurup, M. Ross Bullock, Ronald L. Hayes, Zhiqun Zhang, Zhihui Yang, Ayah Istanbouli, Sehajpreet Kaur, Helen M. Bramlett, Kevin K. W. Wang, Zoha Irfan, Jiepei Zhu, Iktej Singh Jabbal, Michael Wang, Michael Cohn, Yueqiang Fu, Ahmed Moghieb, Samuel J. Ruiz, Robert Logan Patterson, and W. Dalton Dietrich
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Oncology ,medicine.medical_specialty ,Serum biomarkers ,business.industry ,Internal medicine ,medicine ,macromolecular substances ,medicine.disease ,business ,Spinal cord injury - Abstract
Acute spinal cord injury (SCI) results in catastrophic neurological impairment. We aimed to examine the temporal profile and severity correlation of biomarkers, and their relationship with the American Spinal Injury Association Scale (AIS) improvement in human SCI. 15 SCI and 10 non-SCI healthy subjects were classified according to the initial and discharge AIS grade. Serial cerebrospinal fluid (CSF) and serum samples were collected. Spectrin breakdown products (SBDP) 150, SBDP145, glial fibrillary acidic protein (GFAP), and GFAP breakdown product (GBDP) 38/44K were found to be elevated in the acute phase CSF samples in SCI patients on immunoblotting. SBDP150, ubiquitin C-terminal hydrolase-L1 (UCH-L1), GFAP, S100B, neurofilament light chain protein (NF-L), Tau & interleukin (IL) -6 were elevated in the acute phase CSF and serum samples on ELISA. CSF SBDP150, UCH-L1, GFAP, S100B and Tau were seen to peak on day 1 after injury, while CSF IL-6 and NF-L peaked on day 5. Serum SBDP150, IL-6, S100B, GFAP, UCHL-1 and Tau peaked on day 1, while serum NF-L peaked on day 5 post-injury. CSF alpha II-spectrin, SBDP150/145, and GBDP 44-38K levels (by immunoblots), CSF SBDP150, S100B, GFAP, UCHL-1 and Tau (ELISA) and serum UCHL-1 and Tau (ELISA) at specific time points showed SCI severity-correlation. CSF SBDP150, GFAP, and Tau and serum UCHL-1 and Tau (ELISA) were seen to have the best correlation with the severity at discharge. Receiver Operating Characteristic Curve analysis showed that CSF and serum biomarkers (SBDP150, IL-6, S100B, GFAP, NF-L, UCHL-1 and Tau) were associated with the severity of SCI.
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- 2021
9. Pathobiology of Traumatic Brain Injury
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Liesl N. Close, Liz. Quesada, and M. Ross Bullock
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Pathology ,medicine.medical_specialty ,Traumatic brain injury ,business.industry ,medicine ,medicine.disease ,business - Published
- 2021
10. Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study
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Opeolu Adeoye, Neeraj Badjatia, Amber Nolan, Dana P. Goldman, Christopher J. Lindsell, Thomas W. McAllister, Seth A. Seabury, Alex B. Valadka, Joel H. Kramer, Joan Machamer, Raquel C. Gardner, Gabriella Satris, Brandon Foreman, Geoffrey T. Manley, Arthur W. Toga, David O. Okonkwo, Ann-Christine Duhaime, Randall Merchant, C. Dirk Keene, Gillian Hotz, Alastair J. Martin, Jonathan Rosand, David M. Schnyer, Michael McCrea, Murray B. Stein, John K. Yue, Sabrina R Taylor, Claudia S. Robertson, Étienne Gaudette, Kevin K.W. Wang, Laura B. Ngwenya, Natalie Kreitzer, M. Ross Bullock, Rao P. Gullapalli, Shankar P. Gopinath, Lindsay D. Nelson, Yelena G. Bodien, J. Claude Hemphill, Karen Crawford, John D. Corrigan, Amy J. Markowitz, Joseph T. Giacino, Mark Sherer, Richard G. Ellenbogen, Christopher J. Madden, Daniel P. Perl, Ross Zafonte, Miri Rabinowitz, V. Ramana Feeser, Mary J. Vassar, Track-Tbi Investigators, Esther L. Yuh, Sureyya Dikmen, Florence Noel, Nancy R. Temkin, Kim Boase, Jason Barber, Angelle M. Sander, Harvey S. Levin, Frederick K. Korley, Luis Gonzalez, Randall M. Chesnut, Eva M. Palacios, Pratik Mukherjee, Adam R. Ferguson, Ava M. Puccio, Ramon Diaz-Arrastia, and Sonia Jain
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Moderate to severe ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Traumatic brain injury ,Glasgow Outcome Scale ,Neuropsychological Tests ,Cohort Studies ,Disability Evaluation ,Interquartile range ,Activities of Daily Living ,Brain Injuries, Traumatic ,Medicine ,Humans ,In patient ,Glasgow Coma Scale ,Longitudinal Studies ,Prospective Studies ,Cause of death ,Original Investigation ,business.industry ,Persistent Vegetative State ,Disability Rating Scale ,Recovery of Function ,Middle Aged ,medicine.disease ,Prognosis ,Treatment Outcome ,Withholding Treatment ,Female ,Neurology (clinical) ,business ,Cohort study - Abstract
Importance Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. Objective To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. Design, Setting, and Participants This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. Exposures Moderate or severe TBI. Main Outcomes and Measures The Glasgow Outcome Scale–Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. Results A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. Conclusions and Relevance In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.
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- 2021
11. Potential of Human Neural Stem Cell Transplantation to Treat Acute Subdural Hematoma
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Markus S. Spurlock, Shoji Yokobori, Karl Johe, Shyam Gajavelli, Tom Hazel, Lee Onn Chieng, and M. Ross Bullock
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Transplantation ,medicine.medical_specialty ,business.industry ,medicine ,Surgery ,Neurology (clinical) ,business ,Acute subdural hematoma ,Neural stem cell - Published
- 2019
12. Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations
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J. Russell Huie, Stefania Mondello, Christopher J. Lindsell, Luca Antiga, Esther L. Yuh, Elisa R. Zanier, Serge Masson, Bedda L. Rosario, Adam R. Ferguson, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Sonia Jain, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, David Okonkwo, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, David Schnyer, Seth Seabury, Murray Stein, Sabrina Taylor, Nancy Temkin, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, Ross Zafonte, Cecilia Ackerlund, Hadie Adams, Vanni Agnoletti, Judith Allanson, Krisztina Amrein, Norberto Andaluz, Nada Andelic, Lasse Andreassen, Audny Anke, Azasevac Antun, Anna Antoni, Hilko Ardon, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Camelia Baciu, Rafael Badenes, Ronald Bartels, Pál Barzó, Ursula Bauerfeind, Romuald Beauvais, Ronny Beer, Francisco Javier Belda, Bo Michael Bellander, Antonio Belli, Rémy Bellier, Habib Benali, Thierry Benard, Maurizio Berardino, Luigi Beretta, Christopher Beynon, Federico Bilotta, Harald Binder, Erta Biqiri, Morten Blaabjerg, Hugo den Boogert, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Lozano Guillermo Carbayo, Marco Carbonara, Elsa Carise, K. Carpenter, Ana M. Castaño León, Francesco Causin, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Maryse Cnossen, Mark Coburn, Jonathan Coles, Lizzie Coles-Kemp, Johnny Collett, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot Fizelier, François Damas, Pierre Damas, Helen Dawes, Véronique De Keyser, Francesco Della Corte, Bart Depreitere, Godard C.W. de Ruiter, Dula Dilvesi, Shenghao Ding, Diederik Dippel, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy Loup Dulière, Heiko Engemann, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Junfeng Feng, Kelly Foks, Francesca Fossi, Gilles Francony, Ulderico Freo, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Karin Geleijns, Pradeep George, Alexandre Ghuysen, Lelde Giga, Benoit Giraud, Ben Glocker, Jagos Golubovic, Pedro A. Gomez, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Asta Kristine Håberg, Bram Jacobs, Iain Haitsma, Jed A. Hartings, Raimund Helbok, Eirik Helseth, Daniel Hertle, Astrid Hoedemaekers, Stefan Hoefer, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Stefan Jankowski, Mike Jarrett, Bojan Jelaca, Ji yao Jiang, Kelly Jones, Konstantinos Kamnitsas, Mladen Karan, Ari Katila, Maija Kaukonen, Thomas Kerforne, Riku Kivisaari, Angelos G. Kolias, Bálint Kolumbán, Erwin Kompanje, Ksenija Kolundzija, Daniel Kondziella, Lars Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Christian Ledig, Rolf Lefering, Valerie Legrand, Jin Lei, Leon Levi, Roger Lightfoot, Hester Lingsma, Dirk Loeckx, Angels Lozano, Andrew I.R. Maas, Stephen MacDonald, Marc Maegele, Majdan Marek, Sebastian Major, Alex Manara, Geoffrey Manley, Didier Martin, Leon Francisco Martin, Costanza Martino, Hugues Maréchal, Armando Maruenda, Alessandro Masala, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Cristina Morganti Kossmann, Davide Mulazzi, Holger Mühlan, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, Quentin Noirhomme, József Nyirádi, Mauro Oddo, Annemarie Oldenbeuving, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Adriana Patruno, Jean François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Floury Sébastien Pili, Matti Pirinen, Horia Ples, Maria Antonia Poca, Suzanne Polinder, Inigo Pomposo, Jussi Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Veronika Rehorčíková, Jonathan Rhodes, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Gerwin Roks, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Marco Sacchi, Barbara Sahakian, Juan Sahuquillo, Oliver Sakowitz, Francesca Sala, Renan Sanchez Porras, Janos Sandor, Edgar Santos, Luminita Sasu, Davide Savo, Nadine Schäffer, Inger Schipper, Barbara Schlößer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Michael Schöll, Charlie Sewalt, Özcan Sir, Toril Skandsen, Lidwien Smakman, Dirk Smeets, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Nicole Steinbüchel, Ana Stevanovic, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Fabio Silvio Taccone, Riikka Takala, Viktória Tamás, Päivi Tanskanen, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Ralph Telgmann, Guido Teodorani, Alice Theadom, Matt Thomas, Dick Tibboel, Christos Tolias, Jean Flory Luaba Tshibanda, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Gregory Van der Steen, Mathieu van der Jagt, JV de Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Julia Van Waesberghe, Audrey Vanhaudenhuyse, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Giacinta Vizzino, Carmen Vleggeert Lankamp, Victor Volovici, Daphne Voormolen, Peter Vulekovic, Zoltán Vámos, Derick Wade, Kevin K.W. Wang, Lei Wang, Lars Wessels, Eveline Wiegers, Eno Wildschut, Guy Williams, Lindsay Wilson, Maren K.L. Winkler, Stefan Wolf, Peter Ylén, Alexander Younsi, Menashe Zaaroor, Frederik Zeiler, Yang Zhihui, Agate Ziverte, Fabrizio Zumbo, Huie, J Russell, Mondello, Stefania, Lindsell, Christopher J, Antiga, Luca, Yuh, Esther L, Zanier, Elisa R, Masson, Serge, Rosario, Bedda L, Ferguson, Adam R (Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators), Beretta, Luigi, Huie, J, Mondello, S, Lindsell, C, Antiga, L, Yuh, E, Zanier, E, Masson, S, Rosario, B, Ferguson, A, Citerio, G, and Molecular Neuroscience and Ageing Research (MOLAR)
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Traumatic ,030506 rehabilitation ,Data Interpretation ,Data management ,data sharing ,TERMINAL HYDROLASE-L1 ,Big data ,Poison control ,0302 clinical medicine ,Brain Injuries, Traumatic ,TBI ,Medicine ,Biomarker discovery ,Common Data Elements ,traumatic brain injury ,Injuries and accidents ,Statistical ,Reference Standards ,NET RECLASSIFICATION INDEX ,Data Interpretation, Statistical ,Biomarker (medicine) ,biomarker ,0305 other medical science ,Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators ,CT ,The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators ,medicine.medical_specialty ,Physical Injury - Accidents and Adverse Effects ,Clinical Sciences ,Context (language use) ,Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0] ,Traumatic Brain Injury (TBI) ,Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators ,03 medical and health sciences ,MICROARRAY ,Special Section: Statistical Methods in Tbi Research ,Humans ,biomarkers ,Intensive care medicine ,Traumatic Head and Spine Injury ,Neurology & Neurosurgery ,business.industry ,Information Dissemination ,OUTCOME PREDICTION ,Neurosciences ,COMMON DATA ELEMENTS ,Precision medicine ,Brain Disorders ,DIFFUSE AXONAL INJURY ,Data sharing ,Good Health and Well Being ,Brain Injuries ,DISCOVERY ,TRACK ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Contains fulltext : 238746.pdf (Publisher’s version ) (Closed access) Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.
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- 2021
13. Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months after Mild Traumatic Brain Injury
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Murray B. Stein, Esther Yuh, Sonia Jain, David O. Okonkwo, Christine L. Mac Donald, Harvey Levin, Joseph T. Giacino, Sureyya Dikmen, Mary J. Vassar, Ramon Diaz-Arrastia, Claudia S. Robertson, Lindsay D. Nelson, Michael McCrea, Xiaoying Sun, Nancy Temkin, Sabrina R. Taylor, Amy J. Markowitz, Geoffrey T. Manley, Pratik Mukherjee, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur Toga, Alex Valadka, Paul Vespa, Kevin Wang, John K. Yue, and Ross Zafonte
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Traumatic brain injury ,Cognitive Neuroscience ,Hippocampus ,behavioral disciplines and activities ,Amygdala ,050105 experimental psychology ,Article ,Stress Disorders, Post-Traumatic ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,Biological Psychiatry ,Brain Concussion ,Cognitive reserve ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Glasgow Coma Scale ,Brain ,Magnetic resonance imaging ,Emergency department ,medicine.disease ,medicine.anatomical_structure ,Anesthesia ,Neurology (clinical) ,business ,Insula ,030217 neurology & neurosurgery - Abstract
Background Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. Methods Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13–15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. Results Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. Conclusions Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.
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- 2020
14. Sonic Hedgehog signalling promotes perilesion cell proliferation and functional improvement following cortical contusion injury
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Brandon R. Desousa, M. Ross Bullock, Diederik Bulters, Elshadaie Solomon, Shyam Gajavelli, Ashley K. Pringle, Benjamin J. Coles, Malik Zaben, Anan Shtaya, Aminul I. Ahmed, and Nedal Dabab
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animal structures ,Cyclopamine ,chemistry.chemical_compound ,sonic hedgehog ,medicine ,Sonic hedgehog ,biology ,Glial fibrillary acidic protein ,business.industry ,traumatic brain injury ,General Medicine ,Neural stem cell ,Hedgehog signaling pathway ,Doublecortin ,Cell biology ,endogenous stem cells ,motor recovery ,medicine.anatomical_structure ,chemistry ,nervous system ,Cerebral cortex ,biology.protein ,cerebral cortex ,Original Article ,Smoothened ,business - Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability globally. No drug treatments are available, so interest has turned to endogenous neural stem cells (NSCs) as alternative strategies for treatment. We hypothesized that regulation of cell proliferation through modulation of the sonic hedgehog pathway, a key NSC regulatory pathway, could lead to functional improvement. We assessed sonic hedgehog (Shh) protein levels in the cerebrospinal fluid (CSF) of patients with TBI. Using the cortical contusion injury (CCI) model in rodents, we used pharmacological modulators of Shh signaling to assess cell proliferation within the injured cortex using the marker 5-Ethynyl-2’-deoxyuridine (EdU); 50mg/mL. The phenotype of proliferating cells was determined and quantified. Motor function was assessed using the rotarod test. In patients with TBI there is a reduction of Shh protein in CSF compared with control patients. In rodents, following a severe CCI, quiescent cells become activated. Pharmacologically modulating the Shh signaling pathway leads to changes in the number of newly proliferating injury-induced cells. Upregulation of Shh signaling with Smoothened agonist (SAG) results in an increase of newly proliferating cells expressing glial fibrillary acidic protein (GFAP), whereas the Shh signaling inhibitor cyclopamine leads to a reduction. Some cells expressed doublecortin (DCX) but did not mature into neurons. The SAG-induced increase in proliferation is associated with improved recovery of motor function. Localized restoration of Shh in the injured rodent brain, via increased Shh signaling, has the potential to sustain endogenous cell proliferation and the mitigation of TBI-induced motor deficits albeit without the neuronal differentiation.
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- 2020
15. Prognostic Value of Spreading Depolarizations in Patients With Severe Traumatic Brain Injury
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Jason M. Hinzman, Anthony J. Strong, David O. Okonkwo, Bruce E. Mathern, M. Ross Bullock, Clemens Pahl, Brandon Foreman, J. Adam Wilson, Norberto Andaluz, Jed A. Hartings, Jens P. Dreier, Ava M. Puccio, Laura B. Ngwenya, Lori Shutter, Achala Vagal, Laura Pahren, Hester F. Lingsma, and Public Health
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Adult ,Male ,Subarachnoid hemorrhage ,Traumatic brain injury ,Action Potentials ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Intensive care ,Brain Injuries, Traumatic ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Prospective cohort study ,Electrocorticography ,Aged ,Original Investigation ,medicine.diagnostic_test ,business.industry ,Cortical Spreading Depression ,Brain ,Middle Aged ,Prognosis ,medicine.disease ,Cortical spreading depression ,Anesthesia ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Importance Advances in treatment of traumatic brain injury are hindered by the inability to monitor pathological mechanisms in individual patients for targeted neuroprotective treatment. Spreading depolarizations, a mechanism of lesion development in animal models, are a novel candidate for clinical monitoring in patients with brain trauma who need surgery. Objective To test the null hypothesis that spreading depolarizations are not associated with worse neurologic outcomes. Design, Setting, and Participants This prospective, observational, multicenter cohort study was conducted from February 2009 to August 2013 in 5 level 1 trauma centers. Consecutive patients who required neurological surgery for treatment of acute brain trauma and for whom research consent could be obtained were enrolled; participants were excluded because of technical problems in data quality, patient withdrawal, or loss to follow-up. Primary statistical analysis took place from April to December 2018. Evaluators of outcome assessments were blinded to other measures. Interventions A 6-contact electrode strip was placed on the brain surface during surgery for continuous electrocorticography during intensive care. Main Outcomes and Measures Electrocorticography was scored for depolarizations, following international consensus procedures. Six-month outcomes were assessed by the Glasgow Outcome Scale–Extended score. Results A total of 157 patients were initially enrolled; 19 were subsequently excluded. The 138 remaining patients (104 men [75%]; median [interquartile range] age, 45 [29-64] years) underwent a median (interquartile range) of 75.5 (42.2-117.1) hours of electrocorticography. A total of 2837 spreading depolarizations occurred in 83 of 138 patients (60.1% incidence) who, compared with patients who did not have spreading depolarizations, had lower prehospital systolic blood pressure levels (mean [SD], 133 [31] mm Hg vs 146 [33] mm Hg;P = .03), more traumatic subarachnoid hemorrhage (depolarization incidences of 17 of 37 [46%], 18 of 32 [56%], 22 of 33 [67%], and 23 of 30 patients [77%] for Morris-Marshall Grades 0, 1, 2, and 3/4, respectively;P = .047), and worse radiographic pathology (in 38 of 73 patients [52%] and 42 of 60 patients [70%] for Rotterdam Scores 2-4 vs 5-6, respectively;P = .04). Of patients with depolarizations, 32 of 83 (39%) had only sporadic events that induced cortical spreading depression of spontaneous electrical activity, whereas 51 of 83 patients (61%) exhibited temporal clusters of depolarizations (≥3 in a 2-hour span). Nearly half of those with clusters (23 of 51 [45%]) also had depolarizations in an electrically silent area of the cortex (isoelectric spreading depolarization). Patients with clusters did not improve in motor neurologic examinations from presurgery to postelectrocorticography, while other patients did improve. In multivariate ordinal regression adjusting for baseline prognostic variables, the occurrence of depolarization clusters had an odds ratio of 2.29 (95% CI, 1.13-4.65;P = .02) for worse outcomes. Conclusions and Relevance In this cohort study of patients with acute brain trauma, spreading depolarizations were predominant but heterogeneous and independently associated with poor neurologic recovery. Monitoring the occurrence of spreading depolarizations may identify patients most likely to benefit from targeted management strategies.
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- 2020
16. Development and assessment of competency-based neurotrauma course curriculum for international neurosurgery residents and neurosurgeons
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José Fernández-Alén, M. Ross Bullock, Michael Bierschneider, Andres M. Rubiano, Gregory W.J. Hawryluk, Francesco Biroli, Michael Cunningham, Aurelia Peraud, Maya A. Babu, Christian Matula, Sergio A. Calero-Martinez, and Rubiano, Andrés M. [0000-0001-8931-3254]
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Standardization ,Psychological intervention ,Neurosurgery ,Neurosurgical Procedures ,030218 nuclear medicine & medical imaging ,Project manager ,Likert scale ,Education ,03 medical and health sciences ,0302 clinical medicine ,Cursos ,Continuing medical education ,Humans ,Neurocirujanos ,Curriculum ,Disease burden ,Competence-based ,Medical education ,Internship and Residency ,General Medicine ,Guía de estudio ,Neurosurgeons ,Surgery ,Education, Medical, Continuing ,Neurology (clinical) ,Faculty development ,Psychology ,Neurotrauma ,030217 neurology & neurosurgery - Abstract
OBJECTIVETraumatic brain injuries (TBIs) are a significant disease burden worldwide. It is imperative to improve neurosurgeons’ training during and after their medical residency with appropriate neurotrauma competencies. Unfortunately, the development of these competencies during neurosurgeons’ careers and in daily practice is very heterogeneous. This article aimed to describe the development and evaluation of a competency-based international course curriculum designed to address a broad spectrum of needs for taking care of patients with neurotrauma with basic and advanced interventions in different scenarios around the world.METHODSA committee of 5 academic neurosurgeons was involved in the task of building this course curriculum. The process started with the identification of the problems to be addressed and the subsequent performance needed. After this, competencies were defined. In the final phase, educational activities were designed to achieve the intended learning outcomes. In the end, the entire process resulted in competency and outcomes-based education strategy, including a definition of all learning activities and learning outcomes (curriculum), that can be integrated with a faculty development process, including training. Further development was completed by 4 additional academic neurosurgeons supported by a curriculum developer specialist and a project manager. After the development of the course curriculum, template programs were developed with core and optional content defined for implementation and evaluation.RESULTSThe content of the course curriculum is divided into essentials and advanced concepts and interventions in neurotrauma care. A mixed sample of 1583 neurosurgeons and neurosurgery residents attending 36 continuing medical education activities in 30 different cities around the world evaluated the course. The average satisfaction was 97%. The average usefulness score was 4.2, according to the Likert scale.CONCLUSIONSAn international competency-based course curriculum is an option for creating a well-accepted neurotrauma educational process designed to address a broad spectrum of needs that a neurotrauma practitioner faces during the basic and advanced care of patients in different regions of the world. This process may also be applied to other areas of the neurosurgical knowledge spectrum. Moreover, this process allows worldwide standardization of knowledge requirements and competencies, such that training may be better benchmarked between countries regardless of their income level.
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- 2020
17. Levels of caspase-1 in cerebrospinal fluid of patients with traumatic brain injury: correlation with intracranial pressure and outcome
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Catalina Crespí, Osman Salazar, M. Ross Bullock, Juan Antonio Llompart-Pou, Jon Pérez-Bárcena, Javier Ibáñez, Juan Pablo de Rivero Vaccari, Victor Goliney, and Guillem Frontera
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Traumatic brain injury ,Inflammasomes ,Caspase 1 ,Intracranial Hypotension ,Nerve Tissue Proteins ,Gastroenterology ,Cerebral Ventricles ,Ventriculostomy ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Cerebrospinal fluid ,Internal medicine ,Brain Injuries, Traumatic ,medicine ,Humans ,In patient ,Prospective Studies ,Intracranial pressure ,Aged ,Aged, 80 and over ,business.industry ,Area under the curve ,General Medicine ,Middle Aged ,medicine.disease ,Immunity, Innate ,Treatment Outcome ,030220 oncology & carcinogenesis ,Area Under Curve ,Cohort ,Drainage ,Female ,Intracranial Hypertension ,business ,030217 neurology & neurosurgery ,External ventricular drain - Abstract
OBJECTIVE The objectives of this study were to evaluate levels of inflammasome-signaling proteins in serum and CSF of patients with traumatic brain injury (TBI), and to correlate these protein levels with intracranial pressure (ICP) and clinical outcomes at 6 months after injury. METHODS This is a prospective and observational study in patients with moderate and severe TBI who required an external ventricular drain as part of their treatment. Serum and CSF samples were collected 3 times a day for the first 5 days after TBI. The authors have determined the protein concentration of caspase-1 in the CSF and serum of patients with TBI by using commercially available enzyme-linked immunosorbent assays. The ICP value was recorded hourly. The 6-month outcome was assessed using the Glasgow Outcome Scale–Extended. RESULTS A total of 21 patients were included in this study, and a total of 234 paired serum-CSF samples were analyzed. The area under the curve (AUC) value of caspase-1 in CSF during the 5-day period was 2452.9 pg/mL·hr in the group of patients with high ICP vs 617.6 pg/mL·hr in the patients with low ICP. The differences were mainly on day 2 (19.7 pg/mL vs 1.8 pg/mL; p = 0.06) and day 3 (13.9 pg/mL vs 1 pg/mL; p = 0.05). The AUC value of caspase in CSF during the 5-day period was 1918.9 pg/mL·hr in the group of patients with poor outcome versus 924.5 pg/mL·hr in the patients with good outcome. The protein levels of caspase-1 in CSF were higher in patients with unfavorable outcomes during the first 96 hours after TBI. CONCLUSIONS In this cohort of patients with TBI who were admitted to the neurosurgical ICU, the inflammasome protein caspase-1 is increased in the CSF of patients with high ICP, especially on days 2 and 3 after TBI. Also the protein levels of caspase-1 in CSF were higher in patients with poor outcome during the first 96 hours after TBI. Moreover, not only the absolute value of caspase-1 in CSF but also its trend is associated with poor outcomes.
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- 2019
18. Microglial Inflammasome Activation in Penetrating Ballistic-Like Brain Injury
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Shyam Gajavelli, Markus S. Spurlock, Cody B Andreoni, M. Ross Bullock, Robert W. Keane, W. Dalton Dietrich, Juan Pablo de Rivero Vaccari, and Stephanie W. Lee
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Male ,0301 basic medicine ,Inflammasomes ,Traumatic brain injury ,Inflammation ,Inhibitor of apoptosis ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Brain Injuries, Traumatic ,medicine ,Animals ,Head Injuries, Penetrating ,Microglia ,Chemistry ,Pyroptosis ,Interleukin ,Inflammasome ,Original Articles ,medicine.disease ,Rats ,Cell biology ,XIAP ,030104 developmental biology ,medicine.anatomical_structure ,Neurology (clinical) ,medicine.symptom ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Penetrating traumatic brain injury (PTBI) is a significant cause of death and disability in the United States. Inflammasomes are one of the key regulators of the interleukin (IL)-1β mediated inflammatory responses after traumatic brain injury. However, the contribution of inflammasome signaling after PTBI has not been determined. In this study, adult male Sprague-Dawley rats were subjected to sham procedures or penetrating ballistic-like brain injury (PBBI) and sacrificed at various time-points. Tissues were assessed by immunoblot analysis for expression of IL-1β, IL-18, and components of the inflammasome: apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, X-linked inhibitor of apoptosis protein (XIAP), nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3), and gasdermin-D (GSDMD). Specific cell types expressing inflammasome proteins also were evaluated immunohistochemically and assessed quantitatively. After PBBI, expression of IL-1β, IL-18, caspase-1, ASC, XIAP, and NLRP3 peaked around 48 h. Brain protein lysates from PTBI animals showed pyroptosome formation evidenced by ASC laddering, and also contained increased expression of GSDMD at 48 h after injury. ASC-positive immunoreactive neurons within the perilesional cortex were observed at 24 h. At 48 h, ASC expression was concentrated in morphologically activated cortical microglia. This expression of ASC in activated microglia persisted until 12 weeks following PBBI. This is the first report of inflammasome activation after PBBI. Our results demonstrate cell-specific patterns of inflammasome activation and pyroptosis predominantly in microglia, suggesting a sustained pro-inflammatory state following PBBI, thus offering a therapeutic target for this type of brain injury.
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- 2018
19. Early Craniectomy Improves Intracranial and Cerebral Perfusion Pressure after Severe Traumatic Brain Injury
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Daniel J. Baldor, Jonathan R. Jagid, Casey J. Allen, M. Ross Bullock, Mena M. Hanna, Nicholas Namias, and Kenneth G. Proctor
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business.industry ,Traumatic brain injury ,medicine.medical_treatment ,Glasgow Coma Scale ,Hemodynamics ,030208 emergency & critical care medicine ,General Medicine ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Midline shift ,Anesthesia ,Medicine ,Injury Severity Score ,Decompressive craniectomy ,Cerebral perfusion pressure ,business ,030217 neurology & neurosurgery ,Intracranial pressure - Abstract
After traumatic brain injury, decompressive craniectomy (DC) is a second-tier, late therapy for refractory intracranial hypertension. We hypothesize that early DC, based on CT evidence of intracranial hypertension, improves intracranial pressure (ICP) and cerebral perfusion pressure (CPP). From September 2008 to January 2015, 286 traumatic brain injury patients requiring invasive ICP monitoring at a single Level I trauma center were reviewed. DC and non-DC patients were propensity score matched 1:1, based on demographics, hemodynamics, injury severity score (ISS), Glasgow Coma Scale (GCS), transfusion requirements, and need for vasopressor therapy. Data are presented as M ± SD or median (IQR) and compared at P ≤ 0.05. The study population was 42 ± 17 years, 84 per cent male, ISS = 29 ± 11, GCS = 6 (5), length of stay (LOS) = 32(40) days, and 28 per cent mortality. There were 116/286 (41%) DC, of which 105/116 (91%) were performed at the time of ICP placement. For 50 DC propensity matched to 50 non-DC patients, the midline shift was 7(11) versus 0(5) mm ( P < 0.001), abnormal ICP (hours > 20 mm Hg) was 1(10) versus 8(16) ( P = 0.017), abnormal CPP (hours < 60 mm Hg) was 0(6) versus 4(9) ( P = 0.008), daily minimum CPP (mm Hg) was 67(13) versus 62(17) ( P = 0.010), and daily maximum ICP (mm Hg) was 18(9) versus 22(11) ( P < 0.001). However, LOS [33(37) versus 25(34) days], mortality (24 versus 30%), and Glasgow Outcome Score Extended [3.0(3.0) versus 3.0(4.0)] did not improve significantly. Early DC for CT evidence of intracranial hypertension decreased abnormal ICP and CPP time and improved ICP and CPP thresholds, but had no obvious effect on the outcome.
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- 2018
20. Does Vasopressin Exacerbate Cerebral Edema in Patients with Severe Traumatic Brain Injury?
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Carl I. Schulman, M. Ross Bullock, Ty K. Subhawong, Kenneth G. Proctor, Casey J. Allen, Mena M. Hanna, and Lydia Chelala
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Vasopressin ,Traumatic brain injury ,business.industry ,030208 emergency & critical care medicine ,General Medicine ,medicine.disease ,Cerebral edema ,03 medical and health sciences ,0302 clinical medicine ,nervous system ,Osmotherapy ,Anesthesia ,Edema ,medicine ,Intracranial pressure monitoring ,medicine.symptom ,Cerebral perfusion pressure ,business ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Intracranial pressure - Abstract
Arginine vasopressin (AVP) is often used as an alternative pressor to catecholamines (CATs). However, unlike CATs, AVP is a powerful antidiuretic that could promote edema. We tested the hypothesis that AVP promoted cerebral edema and/or increased requirements for osmotherapy, relative to those who received CATs, for cerebral perfusion pressure (CPP) management after traumatic brain injury (TBI). This is a retrospective review of 286 consecutive TBI patients with intracranial pressure monitoring at a single institution from September 2008 to January 2015. Cerebral edema was quantitated using CT attenuation in prespecified areas of gray and white matter. Results: To maintain CPP >60 mm Hg, 205 patients required no vasopressors, 41 received a single CAT, 12 received AVP, and 28 required both. Those who required no pressors were generally less injured; required less hyperosmolar therapy and less total fluid; and had lower plasma Na, lower intracranial pressure, less edema, and lower mortality (all P < 0.05). Edema; daily mean, minimum, and maximum Na levels; and mortality were similar with AVP versus CATs, but the daily requirement of mannitol and 3 per cent NaCl were reduced by 45 and 35 per cent (both P < 0.05). In patients with TBI who required CPP therapy, AVP reduced the requirements for hyperosmolar therapy and did not delay resolution or increase cerebral edema compared with CATs.
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- 2018
21. Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study
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John K. Yue, Arthur W. Toga, Joan Machamer, M. Ross Bullock, Pratik Mukherjee, Sureyya Dikmen, Michael McCrea, Murray B. Stein, Brandon Foreman, Paul M. Vespa, Esther L. Yuh, Randall Merchant, David O. Okonkwo, Gillian Hotz, Neeraj Badjatia, Jonathan Rosand, Alex B. Valadka, Joseph T. Giacino, Thomas W. McAllister, David M. Schnyer, Ava M. Puccio, Adam R. Ferguson, Seth A. Seabury, Luis Alonso González, Claudia S. Robertson, Natalie Kreitzer, John D. Corrigan, J. Claude Hemphill, Ann-Christine Duhaime, Christopher J. Madden, Yelena G. Bodien, Karen Crawford, Harvey S. Levin, Ramon Diaz-Arrastia, Shankar P. Gopinath, Rao P. Gullapalli, Joel H. Kramer, Frederick K. Korley, Richard G. Ellenbogen, Alastair J. Martin, Sonia Jain, Raquel C. Gardner, V. Ramana Feeser, Jason Barber, Gabriella Satris, Opeolu Adeoye, Eva M. Palacios, Mark Sherer, Angelle M. Sander, Sabrina R Taylor, Geoffrey T. Manley, Christopher J. Lindsell, Étienne Gaudette, Kevin K.W. Wang, Florence Noel, Nancy R. Temkin, Kim Boase, Ross Zafonte, Miri Rabinowitz, Daniel P. Perl, Mary J. Vassar, Lindsay D. Nelson, and Randall M. Chesnut
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medicine.medical_specialty ,business.industry ,Traumatic brain injury ,Glasgow Outcome Scale ,Trauma center ,Glasgow Coma Scale ,medicine.disease ,Natural history ,03 medical and health sciences ,0302 clinical medicine ,Traumatic injury ,Orthopedic surgery ,Physical therapy ,Medicine ,030212 general & internal medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Most traumatic brain injuries (TBIs) are classified as mild (mTBI) based on admission Glasgow Coma Scale (GCS) scores of 13 to 15. The prevalence of persistent functional limitations for these patients is unclear.To characterize the natural history of recovery of daily function following mTBI vs peripheral orthopedic traumatic injury in the first 12 months postinjury using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, and, using clinical computed tomographic (CT) scans, examine whether the presence (CT+) or absence (CT-) of acute intracranial findings in the mTBI group was associated with outcomes.TRACK-TBI, a cohort study of patients with mTBI presenting to US level I trauma centers, enrolled patients from February 26, 2014, to August 8, 2018, and followed up for 12 months. A total of 1453 patients at 11 level I trauma center emergency departments or inpatient units met inclusion criteria (ie, mTBI [n = 1154] or peripheral orthopedic traumatic injury [n = 299]) and were enrolled within 24 hours of injury; mTBI participants had admission GCS scores of 13 to 15 and clinical head CT scans. Patients with peripheral orthopedic trauma injury served as the control (OTC) group.Participants with mTBI or OTC.The Glasgow Outcome Scale Extended (GOSE) scale score, reflecting injury-related functional limitations across broad life domains at 2 weeks and 3, 6, and 12 months postinjury was the primary outcome. The possible score range of the GOSE score is 1 (dead) to 8 (upper good recovery), with a score less than 8 indicating some degree of functional impairment.Of the 1453 participants, 953 (65.6%) were men; mean (SD) age was 40.9 (17.1) years in the mTBI group and 40.9 (15.4) years in the OTC group. Most participants (mTBI, 87%; OTC, 93%) reported functional limitations (GOSE8) at 2 weeks postinjury. At 12 months, the percentage of mTBI participants reporting functional limitations was 53% (95% CI, 49%-56%) vs 38% (95% CI, 30%-45%) for OTCs. A higher percentage of CT+ patients reported impairment (61%) compared with the mTBI CT- group (49%; relative risk [RR], 1.24; 95% CI, 1.08-1.43) and a higher percentage in the mTBI CT-group compared with the OTC group (RR, 1.28; 95% CI, 1.02-1.60).Most patients with mTBI presenting to US level I trauma centers report persistent, injury-related life difficulties at 1 year postinjury, suggesting the need for more systematic follow-up of patients with mTBI to provide treatments and reduce the risk of chronic problems after mTBI.
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- 2019
22. Risk of Posttraumatic Stress Disorder and Major Depression in Civilian Patients After Mild Traumatic Brain Injury: A TRACK-TBI Study
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Murray B, Stein, Sonia, Jain, Joseph T, Giacino, Harvey, Levin, Sureyya, Dikmen, Lindsay D, Nelson, Mary J, Vassar, David O, Okonkwo, Ramon, Diaz-Arrastia, Claudia S, Robertson, Pratik, Mukherjee, Michael, McCrea, Christine L, Mac Donald, John K, Yue, Esther, Yuh, Xiaoying, Sun, Laura, Campbell-Sills, Nancy, Temkin, Geoffrey T, Manley, Opeolu, Adeoye, Neeraj, Badjatia, Kim, Boase, Yelena, Bodien, M Ross, Bullock, Randall, Chesnut, John D, Corrigan, Karen, Crawford, Ann-Christine, Duhaime, Richard, Ellenbogen, V Ramana, Feeser, Adam, Ferguson, Brandon, Foreman, Raquel, Gardner, Etienne, Gaudette, Luis, Gonzalez, Shankar, Gopinath, Rao, Gullapalli, J Claude, Hemphill, Gillian, Hotz, Frederick, Korley, Joel, Kramer, Natalie, Kreitzer, Chris, Lindsell, Joan, Machamer, Christopher, Madden, Alastair, Martin, Thomas, McAllister, Randall, Merchant, Florence, Noel, Eva, Palacios, Daniel, Perl, Ava, Puccio, Miri, Rabinowitz, Jonathan, Rosand, Angelle, Sander, Gabriela, Satris, David, Schnyer, Seth, Seabury, Mark, Sherer, Sabrina, Taylor, Arthur, Toga, Alex, Valadka, Paul, Vespa, Kevin, Wang, and Ross, Zafonte
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Traumatic brain injury ,Comorbidity ,behavioral disciplines and activities ,Stress Disorders, Post-Traumatic ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Risk Factors ,mental disorders ,Brain Injuries, Traumatic ,Prevalence ,Medicine ,Humans ,Glasgow Coma Scale ,Longitudinal Studies ,Prospective Studies ,Young adult ,Psychiatry ,Prospective cohort study ,Depression (differential diagnoses) ,Original Investigation ,Depressive Disorder, Major ,business.industry ,Emergency department ,medicine.disease ,030227 psychiatry ,Psychiatry and Mental health ,Case-Control Studies ,Major depressive disorder ,Female ,business ,Emergency Service, Hospital ,030217 neurology & neurosurgery - Abstract
IMPORTANCE: Traumatic brain injury (TBI) has been associated with adverse mental health outcomes, such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), but little is known about factors that modify risk for these psychiatric sequelae, particularly in the civilian sector. OBJECTIVE: To ascertain prevalence of and risk factors for PTSD and MDD among patients evaluated in the emergency department for mild TBI (mTBI). DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal cohort study (February 2014 to May 2018). Posttraumatic stress disorder and MDD symptoms were assessed using the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9 Item. Risk factors evaluated included preinjury and injury characteristics. Propensity score weights-adjusted multivariable logistic regression models were performed to assess associations with PTSD and MDD. A total of 1155 patients with mTBI (Glasgow Coma Scale score, 13-15) and 230 patients with nonhead orthopedic trauma injuries 17 years and older seen in 11 US hospitals with level 1 trauma centers were included in this study. MAIN OUTCOMES AND MEASURES: Probable PTSD (PTSD Checklist for DSM-5 score, ≥33) and MDD (Patient Health Questionnaire-9 Item score, ≥15) at 3, 6, and 12 months postinjury. RESULTS: Participants were 1155 patients (752 men [65.1%]; mean [SD] age, 40.5 [17.2] years) with mTBI and 230 patients (155 men [67.4%]; mean [SD] age, 40.4 [15.6] years) with nonhead orthopedic trauma injuries. Weights-adjusted prevalence of PTSD and/or MDD in the mTBI vs orthopedic trauma comparison groups at 3 months was 20.0% (SE, 1.4%) vs 8.7% (SE, 2.2%) (P
- Published
- 2019
23. Human Lung Cell Pyroptosis Following Traumatic Brain Injury
- Author
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M. Ross Bullock, Gregory E. Conner, Juan Pablo de Rivero Vaccari, W. Dalton Dietrich, Oliver Umland, Robert W. Keane, and Nadine Kerr
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Traumatic brain injury ,Inflammasomes ,Caspase 1 ,caspase-1 ,Inflammation ,Lung injury ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,inflammasome ,Brain Injuries, Traumatic ,Medicine ,Humans ,Lung ,030304 developmental biology ,Aged ,Aged, 80 and over ,0303 health sciences ,business.industry ,pyroptosis ,Pyroptosis ,Endothelial Cells ,Inflammasome ,General Medicine ,Extracellular vesicle ,Lung Injury ,Middle Aged ,medicine.disease ,brain injury ,3. Good health ,CARD Signaling Adaptor Proteins ,medicine.anatomical_structure ,ROC Curve ,inflammation ,Female ,medicine.symptom ,business ,extracellular vesicles ,030217 neurology & neurosurgery ,Biomarkers ,medicine.drug - Abstract
Approximately 30% of traumatic brain injured patients suffer from acute lung injury or acute respiratory distress syndrome. Our previous work revealed that extracellular vesicle (EV)-mediated inflammasome signaling plays a crucial role in the pathophysiology of traumatic brain injury (TBI)-induced lung injury. Here, serum-derived EVs from severe TBI patients were analyzed for particle size, concentration, origin, and levels of the inflammasome component, an apoptosis-associated speck-like protein containing a caspase-recruiting domain (ASC). Serum ASC levels were analyzed from EV obtained from patients that presented lung injury after TBI and compared them to EV obtained from patients that did not show any signs of lung injury. EVs were co-cultured with lung human microvascular endothelial cells (HMVEC-L) to evaluate inflammasome activation and endothelial cell pyroptosis. TBI patients had a significant increase in the number of serum-derived EVs and levels of ASC. Severe TBI patients with lung injury had a significantly higher level of ASC in serum and serum-derived EVs compared to individuals without lung injury. Only EVs isolated from head trauma patients with gunshot wounds were of neural origin. Delivery of serum-derived EVs to HMVEC-L activated the inflammasome and resulted in endothelial cell pyroptosis. Thus, serum-derived EVs and inflammasome proteins play a critical role in the pathogenesis of TBI-induced lung injury, supporting activation of an EV-mediated neural-respiratory inflammasome axis in TBI-induced lung injury.
- Published
- 2019
- Full Text
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24. Association of Sex and Age With Mild Traumatic Brain Injury–Related Symptoms: A TRACK-TBI Study
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Adam R. Ferguson, Yelena G. Bodien, Pratik Mukherjee, Ramon Diaz-Arrastia, Ann-Christine Duhaime, Murray B. Stein, Jeffrey Brennan, John K. Yue, Karen Crawford, Amy J. Markowitz, Ross Zafonte, Alastair J. Martin, Gillian Hotz, Claudia S. Robertson, Michael McCrea, Esther L. Yuh, Jonathan Rosand, David M. Schnyer, Randall Merchant, Brandon Foreman, Opeolu Adeoye, Miri Rabinowitz, Laura B. Ngwenya, Amber Nolan, Richard G. Ellenbogen, Joel H. Kramer, M. Ross Bullock, C. Dirk Keene, Christopher J. Lindsell, Track-Tbi Investigators, Jason Barber, Angelle M. Sander, Shankar P. Gopinath, Xiaoying Sun, V. Ramana Feeser, Arthur W. Toga, Seth A. Seabury, Alex B. Valadka, Neeraj Badjatia, Natalie Kreitzer, Florence Noel, J. Claude Hemphill, Nancy R. Temkin, Joan Machamer, Kim Boase, Harvey S. Levin, Luis Gonzalez, Sonia Jain, Randall M. Chesnut, Thomas W. McAllister, Ava M. Puccio, Gabriella Satris, John D. Corrigan, Raquel C. Gardner, Geoffrey T. Manley, Rao P. Gullapalli, Joseph T. Giacino, Christopher J. Madden, Frederick K. Korley, Eva M. Palacios, Sabrina R Taylor, Étienne Gaudette, Kevin K.W. Wang, David O. Okonkwo, Mary J. Vassar, Sureyya Dikmen, and Lindsay D. Nelson
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Traumatic brain injury ,Risk Assessment ,Severity of Illness Index ,Brain Injuries, Traumatic ,Severity of illness ,medicine ,Humans ,Cognitive Dysfunction ,Glasgow Coma Scale ,Prospective Studies ,Sex Distribution ,Prospective cohort study ,Brain Concussion ,Depression (differential diagnoses) ,Original Investigation ,Aged ,Post-Concussion Syndrome ,business.industry ,Research ,General Medicine ,Middle Aged ,Rivermead post-concussion symptoms questionnaire ,medicine.disease ,Online Only ,Neurology ,Orthopedic surgery ,Anxiety ,Female ,medicine.symptom ,business - Abstract
Key Points Question Do postacute mild traumatic brain injury (mTBI) symptoms differ between men and women? Findings In this cohort study of 2000 patients with mTBI, the severity of cognitive and somatic symptoms on the Rivermead Post Concussion Symptoms Questionnaire at 12 months after injury was significantly worse in women than in men, whereas this difference was not significant in an orthopedic trauma control group. The association between mTBI and somatic symptoms was greater in women aged 35 to 49 years than those aged 17 to 34 years or older than 50 years. Meaning Sex and age may be important factors in the individualized, postacute treatment of patients with mTBI., This cohort study uses data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study to assess whether patient sex and age are associated with mild traumatic brain injury symptoms., Importance Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. Objective To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. Design, Setting, and Participants The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. Exposures Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. Main Outcomes and Measures Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). Results A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate–corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate–corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02). Conclusions and Relevance This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.
- Published
- 2021
25. Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury
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Joel H. Kramer, Joan Machamer, Raquel C. Gardner, Michael McCrea, Rao P. Gullapalli, Harvey S. Levin, Frederick K. Korley, Benjamin L. Brett, Mary J. Vassar, Thomas W. McAllister, Geoffrey T. Manley, Ava M. Puccio, Eva M. Palacios, Mark D. Kramer, Joseph T. Giacino, Luis Gonzalez, Karen Crawford, Amy J. Markowitz, Mark Sherer, Jason Barber, Lindsay D. Nelson, Randall M. Chesnut, Angelle M. Sander, M. Ross Bullock, Christopher J. Madden, Richard G. Ellenbogen, Murray B. Stein, John K. Yue, Shankar P. Gopinath, John D. Corrigan, Alex B. Valadka, Natalie Kreitzer, V. Ramana Feeser, J. Claude Hemphill, Pratik Mukherjee, Yelena G. Bodien, Laura B. Ngwenya, Neeraj Badjatia, John Whyte, Sabrina R Taylor, Sonia Jain, Ann-Christine Duhaime, Gillian Hotz, Étienne Gaudette, Gabriella Satris, Jonathan Rosand, Kevin K.W. Wang, David M. Schnyer, Alastair J. Martin, Claudia S. Robertson, Adam R. Ferguson, Esther L. Yuh, Florence Noel, Ramon Diaz-Arrastia, Sureyya Dikmen, Nancy R. Temkin, Kim Boase, Arthur W. Toga, Track-Tbi Investigators, David O. Okonkwo, Randall Merchant, Ross Zafonte, Opeolu Adeoye, Miri Rabinowitz, Seth A. Seabury, Christopher J. Lindsell, Brandon Foreman, and C. Dirk Keene
- Subjects
Traumatic brain injury ,business.industry ,Trail Making Test ,Glasgow Coma Scale ,Wechsler Adult Intelligence Scale ,General Medicine ,NIH Toolbox ,Rivermead post-concussion symptoms questionnaire ,medicine.disease ,medicine ,business ,Prospective cohort study ,Cohort study ,Clinical psychology - Abstract
Importance Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. Objective To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. Design, setting, and participants This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. Exposures TBI. Main outcomes and measures Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Results Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34). Conclusions and relevance In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.
- Published
- 2021
26. Past, Present, and Future of Traumatic Brain Injury Research
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Gregory W.J. Hawryluk and M. Ross Bullock
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0301 basic medicine ,medicine.medical_specialty ,Traumatic brain injury ,Poison control ,Context (language use) ,Suicide prevention ,03 medical and health sciences ,0302 clinical medicine ,Brain Injuries, Traumatic ,Injury prevention ,Humans ,Medicine ,Intensive care medicine ,Cause of death ,Clinical Trials as Topic ,business.industry ,Research ,Human factors and ergonomics ,General Medicine ,medicine.disease ,Clinical trial ,030104 developmental biology ,Surgery ,Neurology (clinical) ,Medical emergency ,business ,030217 neurology & neurosurgery - Abstract
Traumatic brain injury (TBI) is the greatest cause of death and severe disability in young adults; its incidence is increasing in the elderly and in the developing world. Outcome from severe TBI has improved dramatically as a result of advancements in trauma systems and supportive critical care, however we remain without a therapeutic which acts directly to attenuate brain injury. Recognition of secondary injury and its molecular mediators has raised hopes for such targeted treatments. Unfortunately, over 30 late-phase clinical trials investigating promising agents have failed to translate a therapeutic for clinical use. Numerous explanations for this failure have been postulated and are reviewed here. With this historical context we review ongoing research and anticipated future trends which are armed with lessons from past trials, new scientific advances, as well as improved research infrastructure and funding. There is great hope that these new efforts will finally lead to an effective therapeutic for TBI as well as better clinical management strategies.
- Published
- 2016
27. Hypothermia in Traumatic Brain Injury
- Author
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M. Ross Bullock, Aminul I. Ahmed, and W. Dalton Dietrich
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Intracranial Pressure ,Traumatic brain injury ,Neuroprotection ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Hypothermia, Induced ,law ,Brain Injuries, Traumatic ,Humans ,Medicine ,In patient ,Intracranial pressure ,business.industry ,Brain ,030208 emergency & critical care medicine ,General Medicine ,Hypothermia ,medicine.disease ,nervous system diseases ,Treatment Outcome ,Moderate hypothermia ,Anesthesia ,Surgery ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
For over 50 years, clinicians have used hypothermia to manage traumatic brain injury (TBI). In the last two decades numerous trials have assessed whether hypothermia is of benefit in patients. Mild to moderate hypothermia reduces the intracranial pressure (ICP). Randomized control trials for short-term hypothermia indicate no benefit in outcome after severe TBI, whereas longer-term hypothermia could be of benefit by reducing ICP. This article summarises current evidence and gives recommendations based upon the conclusions.
- Published
- 2016
28. Early Craniectomy Improves Intracranial and Cerebral Perfusion Pressure after Severe Traumatic Brain Injury
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Casey J, Allen, Daniel J, Baldor, Mena M, Hanna, Nicholas, Namias, M Ross, Bullock, Jonathan R, Jagid, and Kenneth G, Proctor
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Adult ,Male ,Decompressive Craniectomy ,Length of Stay ,Middle Aged ,Perfusion ,Injury Severity Score ,Cerebrovascular Circulation ,Brain Injuries, Traumatic ,Humans ,Female ,Glasgow Coma Scale ,Intracranial Hypertension ,Propensity Score - Abstract
After traumatic brain injury, decompressive craniectomy (DC) is a second-tier, late therapy for refractory intracranial hypertension. We hypothesize that early DC, based on CT evidence of intracranial hypertension, improves intracranial pressure (ICP) and cerebral perfusion pressure (CPP). From September 2008 to January 2015, 286 traumatic brain injury patients requiring invasive ICP monitoring at a single Level I trauma center were reviewed. DC and non-DC patients were propensity score matched 1:1, based on demographics, hemodynamics, injury severity score (ISS), Glasgow Coma Scale (GCS), transfusion requirements, and need for vasopressor therapy. Data are presented as M ± SD or median (IQR) and compared at P ≤ 0.05. The study population was 42 ± 17 years, 84 per cent male, ISS = 29 ± 11, GCS = 6(5), length of stay (LOS) = 32(40) days, and 28 per cent mortality. There were 116/286 (41%) DC, of which 105/116 (91%) were performed at the time of ICP placement. For 50 DC propensity matched to 50 non-DC patients, the midline shift was 7(11) versus 0(5) mm (P0.001), abnormal ICP (hours20 mm Hg) was 1(10) versus 8(16) (P = 0.017), abnormal CPP (hours60 mm Hg) was 0(6) versus 4(9) (P = 0.008), daily minimum CPP (mm Hg) was 67(13) versus 62(17) (P = 0.010), and daily maximum ICP (mm Hg) was 18(9) versus 22(11) (P0.001). However, LOS [33(37) versus 25(34) days], mortality (24 versus 30%), and Glasgow Outcome Score Extended [3.0(3.0) versus 3.0(4.0)] did not improve significantly. Early DC for CT evidence of intracranial hypertension decreased abnormal ICP and CPP time and improved ICP and CPP thresholds, but had no obvious effect on the outcome.
- Published
- 2018
29. Does Vasopressin Exacerbate Cerebral Edema in Patients with Severe Traumatic Brain Injury?
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Casey J, Allen, Ty K, Subhawong, Mena M, Hanna, Lydia, Chelala, M Ross, Bullock, Carl I, Schulman, and Kenneth G, Proctor
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Adult ,Male ,Trauma Severity Indices ,Vasopressins ,Brain Edema ,Middle Aged ,Catecholamines ,Treatment Outcome ,Cerebrovascular Circulation ,Brain Injuries, Traumatic ,Humans ,Vasoconstrictor Agents ,Female ,Retrospective Studies - Abstract
Arginine vasopressin (AVP) is often used as an alternative pressor to catecholamines (CATs). However, unlike CATs, AVP is a powerful antidiuretic that could promote edema. We tested the hypothesis that AVP promoted cerebral edema and/or increased requirements for osmotherapy, relative to those who received CATs, for cerebral perfusion pressure (CPP) management after traumatic brain injury (TBI). This is a retrospective review of 286 consecutive TBI patients with intracranial pressure monitoring at a single institution from September 2008 to January 2015. Cerebral edema was quantitated using CT attenuation in prespecified areas of gray and white matter.To maintain CPP60 mm Hg, 205 patients required no vasopressors, 41 received a single CAT, 12 received AVP, and 28 required both. Those who required no pressors were generally less injured; required less hyperosmolar therapy and less total fluid; and had lower plasma Na, lower intracranial pressure, less edema, and lower mortality (all P0.05). Edema; daily mean, minimum, and maximum Na levels; and mortality were similar with AVP versus CATs, but the daily requirement of mannitol and 3 per cent NaCl were reduced by 45 and 35 per cent (both P0.05). In patients with TBI who required CPP therapy, AVP reduced the requirements for hyperosmolar therapy and did not delay resolution or increase cerebral edema compared with CATs.
- Published
- 2018
30. Oxygen Management and Prevention of Cerebral Ischemia
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M. Ross Bullock and Ashley Ralston
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medicine.medical_specialty ,Traumatic brain injury ,business.industry ,Ischemia ,Brain tissue ,Hyperbaric hyperoxia ,medicine.disease ,Intensive care unit ,law.invention ,Oxygen monitoring ,Early results ,law ,medicine ,business ,Intensive care medicine - Abstract
In this chapter, we discuss the current practices, controversies, and current and future research concerning oxygen management of severe traumatic brain injury (TBI) patients in the intensive care unit (ICU). Prevention of secondary injuries is paramount to the care of TBI patients, so understanding the different mechanisms of secondary injury in TBI patients (including ischemia, mitochondrial damage, and free radical formation) will contribute to their prevention, with the ultimate goal of improving neurologic outcomes. Although many of the data regarding brain tissue oxygen monitoring and directed management are still controversial, different techniques and systems used for monitoring have been proven safe and potentially beneficial. Recent studies investigate the unique option of hyperbaric hyperoxia treatment for severely injured TBI patients, with promising early results.
- Published
- 2018
31. Chronic subdural hematoma management
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M. Ross Bullock and Aminul I. Ahmed
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medicine.medical_specialty ,Chronic subdural hematoma ,business.industry ,medicine ,business ,Surgery - Published
- 2017
32. Temperature Management in Neurological and Neurosurgical Intensive Care Unit
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M. Ross Bullock, Mohammed Fazlur Rehman, Mauro Oddo, Chad Miller, and Michelle Hill
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Anesthesiology and Pain Medicine ,Critical Care and Intensive Care Medicine - Published
- 2015
33. Intraoperative Temperature Management
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J. Javier Provencio, Samuel A. Tisherman, Fred Rincon, and M. Ross Bullock
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medicine.medical_specialty ,Anesthesiology and Pain Medicine ,Text mining ,business.industry ,Treatment outcome ,Emergency medicine ,Severity of illness ,medicine ,MEDLINE ,Hypothermia ,medicine.symptom ,Critical Care and Intensive Care Medicine ,business - Published
- 2015
34. Glucose and oxygen metabolism after penetrating ballistic-like brain injury
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Shoji Yokobori, Frank C. Tortella, Deborah A. Shear, Clayton Jackson, Julio Diaz, Daniel Diaz, Markus S. Spurlock, M. Ross Bullock, Weizhao Zhao, Lai Y Leung, Shimoda Kentaro, Alexandra Wick, and Shyam Gajavelli
- Subjects
Male ,medicine.medical_specialty ,Pathology ,Cerebellum ,Traumatic brain injury ,Glucose uptake ,Rats, Sprague-Dawley ,Internal medicine ,Cortex (anatomy) ,cerebral metabolism ,medicine ,Animals ,Head Injuries, Penetrating ,Cause of death ,business.industry ,Penumbra ,Neurodegeneration ,neurodegeneration ,Neurodegenerative Diseases ,medicine.disease ,Pathophysiology ,Rats ,Oxygen ,Disease Models, Animal ,medicine.anatomical_structure ,Glucose ,Neurology ,2-deoxy glucose ,Cardiology ,Original Article ,Wounds, Gunshot ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Fluorojade B - Abstract
Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies.
- Published
- 2015
35. Outcome and Surgical Management for Geriatric Traumatic Brain Injury: Analysis of 888 Cases Registered in the Japan Neurotrauma Data Bank
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Masahiro Tado, Kentaro Shimoda, Yoichi Katayama, Atsuo Yoshino, M. Ross Bullock, and Takeshi Maeda
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Male ,medicine.medical_specialty ,Pediatrics ,Databases, Factual ,Traumatic brain injury ,Cost-Benefit Analysis ,medicine.medical_treatment ,Population ,Clinical Neurology ,Poison control ,Neurosurgical Procedures ,Elderly ,Japan ,Injury prevention ,medicine ,Humans ,Glasgow Coma Scale ,education ,Craniotomy ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Glasgow Outcome Scale ,Age Factors ,Odds ratio ,Prognosis ,medicine.disease ,Surgery ,Treatment Outcome ,Brain Injuries ,Surgical management ,Female ,Neurology (clinical) ,business - Abstract
Objective As the aged population is rapidly growing globally, geriatric traumatic brain injury (TBI) becomes an increasing problem. There are higher mortality and poorer functional outcome in the geriatric TBI population (≥65 years) compared with younger groups despite neurosurgical interventions. Therefore, current treatment priorities and cost-effectiveness should be critically examined. We evaluated the benefit of surgical management in the elderly (≥65 years) after TBI. Methods A total of 3194 patients with confirmed TBI were enrolled from 1998 to 2011, in the Japan Neurotrauma Data Bank. Retrospective analysis was conducted from the Japan Neurotrauma Data Bank on 888 (28%) patients (≥65 years) who did and did not undergo surgery. In particular, the effect of low Glasgow coma scale (GCS) (3–5) was compared with outcome with and without surgery. Results Of all the patients 65 years of age and over, 478 (54%) were given surgical management (craniectomy, craniotomy, or burr-hole evacuation). This group of patients had significantly more favorable outcome at 6 months (18% vs. 7%) and less mortality (62% vs. 81%). However, within this surgical group, patients with initial GCS scores of 3–5 had significantly more unfavorable outcome (96% vs. 79%) and more mortality (87% vs. 57%) compared with those with GCS scores of 6–15. Conclusions We confirmed that age is a major determinant of outcome after TBI. In addition, we found that neurosurgical management is associated with the improvement of the prognosis and a decrease in the rate of mortality in geriatric TBI. However, surgical management was not shown to be an effective treatment in elderly patients with GCS scores of 3–5.
- Published
- 2014
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36. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial
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John M. McGregor, Christos Lazaridis, David O. Okonkwo, Peter D. LeRoux, Michael J. Weaver, Ramon Diaz-Arrastia, Christopher J. Madden, Gerald A. Grant, Jack Jallo, Randall M. Chesnut, Dick Moberg, M. Ross Bullock, Jason Barber, Nancy R. Temkin, Lori Shutter, Carol Moore, Norberto Andaluz, and Ava M. Puccio
- Subjects
Adult ,Male ,Intracranial Pressure ,Traumatic brain injury ,Critical Care and Intensive Care Medicine ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Brain Injuries, Traumatic ,medicine ,Humans ,Glasgow Coma Scale ,Single-Blind Method ,Prospective Studies ,Prospective cohort study ,Monitoring, Physiologic ,business.industry ,Neurointensive care ,Brain ,030208 emergency & critical care medicine ,Oxygenation ,Hypoxia (medical) ,Middle Aged ,medicine.disease ,Clinical trial ,Oxygen ,Intensive Care Units ,Anesthesia ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study.Randomized prospective clinical trial.Ten ICUs in the United States.One hundred nineteen severe traumatic brain injury patients.Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended.A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p0.0001). Intracranial pressure control was similar in both groups. Safety and feasibility of the tiered treatment protocol were confirmed. There were no procedure-related complications. Treatment of secondary injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy.Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of intracranial pressure plus brain tissue oxygenation-directed treatment of severe traumatic brain injury is warranted.
- Published
- 2017
37. Cooling Strategies Targeting Trauma
- Author
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Moderator: M. Ross Bullock, Participants: Carl I. Schulman, Jesse J. Corry, and Athina Pappas
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Anesthesiology and Pain Medicine ,Critical Care and Intensive Care Medicine - Published
- 2014
38. Intraoperative Temperature Management
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Moderator: W. Dalton Dietrich, Participants: M. Ross Bullock, Justin B. Lundbye, and W. Dalton Dietrich
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Disease Models, Animal ,Intraoperative Care ,Anesthesiology and Pain Medicine ,Hypothermia, Induced ,Brain Injuries ,Animals ,Humans ,Critical Care and Intensive Care Medicine ,Spinal Cord Injuries - Published
- 2014
39. Surgical management of traumatic brain injury: a comparative-effectiveness study of 2 centers
- Author
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M. Ross Bullock, Bruce E. Mathern, Christos M. Tolias, Martin Fabricius, Richard Stanger, Anthony J. Strong, Steven Vidgeon, Clemens Pahl, Jed A. Hartings, Chris Zacko, Thomas Ridder, Achala Vagal, and Norberto Andaluz
- Subjects
Traumatic brain injury ,business.industry ,Decompression ,medicine.medical_treatment ,Glasgow Coma Scale ,Brain Contusion ,medicine.disease ,Anesthesia ,medicine ,Decompressive craniectomy ,business ,Prospective cohort study ,Stroke ,Craniotomy - Abstract
Object Mass lesions from traumatic brain injury (TBI) often require surgical evacuation as a life-saving measure and to improve outcomes, but optimal timing and surgical technique, including decompressive craniectomy, have not been fully defined. The authors compared neurosurgical approaches in the treatment of TBI at 2 academic medical centers to document variations in real-world practice and evaluate the efficacies of different approaches on postsurgical course and long-term outcome. Methods Patients 18 years of age or older who required neurosurgical lesion evacuation or decompression for TBI were enrolled in the Co-Operative Studies on Brain Injury Depolarizations (COSBID) at King's College Hospital (KCH, n = 27) and Virginia Commonwealth University (VCU, n = 24) from July 2004 to March 2010. Subdural electrode strips were placed at the time of surgery for subsequent electrocorticographic monitoring of spreading depolarizations; injury characteristics, physiological monitoring data, and 6-month outcomes were collected prospectively. CT scans and medical records were reviewed retrospectively to determine lesion characteristics, surgical indications, and procedures performed. Results Patients enrolled at KCH were significantly older than those enrolled at VCU (48 vs 34 years, p < 0.01) and falls were more commonly the cause of TBI in the KCH group than in the VCU group. Otherwise, KCH and VCU patients had similar prognoses, lesion types (subdural hematomas: 30%–35%; parenchymal contusions: 48%–52%), signs of mass effect (midline shift ≥ 5 mm: 43%–52%), and preoperative intracranial pressure (ICP). At VCU, however, surgeries were performed earlier (median 0.51 vs 0.83 days posttrauma, p < 0.05), bone flaps were larger (mean 82 vs 53 cm2, p < 0.001), and craniectomies were more common (performed in 75% vs 44% of cases, p < 0.05). Postoperatively, maximum ICP values were lower at VCU (mean 22.5 vs 31.4 mm Hg, p < 0.01). Differences in incidence of spreading depolarizations (KCH: 63%, VCU: 42%, p = 0.13) and poor outcomes (KCH: 54%, VCU: 33%, p = 0.14) were not significant. In a subgroup analysis of only those patients who underwent early (< 24 hours) lesion evacuation (KCH: n = 14; VCU: n = 16), however, VCU patients fared significantly better. In the VCU patients, bone flaps were larger (mean 85 vs 48 cm2 at KCH, p < 0.001), spreading depolarizations were less common (31% vs 86% at KCH, p < 0.01), postoperative ICP values were lower (mean: 20.8 vs 30.2 mm Hg at KCH, p < 0.05), and good outcomes were more common (69% vs 29% at KCH, p < 0.05). Spreading depolarizations were the only significant predictor of outcome in multivariate analysis. Conclusions This comparative-effectiveness study provides evidence for major practice variation in surgical management of severe TBI. Although ages differed between the 2 cohorts, the results suggest that a more aggressive approach, including earlier surgery, larger craniotomy, and removal of bone flap, may reduce ICP, prevent cortical spreading depolarizations, and improve outcomes. In particular, patients requiring evacuation of subdural hematomas and contusions may benefit from decompressive craniectomy in conjunction with lesion evacuation, even when elevated ICP is not a factor in the decision to perform surgery.
- Published
- 2014
40. Traumatic Brain Injury at Your Fingertips!
- Author
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Nauman S. Chaudhry, Faiz U. Ahmad, Michael Wang, and M. Ross Bullock
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medicine.medical_specialty ,Communication Aids for Disabled ,Traumatic brain injury ,business.industry ,medicine ,Emergency medical services ,Surgery ,Neurology (clinical) ,Medical emergency ,Neurosurgery ,medicine.disease ,business - Published
- 2014
41. Vasopressin for cerebral perfusion pressure management in patients with severe traumatic brain injury
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Gerardo A. Guarch, Alexander M. Busko, Chad M. Thorson, Kenneth G. Proctor, M. Ross Bullock, Jonathan R. Jagid, Jassin A. Jouria, Evan J. Valle, Michael P. Ogilvie, Robert M. Van Haren, Alan S. Livingstone, and Leo Harris
- Subjects
Adult ,Male ,endocrine system ,Vasopressin ,Intracranial Pressure ,Vasopressins ,Traumatic brain injury ,Blood Pressure ,Critical Care and Intensive Care Medicine ,law.invention ,Injury Severity Score ,Randomized controlled trial ,law ,Humans ,Vasoconstrictor Agents ,Medicine ,Prospective Studies ,Cerebral perfusion pressure ,Adverse effect ,business.industry ,medicine.disease ,Intensive care unit ,Treatment Outcome ,nervous system ,Brain Injuries ,Anesthesia ,Intracranial pressure monitoring ,Female ,Surgery ,business ,hormones, hormone substitutes, and hormone antagonists ,Follow-Up Studies - Abstract
BACKGROUND After traumatic brain injury (TBI), catecholamines (CAs) may be needed to maintain adequate cerebral perfusion pressure (CPP), but there are no recommended alternative vasopressor therapies. This is an interim report of the first study to test the hypothesis that arginine vasopressin (AVP) is a safe and effective alternative to CAs for the management of CPP in patients with severe TBI. METHODS Since 2008, all TBI patients requiring intracranial pressure monitoring at this Level 1 trauma center have been eligible for a randomized trial to receive either CA or AVP if vasopressors were required to maintain CPP greater than 60 mm Hg. RESULTS To date, 96 patients have been consented and randomized. Demographics, vital signs, and laboratory values were similar. As treated, 60 required no vasopressors and were the least severely injured group with the best outcomes. Twenty-three patients received CA (70% levophed, 22% dopamine, 9% phenylephrine) and 12 patients received AVP. The two vasopressor groups had similar demographics, but Injury Severity Score (ISS) and fluid requirements on intensive care unit Day 1 were worse in the AVP versus the CA groups (all p < 0.05) before treatment. These differences indicate more severe injury with accompanying hemodynamic instability. Nevertheless, adverse events were not increased with AVP versus CA. Trends favored AVP versus CA, but no apparent differences were statistically significant at this interim point. There was no difference in mortality rates between CA and AVP. CONCLUSION These preliminary results suggest that AVP is a safe and effective alternative to CA for the management of CPP after TBI and support the continued investigation and use of AVP when vasopressors are required for CPP management in TBI patients. LEVEL OF EVIDENCE Therapeutic study, level II.
- Published
- 2013
42. Inflammasome proteins as biomarkers of traumatic brain injury
- Author
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Juan Pablo de Rivero Vaccari, Robert W. Keane, Jon Pérez-Bárcena, W. Dalton Dietrich, Javier Ibáñez, M. Ross Bullock, Nadine Kerr, Stephanie W. Lee, and Catalina Crespí
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Male ,0301 basic medicine ,Oncology ,Serum Proteins ,Critical Care and Emergency Medicine ,Traumatic Brain Injury ,Inflammasomes ,Physiology ,humanos ,Interleukin-1beta ,Pathology and Laboratory Medicine ,proteínas adaptadoras de señalización CARD ,Biochemistry ,Nervous System ,0302 clinical medicine ,Cerebrospinal fluid ,Brain Injuries, Traumatic ,Medicine and Health Sciences ,Brain Damage ,inflamasomas ,Immune Response ,mediana edad ,Trauma Medicine ,Cerebrospinal Fluid ,Aged, 80 and over ,anciano ,Immune System Proteins ,Multidisciplinary ,Caspase 1 ,Interleukin-18 ,Area under the curve ,caspasa 1 ,Interleukin ,Inflammasome ,adulto ,Middle Aged ,Blood proteins ,interleucina-18 ,Body Fluids ,Head Injury ,Neurology ,Medicine ,Biomarker (medicine) ,Female ,Anatomy ,medicine.symptom ,Traumatic Injury ,Research Article ,medicine.drug ,Adult ,medicine.medical_specialty ,Traumatic brain injury ,Science ,traumatismos cerebrales ,Immunology ,interleucina-1beta ,Brain damage ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Internal medicine ,medicine ,Humans ,Aged ,Inflammation ,business.industry ,Biology and Life Sciences ,Proteins ,medicine.disease ,CARD Signaling Adaptor Proteins ,030104 developmental biology ,Brain Injuries ,business ,Neurotrauma ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Background The inflammasome plays an important role in the inflammatory innate immune response after central nervous system (CNS) injury. Inhibition of the inflammasome after traumatic brain injury (TBI) results in improved outcomes by lowering the levels of caspase-1 and interleukin (IL)-1b. We have previously shown that inflammasome proteins are elevated in the cerebrospinal fluid (CSF) of patients with TBI and that higher levels of these proteins were consistent with poorer outcomes after TBI when compared to patients that presented these inflammasome proteins at lower levels. Methods and findings Here we extend our work by analyzing serum from 21 TBI patients and CSF from 18 TBI patients compared to 120 serum samples and 30 CSF samples from no-TBI donor controls for the expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin(IL)-1b and IL-18. Analysis was carried out using the Ella Simple Plex system (Protein Simple) to determine the sensitivity and specificity of inflammasome proteins as biomarkers of TBI. Receiver operator characteristic (ROC) curves, confidence intervals and likelihood ratios for each biomarker was determined. ROC curves, confidence intervals, sensitivity and specificity for each biomarker examined revealed that caspase-1 (0.93 area under the curve (AUC)) and ASC (0.90 AUC) in serum and ASC (1.0 AUC) and IL-18 (0.84 AUC) in CSF are promising biomarkers of TBI pathology. Importantly, higher protein levels (above 547.6 pg/ml) of ASC (0.91 AUC) were consistent with poorer outcomes after TBI as determined by the Glasgow Outcome Scale-Extended (GOSE). Conclusion These findings indicate that inflammasome proteins are excellent diagnostic and predictive biomarkers of TBI., This work was supported by a STTR grant (4R42NS086274-012) from the NINDS/NIH to RWK: https://www.nih.gov/; and by a public grant from Fondo de Investigacion Sanitaria (FIS PI16/00737) to JPB: https://portalfis.isciii.es/es/Paginas/inicio.aspx.No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; This work was supported by a STTR grant (4R42NS086274-012) from the NINDS/NIH to RWK and WDD and by a public grant from Fondo de Investigacion Sanitaria (FIS PI16/00737) to JPB.
- Published
- 2018
43. Management of simultaneous traumatic brain injury and aortic injury
- Author
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Robert M. Van Haren, Ryan S. Kitagawa, Shoji Yokobori, David Cohen, M. Ross Bullock, Faiz U. Ahmad, and Samuel R. Beckerman
- Subjects
Retrospective review ,business.industry ,Traumatic brain injury ,Sedation ,Trauma center ,Aortic injury ,medicine.disease ,Blood pressure ,Anesthesia ,Medicine ,In patient ,medicine.symptom ,business ,Surgical interventions - Abstract
Object Simultaneous traumatic brain injury (TBI) and aortic injury has been considered unsurvivable for many years because treatments such as sedation and blood pressure goals conflict for these 2 conditions. Additionally, surgical interventions for aortic injury often require full anticoagulation, which is contraindicated in patients with TBI. For these reasons, and due to the relative rarity of aortic injury/TBI, little data are available to guide treating physicians. Methods A retrospective review was performed on all simultaneous TBI and aortic injury cases from 2000 to 2012 at a university-affiliated, Level I trauma center. Patient demographics, imaging studies, interventions, and outcomes were analyzed. Traumatic brain injury/aortic injury cases treated with endovascular stenting were specifically studied to determine trends in procedure timing, use of anticoagulation, and neurological outcome. Results Thirty-three patients with concurrent TBI and aortic injury were identified over a 12-year period. The median patient age was 44 years (range 16–86 years) and the overall mortality rate after imaging diagnosis was 46%. All surviving patients were awake and neurologically functional at discharge, and 83% were discharged home or to rehabilitation facilities. Patients who died had a higher Injury Severity Scale score (p = 0.006). Severe TBI (p = 0.045) or hemodynamic instability (p = 0.015) upon arrival to the hospital was also correlated with increased mortality rates. Thirty-three percent of aortic injury/TBI patients (n = 11) underwent endovascular stenting, and 7 of these patients received intravenous anticoagulation therapy at the time of surgery. Six of these 7 anticoagulation-treated patients experienced no significant progression on postoperative brain CT, whereas 1 patient died of hemodynamic instability prior to undergoing further imaging. Conclusions Simultaneous TBI and aortic injury is a rare condition with a historically poor prognosis. However, these results suggest that many patients can survive with a good quality of life. Technological advances such as endovascular aortic stenting may improve patient outcome, and anticoagulation is not absolutely contraindicated after TBI.
- Published
- 2013
44. Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model
- Author
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M. Ross Bullock, Shyam Gajavelli, Stefania Mondello, Helen M. Bramlett, Shoji Yokobori, Jixiang Mo-Seaney, and W. Dalton Dietrich
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medicine.medical_specialty ,business.industry ,Traumatic brain injury ,medicine.medical_treatment ,Ischemia ,Brain damage ,Hypothermia ,medicine.disease ,Neuroprotection ,Surgery ,Hematoma ,Anesthesia ,medicine ,medicine.symptom ,business ,Reperfusion injury ,Craniotomy - Abstract
Object In patients who have sustained a traumatic brain injury (TBI), hypothermia therapy has not shown efficacy in multicenter clinical trials. Armed with the post hoc data from the latest clinical trial (National Acute Brain Injury Study: Hypothermia II), the authors hypothesized that hypothermia may be beneficial in an acute subdural hematoma (SDH) rat model by blunting the effects of ischemia/reperfusion injury. The major aim of this study was to test the efficacy of temperature management in reducing brain damage after acute SDH. Methods The rats were induced with acute SDH and placed into 1 of 4 groups: 1) normothermia group (37°C); 2) early hypothermia group, head and body temperature reduced to 33°C 30 minutes prior to craniotomy; 3) late hypothermia group, temperature lowered to 33°C 30 minutes after decompression; and 4) sham group, no acute SDH (only craniotomy with normothermia). To assess for neuronal and glial cell damage, the authors analyzed microdialysate concentrations of GFAP and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) by using a 100-kD probe. Fluoro-Jade B–positive neurons and injury volume with 2,3,5-triphenyltetrazolium chloride staining were also measured. Results In the early phase of reperfusion (30 minutes, 2.5 hours after decompression), extracellular UCH-L1 in the early hypothermia group was significantly lower than in the normothermia group (early, 4.9 ± 1.0 ng/dl; late, 35.2 ± 12.1 ng/dl; normothermia, 50.20 ± 28.3 ng/dl; sham, 3.1 ± 1.3 ng/dl; early vs normothermia, p < 0.01; sham vs normothermia, p < 0.01, analyzed using ANOVA followed by a post hoc Bonferroni test). In the late phase of reperfusion (> 2.5 hours after decompression), extracellular GFAP in the early hypothermia group was also lower than in the normothermia and late hypothermia groups (early, 5.5 ± 2.9 ng/dl; late, 7.4 ± 3.4 ng/dl; normothermia, 15.3 ± 8.4 ng/dl; sham, 3.3 ± 1.0 ng/dl; normothermia vs sham; p < 0.01). The number of Fluoro-Jade B–positive cells in the early hypothermia group was significantly smaller than that in the normothermia group (normothermia vs early: 774,588 ± 162,173 vs 180,903 ± 42,212, p < 0.05). Also, the injury area and volume were smaller in the early hypothermia group in which hypothermia was induced before craniotomy and cerebral reperfusion (early, 115.2 ± 15.4 mm3; late, 344.7 ± 29.1 mm3; normothermia, 311.2 ± 79.2 mm3; p < 0.05). Conclusions The data suggest that early, preoperatively induced hypothermia could mediate the reduction of neuronal and glial damage in the reperfusion phase of ischemia/reperfusion brain injury.
- Published
- 2013
45. Major blunt head injury
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M. Ross Bullock, Brian Hood, and Leo Harris
- Subjects
Resuscitation ,Traumatic brain injury ,business.industry ,medicine.medical_treatment ,Head injury ,medicine.disease ,Hypoxemia ,Blood pressure ,Anesthesia ,Breathing ,medicine ,Intubation ,medicine.symptom ,Airway ,business - Abstract
Every scene, independent of the potential for head injury should begin with the establishment of an airway, ensuring breathing and circulation. The deleterious influence of hypotension (
- Published
- 2016
46. Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group
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Erdem Güresir, Sergei A. Kirov, Egill Rostrup, Christoph Drenckhahn, Martyn G. Boutelle, Brian A. MacVicar, Michael Schöll, Andrew I R Maas, Michael Scheel, Daniel Kondziella, Clemens Reiffurth, Johannes Platz, Jason M. Hinzman, Juan Sahuquillo, M. Ross Bullock, Frank Richter, Tomas Watanabe, Ilan Shelef, Kazutaka Sugimoto, Martin Lauritzen, Bart Feyen, Julia S. Bretz, Brandon Foreman, David O. Okonkwo, Eun Jeung Kang, Hartmut Vatter, Markus Dahlem, Anthony J. Strong, Ana I Oliveira-Ferreira, Jens P. Dreier, Nils Hecht, Baptiste Balança, Otto W. Witte, Christina M. Kowoll, Yoash Chassidim, Sharon L. Jewell, Rudolf Graf, Nina Eriksen, Thomas Lieutaud, Gerrit Brinker, Johannes Woitzik, Alon Friedman, Andrew P. Carlson, Nora F. Dengler, Henning Piilgaard, Bente Pakkenberg, Svetlana Lublinsky, Lee S Chung, Maren K.L. Winkler, Gajanan S. Revankar, C. William Shuttleworth, Christian Dohmen, Jan Claassen, Janos Luckl, Delphine Feuerstein, André P. Schulte, Michiyasu Suzuki, Edgar Santos, Michael Reiner, Denny Milakara, Peter Vajkoczy, Jed A. Hartings, Lori Shutter, Sebastian Major, Stéphane Marinesco, Daniel N. Hertle, Martin Fabricius, Michel D. Ferrari, Paul Jahnke, Viktor Horst, Uwe Heinemann, Alois Josef Schiefecker, Oliver W. Sakowitz, Peter Martus, M. Brandon Westover, Cenk Ayata, Renán Sánchez-Porras, Rick M. Dijkhuizen, Kc Brennan, Christian K. Friberg, Norberto Andaluz, R. David Andrew, Karl Schoknecht, Eric Rosenthal, Oscar Herreras, Georg Bohner, Raimund Helbok, Anna Maslarova, Eszter Farkas, and Arn M. J. M. van den Maagdenberg
- Subjects
0301 basic medicine ,Spreading depolarization ,cerebral blood flow ,Review ,Epileptogenesis ,0302 clinical medicine ,anoxic depolarization ,asphyxial depolarization ,Gray Matter ,Electrocorticography ,Review Articles ,brain edema ,spreading depression ,medicine.diagnostic_test ,spreading ischemia ,Cortical Spreading Depression ,Depolarization ,Stroke ,peri-infarct depolarization ,neurocritical care ,Neurology ,Cerebral blood flow ,Cortical spreading depression ,Cerebrovascular Circulation ,Practice Guidelines as Topic ,brain trauma ,neuroprotection ,Cardiology and Cardiovascular Medicine ,Critical Care ,subarachnoid hemorrhage ,neurovascular coupling ,Ischemia ,Focal ischemia ,03 medical and health sciences ,Journal Article ,medicine ,Humans ,vasospasm ,business.industry ,Neurointensive care ,medicine.disease ,intracerebral hemorrhage ,Neurophysiological Monitoring ,global ischemia ,030104 developmental biology ,Brain Injuries ,focal ischemia ,epilepsy ,epileptogenesis ,Human medicine ,Neurology (clinical) ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.
- Published
- 2016
47. Excitotoxicity and Metabolic Crisis Are Associated with Spreading Depolarizations in Severe Traumatic Brain Injury Patients
- Author
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Anna Teresa Mazzeo, Jed A. Hartings, M. Ross Bullock, J. Adam Wilson, and Jason M. Hinzman
- Subjects
0301 basic medicine ,Microdialysis ,Traumatic brain injury ,Excitotoxicity ,Poison control ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Neurochemistry ,electrocorticography ,electrocorticography, multi-modal monitoring, spreading depression ,spreading depression ,business.industry ,Glutamate receptor ,Original Articles ,medicine.disease ,multi-modal monitoring ,030104 developmental biology ,Anesthesia ,Cortical spreading depression ,Neurology (clinical) ,business ,Anaerobic exercise ,030217 neurology & neurosurgery - Abstract
Cerebral microdialysis has enabled the clinical characterization of excitotoxicity (glutamate >10 μM) and non-ischemic metabolic crisis (lactate/pyruvate ratio [LPR] >40) as important components of secondary damage in severe traumatic brain injury (TBI). Spreading depolarizations (SD) are pathological waves that occur in many patients in the days following TBI and, in animal models, cause elevations in extracellular glutamate, increased anaerobic metabolism, and energy substrate depletion. Here, we examined the association of SD with changes in cerebral neurochemistry by placing a microdialysis probe alongside a subdural electrode strip in peri-lesional cortex of 16 TBI patients requiring neurosurgery. In 107 h (median; range: 76–117 h) of monitoring, 135 SDs were recorded in six patients. Glutamate (50 μmol/L) and lactate (3.7 mmol/L) were significantly elevated on day 0 in patients with SD compared with subsequent days and with patients without SD, whereas pyruvate was decreased in the latter group on days 0 and 1 (two-way analysis of variance [ANOVA], p values 10 μmol/L and >40 μmol/L, respectively). Taken together with previous studies, these preliminary clinical results suggest SDs are a key pathophysiological process of secondary brain injury associated with non-ischemic glutamate excitotoxicity and severe metabolic crisis in severe TBI patients.
- Published
- 2015
48. Low-Dose Recombinant Tissue-Type Plasminogen Activator Enhances Clot Resolution in Brain Hemorrhage
- Author
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Stanley Tuhrim, Daniel F. Hanley, Michael A. Williams, Wendy C. Ziai, Neal J. Naff, Mario Zuccarello, Karen Lane, Salvador Cruz-Flores, William M. Coplin, David G. Brock, Stephan A. Mayer, Penelope M. Keyl, Stephen J. Haines, M. Ross Bullock, Anthony Marmarou, Raj K. Narayan, Nichol McBee, Issam A. Awad, and Denise H. Rhoney
- Subjects
Male ,medicine.medical_treatment ,Tissue plasminogen activator ,Cohort Studies ,Placebos ,medicine ,Humans ,Thrombolytic Therapy ,Cerebral perfusion pressure ,Blood Coagulation ,Cerebral Hemorrhage ,Intracranial pressure ,Advanced and Specialized Nursing ,Intracerebral hemorrhage ,business.industry ,Thrombosis ,Thrombolysis ,Middle Aged ,Respiration Disorders ,medicine.disease ,Recombinant Proteins ,Up-Regulation ,Treatment Outcome ,Intraventricular hemorrhage ,Tissue Plasminogen Activator ,Anesthesia ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Plasminogen activator ,medicine.drug - Abstract
Background and Purpose— Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. Methods— Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. Results— Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P =0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. Conclusions— Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment. Clinical Trial Registration— Participant enrollment began before July 1, 2005.
- Published
- 2011
49. Spreading depolarizations have prolonged direct current shifts and are associated with poor outcome in brain trauma
- Author
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Anthony J. Strong, Lori Shutter, Jens P. Dreier, Tomas Watanabe, Martin Fabricius, M. Ross Bullock, David O. Okonkwo, Johannes Woitzik, Clemens Pahl, Jed A. Hartings, and Ava M. Puccio
- Subjects
Adult ,Male ,Traumatic brain injury ,Electroencephalography ,Severity of Illness Index ,Statistics, Nonparametric ,Intensive care ,medicine ,Humans ,Depression (differential diagnoses) ,Aged ,Cerebral Cortex ,Chi-Square Distribution ,medicine.diagnostic_test ,Brain Neoplasms ,business.industry ,Penumbra ,Cortical Spreading Depression ,Human brain ,Middle Aged ,medicine.disease ,Electric Stimulation ,Electrophysiology ,medicine.anatomical_structure ,Anesthesia ,Cortical spreading depression ,Female ,Neurology (clinical) ,business - Abstract
Cortical spreading depolarizations occur spontaneously after ischaemic, haemorrhagic and traumatic brain injury. Their effects vary spatially and temporally as graded phenomena, from infarction to complete recovery, and are reflected in the duration of depolarization measured by the negative direct current shift of electrocorticographic recordings. In the focal ischaemic penumbra, peri-infarct depolarizations have prolonged direct current shifts and cause progressive recruitment of the penumbra into the core infarct. In traumatic brain injury, the effects of spreading depolarizations are unknown, although prolonged events have not been observed in animal models. To determine whether detrimental penumbral-type depolarizations occur in human brain trauma, we analysed electrocorticographic recordings obtained by subdural electrode-strip monitoring during intensive care. Of 53 patients studied, 10 exhibited spreading depolarizations in an electrophysiologic penumbra (i.e. isoelectric cortex with no spontaneous activity). All 10 patients (100%) with isoelectric spreading depolarizations had poor outcomes, defined as death, vegetative state, or severe disability at 6 months. In contrast, poor outcomes were observed in 60% of patients (12/20) who had spreading depolarizations with depression of spontaneous activity and only 26% of patients (6/23) who had no depolarizations (χ2, P0.001). Spontaneous electrocorticographic activity and direct current shifts of depolarizations were further examined in nine patients. Direct current shift durations (n=295) were distributed with a significant positive skew (range 0:51-16:19 min:s), evidencing a normally distributed group of short events and a sub-group of prolonged events. Prolonged direct current shifts were more commonly associated with isoelectric depolarizations (median 2 min 36 s), whereas shorter depolarizations occurred with depression of spontaneous activity (median 2 min 10 s; P0.001). In the latter group, direct current shift durations correlated with electrocorticographic depression periods, and were longer when preceded by periodic epileptiform discharges than by continuous delta (0.5-4.0 Hz) or higher frequency activity. Prolonged direct current shifts (3 min) also occurred mainly within temporal clusters of events. Our results show for the first time that spreading depolarizations are associated with worse clinical outcome after traumatic brain injury. Furthermore, based on animal models of brain injury, the prolonged durations of depolarizations raise the possibility that these events may contribute to maturation of cortical lesions. Prolonged depolarizations, measured by negative direct current shifts, were associated with (i) isoelectricity or periodic epileptiform discharges; (ii) prolonged depression of spontaneous activity and (iii) occurrence in temporal clusters. Depolarizations with these characteristics are likely to reflect a worse prognosis.
- Published
- 2011
50. Alterations in Cerebral Oxidative Metabolism following Traumatic Brain Injury
- Author
-
Richard A. Rammo, M. Ross Bullock, Michael De Fazio, and Kristine O’Phelan
- Subjects
Microdialysis ,Pathology ,medicine.medical_specialty ,Neurology ,Traumatic brain injury ,Poison control ,Critical Care and Intensive Care Medicine ,Young Adult ,Therapeutic approach ,Pyruvic Acid ,Extracellular ,medicine ,Humans ,Lactic Acid ,business.industry ,Brain ,medicine.disease ,Pathophysiology ,Oxygen ,Brain Injuries ,Anesthesia ,Female ,Wounds, Gunshot ,Neurology (clinical) ,Gunshot wound ,Tomography, X-Ray Computed ,business - Abstract
Traumatic brain injury (TBI) generates regional alterations in cerebral metabolism, leading to the potential evolution of persistent metabolic dysfunction. In the case of penetrating, firearm-related TBI, the pathophysiological mechanisms underlying these acute-phase metabolic derangements are not entirely understood—hindering the potential effectiveness of therapeutic intervention. The use of cerebral microdialysis to monitor biochemical alterations that occur, post-TBI, provides critical insight into the events that perpetuate neurological deterioration. Cerebral microdialysis was used to monitor alterations in the brain tissue chemistry of a 22-year-old female patient who sustained a penetrating gunshot wound to the head. Extracellular glucose, lactate, pyruvate, and lactate pyruvate ratio (LPR) were monitored over the course of the first-week post-injury. Analysis of the microdialysate revealed sustained elevations in LPR with peaks in excess of those seen in patients who have sustained permanent ischemic injury. This interval of persistently elevated LPR was followed by a spontaneous reduction of values, to levels below the defined threshold for metabolic crisis, over a period of several days. Microdialysis studies may significantly improve the understanding of the metabolic alterations that occur in patients who sustain a variety of forms of neurotrauma. Ultimately, monitoring these variations in brain tissue chemistry will improve the insight into the neuropathological mechanisms underlying penetrating traumatic brain injury, and enhance the therapeutic approach of these patients.
- Published
- 2011
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