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101. Additional file 1 of Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury

Author

Lassarén, Philipp, Lindblad, Caroline, Frostell, Arvid, Carpenter, Keri L. H., Guilfoyle, Mathew R., Hutchinson, Peter J. A., Helmy, Adel, and Thelin, Eric Peter

Abstract

Additional file 1. Title of data: Baseline data. Description of data: Columns for the first eight rows are for each patient (C, control; I, intervention); moreover, the first four rows have time along the horizontal axis. Columns for the final row are for each cytokine. Rows 1-3 display changes over time of white cell count (WCC), C-reactive protein (CRP) and temperature, with corresponding lines of best fit. Row 4 displays infection status of patients over time. Row 5 shows infection (VAP, ventilator-associated pneumonia; IAS intra-abdominal sepsis; CI, chest infection), severe adverse events (SAE), sex (M, male; F, female) and years of age for each patient. Row 6 shows Stockholm computed tomography (CT) score for each patient, coloured after whether a deterioration was observed during hospital stay. Row 7 shows injury severity score (ISS) for each patient. Row 8 shows fraction of missingness in each compartment and for each patient. Row 9 shows fraction of missing cytokines in each compartment. The chest infection was a result of mucous plugging resulting in a right lower lobe collapse, hence not fulfilling VAP criteria.

Published
2021
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103. sj-pdf-1-jcb-10.1177_0271678X211042112 - Supplemental material for Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction

Author

Khellaf, Abdelhakim, Garcia, Nuria Marco, Tajsic, Tamara, Alam, Aftab, Stovell, Matthew G, Killen, Monica J, Howe, Duncan J, Guilfoyle, Mathew R, Jalloh, Ibrahim, Timofeev, Ivan, Murphy, Michael P, Carpenter, T Adrian, Menon, David K, Ercole, Ari, Hutchinson, Peter J, Carpenter, Keri LH, Thelin, Eric P, and Helmy, Adel

Subjects
110320 Radiology and Organ Imaging, FOS: Clinical medicine, FOS: Biological sciences, Medicine, Cell Biology, 110305 Emergency Medicine, 110306 Endocrinology, Biochemistry, 69999 Biological Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X211042112 for Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction by Abdelhakim Khellaf, Nuria Marco Garcia, Tamara Tajsic, Aftab Alam, Matthew G Stovell, Monica J Killen, Duncan J Howe, Mathew R Guilfoyle, Ibrahim Jalloh, Ivan Timofeev, Michael P Murphy, T Adrian Carpenter, David K Menon, Ari Ercole, Peter J Hutchinson, Keri LH Carpenter, Eric P Thelin and Adel Helmy in Journal of Cerebral Blood Flow & Metabolism

Published
2021
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107. The endoscope-assisted supraorbital 'keyhole' approach for anterior skull base meningiomas: an updated meta-analysis

Author

Khan, Danyal Z., Muskens, Ivo S., Mekary, Rania A., Zamanipoor Najafabadi, Amir H., Helmy, Adel E., Reisch, Robert, Broekman, Marike L. D., Marcus, Hani J., Khan, Danyal Z. [0000-0001-9213-2550], Apollo - University of Cambridge Repository, and Khan, Danyal Z [0000-0001-9213-2550]

Subjects
Male, Natural Orifice Endoscopic Surgery, Cerebrospinal Fluid Leak, Supraorbital keyhole, Tumor – Meningioma, Middle Aged, Vascular System Injuries, Eye, Skull Base Neoplasms, Original Article - Tumor - Meningioma, Postoperative Complications, Neuroendoscopy, Meningeal Neoplasms, Humans, Skull base surgery, Female, Endoscopic transsphenoidal surgery, Olfactory groove meningioma, Meningioma, Microscopic transcranial surgery, Tuberculum Sellae Meningioma
Abstract

Introduction: The gold-standard treatment for symptomatic anterior skull base meningiomas is surgical resection. The endoscope-assisted supraorbital “keyhole” approach (eSKA) is a promising technique for surgical resection of olfactory groove (OGM) and tuberculum sellae meningioma (TSM) but has yet to be compared with the microscopic transcranial (mTCA) and the expanded endoscopic endonasal approach (EEA) in the context of existing literature. Methods: An updated study-level meta-analysis on surgical outcomes and complications of OGM and TSM operated with the eSKA, mTCA, and EEA was conducted using random-effect models. Results: A total of 2285 articles were screened, yielding 96 studies (2191 TSM and 1510 OGM patients). In terms of effectiveness, gross total resection incidence was highest in mTCA (89.6% TSM, 91.1% OGM), followed by eSKA (85.2% TSM, 84.9% OGM) and EEA (83.9% TSM, 82.8% OGM). Additionally, the EEA group had the highest incidence of visual improvement (81.9% TSM, 54.6% OGM), followed by eSKA (65.9% TSM, 52.9% OGM) and mTCA (63.9% TSM, 45.7% OGM). However, in terms of safety, the EEA possessed the highest cerebrospinal fluid leak incidence (9.2% TSM, 14.5% OGM), compared with eSKA (2.1% TSM, 1.6% OGM) and mTCA (1.6% TSM, 6.5% OGM). Finally, mortality and intraoperative arterial injury were 1% or lower across all subgroups. Conclusions: In the context of diverse study populations, the eSKA appeared not to be associated with increased adverse outcomes when compared with mTCA and EEA and offered comparable effectiveness. Case-selection is paramount in establishing a role for the eSKA in anterior skull base tumours.

Published
2020

108. Temporal profile of intracranial pressure and cerebrovascular reactivity in severe traumatic brain injury and association with fatal outcome: An observational study

Author

Adams, Hadie, Donnelly, Joseph, Czosnyka, Marek, Kolias, Angelos G., Helmy, Adel, Menon, David K., Smielewski, Peter, and Hutchinson, Peter J.

Subjects
Intracranial pressure -- Complications and side effects, Brain injuries -- Risk factors, Cerebrovascular disorders -- Complications and side effects, Biological sciences
Abstract

Background Both intracranial pressure (ICP) and the cerebrovascular pressure reactivity represent the dysregulation of pathways directly involved in traumatic brain injury (TBI) pathogenesis and have been used to inform clinical management. However, how these parameters evolve over time following injury and whether this evolution has any prognostic importance have not been studied. Methods and findings We analysed the temporal profile of ICP and pressure reactivity index (PRx), examined their relation to TBI-specific mortality, and determined if the prognostic relevance of these parameters was affected by their temporal profile using mixed models for repeated measures of ICP and PRx for the first 240 hours from the time of injury. A total of 601 adults with TBI, admitted between September 2002 to January 2016, and with high-resolution continuous monitoring from a single centre, were studied. At 6 months postinjury, 133 (19%) patients had a fatal outcome; of those, 88 (78%) died from nonsurvivable TBI or brain death. The difference in mean ICP between those with a fatal outcome and functional survivors was only significant for the first 168 hours after injury (all p < 0.05). For PRx, those patients with a fatal outcome also had a higher (more impaired) PRx throughout the first 120 hours after injury (all p < 0.05). The separation of ICP and PRx was greatest in the first 72 hours after injury. Mixed models demonstrated that the explanatory power of the PRx decreases over time; therefore, the prognostic weight assigned to PRx should similarly decrease. However, the ability of ICP to predict a fatal outcome remained relatively stable over time. As control of ICP is the central purpose of TBI management, it is likely that some of the information that is reflected in the natural history of ICP changes is no longer apparent because of therapeutic intervention. Conclusions We demonstrated the temporal evolution of ICP and PRx and their relationship with fatal outcome, indicating a potential early prognostic and therapeutic window. The combination of dynamic monitoring variables and their time profile improved prediction of outcome. Therefore, time-driven dynamic modelling of outcome in patients with severe TBI may allow for more accurate and clinically useful prediction models. Further research is needed to confirm and expand on these findings., Author(s): Hadie Adams 1,*, Joseph Donnelly 1, Marek Czosnyka 1,2, Angelos G. Kolias 1, Adel Helmy 1, David K. Menon 3, Peter Smielewski 1, Peter J. Hutchinson 1 Introduction Traumatic [...]

Published
2017
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112. Contributors

Author

Aarabi, Bizhan, Abbott, Rick, Abd-El-Barr, Muhammad M., Abel, Taylor J., Abou-Al-Shaar, Hussam, Acar, Feridun, Achey, Rebecca L., Ackerman, Laurie L., Adappa, Nithin D., Adelson, P. David, Agarwal, Nitin, Aguirre-Padilla, David H., Ahluwalia, Manmeet S., Ahmad, Shahjehan, Ahmed, A. Karim, Ahmed, Raheel, Aisiku, Imoigele P., Akbar, Muhammad A., Akram, Harith, Alaraj, Ali, Albrecht, Jennifer S., Albuquerque, Felipe C., Alexander, Michael J., Alexandrov, Andrei V., Alexopoulos, Andreas V., Ali, Zarina S., Al-Khalili, Kenan, Al-Mefty, Ossama, Al-Mefty, Rami O., Alnahhas, Iyad, Alrobaian, Malek, Al-Saiegh, Fadi, Alterman, Ron L., Altshuler, David B., Amenta, Peter S., Ames, Christopher P., Amin-Hanjani, Sepideh, Ammirati, Mario, Andaluz, Norberto, Anderson, Richard C.E., Andrade, Pablo, Ares, William J., Arle, Jeffrey E., Arnaout, Omar, Arnold, Paul M., Assina, Rachid, Aszmann, Oskar C., Attenello, Frank J., III, Attia, Albert, Avellino, Anthony M., Awad, Issam A., Ayantayo, Temitayo O., Bader, Edward R., Badhiwala, Jetan H., Baehring, Joachim M., Bagic´, Anto I., Bagley, Stephen J., Bai, Michael Y., Bailes, Julian E., Bain, Mark, Baker, Turner, Ball, Perry A., Ballester, Leomar Y., Balu, Ramani, Ban, Vin Shen, Barak, Tanyeri, Baranoski, Jacob F., Barbaro, Nicholas M., Barber, Sean M., Barker, Frederick G., II, Barnett, Gene H., Barone, Constance M., Barrow, Daniel Louis, Basma, Jaafar, Batchelor, Tracy T., Batjer, H. Hunt, Beattie, Michael S., Beaumont, Andrew, Beaumont, Thomas L., Bederson, Joshua B., Belani, Puneet, Belzberg, Allan J., Benet, Arnau, Ben-Haim, Sharona, Berenstein, Alejandro, Berga, Sarah L., Berger, Mitchel S., Bergsneider, Marvin, Bernstock, Joshua D., Bhatia, Sanjay, Bi, Wenya Linda, Bigder, Mark G., Bijlenga, Philippe, Bingaman, William, Birk, Harjus S., Bishop, Allen T., Blakeley, Jaishri O., Blomstedt, Patric, Blue, Rachel, Blumenthal, Scott, Boaro, Alessandro, Boddu, James V., Bohnen, Angela, Bok, Arnold P., Boone, Myles D., Boop, Frederick A., Boszczyk, Bronek M., Bowyer, Susan M., Brahimaj, Bledi C., Brem, Henry, Brem, Steven, Bresnahan, Jacqueline C., Brinjikji, Waleed, Brinkmann, Benjamin H., Brînzeu, Andrei, Britz, Gavin W., Brockmeyer, Douglas L., Brown, Desmond A., Brown, Justin M., Brown, Matthew T., Brown, Robert D., Jr., Bruce, Jeffrey N., Bruckman, Karl C., Bruhat, Alexis, Brunstrom-Hernandez, Janice E., Brunswick, Andrew, Bruzek, Amy K., Buchanan, Ian A., Budohoski, Karol P., Buell, Thomas J., Büki, András, Bunevicius, Adomas, Burchiel, Kim J., Bydon, Mohamad, Byrne, Richard W., Cabrejo, Raysa, Cabrilo, Ivan, Cahill, Daniel P., Caplan, Justin M., Carlson, Andrew P., Carrión-Penagos, Julián, Carroll, Benjamin W., Cascino, Gregory D., Castaneyra-Ruiz, Leandro, Castinetti, Frederic, Cavalcanti, Daniel D., Cawley, C. Michael, Cernak, Ibolja, Cetas, Justin S., Chan, Michael D., Ka-Ying Chan, Vivien, Chang, Chih-Chang, Chang, Louis, Chang, Steven D., Charbel, Fady T., Charest-Morin, Raphaële, Chari, Aswin, Chaudhary, Navjot, Chauvel, Patrick, Chen, Kevin S., Chen, Liang, Cheng, Joseph, Cherian, Jacob, Cheung, Kenneth M.C., Cheyuo, Cletus, Chiang, Veronica L., Chiarelli, Peter A., Chiocca, E. Antonio, Chitale, Rohan V., Cho, Catherine, Choi, Heejung, Chou, Dean, Christian, Cindy W., Christiansen, Peter A., Church, Ephraim W., Clarke, Jennifer L., Cleary, Daniel R., Clune, James E., Cohen, Justin D., Cohen-Inbar, Or, Colasanti, Roberto, Collins, John M., Comair, Youssef G., Conner, Andrew K.P., Connolly, E. Sander, Jr., Cooper, Jared B., Corcos, Daniel Montie, Coric, Domagoj, Costa, Anthony B., Couldwell, William T., Crino, Peter B., Crofton, Andrew R., Cullen, D. Kacy, Curt, Armin, Dacey, Ralph G., Jr., Daci, Rrita, Dailey, Andrew T., D’Alessandris, Quintino Giorgio, Damisah, Eyiyemisi C., Daniels, David J., Das, Sunit, Davanzo, Justin R., David, Carlos A., David, David J., Davidson, Benjamin, Davis, Gavin A., Day, Arthur L., Dea, Nicolas, De Donato, Giuseppe, Deiner, Stacie, De la Garza, Carlos, Delavari, Nader, Del Brutto, Oscar H., Delman, Bradley N., DeLong, Mahlon R., DeMonte, Franco, de Oliveira, Evandro, Derman, Peter B., Desai, Arati, Deshpande, Krutika, Diaz, Michele, Diaz-Arrastia, Ramon R., DiGiorgio, Anthony M., DiLuna, Michael L., DiMeco, Francesco, Dlouhy, Brian J., Doğruel, Yücel, Donahue, Joseph H., Donoho, Daniel A., Doshi, Amish H., Dreier, Jens P., Driver, Joseph, Drofa, Alexander, Ducruet, Andrew F., Duffau, Hugues, Duhaime, Ann-Christine, Dumont, Aaron S., Duncan, John S., Dunn, Gavin P., Dunn, Ian F., Eberwine, James H., Eckardt, Gerald W., Edem, Idara J., Edwards, Michael S.B., Egemen, Emrah, Eisenbarth, Rachel, Eisenberg, Howard, Elder, J. Bradley, Elhammady, Mohamed Samy, Elias, W. Jeffrey, Ellingson, Benjamin M., Ellis, Jason A., Elswick, Clay M., Emch, Todd M., Emerson, Samuel, Ene, Chibawanye I., Englot, Dario J., Erdman, John H., III, Eskandari, Ramin, Essayed, Walid Ibn, Everson, Richard G., Fadul, Camilo E., Fan, Yi, Farina, Dario, Farrell, Christopher J., Feghali, James, Fehlings, Michael G., Fehnel, Katie Pricola, Feigin, Valery L., Feldman, Eva L., Feldman, Michael J., Feldstein, Neil, Fenno, Lief E., Ferguson, Adam R., Feroze, Abdullah H., Fessler, Richard G., Filler, Aaron G., Findlay, J. Max, Finn, Michael A., Finnell, Richard H., Fisher, Charles G., Flamm, Eugene S., Flanders, Tracy M., Flemming, Kelly D., Flores-Sarnat, Laura, Follett, Kenneth A., Fontes, Ricardo B.V., Ford, Paul J., Foreman, Brandon P., Foreman, Paul M., Fornoff, Linden E., Fouda, Mohammed A., Foyouzi, Nastaran, Franco, Daniel, Franzini, Andrea, Fridley, Jared S., Friedlander, Robert M., Frisoli, Fabio A., Fry, Donald E., Gregory Fu, Kai-Ming, Fujita, Naohide, Fulbright, Robert K., Fulkerson, Daniel H., Fuller, Gregory N., Fusco, Matthew R., Galanopoulou, Aristea S., Gallagher, Gary W., Galvan, Adriana, Gander, Phillip E., Gandhi, Chirag D., Gao, Guoyi, Garcia, Hector H., García, Paul S., Gardner, Paul A., Gardner, Raquel C., Garzon-Muvdi, Tomas, Gavin, Cormac G., Gea-Banacloche, Juan C., George, Timothy M., Georgoulis, George D., Gerard, Carter S., Gerety, Patrick A., Gerszten, Kristina, Gerszten, Peter C., Ghaith, Abdul Karim, Ghatan, Saadi, Ghobrial, George M., Ghogawala, Zoher, Ghosh, Chaitali, Giacino, Joseph T., Giacobbe, Peter, Gianaris, Thomas J., Giannotta, Steven L., Giglio, Pierre, Gilad, Ronit, Gill, Brian J.A., Gillick, John L., Gilmer, Holly S., Gjedde, Albert H., Glenn, Chad A., Godil, Saniya S., Goel, Atul, Gokaslan, Ziya L., Goldberg, Jacob L., Goldstein, Hannah E., Golub, Danielle, Gonzalez, Glenn A., Gonzalez-Martinez, Jorge Á., Goodden, John R., Goodman, J. Clay, Goodrich, James Tait, Goodwin, C. Rory, Gordon, David S., Gottfried, Oren N., Goumnerova, Liliana C., Goyal, Anshit, Grady, M. Sean, Graffeo, Christopher S., Grafman, Jordan H., Gragnaniello, Cristian, Grande, Andrew W., Grant, Gerald A., Grebenciucova, Elena, Greenfield, Jeffrey, Grimaudo, Heather C., Groff, Michael W., Gross, Robert E., Grossman, Rachel, Groves, Mari L., Gstoettner, Clemens, Guenette, Jeffrey P., Günel, Murat, Gupta, Nalin, Gutman, Matthew J., Guyer, Richard D., Hachem, Laureen D., Haddad, Georges F., Hadjipanayis, Constantinos G., Hafez, Daniel M., Hagan, John P., Haglund, Michael M., Haines, Stephen J., Haldeman, Clayton L., Halvorson, Kyle G., Hamberger, Marla J., Hamdi, Hussein, Hamilton, D. Kojo, Hamilton, Kimberly M., Hamilton, Mark G., Hankinson, Todd C., Haq, Ihtsham ul, Harbaugh, Robert E., Hardesty, Douglas A., Hardigan, Trevor, Hariz, Marwan, Harrigan, Mark R., Harrop, James S., Hartings, Jed A., Härtl, Roger, Harward, Stephen C., II, Hasbun, Rodrigo, Hawryluk, Gregory W.J., Hayman, Erik, Hayward, Richard D., He, Lucy, Healy, Andrew T., Heary, Robert F., Heiden, Petra, Heinricher, Mary M., Heller, Robert S., Retel Helmrich, Isabel R.A., Helmy, Adel, Heman-Ackah, Sabrina M., Hendricks, Benjamin K., Herendeen, John S., Heros, Roberto C., Herrup, Karl, Hervey-Jumper, Shawn L., Heuer, Gregory G., Heyer, Eric J., Higuchi, Yoshinori, Hillary, Frank G., Ho, Winson S., Hoang, Nguyen, Hoang, Stanley, Hoelscher, Christian, Hoffer, S. Alan, Hofstetter, Christoph, Holland, Eric C., Holland, Ryan M., Holste, Katherine, Hongo, Kazuhiro, Horisawa, Shiro, Horner, Philip J., Howard, Matthew A., III, Hsueh, Brian, Huang, Judy, Huang, Kevin T., Huang, Michael C., Huang, Raymond Y., Hudgins, Eric, Huguenard, Anna, Hunt, Matthew A., Hurlbert, R. John, Hussein, Ahmed E., Hutchinson, Peter J., Huttner, Anita, Huys, Daniel, Hwang, Steven W., Iaccarino, Mary A., Ibrahim, Mohab, Iliff, Jeffrey J., Ilyas, Adeel, Ingram, Susan L., Isaacs, Albert M., Isaias, Ioannis U., Iskandar, Bermans J., Iyer, Aditya K., Jabbour, Pascal, Jackson, Christopher M., Jadhav, Ashutosh P., Jakobs, Martin, Jallo, George I., Jane, John A., Jr., Janigro, Damir, Jankowitz, Brian T., Jea, Andrew, Jehi, Lara, Jellinger, Kurt A., Jenson, Amanda V., Jho, Diana, Jiang, Bowen, Jiang, Fan, Jimenez, David F., Jimenez, Lincoln, Jin, Haiyan, Jo, Jasmin T., Johanson, Conrad E., Johnson, Luke A., Johnson, Mark D., Johnson, Nathaniel, Jones, Adrian C., Jones, Kristen E., Jones, Tuckerman, Joseph, Jacob R., Joshi, Krishna C., Joshi, Rushikesh S., Jovin, Tudor G., Julian, Alex, Juraschka, Kyle, Abdo do Seixo Kadri, Paulo, Kalani, M. Yashar S., Kalanithi, Paul S.A., Kalfas, Iain H., Kalnins, Aleksandrs Uldis, Kamath, Ashwin A., Kanev, Paul M., Kang, Daniel G., Kang, James D., Kanter, Adam S., Kaplitt, Michael G., Kappel, Ari D., Karikari, Isaac, Karsy, Michael, Kasliwal, Manish K., Kaufmann, Anthony M., Kawasaki, Hiroto, Kellner, Christopher P., Kelly, Alexander P., Kemeny, Andras A., Kestle, John R.W., Khalsa, Siri S., Khan, Imad S., Khan, Nadia, Khan, Tariq, Khanna, Omaditya, Khanna, Ryan, Kigerl, Kristina A., Kim, Dong H., Kim, Louis J., Kim, Paul K., Kim, Thomas A., Kim, Won, Kirnaz, Sertaç, Kirsch, Wolff, Kitchen, Neil D., Klein, Joshua P., Kliot, Michel, Knightly, John J., Knisely, Jonathan, Knopman, Jared, Ko, Andrew L., Kobayashi, Katsuya, Kobets, Andrew J., Koch, Matthew J., Kocharian, Gary, Koerner, John D., Kohara, Kotaro, Kohn, Max, Kolias, Angelos G., Koo, Clara S., Kosztowski, Thomas, Kotecha, Rupesh R., Kovach, Christopher K., Kraemer, Mark R., Krauss, Joachim K., Krieg, Sandro M., Krieger, Mark D., Krishnaney, Ajit A., Ksendzovsky, Alexander, Kulkarni, Abhaya V., Vijay Kumar, Gomatam R., Kumar, Sachin A., Kung, David K., Kuo, Jeffrey V., Kvint, Svetlana, Kwan, Kenny, Issa Laack, Nadia N., Ladner, Travis R., Lafage, Renaud, Lafage, Virginie, Lam, Arthur M., Lamm, Adam G., Landazuri, Patrick, Lanzino, Giuseppe, Larson, Paul, Lau, Catherine Y., Lau, Darryl, Lavine, Sean D., Lawler, Sean E., Laws, Edward R., Jr., Lawton, Michael T., Laxpati, Nealen G., Lebed, Brett D., Lee, Cheng-Chia, Lee, Jonathan J., Lee, Ryan P., Lee, Sangmi, Lehman, Ronald A., Jr., Lenke, Lawrence G., Le Roux, Peter D., Leuthardt, Eric C., Levin, Emily, Levy, Elad I., Lewis, Evan M., Lhatoo, Samden, Li, Dianyou, Li, Yingda, Ching Ng, Angela Li, Liau, Linda M., Liebenow, Brittany, Lieberman, Isador H., Limbrick, David D., Jr., Lin, Emily, Lin, Kant Y., Lin, Zhengyu, Lingsma, Hester F., Linskey, Mark E., Lipsman, Nir, Litvack, Zachary N., Liu, James K.C., Liu, Kenneth C., Liu, Wei, Lober, Robert M., Lohkamp, Laura-Nanna, Lonser, Russell R., Louvi, Angeliki, Lozano, Andres M., Lu, Victor M., Luciano, Mark G., Lukas, Rimas V., Luo, Lan, Ma, Lijun, Maas, Andrew I.R., Macdonald, R. Loch, Mack, William J., Mackey, Kimberly A., Macki, Mohamed, MacLachlan, Lara S., Madarash, Holly Oemke, Madsen, Peter J., Maegele, Marc, Magistretti, Pierre J., Mahan, Mark A., Maher, Cormac O., Mahtabfar, Aria, Majeed, Kashif, Makarenko, Serge, Makley, Amy T., Malessy, Martijn J.A., Malik, Athar N., Mallucci, Conor, Mambelli, Dorian D., Mammi, Marco, Mangano, Francesco T., Maniker, Allen H., Manley, Geoffrey T., Manolidis, Spiros, Maroon, Joseph C., Martin, Alastair, Martin, Neil A., Martirosian, Vahan, Martirosyan, Nikolay L., Maslink, Colin, Massie, Lara, Mathur, Amit M., Matias, Caio M., Mauer, Kimberly M., Maulucci, Christopher M., Maurer, Robert K., Mazur, Marcus D., Mazwi, Nicole, McAllister, James P., II, McClain, Craig D., McCormack, Ryan M., McCrea, Michael A., McCutcheon, Ian E., McDermott, Michael W., McDougall, Cameron G., McDougall, Cameron M., McEvoy, Andrew W., McGrath, Hari, McGrath, Lynn, Jr., McKhann, Guy M., McMahon, J. Tanner, McPheeters, Matthew J., Meaney, David F., Medel, Ricky, Medress, Zachary, Mehta, Minesh P., Menacho, Sarah T., Menezes, Arnold H., Menon, David K., Mergeche, Joanna L., Meyer, Fredric B., Meyer, Jenna, Meyer, Scott A., Meyers, Philip M., Midha, Rajiv, Miller, Charles A., Miller, Jonathan P., Miller, Neil R., Mirza, Farhan A., Mirzadeh, Zaman, Miserocchi, Anna, Misra, Basant K., Missios, Symeon, Miyagishima, Danielle F., Miyashiro, Kevin Y., Mizuno, Junichi, Mizuno, Shuichi, Mocco, J., Mohyeldin, Ahmed, Mokin, Maxim, Molinaro, Annette M., Moliterno, Jennifer, Monteith, Stephen J., Montenegro, Thiago S., Mooney, Michael A., Moosa, Shayan, Morales, Diego M., Morgan, Clinton D., Morgan, Isabella, Morgan, Michael Kerin, Mortimer, Vance R., Moss, Nelson, Moss, S. David, Mukherjee, Pratik, Mummaneni, Praveen V., Munich, Stephan A., Muraszko, Karin, Murthy, Saikiran G., Mushlin, Harry, Mussi, Antônio C.M., Nagel, Sean J., Nagy, Gábor, Nair, Dileep R., Najm, Imad M., Nakaji, Peter, Nakajima, Takeshi, Nasser, Rani, Nater, Anick, Navarro, Jovany Cruz, Nayak, Lakshmi, Neira, Justin A., Nelson, Lindsay D., Neman, Josh, Newell, David W., Nguyen, James H., Ngwenya, Laura Benjamin, Nicolato, Antonio, Nimjee, Shahid M., Nishimura, Sayoko, Niu, Tianyi, Norris, Scott A., Noureldine, Mohammad Hassan A., Nurmikko, Turo J., Nuwer, Marc R., Oberheim-Bush, Nancy Ann, Ochiai, Taku, Oh, Nathan, Oh, Taemin, Okonkwo, David O., Okun, Michael S., Oldfield, Edward H., Brigid O’Leary, Joanna Shawn, Olivi, Alessandro, O’Neill, Francis, Oppenlander, Mark E., Osbun, Joshua W., O’Toole, John E., Özduman, Koray, Ozpinar, Alp, Pain, Margaret, Palacios, Eva M., Palmer, James N., Pamir, M. Necmettin, Pamoukian, Vicken, Panesar, Sandip S., Panov, Fedor E., Paramasivam, Srinivasan, Park, Christine, Park, Jon, Park, Paul, Park, T.S., Parker, Whitney E., Parsa, Andrew T., Partington, Michael D., Patel, Aman B., Patel, Bhuvic, Patel, Smruti K., Patel, Vaibhav M., Patil, Parag G., Payne, Russell, Peeters, Sophie M., Pekmezci, Melike, Pendharkar, Arjun V., Penn, Richard Deren, Pennicooke, Brenton H., Pennington, Zach, Della Pepa, Giuseppe Maria, Perin, Alessandro, Perlmutter, Joel S., Persing, J. Scott, Persing, John A., Persing, Sarah M., Peters, Matthew E., Petersen, Erika A., Petrov, Dmitriy, Pham, Martin, Picht, Thomas, Piepmeier, Joseph M., Pikis, Stylianos, Pilcher, Webster H., Pinckard-Dover, Heather N., Pineda, José A., Pinter, Joseph D., Pisculli, Mary L., Pittman, Thomas, Plesnila, Nikolaus, Pollack, Ian F., Pollock, Bruce E., Polly, David W., Jr., Polster, Sean P., Popovich, Phillip G., Post, Kalmon D., Potts, Matthew B., Pouratian, Nader, Powers, Alexander K., Prager, Briana C., Prashant, Giyarpuram N., Prestigiacomo, Charles J., Prevedello, Daniel M., Proctor, Mark R., Prolo, Laura M., Prost, Robert W., Puduvalli, Vinay K., Purger, David A., Qualmann, Krista J., Quiñones-Hinojosa, Alfredo, Raffa, Scott J., Raghavan, Prashant, Rahal, Jason Pierce, Rajappa, Prajwal, Ram, Zvi, Ranjan, Manish, Rao, Ganesh, M.S. Raper, Daniel, Rapoport, Benjamin I., Raskin, Jeffrey S., Raslan, Ahmed M., Rasmussen, Peter, Rasouli, Jonathan J., Ravindra, Vijay M., Ray, Dibyendu K., Ray, Wilson Z., Raz, Eytan, Raza, Shaan M., Régis, Jean, Reilly, Peter L., Reith, Florence C.M., Rennert, Robert C., Resnick, Daniel K., Reynolds, Renée, Rezai, Ali R., Rhines, Laurence D., Rhoton, Albert L., Jr., Ribalta, Teresa, Richardson, R. Mark, Riggins, Gregory J., Riina, Howard A., Rinaldo, Lorenzo, Rincon-Torroella, Jordina, Ringer, Andrew J., Riva-Cambrin, Jay, Rizk, Elias, Robert, Stephanie M., Robertson, Claudia, Robertson, Jon H., Robinson, Leslie C., Robinson, Michael W., Robinson, Shenandoah, Roche, Aidan D., Roche, Pierre-Hugues, Rogg, Jeffrey M., Roguski, Marie, Roland, Jarod L., Rolston, John D., Rosenberg, William S., Rosenow, Joshua M., Rosenthal, Guy, Rosenwasser, Robert H., Roser, Florian, Rosner, Michael K., Rosseau, Gail, Rossi, Vincent J., Rovner, Eric S., Rubiano, Andres M., Rubio, Roberto Rodriguez, Rucker, Janet C., Rui, Yanning, Russin, Jonathan J., Rutka, James T., Saadeh, Yamaan S., Saatian, Behnaz, Sack, Kenneth D., Sader, Nicholas, Safaee, Michael M., Safain, Mina G., Sagher, Oren, Sahgal, Arjun, Saigal, Rajiv, Saito, Nobuhito, Saleh, Mohamed, Salinas, Ryan D., Salminger, Stefan, Samarage, H. Milan, Samdani, Amer F., Sand, Lauren A., Sani, Sepehr, Sankaran, Sujatha, Sansur, Charles A., Santarius, Thomas, Santiago, Paul, Santiago-Dieppa, David R., Santiago-Sim, Teresa, Sarkiss, Christopher A., Sarnat, Harvey B., Sarris, Christina E., Sather, Michael, Savastano, Luis E., Sawaya, Raymond, Schaller, Karl, Schiff, Nicholas D., Schipmann, Stephanie, Schlachter, Leslie, Schlesinger, David J., Schmidt, Franziska A., Schmidt, Meic H., Schneider, Lonnie, Schramm, Johannes, Schuele, Stephan U., Schulder, Michael, Schupper, Alexander J., Schwab, Frank J., Schwartz, Theodore H., Sciubba, Daniel M., Scott, R. Michael, Scullen, Tyler A., Selden, Nathan R., Sellin, Jonathan N., Selman, Warren R., Sen, Chandranath, Serizawa, Toru, Serrone, Joseph C., Sgubin, Donatella, Shaffrey, Christopher I., Shah, Kushal J., Shah, Lubdha M., Shah, Manish N., Shahlaie, Kiarash, Shapiro, Maksim, Sharan, Ashwini, Sharma, Deepak, Sharma, Mohan R., Sheehan, Jason P., Sheehan, Jonas M., Sheikhi, Lila, Shiflett, James M., Shigamatsu, Tomoyoshi, Shilpakar, Sushil Krishna, Shils, Jay L., Shimony, Nir, Shin, Alexander Y., Siddiqui, Adnan H., Sidhu, Meneka K., Silveira, Luke A., Silver, Jerry, Sindou, Marc, Singh, Jeffrey M., Singh, Manish K., Sizdahkhani, Saman, Skirboll, Stephen, Slavin, Justin, Smith, Brandon W., Smith, Edward R., Smith, Justin S., Smith, Kris A., Smith, Luke G.F., Smith, Timothy R., Smith, Yoland, Solomon, David A., Solomon, Robert A., Soltys, Scott G., Somji, Mohamed, Sorenson, Jeffrey M., Soriano, Sulpicio G., Sorscher, Michelle, Souweidane, Mark M., Spencer, Dennis D., Spetzler, Robert F., Spinazzi, Eleonora F., Spinner, Robert J., Sribnick, Eric A., Srinivasan, Visish M., Stabingas, Kristen, Stapleton, Christopher J., Starke, Robert M., Starr, Philip, St. Clair, Eric G., Stedelin, Brittany, Stefko, S. Tonya, Steinberg, Gary K., Stern, Matthew A., Steyerberg, Ewout W., Stieg, Philip E., Stone, Scellig S.D., Stoodley, Marcus, Strahle, Jennifer M., Stricsek, Geoffrey, Strong, Anthony, Strowd, Roy E., III, Stummer, Walter, Su, YouRong S., Sughrue, Michael E., Suh, John H., Sulaiman, Wale A.R., Sun, Bomin, Sun, Matthew Z., Sun, Xiaonan Richard, Sundaram, Vikram K., Sweid, Ahmad, Syed, Hasan R., Tagliati, Michele, Taira, Takaomi, Tajsic, Tamara, Takagi, Yasushi, Takeoka, Yoshiki, Tamargo, Rafael J., Tanaka, Shota, Tandon, Nitin, Tang, Daniel D., Tanweer, Omar, Tate, Matthew C., Tatsui, Claudio E., Taylor, Jennie W., Taylor, Jesse A., Taylor, Michael D., Templer, Jessica W., Teo, Charles, Tessier, Jeffrey M., Theadom, Alice, Theodore, Nicholas, Thinwa, Josephine W., Thompson, B. Gregory, Jr., Thompson, Eric M., Thompson, Stephen A., Thon, Niklas, Thurtell, Matthew J., Tilton, Ann H., Timmons, Shelly D., Tonn, Jörg-Christian, Toth, Gabor, Toussaint, Charles P., Tran, Minh H., Trapp, Bruce D., Traylor, Jeffrey I., Trifiletti, Daniel M., Tse, Kai-Hei, Tubbs, R. Shane, Tuleasca, Constantin, Tunkel, Allan R., Türe, Ugur, Umansky, Daniel, Unda, Santiago R., Ung, Timothy H., Upadhyayula, Pavan S., Uribe, Juan S., Uy, Benjamin R., Vaccaro, Alexander R., Vakharia, Kunal, Vakharia, Vejay N., Valvassori, Luca, van den Bent, Martin J., Van Gompel, Jamie J., Vasquez, Carlos M., Vasudeva, Viren S., Vasudevan, Kumar, Vellimana, Ananth K., Verlicchi, Angela, Vervoordt, Samantha M., Viapiano, Mariano S., Vide, Sérgio, Villa, Genaro R., Virk, Michael S., Visser-Vandewalle, Veerle, Vitek, Jerrold L., Vivas-Buitrago, Tito, Vo, Chau D., Vogelbaum, Michael A., Vollmer, Dennis G., Wackym, P. Ashley, Wainwright, Mark S., Wali, Arvin R., Walker, Corey T., Walters, Beverly C., Wang, Anthony C., Wang, Arthur, Wang, Huan, Wang, Joshua L., Wang, Kevin K.W., Wang, Michael Y., Wang, Minghao, Wang, Shelly, Wang, Tao, Wang, Tony R., Wang, Vincent Y., Waqas, Muhammad, Warf, Benjamin C., Weiner, Howard L., Weingart, Jon D., Weinstein, Lawrence, Weiss, Martin H., Weiss, Nirit, Welch, Babu G., Wellons, John C., III, Wen, Hung Tzu, Wen, Patrick Y., West, G. Alexander, Wewel, Joshua T., Whitehead, William E., Whiting, Alexander C., Whiting, Donald M., Wichmann, Thomas, Wilkinson, D. Andrew, Williams, Michael A., Williams-Medina, Alberto R., Williamson, Theresa, Wilson, Lindsay, Winer, Jesse L., Winfree, Christopher J., Winkler, Ethan A., Winn, H. Richard, Wintermark, Max, Wipplinger, Christoph, Witiw, Christopher D., Wolfla, Christopher E., Wolinsky, Jean-Paul, Wong, Eric T., Worrell, Gregory A., Wrensch, Margaret R., Wright, Christina H., Wu, Jau-Ching, Wu, Jenny, Wu, Kyle C., Wu, Pang Hung, Xu, David S., Xu, Linda Wei, Xu, Yifan, Xu, Zhen, Xu, Zhiyuan, Yaeger, Kurt A., Yahanda, Alexander T., Yan, Rachel E., Yan, Yuanqing, Yang, George L., Yasuno, Katsuhito, Yen, Chun-Po, Yokota, Kazuya, Yolcu, Yagiz Ugur, Young, Timothy P., Yu, Jennifer S., Yue, John K., Yuh, Esther L., Zabramski, Joseph M., Zacest, Andrew, Zacko, J. Christopher, Zada, Gabriel, Zafonte, Ross D., Zager, Eric L., Zakare-Fagbamila, Rasheedat T., Zakeri, Amanda, Zanotti, Bruno, Zawar, Ifrah, Zeineddine, Hussein A., Zellner, Elizabeth G., Zhan, Shikun, Zhang, Chencheng, Zhang, Michael, Zhang, Yingying, Zibly, Zion, Zigler, Jack E., Zipfel, Gregory J., Zipser, Carl Moritz, Zrinzo, Ludvic, and Zumofen, Daniel W.

Published
2023
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115. Primum non nocere: a call for balance when reporting on CTE

Author

Stewart, William, Allinson, Kieren, Al-Sarraj, Safa, Bachmeier, Corbin, Barlow, Karen, Belli, Antonio, Burns, Mark P, Carson, Alan, Crawford, Fiona, Dams-O'Connor, Kristen, Diaz-Arrastia, Ramon, Dixon, C Edward, Edlow, Brian L, Ferguson, Scott, Fischl, Bruce, Folkerth, Rebecca D, Gentleman, Steve, Giza, Christopher C, Grady, M Sean, Helmy, Adel, Herceg, Mark, Holton, Janice L, Howell, David, Hutchinson, Peter J, Iacono, Diego, Iglesias, Juan E, Ikonomovic, Milos D, Johnson, Victoria E, Keene, C Dirk, Kofler, Julia K, Koliatsos, Vassilis E, Lee, Edward B, Levin, Harvey, Lifshitz, Jonathan, Ling, Helen, Loane, David J, Love, Seth, Maas, Andrew IR, Marklund, Niklas, Master, Christina L, McElvenny, Damien M, Meaney, David F, Menon, David K, Montine, Thomas J, Mouzon, Benoit, Mufson, Elliott J, Ojo, Joseph O, Prins, Mayumi, Revesz, Tamas, Ritchie, Craig W, Smith, Colin, Sylvester, Richard, Tang, Cheuk Y, Trojanowski, John Q, Urankar, Kathryn, Vink, Robert, Wellington, Cheryl, Wilde, Elisabeth A, Wilson, Lindsay, Yeates, Keith, and Smith, Douglas H

Published
2019
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120. Complex Autoantibody Responses Occur Following Moderate to Severe Traumatic Brain Injury

Author

Needham, Edward J, primary, Stoevesandt, Oda, additional, Thelin, Eric P, additional, Zetterberg, Henrik, additional, Zanier, Elisa R, additional, Nimer, Faiez Al, additional, Ashton, Nicholas J, additional, Outtrim, Joanne G, additional, Newcombe, Virginia FJ, additional, Mousa, Hani S, additional, Simren, Joel, additional, Blennow, Kaj, additional, Yang Z, Zhihui, additional, Hutchinson, Peter J, additional, Piehl, Fredrik, additional, Helmy, Adel E, additional, Taussig, Mike J, additional, Wang, Kevin KW, additional, Jones, Joanne L, additional, Menon, David K, additional, and Coles, Alasdair J, additional

Published
2020
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123. A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain

Author

Jalloh, Ibrahim, Helmy, Adel, Howe, Duncan J, Shannon, Richard J, Grice, Peter, Mason, Andrew, Gallagher, Clare N, Murphy, Michael P, Pickard, John D, Menon, David K, Carpenter, T Adrian, Hutchinson, Peter J, Carpenter, Keri LH, Helmy, Adel [0000-0002-0531-0556], Grice, Peter [0000-0003-4658-4534], Murphy, Mike [0000-0003-1115-9618], Pickard, John [0000-0002-5762-6667], Menon, David [0000-0002-3228-9692], Carpenter, Adrian [0000-0002-2939-8222], Hutchinson, Peter [0000-0002-2796-1835], Carpenter, Keri [0000-0001-8236-7727], and Apollo - University of Cambridge Repository

Subjects
Adult, Brain Chemistry, Male, Magnetic Resonance Spectroscopy, Adolescent, microdialysis, Glutamine, education, Citric Acid Cycle, Original Articles, traumatic brain injury (human), Middle Aged, NMR, nervous system diseases, Young Adult, nervous system, 3-13C lactate, brain metabolism, Brain Injuries, Traumatic, Humans, Female, Lactic Acid, Dialysis, Oxidation-Reduction
Abstract

Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-13C lactate metabolism in TBI with “normal” control brain and muscle, measuring 13C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3-13C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3-13C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate 13C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0–11.1) % in TBI and 5.7 (4.6–6.8) % in control brain, for C3 0 (0–5.0) % in TBI and 0 (0–0) % in control brain, and for C2 2.9 (0–5.7) % in TBI and 1.8 (0–3.4) % in control brain. 13C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-13C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited 13C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI “emergency option.”

Published
2018
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124. The relationship between neurosurgical instruments and disease transmission: Society of British Neurological Surgeons perspective

Author

Hutchinson, Peter JA, White, Barrie, Helmy, Adel, Thorne, John, Jenkins, Alistair, Kerr, Richard, Kitchen, Neil, May, Paul, Society Of British Neurological Surgeons, Hutchinson, Peter [0000-0002-2796-1835], Helmy, Adel [0000-0002-0531-0556], and Apollo - University of Cambridge Repository

Subjects
Neurosurgeons, Humans, Neurosurgical Procedures
Published
2018

125. Elucidating Pro-Inflammatory Cytokine Responses after Traumatic Brain Injury in a Human Stem Cell Model

Author

Thelin, Eric Peter, Hall, Claire E, Gupta, Kunal, Carpenter, Keri LH, Chandran, Siddharthan, Hutchinson, Peter J, Patani, Rickie, Helmy, Adel, Thelin, Eric [0000-0002-2338-4364], Carpenter, Keri [0000-0001-8236-7727], Hutchinson, Peter [0000-0002-2796-1835], Helmy, Adel [0000-0002-0531-0556], and Apollo - University of Cambridge Repository

Subjects
cytokine exposure, Inflammation, Neural Stem Cells, interleukin-1β, interleukin-6, tumor necrosis factor, Brain Injuries, Traumatic, Cytokines, Humans, in vitro, human embryonic stem cell-derived neurons, Cells, Cultured
Abstract

Cytokine mediated inflammation likely plays an important role in secondary pathology after traumatic brain injury (TBI). The aim of this study was to elucidate secondary cytokine responses in an in vitro enriched (>80%) human stem cell-derived neuronal model. We exposed neuronal cultures to pre-determined and clinically relevant pathophysiological levels of tumor necrosis factor-α (TNF), interleukin-6 (IL-6) and interleukin-1β (IL-1β), shown to be present in the inflammatory aftermath of TBI. Data from this reductionist human model were then compared with our in vivo data. Human embryonic stem cell (hESC)-derived neurons were exposed to recombinant TNF (1-10,000 pg/mL), IL-1β (1-10,000 pg/mL), and IL-6 (0.1-1000 ng/mL). After 1, 24, and 72 h, culture supernatant was sampled and analyzed using a human cytokine/chemokine 42-plex Milliplex kit on the Luminex platform. The culture secretome revealed both a dose- and/or time-dependent release of cytokines. The IL-6 and TNF exposure each resulted in significantly increased levels of >10 cytokines over time, while IL-1β increased the level of C-X-C motif chemokine 10 (CXCL10/IP10) alone. Importantly, these patterns are consistent with our in vivo (human) TBI data, thus validating our human stem cell-derived neuronal platform as a clinically useful reductionist model. Our data cumulatively suggest that IL-6 and TNF have direct actions, while the action of IL-1β on human neurons likely occurs indirectly through inflammatory cells. The hESC-derived neurons provide a valuable platform to model cytokine mediated inflammation and can provide important insights into the mechanisms of neuroinflammation after TBI.

Published
2018

126. Prehospital Intubation and Outcome in Traumatic Brain Injury-Assessing Intervention Efficacy in a Modern Trauma Cohort

Author

Rubenson Wahlin, Rebecka, Nelson, David W, Bellander, Bo-Michael, Svensson, Mikael, Helmy, Adel, Thelin, Eric Peter, Helmy, Adel [0000-0002-0531-0556], Thelin, Eric [0000-0002-2338-4364], and Apollo - University of Cambridge Repository

Subjects
traumatic brain injury, prehospital trauma care, emergency medical services, human, advanced airway management
Abstract

BACKGROUND: Prehospital intubation in traumatic brain injury (TBI) focuses on limiting the effects of secondary insults such as hypoxia, but no indisputable evidence has been presented that it is beneficial for outcome. The aim of this study was to explore the characteristics of patients who undergo prehospital intubation and, in turn, if these parameters affect outcome. MATERIAL AND METHODS: Patients ≥15 years admitted to the Department of Neurosurgery, Stockholm, Sweden with TBI from 2008 through 2014 were included. Data were extracted from prehospital and hospital charts, including prospectively collected Glasgow Outcome Score (GOS) after 12 months. Univariate and multivariable logistic regression models were employed to examine parameters independently correlated to prehospital intubation and outcome. RESULTS: A total of 458 patients were included (n = 178 unconscious, among them, n = 61 intubated). Multivariable analyses indicated that high energy trauma, prehospital hypotension, pupil unresponsiveness, mode of transportation, and distance to the hospital were independently correlated with intubation, and among them, only pupil responsiveness was independently associated with outcome. Prehospital intubation did not add independent information in a step-up model versus GOS (p = 0.154). Prehospital reports revealed that hypoxia was not the primary cause of prehospital intubation, and that the procedure did not improve oxygen saturation during transport, while an increasing distance from the hospital increased the intubation frequency. CONCLUSION: In this modern trauma cohort, prehospital intubation was not independently associated with outcome; however, hypoxia was not a common reason for prehospital intubation. Prospective trials to assess efficacy of prehospital airway intubation will be difficult due to logistical and ethical considerations.

Published
2018

127. A systematic review of cerebral microdialysis and outcomes in TBI: relationships to patient functional outcome, neurophysiologic measures, and tissue outcome

Author

Zeiler, Frederick A, Thelin, Eric Peter, Helmy, Adel, Czosnyka, Marek, Hutchinson, Peter JA, Menon, David K, Zeiler, Frederick [0000-0003-1737-0510], Thelin, Eric [0000-0002-2338-4364], Helmy, Adel [0000-0002-0531-0556], Czosnyka, Marek [0000-0003-2446-8006], Hutchinson, Peter [0000-0002-2796-1835], Menon, David [0000-0002-3228-9692], and Apollo - University of Cambridge Repository

Subjects
Cerebral microdialysis, Brain Chemistry, Glucose, Microdialysis, Brain Injuries, Traumatic, Systematic review, Glasgow Outcome Scale, Glutamic Acid, Humans, Lactic Acid, Functional outcome, Prognosis, Patient outcome
Abstract

OBJECTIVE: To perform a systematic review on commonly measured cerebral microdialysis (CMD) analytes and their association to: (A) patient functional outcome, (B) neurophysiologic measures, and (C) tissue outcome; after moderate/severe TBI. The aim was to provide a foundation for next-generation CMD studies and build on existing pragmatic expert guidelines for CMD. METHODS: We searched MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to October 2016). Strength of evidence was adjudicated using GRADE. RESULTS: (A) Functional Outcome: 55 articles were included, assessing outcome as mortality or Glasgow Outcome Scale (GOS) at 3-6 months post-injury. Overall, there is GRADE C evidence to support an association between CMD glucose, glutamate, glycerol, lactate, and LPR to patient outcome at 3-6 months. (B) Neurophysiologic Measures: 59 articles were included. Overall, there currently exists GRADE C level of evidence supporting an association between elevated CMD measured mean LPR, glutamate and glycerol with elevated ICP and/or decreased CPP. In addition, there currently exists GRADE C evidence to support an association between elevated mean lactate:pyruvate ratio (LPR) and low PbtO2. Remaining CMD measures and physiologic outcomes displayed GRADE D or no evidence to support a relationship. (C) Tissue Outcome: four studies were included. Given the conflicting literature, the only conclusion that can be drawn is acute/subacute phase elevation of CMD measured LPR is associated with frontal lobe atrophy at 6 months. CONCLUSIONS: This systematic review replicates previously documented relationships between CMD and various outcome, which have driven clinical application of the technique. Evidence assessments do not address the application of CMD for exploring pathophysiology or titrating therapy in individual patients, and do not account for the modulatory effect of therapy on outcome, triggered at different CMD thresholds in individual centers. Our findings support clinical application of CMD and refinement of existing guidelines.

Published
2017

130. Randomised evaluation of early vs late cranioplasty investigating cognitive and functional recovery: protocol for a single centre, pilot, randomised trial

Author

Mee, Harry, Kolias, Angelos, Anwar, Fahim, Timofeev, Ivan, Helmy, Adel, Turner, Carole, Caldwell, Karen, Tarantino, Sylvia, Browne, Georgina, Woodbury, Emma, Gregson, Barbara, Warburton, Elizabeth, and Hutchinson, Peter

Subjects
ddc: 610, cardiovascular system, cardiovascular diseases, 610 Medical sciences, Medicine
Abstract

Background: Patients with significant brain swelling and/or raised intracranial pressure after a traumatic brain injury (TBI) or middle cerebral artery infarct (MCA infarct) can undergo a craniectomy [ref:1], [ref:2] to help in the management of raised intracranial pressures.[for full text, please go to the a.m. URL], 15th Congress of the European Forum for Research in Rehabilitation (EFRR)

Published
2019
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133. Monitoring the Neuroinflammatory Response Following Acute Brain injury

Author

Thelin, Eric Peter, Tajsic, Tamara, Zeiler, Frederick Adam, Menon, David K., Hutchinson, Peter J. A., Carpenter, Keri L. H., Morganti-Kossmann, Maria Cristina, Helmy, Adel, Thelin, Eric [0000-0002-2338-4364], Zeiler, Frederick [0000-0003-1737-0510], Menon, David [0000-0002-3228-9692], Hutchinson, Peter [0000-0002-2796-1835], Carpenter, Keri [0000-0001-8236-7727], Helmy, Adel [0000-0002-0531-0556], and Apollo - University of Cambridge Repository

Subjects
multimodal monitoring, secondary brain injury, subarachnoid hemorrhage, traumatic brain injury, Review, Neuroscience, neuroinflammation
Abstract

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are major contributors to morbidity and mortality. Following the initial insult, patients may deteriorate due to secondary brain damage. The underlying molecular and cellular cascades incorporate components of the innate immune system. There are different approaches to assess and monitor cerebral inflammation in the neuro intensive care unit. The aim of this narrative review is to describe techniques to monitor inflammatory activity in patients with TBI and SAH in the acute setting. The analysis of pro- and anti-inflammatory cytokines in compartments of the central nervous system (CNS), including the cerebrospinal fluid and the extracellular fluid, represent the most common approaches to monitor surrogate markers of cerebral inflammatory activity. Each of these compartments has a distinct biology that reflects local processes and the cross-talk between systemic and CNS inflammation. Cytokines have been correlated to outcomes as well as ongoing, secondary injury progression. Alongside the dynamic, focal assay of humoral mediators, imaging, through positron emission tomography, can provide a global in vivo measurement of inflammatory cell activity, which reveals long-lasting processes following the initial injury. Compared to the innate immune system activated acutely after brain injury, the adaptive immune system is likely to play a greater role in the chronic phase as evidenced by T-cell-mediated autoreactivity toward brain-specific proteins. The most difficult aspect of assessing neuroinflammation is to determine whether the processes monitored are harmful or beneficial to the brain as accumulating data indicate a dual role for these inflammatory cascades following injury. In summary, the inflammatory component of the complex injury cascade following brain injury may be monitored using different modalities. Using a multimodal monitoring approach can potentially aid in the development of therapeutics targeting different aspects of the inflammatory cascade and improve the outcome following TBI and SAH.

Published
2017

142. Elucidating pro-inflammatory cytokine responses following traumatic brain injury in a human stem cell model

Author

Thelin, Eric Peter, Hall, Claire E, Gupta, Kunal, Carpenter, Keri, Chandran, Siddharthan, Hutchinson, Peter John, Patani, Rickie, and Helmy, Adel

Abstract

Cytokine mediated inflammation likely plays an important role in secondary pathology following traumatic brain injury (TBI). The aim of this study was to elucidate secondary cytokine responses in an in vitro enriched (>80%) human stem cell-derived neuronal model. We exposed neuronal cultures to pre-determined and clinically relevant pathophysiological levels of Tumor Necrosis Factor- (TNF), Interleukin-6 (IL-6) and Interleukin-1β (IL-1β), shown to be present in the inflammatory aftermath of TBI. Data from this reductionist human model were then compared to our in vivo data. Human embryonic stem cell (hESC)-derived neurons were exposed to recombinant TNF (1-10,000 pg/ml), IL-1β (1-10,000 pg/ml) and IL-6 (0.1-1,000 ng/ml). Following 1, 24 and 72 hours, culture supernatant was sampled and analysed using a human cytokine/chemokine 42-plex Milliplex kit on the Luminex platform. The culture secretome revealed both a dose- and/or time-dependent release of cytokines. IL-6 and TNF exposure each resulted in significantly increased levels of >10 cytokines over time, while IL-1β increased the level of C-X-C motif chemokine 10 (CXCL10/IP10) alone. Importantly, these patterns are consistent with our in vivo (human) TBI data, thus validating our human stem cell-derived neuronal platform as a clinically useful reductionist model. Our data cumulatively suggest that IL-6 and TNF have direct actions, while the action of IL-1β on human neurons likely occurs indirectly through inflammatory cells. HESC-derived neurons provide a valuable platform to model cytokine mediated inflammation and can provide important insights into the mechanisms of neuroinflammation following TBI.

Published
2017
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143. Systemic, local, and imaging biomarkers of brain injury: more needed, and better use of those already established?

Author

Carpenter, Keri L. H., Czosnyka, Marek, Jalloh, Ibrahim, Newcombe, Virginia F. J., Helmy, Adel, Shannon, Richard J., Budohoski, Karol P., Kolias, Angelos G., Kirkpatrick, Peter J., Carpenter, Thomas Adrian, Menon, David K., Hutchinson, Peter J., Carpenter, Keri [0000-0001-8236-7727], Czosnyka, Marek [0000-0003-2446-8006], Newcombe, Virginia [0000-0001-6044-9035], Helmy, Adel [0000-0002-0531-0556], Kolias, Angelos [0000-0003-3992-0587], Carpenter, Adrian [0000-0002-2939-8222], Menon, David [0000-0002-3228-9692], Hutchinson, Peter [0000-0002-2796-1835], and Apollo - University of Cambridge Repository

Subjects
education, cerebral energy metabolism, biomarkers, imaging, blood brain barrier, blood–brain barrier, multimodality monitoring, lcsh:RC346-429, acute brain injury (human), cell death, Neurology, inflammation, Neurology (clinical), lcsh:Neurology. Diseases of the nervous system, Neuroscience
Abstract

Much progress has been made over the past two decades in the treatment of severe acute brain injury, including traumatic brain injury and subarachnoid hemorrhage, resulting in a higher proportion of patients surviving with better outcomes. This has arisen from a combination of factors. These include improvements in procedures at the scene (pre-hospital) and in the hospital emergency department, advances in neuromonitoring in the intensive care unit, both continuously at the bedside and intermittently in scans, evolution and refinement of protocol-driven therapy for better management of patients, and advances in surgical procedures and rehabilitation. Nevertheless, many patients still experience varying degrees of long-term disabilities post-injury with consequent demands on carers and resources, and there is room for improvement. Biomarkers are a key aspect of neuromonitoring. A broad definition of a biomarker is any observable feature that can be used to inform on the state of the patient, e.g., a molecular species, a feature on a scan, or a monitoring characteristic, e.g., cerebrovascular pressure reactivity index. Biomarkers are usually quantitative measures, which can be utilized in diagnosis and monitoring of response to treatment. They are thus crucial to the development of therapies and may be utilized as surrogate endpoints in Phase II clinical trials. To date, there is no specific drug treatment for acute brain injury, and many seemingly promising agents emerging from pre-clinical animal models have failed in clinical trials. Large Phase III studies of clinical outcomes are costly, consuming time and resources. It is therefore important that adequate Phase II clinical studies with informative surrogate endpoints are performed employing appropriate biomarkers. In this article, we review some of the available systemic, local, and imaging biomarkers and technologies relevant in acute brain injury patients, and highlight gaps in the current state of knowledge.

Published
2015

144. Gut-educated IgA plasma cells defend the meningeal venous sinuses.

Author

Fitzpatrick, Zachary, Frazer, Gordon, Ferro, Ashley, Clare, Simon, Bouladoux, Nicolas, Ferdinand, John, Tuong, Zewen Kelvin, Negro-Demontel, Maria Luciana, Kumar, Nitin, Suchanek, Ondrej, Tajsic, Tamara, Harcourt, Katherine, Scott, Kirsten, Bashford-Rogers, Rachel, Helmy, Adel, Reich, Daniel S., Belkaid, Yasmine, Lawley, Trevor D., McGavern, Dorian B., and Clatworthy, Menna R.

Abstract

The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges—the membranes that surround the brain and spinal cord—contain a diverse population of immune cells1. So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positioned adjacent to dural venous sinuses: regions of slow blood flow with fenestrations that can potentially permit blood-borne pathogens to access the brain2. Peri-sinus IgA plasma cells increased with age and following a breach of the intestinal barrier. Conversely, they were scarce in germ-free mice, but their presence was restored by gut re-colonization. B cell receptor sequencing confirmed that meningeal IgA+ cells originated in the intestine. Specific depletion of meningeal plasma cells or IgA deficiency resulted in reduced fungal entrapment in the peri-sinus region and increased spread into the brain following intravenous challenge, showing that meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface. IgA-secreting plasma cells that originate in the intestine are found in the meninges, where they protect the brain against pathogens. [ABSTRACT FROM AUTHOR]

Published
2020
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145. Single procedure revision cranioplasty with intra-operative autoclave following titanium plate exposure.

Author

Moneim, Joseph, Wenlock, Rhys D., Wells, Adam J., Price, Richard D., Timofeev, Ivan, Helmy, Adel, and Hutchinson, Peter J.

Subjects
AUTOCLAVES, TITANIUM, REOPERATION, REVISIONS
Abstract

Background: Patients with titanium cranioplasties can develop skin defects and plate exposure requiring revision surgery to prevent infection. The management of these patients has historically been staged surgery to remove the exposed plate followed by re-implantation of a sterile plate at a later date. Objectives: We describe an alternative where the exposed plate is removed, sterilised by autoclaving and re-implanted, in one operation. Methods: Patients with exposed titanium cranioplasties who underwent single-stage revisions were identified over a 30-month period. All patients received antibiotics post-procedure and were followed up. Results: Between June 2015 and December 2017 four patients had five single-stage revision cranioplasties with intraoperative autoclave sterilisation (SSRC). The mean time from initial procedure to revision was 5.6years. The mean time from plate exposure to surgery was 7 days. Plate exposure recurred in 60% (3/5) of cases post-SSRC. Two of these had the plate removed. The other had a second SSRC. On average recurrent plate exposure developed 17 months after SSRC. The 2 cases who had the plate removed remained complication-free to last follow up at 25 and 52 months after SSRC. Conclusions: Single procedure revision cranioplasty with intra-operative autoclave following titanium plate exposure may be considered as an option in patients with plate exposure who do not have other evidence on infection but we found recurrent plate exposure occurred in 50%. [ABSTRACT FROM AUTHOR]

Published
2020
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146. Phosphorus spectroscopy in acute TBI demonstrates metabolic changes that relate to outcome in the presence of normal structural MRI

Author

Stovell, Matthew G, primary, Mada, Marius O, additional, Carpenter, T Adrian, additional, Yan, Jiun-Lin, additional, Guilfoyle, Mathew R, additional, Jalloh, Ibrahim, additional, Welsh, Karen E, additional, Helmy, Adel, additional, Howe, Duncan J, additional, Grice, Peter, additional, Mason, Andrew, additional, Giorgi-Coll, Susan, additional, Gallagher, Clare N, additional, Murphy, Michael P, additional, Menon, David K, additional, Hutchinson, Peter J, additional, and Carpenter, Keri LH, additional

Published
2018
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147. A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain

Author

Jalloh, Ibrahim, primary, Helmy, Adel, additional, Howe, Duncan J., additional, Shannon, Richard J., additional, Grice, Peter, additional, Mason, Andrew, additional, Gallagher, Clare N., additional, Murphy, Michael P., additional, Pickard, John D., additional, Menon, David K., additional, Carpenter, T. Adrian, additional, Hutchinson, Peter J., additional, and Carpenter, Keri L.H., additional

Published
2018
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