1. Parsimonious immune-response endotypes and global outcome in patients with traumatic brain injuryResearch in context
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Romit J. Samanta, Anne-Cécile Chiollaz, Edward Needham, John K. Yue, Adel Helmy, Elisa R. Zanier, Kevin K.W. Wang, Firas Kobeissy, Jussi P. Posti, Charlotte Summers, Geoffrey T. Manley, Andrew IR. Maas, Olli Tenovuo, Jean-Charles Sanchez, David K. Menon, Neeraj Badjatia, Ramon Diaz-Arrastia, Ann-Christine Duhaime, V Ramana Feeser, Shankar Gopinath, Ramesh Grandhi, Ruchira J. Ha, Dirk Keene, Christopher Madden, Michael McCrea, Randall Merchant, Laura B. Ngwenya, Richard B. Rodgers, David Schnyer, Sabrina R. Taylor, Ross Zafonte, Cecilia Ackerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Ronny Beer, Bo-Michael Bellander, Habib Benali, Maurizio Berardino, Luigi Beretta, Erta Beqiri, Morten Blaabjerg, Stine Borgen Lund, Camilla Brorsson, Andras Buki, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Erzsébet Ezer, Martin Fabricius, Kelly Foks, Shirin Frisvold, Alex Furmanov, Damien Galanaud, Dashiell Gantner, Alexandre Ghuysen, Lelde Giga, Jagoš Golubović, Pedro A. Gomez, Benjamin Gravesteijn, Francesca Grossi, Deepak Gupta, Iain Haitsma, Raimund Helbok, Eirik Helseth, Jilske Huijben, Peter J. Hutchinson, Stefan Jankowski, Faye Johnson, Mladen Karan, Angelos G. Kolias, Daniel Kondziella, Evgenios Kornaropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Steven Laureys, Fiona Lecky, Didier Ledoux, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Catherine McMahon, David Menon, Tomas Menovsky, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, József Nyirádi, Fabrizio Ortolano, Jean-François Payen, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Horia Ples, Inigo Pomposo, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Oddrun Sandrød, Kari Schirmer-Mikalsen, Rico Frederik Schou, Charlie Sewalt, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Matt Thomas, Dick Tibboel, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Roel van Wijk, Alessia Vargiolu, Emmanuel Vega, Anne Vik, Rimantas Vilcinis, Victor Volovici, Peter Vulekovic, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Alexander Younsi, Frederick A. Zeiler, Agate Ziverte, and Tommaso Zoerle
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Traumatic brain injury ,Stratified medicine ,Inflammation ,Clustering ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.
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- 2024
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