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9 results on '"Grandhi, Ramesh"'

1. Parsimonious immune-response endotypes and global outcome in patients with traumatic brain injury

Author

Samanta, R, Chiollaz, A, Needham, E, Yue, J, Helmy, A, Zanier, E, Wang, K, Kobeissy, F, Posti, J, Summers, C, Manley, G, Maas, A, Tenovuo, O, Sanchez, J, Menon, D, Badjatia, N, Diaz-Arrastia, R, Duhaime, A, Feeser, V, Gopinath, S, Grandhi, R, Ha, R, Keene, D, Madden, C, Mccrea, M, Merchant, R, Ngwenya, L, Rodgers, R, Schnyer, D, Taylor, S, Zafonte, R, Ackerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Beer, R, Bellander, B, Benali, H, Berardino, M, Beretta, L, Beqiri, E, Blaabjerg, M, Lund, S, Brorsson, C, Buki, A, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Castaño-León, A, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, De Keyser, V, Degos, V, Della Corte, F, Boogert, H, Depreitere, B, Đilvesi, Đ, Dixit, A, Dreier, J, Dulière, G, Ercole, A, Ezer, E, Fabricius, M, Foks, K, Frisvold, S, Furmanov, A, Galanaud, D, Gantner, D, Ghuysen, A, Giga, L, Golubović, J, Gomez, P, Gravesteijn, B, Grossi, F, Gupta, D, Haitsma, I, Helbok, R, Helseth, E, Huijben, J, Hutchinson, P, Jankowski, S, Johnson, F, Karan, M, Kolias, A, Kondziella, D, Kornaropoulos, E, Koskinen, L, Kovács, N, Kowark, A, Lagares, A, Laureys, S, Lecky, F, Ledoux, D, Lightfoot, R, Lingsma, H, Manara, A, Maréchal, H, Martino, C, Mattern, J, Mcmahon, C, Menovsky, T, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nyirádi, J, Ortolano, F, Payen, J, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Ples, H, Pomposo, I, Puybasset, L, Rădoi, A, Ragauskas, A, Raj, R, Rhodes, J, Richter, S, Rocka, S, Roe, C, Roise, O, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandrød, O, Schirmer-Mikalsen, K, Frederik Schou, R, Sewalt, C, Smielewski, P, Sorinola, A, Stamatakis, E, Steyerberg, E, Stocchetti, N, Sundström, N, Takala, R, Tamás, V, Tamosuitis, T, Thomas, M, Tibboel, D, Tolias, C, Trapani, T, Tudora, C, Unterberg, A, Vajkoczy, P, Valeinis, E, Vallance, S, Vámos, Z, Van der Steen, G, van Dijck, J, van Essen, T, van Wijk, R, Vargiolu, A, Vega, E, Vik, A, Vilcinis, R, Volovici, V, Vulekovic, P, Wiegers, E, Williams, G, Winzeck, S, Wolf, S, Younsi, A, Zeiler, F, Ziverte, A, Zoerle, T, Samanta, Romit J., Chiollaz, Anne-Cécile, Needham, Edward, Yue, John K., Helmy, Adel, Zanier, Elisa R., Wang, Kevin K. W., Kobeissy, Firas, Posti, Jussi P., Summers, Charlotte, Manley, Geoffrey T., Maas, Andrew IR., Tenovuo, Olli, Sanchez, Jean-Charles, Menon, David K., Badjatia, Neeraj, Diaz-Arrastia, Ramon, Duhaime, Ann-Christine, Feeser, V Ramana, Gopinath, Shankar, Grandhi, Ramesh, Ha, Ruchira J., Keene, Dirk, Madden, Christopher, McCrea, Michael, Merchant, Randall, Ngwenya, Laura B., Rodgers, Richard B., Schnyer, David, Taylor, Sabrina R., Zafonte, Ross, Ackerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Beer, Ronny, Bellander, Bo-Michael, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Beqiri, Erta, Blaabjerg, Morten, Lund, Stine Borgen, Brorsson, Camilla, Buki, Andras, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Castaño-León, Ana M., Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark Steven, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Ezer, Erzsébet, Fabricius, Martin, Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Galanaud, Damien, Gantner, Dashiell, Ghuysen, Alexandre, Giga, Lelde, Golubović, Jagoš, Gomez, Pedro A., Gravesteijn, Benjamin, Grossi, Francesca, Gupta, Deepak, Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Huijben, Jilske, Hutchinson, Peter J., Jankowski, Stefan, Johnson, Faye, Karan, Mladen, Kolias, Angelos G., Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Manara, Alex, Maréchal, Hugues, Martino, Costanza, Mattern, Julia, McMahon, Catherine, Menon, David, Menovsky, Tomas, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nyirádi, József, Ortolano, Fabrizio, Payen, Jean-François, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Ples, Horia, Pomposo, Inigo, Puybasset, Louis, Rădoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rhodes, Jonathan, Richter, Sophie, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandrød, Oddrun, Schirmer-Mikalsen, Kari, Frederik Schou, Rico, Sewalt, Charlie, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Thomas, Matt, Tibboel, Dick, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Valeinis, Egils, Vallance, Shirley, Vámos, Zoltán, Van der Steen, Gregory, van Dijck, Jeroen T. J. M., van Essen, Thomas A., van Wijk, Roel, Vargiolu, Alessia, Vega, Emmanuel, Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, Vulekovic, Peter, Wiegers, Eveline, Williams, Guy, Winzeck, Stefan, Wolf, Stefan, Younsi, Alexander, Zeiler, Frederick A., Ziverte, Agate, Zoerle, Tommaso, Samanta, R, Chiollaz, A, Needham, E, Yue, J, Helmy, A, Zanier, E, Wang, K, Kobeissy, F, Posti, J, Summers, C, Manley, G, Maas, A, Tenovuo, O, Sanchez, J, Menon, D, Badjatia, N, Diaz-Arrastia, R, Duhaime, A, Feeser, V, Gopinath, S, Grandhi, R, Ha, R, Keene, D, Madden, C, Mccrea, M, Merchant, R, Ngwenya, L, Rodgers, R, Schnyer, D, Taylor, S, Zafonte, R, Ackerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Beer, R, Bellander, B, Benali, H, Berardino, M, Beretta, L, Beqiri, E, Blaabjerg, M, Lund, S, Brorsson, C, Buki, A, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Castaño-León, A, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, De Keyser, V, Degos, V, Della Corte, F, Boogert, H, Depreitere, B, Đilvesi, Đ, Dixit, A, Dreier, J, Dulière, G, Ercole, A, Ezer, E, Fabricius, M, Foks, K, Frisvold, S, Furmanov, A, Galanaud, D, Gantner, D, Ghuysen, A, Giga, L, Golubović, J, Gomez, P, Gravesteijn, B, Grossi, F, Gupta, D, Haitsma, I, Helbok, R, Helseth, E, Huijben, J, Hutchinson, P, Jankowski, S, Johnson, F, Karan, M, Kolias, A, Kondziella, D, Kornaropoulos, E, Koskinen, L, Kovács, N, Kowark, A, Lagares, A, Laureys, S, Lecky, F, Ledoux, D, Lightfoot, R, Lingsma, H, Manara, A, Maréchal, H, Martino, C, Mattern, J, Mcmahon, C, Menovsky, T, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nyirádi, J, Ortolano, F, Payen, J, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Ples, H, Pomposo, I, Puybasset, L, Rădoi, A, Ragauskas, A, Raj, R, Rhodes, J, Richter, S, Rocka, S, Roe, C, Roise, O, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandrød, O, Schirmer-Mikalsen, K, Frederik Schou, R, Sewalt, C, Smielewski, P, Sorinola, A, Stamatakis, E, Steyerberg, E, Stocchetti, N, Sundström, N, Takala, R, Tamás, V, Tamosuitis, T, Thomas, M, Tibboel, D, Tolias, C, Trapani, T, Tudora, C, Unterberg, A, Vajkoczy, P, Valeinis, E, Vallance, S, Vámos, Z, Van der Steen, G, van Dijck, J, van Essen, T, van Wijk, R, Vargiolu, A, Vega, E, Vik, A, Vilcinis, R, Volovici, V, Vulekovic, P, Wiegers, E, Williams, G, Winzeck, S, Wolf, S, Younsi, A, Zeiler, F, Ziverte, A, Zoerle, T, Samanta, Romit J., Chiollaz, Anne-Cécile, Needham, Edward, Yue, John K., Helmy, Adel, Zanier, Elisa R., Wang, Kevin K. W., Kobeissy, Firas, Posti, Jussi P., Summers, Charlotte, Manley, Geoffrey T., Maas, Andrew IR., Tenovuo, Olli, Sanchez, Jean-Charles, Menon, David K., Badjatia, Neeraj, Diaz-Arrastia, Ramon, Duhaime, Ann-Christine, Feeser, V Ramana, Gopinath, Shankar, Grandhi, Ramesh, Ha, Ruchira J., Keene, Dirk, Madden, Christopher, McCrea, Michael, Merchant, Randall, Ngwenya, Laura B., Rodgers, Richard B., Schnyer, David, Taylor, Sabrina R., Zafonte, Ross, Ackerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Beer, Ronny, Bellander, Bo-Michael, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Beqiri, Erta, Blaabjerg, Morten, Lund, Stine Borgen, Brorsson, Camilla, Buki, Andras, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Castaño-León, Ana M., Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark Steven, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Ezer, Erzsébet, Fabricius, Martin, Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Galanaud, Damien, Gantner, Dashiell, Ghuysen, Alexandre, Giga, Lelde, Golubović, Jagoš, Gomez, Pedro A., Gravesteijn, Benjamin, Grossi, Francesca, Gupta, Deepak, Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Huijben, Jilske, Hutchinson, Peter J., Jankowski, Stefan, Johnson, Faye, Karan, Mladen, Kolias, Angelos G., Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Manara, Alex, Maréchal, Hugues, Martino, Costanza, Mattern, Julia, McMahon, Catherine, Menon, David, Menovsky, Tomas, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nyirádi, József, Ortolano, Fabrizio, Payen, Jean-François, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Ples, Horia, Pomposo, Inigo, Puybasset, Louis, Rădoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rhodes, Jonathan, Richter, Sophie, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandrød, Oddrun, Schirmer-Mikalsen, Kari, Frederik Schou, Rico, Sewalt, Charlie, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Thomas, Matt, Tibboel, Dick, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Valeinis, Egils, Vallance, Shirley, Vámos, Zoltán, Van der Steen, Gregory, van Dijck, Jeroen T. J. M., van Essen, Thomas A., van Wijk, Roel, Vargiolu, Alessia, Vega, Emmanuel, Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, Vulekovic, Peter, Wiegers, Eveline, Williams, Guy, Winzeck, Stefan, Wolf, Stefan, Younsi, Alexander, Zeiler, Frederick A., Ziverte, Agate, and Zoerle, Tommaso

Abstract

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.

Published
2024

2. Performance of the IMPACT and CRASH prognostic models for traumatic brain injury in a contemporary multicenter cohort: a TRACK-TBI study.

Author

Yue, John, Yue, John, Lee, Young, Sun, Xiaoying, van Essen, Thomas, Elguindy, Mahmoud, Belton, Patrick, Pisică, Dana, Mikolic, Ana, Deng, Hansen, Kanter, John, McCrea, Michael, Bodien, Yelena, Satris, Gabriela, Wong, Justin, Ambati, Vardhaan, Grandhi, Ramesh, Puccio, Ava, Mukherjee, Pratik, Valadka, Alex, Tarapore, Phiroz, Huang, Michael, DiGiorgio, Anthony, Markowitz, Amy, Yuh, Esther, Okonkwo, David, Steyerberg, Ewout, Lingsma, Hester, Menon, David, Maas, Andrew, Jain, Sonia, Manley, Geoffrey, Yue, John, Yue, John, Lee, Young, Sun, Xiaoying, van Essen, Thomas, Elguindy, Mahmoud, Belton, Patrick, Pisică, Dana, Mikolic, Ana, Deng, Hansen, Kanter, John, McCrea, Michael, Bodien, Yelena, Satris, Gabriela, Wong, Justin, Ambati, Vardhaan, Grandhi, Ramesh, Puccio, Ava, Mukherjee, Pratik, Valadka, Alex, Tarapore, Phiroz, Huang, Michael, DiGiorgio, Anthony, Markowitz, Amy, Yuh, Esther, Okonkwo, David, Steyerberg, Ewout, Lingsma, Hester, Menon, David, Maas, Andrew, Jain, Sonia, and Manley, Geoffrey

Abstract

OBJECTIVE: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients. METHODS: The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic). RESULTS: Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectivel

Published
2024

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

Author

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

Abstract

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

Published
2024

4. Involvement of peptidylarginine deiminase 4 in eosinophil extracellular trap formation and contribution to citrullinated histone signal in thrombi

Author

Martinod, Kimberly, Denorme, Frederik, Meyers, Severien, Crescente, Marilena, Van Bruggen, Stijn, Stroobants, Mathias, Siegel, Patrick M, Grandhi, Ramesh, Glatz, Katharina, Witsch, Thilo, Martinod, Kimberly, Denorme, Frederik, Meyers, Severien, Crescente, Marilena, Van Bruggen, Stijn, Stroobants, Mathias, Siegel, Patrick M, Grandhi, Ramesh, Glatz, Katharina, and Witsch, Thilo

Abstract

Background: Extracellular traps formed by neutrophils (NETs) and eosinophils (EETs) have been described in coronary thrombi, contributing to thrombus stability. A key mechanism during NET formation is histone modification by the enzyme PAD4. Citrullinated histones, the product of PAD4 activity, are often attributed to neutrophils. Eosinophils also express high levels of PAD4. Objectives: We aimed to explore the contribution of PAD4 to EET formation. Methods: We performed immunohistological analyses on thrombi, including a large, intact, and eosinophil-containing thrombus retrieved from the right coronary artery using an aspiration catheter and stroke thrombi from thrombectomy retrieval. We studied eosinophils for their capability to form PAD4-dependent EETs in response to strong ET-inducing agonists as well as activated platelets and bacteria. Results: Histopathology and immunofluorescence microscopy identified a coronary thrombus rich in platelets and neutrophils, with distinct areas containing von Willebrand factor and citrullinated histone H3 (H3Cit). Eosinophils were also identified in leukocyte-rich areas. The majority of the H3Cit+ signal colocalized with myeloperoxidase, but some colocalized with eosinophil peroxidase, indicating EETs. Eosinophils isolated from healthy volunteers produced H3Cit+ EETs, indicating an involvement of PAD4 activity. The selective PAD4 inhibitor GSK484 blocked this process, supporting PAD4 dependence of H3Cit+ EET release. Citrullinated histones were also present in EETs produced in response to live Staphylococci. However, limited evidence for EETs was found in mouse models of venous thrombosis or infective endocarditis. Conclusion: As in NETosis, PAD4 can catalyze the formation of EETs. Inhibition of PAD4 decreases EET formation, supporting the future utility of PAD4 inhibitors as possible antithrombotic agents.

Published
2024

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

Author

Kelly-Hedrick, Margot, Kelly-Hedrick, Margot, Liu, Sunny, Temkin, Nancy, Barber, Jason, Komisarow, Jordan, Ohnuma, Tetsu, Colton, Katharine, Treggiari, Miriam, Monson, Eric, Vavilala, Monica, Grandhi, Ramesh, Laskowitz, Daniel, Mathew, Joseph, Hernandez, Adrian, James, Michael, Raghunathan, Karthik, Goldstein, Ben, Markowitz, Amy, Krishnamoorthy, Vijay, Manley, Geoff, Kelly-Hedrick, Margot, Kelly-Hedrick, Margot, Liu, Sunny, Temkin, Nancy, Barber, Jason, Komisarow, Jordan, Ohnuma, Tetsu, Colton, Katharine, Treggiari, Miriam, Monson, Eric, Vavilala, Monica, Grandhi, Ramesh, Laskowitz, Daniel, Mathew, Joseph, Hernandez, Adrian, James, Michael, Raghunathan, Karthik, Goldstein, Ben, Markowitz, Amy, Krishnamoorthy, Vijay, and Manley, Geoff

Abstract

OBJECTIVES: We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN: Retrospective cohort study. SETTING: ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS: Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of <13) were admitted to the ICU after a blunt TBI. INTERVENTIONS: None. MEASUREMENTS: Primary exposure was a beta blocker during the first 7 days in the ICU, with a primary outcome of 6-month Glasgow Outcome Scale-Extended (GOSE). Secondary outcomes included: length of hospital stay, in-hospital mortality, 6-month and 12-month mortality, 12-month GOSE score, and 6-month and 12-month measures of disability, well-being, quality of life, and life satisfaction. MAIN RESULTS: Of the 450 eligible participants, 57 (13%) received early beta blockers (BB+ group). The BB+ group was on average older, more likely to be on a preinjury beta blocker, and more likely to have a history of hypertension. In the BB+ group, 34 participants (60%) received metoprolol only, 19 participants (33%) received propranolol only, 3 participants (5%) received both, and 1 participant (2%) received atenolol only. In multivariable regression, there was no difference in the odds of a higher GOSE score at 6 months between the BB+ group and BB- group (odds ratio = 0.86; 95% CI, 0.48-1.53). There was no association between BB exposure and secondary outcomes. CONCLUSIONS: About one-sixth of subjects in our study received early beta blockers, and within this group, dose, and timing of beta-blocker administration varied substantially. No significant differences in GOSE score at 6 months were demonstrated, although our ability to draw conclusions is limite

Published
2023

6. Association of Noncontrast Computed Tomography and Perfusion Modalities With Outcomes in Patients Undergoing Late-Window Stroke Thrombectomy

Author

Porto, Guilherme B F, Chen, Ching-Jen, Al Kasab, Sami, Essibayi, Muhammed Amir, Almallouhi, Eyad, Hubbard, Zachary, Chalhoub, Reda, Alawieh, Ali, Maier, Ilko, Psychogios, Marios-Nikos, Wolfe, Stacey Q, Jabbour, Pascal, Rai, Ansaar, Starke, Robert M, Shaban, Amir, Arthur, Adam, Kim, Joon-Tae, Yoshimura, Shinichi, Grossberg, Jonathan, Kan, Peter, Fragata, Isabel, Polifka, Adam, Osbun, Joshua, Mascitelli, Justin, Levitt, Michael R, Williamson, Richard, Romano, Daniele G, Crosa, Roberto, Gory, Benjamin, Mokin, Maxim, Limaye, Kaustubh S, Casagrande, Walter, Moss, Mark, Grandhi, Ramesh, Yoo, Albert, Spiotta, Alejandro M, Park, Min S, Porto, Guilherme B F, Chen, Ching-Jen, Al Kasab, Sami, Essibayi, Muhammed Amir, Almallouhi, Eyad, Hubbard, Zachary, Chalhoub, Reda, Alawieh, Ali, Maier, Ilko, Psychogios, Marios-Nikos, Wolfe, Stacey Q, Jabbour, Pascal, Rai, Ansaar, Starke, Robert M, Shaban, Amir, Arthur, Adam, Kim, Joon-Tae, Yoshimura, Shinichi, Grossberg, Jonathan, Kan, Peter, Fragata, Isabel, Polifka, Adam, Osbun, Joshua, Mascitelli, Justin, Levitt, Michael R, Williamson, Richard, Romano, Daniele G, Crosa, Roberto, Gory, Benjamin, Mokin, Maxim, Limaye, Kaustubh S, Casagrande, Walter, Moss, Mark, Grandhi, Ramesh, Yoo, Albert, Spiotta, Alejandro M, and Park, Min S

Abstract

Importance: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy. Objective: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI). Design, setting, and participants: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel occlusion from 2013 to 2021. Patients were selected by NCCT, CTP, and DWI. Admission Alberta Stroke Program Early CT Score (ASPECTS) as well as confounding variables were adjusted. Follow-up duration was 90 days. Data were analyzed from November 2021 to March 2022. Exposures: Selection by NCCT, CTP, or DWI. Main outcomes and measures: Primary outcome was functional independence (modified Rankin scale 0-2) at 90 days. Results: Among 3356 patients, 733 underwent late-window mechanical thrombectomy. The median (IQR) age was 69 (58-80) years, 392 (53.5%) were female, and 449 (65.1%) were White. A total of 419 were selected with NCCT, 280 with CTP, and 34 with DWI. Mean (IQR) admission ASPECTS were comparable among groups (NCCT, 8 [7-9]; CTP, 8 [7-9]; DWI 8, [7-9]; P = .37). There was no difference in the 90-day rate of functional independence (aOR, 1.00; 95% CI, 0.59-1.71; P = .99) after adjusting for confounders. Symptomatic intracerebral hemorrhage (NCCT, 34 [8.6%]; CTP, 37 [13.5%]; DWI, 3 [9.1%]; P = .12) and mortality (NCCT, 78 [27.4%]; CTP, 38 [21.1%]; DWI, 7 [29.2%]; P = .29) were similar among groups. Conclusions and relevance: In this cohort study, comparable outcomes were observed in patients in the late window irrespective of ne

Published
2022

7. Emerging Utility of Applied Magnetic Resonance Imaging in the Management of Traumatic Brain Injury.

Author

Nadel, Jeffrey, Nadel, Jeffrey, McNally, Joseph Scott, DiGiorgio, Anthony, Grandhi, Ramesh, Nadel, Jeffrey, Nadel, Jeffrey, McNally, Joseph Scott, DiGiorgio, Anthony, and Grandhi, Ramesh

Abstract

Traumatic brain injury (TBI) is a widespread and expensive problem globally. The standard diagnostic workup for new TBI includes obtaining a noncontrast computed tomography image of the head, which provides quick information on operative pathologies. However, given the limited sensitivity of computed tomography for identifying subtle but meaningful changes in the brain, magnetic resonance imaging (MRI) has shown better utility for ongoing management and prognostication after TBI. In recent years, advanced applications of MRI have been further studied and are being implemented as clinical tools to help guide care. These include functional MRI, diffusion tensor imaging, MR perfusion, and MR spectroscopy. In this review, we discuss the scientific basis of each of the above techniques, the literature supporting their use in TBI, and how they may be clinically implemented to improve the care of TBI patients.

Published
2021

8. Emerging Utility of Applied Magnetic Resonance Imaging in the Management of Traumatic Brain Injury.

Author

Nadel, Jeffrey, Nadel, Jeffrey, McNally, Joseph Scott, DiGiorgio, Anthony, Grandhi, Ramesh, Nadel, Jeffrey, Nadel, Jeffrey, McNally, Joseph Scott, DiGiorgio, Anthony, and Grandhi, Ramesh

Abstract

Traumatic brain injury (TBI) is a widespread and expensive problem globally. The standard diagnostic workup for new TBI includes obtaining a noncontrast computed tomography image of the head, which provides quick information on operative pathologies. However, given the limited sensitivity of computed tomography for identifying subtle but meaningful changes in the brain, magnetic resonance imaging (MRI) has shown better utility for ongoing management and prognostication after TBI. In recent years, advanced applications of MRI have been further studied and are being implemented as clinical tools to help guide care. These include functional MRI, diffusion tensor imaging, MR perfusion, and MR spectroscopy. In this review, we discuss the scientific basis of each of the above techniques, the literature supporting their use in TBI, and how they may be clinically implemented to improve the care of TBI patients.

Published
2021

9. Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke: A Multi-Institutional Experience of Technical and Clinical Outcomes.

Author

Ravindra, Vijay M, Ravindra, Vijay M, Alexander, Matthew, Taussky, Philipp, Bollo, Robert J, Hassan, Ameer E, Scoville, Jonathan P, Griauzde, Julius, Awad, Al-Wala, Jumaa, Mouhammad, Zaidi, Syed, Lee, Jonathan J, Hafeez, Muhammad Ubaid, Nascimento, Fábio A, LoPresti, Melissa A, Couldwell, William T, Hetts, Steven W, Lam, Sandi K, Kan, Peter, Grandhi, Ramesh, Ravindra, Vijay M, Ravindra, Vijay M, Alexander, Matthew, Taussky, Philipp, Bollo, Robert J, Hassan, Ameer E, Scoville, Jonathan P, Griauzde, Julius, Awad, Al-Wala, Jumaa, Mouhammad, Zaidi, Syed, Lee, Jonathan J, Hafeez, Muhammad Ubaid, Nascimento, Fábio A, LoPresti, Melissa A, Couldwell, William T, Hetts, Steven W, Lam, Sandi K, Kan, Peter, and Grandhi, Ramesh

Abstract

BackgroundEndovascular thrombectomy is a promising treatment for acute ischemic stroke in children, but outcome and technical data in pediatric patients with large-vessel occlusions are lacking.ObjectiveTo assess technical and clinical outcomes of thrombectomy in pediatric patients.MethodsWe undertook a retrospective cohort study of pediatric patients who experienced acute ischemic stroke from April 2017 to April 2019 who had immediate, 30-, and 90-d follow-up. Patients were treated with endovascular thrombectomy at 5 US pediatric tertiary care facilities. We recorded initial and postprocedural modified Thrombolysis in Cerebral Infarction (mTICI) grade ≥ 2b, initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and pediatric modified Rankin scale (mRS) score 0 to 2 at 90 d.ResultsThere were 23 thrombectomies in 21 patients (mean age 11.6 ± 4.9 yr, median 11.5, range 2.1-19; 52% female). A total of 19 (83%) thrombectomies resulted in mTICI grade ≥ 2b recanalization. The median PedNIHSS score was 13 on presentation (range 4-33) and 2 (range 0-26) at discharge (mean reduction 11.3 ± 6.1). A total of 14 (66%) patients had a mRS score of 0 to 2 at 30-d follow-up; 18/21 (86%) achieved that by 90 d. The median mRS was 1 (range 0-4) at 30 d and 1 (range 0-5) at 90 d. One patient required a blood transfusion after thrombectomy.ConclusionIn this large series of pediatric patients treated with endovascular thrombectomy, successful recanalization was accomplished via a variety of approaches with excellent clinical outcomes; further prospective longitudinal study is needed.

Published
2020

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