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1. Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial

Author

Hollmén, Carita, Parkkola, Riitta, Vorobyev, Victor, Saunavaara, Jani, Laitio, Ruut, Arola, Olli, Hynninen, Marja, Bäcklund, Minna, Martola, Juha, Ylikoski, Emmi, Roine, Risto O., Tiainen, Marjaana, Scheinin, Harry, Maze, Mervyn, Vahlberg, Tero, and Laitio, Timo T.

Published
2024
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2. Comparison of the prognostic value of early-phase proton magnetic resonance spectroscopy and diffusion tensor imaging with serum neuron-specific enolase at 72 h in comatose survivors of out-of-hospital cardiac arrest—a substudy of the XeHypotheca trial

Author

Koskensalo, Kalle, Virtanen, Sami, Saunavaara, Jani, Parkkola, Riitta, Laitio, Ruut, Arola, Olli, Hynninen, Marja, Silvasti, Päivi, Nukarinen, Eija, Martola, Juha, Silvennoinen, Heli M, Tiainen, Marjaana, Roine, Risto O, Scheinin, Harry, Saraste, Antti, Maze, Mervyn, Vahlberg, Tero, and Laitio, Timo T

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Cardiovascular, Biomedical Imaging, Clinical Research, Humans, Biomarkers, Coma, Diffusion Tensor Imaging, Out-of-Hospital Cardiac Arrest, Phosphopyruvate Hydratase, Prognosis, Proton Magnetic Resonance Spectroscopy, Seizures, Survivors, Diffusion tensor imaging, 1H-MRS, Neuron-specific enolase, Cardiac arrest, Brain hypoxia-ischemia, Prognostication, XeHYPOTHECA Research Group, Brain hypoxia–ischemia, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

PurposeWe compared the predictive accuracy of early-phase brain diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and serum neuron-specific enolase (NSE) against the motor score and epileptic seizures (ES) for poor neurological outcome after out-of-hospital cardiac arrest (OHCA).MethodsThe predictive accuracy of DTI, 1H-MRS, and NSE along with motor score at 72 h and ES for the poor neurological outcome (modified Rankin Scale, mRS, 3 - 6) in 92 comatose OHCA patients at 6 months was assessed by area under the receiver operating characteristic curve (AUROC). Combined models of the variables were included as exploratory.ResultsThe predictive accuracy of fractional anisotropy (FA) of DTI (AUROC 0.73, 95% CI 0.62-0.84), total N-acetyl aspartate/total creatine (tNAA/tCr) of 1H-MRS (0.78 (0.68 - 0.88)), or NSE at 72 h (0.85 (0.76 - 0.93)) was not significantly better than motor score at 72 h (0.88 (95% CI 0.80-0.96)). The addition of FA and tNAA/tCr to a combination of NSE, motor score, and ES provided a small but statistically significant improvement in predictive accuracy (AUROC 0.92 (0.85-0.98) vs 0.98 (0.96-1.00), p = 0.037).ConclusionNone of the variables (FA, tNAA/tCr, ES, NSE at 72 h, and motor score at 72 h) differed significantly in predicting poor outcomes in this patient group. Early-phase quantitative neuroimaging provided a statistically significant improvement for the predictive value when combined with ES and motor score with or without NSE. However, in clinical practice, the additional value is small, and considering the costs and challenges of imaging in this patient group, early-phase DTI/MRS cannot be recommended for routine use.Trial registrationClinicalTrials.gov NCT00879892, April 13, 2009.

Published
2023

3. Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial

Author

Phan, Timmy, Selmes, Christine, Lees, Kennedy, Kaste, Markku, MacIsaac, Rachael, Wellings, Tom, Loiselle, Andre, Pepper, Elizabeth, Miteff, Ferdi, Krishnamurthy, Venkatesh, Ang, Timothy, Alanati, Khaled, Gangadharan, Shyam, Zareie, Hossein, Starling, Rita, Dunkerton, Sophie, He, Jiacheng, Datta, Raka, Royan, Angela, Kerr, Erin, Kaauwai, Lara, Belevski, Linda, Ormond, Sally, Johnson, Annalese, Evans, Malcolm, Lachapelle, Nicole, Ombelet, Fouke, Bladin, Chris, Dewey, Helen, Wong, Joseph, Park, Peter, Cody, Ross, Tan, Peter, Callaly, Edward, Senanayake, Channa, Thomas, Grace, Liu, Jennifer, Busch, Tessa, Stuart, Narelle, Chung, Malcohm, Yassi, Nawaf, Valente, Michael, Sharobeam, Angelos, Cooley, Regan, Zhao, Henry, Alemseged, Fana, Williams, Cameron, Ng, Jo Lyn, Balabanski, Anna, dos Santos, Angela, Williamson, John, Pavlin-Premrl, Davor, Beharry, James, Ma, Margaret, Park, Ashley, Yan, Bernard, Hand, Peter, Jackson, David, McDonald, Amy, Fisicchia, Laura, Parsons, Nicola, Olenko, Liudmyla, Johns, Hannah, Guha, Prodipta, Rokaha, Birendra, Dhimal, Niruta, Harvey, Jackson, Cagi, Lavenia, Chia, Nicholas, Goh, Rudy, Palanikumar, Log, El-Masri, Shaddy, Mahadevan, Joshua, Kuranawai, Craig, Waters, Michael, Vallat, Wilson, Cheong, Eddie, Drew, Roy, Cordato, Dennis, McDougall, Alan, Cappelen-Smith, Cecilia, Venkat, Abhay, Edwards, Leon, Blair, Christopher, Thomas, James, Helou, Jacob, Green, Daniel, Nguyen, Tram, Pham, Timmy, Khan, Jasmeen, Miller, Megan, Loubiere, Laurence, Buck, Brian, Butcher, Ken, Fairall, Paige, Butt, Asif, Kalashyan, Hayrapet, Nomani, Ali, Lloret, Mar, Mishra, Sachin, Thirunavukkarasu, Sibi, Sivakumar, Leka, D'Souza, Atlantic, Tsai, Chon-Haw, Tseng, Billy, Tai, Iris, Chiang, I-Husan, Kuan, Angela, Tsai, Vivian, Hsu, Alice, Hsu, Sammi, Alchin, Deborah, Sanjuan, Estela, Fink, John, Wilson, Duncan, Mason, Deborah, Berry-Norohna, Alexander, Winders, Joel, Eagle, Jane, Green, Rosemary, Bremner, Kathleen, Celestino, Sherisse, Lee, Jiunn-Tay, Chou, Chung-Hsing, Tsai, Chia-Kuang, Sung, Yueh-Feng, Tsai, Chia-Lin, Lin, Yu-Kai, Kao, Hung-Wen, Vuong, Jason, Thirugnanachandran, Tharani, Hervet, Marie Veronic, Simmons, Karen, Sabet, Arman, Bailey, Peter, Urbi, Berzenn, Kurakose, Sumole, Martinez-Majander, Nicolas, Räty, Silja, Tiainen, Marjaana, Sibolt, Gerli, Ivanoff, Terhi, Sanz, Ana Calleja, García, Elisa Cortijo, De Lera Alfonso, Mercedes C., Araque, Maria Ester Ramos, Gómez, Alicia Sierra, Peñacoba, Gonzalo Valle, Vicente, Beatriz Gómez, Muñoz, Javier Reyes, Muñoz Rubio, Pedro Luis, Shah, Darshan, Harrison, Emma, Bendall, Carol, Subramanian, Ganesh, Jeng, Jiann-Shing, Tang, Sung-Chun, Tsai, Li-Kai, Yeh, Shin-Joe, Chen, Chih-Hao, Chung, Tai-Chun, Wong, Andrew, Muller, Claire, Skinner, Genevieve, Gunathilagan, Gunaratnam, Natarajan, Indira, Coutts, Shelagh, Menon, Bijoy, Kenney, Carol, Clarke, Brian, Ghatala, Rita, Mudd, Paul, Chen, Chih-Hung, Lemmens, Robin, Demeestere, Jelle, Mahant, Neil, Sun, Mu-Chien, Parsons, Mark W, Yogendrakumar, Vignan, Churilov, Leonid, Garcia-Esperon, Carlos, Campbell, Bruce C V, Russell, Michelle L, Sharma, Gagan, Chen, Chushuang, Lin, Longting, Chew, Beng Lim, Ng, Felix C, Deepak, Akshay, Choi, Philip M C, Kleinig, Timothy J, Cordato, Dennis J, Wu, Teddy Y, Fink, John N, Ma, Henry, Phan, Thanh G, Markus, Hugh S, Molina, Carlos A, Strbian, Daniel, Meretoja, Atte, Arenillas, Juan F, Buck, Brian H, Devlin, Michael J, Brown, Helen, Butcher, Ken S, O'Brien, Billy, Wijeratne, Tissa, Bivard, Andrew, Grimley, Rohan S, Agarwal, Smriti, Munshi, Sunil K, Donnan, Geoffrey A, Davis, Stephen M, Miteff, Ferdinand, Spratt, Neil J, and Levi, Christopher R

Published
2024
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6. Management of Poststroke Hyperglycemia: Results of the TEXAIS Randomized Clinical Trial

Author

Bladin, Christopher F., Wah Cheung, Ngai, Dewey, Helen M., Churilov, Leonid, Middleton, Sandy, Thijs, Vincent, Ekinci, Elif, Levi, Christopher R., Lindley, Richard, Donnan, Geoffrey A., Parsons, Mark W., Meretoja, Atte, Tiainen, Marjaana, Choi, Philip M.C., Cordato, Dennis, Brown, Helen, Campbell, Bruce C.V., Davis, Stephen M., Cloud, Geoffrey, Grimley, Rohan, Lee-Archer, Matthew, Ghia, Darshan, Sanders, Lauren, Markus, Romesh, Muller, Claire, Salvaris, Patrick, Wu, Teddy, and Fink, John

Published
2023
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7. Higher versus lower blood pressure targets after cardiac arrest: Systematic review with individual patient data meta-analysis

Author

Niemelä, Ville, Siddiqui, Faiza, Ameloot, Koen, Reinikainen, Matti, Grand, Johannes, Hästbacka, Johanna, Hassager, Christian, Kjaergaard, Jesper, Åneman, Anders, Tiainen, Marjaana, Nielsen, Niklas, Harboe Olsen, Markus, Jorgensen, Caroline Kamp, Juul Petersen, Johanne, Dankiewicz, Josef, Saxena, Manoj, Jakobsen, Janus C., and Skrifvars, Markus B.

Published
2023
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8. Effect of Inhaled Xenon on Cardiac Function in Comatose Survivors of Out-of-Hospital Cardiac Arrest—A Substudy of the Xenon in Combination With Hypothermia After Cardiac Arrest Trial

Author

Saraste, Antti, Ballo, Haitham, Arola, Olli, Laitio, Ruut, Airaksinen, Juhani, Hynninen, Marja, Bäcklund, Minna, Ylikoski, Emmi, Wennervirta, Johanna, Pietilä, Mikko, Roine, Risto O, Harjola, Veli-Pekka, Niiranen, Jussi, Korpi, Kirsi, Varpula, Marjut, Scheinin, Harry, Maze, Mervyn, Vahlberg, Tero, Laitio, Timo, Virtanen, Sami, Parkkola, Riitta, Saunavaara, Jani, Martola, Juha, Silvennoinen, Heli, Tiainen, Marjaana, Grönlund, Juha, Inkinen, Outi, Silvasti, Päivi, Nukarinen, Eija, and Olkkola, Klaus T

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Cardiovascular, Clinical Research, Heart Disease, Clinical Trials and Supportive Activities, cardiac arrest, cardiac function, cardioprotection, echocardiography, ejection fraction, myocardial strain, Clinical sciences
Abstract

This explorative substudy aimed at determining the effect of inhaled xenon on left ventricular function by echocardiography in comatose survivors of out-of-hospital cardiac arrest.DesignA randomized two-group single-blinded phase 2 clinical drug trial.SettingA multipurpose ICU in two university hospitals.PatientsOf the 110 randomized comatose survivors after out-of-hospital cardiac arrest with a shockable rhythm in the xenon in combination with hypothermia after cardiac arrest trial, 38 patients (24-76 yr old) with complete echocardiography were included in this study.InterventionsPatients were randomized to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours or hypothermia treatment alone. Echocardiography was performed at hospital admission and 24 ± 4 hours after hypothermia.Measurements and main resultsLeft ventricular ejection fraction, myocardial longitudinal systolic strain, and diastolic function were analyzed blinded to treatment. There were 17 xenon and 21 control patients in whom echocardiography was completed. Clinical characteristics did not differ significantly between the groups. At admission, ejection fraction was similar in xenon and control patients (39% ± 10% vs 38% ± 11%; p = 0.711) but higher in xenon than control patients after hypothermia (50% ± 10% vs 42% ± 10%; p = 0.014). Global longitudinal systolic strain was similar in xenon and control patients at admission (-9.0% ± 3.8% vs -8.1% ± 3.6%; p = 0.555) but better in xenon than control patients after hypothermia (-14.4.0% ± 4.0% vs -10.5% ± 4.0%; p = 0.006). In patients with coronary artery disease, longitudinal strain improved in the nonischemic myocardial segments in xenon patients. There were no changes in diastolic function between the groups.ConclusionsAmong comatose survivors of a cardiac cause out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia was associated with greater recovery of left ventricular systolic function in comparison with hypothermia alone.

Published
2021

10. Thrombolysis in stroke patients with elevated inflammatory markers

Author

Altersberger, Valerian L., Enz, Lukas S., Sibolt, Gerli, Hametner, Christian, Nannoni, Stefania, Heldner, Mirjam R., Stolp, Jeffrey, Jovanovic, Dejana R., Zini, Andrea, Pezzini, Alessandro, Wegener, Susanne, Cereda, Carlo W., Ntaios, George, Räty, Silja, Gumbinger, Christoph, Heyse, Miriam, Polymeris, Alexandros A., Zietz, Annaelle, Schaufelbuehl, Anna, Strambo, Davide, Padlina, Giovanna, Slavova, Nedelina, Tiainen, Marjaana, Valkonen, Kati, Velzen, Twan J. van, Bigliardi, Guido, Stanarcevic, Predrag, Magoni, Mauro, Luft, Andreas, Bejot, Yannick, Vandelli, Laura, Padjen, Visnja, Nederkoorn, Paul J., Arnold, Marcel, Michel, Patrik, Ringleb, Peter A., Curtze, Sami, Engelter, Stefan T., and Gensicke, Henrik

Published
2022
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12. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial

Author

Alonso, Angelika, Arquizan, Caroline, Barreau, Xavier, Beaujeux, Rémy, Behme, Daniel, Boeckh-Behrens, Tobias, Boehme, Christian, Boix, Martí, Boulouis, Grégoire, Bricout, Nicolas, Broc, Nicolas, Cereda, Carlo W., Chabert, Emmanuel, Cho, Tae-Hee, Cianfoni, Alessandro, Costalat, Vincent, Denier, Christian, Di Maria, Frederico, du Mesnil de Rochemont, Richard, Fearon, Patricia, Ferrier, Anna, Fischer, Sebastian, Gauberti, Maxime, Gaudron, Marie, Gimenez, Laetitia, Globas, Christoph, Görtler, Michael, Goyal, Mayank, Hilker-Roggendorf, Ruediger, Hill, Michael D., Hua, Vi Tuan, Humbertjean, Lisa, Jansen, Olav, Jung, Simon, Kägi, Georg, Kelly, Michael E., Kleffner, Ilka, Knoflach, Michael, Nedeltchev, Krassen, Krause, Lars Udo, Lappalainen, Kimmo, Lefebvre, Margaux, Leyon, Joe, Liao, Liang, Liegey, Jean-Sebastien, Loehr, Christian, Michel, Patrik, Nannoni, Stefania, Nicholson, Patrick, Nico, Lorena, Obadia, Michael, Ognard, Julien, Ogungbemi, Ayokunle, Olivot, Jean-Marc, Escalard, Simon, Pasi, Marco, Peeling, Lissa, Perez, Jane, Petersen, Martina, Piechowiak, Eike, Raposo, Roberto, Räty, Silja, Reitz, Sarah C., Remollo, Sebastià, Remonda, Luca, Rennie, Ian, Requena, Manuel, Riabikin, Alexander, Riva, Roberto, Rouchaud, Aymeric, Rosi, Andrea, Rubiera, Marta, Spelle, Laurent, Schnieder, Marlena, Schaafsma, Joanna D., Schubert, Tilman, Schulz, Jörg B., Siddiqui, Mohammed, Soize, Sébastien, Sonnberger, Michael, Touze, Emmanuel, Triquenot, Aude, Turc, Guillaume, Vieira, Lucy, Ben Hassen, Wagih, Wagner, Judith N., Wasser, Katrin, Weber, Johannes, Wenz, Holger, Weisenburger-Lile, David, Wodarg, Fritz, Wolff, Valérie, Wunderlich, Silke, Fischer, Urs, Kaesmacher, Johannes, Strbian, Daniel, Eker, Omer, Cognard, Christoph, Plattner, Patricia S, Bütikofer, Lukas, Mordasini, Pasquale, Deppeler, Sandro, Pereira, Vitor M, Albucher, Jean François, Darcourt, Jean, Bourcier, Romain, Benoit, Guillon, Papagiannaki, Chrysanthi, Ozkul-Wermester, Ozlem, Sibolt, Gerli, Tiainen, Marjaana, Gory, Benjamin, Richard, Sébastien, Liman, Jan, Ernst, Marielle Sophie, Boulanger, Marion, Barbier, Charlotte, Mechtouff, Laura, Zhang, Liqun, Marnat, Gaultier, Sibon, Igor, Nikoubashman, Omid, Reich, Arno, Consoli, Arturo, Lapergue, Bertrand, Ribo, Marc, Tomasello, Alejandro, Saleme, Suzana, Macian, Francisco, Moulin, Solène, Pagano, Paolo, Saliou, Guillaume, Carrera, Emmanuel, Janot, Kevin, Hernández-Pérez, María, Pop, Raoul, Schiava, Lucie Della, Luft, Andreas R, Piotin, Michel, Gentric, Jean Christophe, Pikula, Aleksandra, Pfeilschifter, Waltraud, Arnold, Marcel, Siddiqui, Adnan H, Froehler, Michael T, Furlan, Anthony J, Chapot, René, Wiesmann, Martin, Machi, Paolo, Diener, Hans-Christoph, Kulcsar, Zsolt, Bonati, Leo H, Bassetti, Claudio L, Mazighi, Mikael, Liebeskind, David S, Saver, Jeffrey L, and Gralla, Jan

Published
2022
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16. Prognostic Value of Early Phase 1H Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging in Comatose Survivors of Out-of-Hospital Cardiac Arrest - A Sub-Study of the Xe-Hypotheca Trial

Author

Laitio, Timo, Koskensalo, Kalle, Virtanen, Sami, Saunavaara, Jani, Parkkola, Riitta, Laitio, Ruut, Arola, Olli, Hynninen, Marja, Silvasti, Päivi, Nukarinen, Eija, Martola, Juha, Silvennoinen, Heli M, Tiainen, Marjaana, Roine, Risto O, Scheinin, Harry, Maze, Mervyn, and Vahlberg, Tero

Subjects
Diffusion tensor imaging, 1H-MRS, cardiac arrest, prognostication
Published
2018

17. Inhaled Xenon Attenuates Myocardial Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest The Xe-Hypotheca Trial

Author

Arola, Olli, Saraste, Antti, Laitio, Ruut, Airaksinen, Juhani, Hynninen, Marja, Bäcklund, Minna, Ylikoski, Emmi, Wennervirta, Johanna, Pietilä, Mikko, Roine, Risto O, Harjola, Veli-Pekka, Niiranen, Jussi, Korpi, Kirsi, Varpula, Marjut, Scheinin, Harry, Maze, Mervyn, Vahlberg, Tero, Laitio, Timo, Group, Xe-HYPOTHECA Study, Virtanen, Sami, Parkkola, Riitta, Saunavaara, Jani, Martola, Juha, Silvennoinen, Heli, Tiainen, Marjaana, Grönlund, Juha, Inkinen, Outi, Silvasti, Päivi, Nukarinen, Eija, and Olkkola, Klaus T

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease, Clinical Research, Cardiovascular, Heart Disease - Coronary Heart Disease, Administration, Inhalation, Aged, Cardiopulmonary Resuscitation, Coma, Female, Finland, Heart, Hemodynamics, Humans, Hypothermia, Induced, Intensive Care Units, Male, Middle Aged, Myocardium, Out-of-Hospital Cardiac Arrest, Percutaneous Coronary Intervention, Treatment Outcome, Troponin T, Xenon, cardioprotection, hypothermia, out-of-hospital cardiac arrest, xenon, Xe-HYPOTHECA Study Group, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BACKGROUND:The authors previously reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). OBJECTIVES:A pre-defined secondary objective was to assess the effect of inhaled xenon on myocardial ischemic damage in the same study population. METHODS:A total of 110 comatose patients who had experienced OHCA from a cardiac cause were randomized to receive either inhaled xenon (40% end-tidal concentration) combined with hypothermia (33°C) for 24 h (n = 55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin-T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post-cardiac arrest. All available cases were analyzed for troponin-T release. RESULTS:Troponin-T measurements were available from 54 xenon patients and 54 control patients. The baseline characteristics did not differ significantly between the groups. After adjustments for age, sex, study site, primary coronary percutaneous intervention (PCI), and norepinephrine dose, the mean ± SD post-arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 ± 1.54 in the xenon group and 1.56 ± 1.38 in the control group (adjusted mean difference -0.66; 95% confidence interval: -1.16 to -0.16; p = 0.01). The effect of xenon on the change in the troponin-T values did not differ in patients with or without PCI or in those with a diagnosis of ST-segment elevation myocardial infarction (group by PCI or ST-segment elevation myocardial infarction interaction effect; p = 0.86 and p = 0.71, respectively). CONCLUSIONS:Among comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon combined with hypothermia suggested a less severe myocardial injury as demonstrated by the significantly reduced release of troponin-T.

Published
2017

21. Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial

Author

Meretoja, Atte, Yassi, Nawaf, Wu, Teddy Y, Churilov, Leonid, Sibolt, Gerli, Jeng, Jiann-Shing, Kleinig, Timothy, Spratt, Neil J, Thijs, Vincent, Wijeratne, Tissa, Cho, Der-Yang, Shah, Darshan, Cloud, Geoffrey C, Phan, Thanh, Bladin, Christopher, Moey, Andrew, Aviv, Richard I, Barras, Christen D, Sharma, Gagan, Hsu, Chung Y, Ma, Henry, Campbell, Bruce C V, Mitchell, Peter, Yan, Bernard, Parsons, Mark W, Tiainen, Marjaana, Curtze, Sami, Strbian, Daniel, Tang, Sung-Chun, Harvey, Jackson, Levi, Christopher, Donnan, Geoffrey A, and Davis, Stephen M

Published
2020
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22. Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Author

Wihersaari, Lauri, Ashton, Nicholas J., Reinikainen, Matti, Jakkula, Pekka, Pettilä, Ville, Hästbacka, Johanna, and Tiainen, Marjaana

Subjects
Brain damage -- Care and treatment -- Patient outcomes, Neurons -- Comparative analysis, Medical research -- Comparative analysis, Medicine, Experimental -- Comparative analysis, Cardiac arrest -- Patient outcomes -- Care and treatment, Neurophysiology -- Comparative analysis, Health care industry
Abstract

Purpose Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO.sub.2), arterial oxygen tension (PaO.sub.2), and mean arterial pressure (MAP). Methods We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1-2 and poor outcome as CPC 3-5. Results Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range [IQR] 11-31) pg/ml in patients with good outcome and 2343 (587-5829) pg/ml in those with poor outcome, p < 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval [CI] 0.97-1.00) at 24 h, 0.98 (0.97-1.00) at 48 h, and 0.98 (0.95-1.00) at 72 h. NfL concentrations were lower in the higher MAP (80-100 mmHg) group than in the lower MAP (65-75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml, p = 0.04). PaCO.sub.2 and PaO.sub.2 targets did not associate with NfL levels. Conclusions NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations., Author(s): Lauri Wihersaari [sup.1], Nicholas J. Ashton [sup.2] [sup.3] [sup.4] [sup.5], Matti Reinikainen [sup.1], Pekka Jakkula [sup.6], Ville Pettilä [sup.6], Johanna Hästbacka [sup.6], Marjaana Tiainen [sup.7], Pekka Loisa [sup.8], Hans [...]

Published
2021
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23. Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

Author

Laitio, Ruut, Hynninen, Marja, Arola, Olli, Virtanen, Sami, Parkkola, Riitta, Saunavaara, Jani, Roine, Risto O, Grönlund, Juha, Ylikoski, Emmi, Wennervirta, Johanna, Bäcklund, Minna, Silvasti, Päivi, Nukarinen, Eija, Tiainen, Marjaana, Saraste, Antti, Pietilä, Mikko, Airaksinen, Juhani, Valanne, Leena, Martola, Juha, Silvennoinen, Heli, Scheinin, Harry, Harjola, Veli-Pekka, Niiranen, Jussi, Korpi, Kirsi, Varpula, Marjut, Inkinen, Outi, Olkkola, Klaus T, Maze, Mervyn, Vahlberg, Tero, and Laitio, Timo

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Clinical Trials and Supportive Activities, Neurosciences, Rehabilitation, Clinical Research, Cardiovascular, Biomedical Imaging, Brain Disorders, Good Health and Well Being, Administration, Inhalation, Adult, Aged, Anisotropy, Cardiopulmonary Resuscitation, Coma, Diffusion Magnetic Resonance Imaging, Female, Finland, Humans, Hypothermia, Induced, Male, Middle Aged, Out-of-Hospital Cardiac Arrest, Single-Blind Method, Statistics, Nonparametric, Survival Analysis, Survivors, Time Factors, Treatment Outcome, White Matter, Xenon, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceEvidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies.ObjectiveTo determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI).Design, setting, and participantsA randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized.InterventionsPatients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group).Main outcomes and measuresThe primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months.ResultsAmong the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053).Conclusions and relevanceAmong comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest.Trial registrationclinicaltrials.gov Identifier: NCT00879892.

Published
2016

24. APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study

Author

Kurki, Samu N., Kantonen, Jonas, Kaivola, Karri, Hokkanen, Laura, Mäyränpää, Mikko I., Puttonen, Henri, Martola, Juha, Pöyhönen, Minna, Kero, Mia, Tuimala, Jarno, Carpén, Olli, Kantele, Anu, Vapalahti, Olli, Tiainen, Marjaana, Tienari, Pentti J., Kaila, Kai, Hästbacka, Johanna, and Myllykangas, Liisa

Published
2021
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30. Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial

Author

Jakkula, Pekka, Pettilä, Ville, Skrifvars, Markus B., Hästbacka, Johanna, Loisa, Pekka, Tiainen, Marjaana, and Wilkman, Erika

Subjects
Blood pressure, Cardiac arrest, Electroencephalography, Neurophysiology, Health care industry
Abstract

Purpose We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury. Methods In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 2.sup.3 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65-75 mmHg) vs. high-normal (80-100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest. Results We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p < 0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 [micro]g/L (15.2-34.9 [micro]g/L) in the low-normal MAP group and 22.0 [micro]g/L (13.6-30.9 [micro]g/L) in the high-normal MAP group, p = 0.522. We found no differences in the secondary outcomes. Conclusions Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes., Author(s): Pekka Jakkula [sup.1], Ville Pettilä [sup.1], Markus B. Skrifvars [sup.1] [sup.2], Johanna Hästbacka [sup.1], Pekka Loisa [sup.3], Marjaana Tiainen [sup.4], Erika Wilkman [sup.1], Jussi Toppila [sup.5], Talvikki Koskue [sup.1], [...]

Published
2018
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31. Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial

Author

Jakkula, Pekka, Reinikainen, Matti, Hästbacka, Johanna, Loisa, Pekka, Tiainen, Marjaana, Pettilä, Ville, and Toppila, Jussi

Subjects
Carbon dioxide -- Analysis, Cardiac arrest -- Analysis, Electroencephalography -- Analysis, Health care industry
Abstract

Purpose We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO.sub.2) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury. Methods Using a 2.sup.3 factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7 kPa) or high-normal (5.8-6.0 kPa) PaCO.sub.2 and to normoxia (arterial oxygen tension [PaO.sub.2] 10-15 kPa) or moderate hyperoxia (PaO.sub.2 20-25 kPa) and to low-normal or high-normal mean arterial pressure during the first 36 h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO.sub.2 and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48 h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6 months. Results In total 120 patients were included in the analyses. There was a clear separation in PaCO.sub.2 (p < 0.001) and PaO.sub.2 (p < 0.001) between the groups. The median (interquartile range) NSE concentration at 48 h was 18.8 [micro]g/l (13.9-28.3 [micro]g/l) in the low-normal PaCO.sub.2 group and 22.5 [micro]g/l (14.2-34.9 [micro]g/l) in the high-normal PaCO.sub.2 group, p = 0.400; and 22.3 [micro]g/l (14.8-27.8 [micro]g/l) in the normoxia group and 20.6 [micro]g/l (14.2-34.9 [micro]g/l) in the moderate hyperoxia group, p = 0.594). High-normal PaCO.sub.2 and moderate hyperoxia increased NIRS values. There were no differences in other secondary outcomes. Conclusions Both high-normal PaCO.sub.2 and moderate hyperoxia increased NIRS values, but the NSE concentration was unaffected. Registration ClinicalTrials.gov, NCT02698917. Registered on January 26, 2016., Author(s): Pekka Jakkula [sup.1], Matti Reinikainen [sup.2], Johanna Hästbacka [sup.1], Pekka Loisa [sup.3], Marjaana Tiainen [sup.5], Ville Pettilä [sup.1], Jussi Toppila [sup.6], Marika Lähde [sup.4], Minna Bäcklund [sup.1], Marjatta Okkonen [...]

Published
2018
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32. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest

Author

Eastwood, Glenn, primary, Nichol, Alistair D., additional, Hodgson, Carol, additional, Parke, Rachael L., additional, McGuinness, Shay, additional, Nielsen, Niklas, additional, Bernard, Stephen, additional, Skrifvars, Markus B., additional, Stub, Dion, additional, Taccone, Fabio S., additional, Archer, John, additional, Kutsogiannis, Demetrios, additional, Dankiewicz, Josef, additional, Lilja, Gisela, additional, Cronberg, Tobias, additional, Kirkegaard, Hans, additional, Capellier, Gilles, additional, Landoni, Giovanni, additional, Horn, Janneke, additional, Olasveengen, Theresa, additional, Arabi, Yaseen, additional, Chia, Yew Woon, additional, Markota, Andrej, additional, Hænggi, Matthias, additional, Wise, Matt P., additional, Grejs, Anders M., additional, Christensen, Steffen, additional, Munk-Andersen, Heidi, additional, Granfeldt, Asger, additional, Andersen, Geir Ø., additional, Qvigstad, Eirik, additional, Flaa, Arnljot, additional, Thomas, Matthew, additional, Sweet, Katie, additional, Bewley, Jeremy, additional, Bäcklund, Minna, additional, Tiainen, Marjaana, additional, Iten, Manuela, additional, Levis, Anja, additional, Peck, Leah, additional, Walsham, James, additional, Deane, Adam, additional, Ghosh, Angajendra, additional, Annoni, Filippo, additional, Chen, Yan, additional, Knight, David, additional, Lesona, Eden, additional, Tlayjeh, Haytham, additional, Svenšek, Franc, additional, McGuigan, Peter J., additional, Cole, Jade, additional, Pogson, David, additional, Hilty, Matthias P., additional, Düring, Joachim P., additional, Bailey, Michael J., additional, Paul, Eldho, additional, Ady, Bridget, additional, Ainscough, Kate, additional, Hunt, Anna, additional, Monahan, Sinéad, additional, Trapani, Tony, additional, Fahey, Ciara, additional, and Bellomo, Rinaldo, additional

Published
2023
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33. Early versus Later Anticoagulation for Stroke with Atrial Fibrillation

Author

Fischer, Urs, primary, Koga, Masatoshi, additional, Strbian, Daniel, additional, Branca, Mattia, additional, Abend, Stefanie, additional, Trelle, Sven, additional, Paciaroni, Maurizio, additional, Thomalla, Götz, additional, Michel, Patrik, additional, Nedeltchev, Krassen, additional, Bonati, Leo H., additional, Ntaios, George, additional, Gattringer, Thomas, additional, Sandset, Else-Charlotte, additional, Kelly, Peter, additional, Lemmens, Robin, additional, Sylaja, P.N., additional, Aguiar de Sousa, Diana, additional, Bornstein, Natan M., additional, Gdovinova, Zuzana, additional, Yoshimoto, Takeshi, additional, Tiainen, Marjaana, additional, Thomas, Helen, additional, Krishnan, Manju, additional, Shim, Gek C., additional, Gumbinger, Christoph, additional, Vehoff, Jochen, additional, Zhang, Liqun, additional, Matsuzono, Kosuke, additional, Kristoffersen, Espen, additional, Desfontaines, Philippe, additional, Vanacker, Peter, additional, Alonso, Angelika, additional, Yakushiji, Yusuke, additional, Kulyk, Caterina, additional, Hemelsoet, Dimitri, additional, Poli, Sven, additional, Paiva Nunes, Ana, additional, Caracciolo, Nicoletta, additional, Slade, Peter, additional, Demeestere, Jelle, additional, Salerno, Alexander, additional, Kneihsl, Markus, additional, Kahles, Timo, additional, Giudici, Daria, additional, Tanaka, Kanta, additional, Räty, Silja, additional, Hidalgo, Rea, additional, Werring, David J., additional, Göldlin, Martina, additional, Arnold, Marcel, additional, Ferrari, Cecilia, additional, Beyeler, Seraina, additional, Fung, Christian, additional, Weder, Bruno J., additional, Tatlisumak, Turgut, additional, Fenzl, Sabine, additional, Rezny-Kasprzak, Beata, additional, Hakim, Arsany, additional, Salanti, Georgia, additional, Bassetti, Claudio, additional, Gralla, Jan, additional, Seiffge, David J., additional, Horvath, Thomas, additional, and Dawson, Jesse, additional

Published
2023
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34. Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry

Author

Ntaios, George, Michel, Patrik, Georgiopoulos, Georgios, Guo, Yutao, Li, Wencheng, Xiong, Jing, Calleja, Patricia, Ostos, Fernando, González-Ortega, Guillermo, Fuentes, Blanca, Alonso de Leciñana, María, Díez-Tejedor, Exuperio, García-Madrona, Sebastian, Masjuan, Jaime, DeFelipe, Alicia, Turc, Guillaume, Gonçalves, Bruno, Domigo, Valerie, Dan, Gheorghe-Andrei, Vezeteu, Roxana, Christensen, Hanne, Christensen, Louisa Marguerite, Meden, Per, Hajdarevic, Lejla, Rodriguez-Lopez, Angela, Díaz-Otero, Fernando, García-Pastor, Andrés, Gil-Nuñez, Antonio, Maslias, Errikos, Strambo, Davide, Werring, David J., Chandratheva, Arvind, Benjamin, Laura, Simister, Robert, Perry, Richard, Beyrouti, Rahma, Jabbour, Pascal, Sweid, Ahmad, Tjoumakaris, Stavropoula, Cuadrado-Godia, Elisa, Campello, Ana Rodríguez, Roquer, Jaume, Moreira, Tiago, Mazya, Michael V., Bandini, Fabio, Matz, Karl, Iversen, Helle K., González-Duarte, Alejandra, Tiu, Cristina, Ferrari, Julia, Vosko, Milan R., Salzer, Helmut J.F., Lamprecht, Bernd, Dünser, Martin W., Cereda, Carlo W., Quintero, Ángel Basilio Corredor, Korompoki, Eleni, Soriano-Navarro, Eduardo, Soto-Ramírez, Luis Enrique, Castañeda-Méndez, Paulo F., Bay-Sansores, Daniela, Arauz, Antonio, Cano-Nigenda, Vanessa, Kristoffersen, Espen Saxhaug, Tiainen, Marjaana, Strbian, Daniel, Putaala, Jukka, and Lip, Gregory Y.H.

Published
2020
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35. Association of prestroke metformin use, stroke severity, and thrombolysis outcome

Author

Westphal, Laura P., Widmer, Roni, Held, Ulrike, Steigmiller, Klaus, Hametner, Christian, Ringleb, Peter, Curtze, Sami, Martinez-Majander, Nicolas, Tiainen, Marjaana, Nolte, Christian H., Scheitz, Jan F., Erdur, Hebun, Polymeris, Alexandros A., Traenka, Christopher, Eskandari, Ashraf, Michel, Patrik, Heldner, Mirjam R., Arnold, Marcel, Zini, Andrea, Vandelli, Laura, Coutinho, Jonathan M., Groot, Adrien E., Padjen, Visnja, Jovanovic, Dejana R., Bejot, Yannick, Brenière, Céline, Turc, Guillaume, Seners, Pierre, Pezzini, Alessandro, Magoni, Mauro, Leys, Didier, Gilliot, Sixtine, Scherrer, Michael J., Kägi, Georg, Luft, Andreas R., Gensicke, Henrik, Nederkoorn, Paul, Tatlisumak, Turgut, Engelter, Stefan T., and Wegener, Susanne

Published
2020
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36. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest

Author

Eastwood, Glenn, Nichol, Alistair D, Hodgson, Carol, Parke, Rachael L, McGuinness, Shay, Nielsen, Niklas, Bernard, Stephen, Skrifvars, Markus B, Stub, Dion, Taccone, Fabio S, Archer, John, Kutsogiannis, Demetrios, Dankiewicz, Josef, Lilja, Gisela, Cronberg, Tobias, Kirkegaard, Hans, Capellier, Gilles, Landoni, Giovanni, Horn, Janneke, Olasveengen, Theresa, Arabi, Yaseen, Chia, Yew Woon, Markota, Andrej, Hænggi, Matthias, Wise, Matt P, Grejs, Anders M, Christensen, Steffen, Munk-Andersen, Heidi, Granfeldt, Asger, Andersen, Geir Ø, Qvigstad, Eirik, Flaa, Arnljot, Thomas, Matthew, Sweet, Katie, Bewley, Jeremy, Bäcklund, Minna, Tiainen, Marjaana, Iten, Manuela, Levis, Anja, Peck, Leah, Walsham, James, Deane, Adam, Ghosh, Angajendra, Annoni, Filippo, Knight, David, Lesona, Eden, Tlayjeh, Haytham, Svenšek, Franc, and McGuigan, Peter J

Subjects
Adult, Hospitalization, Hypercapnia/complications, Coma/complications, Humans, Carbon Dioxide, Out-of-Hospital Cardiac Arrest/therapy
Abstract

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes.METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months.RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups.CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Published
2023

37. Associations of subjective and objective cognitive functioning after COVID-19: A six-month follow-up of ICU, ward, and home-isolated patients

Author

Pihlaja, Riikka E., primary, Kauhanen, Lina-Lotta S., additional, Ollila, Henriikka S., additional, Tuulio-Henriksson, Annamari S., additional, Koskinen, Sanna K., additional, Tiainen, Marjaana, additional, Salmela, Viljami R., additional, Hästbacka, Johanna, additional, and Hokkanen, Laura S., additional

Published
2023
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38. Higher versus lower blood pressure targets after cardiac arrest:Systematic review with individual patient data meta-analysis

Author

Niemelä, Ville, Siddiqui, Faiza, Ameloot, Koen, Reinikainen, Matti, Grand, Johannes, Hästbacka, Johanna, Hassager, Christian, Kjaergaard, Jesper, Åneman, Anders, Tiainen, Marjaana, Nielsen, Niklas, Harboe Olsen, Markus, Jorgensen, Caroline Kamp, Juul Petersen, Johanne, Dankiewicz, Josef, Saxena, Manoj, Jakobsen, Janus C., Skrifvars, Markus B., Niemelä, Ville, Siddiqui, Faiza, Ameloot, Koen, Reinikainen, Matti, Grand, Johannes, Hästbacka, Johanna, Hassager, Christian, Kjaergaard, Jesper, Åneman, Anders, Tiainen, Marjaana, Nielsen, Niklas, Harboe Olsen, Markus, Jorgensen, Caroline Kamp, Juul Petersen, Johanne, Dankiewicz, Josef, Saxena, Manoj, Jakobsen, Janus C., and Skrifvars, Markus B.

Abstract

Purpose: Guidelines recommend targeting mean arterial pressure (MAP) > 65 mmHg in patients after cardiac arrest (CA). Recent trials have studied the effects of targeting a higher MAP as compared to a lower MAP after CA. We performed a systematic review and individual patient data meta-analysis to investigate the effects of higher versus lower MAP targets on patient outcome. Method: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS, BIOSIS, CINAHL, Scopus, the Web of Science Core Collection, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, Google Scholar and the Turning Research into Practice database to identify trials randomizing patients to higher (≥71 mmHg) or lower (≤70 mmHg) MAP targets after CA and resuscitation. We used the Cochrane Risk of Bias tool, version 2 (RoB 2) to assess for risk of bias. The primary outcomes were 180-day all-cause mortality and poor neurologic recovery defined by a modified Rankin score of 4–6 or a cerebral performance category score of 3–5. Results: Four eligible clinical trials were identified, randomizing a total of 1,087 patients. All the included trials were assessed as having a low risk for bias. The risk ratio (RR) with 95% confidence interval for 180-day all-cause mortality for a higher versus a lower MAP target was 1.08 (0.92–1.26) and for poor neurologic recovery 1.01 (0.86–1.19). Trial sequential analysis showed that a 25% or higher treatment effect, i.e., RR < 0.75, can be excluded. No difference in serious adverse events was found between the higher and lower MAP groups. Conclusions: Targeting a higher MAP compared to a lower MAP is unlikely to reduce mortality or improve neurologic recovery after CA. Only a large treatment effect above 25% (RR < 0.75) could be excluded, and future studies are needed to investigate if relevant but lower treatment effect exists. Targeting a higher MAP was not associated with any increase in adverse

Published
2023

39. Intravenous Thrombolysis 4.5–9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration

Author

Altersberger, Valerian L; https://orcid.org/0000-0002-0610-9328, Sibolt, Gerli, Enz, Lukas S, Hametner, Christian, Scheitz, Jan F, Henon, Hilde, Bigliardi, Guido, Strambo, Davide, Martinez‐Majander, Nicolas, Stolze, Lotte J, Heldner, Mirjam R; https://orcid.org/0000-0002-3594-2159, Grisendi, Ilaria, Jovanovic, Dejana R, Bejot, Yannick, Pezzini, Alessandro; https://orcid.org/0000-0001-8629-3315, Leker, Ronen R, Kägi, Georg, Wegener, Susanne; https://orcid.org/0000-0003-4369-7023, Cereda, Carlo W; https://orcid.org/0000-0002-6479-1476, Ntaios, Georges, De Marchis, Gian Marco; https://orcid.org/0000-0002-0342-9780, Bonati, Leo H, Psychogios, Marios, Lyrer, Philippe, Räty, Silja; https://orcid.org/0000-0002-6921-0597, Tiainen, Marjaana, Wouters, Anke, Caparros, François, Heyse, Miriam, Erdur, Hebun; https://orcid.org/0000-0001-5383-9625, et al, Altersberger, Valerian L; https://orcid.org/0000-0002-0610-9328, Sibolt, Gerli, Enz, Lukas S, Hametner, Christian, Scheitz, Jan F, Henon, Hilde, Bigliardi, Guido, Strambo, Davide, Martinez‐Majander, Nicolas, Stolze, Lotte J, Heldner, Mirjam R; https://orcid.org/0000-0002-3594-2159, Grisendi, Ilaria, Jovanovic, Dejana R, Bejot, Yannick, Pezzini, Alessandro; https://orcid.org/0000-0001-8629-3315, Leker, Ronen R, Kägi, Georg, Wegener, Susanne; https://orcid.org/0000-0003-4369-7023, Cereda, Carlo W; https://orcid.org/0000-0002-6479-1476, Ntaios, Georges, De Marchis, Gian Marco; https://orcid.org/0000-0002-0342-9780, Bonati, Leo H, Psychogios, Marios, Lyrer, Philippe, Räty, Silja; https://orcid.org/0000-0002-6921-0597, Tiainen, Marjaana, Wouters, Anke, Caparros, François, Heyse, Miriam, Erdur, Hebun; https://orcid.org/0000-0001-5383-9625, and et al

Abstract

ObjectiveTo investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5–9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection.MethodsProspective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3‐month functional outcome (modified Rankin scale 3–6) and mortality. We compared: (i) IVT >4.5–9 hours versus 0–4.5 hours after stroke onset and (ii) within the >4.5–9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion‐weighted imaging fluid‐attenuated inversion recovery) versus non‐advanced neuroimaging.ResultsOf 15,827 patients, 663 (4.2%) received IVT >4.5–9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset‐to‐treatment time >4.5–9 hours vs onset‐to‐treatment time 0–4.5 hours), the probability of symptomatic intracranial hemorrhage (OR$_{adjusted}$ 0.80, 95% CI 0.53–1.17), poor functional outcome (OR$_{adjusted}$ 1.01, 95% CI 0.83–1.22), and mortality (OR$_{adjusted}$ 0.80, 95% CI 0.61–1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non‐advanced imaging only (9.9% vs 19.7%; OR$_{adjusted}$ 0.51, 95% CI 0.33–0.79).InterpretationThis study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mo

Published
2023

43. Ubiquitin C‐terminal hydrolase L1 after out‐of‐hospital cardiac arrest.

Author

Wihersaari, Lauri, Reinikainen, Matti, Tiainen, Marjaana, Bendel, Stepani, Kaukonen, Kirsi‐Maija, Vaahersalo, Jukka, Romppanen, Jarkko, Pettilä, Ville, and Skrifvars, Markus B.

Subjects
CARDIAC arrest, UBIQUITIN, RECEIVER operating characteristic curves, DEUBIQUITINATING enzymes, INTENSIVE care units
Abstract

Background: We studied the prognostic ability of serum ubiquitin C‐terminal hydrolase L1 (UCH‐L1) after out‐of‐hospital cardiac arrest (OHCA), compared to that of neuron‐specific enolase (NSE). Methods: In this post‐hoc analysis of the FINNRESUSCI study, we measured serum concentrations of UCH‐L1 in 249 OHCA patients treated in 21 Finnish intensive care units in 2010–2011. We evaluated the ability of UCH‐L1 to predict unfavourable outcome at 12 months (defined as cerebral performance category 3–5) by assessing the area under the receiver operating characteristic curve (AUROC), in comparison with NSE. Results: The concentrations of UCH‐L1 were higher in patients with unfavourable outcome than for those with favourable outcome: median concentration 10.8 ng/mL (interquartile range, 7.5–18.5 ng/mL) versus 7.8 ng/mL (5.9–11.8 ng/mL) at 24 h (p <.001), and 16.2 ng/mL (12.2–27.7 ng/mL) versus 11.5 ng/mL (9.0–17.2 ng/mL) (p <.001) at 48 h after OHCA. For UCH‐L1 as a 12‐month outcome predictor, the AUROC was 0.66 (95% confidence interval, 0.60–0.73) at 24 h and 0.66 (0.59–0.74) at 48 h. For NSE, the AUROC was 0.66 (0.59–0.73) at 24 h and 0.72 (0.65–0.80) at 48 h. The prognostic ability of UCH‐L1 was not different from that of NSE at 24 h (p =.82) and at 48 h (p =.23). Conclusion: Concentrations of UCH‐L1 in serum were higher in patients with unfavourable outcome than in those with favourable outcome. However, the ability of UCH‐L1 to predict unfavourable outcome after OHCA was only moderate and not superior to that of NSE. [ABSTRACT FROM AUTHOR]

Published
2023
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46. The predictive value of soluble urokinase plasminogen activator receptor (SuPAR) regarding 90-day mortality and 12-month neurological outcome in critically ill patients after out-of-hospital cardiac arrest. Data from the prospective FINNRESUSCI study

Author

Jalkanen, Ville, Vaahersalo, Jukka, Pettilä, Ville, Kurola, Jouni, Varpula, Tero, Tiainen, Marjaana, Huhtala, Heini, Alaspää, Ari, Hovilehto, Seppo, Kiviniemi, Outi, Kuitunen, Anne, and Tenhunen, Jyrki

Published
2014
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48. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial

Author

Fischer, Urs, primary, Kaesmacher, Johannes, additional, Strbian, Daniel, additional, Eker, Omer, additional, Cognard, Christoph, additional, Plattner, Patricia S, additional, Bütikofer, Lukas, additional, Mordasini, Pasquale, additional, Deppeler, Sandro, additional, Pereira, Vitor M, additional, Albucher, Jean François, additional, Darcourt, Jean, additional, Bourcier, Romain, additional, Benoit, Guillon, additional, Papagiannaki, Chrysanthi, additional, Ozkul-Wermester, Ozlem, additional, Sibolt, Gerli, additional, Tiainen, Marjaana, additional, Gory, Benjamin, additional, Richard, Sébastien, additional, Liman, Jan, additional, Ernst, Marielle Sophie, additional, Boulanger, Marion, additional, Barbier, Charlotte, additional, Mechtouff, Laura, additional, Zhang, Liqun, additional, Marnat, Gaultier, additional, Sibon, Igor, additional, Nikoubashman, Omid, additional, Reich, Arno, additional, Consoli, Arturo, additional, Lapergue, Bertrand, additional, Ribo, Marc, additional, Tomasello, Alejandro, additional, Saleme, Suzana, additional, Macian, Francisco, additional, Moulin, Solène, additional, Pagano, Paolo, additional, Saliou, Guillaume, additional, Carrera, Emmanuel, additional, Janot, Kevin, additional, Hernández-Pérez, María, additional, Pop, Raoul, additional, Schiava, Lucie Della, additional, Luft, Andreas R, additional, Piotin, Michel, additional, Gentric, Jean Christophe, additional, Pikula, Aleksandra, additional, Pfeilschifter, Waltraud, additional, Arnold, Marcel, additional, Siddiqui, Adnan H, additional, Froehler, Michael T, additional, Furlan, Anthony J, additional, Chapot, René, additional, Wiesmann, Martin, additional, Machi, Paolo, additional, Diener, Hans-Christoph, additional, Kulcsar, Zsolt, additional, Bonati, Leo H, additional, Bassetti, Claudio L, additional, Mazighi, Mikael, additional, Liebeskind, David S, additional, Saver, Jeffrey L, additional, Gralla, Jan, additional, Alonso, Angelika, additional, Arquizan, Caroline, additional, Barreau, Xavier, additional, Beaujeux, Rémy, additional, Behme, Daniel, additional, Boeckh-Behrens, Tobias, additional, Boehme, Christian, additional, Boix, Martí, additional, Boulouis, Grégoire, additional, Bricout, Nicolas, additional, Broc, Nicolas, additional, Cereda, Carlo W., additional, Chabert, Emmanuel, additional, Cho, Tae-Hee, additional, Cianfoni, Alessandro, additional, Costalat, Vincent, additional, Denier, Christian, additional, Di Maria, Frederico, additional, du Mesnil de Rochemont, Richard, additional, Fearon, Patricia, additional, Ferrier, Anna, additional, Fischer, Sebastian, additional, Gauberti, Maxime, additional, Gaudron, Marie, additional, Gimenez, Laetitia, additional, Globas, Christoph, additional, Görtler, Michael, additional, Goyal, Mayank, additional, Hilker-Roggendorf, Ruediger, additional, Hill, Michael D., additional, Hua, Vi Tuan, additional, Humbertjean, Lisa, additional, Jansen, Olav, additional, Jung, Simon, additional, Kägi, Georg, additional, Kelly, Michael E., additional, Kleffner, Ilka, additional, Knoflach, Michael, additional, Nedeltchev, Krassen, additional, Krause, Lars Udo, additional, Lappalainen, Kimmo, additional, Lefebvre, Margaux, additional, Leyon, Joe, additional, Liao, Liang, additional, Liegey, Jean-Sebastien, additional, Loehr, Christian, additional, Michel, Patrik, additional, Nannoni, Stefania, additional, Nicholson, Patrick, additional, Nico, Lorena, additional, Obadia, Michael, additional, Ognard, Julien, additional, Ogungbemi, Ayokunle, additional, Olivot, Jean-Marc, additional, Escalard, Simon, additional, Pasi, Marco, additional, Peeling, Lissa, additional, Perez, Jane, additional, Petersen, Martina, additional, Piechowiak, Eike, additional, Raposo, Roberto, additional, Räty, Silja, additional, Reitz, Sarah C., additional, Remollo, Sebastià, additional, Remonda, Luca, additional, Rennie, Ian, additional, Requena, Manuel, additional, Riabikin, Alexander, additional, Riva, Roberto, additional, Rouchaud, Aymeric, additional, Rosi, Andrea, additional, Rubiera, Marta, additional, Spelle, Laurent, additional, Schnieder, Marlena, additional, Schaafsma, Joanna D., additional, Schubert, Tilman, additional, Schulz, Jörg B., additional, Siddiqui, Mohammed, additional, Soize, Sébastien, additional, Sonnberger, Michael, additional, Touze, Emmanuel, additional, Triquenot, Aude, additional, Turc, Guillaume, additional, Vieira, Lucy, additional, Ben Hassen, Wagih, additional, Wagner, Judith N., additional, Wasser, Katrin, additional, Weber, Johannes, additional, Wenz, Holger, additional, Weisenburger-Lile, David, additional, Wodarg, Fritz, additional, Wolff, Valérie, additional, and Wunderlich, Silke, additional

Published
2022
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49. Protocol for an individual patient data meta‐analysis on blood pressure targets after cardiac arrest

Author

Skrifvars, Markus B., primary, Ameloot, Koen, additional, Grand, Johannes, additional, Reinikainen, Matti, additional, Hästbacka, Johanna, additional, Niemelä, Ville, additional, Hassager, Christian, additional, Kjaergaard, Jesper, additional, Åneman, Anders, additional, Tiainen, Marjaana, additional, Nielsen, Niklas, additional, Ullen, Susann, additional, Dankiewicz, Josef, additional, Olsen, Markus Harboe, additional, Jørgensen, Caroline Kamp, additional, Saxena, Manoj, additional, and Jakobsen, Janus C., additional

Published
2022
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50. Interactions in the 2x2x2 factorial randomised clinical STEPCARE trial and the potential effects on conclusions:a protocol for a simulation study

Author

Olsen, Markus Harboe, Jensen, Aksel Karl Georg, Dankiewicz, Josef, Skrifvars, Markus B., Reinikainen, Matti, Tiainen, Marjaana, Saxena, Manoj, Aneman, Anders, Gluud, Christian, Ullen, Susann, Nielsen, Niklas, Jakobsen, Janus Christian, Olsen, Markus Harboe, Jensen, Aksel Karl Georg, Dankiewicz, Josef, Skrifvars, Markus B., Reinikainen, Matti, Tiainen, Marjaana, Saxena, Manoj, Aneman, Anders, Gluud, Christian, Ullen, Susann, Nielsen, Niklas, and Jakobsen, Janus Christian

Abstract

Background: Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2x2x2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest.Methods: By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all- cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errorsDiscussion: This protocol for a simulation study will inform the design of a 2x2x2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results.

Published
2022

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