19 results on '"Heindel, K."'
Search Results
2. CAR-T Tox: CRS/ICANS
- Author
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Garcia Borrega, Jorge, Universitätsklinikum Köln. Klinik I Für Innere Medizin, Kiehl, M., Heindel, K., and Böll, Boris
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Medizin und Gesundheit - Published
- 2021
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3. RICarT : Registry for immune-effector and CAR T associated toxicities
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Garcia Borrega, J., Heindel, K., Schmid, C., von Tresckow, Bastian, Reinhardt, Christian, Marks, R., Luther, M. L., Ayuk, F., Wichmann, D., Beutel, G., Obstfelder, E., Schnetzke, U., Schub, N., Baldus, C., Subklewe, M., von Bergwelt, M., Viardot, A., Schellongowski, P., and Böll, B.
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Medizin ,ComputingMethodologies_GENERAL - Abstract
Poster-Abstract
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- 2021
4. The critically ill CAR T-cell patient Relevant toxicities, their management and challenges in critical care
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Garcia Borrega, J., Heindel, K., Kochanek, M., Warnke, C., Stemmler, J., von Bergwelt-Baildon, M., Liebregts, T., Boell, B., Garcia Borrega, J., Heindel, K., Kochanek, M., Warnke, C., Stemmler, J., von Bergwelt-Baildon, M., Liebregts, T., and Boell, B.
- Abstract
Background CAR-T cell therapy has been implemented as clinical routine treatment option during the last decade. Despite beneficial outcomes in many patients severe side effects and toxicities are seen regularly that can compromise the treatment success. Methods Literature review: CAR T-cell therapy, toxicities and their management Results The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) are seen regularly after CAR T-cell treatment. CRS symptoms can range from mild flu-like symptoms to severe organ dysfunction requiring vasopressor therapy, mechanical ventilation and other intensive care support. ICANS symptoms usually develop later and can range from disorientation and aphasia to potentially life-threatening brain edema. IL-6 is a key factor in the pathophysiology of CRS. The pathophysiology of ICANS is not fully understood. The ASTCT consensus grading is recommended to stratify patients for different management options. An interdisciplinary team including hematologist, intensivist, neurologists and other specialties is needed to optimize the treatment. Discussion Severe and potentially life-threatening toxicities occur regularly after CAR T-cell therapy. Treatment strategies for CRS and ICANS still need to be evaluated prospectively. Due to the increasing number of patients treated with CAR T-cells the number of patients requiring temporary intensive care management due to CRS and ICANS is expected to increase during the next years.
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- 2021
5. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial
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François-Xavier Lescure, Hitoshi Honda, Robert A Fowler, Jennifer Sloane Lazar, Genming Shi, Peter Wung, Naimish Patel, Owen Hagino, Ignacio J. Bazzalo, Marcelo M. Casas, Sebastián A. Nuñez, Yael Pere, Carlos M. Ibarrola, Marco A. Solis Aramayo, Maria C. Cuesta, Andrea E. Duarte, Pablo M. Gutierrez Fernandez, Maria A. Iannantuono, Erica A. Miyazaki, Javier P. Silvio, Dario G. Scublinsky, Alessandra Bales, Daniela Catarino, Elie Fiss, Sara Mohrbacher, Victor Sato, Antonio Baylao, Adilson Cavalcante, Francini Correa, Celso A. de Andrade, Juvencio Furtado, Nelson Ribeiro Filho, Valéria Telles, Leopoldo T. Trevelin, Ricardo Vipich, Rodrigo Boldo, Paula Borges, Suzana Lobo, Graziela Luckemeyer, Luana Machado, Maysa B. Alves, Ana C. Iglessias, Marianna M. Lago, Daniel W. Santos, Hugo Chapdelaine, Emilia L. Falcone, Rahima Jamal, Me-Linh Luong, Madeleine Durand, Stephane Doucet, François-Martin Carrier, Bryan A. Coburn, Lorenzo Del Sorbo, Sharon L. Walmsley, Sara Belga, Luke Y. Chen, Allison D. Mah, Theodore Steiner, Alissa J. Wright, J. Hajek, Neill Adhikari, Robert A. Fowler, Nick Daneman, Kosar A. Khwaja, Jason Shahin, Carolina Gonzalez, Rafael Silva, Marcelo Lindh, Gabriel Maluenda, Patricia Fernandez, Maite Oyonarte, Martin Lasso, Alexandre Boyer, Didier Bronnimann, Hoang-Nam Bui, Charles Cazanave, Helene Chaussade, Arnaud Desclaux, Mailys Ducours, Alexandre Duvignaud, Denis Malvy, Lisa Martin, Didier Neau, Duc Nguyen, Thierry Pistone, Gaetane Soubrane-Wirth, Julie Leitao, Clotilde Allavena, Charlotte Biron, Sabelline Bouchez, Benjamin Gaborit, Antoine Gregoire, Paul Le Turnier, Anne-Sophie Lecompte, Raphael Lecomte, Maeva Lefebvre, Francois Raffi, David Boutoille, Pascale H. Morineau, Romain Guéry, Emmanuel Chatelus, Nathalie Dumoussaud, Renaud Felten, Florina Luca, Bernard Goichot, Francis Schneider, Marie-Caroline Taquet, Matthieu Groh, Mathilde Roumier, Mathilde Neuville, Antoine Bachelard, Valentina Isernia, F-Xavier Lescure, Bao-Chau Phung, Anne Rachline, Aurelie Sautereau, Dorothee Vallois, Yves Bleher, Delphine Boucher, Clémentine Coudon, Jean Esnault, Thomas Guimard, Sophie Leautez-Nainville, Dominique Merrien, Marine Morrier, Pauline Motte-Vincent, Romain Gabeff, Hélène Leclerc, Céline Cozic, Romain Decours, Ronan Février, Gwenhael Colin, Sophie Abgrall, Dorothee Vignes, Raluca Sterpu, Mira Kuellmar, Melanie Meersch-Dini, Raphael Weiss, Alexander Zarbock, Christiane Antony, Marc Berger, Thorsten Brenner, Christian Taube, Frank Herbstreit, Sebastian Dolff, Margarethe Konik, Karsten Schmidt, Markus Zettler, Oliver Witzke, Boris Boell, Jorge Garcia Borrega, Philipp Koehler, Thomas Zander, Fabian Dusse, Othman Al-Sawaf, Philipp Köhler, Dennis Eichenauer, Matthias Kochanek, Alexander Shimabukuro-Vornhagen, Sibylle Mellinghoff, Annika Claßen, Jan-Michel Heger, Charlotte Meyer-Schwickerath, Paul Liedgens, Katrin Heindel, Ana Belkin, Asaf Biber, Mayan Gilboa, Itzchak Levy, Vladislav Litachevsky, Galia Rahav, Anat Finesod Wiedner, Tal Zilberman-Daniels, Yonatan Oster, Jacob Strahilevitz, Sigal Sviri, Elena M. Baldissera, Corrado Campochiaro, Giulio Cavalli, Lorenzo Dagna, Giacomo De Luca, Emanuel Della Torre, Alessandro Tomelleri, Davide Bernasconi De Luca, Amedeo F. Capetti, Massimo Coen, Maria V. Cossu, Massimo Galli, Andrea Giacomelli, Guido A. Gubertini, Stefano Rusconi, Giulia J. Burastero, Margherita Digaetano, Giovanni Guaraldi, Marianna Meschiari, Cristina Mussini, Cinzia Puzzolante, Sara Volpi, Marina Aiello, Alarico Ariani, Alfredo A. Chetta, Annalisa Frizzelli, Andrea Ticinesi, Domenico Tuttolomondo, Stefano Aliberti, Francesco B. Blasi, Marta F. Di Pasquale, Sofia Misuraca, Tommaso Pilocane, Edoardo Simonetta, Alessio M. Aghelmo, Claudio Angelini, Enrico Brunetta, Giorgio W. Canonica, Michele Ciccarelli, Sara Dal Farra, Maria De Santis, Sebastian Ferri, Marco Folci, Giacomo M. Guidelli, Enrico M. Heffler, Ferdinando Loiacono, Giacomo Malipiero, Giovanni Paoletti, Rosa Pedale, Francesca A. Puggioni, Francesca Racca, Aurora Zumbo, Morihiko Satou, Tatyana Lisun, Denis Protsenko, Nikolay Rubtsov, Irina Beloglazova, Daria Fomina, Mariana Lysenko, Sofia Serdotetskova, Vitali Firstov, Ivan Gordeev, Ilia Kokorin, Ksenia Komissarova, Nina Lapochkina, Elena Luchinkina, Valentin Malimon, Sevinch Mamedguseyinova, Ksenia Polubatonova, Natalia Suvorova, Jose Arribas, Alberto M. Borobia Perez, Fernando de la Calle Prieto, Juan Carlos Figueira, Rocio Motejano Sanchez, Marta Mora-Rillo, Concepcion Prados Sanchez, Javier Queiruga Parada, Francisco Fernandez Arnalich, Maria Guerro Barrientos, Alejandro Bendala Estrada, Aranzazu Caballero Marcos, Maria E. Garcia Leoni, Rita García-Martínez, Ana María Collado, Patricia Munoz Garcia, Ana Torres do Rego, María V. Villalba García, Almudena Burrillo, Maricela Valerio Minero, Paloma Gijon Vidaurreta, Sonsoles Infante Herrero, Elena Velilla, Marina Machado, Maria Olmedo, Blanca Pinilla, Benito Almirante Gragera, Maria de la Esperanza Cañas Ruano, Sofia Contreras Medina, Alejandro Cortés Herrera, Vicenç Falcó Ferrer, Ricard Ferrer Roca, Xavier Nuvials Casals, Esteve Ribera Pascuet, Paula Suanzes Diez, Pedro Rebollo Castro, Felipe Garcia Alcaide, Alejandro Soriano, Aina Oliver Caldes, Ana González Cordón, Celia Cardozo, Lorena De la Mora Cañizo, Romina Pena López, Sandra Chamorro, Clara Crespillo-Andujar, Rosa Escudero Sanchez, Jesús Fortún-Abete, Begoña Monge-Maillo, Ana Moreno Zamora, Francesca Norman, Matilde Sanchez Conde, Sergio Serrano Villar, Pilar Vizcarra, Lescure, F. -X., Honda, H., Fowler, R. A., Lazar, J. S., Shi, G., Wung, P., Patel, N., Hagino, O., Bazzalo, I. J., Casas, M. M., Nunez, S. A., Pere, Y., Ibarrola, C. M., Solis Aramayo, M. A., Cuesta, M. C., Duarte, A. E., Gutierrez Fernandez, P. M., Iannantuono, M. A., Miyazaki, E. A., Silvio, J. P., Scublinsky, D. G., Bales, A., Catarino, D., Fiss, E., Mohrbacher, S., Sato, V., Baylao, A., Cavalcante, A., Correa, F., de Andrade, C. A., Furtado, J., Ribeiro Filho, N., Telles, V., Trevelin, L. T., Vipich, R., Boldo, R., Borges, P., Lobo, S., Luckemeyer, G., Machado, L., Alves, M. B., Iglessias, A. C., Lago, M. M., Santos, D. W., Chapdelaine, H., Falcone, E. L., Jamal, R., Luong, M. -L., Durand, M., Doucet, S., Carrier, F. -M., Coburn, B. A., Del Sorbo, L., Walmsley, S. L., Belga, S., Chen, L. Y., Mah, A. D., Steiner, T., Wright, A. J., Hajek, J., Adhikari, N., Daneman, N., Khwaja, K. A., Shahin, J., Gonzalez, C., Silva, R., Lindh, M., Maluenda, G., Fernandez, P., Oyonarte, M., Lasso, M., Boyer, A., Bronnimann, D., Bui, H. -N., Cazanave, C., Chaussade, H., Desclaux, A., Ducours, M., Duvignaud, A., Malvy, D., Martin, L., Neau, D., Nguyen, D., Pistone, T., Soubrane-Wirth, G., Leitao, J., Allavena, C., Biron, C., Bouchez, S., Gaborit, B., Gregoire, A., Le Turnier, P., Lecompte, A. -S., Lecomte, R., Lefebvre, M., Raffi, F., Boutoille, D., Morineau, P. H., Guery, R., Chatelus, E., Dumoussaud, N., Felten, R., Luca, F., Goichot, B., Schneider, F., Taquet, M. -C., Groh, M., Roumier, M., Neuville, M., Bachelard, A., Isernia, V., Phung, B. -C., Rachline, A., Sautereau, A., Vallois, D., Bleher, Y., Boucher, D., Coudon, C., Esnault, J., Guimard, T., Leautez-Nainville, S., Merrien, D., Morrier, M., Motte-Vincent, P., Gabeff, R., Leclerc, H., Cozic, C., Decours, R., Fevrier, R., Colin, G., Abgrall, S., Vignes, D., Sterpu, R., Kuellmar, M., Meersch-Dini, M., Weiss, R., Zarbock, A., Antony, C., Berger, M., Brenner, T., Taube, C., Herbstreit, F., Dolff, S., Konik, M., Schmidt, K., Zettler, M., Witzke, O., Boell, B., Garcia Borrega, J., Koehler, P., Zander, T., Dusse, F., Al-Sawaf, O., Kohler, P., Eichenauer, D., Kochanek, M., Shimabukuro-Vornhagen, A., Mellinghoff, S., Classen, A., Heger, J. -M., Meyer-Schwickerath, C., Liedgens, P., Heindel, K., Belkin, A., Biber, A., Gilboa, M., Levy, I., Litachevsky, V., Rahav, G., Finesod Wiedner, A., Zilberman-Daniels, T., Oster, Y., Strahilevitz, J., Sviri, S., Baldissera, E. M., Campochiaro, C., Cavalli, G., Dagna, L., De Luca, Giacomo., Della Torre, E., Tomelleri, A., Bernasconi De Luca, D., Capetti, A. F., Coen, M., Cossu, M. V., Galli, M., Giacomelli, A., Gubertini, G. A., Rusconi, S., Burastero, G. J., Digaetano, M., Guaraldi, G., Meschiari, M., Mussini, C., Puzzolante, C., Volpi, S., Aiello, M., Ariani, A., Chetta, A. A., Frizzelli, A., Ticinesi, A., Tuttolomondo, D., Aliberti, S., Blasi, F. B., Di Pasquale, M. F., Misuraca, S., Pilocane, T., Simonetta, E., Aghelmo, A. M., Angelini, C., Brunetta, E., Canonica, G. W., Ciccarelli, M., Dal Farra, S., De Santis, M., Ferri, S., Folci, M., Guidelli, G. M., Heffler, E. M., Loiacono, F., Malipiero, G., Paoletti, G., Pedale, R., Puggioni, F. A., Racca, F., Zumbo, A., Satou, M., Lisun, T., Protsenko, D., Rubtsov, N., Beloglazova, I., Fomina, D., Lysenko, M., Serdotetskova, S., Firstov, V., Gordeev, I., Kokorin, I., Komissarova, K., Lapochkina, N., Luchinkina, E., Malimon, V., Mamedguseyinova, S., Polubatonova, K., Suvorova, N., Arribas, J., Borobia Perez, A. M., de la Calle Prieto, F., Figueira, J. C., Motejano Sanchez, R., Mora-Rillo, M., Prados Sanchez, C., Queiruga Parada, J., Fernandez Arnalich, F., Guerro Barrientos, M., Bendala Estrada, A., Caballero Marcos, A., Garcia Leoni, M. E., Garcia-Martinez, R., Collado, A. M., Munoz Garcia, P., Torres do Rego, A., Villalba Garcia, M. V., Burrillo, A., Valerio Minero, M., Gijon Vidaurreta, P., Infante Herrero, S., Velilla, E., Machado, M., Olmedo, M., Pinilla, B., Almirante Gragera, B., Canas Ruano, M. D. L. E., Contreras Medina, S., Cortes Herrera, A., Falco Ferrer, V., Ferrer Roca, R., Nuvials Casals, X., Ribera Pascuet, E., Suanzes Diez, P., Rebollo Castro, P., Garcia Alcaide, F., Soriano, A., Oliver Caldes, A., Gonzalez Cordon, A., Cardozo, C., De la Mora Canizo, L., Pena Lopez, R., Chamorro, S., Crespillo-Andujar, C., Escudero Sanchez, R., Fortun-Abete, J., Monge-Maillo, B., Moreno Zamora, A., Norman, F., Sanchez Conde, M., Serrano Villar, S., and Vizcarra, P.
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Critical Care ,International Cooperation ,Population ,Antibodies, Monoclonal, Humanized ,Placebo ,Severity of Illness Index ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Intensive care ,Severity of illness ,medicine ,Clinical endpoint ,Humans ,Immunologic Factors ,030212 general & internal medicine ,Mortality ,education ,Respiratory Distress Syndrome ,education.field_of_study ,Dose-Response Relationship, Drug ,SARS-CoV-2 ,business.industry ,Hazard ratio ,COVID-19 ,Articles ,Middle Aged ,Receptors, Interleukin-6 ,Sarilumab ,Treatment Outcome ,030228 respiratory system ,Female ,Drug Monitoring ,Cytokine Release Syndrome ,business - Abstract
Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.
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- 2021
6. Stiffness and Instability After MPFL Reconstruction Using a Fluoroscopic Versus Open Technique to Localize the Femoral Attachment Site: A Systematic Review and Meta-analysis.
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Heindel K, Smoak J, Kocan J, Cossell C, Haider MN, Levy BJ, and Bisson L
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Background: Open and fluoroscopic techniques have been described for localization of the femoral attachment site in medial patellofemoral ligament (MPFL) reconstruction. No study to date has evaluated if one technique is superior to another in terms of complications., Purpose: To review the literature comparing clinical outcomes of MPFL reconstruction using the fluoroscopic versus open technique to localize the site of femoral graft placement., Study Design: Systematic review; Level of evidence, 4., Methods: A systematic literature review was performed via PubMed, Embase, and CINAHL to identify articles published between the inception of these databases and March 1, 2022, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. This search yielded 4183 publications for initial review. Studies with at least a 2-year follow-up and complete reporting of patient-reported outcomes, range of motion, recurrent instability, and/or complications (ie, stiffness, infection, persistent pain) were included. We excluded studies of patients with collagen disorders; revision surgeries; surgeries with concomitant procedures; synthetic MPFL reconstruction; MPFL repairs; combined open and radiographic technique; and case series that included <10 patients. A proportional meta-analysis was performed by calculating the pooled estimate of incidence with 95% CIs using a fixed-effects model with double arcsine transformation (Freeman-Tukey) for each type of surgical technique (fluoroscopic or open)., Results: A total of 29 studies met our inclusion criteria, of which 15 studies (566 patients) used the open technique and 14 studies (620 patients) used fluoroscopy. There were no significant differences between the open and fluoroscopic techniques in the incidence of postoperative apprehension ( P = .4826), postoperative subjective instability ( P = .1095), postoperative objective instability ( P = .5583), reoperations ( P = .7981), recurrent dislocation ( P = .6690), or arthrofibrosis ( P = .8118)., Conclusion: Both open and radiographic localization of the femoral graft position in MPFL reconstruction offer similar outcomes and rates of complications., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: K.H. has received grant support from Arthrex; education payments from Arthrex, Smith & Nephew, and Rock Med; and hospitality payments from Zimmer Biomet. C.C. has received grant support from Arthrex and education payments from Arthrex and Smith & Nephew. B.J.L. has received education payments from Prodigy Surgical. L.B. has received royalties from Zimmer Biomet and hospitality payments from Arthrex and Prodigy Surgical. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)
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- 2023
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7. Increased circulating cytokeratin 19 fragment levels in preterm neonates receiving mechanical ventilation are associated with poor outcome.
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Panahabadi S, Heindel K, Mueller A, Holdenrieder S, and Kipfmueller F
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- Bronchopulmonary Dysplasia metabolism, Bronchopulmonary Dysplasia pathology, Bronchopulmonary Dysplasia therapy, Case-Control Studies, Female, Humans, Infant, Newborn, Male, Prognosis, Respiratory Distress Syndrome, Newborn metabolism, Respiratory Distress Syndrome, Newborn pathology, Respiratory Distress Syndrome, Newborn therapy, Survival Rate, Biomarkers metabolism, Bronchopulmonary Dysplasia mortality, Infant, Premature growth & development, Keratin-19 metabolism, Respiration, Artificial mortality, Respiratory Distress Syndrome, Newborn mortality
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Invasive mechanical ventilation and oxygen toxicity are postnatal contributors to chronic lung disease of prematurity, also known as bronchopulmonary dysplasia (BPD). Cyfra 21-1 is a soluble fragment of cytokeratin 19, which belongs to the cytoskeleton stabilizing epithelial intermediate filaments. As a biomarker of structural integrity, Cyfra 21-1 might be associated with airway injury and lung hypoplasia in neonates. Serum Cyfra 21-1 concentrations for 80 preterm and 80 healthy term newborns were measured within 48 h after birth. Preterm infants with the combined endpoint BPD/mortality had significantly higher Cyfra 21-1 levels compared with those without fulfilling BPD/mortality criteria ( P = 0.01). Also, severe RDS (>grade III) was associated with higher Cyfra levels ( P = 0.01). Total duration of oxygen therapy was more than five times longer in neonates with high Cyfra 21-1 levels ( P = 0.01). Infants with higher Cyfra 21-1 values were more likely to receive mechanical ventilation (50% vs. 17.5%). However, the duration of mechanical ventilation was similar between groups. The median Cyfra value was 1.93 ng/mL (IQR: 1.68-2.53 ng/mL) in healthy term neonates and 8.5 ng/mL (IQR: 3.6-16.0 ng/mL) in preterm infants. Using ROC analysis, we calculated a Cyfra cutoff > 8.5 ng/mL to predict BPD/death with an AUC of 0.795 ( P = 0.004), a sensitivity of 88.9%, and a specificity of 55%. Mortality was predicted with a cutoff > 17.4 ng/mL (AUC: 0.94; P = 0.001), a sensitivity of 100%, and a specificity of 84%. These findings suggest that Cyfra 21-1 concentration might be useful to predict poor outcome in premature infants.
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- 2021
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8. Survivorship of the Hip Joint After Acetabulum Fracture.
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Preston G, Heimke IM, Heindel K, Scarcella NR, Furdock R, and Vallier HA
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- Acetabulum surgery, Aged, Hip Joint surgery, Humans, Reoperation, Retrospective Studies, Survivorship, Treatment Outcome, Arthroplasty, Replacement, Hip adverse effects, Hip Fractures surgery
- Abstract
Purpose: The purposes of this study were to determine the rate of failure of the hip joint after acetabulum fracture and to identify risk factors., Methods: Acetabulum fractures treated over 17 years at a level-1 trauma center were reviewed. Patient, injury, and treatment factors were assessed regarding possible association with failure of the hip joint: end-stage arthrosis and/or total hip arthroplasty (THA)., Results: Seventy percent were treated with primary open reduction and internal fixation (ORIF). Seventy-two (12.5%) of 575 fractures underwent THA; 64 were after initial ORIF. The mean follow-up was 80 months, and the median time to THA was 14 months (range 10-200 months). Age, body mass index, fracture type, marginal impaction, and hip dislocations were independent predictors of hip joint failure. The mean injured age of THA patients was 53 versus 43 (P < 0.001). T-type fractures were most likely to fail (21% within 2 years, 45% within 10 years, P = 0.001). Other injury features: marginal impaction and posterior hip dislocation were associated with failure with odds ratios 2.79 and 1.73, respectively (P < 0.001)., Conclusion: Eighty-five percent of native hips survived; the median time to THA was 14 months. Most who had THA had initial posterior fracture-dislocations. Older age, elevated body mass index, T-type pattern, marginal impaction, and hip dislocation increase the likelihood of hip joint failure., (Copyright © 2021 by the American Academy of Orthopaedic Surgeons.)
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- 2021
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9. Clinical Course and Outcome of Patients with SARS-CoV-2 Alpha Variant Infection Compared to Patients with SARS-CoV-2 Wild-Type Infection Admitted to the ICU.
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Garcia Borrega J, Naendrup JH, Heindel K, Hamacher L, Heger E, Di Cristanziano V, Deppe AC, Dusse F, Wetsch WA, Eichenauer DA, Shimabukuro-Vornhagen A, Böll B, and Kochanek M
- Abstract
The alpha variant of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is associated with higher transmissibility and possibly higher mortality compared with wild-type SARS-CoV-2. However, few data are available on the clinical course of infections with the alpha variant compared with wild-type SARS-CoV-2 in critically ill patients in intensive care units (ICUs). Therefore, we retrospectively analyzed patients admitted to our ICU due to SARS-CoV-2 Alpha variant infection and compared characteristics and course to patients with SARS-CoV-2 wild-type infection. The median age of patients with Alpha variant infections was 57 years compared to 62 years in the wild-type group. ICU survival was 41/80 (51%) in the Alpha variant group and 35/80 (44%) in the wild-type group ( p = 0.429). Results of a matched-pair analysis based on age and sex illustrated that 45/58 patients (77.6%) in the Alpha variant group and 38/58 (65.5%) patients in the wild-type group required mechanical ventilation ( p = 0.217). ICU survival was documented for 28/58 patients (48.3%) in the Alpha variant group and 27/58 patients (46.6%) in the wild-type group ( p = 1). Thus, ICU mortality among patients with SARS-CoV-2 infections remains high. Although the Alpha variant group included younger patients requiring mechanical ventilation, no significant differences between patients with the SARS-CoV-2 Alpha variant and the SARS-CoV-2 wild-type, respectively, were detected with respect to clinical course and ICU mortality. For future VOCs, we believe it would be important to obtain valid and rapid data on the clinical course of critically ill patients who test positive for COVID-19 in order to perform appropriate epidemiological planning of intensive care capacity.
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- 2021
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10. [Toxicity after chimeric antigen receptor T-cell therapy : Overview and management of early and late onset side effects].
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Garcia Borrega J, Heindel K, Göreci Y, Warnke C, Onur OA, Kochanek M, Schub N, Ayuk F, Wichmann D, and Böll B
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- Cell- and Tissue-Based Therapy, Cytokine Release Syndrome, Humans, T-Lymphocytes, United States, Immunotherapy, Adoptive adverse effects, Receptors, Chimeric Antigen
- Abstract
Background: The transfusion of chimeric antigen receptor (CAR) T‑cells has become established as a new treatment option in oncology; however, this is regularly associated with immune-mediated side effects, which can also run a severe course and necessitate a specific treatment and intensive medical treatment., Material and Methods: A literature review was carried out on CAR T-cell therapy, toxicities and the management of side effects., Results: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) regularly occur shortly after CAR T-cell treatment. The symptoms of CRS can range from mild flu-like symptoms to multiorgan failure. In addition to mild symptoms, such as disorientation and aphasia, ICANS can also lead to convulsive seizures and brain edema. The management of CRS and ICANS is based on the severity according to the grading of the American Society for Transplantation and Cellular Therapy (ASTCT). Tocilizumab and corticosteroids are recommended for CRS and corticosteroids are used for ICANS. In the further course persisting hypogammaglobulinemia and cytopenia are frequent even months after the initial treatment and promote infections even months after CAR T‑cell therapy., Discussion: Potentially severe complications regularly occur after CAR T-cell therapy. An interdisciplinary cooperation between intensive care physicians, hematologists, neurologists and specialists in other disciplines is of decisive importance for the optimal care of patients after CAR T‑cell therapy.
- Published
- 2021
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11. [Erratum to: Toxicity after chimeric antigen receptor T-cell therapy].
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Garcia Borrega J, Heindel K, Göreci Y, Warnke C, Onur OA, Kochanek M, Schub N, Ayuk F, Wichmann D, and Böll B
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- 2021
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12. [The critically ill CAR T-cell patient : Relevant toxicities, their management and challenges in critical care].
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Garcia Borrega J, Heindel K, Kochanek M, Warnke C, Stemmler J, von Bergwelt-Baildon M, Liebregts T, and Böll B
- Subjects
- Critical Care, Cytokine Release Syndrome, Humans, T-Lymphocytes, Critical Illness therapy, Immunotherapy, Adoptive
- Abstract
Background: CAR‑T cell therapy has been implemented as clinical routine treatment option during the last decade. Despite beneficial outcomes in many patients severe side effects and toxicities are seen regularly that can compromise the treatment success., Methods: Literature review: CAR T‑cell therapy, toxicities and their management RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) are seen regularly after CAR T‑cell treatment. CRS symptoms can range from mild flu-like symptoms to severe organ dysfunction requiring vasopressor therapy, mechanical ventilation and other intensive care support. ICANS symptoms usually develop later and can range from disorientation and aphasia to potentially life-threatening brain edema. IL‑6 is a key factor in the pathophysiology of CRS. The pathophysiology of ICANS is not fully understood. The ASTCT consensus grading is recommended to stratify patients for different management options. An interdisciplinary team including hematologist, intensivist, neurologists and other specialties is needed to optimize the treatment., Discussion: Severe and potentially life-threatening toxicities occur regularly after CAR T‑cell therapy. Treatment strategies for CRS and ICANS still need to be evaluated prospectively. Due to the increasing number of patients treated with CAR T‑cells the number of patients requiring temporary intensive care management due to CRS and ICANS is expected to increase during the next years.
- Published
- 2021
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- View/download PDF
13. Early postnatal changes of circulating N-terminal-pro-B-type natriuretic peptide in neonates with congenital diaphragmatic hernia.
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Heindel K, Holdenrieder S, Patel N, Bartmann P, Schroeder L, Berg C, Merz WM, Mueller A, and Kipfmueller F
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- Electrocardiography, Extracorporeal Membrane Oxygenation, Female, Fetal Blood, Hernias, Diaphragmatic, Congenital mortality, Hernias, Diaphragmatic, Congenital physiopathology, Hernias, Diaphragmatic, Congenital therapy, Humans, Hypertension, Pulmonary mortality, Infant, Infant Mortality, Infant, Newborn, Male, Prospective Studies, Hernias, Diaphragmatic, Congenital blood, Hypertension, Pulmonary diagnosis, Natriuretic Peptide, Brain blood, Peptide Fragments blood
- Abstract
Background: Severity of lung hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction are major contributors to mortality in congenital diaphragmatic hernia (CDH). Therefore, early assessment and management is important to improve outcome. NT-proBNP is an established cardiac biomarker with only limited data for early postnatal risk assessment in CDH newborns., Aims: To investigate the correlation of NT-proBNP at birth, 6 h, 12 h, 24 h, and 48 h with PH and cardiac dysfunction and the prognostic information of NT-proBNP for the use of ECMO support or mortality., Subjects: 44 CDH newborns treated at our institution (December 2014-October 2017) were prospectively enrolled., Outcome Measures: Primary clinical endpoint was either need for ECMO or death within the first 48 h (group A). Infants not receiving ECMO support were allocated to group B. Mortality was tested as secondary endpoint., Results: NT-proBNP levels measured at 6 h, 12 h, 24 h and 48 h postpartum correlated significantly with PH severity following NICU admission and at 24 h, and with severity of cardiac dysfunction at birth, 24 h, 48 h and after 7 days of life. There was no difference in NT-proBNP levels between survivors and non-survivors. NT-proBNP levels were significantly higher in group A at 6 h (p = 0.007), 12 h (p = 0.036), and 24 h (p = 0.007), but not at birth (p = 0.785) or 48 h (p = 0.15) compared to group B., Conclusion: NT-proBNP analysis in the first 48 h of life may be useful to assess PH and cardiac dysfunction in CDH newborns and to predict the need for ECMO support., Competing Interests: Declaration of competing interest Authors state no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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14. Constraining the formation of authigenic carbonates in a seepage-affected cold-water coral mound by lipid biomarkers.
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Feenstra EJ, Birgel D, Heindel K, Wehrmann LM, Jaramillo-Vogel D, Grobéty B, Frank N, Hancock LG, Van Rooij D, Peckmann J, and Foubert A
- Subjects
- Anaerobiosis, Animals, Archaea, Biomarkers, Carbonates, Geologic Sediments, Lipids, Methane, Oxidation-Reduction, Phylogeny, Anthozoa
- Abstract
Cold-water coral (CWC) mounds are build-ups comprised of coral-dominated intervals alternating with a mixed carbonate-siliciclastic matrix. At some locations, CWC mounds are influenced by methane seepage, but the impact of methane on CWC mounds is poorly understood. To constrain the potential impact of methane on CWC mound growth, lipid biomarker investigations were combined with mineralogical and petrographic analyses to investigate the anaerobic oxidation of methane (AOM) and authigenic carbonate formation in sediment from a seep-affected CWC mound in the Gulf of Cadiz. The occurrence of AOM was confirmed by characteristic lipids found within a semi-lithified zone (SLZ) consisting of authigenic aragonite, high-magnesium calcite and calcium-excess dolomite. The formation of high-Mg calcite is attributed to AOM, acting as a lithifying agent. Aragonite is only a minor phase. Ca-excess dolomite in the SLZ and upper parts may be formed by organoclastic sulphate reduction, favouring precipitation by increased alkalinity. The AOM biomarkers in the SLZ include isoprenoid-based archaeal membrane lipids, such as abundant glycerol dibiphytanyl glycerol tetraethers (GDGTs) dominated by GDGT-2. The δ
13 C values of GDGT-2, measured as ether-cleaved monocyclic biphytanes, are as low as -100‰ versus V-PDB. Further, bacterial dialkyl glycerol diethers with two anteiso-C15 alkyl chains and δ13 C values of -81‰ are interpreted as biomarkers of sulphate-reducing bacteria. The lipid biomarker signatures and mineralogical patterns suggest that anaerobic methane-oxidizing archaea of the ANME-1 group thrived in the subsurface at times of slow and diffusive methane seepage. Petrographic analyses revealed that the SLZ was exhumed at some point (e.g. signs of bioerosion of the semi-lithified sediment), providing a hard substrate for CWC larval settlement. In addition, this work reveals that AOM-induced semi-lithification likely played a role in mound stabilization. Lipid biomarker analysis proves to be a powerful tool to disentangle early diagenetic processes induced by microbial metabolisms., (© 2019 John Wiley & Sons Ltd.)- Published
- 2020
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15. Suppressed competitive exclusion enabled the proliferation of Permian/Triassic boundary microbialites.
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Foster WJ, Heindel K, Richoz S, Gliwa J, Lehrmann DJ, Baud A, Kolar-Jurkovšek T, Aljinović D, Jurkovšek B, Korn D, Martindale RC, and Peckmann J
- Abstract
During the earliest Triassic microbial mats flourished in the photic zones of marginal seas, generating widespread microbialites. It has been suggested that anoxic conditions in shallow marine environments, linked to the end-Permian mass extinction, limited mat-inhibiting metazoans allowing for this microbialite expansion. The presence of a diverse suite of proxies indicating oxygenated shallow sea-water conditions (metazoan fossils, biomarkers and redox proxies) from microbialite successions have, however, challenged the inference of anoxic conditions. Here, the distribution and faunal composition of Griesbachian microbialites from China, Iran, Turkey, Armenia, Slovenia and Hungary are investigated to determine the factors that allowed microbialite-forming microbial mats to flourish following the end-Permian crisis. The results presented here show that Neotethyan microbial buildups record a unique faunal association due to the presence of keratose sponges, while the Palaeotethyan buildups have a higher proportion of molluscs and the foraminifera Earlandia . The distribution of the faunal components within the microbial fabrics suggests that, except for the keratose sponges and some microconchids, most of the metazoans were transported into the microbial framework via wave currents. The presence of both microbialites and metazoan associations were limited to oxygenated settings, suggesting that a factor other than anoxia resulted in a relaxation of ecological constraints following the mass extinction event. It is inferred that the end-Permian mass extinction event decreased the diversity and abundance of metazoans to the point of significantly reducing competition, allowing photosynthesis-based microbial mats to flourish in shallow water settings and resulting in the formation of widespread microbialites., Competing Interests: The authors have no conflict of interest to declare., (© 2019 The Authors. The Depositional Record published by John Wiley & Sons Ltd on behalf of International Association of Sedimentologists.)
- Published
- 2020
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16. Diagnosis and Management Strategies for Distal Biceps Rupture.
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Holt J, Preston G, Heindel K, Preston H, and Hill G
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- Arm surgery, Elbow surgery, Humans, Range of Motion, Articular physiology, Rupture diagnosis, Tendon Injuries diagnosis, Treatment Outcome, Muscle, Skeletal surgery, Orthopedic Procedures methods, Rupture surgery, Tendon Injuries surgery
- Abstract
Rupture of the distal biceps tendon most commonly is secondary to mechanical overload during eccentric muscle contraction. Due to deficits of strength and endurance, surgical repair usually is recommended. Although both single- and double-incision approaches have been described, double-incision techniques have been shown to better re-create the native anatomic insertion. However, excellent and comparable clinical outcomes have been demonstrated with both techniques. Fixation with a cortical button and interference screw has been shown to be the strongest construct biomechanically; however, several modern constructs provide adequate strength. Surgical technique should focus on restoration of anatomy, early range of motion, and prevention of complications. [Orthopedics. 2019; 42(6):e492-e501.]., (Copyright 2019, SLACK Incorporated.)
- Published
- 2019
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- View/download PDF
17. Expression of soluble receptor for advanced glycation end products is associated with disease severity in congenital diaphragmatic hernia.
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Kipfmueller F, Heindel K, Geipel A, Berg C, Bartmann P, Reutter H, Mueller A, and Holdenrieder S
- Subjects
- Extracorporeal Membrane Oxygenation, Fetal Blood chemistry, Hernias, Diaphragmatic, Congenital genetics, Hernias, Diaphragmatic, Congenital therapy, Humans, Infant, Newborn, Intensive Care Units, Neonatal, Liver pathology, Prospective Studies, Receptor for Advanced Glycation End Products biosynthesis, Receptor for Advanced Glycation End Products genetics, Respiration, Artificial, Hernias, Diaphragmatic, Congenital pathology, Hypertension, Pulmonary pathology, Lung pathology, Receptor for Advanced Glycation End Products blood
- Abstract
Pulmonary hypertension (PH) and lung hypoplasia are major contributors to morbidity and mortality in newborns with congenital diaphragmatic hernia (CDH). The soluble receptor for advanced glycation end products (sRAGE) is a marker of endothelial function and might be associated with disease severity in CDH newborns. In a cohort of 30 CDH newborns and 20 healthy control newborns, sRAGE concentration was measured at birth and at 6 h, 12 h, 24 h, 48 h, and 7-10 days. In healthy newborns, sRAGE was significantly higher at birth and at 48 h compared with CDH newborns (both P < 0.001). Among CDH newborns, sRAGE was significantly lower at birth ( P = 0.033) and at 7-10 days ( P = 0.035) in patients receiving extracorporeal membrane oxygenation (ECMO) compared with patients not receiving ECMO. In contrast, CDH newborns receiving ECMO had significantly higher values at 6 h ( P = 0.001), 12 h ( P = 0.004), and 48 h (0.032). Additionally, sRAGE correlated significantly with PH severity, intensity and duration of mechanical ventilation, and prenatally assessed markers of CDH severity (lung size, liver herniation). The probability to receive ECMO therapy was five times higher in CDH newborns with sRAGE concentrations below the calculated cutoff of 650 pg/ml at birth ( P = 0.002) and nine times higher in CDH newborns with sRAGE concentrations above the cutoff of 3,500 pg/ml at 6 h ( P = 0.001). These findings suggest a potential involvement of sRAGE in the pathophysiology of CDH and may act as a therapeutic target in future treatment approaches.
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- 2019
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18. Early postnatal echocardiographic assessment of pulmonary blood flow in newborns with congenital diaphragmatic hernia.
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Kipfmueller F, Heindel K, Schroeder L, Berg C, Dewald O, Reutter H, Bartmann P, and Mueller A
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- Cohort Studies, Extracorporeal Membrane Oxygenation, Female, Germany, Hernias, Diaphragmatic, Congenital complications, Humans, Infant, Newborn, Kaplan-Meier Estimate, Male, Persistent Fetal Circulation Syndrome etiology, Persistent Fetal Circulation Syndrome therapy, Prognosis, Pulmonary Artery diagnostic imaging, Pulmonary Artery physiopathology, Ventricular Dysfunction, Right diagnostic imaging, Ventricular Dysfunction, Right etiology, Ventricular Dysfunction, Right therapy, Echocardiography, Hernias, Diaphragmatic, Congenital diagnostic imaging, Persistent Fetal Circulation Syndrome diagnostic imaging, Pulmonary Circulation physiology
- Published
- 2018
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19. Continuous intravenous sildenafil as an early treatment in neonates with congenital diaphragmatic hernia.
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Kipfmueller F, Schroeder L, Berg C, Heindel K, Bartmann P, and Mueller A
- Subjects
- Extracorporeal Membrane Oxygenation, Humans, Infant, Newborn, Infusions, Intravenous, Retrospective Studies, Hernias, Diaphragmatic, Congenital therapy, Hypertension, Pulmonary therapy, Phosphodiesterase 5 Inhibitors administration & dosage, Sildenafil Citrate administration & dosage
- Abstract
Background: Pulmonary hypertension (PH) is an important contributor of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). Treatment options are limited, but sildenafil might improve oxygenation and PH in neonates with CDH., Objective: Aim of this study is to assess effects of intravenous sildenafil on oxygenation and PH in neonates with CDH., Methods: A retrospective chart review was performed in all neonates with CDH born in our institution between September 2012 and December 2014. Indication for sildenafil was an OI > 15, PH > 2/3 systemic pressure, or a difference in pre- and postductal oxygen saturation (≥8%). A sildenafil bolus was administered followed by a maintenance infusion of 1.6 mg/kg/d. Primary outcome was improved oxygenation after starting sildenafil. Patients were compared according to improvement in oxygenation (responder vs non-responder)., Results: A total of 26 of 44 neonates were treated with intravenous sildenafil and in all sildenafil were initiated within the first 24 h of life (median age 3.1 h). Improved oxygenation was observed in 11 infants (42.3%). Among the 15 non-responders (57.6%) ECMO was started in 13 and two infants died without ECMO. Vasopressor support increased significantly during the first hours after commencing sildenafil in responders and non-responders. Echocardiographic indices demonstrated an effect on pulmonary arterial pressure within the first 24 h after starting sildenafil., Conclusions: Treatment of neonates with intravenous sildenafil during the first day of life was associated with acute improvement in oxygenation in more than 40% of patients. However, a significant increase in vasopressor support was observed., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
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