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1. Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE)

Author: Nicola Disma, Katalin Virag, Thomas Riva, Jost Kaufmann, Thomas Engelhardt, Walid Habre, Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, Francis Veyckemans, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Julie Lauweryns, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, René Urbanec, Petra Cajková, Vladimír Mixa, Yvona Sedláčková, Lenka Knoppová, Alena Zlámalová (neé Květoňová), Martin Vavřina, Jiří Žurek, Tom Hansen, Arash Afshari, Anders Bastholm Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Väli, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vähätalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François de la Brière, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Michael Laschat, Frank Wappler, Karin Becke, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Löffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schäfer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Schöler, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yücetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Söhle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Székely, Nandor Kosik, Veronika Maráczi, Janos Schnur, Judit Csillag, János Gál, Gergely Göbl, Balázs Hauser, András Petróczy, Gyula Tövisházi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O’Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria Cristina Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura Brigitta Colantonio, Simona Anna Finamore, Giuliana Anna Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald Rogan Neba, Moreno Favarato, Bruno Guido Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Jurgen de Graaff, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella Mari Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R. Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M. Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B. Boerke, Nil Ekiz, Kristoffer Stensrud, Inger Marie Drage, Erik Ramon Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Marzena Zielinska, Teresa Leal, Maria Soares, Pedro Pina, Sílvia Pinho, Maria Domingas Patuleia, Catarina Cruz Esteves, Helena Salgado, Maria João Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyíri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Dusica Simic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanová, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela Pirtovšek Štupnik, Dolores Méndez, Gema Pino, Paloma Rubio, Alberto Izquierdo, Silvia López, Cristina González Serrano, Jesús Cebrián, Ana Peleteiro, Pilar Del Rey de Diego, Ernesto Martínez García, Carolina Tormo de las Heras, Pablo Troncoso Montero, Celia Arbona, David Artés, Alicia Chamizo, Silvia Serrano, Montserrat Suarez Comas, Francisco Escribá, Cristina Auli, Osvaldo Pérez Pardo, Natalia Sierra Biddle, Ceferina Suárez Castaño, María Isabel Villalobos Rico, Susana Manrique Muñoz, Irene García Martínez, Nuria Montferrer Estruch, Elena Vilardell Ortíz, Rodrigo Poves-Álvarez, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandström, Sporre Bengt, Rainer Dörenberg, Peter Frykholm, Maria Garcia, Ann Kvarnström, Emma Pontén, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Stefan Seiler, Yann Bögli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Laszlo Vutskits, Mattias Casutt, Martin Hölzle, Thomas Hurni, Martin Jöhr, Anna-Ursina Malär, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse Çiğdem Tutuncu, Zehra Hatipoğlu, Dilek Özcengiz, Hale Aksu Erdost, Elvan Öçmen, Çimen Olguner, Hilmi Ayanoglu, Pelin Corman Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbiçer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L. Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet Wolfe Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano Scalia Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, Dowell Julia, Feijten Prisca, Harlet Pierre, Herbineaux Sarah, Leva Brigitte, Plichon Benoît, Virág Katalin, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Anesthesiology, HUS Children and Adolescents, Children's Hospital, Clinicum, Anestesiologian yksikkö, Disma, Nicola, Virag, Katalin, Riva, Thoma, Kaufmann, Jost, Engelhardt, Thoma, Habre, Walid, Breschan, Christian, Likar, Rudolf, Platzer, Manuela, Edelman, Isole, Eger, Johane, Heschl, Stefan, Messerer, Brigitte, Vittinghof, Maria, Kroess, Ruth, Stichlberger, Martina, Kahn, David, Pirotte, Thierry, Pregardien, Caroline, Veyckemans, Franci, Stevens, France, Berghmans, Johan, Bauters, Annemie, De Baerdemaeker, Luc, De Hert, Stefan, Lapage, Koen, Parashchanka, Aliaksandra, Van Limmen, Jurgen, Wyffels, Piet, Lauweryns, Julie, Najafi, Nadia, Vundelinckx, Jori, Butković, Diana, Kerovec Sorić, Ivana, Kralik, Sandra, Markić, Ana, Azman, Josip, Markic, Josko, Pupacic, Daniela, Frelich, Michal, Reimer, Petr, Urbanec, René, Cajková, Petra, Mixa, Vladimír, Sedláčková, Yvona, Knoppová, Lenka, Zlámalová (neé Květoňová), Alena, Vavřina, Martin, Žurek, Jiří, Hansen, Tom, Afshari, Arash, Bille, Anders Bastholm, Ellekvist, Marguerite, Ilmoja, Mari-Lii, Moor, Reet, Kikas, Reet, Väli, Merle, Kallio, Kariantti, Reponen, Elisa, Suominen, Pertti, Suvanto, Sami, Vähätalo, Raisa, Kokki, Hannu, Kokki, Merja, Harju, Jarkko, Kokkonen, Miia, Vieri, Jenni, Manner, Tuula, Amory, Catherine, Ludot, Hugue, Bert, Dina, Godart, Juliette, Laffargue, Anne, Dupont, Hervé, Urbina, Benjamin, Baujard, Catherine, Roulleau, Philippe, Staiti, Giuseppe, Bordes, Maryline, Nouette Gaulain, Karine, Hamonic, Yann, Semjen, Françoi, Jacqmarcq, Olivier, Lejus-Bourdeau, Caroline, Magne, Cécile, Petry, Léa, Ros, Lilica, Zang, Aurélien, Bennis, Mehdi, Coustets, Bernard, Fesseau, Rose, Constant, Isabelle, Khalil, Eliane, Sabourdin, Nada, Audren, Noemie, Descarpentries, Thoma, Fabre, Fanny, Legrand, Aurélien, Druot, Emilie, Orliaguet, Gille, Sabau, Lucie, Uhrig, Lynn, de la Brière, Françoi, Jonckheer, Karin, Mission, Jean-Paul, Scordo, Lucia, Couchepin, Caroline, Dadure, Christophe, De la Arena, Pablo, Hertz, Laurent, Pirat, Philippe, Sola, Chrystelle, Bellon, Myriam, Dahmani, Souhayl, Julien-Marsollier, Florence, Michelet, Daphne, Depret-Donatien, Veronique, Lesage, Anne, Laschat, Michael, Wappler, Frank, Becke, Karin, Brunner, Lena, Oppenrieder, Karin, Badelt, Gregor, Hochmuth, Karin, Koller, Bernhard, Reil, Anita, Richter, Sebastian, Fischer, Thoma, Diers, Anja, Schorer, Clemen, Weyland, Andrea, Cohausz, Ruth, Kretz, Franz-Josef, Löffler, Michaela, Wilbs, Marku, Hoehne, Claudia, Ulrici, Johanna, Goeters, Christiane, Flinspach, Armin, Klages, Matthia, Lindau, Simone, Messroghli, Leila, Zacharowski, Kai, Eisner, Christoph, Mueller, Thoma, Richter, Daniel, Schäfer, Melanie, Weigand, Marku, Weiterer, Sebastian, Ochsenreiter, Miriam, Schöler, Michael, Terboven, Tom, Eggemann, Isabel, Haussmann, Sascha, Leister, Nicola, Menzel, Christoph, Trieschmann, Uwe, Yücetepe, Sirin, Keilig, Susanna, Kranke, Peter, Jelting, Yvonne, Baehner, Torsten, Ellerkmann, Richard, Ghamari, Shahab, Neumann, Claudia, Söhle, Martin, Chloropoulou, Pelagia, Ntritsou, Vagia, Papagiannopoulou, Pinelopi, Garini, Eleana, Karafotia, Afroditi, Mammi, Panagoula, Bali, Evangelia, Iordanidou, Despoina, Malisiova, Anna, Polyzoi, Artemi, Tsiotou, Adelai, Sapi, Erzsebet, Székely, Edgar, Kosik, Nandor, Maráczi, Veronika, Schnur, Jano, Csillag, Judit, Gál, Jáno, Göbl, Gergely, Hauser, Baláz, Petróczy, Andrá, Tövisházi, Gyula, Blain, Stuart, Gallagher, Sarah, Harte, Sinead, Jackson, Mandy, Meehan, Emma, Nawoor, Zeenat, O’Hare, Brendan, Ross, Mark, Lerro, Daniela, Astuto, Marinella, Grasso, Chiara, Scalisi, Rita, Frasacco, Giulia, Lenares, Elena, Leone, Roberto, Grazzini, Maurizia, Minardi, Carmelo, Zadra, Nicola, Cinnella, Gilda, Cotoia, Antonella, Galante, Dario, De Lorenzo, Brita, Kuppers, Beate, Bottazzi, Giulia, Caramelli, Fabio, Mondardini, Maria Cristina, Rossetti, Emanuele, Picardo, Sergio, Vittori, Alessandro, Camporesi, Anna, Wolfler, Andrea, Calderini, Edoardo, Colantonio, Laura Brigitta, Finamore, Simona Anna, Porro, Giuliana Anna, Bonfiglio, Rachele, Kotzeva, Svetlana, Mameli, Leila, Mattioli, Girolamo, Micalizzi, Camilla, Montaguti, Alessia, Pistorio, Angela, Zanaboni, Clelia, Guddo, Anna, Neba, Gerald Rogan, Favarato, Moreno, Locatelli, Bruno Guido, Maffioletti, Micol, Sonzogni, Valter, Garra, Rossella, Sammartino, Maria, Sbaraglia, Fabio, Cortegiani, Andrea, Moscarelli, Alessandra, Attanasi, Elena, Tesoro, Simonetta, Agapiti, Cristina, Pinzoni, Francesca, Vezzoli, Cesare, Bilotta, Federico, Barzdina, Arta, Straume, Zane, Zundane, Anda, Lukosiene, Laura, Maraulaite, Irena, Razlevice, Ilona, Schmitz, Bernd, Mifsud, Stephanie, Aehling, Carolin, Allison, Celia, De Boer, Rient, Emal, Dina, Stevens, Marku, Buitenhuis, Marielle, de Graaff, Jurgen, De Liefde, Inge, Machotta, Andrea, Scoones, Gail, Staals, Lonneke, Tomas, Jeremy, Van der Knijff-van Dortmont, Anouk, Veldhuizen, Marianne, Alders, David, Buhre, Wolfgang, Schafrat, Eva, Schreiber, Jan, Vermeulen, Petronella Mari, Hendriks, Mark, Lako, Sandra, Voet-Lindner, Marieke, Pieters, Barbe, Scheffer, Gert-Jan, Tielens, Luc, Absalom, Anthony R., Bergsma, Margot, De Ruiter, Joke, Meier, Sascha, Volkers, Martin, Zweers, Tjerk, Beukers, Anne M., Boer, Christa, Dertinger, Jurgen, Numan, Sandra, Van Zaane, Ba, Boerke, Wenche B., Ekiz, Nil, Stensrud, Kristoffer, Drage, Inger Marie, Isern, Erik Ramon, Bartkowska-Sniatkowska, Alicja, Grzeskowiak, Malgorzata, Juzwa-Sobieraj, Magdalena, Rosada-Kurasińska, Jowita, Baranowski, Artur, Jakubowska, Karina, Lewandowska, Dorota, Mierzewska-Schmidt, Magdalena, Sawicki, Piotr, Urban-Lechowicz, Magdalena, Przemyslaw, Pomianek, Zielinska, Marzena, Leal, Teresa, Soares, Maria, Pina, Pedro, Pinho, Sílvia, Patuleia, Maria Dominga, Esteves, Catarina Cruz, Salgado, Helena, Santos, Maria João, Badeti, Rodica, Cindea, Iulia, Oana, Loredana, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Tabacaru, Radu, Trante, Irina, Munteanu, Valentin, Morariu, Mihai, Nyíri, Emese, Budic, Ivana, Marjanovic, Vesna, Drašković, Biljana, Pandurov, Marina, Ilic, Jordanka, Mandras, Ana, Rados, Zdenka, Stankovic, Nikola, Suica, Maja, Vasiljevic, Sladjana, Knezevic, Mirjana, Milojevic, Irina, Petrov, Ivana, Puric Racic, Selena, Simic, Dusica, Simic, Irena, Stevic, Marija, Vulicevic, Irena, Cabanová, Barbora, Hanula, Miloslav, Berger, Jelena, Janjatovic, Darja, Pirtovšek Štupnik, Špela, Méndez, Dolore, Pino, Gema, Rubio, Paloma, Izquierdo, Alberto, López, Silvia, González Serrano, Cristina, Cebrián, Jesú, Peleteiro, Ana, Del Rey de Diego, Pilar, Martínez García, Ernesto, Tormo de las Heras, Carolina, Troncoso Montero, Pablo, Arbona, Celia, Artés, David, Chamizo, Alicia, Serrano, Silvia, Suarez Comas, Montserrat, Escribá, Francisco, Auli, Cristina, Pérez Pardo, Osvaldo, Sierra Biddle, Natalia, Suárez Castaño, Ceferina, Villalobos Rico, María Isabel, Manrique Muñoz, Susana, García Martínez, Irene, Montferrer Estruch, Nuria, Vilardell Ortíz, Elena, Poves-Álvarez, Rodrigo, Kohn, Ivan, Lindestam, Ulf, Reinhard, Jarl, Castellheim, Albert, Sandström, Kerstin, Bengt, Sporre, Dörenberg, Rainer, Frykholm, Peter, Garcia, Maria, Kvarnström, Ann, Pontén, Emma, Bruelisauer, Thoma, Erdoes, Gabor, Kaiser, Heiko, Marchon, Mathia, Seiler, Stefan, Bögli, Yann, Dolci, Mirko, Marcucci, Carine, Pichon, Isabelle, Vutskits, Laszlo, Casutt, Mattia, Hölzle, Martin, Hurni, Thoma, Jöhr, Martin, Malär, Anna-Ursina, Mauch, Jacqueline, Erb, Thoma, Oeinck, Karin, Akin, Mine, Keskin, Gulsen, Senayli, Yesim, Kaya, Guner, Kendigelen, Pinar, Tutuncu, Ayse Çiğdem, Hatipoğlu, Zehra, Özcengiz, Dilek, Erdost, Hale Aksu, Öçmen, Elvan, Olguner, Çimen, Ayanoglu, Hilmi, Dincer, Pelin Corman, Umuroglu, Tumay, Azizoglu, Mustafa, Birbiçer, Handan, Doruk, Nurcan, Sagun, Aslı, Baris, Sibel, Dmytriiev, Dmytro, Kuchi, Sridevi, Masip, Nuria, Brooks, Peter, Hare, Alison, Ahmad, Nargi, Casey, Michelle, De Silva, Sam, Dobby, Nadine, Krishnan, Prakash, Sogbodjor, L. Amaki, Walker, Ellie, Walker, Suellen, King, Stephanie, Nicholson, Katy, Quinney, Michelle, Stevens, Paul, Blevin, Andrew, Giombini, Mariangela, Goonasekera, Chulananda, Adil, Sadia, Bew, Stephanie, Bodlani, Carol, Gilpin, Dan, Jinks, Stephanie, Malarkkan, Nalini, Miskovic, Alice, Pad, Rebecca, Wolfe Barry, Juliet, Abbott, Joy, Armstrong, Jame, Cooper, Natalie, Crate, Lindsay, Emery, John, James, Kathryn, King, Hannah, Martin, Paul, Scalia Catenacci, Stefano, Bomont, Rob, Smith, Paul, Mele, Sara, Verzelloni, Alessandra, Dix, Philippa, Bell, Graham, Gordeva, Elena, McKee, Lesley, Ngan, Esther, Scheffczik, Jutta, Tan, Li-En, Worrall, Mark, Cassar, Carmel, Goddard, Kevin, Barlow, Victoria, Oshan, Vimmi, Shah, Khairi, Bell, Sarah, Daniels, Lisa, Gandhi, Monica, Pachter, David, Perry, Chri, Robertson, Andrew, Scott, Carmen, Waring, Lynne, Barnes, David, Childs, Sophie, Norman, Joanne, Sunderland, Robin, Julia, Dowell, Prisca, Feijten, Pierre, Harlet, Sarah, Herbineaux, Brigitte, Leva, Benoît, Plichon, Katalin, Virág, IOO, ACS - Microcirculation, APH - Quality of Care, and ANS - Neuroinfection & -inflammation
Subjects: Male, Time Factors, paediatric, medicine.medical_treatment, morbidity, Severity of Illness Index, 0302 clinical medicine, 030202 anesthesiology, Risk Factors, Clinical endpoint, Anesthesia, Prospective Studies, 610 Medicine & health, Hypoxia, Medical Audit, medicine.diagnostic_test, ddc:617, infants, Incidence (epidemiology), Incidence, Age Factors, anaesthesia, respiratory system, Europe, Treatment Outcome, Cohort, Female, medicine.symptom, Bradycardia, Laryngoscopy, Anesthesia/adverse effects/mortality, Risk Assessment, Europe/epidemiology, 03 medical and health sciences, Laryngoscopy/adverse effects/mortality, Hypoxia/diagnosis/epidemiology/mortality, medicine, Intubation, Intratracheal, Humans, difficult intubation, business.industry, Tracheal intubation, Infant, Newborn, Infant, Perioperative, Newborn, 3126 Surgery, anesthesiology, intensive care, radiology, mortality, neonates, Clinical trial, Intratracheal, Anesthesiology and Pain Medicine, airway, Intubation, Intratracheal/adverse effects/mortality, neonate, Intubation, business, airways
Abstract: Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2
Published: 2021

2. Impact of TP53 Genomic Alterations in Large B-Cell Lymphoma Treated With CD19-Chimeric Antigen Receptor T-Cell Therapy

Author: Michael Scordo, Gal Markel, Gunjan L. Shah, Ruth Scherz-Shouval, Sean M. Devlin, Sergio Giralt, Gilles Salles, Michal J. Besser, Aishat Afuye, Richard J. Lin, Marcel R.M. van den Brink, Anna Alperovich, Jessica Flynn, Parastoo B. Dahi, Joshua A Fein, Maria Lia Palomba, Miguel-Angel Perales, Ettai Markovits, Shimrit Mayer, Roni Shouval, Nishi Shah, Craig S. Sauter, Theodora Anagnostou, Connie L Batlevi, Ana Alarcon Tomas, and Warren Fingrut
Subjects: Oncology, Cancer Research, medicine.medical_specialty, biology, business.industry, medicine.disease, Chimeric antigen receptor, CD19, Lymphoma, Interferon, Internal medicine, biology.protein, Medicine, Biomarker (medicine), Chimeric Antigen Receptor T-Cell Therapy, business, B-cell lymphoma, CD8, medicine.drug
Abstract: PURPOSE Tumor-intrinsic features may render large B-cell lymphoma (LBCL) insensitive to CD19-directed chimeric antigen receptor T cells (CAR-T). We hypothesized that TP53 genomic alterations are detrimental to response outcomes in LBCL treated with CD19-CAR-T. MATERIALS AND METHODS Patients with LBCL treated with CD19-CAR-T were included. Targeted next-generation sequencing was performed on pre–CAR-T tumor samples in a subset of patients. Response and survival rates by histologic, cytogenetic, and molecular features were assessed. Within a cohort of newly diagnosed LBCL with genomic and transcriptomic profiling, we studied interactions between cellular pathways and TP53 status. RESULTS We included 153 adults with relapsed or refractory LBCL treated with CD19-CAR-T (axicabtagene ciloleucel [50%], tisagenlecleucel [32%], and lisocabtagene maraleucel [18%]). Outcomes echoed pivotal trials: complete response (CR) rate 54%, median overall survival (OS) 21.1 months (95% CI, 14.8 to not reached), and progression-free survival 6 months (3.4 to 9.7). Histologic and cytogenetic LBCL features were not predictive of CR. In a subset of 82 patients with next-generation sequencing profiling, CR and OS rates were comparable with the unsequenced cohort. TP53 alterations (mutations and/or copy number alterations) were common (37%) and associated with inferior CR and OS rates in univariable and multivariable regression models; the 1-year OS in TP53-altered LBCL was 44% (95% CI, 29 to 67) versus 76% (65 to 89) in wild-type ( P = .012). Transcriptomic profiling from a separate cohort of patients with newly diagnosed lymphoma (n = 562) demonstrated that TP53 alterations are associated with dysregulation of pathways related to CAR-T-cell cytotoxicity, including interferon and death receptor signaling pathway and reduced CD8 T-cell tumor infiltration. CONCLUSION TP53 is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with LBCL treated with CD19-CAR-T. The role of TP53 should be further validated in independent cohorts.
Published: 2022

3. Population Pharmacokinetics of Melphalan in a Large Cohort of Autologous and Allogeneic Hematopoietic Cell Transplantation Recipients: Towards Individualized Dosing Regimens

Author: Gunjan L. Shah, Jaap Jan Boelens, Rick Admiraal, Michael Scordo, Ryan Schofield, Andrew Lin, Roni Tamari, Anthony J. Proli, Sergio Giralt, Nancy Cruz Sitner, Anna Alperovich, Josel D. Ruiz, Dean Carlow, and Parastoo B. Dahi
Subjects: Adult, Oncology, Melphalan, medicine.medical_specialty, medicine.medical_treatment, Article, Cohort Studies, Internal medicine, medicine, Mucositis, Humans, Pharmacology (medical), Obesity, Dosing, Pharmacology, Chemotherapy, Cumulative dose, business.industry, Hematopoietic Stem Cell Transplantation, medicine.disease, Transplant Recipients, NONMEM, Transplantation, Bone marrow suppression, business, medicine.drug
Abstract: BACKGROUND AND OBJECTIVES High-dose melphalan is an integral part of conditioning chemotherapy prior to both autologous and allogeneic hematopoietic cell transplantation. While underexposure may lead to relapse, overexposure may lead to toxicities include mucositis, diarrhea, bone marrow suppression, and rarely sinusoidal obstruction syndrome. In this study, we describe the population pharmacokinetics of high-dose melphalan as a first step towards individualized dosing. METHODS Melphalan samples were collected in patients receiving an allogeneic or autologous hematopoietic cell transplantation between August 2016 and August 2020 at the Memorial Sloan Kettering Cancer Center. A population-pharmacokinetic model was developed using NONMEM. RESULTS Based on a total of 3418 samples from 452 patients receiving a median cumulative dose of 140 mg/m2, a two-compartment population-pharmacokinetic model was developed. Fat-free mass was a covariate for clearance, central volume of distribution, and inter-compartmental clearance, while glomerular filtration rate predicted clearance. Simulation studies showed that based on fixed body surface area-based dosing, renal impairment has a higher impact in increasing melphalan exposure compared with obesity. CONCLUSIONS The proposed model adequately describes the population pharmacokinetics of melphalan in adult patients receiving a hematopoietic cell transplantation. This model can be used to define the therapeutic window of melphalan, and subsequently to develop individualized dosing regimens aiming for that therapeutic window in all patients.
Published: 2021

4. Acute Kidney Injury in the Modern Era of Allogeneic Hematopoietic Stem Cell Transplantation

Author: Michael Scordo, Edgar A. Jaimes, Matthew Abramson, Insara Jaffer Sathick, Junting Zheng, Molly Maloy, Josel D. Ruiz, and Victoria Gutgarts
Subjects: Adult, Male, medicine.medical_specialty, Epidemiology, medicine.medical_treatment, Renal function, Hematopoietic stem cell transplantation, urologic and male genital diseases, Critical Care and Intensive Care Medicine, Lower risk, Young Adult, Postoperative Complications, Risk Factors, Internal medicine, Humans, Medicine, Acute tubular necrosis, Aged, Retrospective Studies, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Acute kidney injury, Original Articles, Acute Kidney Injury, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Tacrolimus, Calcineurin, Nephrology, Female, business, Kidney disease
Abstract: Background and objectives AKI is a major complication of allogeneic hematopoietic stem cell transplantation, increasing risk of nonrelapse mortality. AKI etiology is often ambiguous due to heterogeneity of conditioning/graft versus host disease regimens. To date, graft versus host disease and calcineurin inhibitor effects on AKI are not well defined. We aimed to describe AKI and assess pre–/post–hematopoietic transplant risk factors in a large recent cohort. Design, setting, participants, & measurements We performed a single-center, retrospective study of 616 allogeneic hematopoietic cell transplant recipients from 2014 to 2017. We defined AKI and CKD based on Kidney Disease Improving Global Outcomes (KDIGO) criteria and estimated GFR using the Chronic Kidney Disease Epidemiology Collaboration equation. We assessed AKI pre–/post–hematopoietic transplant risk factors using cause-specific Cox regression and association of AKI with CKD outcomes using chi-squared test. AKI was treated as a time-dependent variable in relation to nonrelapse mortality. Results Incidence of AKI by day 100 was 64%. Exposure to tacrolimus and other nephrotoxins conferred a higher risk of AKI, but tacrolimus levels were not associated with severity. Reduced-intensity conditioning carried higher AKI risk compared with myeloablative conditioning. Most stage 3 AKIs were due to ischemic acute tubular necrosis and calcineurin inhibitor nephrotoxicity. KRT was initiated in 21 out of 616 patients (3%); of these 21 patients, nine (43%) recovered and five (24%) survived to hospital discharge. T cell–depleted transplants, higher baseline serum albumin, and non-Hispanic ethnicity were associated with lower risk of AKI. CKD developed in 21% (73 of 345) of patients after 12 months. Nonrelapse mortality was higher in those with AKI (hazard ratio, 2.77; 95% confidence interval, 1.8 to 4.27). Conclusions AKI post–hematopoietic cell transplant remains a major concern. Risk of AKI was higher with exposure to calcineurin inhibitors. T cell–depleted hematopoietic cell transplants and higher serum albumin had lower risk of AKI. Of the patients requiring KRT, 43% recovered kidney function. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_09_07_CJN19801220.mp3
Published: 2021

5. Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma

Author: Miguel-Angel Perales, Molly Maloy, Sean M. Devlin, Erica Petrlik, Matthew J. Matasar, Craig H. Moskowitz, Esperanza B. Papadopoulos, Gunjan L. Shah, Josel D. Ruiz, Michael Scordo, Parastoo B. Dahi, Craig S. Sauter, Carlos Rondon-Clavo, Jasme Lee, Roni Tamari, Ann A. Jakubowski, Paul A. Hamlin, and Sergio Giralt
Subjects: Melphalan, Transplantation, medicine.medical_specialty, Chemotherapy, Carmustine, business.industry, medicine.medical_treatment, Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Transplantation, Autologous, Chemotherapy regimen, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, business, Febrile neutropenia, Aged, medicine.drug
Abstract: High-dose chemotherapy and autologous hematopoietic cell transplantation is an effective consolidation therapy in lymphoma; however, its use in elderly patients has been limited because of concerns for greater toxicity in this group. We investigated the toxicities of carmustine, etoposide, cytarabine, and melphalan (BEAM) and autologous hematopoietic cell transplantation (AHCT) in 346 patients in 2 age groups: 279 patients aged 60 to 69 years and 67 patients aged ≥70 years. The majority developed severe toxicities; the most common were febrile neutropenia, gastrointestinal, infections, and cardiovascular. Older patients were at higher risk for grade ≥3 cardiovascular toxicities (hazard ratio [HR], 3.36; 95% confidence interval [CI], 2.25-5.00; P < .001) and skin toxicities (HR, 2.45; 95% CI, 1.08-5.54, P = .032). In the older group, nonrelapse mortality at 100 days and at 2 years was 2.99% (95% CI, 0.55-9.32) and 6.2% (95% CI, 1.97-13.95), respectively, vs 1.79% (95% CI, 0.68-3.92) and 2.91% (95% CI, 1.37-5.42), respectively, in the younger group. When adjusting for the number of grade ≥3 toxicities within the first 100 days, older patients had a 1.71-fold (95% CI, 1.08-2.71) increased risk for progression or death relative to younger patients. Although BEAM followed by AHCT is effective, it is associated with significant organ toxicities, especially in patients aged ≥70 years. Interventions to mitigate toxicities while maintaining efficacy are much needed.
Published: 2021

6. Post–COVID-19 Syndrome: Theoretical Basis, Identification, and Management

Author: Kristine Anne Scordo, Misty M Richmond, and Nancy Munro
Subjects: Adult, Male, medicine.medical_specialty, Critical Care Nursing, 03 medical and health sciences, 0302 clinical medicine, Pulmonary fibrosis, Health care, Pandemic, medicine, Humans, Survivors, 030212 general & internal medicine, Social isolation, Intensive care medicine, Pandemics, Wasting, Aged, Aged, 80 and over, Fatigue Syndrome, Chronic, SARS-CoV-2, business.industry, COVID-19, General Medicine, Middle Aged, medicine.disease, United States, Malnutrition, Practice Guidelines as Topic, Emergency Medicine, Etiology, Education, Medical, Continuing, Female, Curriculum, medicine.symptom, business, Subacute Care, 030217 neurology & neurosurgery, Kidney disease
Abstract: As COVID-19 continues to spread, with the United States surpassing 29 million cases, health care workers are beginning to see patients who have been infected with SARS-CoV-2 return seeking treatment for its longer-term physical and mental effects. The term long-haulers is used to identify patients who have not fully recovered from the illness after weeks or months. Although the acute symptoms of COVID-19 have been widely described, the longer-term effects are less well known because of the relatively short history of the pandemic. Symptoms may be due to persistent chronic inflammation (eg, fatigue), sequelae of organ damage (eg, pulmonary fibrosis, chronic kidney disease), and hospitalization and social isolation (eg, muscle wasting, malnutrition). Health care providers are instrumental in developing a comprehensive plan for identifying and managing post–COVID-19 complications. This article addresses the possible etiology of postviral syndromes and describes reported symptoms and suggested management of post-COVID syndrome.
Published: 2021

7. Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

Author: Fuchs A., Disma N., Virag K., Ulmer F., Habre W., de Graaff J. C., Riva T., NECTARINE Group of the European Society of Anaesthesiology and Intensive Care Clinical Trial Network: Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, Francis Veyckemans, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, René Urbanec, Petra Cajková, Vladimír Mixa, Yvona Sedláčková, Lenka Knoppová, Alena Zlámalová, Martin Vavřina, Jiří Žurek, Tom Hansen, Arash Afshari, Anders Bastholm Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Väli, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vähätalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François de la Brière, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Jost Kaufmann, Michael Laschat, Frank Wappler, Karin Becke, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Löffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schäfer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Schöler, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yücetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Söhle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Székely, Nandor Kosik, Veronika Maráczi, Janos Schnur, Judit Csillag, János Gál, Gergely Göbl, Balázs Hauser, András Petróczy, Gyula Tövisházi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O'Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria Cristina Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura Brigitta Colantonio, Simona Anna Finamore, Giuliana Anna Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald Rogan Neba, Moreno Favarato, Bruno Guido Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella Mari Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B Boerk, Nil Ekiz, Kristoffer Stensrud, Inger Marie Drage, Erik Ramon Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Marzena Zielinska, Teresa Leal, Maria Soares, Pedro Pina, Sílvia Pinho, Maria Domingas Patuleia, Catarina Cruz Esteves, Helena Salgado, Maria João Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyíri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Dusica Simic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanová, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela Pirtovšek Štupnik, Dolores Méndez, Gema Pino, Paloma Rubio, Alberto Izquierdo, Silvia López, Cristina González Serrano, Jesús Cebrián, Ana Peleteiro, Pilar Del Rey de Diego, Ernesto Martínez García, Carolina Tormo de Las Heras, Pablo Troncoso Montero, Celia Arbona, David Artés, Alicia Chamizo, Silvia Serrano, Montserrat Suarez Comas, Francisco Escribá, Cristina Auli, Osvaldo Pérez Pardo, Natalia Sierra Biddle, Ceferina Suárez Castaño, María Isabel Villalobos Rico, Susana Manrique Muñoz, Irene García Martínez, Nuria Montferrer Estruch, Elena Vilardell Ortíz, Rodrigo Poves-Álvarez, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandström, Sporre Bengt, Rainer Dörenberg, Peter Frykholm, Maria Garcia, Ann Kvarnström, Emma Pontén, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Stefan Seiler, Yann Bögli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Laszlo Vutskits, Mattias Casutt, Martin Hölzle, Thomas Hurni, Martin Jöhr, Anna-Ursina Malär, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse Çiğdem Tutuncu, Zehra Hatipoğlu, Dilek Özcengiz, Hale Aksu Erdost, Elvan Öçmen, Çimen Olguner, Hilmi Ayanoglu, Pelin Corman Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbiçer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet Wolfe Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano Scalia Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, Fuchs A., Disma N., Virag K., Ulmer F., Habre W., de Graaff J.C., Riva T., NECTARINE Group of the European Society of Anaesthesiology and Intensive Care Clinical Trial Network: Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, Francis Veyckemans, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, René Urbanec, Petra Cajková, Vladimír Mixa, Yvona Sedláčková, Lenka Knoppová, Alena Zlámalová, Martin Vavřina, Jiří Žurek, Tom Hansen, Arash Afshari, Anders Bastholm Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Väli, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vähätalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François de la Brière, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Jost Kaufmann, Michael Laschat, Frank Wappler, Karin Becke, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Löffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schäfer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Schöler, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yücetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Söhle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Székely, Nandor Kosik, Veronika Maráczi, Janos Schnur, Judit Csillag, János Gál, Gergely Göbl, Balázs Hauser, András Petróczy, Gyula Tövisházi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O'Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria Cristina Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura Brigitta Colantonio, Simona Anna Finamore, Giuliana Anna Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald Rogan Neba, Moreno Favarato, Bruno Guido Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella Mari Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B Boerk, Nil Ekiz, Kristoffer Stensrud, Inger Marie Drage, Erik Ramon Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Marzena Zielinska, Teresa Leal, Maria Soares, Pedro Pina, Sílvia Pinho, Maria Domingas Patuleia, Catarina Cruz Esteves, Helena Salgado, Maria João Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyíri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Dusica Simic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanová, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela Pirtovšek Štupnik, Dolores Méndez, Gema Pino, Paloma Rubio, Alberto Izquierdo, Silvia López, Cristina González Serrano, Jesús Cebrián, Ana Peleteiro, Pilar Del Rey de Diego, Ernesto Martínez García, Carolina Tormo de Las Heras, Pablo Troncoso Montero, Celia Arbona, David Artés, Alicia Chamizo, Silvia Serrano, Montserrat Suarez Comas, Francisco Escribá, Cristina Auli, Osvaldo Pérez Pardo, Natalia Sierra Biddle, Ceferina Suárez Castaño, María Isabel Villalobos Rico, Susana Manrique Muñoz, Irene García Martínez, Nuria Montferrer Estruch, Elena Vilardell Ortíz, Rodrigo Poves-Álvarez, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandström, Sporre Bengt, Rainer Dörenberg, Peter Frykholm, Maria Garcia, Ann Kvarnström, Emma Pontén, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Stefan Seiler, Yann Bögli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Laszlo Vutskits, Mattias Casutt, Martin Hölzle, Thomas Hurni, Martin Jöhr, Anna-Ursina Malär, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse Çiğdem Tutuncu, Zehra Hatipoğlu, Dilek Özcengiz, Hale Aksu Erdost, Elvan Öçmen, Çimen Olguner, Hilmi Ayanoglu, Pelin Corman Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbiçer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet Wolfe Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano Scalia Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, and Anesthesiology
Subjects: Red Blood Cell Transfusion, NEONATE, Haemoglobin levels, 610 Medicine & health, Peri-operative, red blood cell transfusion, neonates, infants, High morbidity, Hemoglobins, TRANSFUSION, medicine, Clinical endpoint, Humans, Anesthesia, Prospective Studies, business.industry, Postmenstrual Age, Infant, Newborn, Perioperative, Europe, Red blood cell, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Observational study, business, 610 Medizin und Gesundheit, Erythrocyte Transfusion
Abstract: BACKGROUND Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12��g��dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (��week 3) onwards. OBJECTIVE To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN A multicentre observational study. SETTING The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g��dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g��dl-1 in week 2 and 8.0 [7.3 to 9.0] g��dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml��kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g��dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION ClinicalTrials.gov, identifier: NCT02350348.
Published: 2021

8. Tailored treatment to MRD response: A phase I/II study for newly diagnosed multiple myeloma patients using high dose twice‐weekly carfilzomib (45 and 56 mg/m2) in combination with lenalidomide and dexamethasone

Author: Malin Hultcrantz, Heather Landau, Sydney Lu, Sean M. Devlin, Ahmet Dogan, Sham Mailankody, Carlyn Tan, Michael Scordo, Oscar B Lahoud, Ola Landgren, Eric L. Smith, Meghan Salcedo, Caleb Ho, Urvi A Shah, Hani Hassoun, Neha Korde, Benjamin Diamond, Gunjan L. Shah, Donna Mastey, Maria E. Arcila, David J. Chung, Kelly Werner, Mikhail Roshal, Alexander M. Lesokhin, Andriy Derkach, Elizabet Tavitian, Sergio Giralt, and Nikoletta Lendvai
Subjects: Oncology, medicine.medical_specialty, MRD Response, M.2, business.industry, Hematology, Tailored treatment, medicine.disease, Correspondences, Carfilzomib, chemistry.chemical_compound, chemistry, Internal medicine, Correspondence, medicine, Progression-free survival, business, Multiple myeloma, Dexamethasone, Lenalidomide, medicine.drug
Published: 2021

9. Efficiency measurements and simulations of a HAPG based Von Hamos spectrometer for large sources

Author: Alessandro Scordo, Marco Miliucci, Florin Sirghi, Catalina Curceanu, and V. De Leo
Subjects: Physics, Spectrometer, Field (physics), business.industry, 010401 analytical chemistry, Resolution (electron density), Ranging, 01 natural sciences, 0104 chemical sciences, Analytical Chemistry, Bragg plane, Optics, 0103 physical sciences, Atom, Reflection (physics), Ray tracing (graphics), 010306 general physics, business, Spectroscopy
Abstract: In this paper we report the reflection efficiency measurements of the VOXES Von Hamos (VH) spectrometer, based on HAPG mosaic crystals, together with ray tracing simulation results. Von Hamos spectrometers are widely used in several fields, ranging from fundamental physics to various practical applications. These types of Bragg spectrometers are usually used in high rate–high resolution experiments, where the typical source size can be as low as a few tens of microns. The VOXES collaboration at the INFN Laboratories of Frascati recently developed a VH spectrometer, making use of HAPG mosaic crystals and optimized X-ray beam optics, which could be used for source sizes up to a few mm in the Bragg plane and some tens of mm in the sagittal plane. Such a spectrometer may open a new era in the field of exotic (kaonic) atom precision measurements, delivering data with unprecedented precision to the nuclear physics community. In order to plan the use of this spectrometer the capabilities in terms of signal collection efficiency need to be checked, reliable ray tracing simulations have to be developed and consistency between data and simulations has to be verified. In this paper, we present this crosscheck for a ρ = 206.7 mm cylindrically bent HAPG crystal using CuKα1,2 and FeKα1,2 XRF lines. For both of them, the experimental results and the simulations are found to be in good agreement within the errors.
Published: 2021

10. How we treat mature B-cell neoplasms (indolent B-cell lymphomas)

Author: Michael Scordo, Lorenzo Falchi, Erel Joffe, Melissa Lumish, Brandon S. Imber, and Gottfried von Keudell
Subjects: Cancer Research, medicine.medical_specialty, Lymphoma, B-Cell, Indolent lymphoma, T cell, Mature B cell neoplasm, Follicular lymphoma, Antineoplastic Agents, Review, Active surveillance, lcsh:RC254-282, Marginal zone lymphoma, Internal medicine, hemic and lymphatic diseases, medicine, Animals, Humans, Hairy cell leukemia, Molecular Targeted Therapy, Molecular Biology, B cell, Hematology, business.industry, lcsh:RC633-647.5, Mature B-Cell Neoplasm, Disease Management, lcsh:Diseases of the blood and blood-forming organs, medicine.disease, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.anatomical_structure, Oncology, Cancer research, Disease Progression, Chimeric Antigen Receptor T-Cell Therapy, Neoplasm Recurrence, Local, Splenic Lymphoma, business
Abstract: Mature B cell neoplasms, previously indolent non-Hodgkin lymphomas (iNHLs), are a heterogeneous group of malignancies sharing similar disease courses and treatment paradigms. Most patients with iNHL have an excellent prognosis, and in many, treatment can be deferred for years. However, some patients will have an accelerated course and may experience transformation into aggressive lymphomas. In this review, we focus on management concepts shared across iNHLs, as well as histology-specific strategies. We address open questions in the field, including the influence of genomics and molecular pathway alterations on treatment decisions. In addition, we review the management of uncommon clinical entities including nodular lymphocyte-predominant Hodgkin lymphoma, hairy cell leukemia, splenic lymphoma and primary lymphoma of extranodal sites. Finally, we include a perspective on novel targeted therapies, antibodies, antibody–drug conjugates, bispecific T cell engagers and chimeric antigen receptor T cell therapy.
Published: 2021

11. Corrigendum to ‘Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE):a prospective European multicentre observational study’ (Br J Anaesth 2021; 126: 1173–81) (British Journal of Anaesthesia (2021) 126(6) (1173–1181), (S0007091221001161), (10.1016/j.bja.2021.02.021))

Author: Nicola Disma, Katalin Virag, Thomas Riva, Jost Kaufmann, Thomas Engelhardt, Walid Habre, Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, Francis Veyckemans, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Julie Lauweryns, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, René Urbanec, Petra Cajková, Vladimír Mixa, Yvona Sedláčková, Lenka Knoppová, Alena Zlámalová (neé Květoňová), Martin Vavřina, Jiří Žurek, Tom Hansen, Arash Afshari, Anders Bastholm Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Väli, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vähätalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François de la Brière, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Michael Laschat, Frank Wappler, Karin Becke, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Löffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schäfer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Schöler, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yücetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Söhle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Székely, Nandor Kosik, Veronika Maráczi, Janos Schnur, Judit Csillag, János Gál, Gergely Göbl, Balázs Hauser, András Petróczy, Gyula Tövisházi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O’Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria Cristina Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura Brigitta Colantonio, Simona Anna Finamore, Giuliana Anna Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald Rogan Neba, Moreno Favarato, Bruno Guido Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Jurgen de Graaff, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella Mari Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R. Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M. Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B. Boerke, Nil Ekiz, Kristoffer Stensrud, Inger Marie Drage, Erik Ramon Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Marzena Zielinska, Teresa Leal, Maria Soares, Pedro Pina, Sílvia Pinho, Maria Domingas Patuleia, Catarina Cruz Esteves, Helena Salgado, Maria João Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyíri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Dusica Simic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanová, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela Pirtovšek Štupnik, Dolores Méndez, Gema Pino, Paloma Rubio, Alberto Izquierdo, Silvia López, Cristina González Serrano, Jesús Cebrián, Ana Peleteiro, Pilar Del Rey de Diego, Ernesto Martínez García, Carolina Tormo de las Heras, Pablo Troncoso Montero, Celia Arbona, David Artés, Alicia Chamizo, Silvia Serrano, Montserrat Suarez Comas, Francisco Escribá, Cristina Auli, Osvaldo Pérez Pardo, Natalia Sierra Biddle, Ceferina Suárez Castaño, María Isabel Villalobos Rico, Susana Manrique Muñoz, Irene García Martínez, Nuria Montferrer Estruch, Elena Vilardell Ortíz, Rodrigo Poves-Álvarez, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandström, Sporre Bengt, Rainer Dörenberg, Peter Frykholm, Maria Garcia, Ann Kvarnström, Emma Pontén, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Stefan Seiler, Yann Bögli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Laszlo Vutskits, Mattias Casutt, Martin Hölzle, Thomas Hurni, Martin Jöhr, Anna-Ursina Malär, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse Çiğdem Tutuncu, Zehra Hatipoğlu, Dilek Özcengiz, Hale Aksu Erdost, Elvan Öçmen, Çimen Olguner, Hilmi Ayanoglu, Pelin Corman Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbiçer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L. Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet Wolfe Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano Scalia Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, Dowell Julia, Feijten Prisca, Harlet Pierre, Herbineaux Sarah, Leva Brigitte, Plichon Benoît, Virág Katalin, Disma N., Virag K., Riva T., Kaufmann J., Engelhardt T., Habre W., Breschan C., Likar R., Platzer M., Edelman I., Eger J., Heschl S., Messerer B., Vittinghof M., Kroess R., Stichlberger M., Kahn D., Pirotte T., Pregardien C., Veyckemans F., Stevens F., Berghmans J., Bauters A., De Baerdemaeker L., De Hert S., Lapage K., Parashchanka A., Van Limmen J., Wyffels P., Lauweryns J., Najafi N., Vundelinckx J., Butkovic D., Kerovec Soric I., Kralik S., Markic A., Azman J., Markic J., Pupacic D., Frelich M., Reimer P., Urbanec R., Cajkova P., Mixa V., Sedlackova Y., Knoppova L., Zlamalova (nee Kvetonova) A., Vavrina M., Zurek J., Hansen T., Afshari A., Bille A.B., Ellekvist M., Ilmoja M.-L., Moor R., Kikas R., Vali M., Kallio K., Reponen E., Suominen P., Suvanto S., Vahatalo R., Kokki H., Kokki M., Harju J., Kokkonen M., Vieri J., Manner T., Amory C., Ludot H., Bert D., Godart J., Laffargue A., Dupont H., Urbina B., Baujard C., Roulleau P., Staiti G., Bordes M., Nouette Gaulain K., Hamonic Y., Semjen F., Jacqmarcq O., Lejus-Bourdeau C., Magne C., Petry L., Ros L., Zang A., Bennis M., Coustets B., Fesseau R., Constant I., Khalil E., Sabourdin N., Audren N., Descarpentries T., Fabre F., Legrand A., Druot E., Orliaguet G., Sabau L., Uhrig L., de la Briere F., Jonckheer K., Mission J.-P., Scordo L., Couchepin C., Dadure C., De la Arena P., Hertz L., Pirat P., Sola C., Bellon M., Dahmani S., Julien-Marsollier F., Michelet D., Depret-Donatien V., Lesage A., Laschat M., Wappler F., Becke K., Brunner L., Oppenrieder K., Badelt G., Hochmuth K., Koller B., Reil A., Richter S., Fischer T., Diers A., Schorer C., Weyland A., Cohausz R., Kretz F.-J., Loffler M., Wilbs M., Hoehne C., Ulrici J., Goeters C., Flinspach A., Klages M., Lindau S., Messroghli L., Zacharowski K., Eisner C., Mueller T., Richter D., Schafer M., Weigand M., Weiterer S., Ochsenreiter M., Scholer M., Terboven T., Eggemann I., Haussmann S., Leister N., Menzel C., Trieschmann U., Yucetepe S., Keilig S., Kranke P., Jelting Y., Baehner T., Ellerkmann R., Ghamari S., Neumann C., Sohle M., Chloropoulou P., Ntritsou V., Papagiannopoulou P., Garini E., Karafotia A., Mammi P., Bali E., Iordanidou D., Malisiova A., Polyzoi A., Tsiotou A., Sapi E., Szekely E., Kosik N., Maraczi V., Schnur J., Csillag J., Gal J., Gobl G., Hauser B., Petroczy A., Tovishazi G., Blain S., Gallagher S., Harte S., Jackson M., Meehan E., Nawoor Z., O'Hare B., Ross M., Lerro D., Astuto M., Grasso C., Scalisi R., Frasacco G., Lenares E., Leone R., Grazzini M., Minardi C., Zadra N., Cinnella G., Cotoia A., Galante D., De Lorenzo B., Kuppers B., Bottazzi G., Caramelli F., Mondardini M.C., Rossetti E., Picardo S., Vittori A., Camporesi A., Wolfler A., Calderini E., Colantonio L.B., Finamore S.A., Porro G.A., Bonfiglio R., Kotzeva S., Mameli L., Mattioli G., Micalizzi C., Montaguti A., Pistorio A., Zanaboni C., Guddo A., Neba G.R., Favarato M., Locatelli B.G., Maffioletti M., Sonzogni V., Garra R., Sammartino M., Sbaraglia F., Cortegiani A., Moscarelli A., Attanasi E., Tesoro S., Agapiti C., Pinzoni F., Vezzoli C., Bilotta F., Barzdina A., Straume Z., Zundane A., Lukosiene L., Maraulaite I., Razlevice I., Schmitz B., Mifsud S., Aehling C., Allison C., De Boer R., Emal D., Stevens M., Buitenhuis M., de Graaff J., De Liefde I., Machotta A., Scoones G., Staals L., Tomas J., Van der Knijff-van Dortmont A., Veldhuizen M., Alders D., Buhre W., Schafrat E., Schreiber J., Vermeulen P.M., Hendriks M., Lako S., Voet-Lindner M., Pieters B., Scheffer G.-J., Tielens L., Absalom A.R., Bergsma M., De Ruiter J., Meier S., Volkers M., Zweers T., Beukers A.M., Boer C., Dertinger J., Numan S., Van Zaane B., Boerke W.B., Ekiz N., Stensrud K., Drage I.M., Isern E.R., Bartkowska-Sniatkowska A., Grzeskowiak M., Juzwa-Sobieraj M., Rosada-Kurasinska J., Baranowski A., Jakubowska K., Lewandowska D., Mierzewska-Schmidt M., Sawicki P., Urban-Lechowicz M., Przemyslaw P., Zielinska M., Leal T., Soares M., Pina P., Pinho S., Patuleia M.D., Esteves C.C., Salgado H., Santos M.J., Badeti R., Cindea I., Oana L., Gurita A., Ilie L., Mocioiu G., Tabacaru R., Trante I., Munteanu V., Morariu M., Nyiri E., Budic I., Marjanovic V., Draskovic B., Pandurov M., Ilic J., Mandras A., Rados Z., Stankovic N., Suica M., Vasiljevic S., Knezevic M., Milojevic I., Petrov I., Puric Racic S., Simic D., Simic I., Stevic M., Vulicevic I., Cabanova B., Hanula M., Berger J., Janjatovic D., Pirtovsek Stupnik S., Mendez D., Pino G., Rubio P., Izquierdo A., Lopez S., Gonzalez Serrano C., Cebrian J., Peleteiro A., Del Rey de Diego P., Martinez Garcia E., Tormo de las Heras C., Troncoso Montero P., Arbona C., Artes D., Chamizo A., Serrano S., Suarez Comas M., Escriba F., Auli C., Perez Pardo O., Sierra Biddle N., Suarez Castano C., Villalobos Rico M.I., Manrique Munoz S., Garcia Martinez I., Montferrer Estruch N., Vilardell Ortiz E., Poves-Alvarez R., Kohn I., Lindestam U., Reinhard J., Castellheim A., Sandstrom K., Bengt S., Dorenberg R., Frykholm P., Garcia M., Kvarnstrom A., Ponten E., Bruelisauer T., Erdoes G., Kaiser H., Marchon M., Seiler S., Bogli Y., Dolci M., Marcucci C., Pichon I., Vutskits L., Casutt M., Holzle M., Hurni T., Johr M., Malar A.-U., Mauch J., Erb T., Oeinck K., Akin M., Keskin G., Senayli Y., Kaya G., Kendigelen P., Tutuncu A.C., Hatipoglu Z., Ozcengiz D., Erdost H.A., Ocmen E., Olguner C., Ayanoglu H., Dincer P.C., Umuroglu T., Azizoglu M., Birbicer H., Doruk N., Sagun A., Baris S., Dmytriiev D., Kuchi S., Masip N., Brooks P., Hare A., Ahmad N., Casey M., De Silva S., Dobby N., Krishnan P., Sogbodjor L.A., Walker E., Walker S., King S., Nicholson K., Quinney M., Stevens P., Blevin A., Giombini M., Goonasekera C., Adil S., Bew S., Bodlani C., Gilpin D., Jinks S., Malarkkan N., Miskovic A., Pad R., Wolfe Barry J., Abbott J., Armstrong J., Cooper N., Crate L., Emery J., James K., King H., Martin P., Scalia Catenacci S., Bomont R., Smith P., Mele S., Verzelloni A., Dix P., Bell G., Gordeva E., McKee L., Ngan E., Scheffczik J., Tan L.-E., Worrall M., Cassar C., Goddard K., Barlow V., Oshan V., Shah K., Bell S., Daniels L., Gandhi M., Pachter D., Perry C., Robertson A., Scott C., Waring L., Barnes D., Childs S., Norman J., Sunderland R., Julia D., Prisca F., Pierre H., Sarah H., Brigitte L., Benoit P., Katalin V., Anesthesiology, APH - Quality of Care, and Amsterdam Neuroscience - Neuroinfection & -inflammation
Subjects: Anesthesiology and Pain Medicine, business.industry, medicine.medical_treatment, Anesthesia, Tracheal intubation, Neonates, anaesthesia, medicine, MEDLINE, Observational study, Audit, business
Abstract: The authors regret that errors were present in the above article. On page 1174, in the second paragraph of the Statistical methods section, the second sentence should read as follows: The incidence of difficult intubation was determined including those whose tracheas were already intubated and is reported as a percentage with a 95% exact binomial CI. On page 1175, in the third paragraph of the Statistical methods section ‘mean standardised difference (MSD)’ should read ‘standardised mean difference (SMD)’ The authors would like to apologise for any inconvenience caused.
Published: 2021

12. Morbidity and mortality after anaesthesia in early life:results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

Author: Nicola Disma, Francis Veyckemans, Katalin Virag, Tom G. Hansen, Karin Becke, Pierre Harlet, Laszlo Vutskits, Suellen M. Walker, Jurgen C. de Graaff, Marzena Zielinska, Dusica Simic, Thomas Engelhardt, Walid Habre, Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Julie Lauweryns, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, Rene Urbanec, Petra Cajkova, Vladimir Mixa, Yvona Sedlačkova, Lenka Knoppova, Alena Zlamalova (nee Květoňova), Martin Vavřina, Jiři Žurek, Tom Hansen, Arash Afshari, Anders B. Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Vali, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vahatalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Herve Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, Francois Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cecile Magne, Lea Petry, Lilica Ros, Aurelien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurelien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, Francois de la Briere, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Jost Kaufmann, Michael Laschat, Frank Wappler, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Loffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schafer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Scholer, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yucetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Sohle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Szekely, Nandor Kosik, Veronika Maraczi, Janos Schnur, Judit Csillag, Janos Gal, Gergely Gobl, Balazs Hauser, Andras Petroczy, Gyula Tovishazi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O’Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria C. Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura B. Colantonio, Simona A. Finamore, Giuliana A. Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald R. Neba, Moreno Favarato, Bruno G. Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Jurgen de Graaff, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der, Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella M. Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R. Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M. Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B. Boerke, Nil Ekiz, Kristoffer Stensrud, Inger M. Drage, Erik R. Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Teresa Leal, Maria Soares, Pedro Pina, Silvia Pinho, Maria Domingas Patuleia, Catarina C. Esteves, Helena Salgado, Maria J. Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyiri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanova, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela P. Štupnik, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandstrom, Sporre Bengt, Rainer Dorenberg, Peter Frykholm, Maria Garcia, Ann Kvarnstrom, Emma Ponten, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Thomas Riva, Stefan Seiler, Yann Bogli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Mattias Casutt, Martin Holzle, Thomas Hurni, Martin Johr, null Anna-Ursina, null Malar, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse C. Tutuncu, Zehra Hatipoğlu, Dilek Ozcengiz, Hale Aksu Erdost, Elvan Ocmen, Cimen Olguner, Hilmi Ayanoglu, Pelin C. Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbicer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L. Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet W. Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano S. Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anesthésiologie, Tampere University, Department of Prehospital Emergency Care, Pain Management and Anaesthesiology, Anesthesiology, APH - Quality of Care, ANS - Neuroinfection & -inflammation, Disma, Nicola, Veyckemans, Franci, Virag, Katalin, Hansen, Tom G., Becke, Karin, Harlet, Pierre, Vutskits, Laszlo, Walker, Suellen M., de Graaff, Jurgen C., Zielinska, Marzena, Simic, Dusica, Engelhardt, Thoma, Habre, Walid, Breschan, Christian, Likar, Rudolf, Platzer, Manuela, Edelman, Isole, Eger, Johane, Heschl, Stefan, Messerer, Brigitte, Vittinghof, Maria, Kroess, Ruth, Stichlberger, Martina, Kahn, David, Pirotte, Thierry, Pregardien, Caroline, Stevens, France, Berghmans, Johan, Bauters, Annemie, De Baerdemaeker, Luc, De Hert, Stefan, Lapage, Koen, Parashchanka, Aliaksandra, Van Limmen, Jurgen, Wyffels, Piet, Lauweryns, Julie, Najafi, Nadia, Vundelinckx, Jori, Butković, Diana, Sorić, Ivana Kerovec, Kralik, Sandra, Markić, Ana, Azman, Josip, Markic, Josko, Pupacic, Daniela, Frelich, Michal, Reimer, Petr, Urbanec, Rene, Cajkova, Petra, Mixa, Vladimir, Sedlačkova, Yvona, Knoppova, Lenka, Zlamalova (nee Květoňova), Alena, Vavřina, Martin, Žurek, Jiři, Hansen, Tom, Afshari, Arash, Bille, Anders B., Ellekvist, Marguerite, Ilmoja, Mari-Lii, Moor, Reet, Kikas, Reet, Vali, Merle, Kallio, Kariantti, Reponen, Elisa, Suominen, Pertti, Suvanto, Sami, Vahatalo, Raisa, Kokki, Hannu, Kokki, Merja, Harju, Jarkko, Kokkonen, Miia, Vieri, Jenni, Manner, Tuula, Amory, Catherine, Ludot, Hugue, Bert, Dina, Godart, Juliette, Laffargue, Anne, Dupont, Herve, Urbina, Benjamin, Baujard, Catherine, Roulleau, Philippe, Staiti, Giuseppe, Bordes, Maryline, Gaulain, Karine Nouette, Hamonic, Yann, Semjen, Francoi, Jacqmarcq, Olivier, Lejus-Bourdeau, Caroline, Magne, Cecile, Petry, Lea, Ros, Lilica, Zang, Aurelien, Bennis, Mehdi, Coustets, Bernard, Fesseau, Rose, Constant, Isabelle, Khalil, Eliane, Sabourdin, Nada, Audren, Noemie, Descarpentries, Thoma, Fabre, Fanny, Legrand, Aurelien, Druot, Emilie, Orliaguet, Gille, Sabau, Lucie, Uhrig, Lynn, de la Briere, Francoi, Jonckheer, Karin, Mission, Jean-Paul, Scordo, Lucia, Couchepin, Caroline, Dadure, Christophe, De la Arena, Pablo, Hertz, Laurent, Pirat, Philippe, Sola, Chrystelle, Bellon, Myriam, Dahmani, Souhayl, Julien-Marsollier, Florence, Michelet, Daphne, Depret-Donatien, Veronique, Lesage, Anne, Kaufmann, Jost, Laschat, Michael, Wappler, Frank, Brunner, Lena, Oppenrieder, Karin, Badelt, Gregor, Hochmuth, Karin, Koller, Bernhard, Reil, Anita, Richter, Sebastian, Fischer, Thoma, Diers, Anja, Schorer, Clemen, Weyland, Andrea, Cohausz, Ruth, Kretz, Franz-Josef, Loffler, Michaela, Wilbs, Marku, Hoehne, Claudia, Ulrici, Johanna, Goeters, Christiane, Flinspach, Armin, Klages, Matthia, Lindau, Simone, Messroghli, Leila, Zacharowski, Kai, Eisner, Christoph, Mueller, Thoma, Richter, Daniel, Schafer, Melanie, Weigand, Marku, Weiterer, Sebastian, Ochsenreiter, Miriam, Scholer, Michael, Terboven, Tom, Eggemann, Isabel, Haussmann, Sascha, Leister, Nicola, Menzel, Christoph, Trieschmann, Uwe, Yucetepe, Sirin, Keilig, Susanna, Kranke, Peter, Jelting, Yvonne, Baehner, Torsten, Ellerkmann, Richard, Ghamari, Shahab, Neumann, Claudia, Sohle, Martin, Chloropoulou, Pelagia, Ntritsou, Vagia, Papagiannopoulou, Pinelopi, Garini, Eleana, Karafotia, Afroditi, Mammi, Panagoula, Bali, Evangelia, Iordanidou, Despoina, Malisiova, Anna, Polyzoi, Artemi, Tsiotou, Adelai, Sapi, Erzsebet, Szekely, Edgar, Kosik, Nandor, Maraczi, Veronika, Schnur, Jano, Csillag, Judit, Gal, Jano, Gobl, Gergely, Hauser, Balaz, Petroczy, Andra, Tovishazi, Gyula, Blain, Stuart, Gallagher, Sarah, Harte, Sinead, Jackson, Mandy, Meehan, Emma, Nawoor, Zeenat, O’Hare, Brendan, Ross, Mark, Lerro, Daniela, Astuto, Marinella, Grasso, Chiara, Scalisi, Rita, Frasacco, Giulia, Lenares, Elena, Leone, Roberto, Grazzini, Maurizia, Minardi, Carmelo, Zadra, Nicola, Cinnella, Gilda, Cotoia, Antonella, Galante, Dario, De Lorenzo, Brita, Kuppers, Beate, Bottazzi, Giulia, Caramelli, Fabio, Mondardini, Maria C., Rossetti, Emanuele, Picardo, Sergio, Vittori, Alessandro, Camporesi, Anna, Wolfler, Andrea, Calderini, Edoardo, Colantonio, Laura B., Finamore, Simona A., Porro, Giuliana A., Bonfiglio, Rachele, Kotzeva, Svetlana, Mameli, Leila, Mattioli, Girolamo, Micalizzi, Camilla, Montaguti, Alessia, Pistorio, Angela, Zanaboni, Clelia, Guddo, Anna, Neba, Gerald R., Favarato, Moreno, Locatelli, Bruno G., Maffioletti, Micol, Sonzogni, Valter, Garra, Rossella, Sammartino, Maria, Sbaraglia, Fabio, Cortegiani, Andrea, Moscarelli, Alessandra, Attanasi, Elena, Tesoro, Simonetta, Agapiti, Cristina, Pinzoni, Francesca, Vezzoli, Cesare, Bilotta, Federico, Barzdina, Arta, Straume, Zane, Zundane, Anda, Lukosiene, Laura, Maraulaite, Irena, Razlevice, Ilona, Schmitz, Bernd, Mifsud, Stephanie, Aehling, Carolin, Allison, Celia, De Boer, Rient, Emal, Dina, Stevens, Marku, Buitenhuis, Marielle, de Graaff, Jurgen, De Liefde, Inge, Machotta, Andrea, Scoones, Gail, Staals, Lonneke, Tomas, Jeremy, Van der, Anouk, Dortmont, Knijff-van, Veldhuizen, Marianne, Alders, David, Buhre, Wolfgang, Schafrat, Eva, Schreiber, Jan, Vermeulen, Petronella M., Hendriks, Mark, Lako, Sandra, Voet-Lindner, Marieke, Pieters, Barbe, Scheffer, Gert-Jan, Tielens, Luc, Absalom, Anthony R., Bergsma, Margot, De Ruiter, Joke, Meier, Sascha, Volkers, Martin, Zweers, Tjerk, Beukers, Anne M., Boer, Christa, Dertinger, Jurgen, Numan, Sandra, Van Zaane, Ba, Boerke, Wenche B., Ekiz, Nil, Stensrud, Kristoffer, Drage, Inger M., Isern, Erik R., Bartkowska-Sniatkowska, Alicja, Grzeskowiak, Malgorzata, Juzwa-Sobieraj, Magdalena, Rosada-Kurasińska, Jowita, Baranowski, Artur, Jakubowska, Karina, Lewandowska, Dorota, Mierzewska-Schmidt, Magdalena, Sawicki, Piotr, Urban-Lechowicz, Magdalena, Przemyslaw, Pomianek, Leal, Teresa, Soares, Maria, Pina, Pedro, Pinho, Silvia, Patuleia, Maria Dominga, Esteves, Catarina C., Salgado, Helena, Santos, Maria J., Badeti, Rodica, Cindea, Iulia, Oana, Loredana, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Tabacaru, Radu, Trante, Irina, Munteanu, Valentin, Morariu, Mihai, Nyiri, Emese, Budic, Ivana, Marjanovic, Vesna, Drašković, Biljana, Pandurov, Marina, Ilic, Jordanka, Mandras, Ana, Rados, Zdenka, Stankovic, Nikola, Suica, Maja, Vasiljevic, Sladjana, Knezevic, Mirjana, Milojevic, Irina, Petrov, Ivana, Racic, Selena Puric, Simic, Irena, Stevic, Marija, Vulicevic, Irena, Cabanova, Barbora, Hanula, Miloslav, Berger, Jelena, Janjatovic, Darja, Štupnik, Špela P., Kohn, Ivan, Lindestam, Ulf, Reinhard, Jarl, Castellheim, Albert, Sandstrom, Kerstin, Bengt, Sporre, Dorenberg, Rainer, Frykholm, Peter, Garcia, Maria, Kvarnstrom, Ann, Ponten, Emma, Bruelisauer, Thoma, Erdoes, Gabor, Kaiser, Heiko, Marchon, Mathia, Riva, Thoma, Seiler, Stefan, Bogli, Yann, Dolci, Mirko, Marcucci, Carine, Pichon, Isabelle, Casutt, Mattia, Holzle, Martin, Hurni, Thoma, Johr, Martin, Anna-Ursina, null, Malar, null, Mauch, Jacqueline, Erb, Thoma, Oeinck, Karin, Akin, Mine, Keskin, Gulsen, Senayli, Yesim, Kaya, Guner, Kendigelen, Pinar, Tutuncu, Ayse C., Hatipoğlu, Zehra, Ozcengiz, Dilek, Erdost, Hale Aksu, Ocmen, Elvan, Olguner, Cimen, Ayanoglu, Hilmi, Dincer, Pelin C., Umuroglu, Tumay, Azizoglu, Mustafa, Birbicer, Handan, Doruk, Nurcan, Sagun, Aslı, Baris, Sibel, Dmytriiev, Dmytro, Kuchi, Sridevi, Masip, Nuria, Brooks, Peter, Hare, Alison, Ahmad, Nargi, Casey, Michelle, De Silva, Sam, Dobby, Nadine, Krishnan, Prakash, Sogbodjor, L. Amaki, Walker, Ellie, Walker, Suellen, King, Stephanie, Nicholson, Katy, Quinney, Michelle, Stevens, Paul, Blevin, Andrew, Giombini, Mariangela, Goonasekera, Chulananda, Adil, Sadia, Bew, Stephanie, Bodlani, Carol, Gilpin, Dan, Jinks, Stephanie, Malarkkan, Nalini, Miskovic, Alice, Pad, Rebecca, Barry, Juliet W., Abbott, Joy, Armstrong, Jame, Cooper, Natalie, Crate, Lindsay, Emery, John, James, Kathryn, King, Hannah, Martin, Paul, Catenacci, Stefano S., Bomont, Rob, Smith, Paul, Mele, Sara, Verzelloni, Alessandra, Dix, Philippa, Bell, Graham, Gordeva, Elena, McKee, Lesley, Ngan, Esther, Scheffczik, Jutta, Tan, Li-En, Worrall, Mark, Cassar, Carmel, Goddard, Kevin, Barlow, Victoria, Oshan, Vimmi, Shah, Khairi, Bell, Sarah, Daniels, Lisa, Gandhi, Monica, Pachter, David, Perry, Chri, Robertson, Andrew, Scott, Carmen, Waring, Lynne, Barnes, David, Childs, Sophie, Norman, Joanne, Sunderland, Robin, HUS Children and Adolescents, Children's Hospital, and Clinicum
Subjects: Male, Time Factors, Health Status, Comorbidity, Intraoperative Complications/diagnosis/epidemiology/mortality/therapy, 0302 clinical medicine, Postoperative Complications, 030202 anesthesiology, Risk Factors, patient safety, Medicine, Anesthesia, Prospective Studies, Prospective cohort study, Intraoperative Complications, Medical Audit, ddc:617, Incidence (epidemiology), Incidence, Age Factors, Gestational age, critical events, Europe, Anesthetics/adverse effects, quality, Surgical Procedures, Operative, outcome, Female, Infant, Premature, Gestational Age, Anesthesia/adverse effects/mortality, Risk Assessment, Europe/epidemiology, 03 medical and health sciences, Humans, Anesthetics, business.industry, Postoperative Complications/diagnosis/epidemiology/mortality/therapy, Postmenstrual Age, Infant, Newborn, Infant, medicine.disease, 3126 Surgery, anesthesiology, intensive care, radiology, neonates, Clinical trial, Surgical Procedures, Operative/adverse effects/mortality, Anesthesiology and Pain Medicine, Blood pressure, Observational study, critical event, neonate, business
Abstract: Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results: Infants (n=5609) born at mean (standard deviation [SD]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2
Published: 2021

13. Prognostic Factors for Postrelapse Survival after ex Vivo CD34+-Selected (T Cell-Depleted) Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma

Author: Heather Landau, Alexandra Gomez-Arteaga, Eric L. Smith, Raymond E. Baser, Sergio Giralt, Arnab K. Ghosh, David J. Chung, Michael Scordo, Parastoo B. Dahi, Oscar B Lahoud, Miguel-Angel Perales, Guenther Koehne, Adam Bryant, Gunjan L. Shah, Brian C. Shaffer, Josel D. Ruiz, and Ola Landgren
Subjects: Oncology, Transplantation, medicine.medical_specialty, Hematopoietic cell, business.industry, T cell, Lymphocyte, CD34, Hematology, medicine.disease, Donor lymphocyte infusion, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Internal medicine, Medicine, business, Multiple myeloma, Ex vivo, 030215 immunology
Abstract: Allogeneic hematopoietic cell transplantation (alloHCT) for multiple myeloma (MM), with its underlying graft-versus-tumor capacity, is a potentially curative approach for high-risk patients. Relapse is the main cause of treatment failure, but predictors for postrelapse survival are not well characterized. We conducted a retrospective analysis to evaluate predictors for postrelapse overall survival (OS) in 60 MM patients who progressed after myeloablative T cell-depleted alloHCT. The median patient age was 56 years, and 82% had high-risk cytogenetics. Patients received a median of 4 lines of therapy pre-HCT, and 88% achieved at least a partial response (PR) before alloHCT. Of the 38% who received preemptive post-HCT therapy, 13 received donor lymphocyte infusions (DLIs) and 10 received other interventions. Relapse was defined as very early ( 24 months; 22%). At relapse, 27% presented with extramedullary disease (EMD). The median postrelapse overall survival (OS) by time to relapse was 4 months for the very early relapse group, 17 months for the early relapse group, and 72 months for the late relapse group (P = .002). Older age, relapse with EMD
Published: 2020

14. Outcomes in patients with DLBCL treated with commercial CAR T cells compared with alternate therapies

Author: Michael Scordo, Gunjan L. Shah, Ariela Noy, Andrew D. Zelenetz, Lorenzo Falchi, Sean M. Devlin, Erel Joffe, Gottfried von Keudell, David Sermer, Miguel-Angel Perales, Craig S. Sauter, Alison J. Moskowitz, Paul A. Hamlin, Anas Younes, Caleb Ho, Mari Lynne Silverberg, Aishat Afuye, Jessica Flynn, Audrey Hamilton, Richard J. Lin, Martina Pennisi, Philip Caron, Ildefonso Rodriguez-Rivera, Parastoo B. Dahi, Anita Kumar, M. Lia Palomba, Joachim Yahalom, Matthew J. Matasar, Colette Owens, Connie L Batlevi, Steven M. Horwitz, and David J. Straus
Subjects: Oncology, medicine.medical_specialty, education.field_of_study, Clinical Trials and Observations, business.industry, T-Lymphocytes, Antigens, CD19, Population, Retrospective cohort study, Hematology, medicine.disease, Single Center, Lymphoma, Prior Therapy, Refractory, Internal medicine, Cohort, medicine, Humans, Lymphoma, Large B-Cell, Diffuse, Prospective Studies, Prospective cohort study, education, business, Retrospective Studies
Abstract: The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Chimeric antigen receptor (CAR) T-cell therapy has been approved for R/R DLBCL after 2 prior lines of therapy based on data from single-arm phase 2 trials, with complete responses (CRs) in 40% to 60% of patients. However, a direct comparison with other treatments is not available and, moreover, its true efficacy in real-world patients is unknown. In this single center, retrospective, observational study of 215 patients, we compared outcomes in patients treated with CAR T-cell therapy (n = 69) with a historical population treated with alternate therapies (n = 146). Patients treated with CAR T cell vs alternate therapies demonstrated a CR rate of 52% vs 22% (P < .001), median progression-free survival (PFS) of 5.2 vs 2.3 months (P = .01), and median overall survival (OS) of 19.3 vs 6.5 months (P = .006), and this advantage appeared to persist irrespective of the number of lines of prior therapy. After adjusting for unfavorable pretreatment disease characteristics, superior overall response rate in the CAR T cohort remained significant; however, differences in PFS and OS between cohorts did not. In addition, patients who responded to alternate therapies demonstrated prolonged remissions comparable to those who responded to CAR T therapy. We contend that in select clinical scenarios alternate therapies may be as efficacious as CAR T therapy; thus, additional study is warranted, ideally with randomized prospective trials.
Published: 2020

15. COVID-19: An Immunopathologic Assault

Author: Kristine Anne Scordo, Nancy Munro, and Misty M Richmond
Subjects: Adult, Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Critical Care, Coronavirus disease 2019 (COVID-19), Health care provider, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Psychological intervention, Critical Care Nursing, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, Humans, Mass Screening, 030212 general & internal medicine, Intensive care medicine, Pandemics, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, SARS-CoV-2, business.industry, Critically ill, COVID-19, General Medicine, Middle Aged, Dilemma, Practice Guidelines as Topic, Emergency Medicine, Female, Coronavirus Infections, business
Abstract: When caring for patients with coronavirus disease 2019 (COVID-19), clinicians have noticed some unusual clinical presentations not observed before, such as profound hypoxia and severe hypotension. Scientists are probing the evidence to explain these issues and many other unanswered questions. Severe acute respiratory syndrome associated with coronavirus 2 presents an unchartered acute and critical care dilemma. Some of the theories and proposed interventions that will improve outcomes for these critically ill patients are explored in this article. Various testing procedures for COVID-19 are described so valid results can be obtained. Clinical presentations are discussed but continue to evolve as the pandemic ravages our society. The psychological impact of this devastation is also addressed from multiple perspectives. The health care provider is faced with an unprecedented, harrowing situation that has become an internal war that also must be confronted. Professional dedication has provided a formidable response to this destructive virus.
Published: 2020

16. Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma

Author: Miguel-Angel Perales, Elena Mead, Sean M. Devlin, Aishat Afuye, Kitsada Wudhikarn, M. Lia Palomba, Michael Scordo, Martina Pennisi, Mari Lynne Silverberg, Marta Garcia-Recio, Molly Maloy, Connie L Batlevi, Gunjan L. Shah, Bianca Santomasso, Parastoo B. Dahi, Jessica Flynn, Craig S. Sauter, and Susan K. Seo
Subjects: Adult, Male, T cell, Antigens, CD19, Infections, Immunotherapy, Adoptive, lcsh:RC254-282, Article, Hypogammaglobulinemia, Young Adult, Anti-Infective Agents, Risk Factors, Medicine, Humans, Cumulative incidence, Risk factor, B cell, Aged, Aged, 80 and over, B-cell lymphoma, business.industry, Incidence, Hematology, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Chimeric antigen receptor, Cytokine release syndrome, medicine.anatomical_structure, Treatment Outcome, Oncology, Immunology, Infectious diseases, Female, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma
Abstract: CD19-targeted chimeric antigen receptor (CAR) T cell therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL). In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), B cell aplasia and hypogammaglobulinemia are common toxicities predisposing these patients to infections. We analyzed 60 patients with DLBCL treated with FDA-approved CD19 CAR T cells and report the incidence, risk factors, and management of infections during the first year after treatment. A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, 1 life-threatening, and 1 fatal infection. Bacteria were the most common causative pathogens. The cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection at 1 year were 63.3%, 57.2%, 29.6%, 44.7%, and 4%, respectively. In multivariate analyses, the use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission. Impaired performance status and history of infections within 30 days before CAR T cell therapy was a risk factor for severe bacterial infection. In conclusion, infections were common within the first 60 days after CAR T cell therapy, however, they were not associated with an increased risk of death.
Published: 2020

17. Geriatric syndromes in 2-year, progression-free survivors among older recipients of allogeneic hematopoietic cell transplantation

Author: Richard J. Lin, Doris M. Ponce, Roni Tamari, Molly Maloy, Gunjan L. Shah, Lucrecia Yáñez San Segundo, Beatriz Korc-Grodzicki, Ioannis Politikos, Sergio Giralt, Craig S. Sauter, Nerea Castillo Flores, Theresa A. Elko, Parastoo B. Dahi, Ann A. Jakubowski, Armin Shahrokni, Brian C. Shaffer, Boglarka Gyurkocza, Raymond E. Baser, Esperanza B. Papadopoulos, Miguel-Angel Perales, Michael Scordo, Juliet N. Barker, Ana Alarcon Tomas, Miriam Sanchez-Escamilla, Christina Cho, and James W. Young
Subjects: Oncology, Transplantation, Disease free survival, medicine.medical_specialty, Hematopoietic cell, Extramural, business.industry, medicine.medical_treatment, MEDLINE, Hematology, Hematopoietic stem cell transplantation, Internal medicine, Homologous chromosome, Medicine, business
Published: 2020

18. DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality

Author: Molly Maloy, Maria Lia Palomba, Marta Garcia-Recio, Martina Pennisi, Mari Lynne Silverberg, Connie L Batlevi, Gunjan L. Shah, Parastoo B. Dahi, Kitsada Wudhikarn, Bianca Santomasso, Craig S. Sauter, Miguel-Angel Perales, Elena Mead, Aishat Afuye, Sean M. Devlin, Jessica Flynn, and Michael Scordo
Subjects: medicine.medical_specialty, Performance status, Clinical Trials and Observations, business.industry, T-Lymphocytes, Incidence (epidemiology), Antigens, CD19, Receptors, Antigen, T-Cell, Hematology, medicine.disease, Immunotherapy, Adoptive, Gastroenterology, Lymphoma, Cytokine release syndrome, Tolerability, Internal medicine, Toxicity, Humans, Medicine, Cumulative incidence, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma
Abstract: Cytokine release syndrome (CRS) immune effector cell–associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell–mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade ≥2 and 289 grade ≥3 toxicities. Common grade ≥3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade ≥3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade ≥3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade ≥3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade ≥3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely associated with mortality. Our study emphasizes the importance of toxicity assessment, which could serve as a benchmark for further research to reduce symptom burdens and improve tolerability in patients treated with CAR T cells.
Published: 2020

19. Use of anti-thymocyte globulin (ATG) for the treatment of pure red cell aplasia and immune-mediated cytopenias after allogeneic hematopoietic cell transplantation: a case series

Author: Alexandra Gomez-Arteaga, Sergio Giralt, Parastoo B. Dahi, Craig S. Sauter, Ann A. Jakubowski, Roni Tamari, Miguel-Angel Perales, Hugo Castro-Malaspina, Josel D. Ruiz, Esperanza B. Papadopoulos, and Michael Scordo
Subjects: Transplantation, Hematopoietic cell, Extramural, business.industry, medicine.medical_treatment, Pure red cell aplasia, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Anti-thymocyte globulin, Immune system, Immunology, medicine, Red cell aplasia, business
Published: 2020

20. Incidence and Risk Factors for Acute and Chronic Kidney Injury after Adult Cord Blood Transplantation

Author: Insara Jaffer Sathick, Ioannis Politikos, Michael Scordo, Thangamani Muthukumar, Edgar A. Jaimes, Molly Maloy, Junting Zheng, Juliet N. Barker, Victoria Gutgarts, Sergio Giralt, Valkal Bhatt, Sean M. Devlin, and Ilya G. Glezerman
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Kidney, urologic and male genital diseases, Mycophenolate, Gastroenterology, Nephrotoxicity, Risk Factors, Internal medicine, Humans, Medicine, Cord blood transplantation, Retrospective Studies, Transplantation, urogenital system, business.industry, Incidence, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Acute kidney injury, Immunosuppression, Hematology, Acute Kidney Injury, medicine.disease, female genital diseases and pregnancy complications, Cord Blood Stem Cell Transplantation, business, Kidney disease
Abstract: Although cord blood transplantation (CBT) extends allograft access, patient comorbidities, chemoradiation, and nephrotoxic medications all contribute to acute kidney injury (AKI) risk. We analyzed AKI in adult myeloablative CBT recipients who underwent transplantation from 2006 to 2017 for hematologic malignancies using cyclosporine A (CSA)/mycophenolate mofetil immunosuppression. Maximum grades of AKI were calculated using Kidney Disease: Improving Global Outcomes (grade 1, 1.5 to2-fold; grade 2, 2 to3-fold; or grade 3, ≥3-fold over baseline) definitions. In total, 153 patients (median 51 years [range, 23-65], 114/153 [75%] acute leukemia, 27/153 [18%] African, 88/153 [58%] cytomegalovirus seropositive, median age-adjusted hematopoietic cell comorbidity index 3 [range, 0-9], median pretransplant albumin 4.0 g/dL [range, 2.6-5.2]) underwent transplantation. The day 100 cumulative incidence of grade 1-3 AKI was 83% (95% confidence interval [CI], 77%-89%) (predominantly grade 2, median onset 40 days, range 0 to 96), and grade 2-3 AKI incidence was 54% (95% CI, 46%-62%) (median onset 43 days, range 0 to 96). Mean CSA level preceding AKI onset was high (360 ng/mL, target range 300-350). In multivariate analysis, African ancestry, addition of haploidentical CD34
Published: 2020

21. Early experience using salvage radiotherapy for relapsed/refractory non‐Hodgkin lymphomas after CD19 chimeric antigen receptor (CAR) T cell therapy

Author: Sergio Giralt, Michael Scordo, Craig S. Sauter, Brandon S. Imber, Jae H. Park, Connie Lee Batlevi, Gunjan L. Shah, M. Lia Palomba, Miguel-Angel Perales, Michel Sadelain, Carl J. DeSelm, Parastoo B. Dahi, Joachim Yahalom, and Renier J. Brentjens
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Allogeneic transplantation, Subsequent Relapse, medicine.medical_treatment, T cell, Antigens, CD19, Cell- and Tissue-Based Therapy, Salvage therapy, Immunotherapy, Adoptive, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Aged, Salvage Therapy, Receptors, Chimeric Antigen, business.industry, Lymphoma, Non-Hodgkin, Hematology, Middle Aged, medicine.disease, Chimeric antigen receptor, Radiation therapy, Transplantation, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, human activities, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: Radiotherapy is potentially an important salvage strategy post-chimeric antigen receptor T cell therapy (CART), but limited data exist. We reviewed 14 patients treated with salvage radiation post-CART progression (SRT). Most received SRT for first post-CART relapse (71%) to sites previously PET-avid pre-CART (79%). Median overall survival (OS) post-SRT was 10 months. Post-SRT, six localized relapses achieved 100% response (3 = complete, 3 = partial), with improved freedom from subsequent relapse (P = 0·001) and OS (P = 0·004) compared to advanced stage relapses. Three were bridged to allogeneic transplantation; at analysis, all were alive/NED. SRT has diverse utility and can integrate with novel agents or transplantation to attempt durable remissions.
Published: 2020

22. Accuracy of Two Point-of-Care Tests for Rapid Diagnosis of Bovine Tuberculosis at Animal Level using Non-Invasive Specimens

Author: Susan Baer, Sarah M Waibel, Jordi B. Torrelles, Wondwossen A. Gebreyes, Sabeen Sidiki, Shu-Hua Wang, Janet Hengesbach, Cristina Tomatis-Souverbielle, Xueliang Pan, Vedat O. Yildiz, Joan-Miquel Balada-Llasat, N Barr, Richard W. Smith, James J. Averill, Julia M. Scordo, Sayeed N Silwani, W. Garret Hunt, and Holden V. Kelley
Subjects: 0301 basic medicine, Lipopolysaccharides, Male, Veterinary medicine, Tuberculosis, 040301 veterinary sciences, Point-of-care testing, lcsh:Medicine, Urine, Sensitivity and Specificity, Article, Specimen Handling, 0403 veterinary science, 03 medical and health sciences, Active tb, medicine, Bovine tuberculosis, Animals, Humans, Antigens, lcsh:Science, 2. Zero hunger, Multidisciplinary, Lipoarabinomannan, business.industry, Diagnostic Tests, Routine, Non invasive, Infectious-disease diagnostics, lcsh:R, Diagnostic test, 04 agricultural and veterinary sciences, medicine.disease, 3. Good health, 030104 developmental biology, Milk, Point-of-Care Testing, Cattle, Female, lcsh:Q, Pathogens, business, Infection, Tuberculosis, Bovine
Abstract: Bovine tuberculosis (BTB) testing in cattle requires a significant investment of time, equipment, and labor. Novel, rapid, cheaper and accurate methods are needed. The Alere Determine TB lipoarabinomannan antigen (LAM-test) is a World Health Organization-endorsed point-of-care urine test designed to detect active TB disease in humans. The Lionex Animal TB Rapid Test (Lionex-test) is a novel animal specific TB diagnostic blood test. An animal level analysis was performed using urine (n = 141) and milk (n = 63) samples from depopulated BTB-suspected cattle to test the accuracy of the LAM-test when compared to results of positive TB detection by any routine BTB tests (BOVIGAM, necropsy, histology, culture, PCR) that are regularly performed by the United States Department of Agriculture (USDA). The agreement between the urine LAM-test and USDA standard tests were poor at varying testing time points. The same milk samples did not elicit statistically significant agreement with the Lionex-test, although positive trends were present. Hence, we cannot recommend the LAM-test as a valid BTB diagnostic test in cattle using either urine or milk. The Lionex-test’s production of positive trends using milk samples suggests larger sample sizes may validate the Lionex-test in accurately diagnosing BTB in cattle using milk samples, potentially providing a quick and reliable field test for BTB.
Published: 2020

23. Impact and safety of chimeric antigen receptor T-cell therapy in older, vulnerable patients with relapsed/refractory large B-cell lymphoma

Author: Yakup Batlevi, Soo Jung Kim, Molly Maloy, Connie Lee Batlevi, Arela Noy, Theresa A. Elko, Stephanie Lobaugh, Elena Mead, Gunjan L. Shah, Sergio Giralt, Miguel-Angel Perales, Michael Scordo, Parastoo B. Dahi, Josel D. Ruiz, Beatriz Korc-Grodzicki, Richard J. Lin, Craig S. Sauter, Hei Ton Chan, Martina Pennisi, Mari Lynne Silverberg, Bianca Santomasso, Paul A. Hamlin, Chelsea A Brooklyn, Sean M. Devlin, and M. Lia Palomba
Subjects: medicine.medical_treatment, Antigens, CD19, Cell- and Tissue-Based Therapy, Receptors, Antigen, T-Cell, Immunotherapy, Adoptive, CD19, Antigen, medicine, Humans, Letters to the Editor, B-cell lymphoma, Receptor, Aged, Receptors, Chimeric Antigen, biology, business.industry, Hematology, Immunotherapy, medicine.disease, Lymphoma, Relapsed refractory, biology.protein, Cancer research, Chimeric Antigen Receptor T-Cell Therapy, Lymphoma, Large B-Cell, Diffuse, business
Published: 2020

24. Presalvage International Staging System Stage and Other Important Outcome Associations in CD34+-Selected Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Author: Sergio Giralt, Michael Scordo, Guenther Koehne, Heather Landau, David J. Chung, Ola Landgren, Molly Maloy, Gunjan L. Shah, Richard J. O'Reilly, Adam Bryant, Eric L. Smith, Patrick Hilden, and Miguel-Angel Perales
Subjects: Melphalan, Transplantation, medicine.medical_specialty, business.industry, medicine.medical_treatment, Incidence (epidemiology), Salvage therapy, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Fludarabine, Internal medicine, medicine, Cumulative incidence, business, Multiple myeloma, medicine.drug
Abstract: Despite ongoing therapeutic advances, multiple myeloma (MM) remains largely incurable, and outcomes in patients who develop resistance to immunomodulatory drugs or proteasome inhibitors remain grim. Allogeneic hematopoietic cell transplantation (alloHCT) is an alternative option that may offer potential for cure. Although rates of transplantation-related morbidity and mortality have decreased in recent years, weighing this approach's potential benefits against nontransplantation therapies demands a thoroughly informed pre-alloHCT assessment. Here we assess the impact of pre-alloHCT variables on important clinical outcomes in a large cohort of relapsed refractory MM (RRMM) CD34+-selected alloHCT recipients. We included all patients with MM who underwent CD34+-selected alloHCT at our center between June 2010 and December 2015. Patients were conditioned with busulfan (0.8 mg/kg × 10), melphalan (70 mg/m2 × 2), and fludarabine (25 mg/m2 × 5), followed by infusion of a CD34+-selected peripheral blood stem cell graft, without post-alloHCT graft-versus-host disease (GVHD) prophylaxis. The 73-patient cohort had a median age of 55 years (range, 37 to 66 years). Overall survival (OS) and progression-free survival (PFS) rates were 70% and 53%, respectively, at 1 year (95% confidence interval [CI], 58% to 79% and 41% to 64%) and 50% and 30%, respectively, at 3 years (95% CI, 38% to 62% and 19% to 41%). The cumulative incidence of relapse was 25% at 1 year (95% CI, 15% to 35%) and 47% at 3 years (95% CI, 35% to 58%). Nonrelapse mortality at 1 year was 22% (95% CI, 13% to 32%). The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 7% at 100 days (95% CI, 3% to 14%), and that of any chronic GVHD (cGVHD) was 8% at 1 year (95% CI, 3% to 16%). International Staging System (ISS) stage II-III assessed before salvage therapy was associated with poorer 3-year OS (30% versus 54%; P = .037) and 3-year PFS (9% versus 33%; P = .013), and increased 3-year relapse incidence (72% versus 39%; P = .004). Older age and GVHD before 6 months (aGVHD grade II-IV or cGVHD of any grade) were also associated with poorer OS, and a greater number of pre-alloHCT lines of therapy was also associated with increased relapse incidence. Our findings reinforce that CD34+-selected alloHCT can achieve prolonged disease control and long-term survival in high- risk, heavily treated refractory MM populations. We also identified numerous pre-alloHCT variables associated with OS, PFS, and relapse. Amongst these, presalvage ISS stage II-III was consistently associated with poorer survival and relapse outcomes. Given the lack of established alternate therapies for patients with RRMM, we advocate the identification of adverse pre-alloHCT variables to inform alloHCT decision making rather than to exclude patient cohorts from this potentially curative treatment option.
Published: 2020

25. Narsoplimab (OMS721), a Masp-2 Inhibitor, for the Treatment of Adult Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HSCT-TMA)

Author: Olaf Penack, Nelson Leung, Michael Scordo, Mehdi Hamadani, Alessandro Rambaldi, Jaap Jan Boelens, Rafael F. Duarte, Sebastian Mayer, Miguel-Angel Perales, Sergio Giralt, Samer K. Khaled, Wlodzimierz Mendrek, Jeffery C Laurence, Vincent T. Ho, Jameela Sathar, Mitchell S. Cairo, Richard E. Champlin, and Sumithira Vasu
Subjects: Transplantation, Thrombotic microangiopathy, medicine.anatomical_structure, business.industry, medicine, Cancer research, Molecular Medicine, Immunology and Allergy, Hematopoietic stem cell, Cell Biology, Hematology, medicine.disease, business
Published: 2021

26. Acute Inflammation Confers Enhanced Protection against Mycobacterium tuberculosis Infection in Mice

Author: Paula A. Pino, Julia M. Scordo, Jordi B. Torrelles, Larry S. Schlesinger, Tucker J. Piergallini, and Joanne Turner
Subjects: 0301 basic medicine, Microbiology (medical), Lipopolysaccharides, Male, Tuberculosis, LPS, Lipopolysaccharide, Physiology, Neutrophils, Population, Inflammation, Microbiology, Proinflammatory cytokine, Mycobacterium tuberculosis, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Immune system, Genetics, medicine, Animals, Humans, education, education.field_of_study, Mice, Inbred BALB C, General Immunology and Microbiology, Ecology, biology, business.industry, lipopolysaccharide, Cell Biology, biology.organism_classification, medicine.disease, QR1-502, 030104 developmental biology, Infectious Diseases, chemistry, Infectious disease (medical specialty), Immunology, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Research Article
Abstract: Inflammation plays a crucial role in the control of Mycobacterium tuberculosis infection. In this study, we demonstrate that an inflammatory pulmonary environment at the time of infection mediated by lipopolysaccharide treatment in mice confers enhanced protection against M. tuberculosis for up to 6 months postinfection. This early and transient inflammatory environment was associated with a neutrophil and CD11b+ cell influx and increased inflammatory cytokines. In vitro infection demonstrated that neutrophils from lipopolysaccharide-treated mice exhibited increased association with M. tuberculosis and had a greater innate capacity for killing M. tuberculosis. Finally, partial depletion of neutrophils in lipopolysaccharide-treated mice showed an increase in M. tuberculosis burden, suggesting neutrophils played a part in the protection observed in lipopolysaccharide-treated mice. These results indicate a positive role for an inflammatory environment in the initial stages of M. tuberculosis infection and suggest that acute inflammation at the time of M. tuberculosis infection can positively alter disease outcome. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis disease, is estimated to infect one-fourth of the world’s population and is one of the leading causes of death due to an infectious disease worldwide. The high-level variability in tuberculosis disease responses in the human populace may be linked to immune processes related to inflammation. In many cases, inflammation appears to exasperate tuberculosis responses; however, some evidence suggests inflammatory processes improve control of M. tuberculosis infection. Here, we show an acute inflammatory stimulus in mice provides protection against M. tuberculosis for up to 6 months, suggesting acute inflammation can positively affect M. tuberculosis infection outcome.
Published: 2021

27. Interferon Gamma Release Assays for Latent Mycobacterium tuberculosis Detection in Elderly Hispanics

Author: Rodriguez Re, Eder Ledezma-Campos, Francisco Mora-Guzmán, Villafañez A, Larry S. Schlesinger, Aguillon G, Joanne Turner, Quirino Cerrillo Ap, Julia M. Scordo, Jordi B. Torrelles, Blanca I. Restrepo, Caso Ja, and Doris Ayala
Subjects: medicine.medical_specialty, Tuberculosis, biology, business.industry, Concordance, Healthy elderly, biology.organism_classification, medicine.disease, Mycobacterium tuberculosis, Age groups, Internal medicine, medicine, Interferon gamma, business, Kappa, medicine.drug
Abstract: SUMMARYBackgroundAging is a tuberculosis co-morbidity. Interferon Gamma Release Assays (IGRAs) are used to detect latent Mycobacterium tuberculosis (M.tb) infection (LTBI) in adults, but their performance in the elderly is not well-established. We aim to evaluate the performance of IGRAs for LTBI detection in healthy elderly Hispanics with recent, remote or no history of M.tb exposure.Study Design and MethodsCross-sectional study in Hispanic elderly (60+y) and adult (18-50y) recent TB contacts (ReC) or community controls (CoC). LTBI was based on a positive T-SPOT.TB and/or QuantiFERON-Gold in-tube or –Plus assay.ResultsWe enrolled 193 CoC (119 adults/74 elderly) and 459 ReC (361 adults/98 elderly). LTBI positivity increased with age in CoC (range 19-59%; trend p vs. 0.688 in adults) and more inconclusive results (indeterminate/borderline; 11.6% vs. 5.8% in adults; p=0.012). Exclusion of inconclusive results improved concordance between assays, notably in elderly ReC, who have the highest TB risk (from kappa 0.532 to 0.800). When both IGRAs were done simultaneously, inconclusive results were resolved in all cases as positive or negative with the other IGRA. The magnitude of the response to M.tb peptides used in the assays was similar between age groups, but responsiveness to mitogens was lower in the elderly.ConclusionsIGRAs are suitable for LTBI detection in the elderly. Discordant and inconclusive findings are more prevalent in the elderly, but results were resolved when performing different IGRAs simultaneously in the same participant.
Published: 2021

28. Antithymocyte globulin exposure in CD34+ T-cell-depleted allogeneic hematopoietic cell transplantation

Author: Audrey Mauguen, Brian C. Shaffer, Ichelle van Roessel, Richard J. O'Reilly, Michael Scordo, Nancy A. Kernan, Christina Cho, Andrew L. Kung, Andromachi Scaradavou, Maria Cancio, Sergio Giralt, Miguel-Angel Perales, Barbara Spitzer, Kevin J. Curran, Madhavi Lakkaraja, Esperanza B. Papadopoulos, Elizabeth Klein, Sean M. Devlin, Farid Boulad, Susan E. Prockop, Ann A. Jakubowski, Gunjan L. Shah, Roni Tamari, Jaap Jan Boelens, Scott Avecilla, and Josel D. Ruiz
Subjects: medicine.medical_specialty, Globulin, T cell, T-Lymphocytes, CD34, Antigens, CD34, Gastroenterology, Immune system, Pharmacokinetics, hemic and lymphatic diseases, Internal medicine, Medicine, Humans, Dosing, Antilymphocyte Serum, Retrospective Studies, biology, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, Transplantation, medicine.anatomical_structure, Pharmacodynamics, biology.protein, Neoplasm Recurrence, Local, business
Abstract: Traditional weight-based dosing results in variable rabbit antithymocyte globulin (rATG) clearance that can delay CD4+ T-cell immune reconstitution (CD4+ IR) leading to higher mortality. In a retrospective pharmacokinetic/pharmacodynamic (PK/PD) analysis of patients undergoing their first CD34+ T-cell–depleted (TCD) allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning with rATG, we estimated post-HCT rATG exposure as area under the curve (arbitrary unit per day/milliliter [AU × day/mL]) using a validated population PK model. We related rATG exposure to nonrelapse mortality (NRM), CD4+ IR (CD4+ ≥50 cells per µL at 2 consecutive measures within 100 days after HCT), overall survival, relapse, and acute graft-versus-host disease (aGVHD) to define an optimal rATG exposure. We used Cox proportional hazard models and multistate competing risk models for analysis. In all, 554 patients were included (age range, 0.1-73 years). Median post-HCT rATG exposure was 47 AU × day/mL (range, 0-101 AU × day/mL). Low post-HCT area under the curve (
Published: 2021

29. Interferon gamma release assays for detection of latent Mycobacterium tuberculosis in older Hispanic people

Author: Mateo Joya-Ayala, Francisco Mora-Guzmán, Doris Ayala, Alejandro Villafañez, Génesis P. Aguillón-Durán, Ana Paulina Quirino-Cerrillo, Larry S. Schlesinger, Jordi B. Torrelles, Blanca I. Restrepo, Eder Ledezma-Campos, Eminé Rodríguez-Reyna, Joanne Turner, and Julia M. Scordo
Subjects: Microbiology (medical), Adult, medicine.medical_specialty, diagnosis, Concordance, Infectious and parasitic diseases, RC109-216, Article, Mycobacterium tuberculosis, older people, Age groups, Latent Tuberculosis, Internal medicine, medicine, Humans, Interferon gamma, Aged, Aged, 80 and over, IGRA, biology, business.industry, Tuberculin Test, Latent TB infection, General Medicine, Hispanic or Latino, biology.organism_classification, Infectious Diseases, Cross-Sectional Studies, Older people, business, Kappa, Interferon-gamma Release Tests, medicine.drug
Abstract: SUMMARY: Background: Interferon gamma release assays (IGRAs) are used to detect latent Mycobacterium tuberculosis (M.tb) infection (LTBI) in adults, but their performance in older people is not well-established. We evaluated IGRAs for LTBI detection in older Hispanic recent TB contacts (ReC) or community controls (CoC). Methods: Cross-sectional assessment of LTBI with T-SPOT.TB and/or QuantiFERON-Gold in-tube or –Plus assay in older (≥60 years) and adult (18–50 years) Hispanic people. Results: We enrolled 193 CoC (119 adults, 74 older persons) and 459 ReC (361 adults, 98 older persons). LTBI positivity increased with age in CoC (19%–59%, P
Published: 2021

30. A Pilot Study Evaluating Lenalidomide and CC-486 in Combination with Radiotherapy for Patients with Plasmacytoma (LENAZART study)

Author: Alexander M. Lesokhin, David J. Chung, Kelly Werner, Sergio Giralt, Sydney X. Lu, Neha Korde, Elizabet Tavitian, Taha Merghoub, Joachim Yahalom, Ola Landgren, Jonathan Landa, Malin Hultcrantz, Sham Mailankody, Francesco Maura, Eric L. Smith, Michael Scordo, Oscar B Lahoud, Dhwani Patel, Richard J. Lin, Christopher A. Barker, Heather Landau, Bernard O'Malley, Urvi A Shah, Carlyn Tan, Sean M. Devlin, Parastoo B. Dahi, Hani Hassoun, and Gunjan L. Shah
Subjects: Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, Radiation therapy, Internal medicine, Medicine, Plasmacytoma, business, Lenalidomide, medicine.drug
Abstract: Background and Scientific Rationale Solitary plasmacytoma of the bone (SPB) is a rare entity representing 5% of all plasma cell dyscrasias. SPB treated with radiation therapy (RT) has a 10% risk of progression to multiple myeloma (MM) over 3 years if there is no marrow involvement, whereas there is a 60% chance of progression over 3 years in patients with minimal marrow involvement. Median time to progression in the latter group is 26 months. Presently, despite mounting evidence of a significant risk of progression to MM, there is no FDA-approved therapy and patients are usually treated with localized RT. This is an area of unmet need. A similar opportunity exists in the setting of MM patients relapsing with localized disease amenable to RT. This group of patients may not immediately require long-term systemic therapy especially if RT combined with epigenetic modulation and lenalidomide results in therapeutically relevant immune responses. A few studies combining lenalidomide and azacitidine have shown responses even in a lenalidomide refractory population with upregulation of cancer testis antigen (CTA) as well as CTA specific T cell responses (Table 1). These synergistic mechanisms focus on: 1) manipulating antigen expression and enhancing antigen presentation (both neoantigens and cancer testis antigens) with oral azacitidine (CC-486), and 2) augmentation of antigen specific immune responses via increased IL2 production leading to an increase in the proliferation of T cells with lenalidomide. This combination with RT would serve to inflame the tumor microenvironment and potentially lead to therapeutically active systemic immune responses via an abscopal effect. Study Design and Methods This is an open-label, single center, single-arm study of CC-486, lenalidomide plus RT, which will enroll a total of 20 patients in two cohorts. Clinical trial registry number NCT04174196, actively recruiting. Study population and inclusion criteria Each cohort will enroll ten patients - Cohort 1: i) Histologically confirmed newly diagnosed solitary plasmacytoma of the bone or lytic bone lesion ii) Minimal marrow involvement (Detectable clonal bone marrow (BM) plasma cells by multicolor flow cytometry and ≤ 10% clonal plasma cells in a BM biopsy by immunohistochemistry, morphology, or flow cytometry) iii) Secretory M protein < 3 g/dL Cohort 2: i) Relapsed multiple myeloma with plasmacytomas appropriate for RT on imaging ii) Relapsed (reappearance of M-spike/serum FLC) or progressive myeloma defined by a 25% increase from nadir in M-spike or involved serum FLC on 2 separate measurements; or with BM involvement by clonal plasma cells detectable by IHC iii) Any prior number of therapies is permitted, including prior RT iv) Allogeneic transplant patients are permitted Statistical methods We estimate the historical rate of stringent complete response (sCR) is approximately 5% (based on the rate for newly diagnosed myeloma with lenalidomide and dexamethasone on the MAIA study of 7.3% and for relapsed myeloma with Rd based on the POLLUX study of 4.6%). The primary endpoint of the study will be reported separately for the two cohorts. With 10 patients in each cohort, the maximum half-width of the exact 95% confidence interval for the response rate is +/- 0.31. A sCR rate of ≥20% would be considered promising for either cohort. Study treatment In the study, patients will be treated with CC-486 100 mg on day 1-21 and lenalidomide 25 mg on day 1-21 for 6 cycles. RT to the plasmacytoma will be initiated after cycle 2. Total dose may vary between 30-50 Gy (45-50 Gy for cohort 1) based on clinical judgement. (Figure 1) Endpoints Primary To provide preliminary efficacy data based on the rate of sCR by 2016 IMWG Criteria on post-treatment BM biopsy and aspirate specimens with no new lesions by PET. Secondary - To assess the safety of this combination. - To estimate the progression free survival and overall survival Exploratory - To evaluate antigen expression at the tumor site pre and post RT - To further characterize the antigen specific T cell response pre and post RT at the tumor site - To assess changes in epigenetic marks - To assess changes in the tumor microenvironment Disclosures Shah: Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Mailankody:Juno Therapeutics, a Bristol-Myers Squibb Company: Research Funding; Allogene Therapeutics: Research Funding; Janssen Oncology: Research Funding; Takeda Oncology: Research Funding; PleXus Communications: Honoraria; Physician Education Resource: Honoraria. Korde:Astra Zeneca: Other: Advisory Board; Amgen: Research Funding. Hultcrantz:GSK: Research Funding; Daiichi Sankyo: Research Funding; Amgen: Research Funding; Intellisphere LLC: Consultancy. Smith:Precision Biosciences: Consultancy; Fate Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy, Patents & Royalties, Research Funding. Shah:Janssen Pharmaceutica: Research Funding; Amgen: Research Funding. Lahoud:MorphoSys: Other: Advisory Board. Scordo:McKinsey & Company: Consultancy; Angiocrine Bioscience, Inc.: Consultancy, Research Funding; Omeros Corporation: Consultancy; Kite - A Gilead Company: Other: Ad-hoc advisory board. Dahi:Kite: Consultancy. Chung:Genentech: Research Funding. Hassoun:Novartis: Consultancy; Celgene: Research Funding; Takeda: Research Funding. Barker:Elekta: Research Funding; Amgen: Research Funding; Alpha Tau Medical: Other: Travel expenses, Research Funding; Merck: Research Funding. Giralt:KITE: Consultancy; MILTENYI: Consultancy, Research Funding; OMEROS: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria; ACTINUUM: Consultancy, Research Funding; TAKEDA: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Seattle Genetics: Research Funding; Pfizer: Consultancy, Honoraria; Merck: Other; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Merck: Other; Glenmark: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Seattle Genetics: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Lesokhin:Janssen: Research Funding; GenMab: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Genentech: Research Funding; Serametrix Inc.: Patents & Royalties. OffLabel Disclosure: CC-486 is an is an oral hypomethylating agent that has been studied in acute myeloid leukemia. This study combines CC-486 with lenalidomide and radiation therapy in plasma cell disorders.
Published: 2020

31. Pilot Study of Telehealth Evaluations in Patients Undergoing Hematopoietic Cell Transplantation

Author: Sheila Kenny, Lauren G. Johnson, Elizabeth S. Rodriguez, Heather Landau, Mariam T. Nawas, Michael Scordo, Craig S. Sauter, Catherine Featherstone, and Sergio Giralt
Subjects: medicine.medical_specialty, Telemedicine, Pilot Projects, Physical examination, Telehealth, Article, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Surveys and Questionnaires, hemic and lymphatic diseases, medicine, Humans, In patient, Transplantation, medicine.diagnostic_test, Hematopoietic cell, business.industry, Hematopoietic Stem Cell Transplantation, Allogeneic hct, Hematology, surgical procedures, operative, 030220 oncology & carcinogenesis, Emergency medicine, Videoconferencing, business, 030215 immunology
Abstract: BACKGROUND: Telehealth involves the use of telecommunication and information technology for the delivery of clinical care and may be a mechanism to alleviate the burden of visits faced by patients undergoing hematopoietic cell transplantation (HCT). Few studies have evaluated the feasibility and acceptability of telehealth visits in the care of HCT patients. METHODS: We conducted 27 telehealth visits with 25 patients undergoing HCT using a videoconferencing system that allows for real-time, two-way interactions and administered satisfaction surveys to patients and providers. RESULTS: Of the 25 patients included in the study, 20 (80%) and five (20%) were undergoing autologous and allogeneic HCT, respectively. The telehealth visits were distributed as follows: 3 inpatient visits upon admission for HCT; 11 inpatient visits between 2–14 days post-HCT; 4 inpatient visits prior to discharge after HCT; 8 outpatient, post-HCT follow-up visits; and 1 handoff to a community oncologist. Out of a total of 54 provider assessments, 7 providers (13%) were unable to complete some part of the physical examination, but no provider reported being unable to manage patients’ symptoms through telehealth. 81% of patients were either satisfied or very satisfied with the telemedicine session. Overall satisfaction was higher among patients than providers (mean scores 4.12 vs. 2.64; scale 1–5, 1: very poor; 5: excellent). Technological barriers resulting in delays and suboptimal physical examination were largely responsible for provider dissatisfaction. CONCLUSIONS: The use of telehealth to deliver comprehensive follow-up care to HCT patients is feasible across different HCT types but is dependent upon quality of data streaming and videoconferencing technologies.
Published: 2020

32. Compliments to complement blockade for TA-TMA

Author: Sergio Giralt and Michael Scordo
Subjects: biology, business.industry, Immunology, Cell Biology, Hematology, Biochemistry, Blockade, Complement (complexity), Monoclonal, biology.protein, Medicine, Thrombotic Microangiopathies, Antibody, business
Published: 2020

33. Standard Antithymocyte Globulin Dosing Results in Poorer Outcomes in Overexposed Patients after Ex Vivo CD34+ Selected Allogeneic Hematopoietic Cell Transplantation

Author: Michael Scordo, Richard J. O'Reilly, Miguel-Angel Perales, Molly Maloy, Hugo Castro-Malaspina, Brian C. Shaffer, Jaap Jan Boelens, Patrick Hilden, Melody Smith, Katie L. Thoren, Gunjan L. Shah, Christina Cho, Roni Tamari, Esperanza B. Papadopoulos, Scott T. Avecilla, Valkal Bhatt, Ann A. Jakubowski, and Sergio Giralt
Subjects: Transplantation, medicine.medical_specialty, Hematopoietic cell, Globulin, biology, business.industry, Hazard ratio, CD34, Hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, 030220 oncology & carcinogenesis, Internal medicine, biology.protein, Medicine, Dosing, business, Ex vivo, 030215 immunology
Abstract: Antithymocyte globulin (ATG) use mitigates the risk of graft rejection and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), but ATG overexposure in the setting of lymphopenia negatively affects immune recovery. We hypothesized that standard empiric weight-based dosing of ATG, used to prevent graft rejection in ex vivo CD34-selected allo-HCT, may lead to serious adverse consequences on outcomes in certain patients. We evaluated 304 patients undergoing myeloablative-conditioned ex vivo CD34-selected allo-HCT with HLA-matched donors for the treatment of hematologic malignancies. Patients received rabbit ATG at a dose of 2.5 mg/kg/day i.v. on days -3 and/or -2. An ATG dosing cutoff of 450 mg was used for statistical analyses to assess the relationship between ATG and overall survival (OS). Among all patients, median total ATG dose was 360 mg (range, 130 to 510 mg); 279 (92%) received a total dose of ATG ≤450 mg, and 25 (8%) received a total dose >450 mg. On the first day of ATG administration (day -3), the median absolute lymphocyte count was .0 K/µL. For patients who received a total dose of ATG >450 mg or ≤450 mg, the incidences of acute and late-acute GVHD grade II-IV were statistically similar. At 3 years post-HCT, for patients who received a total dose of ATG >450 mg or ≤450 mg, nonrelapse mortality (NRM) rates were 35% and 18%, respectively (P = .029), disease-free survival (DFS) rates were 37% and 61%, respectively (P = .003), and OS rates were 40% and 67%, respectively (P = .001). Among all patient and HCT characteristics in multivariable analyses, receipt of a total dose of ATG >450 mg was associated with an increased risk of NRM (hazard ratio [HR], 2.9; P = .01), shorter DFS (HR, 2.0; P = .03), and inferior OS (HR, 2.1; P = .01). In summary, the use of weight-based ATG at a time of relative lymphopenia before ex vivo CD34-selected allo-HCT results in overdosing in heavier patients, leading to higher NRM and lower DFS and OS. Further pharmacokinetic investigation in this setting is critical to determining the optimal dosing strategy for ATG.
Published: 2019

34. Hematopoietic-cell transplantation for lymphoma in the era of genetically engineered cellular therapy

Author: Craig S. Sauter, Michael Scordo, and Richard J. Lin
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, Antigens, CD19, Hematopoietic stem cell transplantation, Article, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Refractory, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Chemotherapy, Hematopoietic cell, business.industry, Genetically engineered, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, Lymphoma, Transplantation, 030104 developmental biology, Lymphoma, Large B-Cell, Diffuse, Genetic Engineering, business, 030215 immunology
Abstract: Second-line platinum-based salvage chemotherapy followed by high-dose chemotherapy and autologous hematopoietic-cell transplantation (AHCT) has remained the standard of care (SOC) for relapsed and primary refractory (r/r) diffuse large B-cell lymphoma (DLBCL) for greater than 2 decades. In the postrituximab era, this strategy has yielded disappointing outcomes for r/r patients with curability in less one-quarter of the patients by intention-to-treat.Given the Food and Drug Administration (FDA) approval of chimeric antigen receptor (CAR) modified T cells directed against CD19 (CD19 CAR T) for DLBCL following two lines of therapy and/or failed AHCT, encouragement with this therapy in the second line for r/r patients has naturally prompted randomized phase III studies against the aforementioned SOC. The predominant hurdle to procession to AHCT is chemotherapy sensitivity after platinum-based salvage therapy.In this review, we will discuss recent investigations to improve response rates in r/r DLBCL with the intent of proceeding to potentially curative AHCT, as well as investigations to decrease progression post-AHCT. In addition, data regarding currently FDA approved CD19 CAR T cells will be reviewed. Within 2-3 years, we will know if the multicenter/multinational studies of CD19 CAR T will replace SOC salvage therapy and AHCT in the second-line. The role of allogeneic HCT will also be briefly reviewed in the context of these therapies.
Published: 2019

35. Surveillance Screening to Reduce Carbapenem Resistance

Author: Kristine Anne Scordo and Heather Arnett
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, business.industry, Transmission (medicine), Public health, High mortality, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Acute care, Health care, Resistant organism, medicine, Colonization, 030212 general & internal medicine, business, Intensive care medicine, Carbapenem resistance
Abstract: Carbapenem-resistant Enterobacteriaceae (CRE) have become a global public health threat due to the widespread dissemination of these highly multidrug-resistant organisms. Colonization rates are especially prevalent in long-term acute care hospitals. The optimal approach for active surveillance screening to decrease CRE transmission is frequently lacking in health care facilities. The economic burden of this resistant organism is speculated to escalate with increasing prevalence. Billions of health care dollars and high mortality rates are attributed to this virulent superbug with limited treatment options, thus lending to the importance of prevention and control of CRE.
Published: 2019

36. Immune Cytopenias after Ex Vivo CD34+-Selected Allogeneic Hematopoietic Cell Transplantation

Author: Molly Maloy, Ann A. Jakubowski, Roni Tamari, Richard J. O'Reilly, Brian C. Shaffer, Gunjan L. Shah, Scott T. Avecilla, Boglarka Gyurkocza, Hugo Castro-Malaspina, Esperanza B. Papadopoulos, Christina Cho, Sergio Giralt, Michael Scordo, Meier Hsu, and Miguel-Angel Perales
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Transplantation Conditioning, CD34, Article, Immune Hemolytic Anemia, Young Adult, Immune system, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Transplantation, Homologous, Cumulative incidence, Adverse effect, Aged, Retrospective Studies, Transplantation, business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Blood Cell Count, Female, business, Ex vivo
Abstract: Immune-mediated cytopenias (ICs), such as immune thrombocytopenia and immune hemolytic anemia, are among the adverse events after allogeneic hematopoietic cell transplantation (allo-HCT). Previous reports suggest that in vivo T cell depletion may increase the incidence of IC after allo-HCT. We evaluated whether a strategy that reduces functional donor T cells via ex vivo CD34+-selection associates with the development of IC in a cohort of 408 patients who underwent allo-HCT for hematologic malignancy. The cumulative incidence of IC at 6, 12, and 36 months after the 30-day landmark post-HCT was 3.4%, 4.9%, and 5.8%, respectively. Among 23 patients who developed IC, 7 died of relapse-related mortality and 4 of nonrelapse mortality. A median 2 types of treatment (range, 1 to 5) was required to resolve IC, and there was considerable heterogeneity in the therapies used. In univariable analyses, a hematologic malignancy Disease Risk Index (DRI) score of 3 was significantly associated with an increased risk of IC compared with a DRI of 1 or 2 (hazard ratio [HR], 4.12; P = .003), and IC (HR, 2.4; P = .03) was associated with increased risk of relapse. In a multivariable analysis that included DRI, IC remained significantly associated with increased risk of relapse (HR, 2.4; P = .03). Our findings show that IC events occur with relatively similar frequency in patients after ex vivo CD34+-selected allo-HCT compared with unmodified allo-HCT, suggesting that reduced donor T cell immunity is not causative of IC. Moreover, we noted a possible link between its development and/or treatment and increased risk of relapse.
Published: 2019

37. Patient-Reported Outcomes with Chimeric Antigen Receptor T Cell Therapy: Challenges and Opportunities

Author: Navneet S. Majhail, Gunjan L. Shah, Michael Scordo, Rajshekhar Chakraborty, Surbhi Sidana, and Betty K. Hamilton
Subjects: Transplantation, medicine.medical_specialty, Receptors, Chimeric Antigen, business.industry, Cost-Benefit Analysis, Context (language use), Hematology, medicine.disease, Immunotherapy, Adoptive, Article, Chimeric antigen receptor, Cell therapy, Clinical trial, Cytokine release syndrome, Cognition, Quality of life, Quality of Life, medicine, Humans, Chimeric Antigen Receptor T-Cell Therapy, Patient Reported Outcome Measures, Adverse effect, Intensive care medicine, business
Abstract: Patient-reported outcomes (PROs) are an important tool to assess the impact of a new therapy on symptom burden and health-related quality of life (HRQoL). Chimeric antigen receptor T (CAR-T) cell therapies have been approved for use in relapsed or refractory leukemia and lymphoma based on promising efficacy in clinical trials. However, data are lacking on patient-reported toxicity and impact on HRQoL. This review provides an overview of the incorporation of PROs in CAR-T cell therapy and the specific challenges in this context. The first step is to demonstrate feasibility of PRO monitoring in the acute phase after CAR-T cell infusion. Apart from core PRO domains like physical functioning, disease-related symptoms, and symptomatic adverse effects, important measures to consider are cognitive functioning and financial toxicity. Because there are no validated PRO instruments in the setting of CAR-T cell therapy, universally validated measures like Patient-Reported Outcomes Measurement Information System (PROMIS) could be considered, which is also recommended in the setting of hematopoietic stem cell transplantation. Given the timeline of toxicities with CAR-T cell therapy, PRO instruments should be administered at baseline and at least weekly in the first 30 days. Subsequently, frequent monitoring of PROs in the first year might be helpful in identifying short- and intermediate-term toxicities, functional limitations, and neuropsychiatric effects. The major potential challenge in acute phase would be missing data when patients develop severe cytokine release syndrome or neurotoxicity. Designing a strategy for handling missing data is crucial. The long-term safety of CAR-T cell therapy is not well characterized because of short follow-up in most studies reported thus far. PROs should be measured at least yearly after the first year to identify potential late effects like cognitive deficit or autoimmune manifestations. Collaboration between institutions performing cellular therapy and engagement with patients, clinicians, and statisticians with expertise in PROs are crucial for setting a comprehensive agenda on integration of PROs with CAR-T cell therapy.
Published: 2019

38. Etoricoxib‐induced immune hemolytic anemia: first case presenting acute kidney failure

Author: P. Camino, B. Coca Mogro, V. L. Valiente, L. Burgos Pratx, W. Scordo, H.J. Salamone, and Diego Mario Santoro
Subjects: medicine.medical_specialty, Anemia, medicine.medical_treatment, Immunology, 030204 cardiovascular system & hematology, Gastroenterology, Immune Hemolytic Anemia, 03 medical and health sciences, 0302 clinical medicine, Coombs test, Internal medicine, medicine, Immunology and Allergy, Kidney, biology, medicine.diagnostic_test, business.industry, Hematology, medicine.disease, medicine.anatomical_structure, biology.protein, Hemodialysis, Cyclooxygenase, Antibody, business, Etoricoxib, 030215 immunology, medicine.drug
Abstract: Background Etoricoxib is a selective inhibitor of cyclooxygenase 2 used mainly to treat osteoarticular pain. Here, we report the case of a patient who developed acute kidney failure and immune hemolytic anemia after the use of etoricoxib. Study design and methods An 83-year-old female patient developed immune hemolytic anemia and acute kidney failure after treatment with etoricoxib for articular pain. Given the acute kidney failure, she required five hemodialysis sessions. She was discharged after 17 days. The case of immune hemolytic anemia and kidney failure was fully resolved. Results The direct antiglobulin test was not only positive for IgG but also for C3b and C3d, showing a very intense reactivity (++++). The eluate's reactivity was weaker (++) and showed no defined specificity. The investigation of unexpected antibodies in the serum of the patient showed a reactivity pattern similar to the eluate's: weak reactivity without specificity. The serum of the patient was compared to urine and plasma samples of two groups of volunteers. The indirect antiglobulin test showed only a very strong reactivity with the urine samples of the volunteers who had received etoricoxib. Discussion Considering that positive eluate is not the typical serologic profile of drug-induced immune hemolytic anemia, developing in-house techniques to show the causal link between them may be of interest to guide the treatment and avoid the empirical use of drugs. Conclusion Etoricoxib must be considered as a possible cause of acute kidney failure in cases of immune hemolytic anemia.
Published: 2019

39. Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant

Author: Kwang Woo Ahn, Mohamed A. Kharfan-Dabaja, Nirav N. Shah, Farhad Khimani, Praveen Ramakrishnan Geethakumari, Sairah Ahmed, Yue Chen, Sachiko Seo, Nilanjan Ghosh, Narendranath Epperla, Mehdi Hamadani, Sanghee Hong, Amer Beitinjaneh, Pashna N. Munshi, Tim Prestidge, Leona Holmberg, Victor A. Chow, Michael Scordo, Yago Nieto, Natalie S Grover, Umar Farooq, Nada Hamad, Reem Karmali, Gerhard C. Hildebrandt, Andrew R. Rezvani, Jean A. Yared, Antonio Jimenez-Jimenez, Maxwell M. Krem, Bhagirathbhai Dholaria, Evgeny Klyuchnikov, Craig S. Sauter, David J. Inwards, Peter A. Riedell, Trent P Wang, Farrukh T. Awan, Alex F. Herrera, Andy I. Chen, Melhem Solh, and Vaishalee P. Kenkre
Subjects: Oncology, Central Nervous System, Male, Cancer Research, medicine.medical_specialty, Transplantation Conditioning, Lymphoma, medicine.medical_treatment, ThioTEPA, Hematopoietic stem cell transplantation, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Busulfan, Cyclophosphamide, Original Investigation, Aged, business.industry, Lymphoma, Non-Hodgkin, Hazard ratio, Primary central nervous system lymphoma, Hematopoietic Stem Cell Transplantation, Middle Aged, medicine.disease, Transplantation, 030220 oncology & carcinogenesis, Cohort, Neoplasm Recurrence, Local, business, Thiotepa, Cohort study, medicine.drug
Abstract: IMPORTANCE: Primary central nervous system lymphoma (PCNSL) requires induction and consolidation to achieve potential cure. High-dose therapy and autologous hematopoietic cell transplant (AHCT) is an accepted and effective consolidation strategy for PCNSL, but no consensus exists on the optimal conditioning regimens. OBJECTIVE: To assess the outcomes in patients with PCNSL undergoing AHCT with the 3 most commonly used conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), thiotepa/carmustine (TT-BCNU), and carmustine/etoposide/cytarabine/melphalan (BEAM). DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study used registry data from the Center for International Blood and Marrow Transplant Research registry. The Center is a working group of more than 380 transplantation centers worldwide that contributed detailed data on HCT to a statistical center at the Medical College of Wisconsin, Milwaukee. The participant data were from 603 adult patients with PCNSL who underwent AHCT as initial, or subsequent, consolidation between January 2010 and December 2018. Patients were excluded if they had a non-Hodgkin lymphoma subtype other than diffuse large B-cell lymphoma, systemic non-Hodgkin lymphoma, or HIV; received an uncommon conditioning regimen; or were not in partial remission or complete remission prior to AHCT. Statistical analysis was performed from July 5, 2020, to March 1, 2021. INTERVENTIONS: Patients received 1 of 3 conditioning regimens: TBC (n = 263), TT-BCNU (n = 275), and BEAM (n = 65). MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival. RESULTS: Of 603 patients, the mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%) (P = .03) owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34; 95% CI, 2.45-7.70; P
Published: 2021

40. Local immune responses to tuberculin skin challenge in Mycobacterium bovis BCG-vaccinated baboons: a pilot study of younger and older animals

Author: Colwyn A. Headley, Tucker J. Piergallini, Olga Gonzalez, Joanne Turner, Vida L. Hodara, Nicole Reuter, Luis D. Giavedoni, James F. Papin, and Julia M. Scordo
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Aging, Immunology, Short Report, Tuberculin, lcsh:Geriatrics, Peripheral blood mononuclear cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, biology.animal, Medicine, Vaccine immunity, Tissue recall responses, Mycobacterium bovis, Tuberculin skin test, biology, business.industry, biology.organism_classification, Vaccination, lcsh:RC952-954.6, 030104 developmental biology, biology.protein, Antibody, lcsh:RC581-607, business, 030217 neurology & neurosurgery, Baboon
Abstract: Individuals over the age of 65 are highly susceptible to infectious diseases, which account for one-third of deaths in this age group. Vaccines are a primary tool to combat infection, yet they are less effective in the elderly population. While many groups have aimed to address this problem by studying vaccine-induced peripheral blood responses in the elderly, work from our lab and others demonstrate that immune responses to vaccination and infectious challenge may differ between tissue sites and the periphery. In this pilot study, we established an in vivo delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and tuberculin skin test (TST) in two adult and two aged baboons. Vaccination generates BCG-specific immune cells that are recruited to the skin upon tuberculin challenge. We tested short term recall responses (8 weeks post-vaccination) and long term recall responses (25 weeks post-vaccination) by performing skin punch biopsies around the site of tuberculin injection. In short term recall responses, we found increased oxidation and decreased production of immune proteins in aged baboon skin at the site of TST challenge, in comparison to adult skin. Differences between adult and aged animals normalized in the long term response to tuberculin. In vitro, aged peripheral blood mononuclear cells had increased migration and functional responses to antigen-specific stimulation, suggesting that age-related changes in the tissue in vivo impairs aged immune recall responses to antigenic challenge. These findings highlight the impact of age-associated changes in the local tissue environment in memory recall responses, which may be more broadly applied to the study of other tissues. Moreover, these findings should be considered in future studies aimed at understanding and improving aging immune responses to vaccination and tissue challenge.
Published: 2021

41. P-216: Daratumumab, Carfilzomib, Lenalidomide, & Dexamethasone for relapsed/refractory Myeloma with salvage autologous hematopoietic cell transplant: interim analysis of the multicenter 2nd chance protocol

Author: Neha Korde, Heather Landau, Obadi Obadi, Ruthee Bayer, Allison Parascondola, Malin Hultcrantz, Jennifer Acosta, Oscar B Lahoud, David J. Chung, Sham Mailankody, Saurabh Chhabra, Leeann Marcello, Christine S. Ferrer, Alexander M. Lesokhin, Sergio Giralt, Luciano J. Costa, Hani Hassoun, Gunjan L. Shah, Cesar Rodriguez, Susan Bal, Carlyn Tan, Jonathan Lambird, Leah Shulman, Urvi A Shah, and Michael Scordo
Subjects: Melphalan, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Daratumumab, Hematology, medicine.disease, Interim analysis, Carfilzomib, Transplantation, chemistry.chemical_compound, chemistry, Internal medicine, Multicenter trial, medicine, business, Multiple myeloma, Lenalidomide, medicine.drug
Abstract: Background Despite major advances in multiple myeloma (MM) therapy, most patients relapse after primary treatment. We present the interim analysis of a phase II multicenter trial evaluating the efficacy of daratumumab, carfilzomib (27 mg/m2 twice weekly), lenalidomide, & dexamethasone (Dara-KRD) with high-dose melphalan and autologous hematopoietic cell transplantation (AHCT) in patients after 1-3 prior lines to induce a complete response and provide patients a 2nd chance at long term disease control. Methods Patients received 4 cycles of Dara-KRD followed by AHCT and 4 additional cycles of Dara-KRD followed by maintenance at investigator discretion with a primary endpoint of best overall response by the end of cycle 8. Using a Simon’s two-stage optimal design, 7/22 patients need to achieve a CR to continue. Patient reported outcomes were monitored monthly using the MDASI-MM and NCI PRO-CTCAE. Data cutoff was 7/15/21. Results Between 7/2018 and 7/2020, 23 patients enrolled with 22 evaluable for interim analysis (one did not complete one cycle of treatment and was replaced). Patients had a median age of 65 (range 29-73), with 68% male, 64% white, and 18% black. Time from initial MM diagnosis to enrollment was a median of 4.4 years (range 0.4 -10.6). At initial diagnosis, 36% of patients had ISS stage I disease and 31% had unknown ISS staging. High risk cytogenetics were seen in 36%, with 2 patients having del17p, 2 t(4;14), 1 t(14;16), and 4 gain 1q. Eight-six percent had 1 line of treatment before enrollment with no patients having prior daratumumab, 14% receiving prior carfilzomib, and 86% having had a prior AHCT a median of 3.6 years (range 0.8-9.3) prior to enrollment. Eighty-two percent underwent AHCT and 59% completed all study treatments. Responses deepened post-AHCT prior to the second 4 cycles of Dara-KRD in most cases. Best overall response on study was a CR in 45% (10/22), >VGPR in 77%, and >PR in 82%. Three patients have died, 1 from infection during the pre-HCT cycles and 2 from disease progression. Conclusion Dara-KRD with salvage AHCT induced high overall response rates, meeting the pre-specified cutoff for promising results. Enrollment is ongoing for the second stage of the study using subcutaneous daratumumab and weekly carfilzomib. Full interim analysis and patient reported outcomes will be presented.
Published: 2021

42. Dynamics of minimal residual disease in patients with multiple myeloma on continuous lenalidomide maintenance: a single-arm, single-centre, phase 2 trial

Author: Michael Scordo, Lakshmi V. Ramanathan, Heather Landau, Kazunori Murata, Eric L. Smith, Sean M. Devlin, Sydney X. Lu, Hani Hassoun, Urvi A Shah, Gunjan L. Shah, Ola Landgren, Caleb Ho, Neha Korde, Benjamin Diamond, Ahmet Dogan, Sham Mailankody, Carlyn Tan, Oscar B Lahoud, Kylee H Maclachlan, Tim J Peterson, Maria E. Arcila, David J. Chung, Andriy Derkach, Katie L. Thoren, Francesco Maura, Alexander M. Lesokhin, Even H Rustad, Sergio Giralt, Mikhail Roshal, and Malin Hultcrantz
Subjects: Male, medicine.medical_specialty, Neoplasm, Residual, Phases of clinical research, Administration, Oral, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Clinical endpoint, Humans, Progression-free survival, Lenalidomide, Multiple myeloma, Aged, business.industry, Cancer, Hematology, Middle Aged, medicine.disease, Minimal residual disease, Progression-Free Survival, Clinical trial, 030220 oncology & carcinogenesis, Female, Neoplasm Grading, business, Multiple Myeloma, 030215 immunology, medicine.drug, Follow-Up Studies
Abstract: Background Lenalidomide maintenance improves progression-free survival for patients with multiple myeloma, although its optimal duration is unknown. Clearance of minimal residual disease (MRD) in the bone marrow results in superior outcomes, although its attainment or sustainment does not alter clinical decision-making. Studies that have evaluated MRD serially are limited in length. We therefore aimed to evaluate longitudinal changes in MRD-status (dynamics) and their association with progression-free survival in patients with multiple myeloma.In this single-centre, single-arm, phase 2 study, we enrolled patients aged 18 years and older from the Memorial Sloan Kettering Cancer Center (New York, NY, USA) who had newly diagnosed multiple myeloma following unrestricted frontline therapy and an Eastern Cooperative Oncology Group Performance Status of 2 or lower, including patients who started maintenance before study enrolment. All participants received lenalidomide maintenance at 10 mg for 21 days of 28-day cycles until progression or unacceptable toxic effects for up to 5 years on protocol. The primary endpoint was progression-free survival at 60 months per protocol and key secondary endpoints were MRD rates after completion of the 12th, 24th, and 36th cycle of maintenance and the association between progression-free survival and annual measurement of MRD status. MRD was assessed from first-pull bone marrow aspirates at baseline and annually by flow cytometry per International Myeloma Working Group criteria, (limit of detection of at least 1 × 10Between Sept 8, 2015, and Jan 25, 2019, 108 patients (100 evaluable for the primary endpoint) were enrolled. Median follow-up was 40·7 months (95% CI 38·7-45·0). At 60 months, progression-free survival was 64% (95% CI 52-79). Median progression-free survival was unreached (95% CI unreached-unreached). MRD dynamics were assessed using 340 MRD assessments done over 5 years for 103 evaluable patients. Patients who sustained MRD negativity for 2 years (n=34) had no recorded disease progression at median 19·8 months (95% CI 15·8-22·3) past the 2-year maintenance landmark. By contrast, patients who lost their MRD-negative responses (n=10) were more likely to progress than those with sustained MRD negativity (HR infinite; p0·0001) and those with persistent MRD positivity (HR 5·88, 95% CI 1·18-33·33; p=0·015) at the 2-year landmark. Haematological and non-haematological serious adverse events occurred in 19 patients (18%). The most common adverse events of grade 3 or worse were decreased lymphocyte count in 48 (44%) patients and decreased neutrophil count in 47 (44%) patients. One death occurred on study due to sepsis and heart failure and was considered unrelated to the study drug.Serial measurements of MRD allow for dynamic assessment of risk for disease progression. Early intervention should be investigated for patients with loss of MRD negativity. Sustained MRD positivity is not categorically an unfavourable outcome and might portend prolonged stability of low-level disease.Memorial Sloan Kettering and Celgene.
Published: 2021

43. The Simplified Comorbidity Index: a new tool for prediction of nonrelapse mortality in allo-HCT

Author: Avichai Shimoni, James W. Young, Roni Tamari, Sean M. Devlin, Scott Avecilla, Michael Scordo, Josel D. Ruiz, Miguel-Angel Perales, James P Sullivan, Joshua A Fein, Ann A. Jakubowski, Doris M. Ponce, Christina Cho, Esperanza B. Papadopoulos, Ana Alarcon Tomas, Craig S. Sauter, Marcel R. M. van den Brink, Brian C. Shaffer, Sergio Giralt, Boglarka Gyurkocza, Gunjan L. Shah, Lucrecia Yáñez San Segundo, Alexander Geyer, Nerea Castillo Flores, Richard J. O'Reilly, Ioannis Politikos, Roni Shouval, Richard J. Lin, Juliet N. Barker, Arnon Nagler, Miriam Sanchez-Escamilla, and P.B. Dahi
Subjects: Adult, medicine.medical_specialty, Transplantation Conditioning, Proportional hazards model, business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, Disease, Comorbidity, Middle Aged, medicine.disease, Transplantation, hemic and lymphatic diseases, Internal medicine, Cohort, medicine, Humans, Transplantation, Homologous, Nonrelapse mortality, business, Comorbidity index, Proportional Hazards Models
Abstract: Individual comorbidities have distinct contributions to nonrelapse mortality (NRM) following allogeneic hematopoietic cell transplantation (allo-HCT). We studied the impact of comorbidities individually and in combination in a single-center cohort of 573 adult patients who underwent CD34-selected allo-HCT following myeloablative conditioning. Pulmonary disease, moderate to severe hepatic comorbidity, cardiac disease of any type, and renal dysfunction were associated with increased NRM in multivariable Cox regression models. A Simplified Comorbidity Index (SCI) composed of the 4 comorbidities predictive of NRM, as well as age >60 years, stratified patients into 5 groups with a stepwise increase in NRM. NRM rates ranged from 11.4% to 49.9% by stratum, with adjusted hazard ratios of 1.84, 2.59, 3.57, and 5.38. The SCI was also applicable in an external cohort of 230 patients who underwent allo-HCT with unmanipulated grafts following intermediate-intensity conditioning. The area under the receiver operating characteristic curve (AUC) of the SCI for 1-year NRM was 70.3 and 72.0 over the development and external-validation cohorts, respectively; corresponding AUCs of the Hematopoietic Cell Transplantation–specific Comorbidity Index (HCT-CI) were 61.7 and 65.7. In summary, a small set of comorbidities, aggregated into the SCI, is highly predictive of NRM. The new index stratifies patients into distinct risk groups, was validated in an external cohort, and provides higher discrimination than does the HCT-CI.
Published: 2021

44. Acute inflammation, mediated by lung neutrophils, confers enhanced protection against Mycobacterium tuberculosis infection in mice

Author: Paula A. Pino, Joanne Turner, Jordi B. Torrelles, Tucker J. Piergallini, and Julia M. Scordo
Subjects: Lung, biology, Disease outcome, business.industry, Monocyte, Inflammation, biology.organism_classification, In vitro, Proinflammatory cytokine, Mycobacterium tuberculosis, medicine.anatomical_structure, Immunology, medicine, Macrophage, medicine.symptom, business
Abstract: Inflammation plays a crucial role in the control of Mycobacterium tuberculosis (M.tb) infection. In this study, we demonstrate that an inflammatory pulmonary environment at the time of infection mediated by liposaccharide (LPS) treatment in mice confers enhanced protection against M.tb for up to 6 months post infection. This transient protective inflammatory environment was associated with a neutrophil and monocyte/macrophage influx as well as increased inflammatory cytokines. In vitro infection of neutrophils from LPS treated mice demonstrated that LPS neutrophils exhibited increased recognition of M.tb, and had a greater innate capacity for killing M.tb. Finally, partial depletion of neutrophils in LPS treated mice showed an increase in M.tb burden, suggesting neutrophils conferred the enhanced protection observed in LPS treated mice. These results indicate a positive role of an inflammatory environment during initial M.tb infection, and suggests that acute inflammation at the time of M.tb infection can positively alter disease outcome.
Published: 2021

45. Author Correction: Accelerated single cell seeding in relapsed multiple myeloma

Author: Michael Scordo, Heather Landau, Minal Patel, Alvin Makohon-Moore, Juan S. Medina-Martinez, Ola Landgren, Lance Zhang, David J. Chung, Benjamin Diamond, Ahmet Dogan, Gunes Gundem, Sergio Giralt, Elli Papaemmanuil, Eric Alden Smith, Venkata Yellapantula, Patrick Blaney, Alexander M. Lesokhin, Cody Ashby, Gary A. Ulaner, Neha Korde, Oscar B Lahoud, Frits van Rhee, Yangyu Zhou, Christine A. Iacobuzio-Donahue, Max Levine, Kylee H Maclachlan, Francesco Maura, Yanming Zhang, Urvi A Shah, Even H Rustad, Priscilla Baez, Sham Mailankody, Eileen M Boyle, Sydney Lu, Rajya Kappagantula, Juan E. Arango Ossa, Hani Hassoun, Gunjan L. Shah, Jonathan U. Peled, Marc A. Attiyeh, Gareth J. Morgan, and Malin Hultcrantz
Subjects: Oncology, Male, medicine.medical_specialty, Cell Survival, Science, Cell seeding, General Physics and Astronomy, Myeloma, Transplantation, Autologous, General Biochemistry, Genetics and Molecular Biology, Clonal Evolution, Text mining, Spatio-Temporal Analysis, Internal medicine, Positron Emission Tomography Computed Tomography, Antineoplastic Combined Chemotherapy Protocols, Cancer genomics, Medicine, Chemotherapy, Humans, Neoplasm Invasiveness, Author Correction, Melphalan, Multiple myeloma, Multidisciplinary, Dose-Response Relationship, Drug, Whole Genome Sequencing, business.industry, Hematopoietic Stem Cell Transplantation, General Chemistry, Middle Aged, medicine.disease, Mutation, Disease Progression, Neoplasm Recurrence, Local, Single-Cell Analysis, business, Multiple Myeloma
Abstract: Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient's life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant.
Published: 2021

46. Productivity and nutritional and nutraceutical value of strawberry fruits (Fragaria x ananassa Duch.) cultivated under irrigation with treated wastewaters

Author: Cristina Vanessa Agata Scordo, Francesca Tozzi, Maria Concetta Bruzzoniti, Edgardo Giordani, Massimo Del Bubba, Donatella Fibbi, Laila Mandi, Naaila Ouazzani, and Lapo Renai
Subjects: Irrigation, Agricultural Irrigation, 030309 nutrition & dietetics, Biology, Wastewater, Fragaria, Antioxidants, Crop, Anthocyanins, 03 medical and health sciences, 0404 agricultural biotechnology, Nutraceutical, Flavonols, Food Quality, Cultivar, polyphenols, chemistry.chemical_classification, 0303 health sciences, Nutrition and Dietetics, business.industry, circular economy, fruit yield, sugars, wastewater reuse, Water, 04 agricultural and veterinary sciences, 040401 food science, Horticulture, chemistry, Agriculture, Fruit, Dietary Supplements, Food quality, business, Agronomy and Crop Science, Nutritive Value, Food Science, Biotechnology
Abstract: BACKGROUND Agriculture represents a productive sector typically characterized by a high water demand, whereas freshwater (FW) availability is a problem of increasing concern in the world and FW resources are becoming insufficient for sustaining agricultural irrigation. The reuse of treated wastewaters (TWWs) for crop irrigation could be an efficient tool for reducing water shortage. Hence, the present study evaluated the food quality of Fragaria x ananassa (cultivar Camarosa) fruits irrigated with four types of treated wastewaters (TWWs). Strawberries were analysed for yield, sucrose, fructose, glucose, total soluble polyphenols (TSP), total monomeric anthocyanins (TMA), and antiradical and antioxidant capacity. In addition, a targeted quantification of the most representative phenolic compounds of strawberry was performed. RESULTS TWWs complied the Italian ministerial decree 185/2003 for wastewater reuse, with very few exceptions, mainly represented by chloride concentrations (258-643 mg L-1 versus a legal threshold of 250 mg L-1 ). The reuse of TWWs reduced fruit yield (10-26%) compared to irrigation with tap water as a control. Irrigation with TWWs gave also rise to the decrease of total sugars (14-26%), TSP (2-10%) and TMA (29-49%). Individual phenolic acids, flavonols and flavanols were quite stable in response to the irrigation with TWWs, whereas anthocyanidins decreased significantly. CONCLUSION Although TWWs negatively affected fruit quality, the nutritional and nutraceutical parameters determined in the present study were in line with data previously reported for strawberries purchased in the market or cultivated in research orchards, thus suggesting that the use of TWWs does not prevent the fruit marketability. © 2020 Society of Chemical Industry.
Published: 2021

47. Anti-Thymocyte Globulin Exposure in CD34+T Cell Depleted Allogeneic Hematopoietic Cell Transplantation

Author: Gunjan L. Shah, Andrew L. Kung, Sean M. Devlin, Richard J. O'Reilly, Miguel-Angel Perales, Andromachi Scaradavou, Esperanza B. Papadopoulos, Jaap Jan Boelens, Roni Tamari, Elizabeth Klein, Madhavi Lakkaraja, Brian C. Shaffer, Scott Avecilla, Farid Boulad, Christina Cho, Barbara Spitzer, Josel D. Ruiz, Ichelle van Roessel, Ann A. Jakubowski, Sergio Giralt, Susan E. Prockop, Audrey Mauguen, Nancy A. Kernan, Kevin J. Curran, Michael Scordo, and Maria Cancio
Subjects: Oncology, medicine.medical_specialty, Hematopoietic cell, business.industry, Institutional review board, Competing risks, Anti-thymocyte globulin, Transplantation, Internal medicine, Overall survival, Medicine, Cellular immunotherapy, business, Host disease
Abstract: Background: Traditional weight-based dosing results in variable rabbit anti-thymocyte-globulin (rATG) clearance that can delay CD4+Tcell immune reconstitution (CD4+IR) leading to higher mortality. Methods: In a retrospective, pharmacokinetic (PK)/pharmacodynamic analysis of patients undergoing their first CD34+ T-cell depleted (TCD) Allogeneic Hematopoietic Cell Transplantation (HCT) after myeloablative conditioning with rATG, we estimated post-HCT rATG exposure as area-under-the-curve (AUC;AU*d/L) using a validated population-PK model. We related rATG exposure to non-relapse mortality (NRM), CD4+IR (CD4+≥50/µL at two consecutive measures within 100 days after HCT), overall survival, relapse, and acute-graft versus host disease (GVHD) to deﬁne an optimal rATG-exposure. Cox-proportional hazard models, and multi-state competing risk models were used. Results: 554 patients were included (age 0.1-73 years). Median post-HCT rATG exposure was 47AU*d/L (range 0–101). Low post–HCT AUC ( 55AU*d/L and 30-55AU*d/L groups, respectively, compared to
Published: 2021

48. Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets

Author: Justin Ferdin, Vida L. Hodara, Dhiraj Kumar Singh, Shalini Gautam, Shabaana A. Khader, Shannan Hall-Ursone, Shashank Ganatra, Yenny Goez-Gazi, Tae-Hyung Lee, Benjamin Klaffke, Riti Sharan, Elizabeth Clemmons, Cynthia Alvarez, Olga Gonzalez, Christopher H. Chen, Kathleen M. Brasky, Laura M. Parodi, Kendra J. Alfson, Rajesh Thippeshappa, Alyssa Schami, Joanne Turner, Richard Copin, Andra K. Voges, Angélica Olmo-Fontánez, Makedonka Mitreva, Michal Gazi, Amanda Mannino, Patrice A. Frost, Ruby Escobedo, Alyssa Blakley, Deepak Kaushal, Edward J. Dick, Julia M. Scordo, Dharani Ajithdoss, John Dutton, Journey Cole, Hilary M. Staples, Christos A. Kyratsous, Priscilla Escareno, Luis D. Giavedoni, Ricardo Carrion, Bruce A. Rosa, Maya Gough, Luis Martinez-Sobrido, Mushtaq Ahmed, Bindu Singh, Roy N. Platt, Cory R. A. Hallam, Ken Sayers, Jessica Callery, Jordi B. Torrelles, Adelekan Oyejide, Jean L. Patterson, Andreu G. Vilanova, Carmen Bartley, Tim J. Anderson, Xavier Alvarez, Anna Goodroe, Larry S. Schlesinger, Corinna N. Ross, Alina Baum, and Ayan Chatterjee
Subjects: Male, Microbiology (medical), viruses, Immunology, Adaptive Immunity, Antibodies, Viral, Macaque, Bronchoalveolar Lavage, Applied Microbiology and Biotechnology, Microbiology, 03 medical and health sciences, Immune system, biology.animal, medicine, Genetics, Animals, Humans, Myeloid Cells, Viral shedding, Lung, 030304 developmental biology, Pneumonitis, Inflammation, 0303 health sciences, Immunity, Cellular, biology, medicine.diagnostic_test, 030306 microbiology, business.industry, SARS-CoV-2, Monkey Diseases, COVID-19, Callithrix, Cell Biology, Viral Load, medicine.disease, Acquired immune system, Macaca mulatta, Virus Shedding, Bronchoalveolar lavage, Immunoglobulin G, Female, business, Viral load, Bronchoalveolar Lavage Fluid, Baboon, Papio
Abstract: Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.
Published: 2020
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49. Age Impacts the Local Immune Response to Tuberculin Skin Challenge in Mycobacterium Bovis BCG-vaccinated Baboons

Author: Luis D. Giavedoni, James F. Papin, Tucker J. Piergallini, Vida L. Hodara, Olga Gonzalez, Joanne Turner, Colwyn A. Headley, Nicole Reuter, and Julia M. Scordo
Subjects: Mycobacterium bovis, Immune system, biology, business.industry, Immunology, Medicine, Tuberculin, business, biology.organism_classification
Abstract: Background - Individuals over the age of 65 are highly susceptible to infectious diseases, which account for one-third of deaths in this age group. Vaccines are a primary tool to combat infection, yet they are less effective in the elderly population. While many groups have aimed to address this problem by studying vaccine-induced peripheral blood responses in the elderly, work from our lab and others demonstrate that immune responses to vaccination and infectious challenge may differ between tissue sites and the periphery. To improve health outcomes in our aged population, we must study vaccine responses in the tissue. Here we established an in vivo delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and tuberculin skin test (TST) in adult and aged baboons. Vaccination generates BCG-specific immune cells that are recruited to the skin upon tuberculin challenge. We tested short-term recall responses (8 weeks post-vaccination) and long term recall responses (25 weeks post-vaccination) by performing skin punch biopsies around the site of tuberculin injection. In parallel, we determined BCG-induced responses in the peripheral blood of vaccinated animals. Results - In short term recall responses, we found increased oxidation and decreased production of immune proteins in aged baboon skin at the site of TST challenge, in comparison to adult skin. Differences between adult and aged animals normalized in the long term response to tuberculin. Phenotypic analysis of aged peripheral blood cells found several age-related changes in immune cell populations, independent of BCG vaccination, and no impairment in functional responses. Moreover, aged peripheral blood mononuclear cells had increased migration in vitro, suggesting that age-related changes in the tissue in vivo impairs aged immune recall responses to antigenic challenge. Conclusions - These findings highlight the impact of age-associated changes in the local tissue environment in memory recall responses, which may be more broadly applied to the study of other tissues. Moreover, these findings should be considered in future studies aimed at understanding and improving aging immune responses to vaccination and tissue challenge.
Published: 2020

50. Traffic data acquirement by unmanned aerial vehicle

Author: Giuseppe Salvo, Alessandro Vitale, Luigi Caruso, Giuseppe Guido, Alessandro Scordo, Salvo, Giuseppe, Caruso, Luigi, Scordo, Alessandro, Guido, Giuseppe, and Vitale, Alessandro
Subjects: 0209 industrial biotechnology, Atmospheric Science, Traffic data, Geographic information system, Relation (database), UAV, GPS, 02 engineering and technology, vehicle trajectorie, Vehicle Information and Communication System, Transport engineering, lcsh:Oceanography, 020901 industrial engineering & automation, Computers in Earth Science, 0502 economics and business, lcsh:GC1-1581, Computers in Earth Sciences, Simulation, General Environmental Science, Road user, 050210 logistics & transportation, business.industry, Applied Mathematics, lcsh:QE1-996.5, 05 social sciences, Traffic flow, Video image, lcsh:Geology, Geography, Settore ICAR/05 - Trasporti, Global Positioning System, business, vehicle trajectories
Abstract: This paper presents a methodology aimed to acquire traffic flow data through the employment of unmanned aerial vehicles (UAVs). The study is focused on the determination of driving behavior parameters of road users and on the reconstruction of traffic flow Origin/Destination matrix. The methodology integrates UAV flights with video image processing technique, and the capability of geographic information systems, to represent spatiotemporal phenomena. In particular, analyzing different intersections, the attention of the authors is focused on users’ gap acceptance in a naturalistic drivers’ behavior condition (drivers are not influenced by the presence of instruments and operators on the roadway) and on the reconstruction of vehicle paths. Drivers’ level of aggressiveness is determined by understanding how drivers decide that a gap is crossable and, consequently, how their behavior is critical in relation to a moving stream of traffic with serious road safety implications. The results of these experiments highlight the usefulness of the UAVs technology, that combined with video processing technique allows the capture of real traffic conditions with a good level of accuracy.
Published: 2017

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