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1. Impact of Hemoglobin Levels on Composite Cardiac Arrest or Stroke Outcome in Patients With Respiratory Failure Due to COVID-19

Author

Shi Nan Feng, BSPH, Thu-Lan Kelly, PhD, John F. Fraser, MD, PhD, Gianluigi Li Bassi, MD, PhD, Jacky Suen, PhD, Akram Zaaqoq, MD, MPH, Matthew J. Griffee, MD, Rakesh C. Arora, MD, Nicole White, PhD, Glenn Whitman, MD, Chiara Robba, MD, PhD, Denise Battaglini, MD, PhD, Sung-Min Cho, DO, MHS, on behalf of COVID-19 Critical Care Consortium (CCCC), Robert Bartlett, John F. Fraser, Gianluigi Li Bassi, Jacky Y. Suen, Heidi J. Dalton, John Laffey, Daniel Brodie, Eddy Fan, Antoni Torres, Davide Chiumello, Alyaa Elhazm, Carol Hodgson, Shingo Ichiba, Carlos Luna, Srinivas Murthy, Alistair Nichol, Pauline Yeung Ng, Mark Ogino, Aidan Burrell, Antonio Pesenti, Tala Al-Dabbous, Huda Alfoudri, Mohammed Shamsah, Subbarao Elapavaluru, Ashley Berg, Christina Horn, Yunis Mayasi, Stephan Schroll, Dan Meyer, Jorge Velazco, Ludmyla Ploskanych, Wanda Fikes, Rohini Bagewadi, Marvin Dao, Haley White, Alondra Berrios Laviena, Ashley Ehlers Maysoon, Shalabi-McGuire, Trent Witt, Lorenzo Grazioli, Luca Lorini, E. Wilson Grandin, Jose Nunez, Tiago Reyes, Diarmuid O’Briain, Stephanie Hunter, Mahesh Ramanan, Julia Affleck, Hemanth Hurkadli Veerendra, Sumeet Rai, Josie Russell-Brown, Mary Nourse, Mark Joseph, Brook Mitchell, Martha Tenzer, Ryuzo Abe, Hwa Jin Cho, In Seok Jeong, Nadeem Rahman, Vivek Kakar, Andres Oswaldo Razo Vazquez, Nicolas Brozzi, Omar Mehkri, Sudhir Krishnan Abhijit, Duggal Stuart Houltham, Jerónimo Graf, Roderigo Diaz, Roderigo Orrego, Camila Delgado, Joyce González, Maria Soledad Sanchez, Michael Piagnerelli, Josefa Valenzuela Sarrazin, A/Prof. Gustavo Zabert, Lucio Espinosa, Paulo Delgado, Victoria Delgado, Diego Fernando, Bautista Rincón, Angela Maria Marulanda Yanten, Melissa Bustamante Duque, Alyaa Elhazmi, Abdullah Al-Hudaib, Maria Callahan, M. Azhari Taufik, Elizabeth Yasmin Wardoyo, Margaretha Gunawan, Nurindah S Trisnaningrum, Vera Irawany, Muhammad Rayhan, Mauro Panigada, Alberto Zanella, Giacomo Grasselli, Sebastiano Colombo, Chiara Martinet, Gaetano Florio, Massimo Antonelli, Simone Carelli, Domenico L. Grieco, Motohiro Asaki, Kota Hoshino, Leonardo Salazar, Mary Alejandra Mendoza Monsalve, Bairbre McNicholas, David Cosgrave, Joseph McCaffrey, Allison Bone, Yusuff Hakeem, James Winearls, Mandy Tallott, David Thomson, Christel Arnold-Day, Jerome Cupido, Zainap Fanie, Malcom Miller, Lisa Seymore, Dawid van Straaten, Ali Ait Hssain, Jeffrey Aliudin, Al-Reem Alqahtani, Khoulod Mohamed, Ahmed Mohamed, Darwin Tan, Joy Villanueva, Ahmed Zaqout, Ethan Kurtzman, Arben Ademi, Ana Dobrita, Khadija El Aoudi, Juliet Segura, Gezy Giwangkancana, Shinichiro Ohshimo, Javier Osatnik, Anne Joosten, Minlan Yang, Ana Motos, Francisco Arancibia, Virginie Williams, Alexandre Noel, Nestor Luque, Marina Fantini, Ruth Noemi Jorge García, Enrique Chicote Alvarez, Anna Greti, Adrian Ceccato, Angel Sanchez, Ana Loza Vazquez, Ferran Roche-Campo, Diego Franch-Llasat, Divina Tuazon, Marcelo Amato, Luciana Cassimiro, Flavio Pola, Francis Ribeiro, Guilherme Fonseca, Heidi Dalton, Mehul Desai, Erik Osborn Hala Deeb, Antonio Arcadipane, Gennaro Martucci, Giovanna Panarello, Chiara Vitiello, Claudia Bianco, Giovanna Occhipinti, Matteo Rossetti, Raffaele Cuffaro, Sung-Min Cho, Glenn Whitman, Hiroaki Shimizu, Naoki Moriyama, Jae-Burm Kim, Nobuya Kitamura, Johannes Gebauer, Toshiki Yokoyama, Abdulrahman Al-Fares, Sarah Buabbas, Esam Alamad, Fatma Alawadhi, Kalthoum Alawadi, Hiro Tanaka, Satoru Hashimoto, Masaki Yamazaki, Tak-Hyuck Oh, Mark Epler, Cathleen Forney, Louise Kruse, Jared Feister, Joelle Williamson, Katherine Grobengieser, Eric Gnall, Sasha Golden, Mara Caroline, Timothy Shapiro, Colleen Karaj, Lisa Thome, Lynn Sher, Mark Vanderland, Mary Welch, Sherry McDermott, Matthew Brain, Sarah Mineall, Dai Kimura, Luca Brazzi, Gabriele Sales, Giorgia Montrucchio, Tawnya Ogston, Dave Nagpal, Karlee Fischer, Roberto Lorusso, Rajavardhan Rangappa, Sujin Rai, Argin Appu, Mariano Esperatti, Nora Angélica Fuentes, Maria Eugenia Gonzalez, Edmund G. Carton, Ayan Sen, Amanda Palacios, Deborah Rainey, Gordan Samoukoviv, Josie Campisi, Lucia Durham, Emily Neumann, Cassandra Seefeldt, Octavio Falcucci, Amanda Emmrich, Jennifer Guy, Carling Johns, Kelly Potzner, Catherine Zimmermann, Angelia Espinal, Nina Buchtele, Michael Schwameis, Andrea Korhnfehl, Roman Brock, Thomas Staudinger, Stephanie-Susanne, Stecher Michaela Barnikel, Sófia Antón, Alexandra Pawlikowski, Akram Zaaqoq, Lan Anh Galloway, Caitlin Merley, Marc Csete, Luisa Quesada, Isabela Saba, Daisuke Kasugai, Hiroaki Hiraiwa, Taku Tanaka, Eva Marwali, Yoel Purnama, Santi Rahayu Dewayanti, Ardiyan, Dafsah Arifa Juzar, Debby Siagian, Yih-Sharng Chen, Indrek Ratsep, Andra-Maris Post, Piret Sillaots, Anneli Krund, Merili-Helen Lehiste, Tanel Lepik, Frank Manetta, Effe Mihelis, Iam Claire Sarmiento, Mangala Narasimhan, Michael Varrone, Mamoru Komats, Julia Garcia-Diaz, Catherine Harmon, S. Veena Satyapriya, Amar Bhatt, Nahush A. Mokadam, Alberto Uribe, Alicia Gonzalez, Haixia Shi, Johnny McKeown, Joshua Pasek, Juan Fiorda, Marco Echeverria, Rita Moreno, Bishoy Zakhary, Marco Cavana, Alberto Cucino, Giuseppe Foti, Marco Giani, Benedetta Fumagalli, Valentina Castagna, Andrea Dell’Amore, Paolo Navalesi, Hoi-Ping Shum, Alain Vuysteke, Asad Usman, Andrew Acker, Benjamin Smood, Blake Mergler, Federico Sertic, Madhu Subramanian, Alexandra Sperry, Nicolas Rizer, Erlina Burhan, Menaldi Rasmin, Ernita Akmal, Faya Sitompul, Navy Lolong, Bhat Naivedh, Simon Erickson, Peter Barrett, David Dean, Julia Daugherty, Antonio Loforte, Irfan Khan, Mohammed Abraar Quraishi, Olivia DeSantis, Dominic So, Darshana Kandamby, Jose M. Mandei, Hans Natanael, Eka YudhaLantang, Anastasia Lantang, Surya Oto Wijaya, Anna Jung, George Ng, Wing Yiu Ng, Shu Fang, Alexis Tabah, Megan Ratcliffe, Maree Duroux, Shingo Adachi, Shota Nakao, Pablo Blanco, Ana Prieto, Jesús Sánchez, Meghan Nicholson, Warwick Butt, Alyssa Serratore, Carmel Delzoppo, Pierre Janin, Elizabeth Yarad, Richard Totaro, Jennifer Coles, Bambang Pujo, Robert Balk, Andy Vissing, Esha Kapania, James Hays, Samuel Fox, Garrett Yantosh, Pavel Mishin, Saptadi Yuliarto, Kohar Hari Santoso, Susanthy Djajalaksana, Arie Zainul Fatoni, Masahiro Fukuda, Keibun Liu, Paolo Pelosi, Denise Battaglini, Juan Fernando Masa Jiménez, Diego Bastos, Sérgio Gaião, Desy Rusmawatiningtyas, Young-Jae Cho, Su Hwan Lee, Tatsuya Kawasaki, Laveena Munshi, Pranya Sakiyalak, Prompak Nitayavardhana, Tamara Seitz, Rakesh Arora, David Kent, Daniel Marino, Swapnil Parwar, Andrew Cheng, Jennene Miller, Shigeki Fujitani, Naoki Shimizu, Jai Madhok, Clark Owyang, Hergen Buscher, Claire Reynolds, Olavi Maasikas, Aleksan Beljantsev, Vladislav Mihnovits, Takako Akimoto, Mariko Aizawa, Kanako Horibe, Ryota Onodera, Meredith Young, Timothy George, Kiran Shekar, Niki McGuinness, Lacey Irvine, Brigid Flynn, Tomoyuki Endo, Kazuhiro Sugiyama, Keiki Shimizu, Kathleen Exconde, Leslie Lussier, Gösta Lotz, Maximilian Malfertheiner, Lars Maier, Esther Dreier, Neurinda Permata Kusumastuti, Colin McCloskey, Al-Awwab Dabaliz, Tarek B Elshazly, Josiah Smith, Konstanty S. Szuldrzynski, Piotr Bielański, Keith Wille, Ken Kuljit, S. Parhar, Kirsten M. Fiest, Cassidy Codan, Anmol Shahid, Mohamed Fayed, Timothy Evans, Rebekah Garcia, Ashley Gutierrez, Tae Song, Rebecca Rose, Suzanne Bennett, Denise Richardson, Giles Peek, Lovkesh Arora, Kristina Rappapport, Kristina Rudolph, Zita Sibenaller, Lori Stout, Alicia Walter, Daniel Herr, Nazli Vedadi, Shaun Thompson, Julie Hoffman, Xiaonan Ying, Ryan Kennedy, Muhammed Elhadi, Matthew Griffee, Anna Ciullo, Yuri Kida, Ricard Ferrer Roca, JordI Riera, Sofia Contreras, Cynthia Alegre, Christy Kay, Irene Fischer, Elizabeth Renner, Hayato Taniguci, John Fraser, Jacky Suen, Adrian Barnett, Nicole White, Kristen Gibbons, Simon Forsyth, Amanda Corley, India Pearse, Samuel Hinton, Gabriella Abbate, Halah Hassan, Silver Heinsar, Varun A Karnik, Katrina Ki, Hollier F. O’Neill, Nchafatso Obonyo, Leticia Pretti Pimenta, Janice D. Reid, Kei Sato, Aapeli Vuorinen, Karin S. Wildi, Emily S. Wilson, Stephanie Yerkovich, James Lee, Daniel Plotkin, Barbara Wanjiru Citarella, Laura Merson, Emma Hartley, Bastian Lubis, Takanari Ikeyama, Balu Bhaskar, Jae-Seung Jung, Shay McGuinness, Glenn Eastwood, Sandra Rossi Marta, Fabio Guarracino, Stacy Gerle, Emily Coxon, Bruno Claro, Daniel Loverde, Namrata Patil, Vieri Parrini, Angela McBride, Kathryn Negaard, Angela Ratsch, Ahmad Abdelaziz, Juan David Uribe, Adriano Peris, Mark Sanders, Dominic Emerson, Muhammad Kamal, Pedro Povoa, Roland Francis, Ali Cherif, Sunimol Joseph, Matteo Di Nardo, Micheal Heard, Kimberly Kyle, Ray A Blackwell, Patrick Biston, Hye Won Jeong, Reanna Smith, Yogi Prawira, Arturo Huerta Garcia, Nahikari Salterain, Bart Meyns, Marsha Moreno, Rajat Walia, Amit Mehta, Annette Schweda, Moh Supriatna, Cenk Kirakli, Melissa Williams, Kyung Hoon Kim, Alexandra Assad, Estefania Giraldo, Wojtek Karolak, Martin Balik, Elizabeth Pocock, Evan Gajkowski, Kanamoto Masafumi, Nicholas Barrett, Yoshihiro Takeyama, Sunghoon Park, Faizan Amin, Fina Meilyana Andriyani, Serhii Sudakevych, Magdalena Vera, Rodrigo Cornejo, Patrícia Schwarz, Ana Carolina Mardini, Thais de Paula, Ary Serpa Neto, Andrea Villoldo, Alexandre Siciliano Colafranceschi, Alejandro Ubeda Iglesias, Juan Granjean, Lívia Maria Garcia Melro, Giovana Fioravante Romualdo, Diego Gaia, Helmgton Souza, Filomena Galas, Rafael Máñez Mendiluce, Alejandra Sosa, Ignacio Martinez, Hiroshi Kurosawa, Juan Salgado, Beate Hugi-Mayr, Eric Charbonneau, Vitor Salvatore Barzilai, Veronica Monteiro, Rodrigo Ribeiro de Souza, Michael Harper, Hiroyuki Suzuki, Celina Adams, Jorge Brieva, George Nyale, Faisal Saleem Eltatar, Jihan Fatani, Husam Baeissa, Ayman AL Masri, Ahmed Rabie, Mok Yee Hui, Masahiro Yamane, Hanna Jung, Ayorinde Mojisola Margaret, Newell Nacpil, Katja Ruck, Rhonda Bakken, Claire Jara, Tim Felton, Lorenzo Berra, Bobby Shah, Arpan Chakraborty, Monika Cardona, Gerry Capatos, Bindu Akkanti, Abiodun Orija, Harsh Jain, Asami Ito, Brahim Housni, Sennen Low, Koji Iihara, Joselito Chavez, Kollengode Ramanathan, Gustavo Zabert, Krubin Naidoo, Ian Seppelt, Marlice VanDyk, Sarah MacDonald, Randy McGregor, Teka Siebenaler, Hannah Flynn, Kristi Lofton, Toshiyuki Aokage, Kazuaki Shigemitsu, Andrea Moscatelli, Giuseppe Fiorentino, Matthias Baumgaertel, Serge Eddy Mba, Jana Assy, Amelya Hutahaean, Holly Roush, Kay A Sichting, Francesco Alessandri, Debra Burns, Gavin Salt, Carl P. Garabedian, Jonathan Millar, Malcolm Sim, Adrian Mattke, Danny McAuley, Jawad Tadili, Tim Frenzel, Yaron Bar-Lavie, Aaron Blandino Ortiz, Jackie Stone, Antony Attokaran, Michael Farquharson, Brij Patel, Derek Gunning, Kenneth Baillie, Pia Watson, Kenji Tamai, Gede Ketut Sajinadiyasa, Dyah Kanyawati, Marcello Salgado, Assad Sassine, Bhirowo Yudo, Scott McCaul, Bongjin Lee, Sang Min Lee, Arnon Afek, Yoshiaki Iwashita, Bambang Pujo Semedi, Jack Metiva, Nicole Van Belle, Ignacio Martin-Loeches, Lenny Ivatt, Chia Yew Woon, Hyun Mi Kang, Timothy Smith, Erskine James, Nawar Al-Rawas, Yudai Iwasaki, Kenny Chan King-Chung, Vadim Gudzenko, Fabio Taccone, Fajar Perdhana, Yoan Lamarche, Joao Miguel Ribeiro, Nikola Bradic, Klaartje Van den Bossche, Oude Lansink, Gurmeet Singh, Gerdy Debeuckelaere, Henry T. Stelfox, Cassia Yi, Jennifer Elia, Thomas Tribble, Shyam Shankar, Raj Padmanabhan, Bill Hallinan, Luca Paoletti, Yolanda Leyva, Tatuma Fykuda, Jenelle Badulak, Jillian Koch, Amy Hackman, Lisa Janowaik, Deb Hernandez, Jennifer Osofsky, Katia Donadello, Aizah Lawang, Josh Fine, and Benjamin Davidson

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Published
2024
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2. Patient-reported outcomes and neurotoxicity markers in patients treated with bispecific LV20.19 CAR T cell therapy

Author

Jennifer M. Knight, Aniko Szabo, Igli Arapi, Ruizhe Wu, Amanda Emmrich, Edward Hackett, Garrett Sauber, Sharon Yim, Bryon Johnson, Parameswaran Hari, Dina Schneider, Boro Dropulic, Rachel N. Cusatis, Steve W. Cole, Cecilia J. Hillard, and Nirav N. Shah

Subjects
Medicine
Abstract

Knight et al. assess short-term patient-reported outcomes (PROs) and markers of neurotoxicity in patients with leukaemia or lymphoma treated with LV20.19 CAR T cells. In this small trial cohort, the authors report improvements in mood following CAR T infusion and identify kynurenine pathway molecules as potential markers of mood and neurotoxicity.

Published
2022
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3. Assessment of 28-Day In-Hospital Mortality in Mechanically Ventilated Patients With Coronavirus Disease 2019: An International Cohort Study

Author

Gianluigi Li Bassi, MD, PhD, Jacky Y. Suen, BSc, PhD, Nicole White, PhD, Heidi J. Dalton, MD, MCCM, Jonathon Fanning, BSc, MBBS, PhD, FANZCA, FCICM, Amanda Corley, RN, Sally Shrapnel, MBBS, BMedSc, MSc, PhD, FRACGP, Samuel Hinton, PhD, Simon Forsyth, PhD, Rex Parsons, BSc, MMedStats, John G. Laffey, MD, Eddy Fan, MD, PhD, Robert Bartlett, MD, Daniel Brodie, MD, Aidan Burrell, MD, PhD, Davide Chiumello, MD, Alyaa Elhazmi, MD, Giacomo Grasselli, MD, Carol Hodgson, PT, PhD, Shingo Ichiba, MD, Carlos Luna, MD, Eva Marwali, MD, Laura Merson, Bsc, Srinivas Murthy, MD, Alistair Nichol, MD, PhD, Mauro Panigada, MD, Paolo Pelosi, MD, FERS, Antoni Torres, MD, PhD, FERS, Pauline Yeung Ng, MD, Mark Ogino, MD, John F. Fraser, MBChB, PhD, FRCP(Glas), FFARCSI, FRCA, FCICM, on behalf of the COVID-19 Critical Care Consortium, Tala Al-Dabbous, Huda Alfoudri, Mohammed Shamsah, Subbarao Elapavaluru, Ashley Berg, Christina Horn, Stephan Schroll, Jorge Velazco, Ludmyla Ploskanych, Wanda Fikes, Dan Meyer, Ashley Ehlers, Maysoon Shalabi-McGuire, Trent Witt, Lorenzo Grazioli, Luca Lorini, E. Wilson Grandin, Jose Nunez, Tiago Reyes, Diarmuid O’Briain, Stephanie Hunter, Mahesh Ramanan, Julia Affleck, Hemanth Hurkadli Veerendra, Sumeet Rai, Josie Russell-Brown, Mary Nourse, Mark Joseph, Brook Mitchell, Martha Tenzer, Carilion Clinic, Ryuzo Abe, Hwa Jin Cho, In Seok Jeong, Nicolas Brozzi, Omar Mehkri, Sudhir Krishnan, Abhijit Duggal, Stuart Houltham, Jerónimo Graf, Roderigo Diaz, Camila Delgado, Joyce González, Maria Soledad Sanchez, Diego Fernando Bautista Rincón, Angela Maria Marulanda Yanten, Melissa Bustamante Duque, Daniel Brodie, Desy Rusmawatiningtyas, Maria Callahan, M. Azhari Taufik, Elizabeth Yasmin Wardoyo, Margaretha Gunawan, Nurindah S Trisnaningrum, Vera Irawany, Muhammad Rayhan, Mauro Panigada, Antonia Pesenti, Alberto Zanella, Michela Leone, Giacomo Grasselli, Silvia Coppola, Sebastiano Colombo, Massimo Antonelli, Simone Carelli, Domenico L. Grieco, Motohiro Asaki, Kota Hoshino, Leonardo Salazar, Laura Duarte, John Laffey, Bairbre McNicholas, David Cosgrave, Joseph McCaffrey, Allison Bone, Yusuff Hakeem, James Winearls, Mandy Tallott, David Thomson, Christel Arnold-Day, Jerome Cupido, Zainap Fanie, Malcom Miller, Lisa Seymore, Dawid van Straaten, Ali Ait Hssain, Jeffrey Aliudin, Al-Reem Alqahtani, Khoulod Mohamed, Ahmed Mohamed, Darwin Tan, Joy Villanueva, Ahmed Zaqout, Ethan Kurtzman, Arben Ademi, Ana Dobrita, Khadija El Aoudi, Juliet Segura, Gezy Giwangkancana, Shinichiro Ohshimo, Koji Hoshino, Saito Hitoshi, Javier Osatnik, Anne Joosten, Antoni Torres, Minlan Yang, Ana Motos, Carlos Luna, Francisco Arancibia, Virginie Williams, Alexandre Noel, Nestor Luque, Trieu Huynh Trung, Sophie Yacoub, Marina Fantini, Ruth Noemi Jorge García, Enrique Chicote Alvarez, Anna Greti, Adrian Ceccato, Angel Sanchez, Ana Loza Vazquez, Ferran Roche-Campo, Diego Franch-Llasat, Divina Tuazon, Marcelo Amato, Luciana Cassimiro, Flavio Pola, Francis Ribeiro, Guilherme Fonseca, Heidi Dalton, Mehul Desai, Erik Osborn, Hala Deeb, Antonio Arcadipane, Gennaro Martucci, Giovanna Panarello, Chiara Vitiello, Claudia Bianco, Giovanna Occhipinti, Matteo Rossetti, Raffaele Cuffaro, Sung-Min Cho Johns, Hiroaki Shimizu, Naoki Moriyama, Jae-Burm Kim, Nobuya Kitamura, Alyaa Elhazmi, Abdullah Al-Hudaib, Johannes Gebauer, Toshiki Yokoyama, Abdulrahman Al-Fares, Sarah Buabbas, Esam Alamad, Fatma Alawadhi, Kalthoum Alawadi, Hiro Tanaka, Satoru Hashimoto, Masaki Yamazaki, Tak-Hyuck Oh, Mark Epler, Cathleen Forney, Louise Kruse, Jared Feister, Joelle Williamson, Katherine Grobengieser, Eric Gnall, Sasha Golden, Mara Caroline, Timothy Shapiro, Colleen Karaj, Lisa Thome, Lynn Sher, Mark Vanderland, Mary Welch, Sherry McDermott, Matthew Brain, Sarah Mineall, Dai Kimura, Luca Brazzi, Gabriele Sales, Tawnya Ogston, Dave Nagpal, Karlee Fischer, Roberto Lorusso, Mariano Esperatti, Edmund G. Carton, Ayan Sen, Amanda Palacios, Deborah Rainey, Gordan Samoukoviv, Josie Campisi, Emily Neumann, Cassandra Seefeldt, Lucia Durham, Octavio Falcucci, Amanda Emmrich, Jennifer Guy, Carling Johns, Nina Buchtele, Michael Schwameis, Stephanie-Susanne Stecher, Delila Singh, Michaela Barnikel, Lukas Arenz, Akram Zaaqoq, Lan Anh Galloway, Caitlin Merley, Marc Csete, Luisa Quesada, Isabela Saba, Daisuke Kasugai, Hiroaki Hiraiwa, Taku Tanaka, Eva Marwali, Yoel Purnama, Santi Rahayu Dewayanti, Ardiyan, Dafsah Arifa Juzar, Debby Siagian, Kita Jakarta, Yih-Sharng Chen, Mark Ogino, Indrek Ratsep, Getter Oigus, Kristo Erikson, Andra-Maris Post, Lauri Enneveer, Piret Sillaots, Frank Manetta, Effe Mihelis, Iam Claire Sarmiento, Mangala Narasimhan, Michael Varrone, Mamoru Komats, S. Veena Satyapriya, Amar Bhatt, Nahush A. Mokadam, Alberto Uribe, Alicia Gonzalez, Haixia Shi, Johnny McKeown, Joshua Pasek, Juan Fiorda, Marco Echeverria, Rita Moreno, Bishoy Zakhary, Marco Cavana, Alberto Cucino, Giuseppe Foti, Marco Giani, Vincenzo Russotto, Davide Chiumello, Valentina Castagna, Andrea Dell’Amore, Paolo Navalesi, Hoi-Ping Shum, Alain Vuysteke, Asad Usman, Andrew Acker, Benjamin Smood, Blake Mergler, Federico Sertic, Madhu Subramanian, Alexandra Sperry, Nicolas Rizer, Erlina Burhan, Menaldi Rasmin, Ernita Akmal, Faya Sitompul, Navy Lolong, Bhat Naivedh, Simon Erickson, Peter Barrett, David Dean, Julia Daugherty, Antonio Loforte, Irfan Khan, Mohammed Abraar Quraishi, Olivia DeSantis, Dominic So, Darshana Kandamby, Jose M. Mandei, Hans Natanael, Eka YudhaLantang, Anastasia Lantang, Surya Oto Wijaya, Anna Jung, George Ng, Wing Yiu Ng, Pauline Yeung Ng, Alexis Tabah, Megan Ratcliffe, Maree Duroux, Shingo Adachi, Shota Nakao, Pablo Blanco, Ana Prieto, Jesús Sánchez, Meghan Nicholson, Warwick Butt, Alyssa Serratore, Carmel Delzoppo, Pierre Janin, Elizabeth Yarad, Richard Totaro, Jennifer Coles, Bambang Pujo, Robert Balk, Andy Vissing, Esha Kapania, James Hays, Samuel Fox, Garrett Yantosh, Pavel Mishin, Saptadi Yuliarto, Kohar Hari Santoso, Susanthy Djajalaksana, Arie Zainul Fatoni, Masahiro Fukuda, Keibun Liu, Paolo Pelosi, Denise Battaglini, Diego Bastos, Sérgio Gaião, Jessica Buchner, Young-Jae Cho, Su Hwan Lee, Pranya Sakiyalak, Prompak Nitayavardhana, Tamara Seitz, Rakesh Arora, David Kent, Swapnil Parwar, Andrew Cheng, Jennene Miller, Shigeki Fujitani, Naoki Shimizu, Jai Madhok, Clark Owyang, Hergen Buscher, Claire Reynolds, Olavi Maasikas, Aleksan Beljantsev, Vladislav Mihnovits, Takako Akimoto, Mariko Aizawa, Kanako Horibe, Ryota Onodera, Carol Hodgson, Aidan Burrell, Meredith Young, Kiran Shekar, Niki McGuinness, Lacey Irvine, Brigid Flynn, Kazuhiro Sugiyama, Keiki Shimizu, Eddy Fan, Kathleen Exconde, Shingo Ichiba, Leslie Lussier, Gösta Lotz, Lars Maier, Esther Dreier, Neurinda Permata Kusumastuti, Colin McCloskey, Al-Awwab Dabaliz, Tarek B Elshazly, Josiah Smith, Konstanty S. Szuldrzynski, Piotr Bielański, Keith Wille, Srinivas Murthy, Ken Kuljit S. Parhar, Kirsten M. Fiest, Cassidy Codan, Anmol Shahid, Mohamed Fayed, Timothy Evans, Rebekah Garcia, Ashley Gutierrez, Tae Song, Rebecca Rose, Suzanne Bennett, Denise Richardson, Lovkesh Arora, Kristina Rappapport, Kristina Rudolph, Zita Sibenaller, Lori Stout, Alicia Walter, Daniel Herr, Nazli Vedadi, Robert Bartlett, Antonio Pesenti, Shaun Thompson, Lace Sindt, Sean Rajnic, Cale Ewald, Julie Hoffman, Matthew Griffee, Anna Ciullo, Yuri Kida, Ricard Ferrer Roca, JordI Riera, Sofia Contreras, Cynthia Alegre, Christy Kay, Irene Fischer, Elizabeth Renner, Hayato Taniguci, John Fraser, Gianluigi Li Bassi, Jacky Suen, Adrian Barnett, Nicole White, Kristen Gibbons, Simon Forsyth, Amanda Corley, India Pearse, Samuel Hinton, Gabriella Abbate, Halah Hassan, Silver Heinsar, Varun A Karnik, Katrina Ki, Hollier F. O’Neill, Nchafatso Obonyo, Janice D. Reid, Kei Sato, Aapeli Vuorinen, Karin S. Wildi, Emily S. Wood, Stephanie Yerkovich, James Lee, Daniel Plotkin, Laura Merson, Emma Hartley, Bastian Lubis, Takanari Ikeyama, Balu Bhaskar, Jae-Seung Jung, Shay McGuinness, Glenn Eastwood, Sandra Rossi Marta, Fabio Guarracino, Stacy Gerle, Emily Coxon, Bruno Claro, Gonzo Gonzalez-Stawinski, Daniel Loverde, Namrata Patil, Vieri Parrini, Angela McBride, Kathryn Negaard, Angela Ratsch, Ahmad Abdelaziz, Juan David Uribe, Adriano Peris, Mark Sanders, Dominic Emerson, Muhammad Kamal, Pedro Povoa, Roland Francis, Ali Cherif, Sunimol Joseph, Matteo Di Nardo, Micheal Heard, Kimberly Kyle, Ray A Blackwell, Michael Piagnerelli, Patrick Biston, Hye Won Jeong, Reanna Smith, Yogi Prawira, Giorgia Montrucchio, Nadeem Rahman, Vivek Kakar, Josefa Valenzuela Sarrazin, Arturo Huerta Garcia, Nahikari Salterain, Bart Meyns, Marsha Moreno, Rajat Walia, Amit Mehta, Annette Schweda, Moh Supriatna, Bhirowo Yudo, Cenk Kirakli, Melissa Williams, Kyung Hoon Kim, Alexandra Assad, Estefania Giraldo, Wojtek Karolak, Martin Balik, Elizabeth Pocock, Evan Gajkowski, Kanamoto Masafumi, Nicholas Barrett, Yoshihiro Takeyama, Sunghoon Park, Faizan Amin, Fina Meilyana Andriyani, Serhii Sudakevych, Magdalena Vera, Rodrigo Cornejo, Patrícia Schwarz, Ana Carolina Mardini, Ary Serpa Neto, Andrea Villoldo, Alexandre Siciliano Colafranceschi, Alejandro Ubeda, Juan Granjean, Lívia Maria Garcia Melro, Giovana Fioravante Romualdo, Diego Gaia, Helmgton Souza, Filomena Galas, Rafael Máñez Mendiluce, Alejandra Sosa, Ignacio Martinez, Hiroshi Kurosawa, Juan Salgado, Beate Hugi-Mayr, Eric Charbonneau, Vitor Salvatore Barzilai, Veronica Monteiro, Rodrigo Ribeiro de Souza, Michael Harper, Hiroyuki Suzuki, Celina Adams, Jorge Brieva, George Nyale, Faisal Saleem Eltatar, Jihan Fatani, Husam Baeissa, Ayman AL Masri, Ahmed Rabie, Mok Yee Hui, Masahiro Yamane, Hanna Jung, Ayorinde Mojisola, Margaret, Newell Nacpil, Katja Ruck, Rhonda Bakken, Claire Jara, Tim Felton, Lorenzo Berra, Bobby Shah, Arpan Chakraborty, Monika Cardona, Gerry Capatos, Bindu Akkanti, Abiodun Orija, Harsh Jain, Asami Ito, Brahim Housni, Sennen Low, Koji Iihara, Joselito Chavez, Kollengode Ramanathan, Gustavo Zabert, Krubin Naidoo, Ian Seppelt, Marlice VanDyk, Sarah MacDonald, Randy McGregor, Teka Siebenaler, Hannah Flynn, Julia Garcia-Diaz, Catherine Harmon, Kristi Lofton, Toshiyuki Aokage, Kazuaki Shigemitsu, Andrea Moscatelli, Giuseppe Fiorentino, Matthias Baumgaertel, Serge Eddy Mba, Jana Assy, Amelya Hutahaean, Holly Roush, Kay A Sichting, Francesco Alessandri, Debra Burns, Gavin Salt, Carl P. Garabedian, Jonathan Millar, Malcolm Sim, Adrian Mattke, Danny McAuley, Jawad Tadili, Tim Frenzel, Yaron Bar-Lavie, Aaron Blandino Ortiz, Jackie Stone, Antony Attokaran, Michael Farquharson, Brij Patel, Derek Gunning, Kenneth Baillie, Pia Watson, Kenji Tamai, Gede Ketut Sajinadiyasa, Dyah Kanyawati, Marcello Salgado, Assad Sassine, Scott McCaul, Bongjin Lee, Sang Min Lee, Arnon Afek, Yoshiaki Iwashita, Laveena Munshi, Bambang Pujo Semedi, Neurinda Permata, Kusumastuti, Jack Metiva, Nicole Van Belle, Daniel Marino, Ignacio Martin-Loeches, Lenny Ivatt, Chia Yew Woon, Hyun Mi Kang, Timothy Smith, Erskine James, Nawar Al-Rawas, Tomoyuki Endo, Yudai Iwasaki, Kenny Chan King-Chung, Vadim Gudzenko, Fabio Taccone, Fajar Perdhana, Yoan Lamarche, Joao Miguel Ribeiro, Nikola Bradic, Klaartje Van den Bossche, Oude Lansink, Gurmeet Singh, Gerdy Debeuckelaere, Henry T. Stelfox, Cassia Yi, Jennifer Elia, Shu Fang, Thomas Tribble, Shyam Shankar, Raj Padmanabhan, Bill Hallinan, Luca Paoletti, Yolanda Leyva, Tatuma Fykuda, Jenelle Badulak, Jillian Koch, Amy Hackman, Lisa Janowaik, Deb Hernandez, Jennifer Osofsky, Katia Donadello, Aizah Lawang, Josh Fine, Benjamin Davidson, and Andres Oswaldo Razo Vazquez

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

IMPORTANCE:. Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated. OBJECTIVES:. To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS:. Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021. MAIN OUTCOMES AND MEASURES:. Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality. RESULTS:. One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16–1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H2O increase; 95% CI, 0.67–0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15–1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11–1.34; p < 0.001), Paco2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19–2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8–14; p = 0.041), Pao2/Fio2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52–0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88–0.97; p = 0.003). CONCLUSIONS AND RELEVANCE:. This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.

Published
2021
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4. Biobehavioral Research and Hematopoietic Stem Cell Transplantation: Expert Review from the Biobehavioral Research Special Interest Group of the American Society for Transplantation and Cellular Therapy

Author

William A. Wood, Kelly E. Rentscher, Mallory Taylor, Heather S.L. Jim, Bronwen E. Shaw, Effie W. Petersdorf, Karen L. Syrjala, Erin S. Costanzo, Anna Barata, Anela Carrazana Yero, Keayra E. Morris, Debra Lynch Kelly, Amanda Emmrich, Jennifer M. Knight, Shahrukh K. Hashmi, Kathryn E. Flynn, and Linda J. Burns

Subjects
medicine.medical_specialty, medicine.medical_treatment, Cell- and Tissue-Based Therapy, Context (language use), Hematopoietic stem cell transplantation, Article, Cell therapy, Immune Reconstitution, Quality of life (healthcare), Survivorship curve, medicine, Immunology and Allergy, Intensive care medicine, Adverse effect, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Cell Biology, Hematology, Special Interest Group, United States, Public Opinion, Quality of Life, Molecular Medicine, business
Abstract

Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for many hematologic conditions. Despite advances in conditioning and supportive measures, however, there remain significant comorbidities that threaten survivorship. Adverse effects of stress-related biobehavioral processes—defined here as the interactions of behavioral, psychological, and socioenvironmental factors with biology—impact immune recovery and function and are particularly salient in the HCT context, given the importance of immune reconstitution for improved survivorship. However, biobehavioral processes have been underinvestigated in this vulnerable group compared with other cancer populations. Here the Biobehavioral Research Special Interest Group (SIG) of the American Society for Transplantation and Cellular Therapy provides an expert review to inform research directions explicating the biological correlates of behavioral symptoms and evaluate the impact of these on HCT outcomes. The goal of this expert review is to provide a foundation for advancing science that effectively integrates behavioral and biological processes to optimize quality of life and improve clinical outcomes for HCT recipients.

Published
2021

5. Automated assessment of breast margins in deep ultraviolet fluorescence images using texture analysis

Author

Tongtong Lu, Julie M. Jorns, Dong Hye Ye, Mollie Patton, Renee Fisher, Amanda Emmrich, Taly Gilat Schmidt, Tina Yen, and Bing Yu

Subjects
Article, Atomic and Molecular Physics, and Optics, Biotechnology
Abstract

Microscopy with ultraviolet surface excitation (MUSE) is increasingly studied for intraoperative assessment of tumor margins during breast-conserving surgery to reduce the re-excision rate. Here we report a two-step classification approach using texture analysis of MUSE images to automate the margin detection. A study dataset consisting of MUSE images from 66 human breast tissues was constructed for model training and validation. Features extracted using six texture analysis methods were investigated for tissue characterization, and a support vector machine was trained for binary classification of image patches within a full image based on selected feature subsets. A weighted majority voting strategy classified a sample as tumor or normal. Using the eight most predictive features ranked by the maximum relevance minimum redundancy and Laplacian scores methods has achieved a sample classification accuracy of 92.4% and 93.0%, respectively. Local binary pattern alone has achieved an accuracy of 90.3%.

Published
2022

6. Texture analysis of deep ultraviolet fluorescence images for intraoperative assessment of breast tumor margins

Author

Amanda Emmrich, Renee Fisher, Bing Yu, Dong Hye Ye, Tongtong Lu, Taly Gilat-Schmidt, Julie M. Jorns, Tina W.F. Yen, and Mollie Patton

Subjects
Materials science, Ultraviolet light emitting diodes, medicine, Image processing, Texture (crystalline), skin and connective tissue diseases, medicine.disease_cause, Ultraviolet fluorescence, Fluorescence, Normal breast, Ultraviolet, Breast tumor, Biomedical engineering
Abstract

Deep ultraviolet (DUV) excitation has generated high-resolution fluorescence images of fresh and unfixed breast tissues. We report that texture analysis of DUV images can potentially differentiate malignant samples from normal breast tissues.

Published
2021

7. Rapid assessment of breast tumor margins using deep ultraviolet fluorescence scanning microscopy

Author

Taly Gilat Schmidt, Julie M. Jorns, Bing Yu, Tina W.F. Yen, Todd Doehring, Amanda Emmrich, Renee Fisher, Tongtong Lu, Dong Hye Ye, and Mollie Patton

Subjects
Paper, Fluorescence-lifetime imaging microscopy, medicine.medical_treatment, Biomedical Engineering, ultraviolet light, Magnification, Breast Neoplasms, Mastectomy, Segmental, 01 natural sciences, 010309 optics, Biomaterials, Breast cancer, fluorescence imaging, 0103 physical sciences, Breast-conserving surgery, Fluorescence microscope, Ultraviolet light, Medicine, Humans, Breast, Image resolution, Microscopy, Microscopy, Confocal, business.industry, Lumpectomy, Margins of Excision, tumor margin, medicine.disease, Atomic and Molecular Physics, and Optics, Electronic, Optical and Magnetic Materials, Female, breast-conserving surgery, business, Nuclear medicine
Abstract

Significance: Re-excision rates for women with invasive breast cancer undergoing breast conserving surgery (or lumpectomy) have decreased in the past decade but remain substantial. This is mainly due to the inability to assess the entire surface of an excised lumpectomy specimen efficiently and accurately during surgery. Aim: The goal of this study was to develop a deep-ultraviolet scanning fluorescence microscope (DUV-FSM) that can be used to accurately and rapidly detect cancer cells on the surface of excised breast tissue. Approach: A DUV-FSM was used to image the surfaces of 47 (31 malignant and 16 normal/benign) fresh breast tissue samples stained in propidium iodide and eosin Y solutions. A set of fluorescence images were obtained from each sample using low magnification (4×) and fully automated scanning. The images were stitched to form a color image. Three nonmedical evaluators were trained to interpret and assess the fluorescence images. Nuclear–cytoplasm ratio (N/C) was calculated and used for tissue classification. Results: DUV-FSM images a breast sample with subcellular resolution at a speed of 1.0 min/cm2. Fluorescence images show excellent visual contrast in color, tissue texture, cell density, and shape between invasive carcinomas and their normal counterparts. Visual interpretation of fluorescence images by nonmedical evaluators was able to distinguish invasive carcinoma from normal samples with high sensitivity (97.62%) and specificity (92.86%). Using N/C alone was able to differentiate patch-level invasive carcinoma from normal breast tissues with reasonable sensitivity (81.5%) and specificity (78.5%). Conclusions: DUV-FSM achieved a good balance between imaging speed and spatial resolution with excellent contrast, which allows either visual or quantitative detection of invasive cancer cells on the surfaces of a breast surgical specimen.

Published
2020

8. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial

Author

James M Chamberlain, Jaideep Kapur, Shlomo Shinnar, Jordan Elm, Maija Holsti, Lynn Babcock, Alex Rogers, William Barsan, James Cloyd, Daniel Lowenstein, Thomas P Bleck, Robin Conwit, Caitlyn Meinzer, Hannah Cock, Nathan B Fountain, Ellen Underwood, Jason T Connor, Robert Silbergleit, Emily Gray, Sonya Gunter, Amy Fansler, Valerie Stevenson, Erin Bengelink, Deneil Harney, Mickie Speers, Joy Black, Natalie Fisher, Donna Harsh, Arthi Ramakrishnan, Lindsey Harris, Nia Bozeman, Aimee Spiteri, Yuko Palesch, Holly Tillman, Wenle Zhao, Qi Pauls, Chris Arnaud, Catherine R. Dillon, Jodie Riley, Teldon Alford, Cassidy Conner, Lisa Coles, Abhi Sathe, Scott Janis, Adam Hartman, Brandy Fureman, Eugen Trinka, David Treiman, David Wright, Jonathan Ratcliff, Alex Hall, Alaina Williams, Harold Simon, Nicholas Stanley, Roger Humphries, Theresa Mims, Joann Short, Elizabeth Jones, Misty Ottman, Nina Gentile, Derek Isenberg, Hannah Reimer, Vernon Sayoc Kalugdan, Claude Hemphill, Debbie Yi Madhok, Jeany Duncan, Dominica Randazzo, James Quinn, Anita Visweswaran, Rosen Mann, Opeolu Adeoye, Jason McMullan, Brandon Foreman, Sara Keegan, Michelle Biros, Brian Driver, Audrey Hendrickson, Jamie Stang, Christopher Lewandowski, Joseph Miller, Kaleem Chaudhry, Shannen Berry, Craig Warden, Rachel Blake, Jennifer NB Cook, Erin Sabolick, Antoine Selman, Katrina Kissman, Monica Moore, J. Stephen Huff, Lea Becker, Jan Claassen, Angela Velazquez, Cristina Falo, Zlatan Coralic, Jackie Grupp-Phelan, Jill Baren, Angela Ellison, Ashley Woodford, Ima Samba, Marlena Kittick, Ralph Riviello, John Massey, Lisa Bonacquisti, Steven Levine, Sergey Motov, Christian Fromm, Rukhsana Hossain, Antonios Likourezos, Illya Pushkar, Thomas Terndrup, Salman Khaliqdina, Michael Hill, Bjorn Peterson, Alexia Terwilliger, Joseph Holm, Kyra Wicklund, Sandi Wewerka, Robert Welch, Claire Pearson, Vijaya Arun Kumar, Farhan Ayaz, Saikat Bhuiyan, Valerie H. Mika, Lola Morgan, Floyd Jones, Lorraine Dishman, Thomas Henry, Ford Erickson, Abbey Staugaitis, Chloe Lawyer, Kathleen Miller, Clif Callaway, Alexandra Urban, Sara DiFiore, Peter Adams, Brian Baum, Jason Nomura, Barbara Davis, Tom Aufderheide, Amanda Emmrich, Melissa Mena, Jacob Labinski, Chinwe Ogedegbe, Diana McCarthy, Arelis Villot-Santiago, Joshua Goldstein, Eric S. Rosenthal, Abigail Cohen, Chen Mei Su, Greg Tirrell, Melissa Howell, Marissa Hendrickson, Dan Nerheim, Eric Jaton, Barbara Biney, Christopher Gibson, Erica Dahlmeier, Katherine (Lamond) Blackburn, Oluwarotimi (Tim) Vaughan-Ogunlusi, Shahriar Zehtabchi, Richard Sinert, Bryce Petty, Scott Youngquist, Margaret Carlson, Nadege Gilles, Sarah (Zelonis) Weingast, Barney Stern, Jennifer Hopp, Virginia Ganley, Joseph Ornato, Christopher Hogan, Alan Payne, Kate Shreve, Peter Dayan, Nathan Kuppermann, Kurt Denninghoff, Rachel Stanley, Richard Ruddy, E. Brooke Lerner, J. Michael Dean, Charles Casper, Lise Nigrovic, Walt Schalick, Doug Nelson, Bobbe Thomas, Pamela Okada, Amanda Lee, Natasha Truesdale, Steven Chan, Mhadhumithaa Naresh, Venita Robinson, Jieun Hwang, Kristi Carlston, Michael Dela Cruz, Toni Harbour, Reena Karki, Daniel M. Cohen, Amy Nowakowski, Cindy Lin, Erin Fisher Kenny, Dale Steele, Lisa H. Merck, Erin Ryan, Kristin Basso, Lesley (Wasilewski) D'Urso, Kathleen Brown, Gina Nauman, Matthew Ledda, Sean Gillen, Vanessa Grant, Cheryl Vance, Daniel K. Nishijima, Kyle Pimenta, Noelle Herzog, Jonathan Bennett, Christine Eisenhart, Danny Thomas, Duke Wagner, Robert W. Hickey, Rose Azrak, Daniel Rubalcava, Juan Mondragon, Victor Gonzalez, Maha Khalil, Kristina Hart, Sara Parker, Angela Lumba-Brown, Kim Quayle, Sri Chinta, Debra Robinson, Maria Kwok, Brooke Peery, Julie Ochs, and Leonor Suarez

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Levetiracetam, Adolescent, Status epilepticus, 030204 cardiovascular system & hematology, Article, law.invention, Young Adult, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Status Epilepticus, Randomized controlled trial, Double-Blind Method, Fosphenytoin, law, medicine, Humans, 030212 general & internal medicine, Young adult, Child, Stroke, Aged, Aged, 80 and over, Intention-to-treat analysis, Dose-Response Relationship, Drug, business.industry, Valproic Acid, Age Factors, Infant, General Medicine, Emergency department, Middle Aged, medicine.disease, Child, Preschool, Phenytoin, Female, Anticonvulsants, medicine.symptom, business, medicine.drug
Abstract

Summary Background Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups. Methods In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group ( 65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov , NCT01960075 . Findings Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged 65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41–62) of children, 44% (33–55) of adults, and 37% (19–59) of older adults; with fosphenytoin in 49% (38–61) of children, 46% (34–59) of adults, and 35% (17–59) of older adults; and with valproate in 52% (41–63) of children, 46% (34–58) of adults, and 47% (25–70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group. Interpretation Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. Funding National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Published
2020

9. Deep UV fluorescence scanning microscopy for breast tumor margin detection

Author

Renee Fisher, Dong Hye Ye, Mollie Patton, Bing Yu, Tongtong Lu, Amanda Emmrich, Taly Gilat-Schmidt, Todd Doehring, Tina W.F. Yen, and Julie M. Jorns

Subjects
Materials science, business.industry, Scanning electron microscope, medicine.medical_treatment, Lumpectomy, medicine.disease, Fluorescence, chemistry.chemical_compound, Breast cancer, chemistry, Invasive lobular carcinoma, Fluorescence microscope, Breast-conserving surgery, medicine, Propidium iodide, Nuclear medicine, business
Abstract

Breast cancer is the most commonly diagnosed cancer among women. Positive margin status after breast-conserving surgery (BCS) is a predictor of higher rates of local recurrence. Intraoperative margin detection helps to complete tumor excision at the first operation. A margin tool that is capable of imaging all six margins of large lumpectomy specimens with both high resolution and fast speed (within 20 min) is yet to be developed. Deep UV light allows simultaneous excitation of multiple fluorophores and generating surface fluorescence images. We have developed a deep UV fluorescence scanning microscope (DUV-FSM) for slide-free, high-resolution and rapid examination of tumor specimens during BCS. The DUV-FSM uses a deep UV LED for oblique back illumination of freshly excised breast tissues stained with propidium iodide and Eosin Y and motorized XY stages for mosaic scanning. Fluorescence images are captured by a color CCD camera. Both invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) images showed excellent contrast from that of the normal cells in color, tissue texture, and cell density and shapes. This contrast have been consistently observed in all samples (n = 20) we have imaged so far. Statistical analysis showed a significant difference (p

Published
2020

10. Rapid and High-resolution Imaging of Lumpectomy Margins Using Deep Ultraviolet Fluorescence Scanning Microscopy

Author

Tina W.F. Yen, Bing Yu, Julie M. Jorns, Taly Gilat-Schmidt, Renee Fisher, Mollie Patton, Tongtong Lu, Dong Hye Ye, Amanda Emmrich, and Todd Doehring

Subjects
Nuclear magnetic resonance, Materials science, medicine.medical_treatment, Lumpectomy, medicine, Ultraviolet fluorescence, High resolution imaging, Scanning microscopy
Abstract

Background: Re-excision rates for women with invasive breast cancer undergoing breast conserving surgery (BCS or lumpectomy) have decreased in the past decade but remain substantial. This is mainly due to the inability to efficiently and accurately assess the entire surface of an excised lumpectomy specimen during surgery. To address this problem, a deep-ultraviolet scanning fluorescence microscope (DUV-FSM) imaging system was developed and evaluated to determine whether it could accurately detect cancer cells on the surface of excised breast tissue.Methods: 37 (22 malignant and 15 normal/benign) fresh breast tissue samples of variable size were stained in propidium iodide and eosin Y solutions. A set of fluorescence images were obtained from one side of each sample using low magnification (4x) and fully automated scanning. The images from each sample were stitched to form a color image. Routine histopathology was performed on each sample. Three non-medical inspectors were trained to interpret and assess the fluorescence images. Patch-level nuclear-cytoplasm ratio (N/C) was calculated and ROC analysis with the Youden index was used for tissue classification. Results: DUV-FSM images a breast sample with subcellular resolution at a speed of 1.0 minute/cm2. DUV images show excellent visual contrast in color, tissue texture, cell density and shape between invasive lobular carcinoma (ILC), invasive ductal carcinoma (IDC) and their normal counterparts. Visual interpretation of DUV images was able to distinguish invasive carcinoma from normal/benign samples with high sensitivity (95%) and specificity (94.4%). Pairwise comparison of patch-level N/C identified significant differences (pConclusions: DUV-FSM is a simple device that can rapidly image large, unprocessed breast specimens with subcellular resolution and excellent contrast which allows either visual or quantitative detection of invasive cancer cells on the surfaces of a surgical specimen. This study supports further investigation into whether this technology can be used for intraoperative assessment of surgical margins during BCS procedures.

Published
2020

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