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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. 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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3. Risk factors for hemolysis with centrifugal pumps in pediatric extracorporeal membrane oxygenation: Is pump replacement an answer?

Author

Jian H Chu, Srivats Sarathy, Sonali Ramesh, Kristina Rudolph, Madhavan L Raghavan, and Aditya Badheka

Subjects
Advanced and Specialized Nursing, Radiology, Nuclear Medicine and imaging, General Medicine, Cardiology and Cardiovascular Medicine, Safety Research
Abstract

Introduction Hemolysis during pediatric extracorporeal membrane oxygenation (ECMO) is associated with increased risk for renal failure and mortality. Objectives We aim to describe risk factors for hemolysis in pediatric ECMO supported by centrifugal pumps. Methods We conducted an analysis of retrospective data collected at an academic children’s hospital from January 2017 to December 2019. Measurements and results Plasma-free hemoglobin (PFH) levels were measured daily, and hemolysis was defined as PFH>50 mg/dL. Of 46 ECMO runs over 528 ECMO days, hemolysis occurred in 23 (58%) patients over a total of 40 (8%) ECMO days. In multivariable logistic regression models, VA-ECMO (aOR=4.69, 95% CI: 1.01–21.83) and higher hemoglobin (aOR = 1.38, 95% CI: 1.06–1.81) were independently associated with hemolysis. There were also non-significant trends toward increased risk for hemolysis with higher rotational pump speed (aOR=2.39, 95% CI: 0.75–7.65), higher packed red blood cell transfusions (aOR=1.15, 95% CI: 0.99–1.34), and higher cryoprecipitate transfusions (aOR=2.01, 95% CI: 0.83–4.86). Isolated pump exchanges that were performed in 12 patients with hemolysis led to significant decreases in PFH levels within 24 h (89 vs 11 mg/dL, pConclusions Hemolysis is common in pediatric ECMO using centrifugal pumps. Avoidance of high pump speeds and conservative administration of blood products may help to mitigate the risk for hemolysis. Furthermore, pump exchange may be an effective first-line treatment for hemolysis.

Published
2022
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4. Venoarterial to venovenous extracorporeal life support conversion in pediatric acute respiratory distress syndrome

Author

Aditya Badheka, Yuki Nakamura, Marco Ricci, Kristina Rudolph, and Marcelo Auslender

Subjects
endocrine system, medicine.medical_specialty, Acute respiratory distress, 030204 cardiovascular system & hematology, Extracorporeal, Catheterization, Hemodynamic compromise, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, 030212 general & internal medicine, Child, Retrospective Studies, Advanced and Specialized Nursing, Respiratory Distress Syndrome, business.industry, Hemodynamics, General Medicine, Life support, Emergency medicine, Cardiology and Cardiovascular Medicine, business, Safety Research
Abstract

In patients with pediatric acute respiratory distress syndrome (PARDS) and hemodynamic compromise who need venoarterial (VA) extracorporeal life support (ECLS), we have adopted a strategy to promote early VA-to-venovenous (VV) conversion since 2018. A single-center retrospective review was performed of all 22 patients who underwent ECLS for PARDS from 2008 to 2019. Variables were analyzed to determine factors affecting initial cannulation mode and in-hospital mortality. Outcomes were compared between before and after 2018. Of the 22 patients, 9 patients underwent initial VA-support. Small patient size and severe cardiopulmonary compromise prior to ECLS favored initial VA- over VV-support. Lactate level and vasoactive inotrope score at 24 hours post-ECLS initiation predicted in-hospital mortality. After 2018, all five patients with initial VA-support were converted to VV-support at 4.4 ± 1.3 days post-ECLS initiation without complications. In-hospital mortality decreased after 2018 (3/9) compared with before (10/13) (p = 0.041) despite longer ECLS run time (723.4 ± 384.2 vs 286.5 ± 235.1 hours, p = 0.003). The number of ECLS-related complications per ECLS 1000 run hours decreased after 2018 (7.2 ± 4.2 vs 46.9 ± 66.5, p = 0.063). Our strategy to promote early VA-to-VV conversion may be worth further evaluation in larger cohort studies.

Published
2021
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5. Maintaining Mobility in a Patient Who Is Pregnant and Has COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Case Report

Author

Jennifer P Crumley, Alex Mark, Kristina Rudolph, Kevin C. Doerschug, and Anna Krupp

Subjects
Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Ventilators, Psychological intervention, Case Report, Physical Therapy, Sports Therapy and Rehabilitation, Walking, law.invention, 03 medical and health sciences, Early Mobilization, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Pregnancy, law, Acute care, medicine, Extracorporeal membrane oxygenation, Humans, 030212 general & internal medicine, Pregnancy Complications, Infectious, Intensive care medicine, Lung, Physical Therapy Modalities, Mechanical ventilation, business.industry, Acute Care, COVID-19, 030208 emergency & critical care medicine, medicine.disease, Intensive care unit, Life support, Female, AcademicSubjects/MED00110, business
Abstract

Objective Mobilization while receiving life support interventions, including mechanical ventilation and extracorporeal membrane oxygenation (ECMO), is a recommended intensive care unit (ICU) intervention to maintain physical function. The purpose of this case report is to describe a novel approach to implementing early mobility interventions for a patient who was pregnant and receiving ECMO while continuing necessary infectious disease precautions because of diagnosed coronavirus disease-19 (COVID-19). Methods A 27-year-old woman who was pregnant was admitted to the ICU with COVID-19 and rapidly developed acute respiratory failure requiring 9 days of ECMO support. After a physical therapist consultation, the patient was standing at the bedside by hospital day 5 and ambulating by hospital day 9. Results The patient safely participated in physical therapy during ICU admission and was discharged to home with outpatient physical therapy follow-up after 14 days of hospitalization. Conclusion Early mobility is feasible during ECMO with COVID-19, and active participation in physical therapy, including in-room ambulation, may facilitate discharge to home. Innovative strategies to facilitate routine activity in a patient who is critically ill with COVID-19 require an established and highly trained team with a focus on maintaining function. Impact Early mobility while intubated, on ECMO, and infected with COVID-19 is feasible while adhering to infectious disease precautions when it is performed by an experienced interdisciplinary team.

Published
2020
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6. Synthetic Approaches to Anti-Inflammatory Macrolactones of the Oxacyclododecindione Type

Author

Markus Rohr, Kristina Rudolph, Johannes Tauber, Till Opatz, and Gerhard Erkel

Subjects
chemistry.chemical_classification, Double bond, Stereochemistry, medicine.drug_class, Organic Chemistry, Hydroacylation, Total synthesis, Metathesis, Ring (chemistry), Anti-inflammatory, Ring-closing metathesis, chemistry, medicine, Physical and Theoretical Chemistry, Isomerization
Abstract

Various synthetic approaches to the oxacyclododecindione-type macrolactones, known for their potent anti-inflammatory activity, are presented. These include an attempted carbonylative ring closure, a hydroacylation route, and an approach by ring-closing metathesis and double bond isomerization, as well as a strategy including ring-closing metathesis/unsaturation. The last route allowed the preparation of a bioactive analogue of the recently described 14-deoxyoxacyclododecindione.

Published
2015
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7. Total synthesis and biological evaluation of the natural product (−)-cyclonerodiol, a new inhibitor of IL-4 signaling

Author

Jens Langhanki, Till Opatz, Gerhard Erkel, and Kristina Rudolph

Subjects
Acyclic Monoterpenes, Sesquiterpene, Biochemistry, Radical cyclization, Cell Line, chemistry.chemical_compound, Anti-Allergic Agents, Humans, Physical and Theoretical Chemistry, IC50, Interleukin 4, STAT6, Natural product, Organic Chemistry, Total synthesis, Asthma, chemistry, Cyclization, Immunology, Monoterpenes, Interleukin-4, Signal transduction, STAT6 Transcription Factor, Sesquiterpenes, Signal Transduction
Abstract

In a screening program of natural compounds from fungi, the known cyclopentanoid sesquiterpene (-)-cyclonerodiol was identified as a specific inhibitor of the IL-4 induced STAT6 signaling pathway (IC50 = 9.7 μM) which is required for the differentiation of naive CD4 T cells to T helper type 2 (Th2) lymphocytes. As many allergic conditions, including allergic asthma and atopic diseases, are driven by an excessive Th2 response, STAT6 is a promising target for the development of new therapeutics. The compound was synthesized in six steps from (-)-linalool using an epoxide radical cyclization as the key step.

Published
2014
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8. [Untitled]

Author

Harsh Kothari, Aditya Badheka, Shilpa Balikai, Jennifer P Crumley, and Kristina Rudolph

Subjects
Immune reconstitution inflammatory syndrome, business.industry, Immunology, medicine, Primary immunodeficiency, Critical Care and Intensive Care Medicine, medicine.disease, business
Published
2019
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9. [Untitled]

Author

Tricia Michna, Kristina Rudolph, Veerajalandhar Allareddy, Marco Ricci, Marcelo Auslender, Aditya Badheka, and Yuki Nakamura

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Shock (circulatory), medicine, Cardiology, medicine.symptom, Critical Care and Intensive Care Medicine, business
Published
2019
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10. ChemInform Abstract: Synthetic Approaches to Antiinflammatory Macrolactones of the Oxacyclododecindione Type

Author

Gerhard Erkel, Johannes Tauber, Markus Rohr, Till Opatz, and Kristina Rudolph

Subjects
chemistry.chemical_classification, Double bond, chemistry, Stereochemistry, Intramolecular force, Salt metathesis reaction, Oxacyclododecindione, Alkyne, General Medicine, Isomerization
Abstract

A variety of attempts to synthesize oxacyclododecindione macrolactones through carbonylative ring-closure, intramolecular alkyne hydroacyalation, and Ru-catalyzed double bond isomerization fails.

Published
2015
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11. Inhibition of TGF-β signaling by the fungal lactones (S)-curvularin, dehydrocurvularin, oxacyclododecindione and galiellalactone

Author

Kristina Rudolph, Gerhard Erkel, and Annegret Serwe

Subjects
Macrocyclic Compounds, Angiogenesis, medicine.medical_treatment, Immunology, Neovascularization, Physiologic, Breast Neoplasms, Electrophoretic Mobility Shift Assay, Smad2 Protein, Biology, Biochemistry, Lactones, Genes, Reporter, Transforming Growth Factor beta, Cell Line, Tumor, medicine, Immunology and Allergy, Humans, Smad3 Protein, Molecular Biology, Transcription factor, Cell Proliferation, Reporter gene, Matrigel, Dehydrocurvularin, Hematology, Curvularin, Hep G2 Cells, Cell biology, DNA-Binding Proteins, Cytokine, Cell culture, Zearalenone, Signal Transduction
Abstract

TGF-β is a multifunctional cytokine that regulates cell proliferation, differentiation, apoptosis and extracellular matrix production. Deregulation of TGF-β production or signaling plays a pivotal role in a variety of pathological processes such as cancer, metastasis, angiogenesis and fibrosis. Therefore, TGF-β inhibitors should be promising therapeutic agents for the suppression of cancer progression and metastasis as well as fibrotic disorders. In a screening program of natural compounds from fungi inhibiting the TGF-β dependent expression of a reporter gene in HepG2 cells, we found that the fungal lactones (S)-curvularin, dehydrocurvularin, oxacyclododecindione and galiellalactone inhibited the binding of the activated Smad2/3 transcription factors to the DNA and antagonized the cellular effects of TGF-β including reporter gene activation and expression of TGF-β induced genes in HepG2 and MDA-MB-231 cells. The most active compound oxacyclododecindione inhibited TGF-β dependent reporter activity with IC50-values of 190–217 nM. In an in vitro angiogenesis assay, the fungal lactones strongly decreased the formation of capillary-like tubules of MDA-MB-231 cells on Matrigel.

Published
2011

12. Inhibition of TGF-β signaling, vasculogenic mimicry and proinflammatory gene expression by isoxanthohumol

Author

Timm Anke, Gerhard Erkel, Kristina Rudolph, and Annegret Serwe

Subjects
Angiogenesis, Cell Survival, medicine.medical_treatment, Xanthones, Antineoplastic Agents, Biology, Proinflammatory cytokine, chemistry.chemical_compound, Transforming Growth Factor beta, Cell Line, Tumor, medicine, Humans, Pharmacology (medical), Vasculogenic mimicry, RNA, Messenger, Transcription factor, Janus Kinases, Pharmacology, Regulation of gene expression, Reporter gene, Isoxanthohumol, NF-kappa B, Cell biology, Gene Expression Regulation, Neoplastic, STAT Transcription Factors, Cytokine, Oncology, chemistry, Cytokines
Abstract

TGF-β is a multifunctional cytokine that regulates cell proliferation, differentiation, apoptosis and extracellular matrix production. Deregulation of TGF-β production or signaling has been associated with a variety of pathological processes such as cancer, metastasis, angiogenesis and fibrosis. Therefore, TGF-β signaling has emerged as an attractive target for the development of new cancer therapeutics. In a screening program of natural compounds from fungi inhibiting the TGF-β dependent expression of a reporter gene in HepG2 cells, we found that the flavone isoxanthohumol inhibited the binding of the activated Smad2/3 transcription factors to the DNA and antagonized the cellular effects of TGF-β including reporter gene activation and expression of TGF-β induced genes in HepG2 and MDA-MB-231 cells. In an in vitro angiogenesis assay, isoxanthohumol (56 μM) strongly decreased the formation of capillary-like tubules of MDA-MB-231 cells on Matrigel. In addition, we found that isoxanthohumol blocked IFN-γ, IL-4 and IL-6 dependent Jak/Stat signaling and strongly inhibited the induction of pro-inflammatory genes in MonoMac6 cells at the transcriptional level after LPS/TPA treatment.

Published
2010

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