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1. Surviving septic patients endotyped with a functional assay demonstrate active immune responses

Author: Adam D. Price, Ellen R. Becker, Evan L. Barrios, Monty B. Mazer, Patrick W. McGonagill, Christian B. Bergmann, Michael D. Goodman, Robert W. Gould, Mahil Rao, Valerie E. Polcz, Tamara A. Kucaba, Andrew H. Walton, Sydney Miles, Julie Xu, Muxuan Liang, Tyler J. Loftus, Philip A. Efron, Kenneth E. Remy, Scott C. Brakenridge, Vladimir P. Badovinac, Thomas S. Griffith, Lyle L. Moldawer, Richard S. Hotchkiss, and Charles C. Caldwell
Subjects: critical illness, late mortality, procalcitonin, IL-6, prediction modeling, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionSepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients.MethodsThis prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an ‘immunocompetent’, ‘immunosuppressed endotype’, and two ‘mixed’ endotypes.ResultsWhole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. ‘Immunocompetent’ endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the ‘immunosuppressed’ endotype. Similarly, ‘immunocompetent’ endotype patients on day 4 had a higher in-hospital survival compared to the ‘immunosuppressed’ endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality.ConclusionsIncreased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early ‘immunocompetent’ endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies.
Published: 2024
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2. Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic

Author: Anna M. Cervantes-Arslanian, MD, Chakradhar Venkata, MD, Pria Anand, MD, Joseph D. Burns, MD, Charlene J. Ong, MD, Allison M. LeMahieu, MS, Phillip J. Schulte, PhD, Tarun D. Singh, MD, Alejandro A. Rabinstein, MD, Neha Deo, BS, Vikas Bansal, MBBS, MPH, Karen Boman, BS, Juan Pablo Domecq Garces, MD, Donna Lee Armaignac, PhD, APRN, Amy B. Christie, MD, Roman R. Melamed, MD, Yasir Tarabichi, MD, MSCR, Sreekanth R. Cheruku, MD, MPH, Ashish K. Khanna, MD, FCCP, FCCM, FASA, Joshua L. Denson, MD, MS, Valerie M. Banner-Goodspeed, MPH, Harry L. Anderson, III, MD, FACS, FICS, FCCM, FCCP, FAIM, Ognjen Gajic, MD, MS, Vishakha K. Kumar, MD, MBA, Allan Walkey, MD, Rahul Kashyap, MD, MBA, on behalf of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Philippe Clevenbergh, Rolando Claure-Del Granado, Jose A. Mercado, Esdenka Vega-Terrazas, Maria F. Iturricha-Caceres, Ruben Garza, Eric Chu, Victoria Chan, Oscar Y Gavidia, Felipe Pachon, Yeimy A Sanchez, Danijel knežević, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Dimitrios Kantas, Vasileios Koulouras, Estela Pineda, Gabina María Reyes Guillen, Helin Archaga Soto, Ana Karen Vallecillo Lizardo, Csaba Kopitkó, Ágnes Bencze, István Méhész, Zsófia Gerendai,, Girish Vadgaonkar, Rekha Ediga, Shilpa Basety, Shwetha Dammareddy, Phani Sreeharsha Kasumalla, Smitha S. Segu, Tuhin Chakraborty, Epcebha Joyce, Sridhar Papani, Mahesh Kamuram, Mradul Kumar Daga, Munisha Agarwal, Ishan Rohtagi, Anusha Cherian, Sreejith Parameswaran, Magesh Parthiban, Phaneendra Doddaga, Neethi Chandra, Puneet Rijhwani, Ashish Jain, Aviral Gupta, Ram Mohan Jaiswal, Ambika Tyagi, Nimish Mathur, Madhav Prabhu, Vishal Jakati, Mukur Petrolwala, Bharat Ladva, Surapaneni Krishna Mohan, Ekambaram Jyothisree, Umamaheswara Raju, Janaki Manduva, Naresh Kolakani, Shreeja Sripathi, Sheetal Chaitanya, Kamlesh Kumar Agrawal, Vijendra Baghel, Kirti Kumar Patel, Nooshin Dalili, Mohsen Nafa, Wataru Matsuda, Reina Suzuki, Michihito Kyo, Shu Tahara, Mineji Hayakawa, Kunihiko Maekawa, Masamitsu Sanui, Sho Horikita, Yuki Itagaki, Akira Kodate, Yuki Takahashi, Koyo Moriki, Takuya Shiga, Yudai Iwasaki, Hidenobu Shigemitsu, Yuka Mishima, Nobuyuki Nosaka, Michio Nagashima, Abdulrahman Al-Fares, Rene Rodriguez-Gutierrez, Jose Gerardo Gonzalez-Gonzalez, Alejandro Salcido-Montenegro, Adrian Camacho-Ortiz, Mariana Janeth Hermosillo Ulloa, Fatimah Hassan-Hanga, Hadiza Galadanci, Abubakar Shehu Gezawa, Halima M. S. Kabara, Taiwo Gboluwaga Amole, Halima Kabir, Dalha Gwarzo Haliru, Abdullahi S Ibrahim, Muhammad Sohaib Asghar, Mashaal Syed, Syed Anosh Ali Naqvi, Igor Borisovich Zabolotskikh,, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Razan K Alamoudi, Hassan M. AlSharif, Sarah A. Almazwaghi, Mohammed S Elsakran, Mohamed A Aid, Mouaz A Darwich, Omnia M Hagag, Salah A Ali, Alona rocacorba, Kathrine Supeña, Efren Ray Juane, Jenalyn Medina, Jowany Baduria, Marwa Ridha Amer, Mohammed Abdullah, Bawazeer, Talal I. Dahhan, Eiad Kseibi, Abid Shahzad Butt, Syed Moazzum Khurshid, Muath Rabee, Mohammed Abujazar, Razan Alghunaim, Maal Abualkhair, Abeer Turki AlFirm, Yaseen M Arabi, Sheryl Ann Abdukahil, Mohammed A Almazyad, Mohammed I Alarifi, Jara M Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N Asfina, Kaltham M Aldossary, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Ana Andrijevic, Srdjan Gavrilovic, Vladimir Carapic, Bojan Kovacevic, Jovana Bojicic, Stevanovic Predrag, Dejan S Stojakov, Duska K Ignjatovic, Suzana C Bojic, Marina M Bobos, Irina B Nenadic, Milica S Zaric, Marko D Djuric, Vladimir R Djukic, Santiago Y. Teruel, Belen C. Martin, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Varsha P Gharpure, Usman Raheemi, Kenneth W. Dodd, Nicholas Goodmanson, Kathleen Hesse, Paige Bird, Chauncey Weinert, Nathan Schoenrade, Abdulrahman Altaher, Esmael Mayar, Matthew Aronson, Tyler Cooper, Monica Logan, Brianna Miner, Gisele Papo, Eric M. Siegal, Phyllis Runningen, Suzanne Barry, Christopher Woll, Gregory Wu, Erin Carrole, Kathryn Burke, Mustafa Mohammed, Roman R. Melamed, David M. Tierney, Love A. Patel, Vino S. Raj, Barite U. Dawud, Narayana Mazumder, Abbey Sidebottom, Alena M. Guenther, Benjamin D. Krehbiel, Nova J. Schmitz, Stacy L. Jepsen, Lynn Sipsey, Anna Schulte, Whitney Wunderlich, Cecely Hoyt, Abhijit A Raval, Andrea Franks, Katherine Irby, Ronald C. Sanders, Jr., Glenda Hefley, Jennifer M. Jarvis, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Stephen Capizzi, Bethany Alicie, Martha Green, Lori Crockarell, Amelia Drennan, Kathleen Dubuque, Tonya Fambrough, Nikole Gasaway, Briana Krantz, Peiman Nebi, Jan Orga, Margaret Serfass, Alina Simion, Kimberly Warren, Cassie Wheeler, CJ Woolman, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Andrew S. Moyer, George M. Verghese, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Jarrod M Mosier, Karen Lutrick, Beth Salvagio Campbell, Cathleen Wilson, Patrick Rivers, Jonathan Brinks, Mokenge Ndiva Mongoh, Boris Gilson, Donna Lee Armaignac, Don Parris, Maria Pilar Zuniga, Ilea Vargas, Viviana Boronat, Anneka Hutton, Navneet Kaur, Prashank Neupane, Nohemi Sadule-Rios, Lourdes M. Rojas, Aashish Neupane, Priscilla Rivera, Carlos Valle Carlos, Gregory Vincent, Mahesh Amin, Mary E Schelle, Amanda Steadham, Christopher M Howard, Cameron McBride, Jocelyn Abraham, Orlando Garner, Katherine Richards, Keegan Collins, Preethi Antony, Sindhu Mathew, Valerie C. Danesh, Gueorgui Dubrocq, Amber L. Davis, Marissa J Hammers, ill M. McGahey, Amanda C. Farris, Elisa Priest, Robyn Korsmo, Lorie Fares, Kathy Skiles, Susan M. Shor, Kenya Burns, Corrie A Dowell, Gabriela “Hope” Gonzales, Melody Flores, Lindsay Newman, Debora A Wilk, Jason Ettlinger, Jaccallene Bomar, Himani Darji, Alejandro Arroliga, Alejandro C Arroliga, Corrie A. Dowell, Gabriela Hope Conzales, Debora A. Wilk, Paras B. Khandhar, Elizabeth Kring, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Maj Andrew M. Hersh, CPT Stephanie L Wachs, Brittany S. Swigger, Stephanie L Wachs, Capt Lauren A. Sattler, Capt Michael N. Moulton, Kimberly Zammit, Patrick, J McGrath, William Loeffler, Maya, R. Chilbert, Aaron S. Miller, Edwin L. Anderson, Rosemary Nagy, Ravali R. Inja, Pooja A. Nawathe, Isabel Pedraza, Jennifer Tsing, Karen Carr, Anila Chaudhary, Kathleen Guglielmino, Raghavendra Tirupathi, Alymer Tang, Arshad Safi, Cindy Green, Jackie Newell, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Katja M. Gist, Imran A Sayed, John Brinton, Larisa Strom, Kathleen Chiotos, Allison M. Blatz, Giyoung Lee, Ryan H. Burnett, Guy I. Sydney, Danielle M. Traynor, Karissa Nauert, Annika Gonzalez, Mariel Bagley, Anita Santpurkar, Salim Surani, Joshua White, Aftab Khan, Rahul Dhahwal, Sreekanth Cheruku, Farzin Ahmed, Christopher Deonarine, Ashley Jones, Mohammad-Ali Shaikh, David Preston, Jeanette Chin, Vidula Vachharajani, Abhijit Duggal, Prabalini Rajendram, Omar Mehkri, Siddharth Dugar, Michelle Biehl, Gretchen Sacha, Stuart Houltham, Alexander King, Kiran Ashok, Bryan Poynter, Mary Beukemann, Richard Rice, Susan Gole, Valerie Shaner, Adarsh Conjeevaram, Michelle Ferrari, Narendrakumar Alappan, Steven Minear, Jaime Hernandez-Montfort, Syed Sohaib Nasim, Ravi Sunderkrishnan, Debasis Sahoo, Patrick S. Milligan, Sandeep K. Gupta, Joy M. Koglin, Regina Gibson, Lana Johnson, Felicia Preston, Crimson Scott, Bethany Nungester, Dana D Byrne, Christa A Schorr, Katie Grant, Katherine L Doktor, Maura C Porto, Olga Kaplan, James E. Siegler, III, Brian Schonewald, Ashley Woodford, Alan Tsai, Savina Reid, Kuntal Bhowmick, Saba Daneshpooy, Cyrus Mowdawalla, Trishna Akshay Dave, Wilhemina Kennedy, Connor Crudeli, Christopher Ferry, Long Nguyen, Sneha Modi, Niharika Padala, Pavan Jitendra Patel, Belle Lin, Lena Chatterjee, Jamie Qiuyun, Fan Mandi Liu, Rasagna Kota, Annesha Banerjee, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, Sidney Ontai, Brian Contreras, Uzoma Obinwanko, Nneka Amamasi, Amir Sharafi, Sarah Lee, Zahia Esber, Chetna Jinjvadia, Raquel R Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, Margit Kaufman, Gregg Lobel, Nisha Gandhi, Amr Abdelaty, Elizabeth Shaji, Kiana Lim, Juan Marte, Dani Ashley Sosa, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Nicholas Perkins, Prera J. Roth, Banu Sivaraj, Haley Fulton, Madison G Herin, Marissa Crum, Morgan E. Fretwell, Emily-Rose Zhou, Christine Waller, Kara Kallies, Jonean Thorsen, Alec Fitzsimmons, Haley Olsen, Heda R. Dapul, Sourabh Verma, Alan Salas, Ariel Daube, Michelle Korn, Michelle Ramirez, Logi Rajagopalan, Laura Santos, Héctor Collazo Santiago, Ricardo Alan Hernandez, Norma Smalls, Asher G Bercow, Mark Shlomovich, Christine Crandall, Sasko Stojanovski, Kristin Johnson, Kelly Michienzi, Steven Q. Davis, Valentina Jovic, Max Masuda, Amanda Hayes, Katharine Nault, Michael Smith, William Snow, Riley Liptak, Hannah Durant, Valerie Pendleton, Alay Nanavati, Risa Mrozowsk, Namrata Nag, Jeff Brauer, Ashwin Dharmadhikari, Sahib Singh, Franco Laghi, Ghania Naeem, Andrew Wang, Kevin Bliden, Amit Rout, Jaime Barnes, Martin Gesheff, Asha Thomas, Melbin Thomas, Alicia R. Liendo, Jovan Milosavljevic, Kenan Abbasi, Nicholas B. Burley, Nicole Rapista, Samuel Amankwah, Sanjay K Poude, Saroj Timilsina, Sauradeep Sarkar, Oluwasayo Akinyosoye, Shashi K. Yalamanchili, Sheena Moorthy, Sonia Sugumar, Jonathan Ford, Martin C. Taylor, Charlotte Dunderdale, Alyssa Henshaw, Mary K. Brunk, Jessica Hagy, Shehryar Masood, Sushrutha Sridhar, Yuk Ming Liu, Sarah Zavala, Esther Shim, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Christine C. Junia, Robert Lichtenberg, Hasrat Sidhu, Diana Espinoza, Shelden Rodrigues, Maria Jose Zabala, Daniela Goyes, Ammu Susheela, Buddhi Hatharaliyadda, Naveen Rameshkumar, Amulya Kasireddy, Genessis Maldonado, Lisseth Beltran, Akshata Chaugule, Hassan Khan, Namrata Patil, Ruhi Patil, Rodrigo Cartin-Ceba, Ayan Sen, Fahimeh Talaei, Rahul Kashyap, Juan Pablo Domecq, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Romil Singh, Diana J. Valencia Morales, Abigail T. La Nou, Marija Bogojevic, Simon Zec, Devang Sanghavi, Pramod Guru, Pablo Moreno Franco, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Nirmaljot Kaur, Abhisekh Giri, Mohammed Mustafa Hasan, Ashrita Donepudi, Syed Anjum Khan, Nitesh Kumar Jain, Thoyaja Koritala, Alexander Bastidas, Gabriela Orellana, Adriana Briceno Bierwirth, Eliana Milazzo, Juan Guillermo Sierra, Thao Dang, Rahul S Nanchal, Paul A Bergl, Jennifer L Peterson, Jessica Timmer, Kimberly Welker, Travis Yamanaka, Nicholas A. Barreras, Michael Markos, Anita Fareeduddin, Rohan Mehta, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Adriana C Briceno Bierwirth, Gabriela M Orellana, Gerardo Catalasan, Shohana Ahmed, Carlos F Matute, Ahmad Hamdan, Ivania Salinas, Genesis Del Nogal, Angel Tejada, Anna Eschler, Mary Hejna, Emily Lewandowski, Kristen Kusmierski, Clare Martin, Jen-Ting Chen, Aluko Hope, Zoe Tsagaris, Elise Ruen, Aram Hambardzumyan, Nasar A Siddiqi, Lesly Jurado, Lindsey Tincher, Carolyn Brown, Prithvi Sendi, Meghana Nadiger, Balagangadhar Totapally, Bhagat S. Aulakh, Sandeep Tripathi, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Neha Gupta, Brent R Brown, Tracy L Jones, Kassidy Malone, Lauren A Sinko, Amy B Harrell, Shonda C Ayers, Lisa M Settle, Taylor J Sears, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Roberta E. Redfern, Jessica Shoemaker, Jennifer Micham, Lynn Kenney, Gabriel Naimy, Victoria Schauf, Sara Utley, Holly Balcer, Kerry P. J. Pulver, Jennifer Yehle, Alicia Weeks, Terra Inman, Majdi Hamarshi, Jeannette Ploetz, Nick Bennett, Kyle Klindworth, Moustafa Younis, Adham Mohamed, Brian L. Delmonaco, Anthony Franklin, Mitchell Heath, Diane Barkas, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Shina Menon, John K McGuire, Deana Rich, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, John Lin, Cindy Terrill, Brock Montgomery, Sydney Reyes, Summer Reyes, Alex Plattner, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Umang Patel, Jordesha Hodge, Krunal Kumar Patel, Shivani Dalal, Himanshu Kavani, Sam Joseph, Michael A. Bernstein, Ian K. Goff, Matthew Naftilan, Amal Mathew, Deborah Williams, Sue Murdock, Maryanne Ducey, Kerianne Nelson, Jason Block, James Mitchel, Connor G O’Brien, Sylvan Cox, William Marx, Ioana Amzuta, Asad J. Choudhry, Mohammad T. Azam, Kristina L Carter, Michael A Olmos, Brittany M Parker, Julio Quintanilla, Tara A Craig, Brendon J Clough, Jeffrey T Jameson, Utpal S. Bhalala, Joshua Kuehne, Melinda Garcia, Morgan Beebe, Heather Herrera, Chris Fiack, Stephanie Guo, May Vawer, Beth Blackburn, Caleb Darby, Kristy Page, Amanda Brown, Jessie McAbee, Katherine A. Belden, Michael Baram, Devin M. Weber, Rosalie DePaola, Yuwei Xia, Hudson Carter, Aaron Tolley, Mary Barletta, Mark Steele, Laurie Kemble, Joshua L. Denson, A. Scott Gillet, Margo Brown, Rachael Stevens, Andrew Wetherbie, Kevin Tea, Mathew Moore, Abdurrahman Husain, Atul Malhotra, Qais Zawaydeh, Benjamin J Sines, Thomas J Bice, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Rajany V. Dy, Alfredo Iardino, Jill Sharma, Richard Czieki, Julia Christopher, Ryan Lacey, Marwan Mashina, Kushal Patel, Erica C. Bjornstad, Nancy M. Tofil, Scott House, Isabella Aldana, Nikhil K. Meena, Jose D. Caceres, Nikhil K Meena, Sarenthia M. Epps, Harmeen Goraya, Kelsey R. Besett, Ryan James, Lana Y. Abusalem, Akash K. Patel, Lana S Hasan, Dina Gomaa, Michael Goodman, Devin Wakefield, Anthony Spuzzillo, John O. Shinn II, Robert MacLaren, Azra Bihorac, Tezcan Ozrazgat Baslanti, George Omalay, Haleh Hashemighouchani, Julie S. Cupka, Matthew M Ruppert, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Usman Nazir, Garrett Rampon, Jake Riggle, Nathan Dismang, Vicki Montgomery, Janice Sullivan, Sarah Morris, Jennifer Nason, Ozan Akca, Rainer Lenhardt, Rodrigo S. Cavallazzi, Ann Jerde, Alexa Black, Allison Polidori, Haily Griffey, Justin Winkler, Thomas Brenzel, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Pauline Park, Andrew Admon, Sinan Hanna, Rishi Chanderraj, Maria Pliakas, Ann Wolski, Jennifer Cirino, Dima Dandachi, Hariharan Regunath, Maraya N. Camazine, Grant. E. Geiger, Abdoulie O. Njai, Baraa M. Saad, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Nita Khandelwal, T. Eoin West, Ellen S. Caldwell, Lara Lovelace-Macon, Navya Garimella, Denisse B. Dow, Sreekanth R. Cheruku, Catherine Chen, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Erin M. Wilfong, Kelsi Vela, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Patrick G. Lyons, Andrew P Michelson, Sara S. Haluf, Lauren M. Lynch, Nguyet M. Nguyen, Aaron Steinberg, Nicholas Braus, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, Samuel Chakola, Kevin Sheth, Abdalla Ammar, Mahmoud Ammar, Victor Torres Lopez, Charles Dela Cruz,, Akhil Khosla, and Samir Gautam
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: OBJECTIVES:. To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN:. Prospective observational study. SETTING:. One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS:. Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS:. None. RESULTS:. Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0–81.0 yr) versus 61 years (48.0–72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, –0.84, –1.34, and –0.84; p < 0.001). CONCLUSIONS:. Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.
Published: 2022
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3. Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19

Author: Shelsey W. Johnson, MD, Michael A. Garcia, MD, Emily K. Q. Sisson, MA, Christopher R. Sheldrick, PhD, Vishakha K. Kumar, MD, MBA, Karen Boman, BA, Scott Bolesta, PharmD, Vikas Bansal, MBBS, MPH, Amos Lal, MBBS, J. P. Domecq, MD, MS, Roman R. Melamed, MD, Amy B. Christie, MD, Abdurrahman Husain, MD, Santiago Yus, MBBS, Ognjen Gajic, MD, MSc, Rahul Kashyap, MBBS, MBA, Allan J. Walkey, MD, MSc, from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Oscar Y. Gavidia, Felipe Pachon, Yeimy A. Sanchez, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Wataru Matsuda, Reina Suzuki, Masamitsu Sanui, Sho Horikita, Yuki Itagaki, Akira Kodate, Yuki Takahashi, Koyo Moriki, Muhammad Sohaib, Asghar, Mashaal Syed, Syed Anosh, Ali Naqvi, Borisovich Zabolotskikh, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Mohammed A. Almazyad, Mohammed I. Alarifi, Jara M. Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N. Asfina, Kaltham M. Aldossary, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Predrag D. Stevanovic, Dejan S. Stojakov, Duska K. Ignjatovic, Suzana C. Bojic, Marina M. Bobos, Irina B. Nenadic, Milica S. Zaric, Marko D. Djuric, Vladimir R. Djukic, Santiago Yus, Belen C. Martin, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Roman R. Melamed, David M. Tierney, Love A. Patel, Vino S. Raj, Barite U. Dawud, Narayana Mazumder, Abbey Sidebottom, Alena M. Guenther, Benjamin D. Krehbiel, Nova J. Schmitz, Stacy L. Jepsen, Lynn Sipsey, Anna Schulte, Whitney Wunderlich, Cecely Hoyt, Kenneth W. Dodd, Nicholas Goodmanson, Kathleen Hesse, Paige Bird, Chauncey Weinert, Nathan Schoenrade, Abdulrahman Altaher, Esmael Mayar, Matthew Aronson, Tyler Cooper, Monica Logan, Brianna Miner, Gisele Papo, Abdulrahman Al-Fares, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Kimberly Zammit, Patrick J. McGrath, William Loeffler, Maya R. Chilbert, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Salim Surani, Joshua White, Aftab Khan, Rahul Dhahwal, Sreekanth Cheruku, Farzin Ahmed, Christopher Deonarine, Ashley Jones, Mohammad-Ali Shaikh, David Preston, Jeanette Chin, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, Raquel R. Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Katharine Nault, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Mayo Clinic Arizona, Rodrigo Cartin-Ceba, Ayan Sen, Amanda Palacios, Giyth M. Mahdi, Rahul Kashyap, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Juan Pablo Domecq, Romil Singh, Alex Niven, Mayo Clinic, Eau Claire, Abigail T. La Nou, Marija Bogojevic, Barbara Mullen, Devang Sanghavi, Pramod Guru, Pablo Moreno Franco, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Nirmaljot Kaur, Abhisekh Giri, Syed Anjum Khan, Nitesh Kumar Jain, Thoyaja Koritala, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Bhagat S. Aulakh, Sandeep Tripathi, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M. Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Neha Gupta, Tracy L. Jones, Shonda C. Ayers, Amy B. Harrell, Dr. Brent R. Brown, Abdurrahman Husain, Atul Malhotra, Qais Zawaydeh, Dragana Markotić, Ivana Bošnjak, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, and Samuel Chakola
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: OBJECTIVES:. To describe hospital variation in use of “guideline-based care” for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN:. Retrospective, observational study. SETTING:. The Society of Critical Care Medicine’s Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS:. Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS:. Hospital-level use of “guideline-based care” for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS:. Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in “guideline-based care.” A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1–3.4) for receipt of “guideline-based care” compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47–62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use “guideline-based care” quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3–1.9; p = 0.49). CONCLUSIONS:. During the first year of the COVID-19 pandemic, only half of patients received “guideline-based care” for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.
Published: 2022
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4. Variation in Use of Repurposed Medications Among Patients With Coronavirus Disease 2019. From The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 Registry Investigator Group

Author: Michael A. Garcia, MD, Shelsey W. Johnson, MD, Nicholas A. Bosch, MD, MSc, Emily K. Sisson, MA, Christopher R. Sheldrick, PhD, Vishakha K. Kumar, MD, MBA, Karen Boman, BS, Scott Bolesta, PharmD, Vikas Bansal, MBBS, MPH, Neha Deo, BS, J. P. Domecq, MD, Amos Lal, MD, Amy B. Christie, MD, Valerie M. Banner-Goodspeed, MPH, Devang Sanghavi, MD, MHA, Girish Vadgaonkar, MBBS, Ognjen Gajic, MD, MSc, Rahul Kashyap, MBBS, MBA, Allan J. Walkey, MD, MSc, for the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study Investigators, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Philippe Clevenbergh, Dragana Markotić, Ivana Bošnjak, Ruben Garza, Eric Chu, Victoria Chan, Oscar Y Gavidia, Felipe Pachon, Yeimy A Sanchez, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Jose Luis Ramos Coello, Guillermo Perez, Ana Karen Vallecillo Lizardo, Gabina María Reyes Guillen, Helin Archaga Soto, Smitha S. Segu, Tuhin Chakraborty, Epcebha Joyce, Girish Vadgaonkar, Rekha Ediga, Shilpa Basety, Shwetha Dammareddy, Phani Sreeharsha Kasumalla, Umamaheswara Raju, Janaki Manduva, Naresh Kolakani, Shreeja Sripathi, Sheetal Chaitanya, Mradul Kumar Daga, Munisha Agarwal, Ishan Rohtagi, Sridhar Papani, Mahesh Kamuram, Kamlesh Kumar Agrawal, Vijendra Baghel, Kirti Kumar Patel, Surapaneni Krishna Mohan, Ekambaram Jyothisree, Wataru Matsuda, Reina Suzuki, Michihito Kyo, Yuki Itagaki, Akira Kodate, Yuki Takahashi, Koyo Moriki, Fatimah Hassan-Hanga, Hadiza Galadanci, Abubakar Shehu Gezawa, Halima M. S. Kabara, Taiwo Gboluwaga Amole, Halima Kabir, Dalha Gwarzo Haliru, Abdullahi S Ibrahim, Muhammad Sohaib Asghar, Mashaal Syed, Syed Anosh Ali Naqvi, Igor Borisovich Zabolotskikh, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Mohammed A Almazyad, Mohammed I Alarifi, Jara M Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N Asfina, Kaltham M Aldossary, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Bojan Kovacevic, Jovana Bojicic, Predrag D Stevanovic, Dejan S Stojakov, Duska K Ignjatovic, Suzana C Bojic, Marina M Bobos, Irina B Nenadic, Milica S Zaric, Marko D Djuric, Vladimir R Djukic, Santiago Y. Teruel, Belen C. Martin, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Abhijit A Raval, Andrea Franks, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Stephen Capizzi, Bethany Alicie, Martha Green, Lori Crockarell, Amelia Drennan, Kathleen Dubuque, Tonya Fambrough, Nikole Gasaway, Briana Krantz, Peiman Nebi, Jan Orga, Margaret Serfass, Alina Simion, Kimberly Warren, Cassie Wheeler, CJ Woolman, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Andrew S. Moyer, George M. Verghese, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Donna Lee Armaignac, Don Parris, Maria Pilar Zuniga, Ilea Vargas, Viviana Boronat, Anneka Hutton, Navneet Kaur, Prashank Neupane, Nohemi Sadule-Rios, Lourdes M. Rojas, Aashish Neupane, Priscilla Rivera, Carlos Valle Carlos, Gregory Vincent, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Kimberly Zammit, Patrick, J McGrath, William Loeffler, Maya, R Chilbert, Raghavendra Tirupathi, Alymer Tang, Arshad Safi, Cindy Green, Jackie Newell, Katja M. Gist, Imran A Sayed, John Brinton, Larisa Strom, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Norma Smalls, Michael Smith, William Snow, Riley Liptak, Hannah Durant, Valerie Pendleton, Alay Nanavati, Risa Mrozowsk, Yuk Ming Liu, Sarah Zavala, Esther Shim, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Christine C. Junia, Robert Lichtenberg, Hasrat Sidhu, Diana Espinoza, Shelden Rodrigues, Maria Jose Zabala, Daniela Goyes, Ammu Susheela, Buddhi Hatharaliyadda, Naveen Rameshkumar, Amulya Kasireddy, Genessis Maldonado, Lisseth Beltran, Akshata Chaugule, Hassan Khan, Rodrigo Cartin-Ceba, Ayan Sen, Amanda Palacios, Giyth M. Mahdi, Rahul Kashyap, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Juan Pablo Domecq, Romil Singh, Alex Niven, Abigail La Nou, Marija Bogojevic, Barbara Mullen, Devang Sanghavi, Pablo Moreno Franco, Pramod Guru, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu, Lee Mateus, Siva Naga Yarrarapu, Nirmaljot Kaur, Abhisekh Giri, Syed Anjum Khan, Nitesh Kumar Jain, Thoyaja Koritala, Jessica Timmer, Kimberly Welker, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Anna Eschler, Mary Hejna, Emily Lewandowski, Kristen Kusmierski, Clare Martin, Bhagat S. Aulakh, Sandeep Tripathi, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Brian L. Delmonaco, Anthony Franklin, Mitchell Heath, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Paul K Mohabir, Connor G O’Brien, Komal Dasani, Neha Gupta, Tracy L Jones, Shonda C Ayers, Amy B Harrell, Brent R Brown, Megan Edwards, Caleb Darby, Kristy Page, Amanda Brown, Jessie McAbee, Katherine A. Belden, Michael Baram, Devin M. Weber, Rosalie DePaola, Yuwei Xia, Hudson Carter, Aaron Tolley, Mary Barletta, Mary Ferranti, Benjamin J Sines, Thomas J Bice, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Usman Nazir, Garrett Rampon, Jake Riggle, Nathan Dismang, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Dima Dandachi, Hariharan Regunath, Maraya N. Camazine, Grant. E. Geiger, Abdoulie O. Njai, Baraa M. Saad, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, Samuel Chakola, Kevin Sheth, Abdalla Ammar, Mahmoud Ammar, Victor Torres Lopez, Charles Dela Cruz, Akhil Khosla, and Samir Gautam
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: IMPORTANCE:. At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES:. To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS:. Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES:. Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS:. Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40–4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23–6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01–0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34–0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01–1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE:. Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.
Published: 2021
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5. Risk Factors for Critical Coronavirus Disease 2019 and Mortality in Hospitalized Young Adults: An Analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Coronavirus Disease 2019 Registry

Author: Sandeep Tripathi, MD, MS, Imran A. Sayed, MD, Heda Dapul, MD, Jeremy S. McGarvey, MS, Jennifer A. Bandy, RN, Karen Boman, BS, Vishakha K. Kumar, MD, MBA, Vikas Bansal, MBBS, MPH, Lynn Retford, CAE, Sreekanth Cheruku, MD, MPH, Margit Kaufman, MD, FASA, Smith F. Heavner, MS, RN, Valerie C. Danesh, PhD, RN, Catherine A. St. Hill, DVM, PhD, Ashish K. Khanna, MD, Utpal Bhalala, MD, Rahul Kashyap, MBBS, MBA, Ognjen Gajic, MD, MS, Allan J. Walkey, MD, MS, Katja M. Gist, DO, MSc, for The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Philippe Clevenbergh, Rolando Claure-Del Granado, Jose A. Mercado, Esdenka Vega-Terrazas, Maria F. Iturricha-Caceres, Ruben Garza, Eric Chu, Victoria Chan, Oscar Y Gavidia, Felipe Pachon, Yeimy A Sanchez, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Sierra-Hoffman, Fernando Valerio, Oscar Diaz, Jose Luis Ramos Coello, Guillermo Perez, Ana Karen Vallecillo Lizardo, Gabina María Reyes Guillen, Helin Archaga Soto, Mradul Kumar Daga, Munisha Agarwal, Ishan Rohtagi, Anusha Cherian, Sreejith Parameswaran, Magesh Parthiban, Menu Priya A., Girish Vadgaonkar, Rekha Ediga, Shilpa Basety, Shwetha Dammareddy, Phani Sreeharsha Kasumalla, Sridhar Papani, Mahesh Kamuram, Smitha S. Segu, Tuhin Chakraborty, Epcebha Joyce, Umamaheswara Raju, Janaki Manduva, Naresh Kolakani, Shreeja Sripathi, Sheetal Chaitanya, Surapaneni Krishna Mohan, Ekambaram Jyothisree, Kamlesh Kumar Agrawal, Vijendra Baghel, Kirti Kumar Patel, Nooshin Dalili, Mohsen Nafa, Sandeep Tripathi, Yuki Itagaki, Akira Kodate, Reina Suzuki, Yuki Takahashi, Koyo Moriki, Michihito Kyo, Masamitsu Sanui, Sho Horikita, Wataru Matsuda, Shu Tahara, Mineji Hayakawa, Kunihiko Maekawa, Takuya Shiga, Yudai Iwasaki, Abdulrahman AlFares, Rene Rodriguez-Gutierrez, Jose Gerardo Gonzalez-Gonzalez, Alejandro Salcido-Montenegro, Adrian Camacho-Ortiz, Fatimah Hassan-Hanga, Hadiza Galadanci, Abubakar Shehu Gezawa, Halima M. S. Kabara, Taiwo Gboluwaga Amole, Halima Kabir, Dalha Gwarzo, Haliru, Abdullahi S Ibrahim, Muhammad Sohaib Asghar, Mashaal Syed, Syed Anosh Ali Naqvi, Igor Borisovich Zabolotskikh, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Marwa Ridha Amer, Mohammed Abdullah Bawazeer, Talal I. Dahhan, Eiad Kseibi, Abid Shahzad Butt, Syed Moazzum Khurshid, Muath Rabee, Mohammed Abujazar, Razan Alghunaim, Maal Abualkhair, Abeer Turki AlFirm, Razan K Alamoudi, Hassan M. AlSharif, Sarah A. Almazwaghi, Mohammed S Elsakran, Mohamed A Aid, Mouaz A Darwich, Omnia M Hagag, Salah A Ali, Alona rocacorba, Kathrine Supeña, Efren Ray Juane, Jenalyn Medina, Jowany Baduria, Mohammed A Almazyad, Mohammed I Alarifi, Jara M Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N Asfina, Kaltham M Aldossary, Predrag D Stevanovic, Dejan S Stojakov, Duska K Ignjatovic, Suzana C Bojic, Marina M Bobos, Irina B Nenadic, Milica S Zaric, Marko D Djuric, Vladimir R Djukic, Bojan Kovacevic, Jovana Bojicic, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Santiago Y. Teruel, Belen C. Martin, Himat Sulaimonov, Firuza Khudonazarova, Nabi Bakhtibekov, Nekruz Jamshedov, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Varsha P Gharpure, Usman Raheemi, Kenneth W. Dodd, Nicholas Goodmanson, Kathleen Hesse, Paige Bird, Chauncey Weinert, Nathan Schoenrade, Abdulrahman Altaher, Esmael Mayar, Matthew Aronson, Tyler Cooper, Monica Logan, Brianna Miner, Gisele Papo, Eric M. Siegal, Phyllis Runningen, Catherine A. St. Hill, Roman R. Melamed, David M. Tierney, Love A. Patel, Vino S. Raj, Barite U. Dawud, Narayana Mazumder, Abbey Sidebottom, Alena M. Guenther, Benjamin D. Krehbiel, Nova J. Schmitz, Stacy L. Jepsen, Abhijit A Raval, Andrea Franks, Katherine Irby, Ronald C. Sanders, Jr., Glenda Hefley, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Stephen Capizzi, Bethany Alicie, Martha Green, Lori Crockarell, Amelia Drennan, Kathleen Dubuque, Tonya Fambrough, Nikole Gasaway, Briana Krantz, Peiman Nebi, Jan Orga, Margaret Serfass, Alina Simion, Kimberly Warren, Cassie Wheeler, CJ Woolman, Andrew S. Moyer, George M. Verghese, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Jarrod M Mosier, Karen Lutrick, Beth Salvagio Campbell, Cathleen Wilson, Patrick Rivers, Jonathan Brinks, Mokenge Ndiva Mongoh, Boris Gilson, Donna Lee Armaignac, Don Parris, Maria Pilar Zuniga, Ilea Vargas, Viviana Boronat, Anneka Hutton, Navneet Kaur, Prashank Neupane, Nohemi Sadule-Rios, Lourdes M. Rojas, Aashish Neupane, Priscilla Rivera, Carlos Valle Carlos, Gregory Vincent, Mahesh Amin, Mary E Schelle, Amanda Steadham, Christopher M Howard, Cameron McBride, Jocelyn Abraham, Orlando Garner, Katherine Richards, Keegan Collins, Preethi Antony, Sindhu Mathew, Valerie C. Danesh, Gueorgui Dubrocq, Amber L. Davis, Marissa J Hammers, ill M. McGahey, Amanda C. Farris, Elisa Priest, Robyn Korsmo, Lorie Fares, Kathy Skiles, Susan M. Shor, Kenya Burns, Corrie A Dowell, Melody Flores, Lindsay Newman, Debora A Wilk, Jason Ettlinger, Jaccallene Bomar, Himani Darji, Alejandro Arroliga, Alejandro C Arroliga, Corrie A. Dowell, Gabriela Hope Conzales, Debora A. Wilk, Paras B. Khandhar, Elizabeth Kring, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Andrew M. Hersh, Stephanie L Wachs, Brittany S. Swigger, Lauren A. Sattler, Michael N. Moulton, Kimberly Zammit, J Patrick, William McGrath, Maya Loeffler, R Chilbert, Aaron S. Miller, Edwin L. Anderson, Rosemary Nagy, Ravali R. Inja, Raghavendra Tirupathi, Alymer Tang, Arshad Safi, Cindy Green, Jackie Newell, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Katja M. Gist, Imran A Sayed, John Brinton, Larisa Strom, Kathleen Chiotos, Allison M. Blatz, Giyoung Lee, Ryan H. Burnett, Guy I. Sydney, Danielle M. Traynor, Karissa Nauert, Annika Gonzalez, Mariel Bagley, Anita Santpurkar, Salim Surani, Joshua White, Aftab Khan, Rahul Dhahwal, Sreekanth Cheruku, Farzin Ahmed, Christopher Deonarine, Ashley Jones, Mohammad-Ali Shaikh, David Preston, Jeanette Chin, Vidula Vachharajani, Abhijit Duggal, Prabalini Rajendram, Omar Mehkri, Siddharth Dugar, Michelle Biehl, Gretchen Sacha, Stuart Houltham, Alexander King, Kiran Ashok, Bryan Poynter, Mary Beukemann, Richard Rice, Susan Gole, Valerie Shaner, Adarsh Conjeevaram, Michelle Ferrari, Narendrakumar Alappan, Steven Minear, Jaime Hernandez-Montfort, Syed Sohaib Nasim, Ravi Sunderkrishnan, Debasis Sahoo, Patrick S. Milligan, Sandeep K. Gupta, Joy M. Koglin, Regina Gibson, Lana Johnson, Felicia Preston, Crimson Scott, Bethany Nungester, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, Sidney Ontai, Brian Contreras, Uzoma Obinwanko, Nneka Amamasi, Amir Sharafi, Sarah Lee, Zahia Esber, Chetna Jinjvadia, Kimberly Welker, Francis M. Maguire, Jessica Timmer, Raquel R Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, Margit Kaufman, Gregg Lobel, Nisha Gandhi, Amr Abdelaty, Elizabeth Shaji, Kiana Lim, Juan Marte, Dani Ashley Sosa, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Smith F. Heavner-Sullivan, Prera J. Roth, Banu Sivaraj, Haley Fulton, Madison G Herin, Marissa Crum, Morgan E. Fretwell, Emily-Rose Zhou, Christine Waller, Kara Kallies, Jonean Thorsen, Alec Fitzsimmons, Haley Olsen, Heda R. Dapul, Sourabh Verma, Alan Salas, Ariel Daube, Michelle Korn, Michelle Ramirez, Logi Rajagopalan, Laura Santos, Orma Smalls, Atul Malhotra, Abdurrahman Husain, Qais Zawaydeh, J.H. Steuernagle, Steven Q. Davis, Valentina Jovic, Max Masuda, Amanda Hayes, Katharine Nault, Michael Smith, William Snow, Riley Liptak, Hannah Durant, Valerie Pendleton, Alay Nanavati, Risa Mrozowsk, LiManoj K Gupta, Franscene E. Oulds, Akshay Nandavar, Yuk Ming Liu, Sarah Zavala, Esther Shim, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Christine C. Junia, Robert Lichtenberg, Hasrat Sidhu, Diana Espinoza, Shelden Rodrigues, Maria Jose Zabala, Daniela Goyes, Ammu Susheela, Buddhi Hatharaliyadda, Naveen Rameshkumar, Amulya Kasireddy, Genessis Maldonado, Lisseth Beltran, Akshata Chaugule, Hassan Khan, Namrata Patil, Ruhi Patil, Rodrigo Cartin-Ceba, Ayan Sen, Amanda Palacios, Giyth M. Mahdi, Rahul Kashyap, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Cory J. Kudrna, Juan Pablo Domecq Garces, Abigail T. La Nou, Marija Bogojevic, Devang Sanghavi, Pramod Guru, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Syed Anjum Khan, Juan Pablo Domecq, Nitesh Kumar Jain, Thoyaja Koritala, Alexander Bastidas, Gabriela Orellana, Adriana Briceno Bierwirth, Eliana Milazzo, Juan Guillermo Sierra, Thao Dang, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Rahul S Nanchal, Paul A Bergl, Jennifer L Peterson, Travis Yamanaka, Nicholas A. Barreras, Michael Markos, Anita Fareeduddin, Rohan Mehta, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Adriana C Briceno Bierwirth, Gabriela M Orellana, Gerardo Catalasan, Shohana Ahmed, Carlos F Matute, Ahmad Hamdan, Ivania Salinas, Genesis Del Nogal, Angel Tejada, Anna Eschler, Mary Hejna, Emily Lewandowski, Kristen Kusmierski, Clare Martin, Jen-Ting Chen, Aluko Hope, Zoe Tsagaris, Elise Ruen, Aram Hambardzumyan, Prithvi Sendi, Meghana Nadiger, Balagangadhar Totapally, Bhagat S. Aulakh, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Roberta E. Redfern, Jessica Shoemaker, Jennifer Micham, Lynn Kenney, Gabriel Naimy, Sara Utley, Holly Balcer, Kerry P. J. Pulver, Jennifer Yehle, Alicia Weeks, Terra Inman, Brian L. Delmonaco, Anthony Franklin, Mitchell Heath, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Shina Menon, John K McGuire, Deana Rich, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, John Lin, Cindy Terrill, Brock Montgomery, Sydney Reyes, Summer Reyes, Alex Plattner, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Umang Patel, Jordesha Hodge, KrunalKumar Patel, Shivani Dalal, Himanshu Kavani, Sam Joseph, Michael A. Bernstein, Ian K. Goff, Matthew Naftilan, Amal Mathew, Deborah Williams, Sue Murdock, Maryanne Ducey, Kerianne Nelson, Paul K Mohabir, Connor G O’Brien, Komal Dasani, William Marx, Ioana Amzuta, Asad J. Choudhry, Mohammad T. Azam, Kristina L Carter, Michael A Olmos, Brittany M Parker, Julio Quintanilla, Tara A Craig, Brendon J Clough, Jeffrey T Jameson, Neha Gupta, Tracy L Jones, Shonda C Ayers, Amy B Harrell, Dr.Brent R Brown, Utpal S. Bhalala, Joshua Kuehne, Melinda Garcia, Morgan Beebe, Heather Herrera, Chris Fiack, Stephanie Guo, May Vawer, Beth Blackburn, Megan Edwards, Caleb Darby, Kristy Page, Amanda Brown, Jessie McAbee, Katherine A. Belden, Michael Baram, Devin M. Weber, Rosalie DePaola, Yuwei Xia, Hudson Carter, Aaron Tolley, Mark Steele, Laurie Kemble, Joshua L. Denson, A. Scott Gillet, Margo Brown, Rachael Stevens, Andrew Wetherbie, Kevin Tea, Mathew Moore, Benjamin J Sines, Thomas J Bice, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Rajany V. Dy, Alfredo Iardino, Jill Sharma, Richard Czieki, Julia Christopher, Ryan Lacey, Marwan Mashina, Kushal Patel, Erica C. Bjornstad, Nancy M. Tofil, Scott House, Isabella Aldana, Nikhil K. Meena, Jose D. Caceres, Nikhil K Meena, Sarenthia M. Epps, Harmeen Goraya, Kelsey R. Besett, Ryan James, Lana Y. Abusalem, Akash K. Patel, Lana S Hasan, Dina Gomaa, Michael Goodman, Devin Wakefield, Anthony Spuzzillo, John O. Shinn, II, Azra Bihorac, Tezcan Ozrazgat Baslanti, George Omalay, Haleh Hashemighouchani, Julie S. Cupka, Matthew M Ruppert, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Usman Nazir, Garrett Rampon, Jake Riggle, Nathan Dismang, Vicki Montgomery, Janice Sullivan, Sarah Morris, Jennifer Nason, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Pauline Park, Andrew Admon, Sinan Hanna, Rishi Chanderraj, Maria Pliakas, Ann Wolski, Jennifer Cirino, Dima Dandachi, Hariharan Regunath, Maraya N. Camazine, Grant. E. Geiger, Abdoulie O. Njai, Baraa M. Saad, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Nita Khandelwal, T. Eoin West, Ellen S. Caldwell, Lara Lovelace-Macon, Navya Garimella, Denisse B. Dow, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Erin M. Wilfong, Kelsi Vela, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Patrick G. Lyons, Andrew P Michelson, Sara S. Haluf, Lauren M. Lynch, Nguyet M. Nguyen, Aaron Steinberg, Nicholas Braus, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, and Samuel Chakola
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: IMPORTANCE:. Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES:. To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS:. A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES:. Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS:. Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS:. Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.
Published: 2021
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6. Inefficient Recovery of Repeatedly Stimulated Memory CD8 T Cells after Polymicrobial Sepsis Induction Leads to Changes in Memory CD8 T Cell Pool Composition

Author: Steven J. Moioffer, Roger R. Berton, Patrick W. McGonagill, Isaac J. Jensen, Thomas S. Griffith, and Vladimir P. Badovinac
Subjects: Mice, Inbred C57BL, Mice, Memory T Cells, Lymphopenia, Sepsis, Immunology, Humans, Animals, Cytokines, Immunology and Allergy, CD8-Positive T-Lymphocytes, Immunologic Memory
Abstract: Long-lasting sepsis-induced immunoparalysis has been principally studied in primary (1°) memory CD8 T cells; however, the impact of sepsis on memory CD8 T cells with a history of repeated cognate Ag encounters is largely unknown but important in understanding the role of sepsis in shaping the pre-existing memory CD8 T cell compartment. Higher-order memory CD8 T cells are crucial in providing immunity against common pathogens that reinfect the host or are generated by repeated vaccination. In this study, we analyzed peripheral blood from septic patients and show that memory CD8 T cells with defined Ag specificity for recurring CMV infection proliferate less than bulk populations of central memory CD8 T cells. Using TCR-transgenic T cells to generate 1° and higher-order (quaternary [4°]) memory T cells within the same host, we demonstrate that the susceptibility and loss of both memory subsets are similar after sepsis induction, and sepsis diminished Ag-dependent and -independent (bystander) functions of these memory subsets equally. Both the 1° and 4° memory T cell populations proliferated in a sepsis-induced lymphopenic environment; however, due to the intrinsic differences in baseline proliferative capacity, expression of receptors (e.g., CD127/CD122), and responsiveness to homeostatic cytokines, 1° memory T cells become overrepresented over time in sepsis survivors. Finally, IL-7/anti–IL-7 mAb complex treatment early after sepsis induction preferentially rescued the proliferation and accumulation of 1° memory T cells, whereas recovery of 4° memory T cells was less pronounced. Thus, inefficient recovery of repeatedly stimulated memory cells after polymicrobial sepsis induction leads to changes in memory T cell pool composition, a notion with important implications in devising strategies to recover the number and function of pre-existing memory CD8 T cells in sepsis survivors.
Published: 2023

7. Admission Lymphopenia Predicts Infectious Complications and Mortality in Traumatic Brain Injury Victims

Author: Daniel Budreau, Subhashish Chakravarty, Sophia Williams-Perez, Colette Galet, Brady Campbell, and Patrick W. McGonagill
Subjects: Adult, Male, medicine.medical_specialty, Traumatic brain injury, Secondary infection, Subgroup analysis, Infections, Critical Care and Intensive Care Medicine, Cohort Studies, Injury Severity Score, Lymphopenia, Internal medicine, Brain Injuries, Traumatic, medicine, Humans, Registries, Mortality, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Complete blood count, Middle Aged, medicine.disease, Iowa, Polytrauma, Hospitalization, Heart failure, Emergency Medicine, Female, business, Forecasting, Kidney disease
Abstract: BACKGROUND Traumatic brain injury (TBI) is a major cause of mortality and disability associated with increased risk of secondary infections. Identifying a readily available biomarker may help direct TBI patient care. Herein, we evaluated whether admission lymphopenia could predict outcomes of TBI patients. METHODS This is a 10-year retrospective review of TBI patients with a head Abbreviated Injury Score 2 to 6 and absolute lymphocyte counts (ALC) collected within 24 h of admission. Exclusion criteria were death within 24 h of admission and presence of bowel perforation on admission. Demographics, admission data, injury severity score, mechanism of injury, and outcomes were collected. Association between baseline variables and outcomes was analyzed. RESULTS We included 2,570 patients; 946 (36.8%) presented an ALC ≤1000 on admission (lymphopenic group). Lymphopenic patients were significantly older, less likely to smoke, and more likely to have heart failure, hypertension, or chronic kidney disease. Lymphopenia was associated with increased risks of mortality (OR = 1.903 [1.389-2.608]; p
Published: 2021

8. Prolonged Reactive Oxygen Species Production following Septic Insult

Author: Vladimir P. Badovinac, Garry R. Buettner, Isaac J. Jensen, Roger R. Berton, Patrick W. McGonagill, Thomas S. Griffith, Elvia E. Silva, and Brett A. Wagner
Subjects: Adult, Male, Antioxidant, Adolescent, medicine.medical_treatment, Lymphocyte, Immunology, Ascorbic Acid, Severity of Illness Index, Antioxidants, Article, Immature Monocyte, Sepsis, Mice, Young Adult, Immune system, Disease severity, Animals, Humans, Immunology and Allergy, Medicine, Aged, Aged, 80 and over, chemistry.chemical_classification, Reactive oxygen species, Vitamin C, business.industry, General Medicine, Middle Aged, medicine.disease, Healthy Volunteers, Disease Models, Animal, medicine.anatomical_structure, chemistry, Case-Control Studies, Leukocytes, Mononuclear, Female, Reactive Oxygen Species, business
Abstract: The dysregulated host response and organ damage following systemic infection that characterizes a septic event predisposes individuals to a chronic immunoparalysis state associated with severe transient lymphopenia and diminished lymphocyte function, thereby reducing long-term patient survival and quality of life. Recently, we observed lasting production of reactive oxygen species (ROS) in mice that survive sepsis. ROS production is a potent mechanism for targeting infection, but excessive ROS production can prove maladaptive by causing organ damage, impairing lymphocyte function, and promoting inflammaging, concepts paralleling sepsis-induced immunoparalysis. Notably, we observed an increased frequency of ROS-producing immature monocytes in septic hosts that was sustained for greater than 100 days postsurgery. Recent clinical trials have explored the use of vitamin C, a potent antioxidant, for treating septic patients. We observed that therapeutic vitamin C administration for sepsis limited ROS production by monocytes and reduced disease severity. Importantly, we also observed increased ROS production by immature monocytes in septic patients both at admission and ∼28 days later, suggesting a durable and conserved feature that may influence the host immune response. Thus, lasting ROS production by immature monocytes is present in septic patients, and early intervention strategies to reduce it may improve host outcomes, potentially reducing sepsis-induced immunoparalysis.
Published: 2021

9. Use of Cyproheptadine for the Treatment of Serotonin Syndrome

Author: Patrick W. McGonagill, Jared R Frye, Yuk Ming Liu, Kate Pape, Colette Galet, and Andrew M Poggemiller
Subjects: Psychiatry and Mental health, Text mining, business.industry, medicine, MEDLINE, Pharmacology (medical), Cyproheptadine, Young adult, medicine.symptom, Bioinformatics, business, Serotonin syndrome, medicine.drug
Published: 2020

10. Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

Author: Mikaela M. Tremblay, Isaac J. Jensen, Thomas S. Griffith, Weiqun Peng, Micaela G. Fosdick, Qiang Shan, Vladimir P. Badovinac, Xiang Li, Jon C. D. Houtman, Patrick W. McGonagill, and Hai-Hui Xue
Subjects: Male, Mouse, Transcription, Genetic, Cell, CD8-Positive T-Lymphocytes, sepsis, Mice, Immunology and Inflammation, Cytotoxic T cell, homeostatic proliferation, Biology (General), education.field_of_study, General Neuroscience, General Medicine, Middle Aged, Phenotype, Vaccination, medicine.anatomical_structure, Medicine, Female, medicine.symptom, Research Article, central memory, Human, Adult, QH301-705.5, Science, Population, Inflammation, Biology, General Biochemistry, Genetics and Molecular Biology, Sepsis, Immune system, medicine, Animals, Humans, education, Aged, Cell Proliferation, General Immunology and Microbiology, medicine.disease, Chromatin Assembly and Disassembly, Listeria monocytogenes, CD8 T cell, Case-Control Studies, Immunology, Immunologic Memory
Abstract: The global health burden due to sepsis and the associated cytokine storm is substantial. While early intervention has improved survival during the cytokine storm, those that survive can enter a state of chronic immunoparalysis defined by transient lymphopenia and functional deficits of surviving cells. Memory CD8 T cells provide rapid cytolysis and cytokine production following re-encounter with their cognate antigen to promote long-term immunity, and CD8 T cell impairment due to sepsis can pre-dispose individuals to re-infection. While the acute influence of sepsis on memory CD8 T cells has been characterized, if and to what extent pre-existing memory CD8 T cells recover remains unknown. Here, we observed that central memory CD8 T cells (TCM) from septic patients proliferate more than those from healthy individuals. Utilizing LCMV immune mice and a CLP model to induce sepsis, we demonstrated that TCM proliferation is associated with numerical recovery of pathogen-specific memory CD8 T cells following sepsis-induced lymphopenia. This increased proliferation leads to changes in composition of memory CD8 T cell compartment and altered tissue localization. Further, memory CD8 T cells from sepsis survivors have an altered transcriptional profile and chromatin accessibility indicating long-lasting T cell intrinsic changes. The sepsis-induced changes in the composition of the memory CD8 T cell pool and transcriptional landscape culminated in altered T cell function and reduced capacity to control L. monocytogenes infection. Thus, sepsis leads to long-term alterations in memory CD8 T cell phenotype, protective function and localization potentially changing host capacity to respond to re-infection., eLife digest A dirty cut, a nasty burn, a severe COVID infection; there are many ways for someone to develop sepsis. This life-threatening condition emerges when the immune system overreacts to a threat and ends up damaging the body. Even when patients survive, they are often left with a partially impaired immune system that cannot adequately protect against microbes and cancer; this is known as immunoparalysis. Memory CD8 T cells, a type of immune cell that is compromised by sepsis, are a long-lived population of cells that ‘remember’ previous infection or vaccination, and then react faster to prevent the same illness if the person ever encounters the same threat again. Yet it is unclear how exactly sepsis harms the function and representation of memory CD8 T cells, and the immune system in general. Jensen et al. investigated this question, first by showing that sepsis leads to a profound loss of memory CD8 T cells, but that surviving memory CD8 T cells multiply quickly – especially a subpopulation known as central memory CD8 T cells – to re-establish the memory CD8 T cell population. Since the central memory CD8 T cells proliferate better than the other memory T cells this alters the overall composition of the pool of memory CD8 T cells, with central memory cells becoming overrepresented. Further experiments revealed that this biasing toward central memory T cells, due to sepsis, created long-term changes in the distribution of memory CD8 T cells throughout the body. The way the genetic information of these cells was packaged had also been altered, as well as which genes were switched on or off. Overall, these changes reduced the ability of memory CD8 T cells to control infections. Together, these findings help to understand how immunoparalysis can emerge after sepsis, and what could be done to correct it. These findings could also be applied to other conditions – such as COVID-19 – which may cause similar long-term changes to the immune system.
Published: 2021

11. Author response: Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

Author: Thomas S. Griffith, Weiqun Peng, Micaela G. Fosdick, Jon C. D. Houtman, Vladimir P. Badovinac, Xiang Li, Qiang Shan, Isaac J. Jensen, Mikaela M. Tremblay, Patrick W. McGonagill, and Hai-Hui Xue
Subjects: Sepsis, business.industry, Immunology, Medicine, Cytotoxic T cell, business, medicine.disease, Phenotype, Function (biology)
Published: 2021

12. Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry

Author: Utpal S, Bhalala, Katja M, Gist, Sandeep, Tripathi, Karen, Boman, Vishakha K, Kumar, Lynn, Retford, Kathleen, Chiotos, Allison M, Blatz, Heda, Dapul, Sourabh, Verma, Imran A, Sayed, Varsha P, Gharpure, Erica, Bjornstad, Nancy, Tofil, Katherine, Irby, Ronald C, Sanders, Julia A, Heneghan, Melissa, Thomas, Manoj K, Gupta, Franscene E, Oulds, Grace M, Arteaga, Emily R, Levy, Neha, Gupta, Margit, Kaufman, Amr, Abdelaty, Mark, Shlomovich, Shivanand S, Medar, A M, Iqbal O'Meara, Joshua, Kuehne, Shina, Menon, Paras B, Khandhar, Aaron S, Miller, Suzanne M, Barry, Valerie C, Danesh, Ashish K, Khanna, Kimberly, Zammit, Casey, Stulce, Patrick W, McGonagill, Asher, Bercow, Ioana G, Amzuta, Sandeep, Gupta, Mohammed A, Almazyad, Louisdon, Pierre, Prithvi, Sendi, Sidra, Ishaque, Harry L, Anderson, Pooja, Nawathe, Murtaza, Akhter, Patrick G, Lyons, Catherine, Chen, Allan J, Walkey, Azra, Bihorac, Imam, Wada Bello, Judith, Ben Ari, Tanja, Kovacevic, Vikas, Bansal, John T, Brinton, Jerry J, Zimmerman, Rahul, Kashyap, and Kathleen, Johnson
Subjects: Male, medicine.medical_specialty, Adolescent, Comorbidity, Overweight, Critical Care and Intensive Care Medicine, Logistic regression, outcomes, intensive care unit, children, coronavirus disease 2019, multisystem inflammatory syndrome in children, severe acute respiratory syndrome coronavirus 2, Body Mass Index, Interquartile range, Internal medicine, medicine, Humans, Mass index, Hospital Mortality, Child, Retrospective Studies, Study Registry, business.industry, SARS-CoV-2, Age Factors, Online Clinical Investigations, COVID-19, Infant, Retrospective cohort study, Systemic Inflammatory Response Syndrome, Intensive Care Units, Logistic Models, Child, Preschool, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Observational study, Median body, Female, medicine.symptom, business, Child, Hospitalized
Abstract: Supplemental Digital Content is available in the text., Objectives: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. Design: Retrospective study. Setting: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. Patients: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. Interventions: None. Measurements and Main Results: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25–14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16–25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2–7.7 d) and 4 days (1.9–7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. Conclusions: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.
Published: 2021

13. Autoimmunity increases susceptibility to and mortality from sepsis

Author: Isaac J. Jensen, Patrick W. McGonagill, Ashutosh K. Mangalam, Thomas S. Griffith, Vladimir P. Badovinac, and Samantha N. Jensen
Subjects: Adult, Male, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Adolescent, medicine.medical_treatment, Immunology, Datasets as Topic, medicine.disease_cause, Pneumococcal Infections, Autoimmunity, Sepsis, Mice, Young Adult, Risk Factors, Streptococcus pneumoniae, Prevalence, Retrospective analysis, medicine, Animals, Humans, Immunology and Allergy, Aged, Retrospective Studies, Aged, 80 and over, Autoimmune disease, Immune status, business.industry, Multiple sclerosis, Incidence (epidemiology), Experimental autoimmune encephalomyelitis, General Medicine, Middle Aged, medicine.disease, Patient population, Cytokine, Female, Disease Susceptibility, business
Abstract: We recently demonstrated how sepsis influences the subsequent development of experimental autoimmune encephalomyelitis (EAE) presented a conceptual advance in understanding the postsepsis chronic immunoparalysis state. However, the reverse scenario (autoimmunity prior to sepsis) defines a high-risk patient population whose susceptibility to sepsis remains poorly defined. In this study, we present a retrospective analysis of University of Iowa Hospital and Clinics patients demonstrating increased sepsis prevalence among multiple sclerosis (MS), relative to non-MS, patients. To interrogate how autoimmune disease influences host susceptibility to sepsis, well-established murine models of MS and sepsis and EAE and cecal ligation and puncture, respectively, were used. EAE, relative to non-EAE, mice were highly susceptible to sepsis-induced mortality with elevated cytokine storms. These results were further recapitulated in LPS and Streptococcus pneumoniae sepsis models. This work highlights both the relevance of identifying highly susceptible patient populations and expands the growing body of literature that host immune status at the time of septic insult is a potent mortality determinant.
Published: 2021

14. Unanticipated Admission Following Outpatient Laparoscopic Cholecystectomy: Identifying Opportunities for Improvement

Author: Imran Hassan, Paolo Goffredo, Anna C. Beck, Xiang Gao, Patrick W. McGonagill, and Ronald J. Weigel
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Gallbladder Diseases, 030230 surgery, Patient Readmission, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Health care, medicine, Humans, Laparoscopic cholecystectomy, Aged, Retrospective Studies, business.industry, General surgery, General Medicine, Middle Aged, Ambulatory Surgical Procedures, Cholecystectomy, Laparoscopic, 030220 oncology & carcinogenesis, Cholecystectomy, Female, business, Cholangiography
Abstract: Background Unanticipated admissions are a burden to the health care system. Over 400 000 outpatient laparoscopic cholecystectomies (LCs) are performed annually in the United States. The aim of this study is to identify causes of unanticipated admissions and modifiable risk factors. Methods Patients undergoing elective outpatient LCs were identified from the 2013-2015 American College of Surgeons National Surgical Quality Improvement Program database. Results A total of 69 376 patients underwent outpatient LC or LC+ intraoperative cholangiogram (IOC); 2027 (2.9%) were admitted after a median of 5 days (interquartile range 3-8). Admission rates varied by preoperative indications: pancreatitis (4.9%), gallstones with obstruction (3.9%), cholecystitis (3.0%), and gallstones without obstruction (2.6%) ( P = .003). The most frequent causes were infection, retained stones, and other GI complications. Patients admitted for infection or cardiopulmonary complications were older with higher American Society of Anesthesiologists (ASA) ( P < .01), while patients with pain and retained stones were younger with lower ASA ( P < .01). Patients who underwent LC+IOC had a lower admission rate due to retained stones (.17% vs. .31% LC, P = .006). Conclusions Unanticipated admissions following outpatient LC occur infrequently for diverse reasons usually within the first week after surgery. Associated factors are patient and disease related and not at all modifiable. In selected patients, increased IOC use may decrease admissions from retained stones.
Published: 2020

15. The Effect of Improving Basic Preventive Measures in the Perioperative Arena on Staphylococcus aureus Transmission and Surgical Site Infections: A Randomized Clinical Trial

Author: Franklin Dexter, Mark Fisher, Lance C Evans, William J. Sharp, Raven Brenneke, Megan E McDonald, Joshua Godding, Chad R. Tracy, Mark P. Yeager, Alexia Herber, Jeremiah R. Brown, Dionne A. Skeete, Patrick W. McGonagill, Brent Hadder, Nicolas O. Noiseux, Mel J. Sharafuddin, Bradley A. Erickson, Michael J. Goodheart, John Keech, Andrew J. Pugely, Deanna Persons, Jennifer Shanklin, W. Thomas Lawrence, Eli Schmidt, Randy W. Loftus, and Thomas Granchi
Subjects: Adult, Male, medicine.medical_specialty, Staphylococcus aureus, Psychological intervention, law.invention, Treatment and control groups, Randomized controlled trial, law, Health care, Medicine, Humans, Surgical Wound Infection, Perioperative Period, Aged, Infection Control, business.industry, Incidence (epidemiology), General Medicine, Perioperative, Middle Aged, Staphylococcal Infections, Relative risk, Orthopedic surgery, Emergency medicine, Female, business, Risk Reduction Behavior
Abstract: Surgical site infections increase patient morbidity and health care costs. The Centers for Disease Control and Prevention emphasize improved basic preventive measures to reduce bacterial transmission and infections among patients undergoing surgery.To assess whether improved basic preventive measures can reduce perioperative Staphylococcus aureus transmission and surgical site infections.This randomized clinical trial was conducted from September 20, 2018, to September 20, 2019, among 19 surgeons and their 236 associated patients at a major academic medical center with a 60-day follow-up period. Participants were a random sample of adult patients undergoing orthopedic total joint, orthopedic spine, oncologic gynecological, thoracic, general, colorectal, open vascular, plastic, or open urological surgery requiring general or regional anesthesia. Surgeons and their associated patients were randomized 1:1 via a random number generator to treatment group or to usual care. Observers were masked to patient groupings during assessment of outcome measures.Sustained improvements in perioperative hand hygiene, vascular care, environmental cleaning, and patient decolonization efforts.Perioperative S aureus transmission assessed by the number of isolates transmitted and the incidence of transmission among patient care units (primary) and the incidence of surgical site infections (secondary).Of 236 patients (156 [66.1%] women; mean [SD] age, 57 [15] years), 106 (44.9%) and 130 (55.1%) were allocated to the treatment and control groups, respectively, received the intended treatment, and were analyzed for the primary outcome. Compared with the control group, the treatment group had a reduced mean (SD) number of transmitted perioperative S aureus isolates (1.25 [2.11] vs 0.47 [1.13]; P = .002). Treatment reduced the incidence of S aureus transmission (incidence risk ratio; 0.56; 95% CI, 0.37-0.86; P = .008; with robust variance clustering by surgeon: 95% CI, 0.42-0.76; P .001). Overall, 11 patients (4.7%) experienced surgical site infections, 10 (7.7%) in the control group and 1 (0.9%) in the treatment group. Transmission was associated with an increased risk of surgical site infection (8 of 73 patients [11.0%] with transmission vs 3 of 163 [1.8%] without; risk ratio, 5.95; 95% CI, 1.62-21.86; P = .007). Treatment reduced the risk of surgical site infection (hazard ratio, 0.12; 95% CI, 0.02-0.92; P = .04; with clustering by surgeon: 95% CI, 0.03-0.51; P = .004).Improved basic preventive measures in the perioperative arena can reduce S aureus transmission and surgical site infections.ClinicalTrials.gov Identifier: NCT03638947.
Published: 2020

16. Worry and FRET: ROS Production Leads to Fluorochrome Tandem Degradation and impairs Interpretation of Flow Cytometric Results

Author: Vladimir P. Badovinac, Mitchell N. Lefebvre, Thomas S. Griffith, John T. Harty, Isaac J. Jensen, and Patrick W. McGonagill
Subjects: Tandem, media_common.quotation_subject, Immunology, Phycocyanin, Reproducibility of Results, Biology, Carbocyanines, Flow Cytometry, Article, Interpretation (model theory), Infectious Diseases, Förster resonance energy transfer, Biophysics, Fluorescence Resonance Energy Transfer, Immunology and Allergy, Degradation (geology), Animals, Humans, Benzothiazoles, Worry, Reactive Oxygen Species, media_common, Fluorescent Dyes, Granulocytes, Mercaptoethanol
Published: 2020

17. Routine Follow-Up Imaging is Not Warranted for Isolated Traumatic Subarachnoid Hemorrhage

Author: Dionne A. Skeete, Nathan Davidson, Sophia Williams-Perez, Maged D Fam, Patrick W. McGonagill, Lauren Allan, and Colette Galet
Subjects: medicine.medical_specialty, Subarachnoid hemorrhage, business.industry, Medicine, Surgery, Radiology, business, medicine.disease
Published: 2020

18. Is There a Better Way to Treat Pilonidal Disease in the US?

Author: Colette Galet, Lauren Allan, Drew Lilienthal, Cheryl M. Byrnes, and Patrick W. McGonagill
Subjects: medicine.medical_specialty, Pilonidal disease, business.industry, Medicine, Surgery, business, Dermatology
Published: 2020

19. [Untitled]

Author: Kate Pape, Andrew M Poggemiller, Colette Galet, Jared R Frye, Patrick W. McGonagill, and Yuk Ming Liu
Subjects: business.industry, medicine, medicine.symptom, Pharmacology, Cyproheptadine, Critical Care and Intensive Care Medicine, business, Serotonin syndrome, medicine.drug
Published: 2019

20. Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells

Author: Patrick W. McGonagill, Xiaoqiu Liu, Courtney S. Galle, Jeffery L. Meier, Allen W. Wu, Jinxiang Yuan, and Michael J. Keller
Subjects: Gene Expression Regulation, Viral, viruses, Immunology, Vasoactive intestinal peptide, Cytomegalovirus, CREB, Microbiology, Immediate early protein, Cell Line, Immediate-Early Proteins, Virology, Humans, Gene silencing, Gene Silencing, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Protein kinase A, Antigens, Viral, Regulation of gene expression, Dose-Response Relationship, Drug, biology, Cyclic AMP-Dependent Protein Kinases, Molecular biology, Virus-Cell Interactions, Insect Science, Cytomegalovirus Infections, DNA, Viral, biology.protein, Signal transduction, Immediate early gene, Signal Transduction, Transcription Factors, Vasoactive Intestinal Peptide
Abstract: The triggering mechanisms underlying reactivation of human cytomegalovirus (HCMV) in latently infected persons are unclear. During latency, HCMV major immediate-early (MIE) gene expression breaks silence to initiate viral reactivation. Using quiescently HCMV-infected human pluripotent embryonal NTera2 cells (NT2) to model HCMV reactivation, we show that vasoactive intestinal peptide (VIP), an immunomodulatory neuropeptide, immediately and dose-dependently (1 to 500 nM) activates HCMV MIE gene expression. This response requires the MIE enhancer cyclic AMP response elements (CRE). VIP quickly elevates CREB Ser133 and ATF-1 Ser63 phosphorylation levels, although the CREB Ser133 phosphorylation level is substantial at baseline. VIP does not change the level of HCMV genomes in nuclei, Oct4 (pluripotent cell marker), or hDaxx (cellular repressor of HCMV gene expression). VIP-activated MIE gene expression is mediated by cellular protein kinase A (PKA), CREB, and TORC2. VIP induces PKA-dependent TORC2 Ser171 dephosphorylation and nuclear entry, which likely enables MIE gene activation, as TORC2 S171A (devoid of Ser171 phosphorylation) exhibits enhanced nuclear entry and desilences the MIE genes in the absence of VIP stimulation. In conclusion, VIP stimulation of the PKA-CREB-TORC2 signaling cascade activates HCMV CRE-dependent MIE gene expression in quiescently infected NT2 cells. We speculate that neurohormonal stimulation via this signaling cascade is a possible means for reversing HCMV silence in vivo.
Published: 2009

21. Subcapsular hematoma in blunt splenic injury: A significant predictor of failure of nonoperative management

Author: Karen Parker, Jay A. Requarth, Joseph Martin Lopez, Preston R. Miller, Patrick W. McGonagill, Jessica L. Gross, Michael C. Chang, and J. Jason Hoth
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Splenectomy, Critical Care and Intensive Care Medicine, Wounds, Nonpenetrating, Blunt, X ray computed, Medicine, Humans, Embolization, Registries, Treatment Failure, Nonoperative management, Retrospective Studies, Hematoma, medicine.diagnostic_test, business.industry, Retrospective cohort study, Subcapsular Hematoma, Embolization, Therapeutic, Surgery, Treatment Outcome, Angiography, Female, business, Tomography, X-Ray Computed, Spleen
Abstract: In patients with blunt splenic injury (BSI), patient selection, angiography, and embolization have contributed to low nonoperative management (NOM) failure rates. Despite these advances, some patients will fail NOM. We noted that a significant proportion of NOM failures had subcapsular hematomas (SCHs) identified on imaging. We sought to determine if there is a correlation between SCH and higher risk of NOM failure after BSI.Our institutional trauma registry was queried for all patients with BSI during a 2-year period. Charts were reviewed to determine grade, presence of SCH, and outcome of NOM. Under current institutional protocol, all stable patients with BSI Grades III to V and those with contrast blush on computed tomography are referred for angiography and embolization. Failure of NOM was declared if splenectomy was required for bleeding after an initial plan of nonoperation.From May 2012 to May 2014, 312 patients with BSI were identified. A total of 253 patients (81%) underwent NOM. Overall, 15 (5.9%) failed NOM. Of those undergoing NOM, 34 had SCH and 12 failed (35.3% vs. 1.5% without SCH, p = 0.0001). Failure rates in Grades 1 to 4 were 2.3%, 3.8%, 8.8%, and 19.2%, respectively. NOM failure rates in the subset with SCH for Grades I to IV were 20%, 25%, 30.8%, and 80%, respectively. These are significantly higher than patients without SCH in Grades II to IV (0%, p = 0.003; 2.3%, p = 0.008; and 4.8%, p = 0.016) and approach significance in Grade I (1.2%, p = 0.11). There were no SCHs and no failures of NOM in Grade V injuries.The NOM failure rate of BSI patients with SCH is significantly higher than those without SCH. Patients with BSI Grades I to III slated for NOM must be observed as the failure rate approaches 30%. Splenectomy should be considered in patients with Grade IV BSI with SCH, as NOM failure rate is 80%.Therapeutic study, level IV.
Published: 2015

22. 1659: SEVERE LEGIONELLA PNEUMONIA FROM OCCUPATIONAL EXPOSURE REQUIRING EXTRACORPOREAL MEMBRANE OXYGENATION

Author: Patrick W McGonagill and Melissa E. Brunsvold
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, medicine, Legionella Pneumonia, Extracorporeal membrane oxygenation, Occupational exposure, Critical Care and Intensive Care Medicine, Intensive care medicine, business
Published: 2016

23. Phorbol ester-induced human cytomegalovirus major immediate-early (MIE) enhancer activation through PKC-delta, CREB, and NF-kappaB desilences MIE gene expression in quiescently infected human pluripotent NTera2 cells

Author: Patrick W. McGonagill, Jinxiang Yuan, Allen W. Wu, Jeffery L. Meier, Xiaoqiu Liu, and Courtney S. Galle
Subjects: Transcriptional Activation, Cellular differentiation, Immunology, Cytomegalovirus, Biology, CREB, Microbiology, Cell Line, Immediate-Early Proteins, Virology, Phorbol Esters, medicine, Humans, Enhancer, Cyclic AMP Response Element-Binding Protein, Transcription factor, Regulation of gene expression, NF-kappa B, Cell biology, Genome Replication and Regulation of Viral Gene Expression, AP-1 transcription factor, Protein Kinase C-delta, Trichostatin A, Enhancer Elements, Genetic, Insect Science, Cytomegalovirus Infections, biology.protein, Viral genome replication, medicine.drug, Protein Binding, Signal Transduction
Abstract: Novel strategies to mitigate the disease burden resulting from human cytomegalovirus (CMV) (HCMV) reactivation are needed. Knowledge about the ways in which HCMV major immediate-early (MIE) gene expression breaks silence from latency to start the viral replicative cycle has the potential to inform the development of new therapies to preempt viral replication. However, the molecular mechanisms that regulate the switch from HCMV MIE gene silence to activation are poorly understood. The expression of viral MIE genes is required to initiate the productive life cycles of human and animal CMV species, whereas expression is greatly restricted or absent during the latency of these viruses (39, 52, 53, 57). The 550-bp MIE enhancer is the vital regulatory center for the transcriptional activation of the MIE gene locus (39). The enhancer's function is attributed to assorted cis-acting elements that are consensus binding sites for different specific cellular transcription factors (9, 22, 31, 37); several types of cis-acting elements are repeated. Signaling networks relay and integrate information from the cell, the virus, and the extracellular environment to dynamically modulate the functional activities of these cellular transcription factors (9, 24). The composite configuration of the specific cis-acting elements in the HCMV MIE enhancer differs greatly from that of evolutionarily distant cytomegalovirus relatives (39). This may explain why the replacement of this enhancer with the MIE enhancer from murine CMV (MCMV) renders HCMV poorly competent at executing both MIE gene expression and viral genome replication in lytically infected cells (21). HCMV infection of human pluripotent embryonal NTera2/D1 (NT2) cells is a tractable model with which to molecularly characterize the regulatory mechanisms that break HCMV MIE gene expression silence in a setting of viral quiescence (25, 36). These cells become either neurons and astrocytes after treatment with retinoic acid (RA) (2, 3) or epithelial and smooth muscle-like cells after treatment with bone morphogenetic protein 2 (10). Keeping NT2 cells in an undifferentiated state, partly by propagation under progenitor cell growth conditions (36), promotes quiescent HCMV infection and results in greater than 98% of NT2 nuclei containing HCMV pp65 at 1 h postinfection (p.i.) with a multiplicity of infection (MOI) of 3 to 5 (25) and approximately 3 HCMV genome equivalents per nucleus at 24 h p.i. with an MOI of 10 (38). At 48 h p.i., the NT2 cells contain a subset of nonreplicating HCMV genomes having a DNA structure of covalently closed circles with superhelical twists (36). In infected NT2 cells, either the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) (36) or the stimulation of cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity (25, 59) immediately turns on the transcription of HCMV MIE genes in previously dormant HCMV genomes (25, 59). This rapidly induced transcriptional activation is not the result of cellular differentiation (42, 59). Conversely, RA fails to reverse the MIE enhancer/promoter silence in quiescently infected NT2 cells (36), but its use to first convert these cells into differentiated NT2 (NT2-D) cells subsequently enables the activation of the HCMV MIE enhancer/promoter immediately upon viral infection (16). In a similar NT2 cell model, the inhibition of HDAC by TSA was found to disrupt heterochromatin nucleation at the MIE enhancer/promoter (42), akin to the chromatin disruption that accompanies HCMV reactivation in endogenously infected dendritic cells (49). We have shown recently with NT2 cells that the stimulation of the cAMP-PKA-CREB signaling cascade by either vasoactive intestinal peptide (VIP) or forskolin (FSK) activates the HCMV MIE enhancer/promoter via cAMP response elements (CREs) to relieve HCMV genome silence (25, 59). The transcriptional coactivator transducer of regulated CREB-2 (TORC2) is a critical part of this signaling pathway and must also be activated by VIP or FSK via a PKA-dependent mechanism in order to desilence the MIE genes (59). Ancillary data coming from recent work sparked an awareness of phorbol ester's ability to also increase HCMV MIE gene expression levels in quiescently infected NT2 cells (59). This invited speculation that MIE gene activation might be achieved as well through a separate regulatory pathway that involves protein kinase C (PKC) (59). Phorbol esters are diacylglycerol (DAG) mimics that directly bind to and activate the PKC isoforms belonging to the conventional (alpha, beta, and gamma) and novel (delta, epsilon, theta, and nano) subgroups, designated the cPKC and nPKC subgroups, respectively. Phorbol ester also directly targets chimerins, protein kinase D, RasGRPs, Munc13s, and DAG kinase gamma (7). These actions then activate a specific assortment of signaling cascades and target genes that vary in accordance with cell types and growth conditions. NT2 cells are known to contain PKC-alpha, -beta, and -delta isoforms (1, 23, 29, 44, 45, 47), and PKC-alpha, -beta, -gamma, and -epsilon increase in abundance with NT2 cell differentiation (1, 29, 44, 47). A novel PKC-deltaVIII isoform made from a PKC-delta RNA splice variant is upregulated in differentiated NT2 cells and has antiapoptotic functions (23). Thus, the possibility exists that phorbol ester could act directly on any one of a number of different proteins to override HCMV MIE silence in NT2 cells. One previous report indicated that phorbol ester treatment of NT2 cells increases AP1 target gene expression in transient assays but fails to stimulate NT2 cell differentiation unless combined with RA (29). In other cell types, phorbol ester was shown to differentially activate genes through any one or a combination of different specific cellular transcription factors, including AP-1, CREB, ETS, SRF, NF-κB, and SP1 family members, which function in manners that depend on the target gene and cell type. Because the HCMV MIE enhancer contains cognate sites for several members of this transcription factor panoply (e.g., AP-1, CREB, ETS, SRF, NF-κB, and SP1) (39), multiple possibilities underlie an investigation into the mechanisms by which the MIE genes are desilenced in quiescently infected NT2 cells. In this report, we show that phorbol ester stimulation of quiescently infected NT2 cells immediately activates HCMV MIE gene expression through a signaling cascade that involves cellular PKC-delta, CREB, and NF-κB. This response is conveyed by the CRE and NF-κB binding sites (κB) located in the HCMV MIE enhancer. Phorbol ester does not change NT2 cell pluripotent status or viral genome penetration during the time frame in which stimulation activates MIE gene expression. (This work was presented in part at the 34th International Herpesvirus Workshop in Ithaca, NY.)
Published: 2010

24. Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

Author: Isaac J Jensen, Xiang Li, Patrick W McGonagill, Qiang Shan, Micaela G Fosdick, Mikaela M Tremblay, Jon CD Houtman, Hai-Hui Xue, Thomas S Griffith, Weiqun Peng, and Vladimir P Badovinac
Subjects: CD8 T cell, central memory, homeostatic proliferation, sepsis, Medicine, Science, Biology (General), QH301-705.5
Abstract: The global health burden due to sepsis and the associated cytokine storm is substantial. While early intervention has improved survival during the cytokine storm, those that survive can enter a state of chronic immunoparalysis defined by transient lymphopenia and functional deficits of surviving cells. Memory CD8 T cells provide rapid cytolysis and cytokine production following re-encounter with their cognate antigen to promote long-term immunity, and CD8 T cell impairment due to sepsis can pre-dispose individuals to re-infection. While the acute influence of sepsis on memory CD8 T cells has been characterized, if and to what extent pre-existing memory CD8 T cells recover remains unknown. Here, we observed that central memory CD8 T cells (TCM) from septic patients proliferate more than those from healthy individuals. Utilizing LCMV immune mice and a CLP model to induce sepsis, we demonstrated that TCM proliferation is associated with numerical recovery of pathogen-specific memory CD8 T cells following sepsis-induced lymphopenia. This increased proliferation leads to changes in composition of memory CD8 T cell compartment and altered tissue localization. Further, memory CD8 T cells from sepsis survivors have an altered transcriptional profile and chromatin accessibility indicating long-lasting T cell intrinsic changes. The sepsis-induced changes in the composition of the memory CD8 T cell pool and transcriptional landscape culminated in altered T cell function and reduced capacity to control L. monocytogenes infection. Thus, sepsis leads to long-term alterations in memory CD8 T cell phenotype, protective function and localization potentially changing host capacity to respond to re-infection.
Published: 2021
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24 results on '"Patrick W. McGonagill"'

1. Surviving septic patients endotyped with a functional assay demonstrate active immune responses

2. Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic

3. Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19

4. Variation in Use of Repurposed Medications Among Patients With Coronavirus Disease 2019. From The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 Registry Investigator Group

5. Risk Factors for Critical Coronavirus Disease 2019 and Mortality in Hospitalized Young Adults: An Analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Coronavirus Disease 2019 Registry

6. Inefficient Recovery of Repeatedly Stimulated Memory CD8 T Cells after Polymicrobial Sepsis Induction Leads to Changes in Memory CD8 T Cell Pool Composition

7. Admission Lymphopenia Predicts Infectious Complications and Mortality in Traumatic Brain Injury Victims

8. Prolonged Reactive Oxygen Species Production following Septic Insult

9. Use of Cyproheptadine for the Treatment of Serotonin Syndrome

10. Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

11. Author response: Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

12. Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry

13. Autoimmunity increases susceptibility to and mortality from sepsis

14. Unanticipated Admission Following Outpatient Laparoscopic Cholecystectomy: Identifying Opportunities for Improvement

15. The Effect of Improving Basic Preventive Measures in the Perioperative Arena on Staphylococcus aureus Transmission and Surgical Site Infections: A Randomized Clinical Trial

16. Worry and FRET: ROS Production Leads to Fluorochrome Tandem Degradation and impairs Interpretation of Flow Cytometric Results

17. Routine Follow-Up Imaging is Not Warranted for Isolated Traumatic Subarachnoid Hemorrhage

18. Is There a Better Way to Treat Pilonidal Disease in the US?

19. [Untitled]

20. Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells

21. Subcapsular hematoma in blunt splenic injury: A significant predictor of failure of nonoperative management

22. 1659: SEVERE LEGIONELLA PNEUMONIA FROM OCCUPATIONAL EXPOSURE REQUIRING EXTRACORPOREAL MEMBRANE OXYGENATION

23. Phorbol ester-induced human cytomegalovirus major immediate-early (MIE) enhancer activation through PKC-delta, CREB, and NF-kappaB desilences MIE gene expression in quiescently infected human pluripotent NTera2 cells

24. Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

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24 results on '"Patrick W. McGonagill"'

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