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1. 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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2. 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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3. 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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4. Implementation of an Automated Sepsis Screening Tool in a Community Hospital Setting

Author

Bobbi J Hughes, George M Verghese, Penny B Cooper, J Scott Just, and Amy J Markham

Subjects
medicine.medical_specialty, Population, MEDLINE, Hospitals, Community, Logistic regression, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Artificial Intelligence, Intervention (counseling), medicine, Humans, Mass Screening, Screening tool, 030212 general & internal medicine, education, General Nursing, Retrospective Studies, Retrospective review, education.field_of_study, 030504 nursing, business.industry, medicine.disease, Community hospital, Emergency medicine, 0305 other medical science, business
Abstract

Background Early identification of sepsis remains the greatest barrier to compliance with recommended evidence-based bundles. Purpose The purpose was to improve the early identification and treatment of sepsis by developing an automated screening tool. Methods Six variables associated with sepsis were identified. Logistic regression was used to weigh the variables, and a predictive model was developed to help identify patients at risk. A retrospective review of 10 792 records of hospitalizations was conducted including 339 cases of sepsis to retrieve data for the model. Results The final model resulted an area under the curve of 0.857 (95% CI, 0.850-0.863), suggesting that the screening tool may assist in the early identification of patients developing sepsis. Conclusion By using artificial intelligence capabilities, we were able to screen 100% of our inpatient population and deliver results directly to the caregiver without any manual intervention by nursing staff.

Published
2020

5. Outcomes and factors influencing outcomes of critically ill HIV-positive patients in a tertiary care center in South India

Author

Shilpa Reynal D'sa, I Ramya, Sowmya Sathyendra, Anand Zachariah, Shubankar Mitra, George M Verghese, C Vignesh Kumar, and Ronald Albert Benton Carey

Subjects
medicine.medical_specialty, ARDS, Human immunodeficiency virus (HIV), lcsh:Medicine, 030209 endocrinology & metabolism, medicine.disease_cause, mortality outcomes, law.invention, Sepsis, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, medicine, 030212 general & internal medicine, intensive care, business.industry, Critically ill, Incidence (epidemiology), lcsh:R, medicine.disease, Intensive care unit, Emergency medicine, Cohort, HIV-positive patients, Original Article, business
Abstract

The incidence of (Human immune deficiency) HIV in India has fallen by 58% since the onset of the HIV epidemic. As of 2016 there are 2.1 million people living in India with HIV and only 49% of the adults with HIV are on ART (1). The HIV infected individuals may require intensive care due to various reasons. This study attempts to look at the outcomes of these patients admitted in the intensive care unit and the predictors of these outcomes. Aims: 1. To assess the outcomes of critically ill HIV infected patients admitted in the medical intensive care unit. 2. Assessment of the factors that are likely to influence the outcome. Materials and Methods: it is a retrospective medical review of all the patient records available on our electronic database. The study period was January 2008 – October 2013. Results: in our study cohort the commonest reason for admission into the intensive care unit was sepsis associated with multi organ dysfunction (64%).A low CD 4 count, renal failure acute respiratory distress syndrome, and hypotension and multi organ dysfunction were predictive of a poor outcome in our study. Conclusion: The most common cause of admission of PLHIV in ours study cohort was Infections, ART associated side effects and low CD4 counts, presence of multi organ dysfunction, acute respiratory distress syndrome (ARDS), hypotension were associated with adverse outcomes.

Published
2019

6. The Interhospital Medical Intensive Care Unit Transfer Instrument Facilitates Early Implementation of Critical Therapies and Is Associated With Fewer Emergent Procedures Upon Arrival

Author

Howard Charles Malpass, George M. Verghese, Jessica Keim-Malpass, and Kyle B. Enfield

Subjects
Adult, Male, Patient Transfer, Emergency Medical Services, medicine.medical_specialty, Critical Care, Non-Randomized Controlled Trials as Topic, Critical Illness, medicine.medical_treatment, Pilot Projects, Hospital mortality, Critical Care and Intensive Care Medicine, law.invention, law, Outcome Assessment, Health Care, Epidemiology, medicine, Humans, Intubation, Hospital Mortality, Intensive care medicine, APACHE, Aged, Icu mortality, Critically ill, business.industry, Length of Stay, Middle Aged, Intensive care unit, Intensive Care Units, Medical intensive care unit, Emergency medicine, Feasibility Studies, Female, business, Central venous catheter
Abstract

Background: Interhospital transportation of critically ill patients is challenging. The risk incurred by the patient is compounded when stabilization and application of appropriate therapies are delayed. The purpose of this study was to first develop an interhospital intensive care unit (ICU) transfer instrument to systematize communication and determine feasibility of use. Then, the transfer instrument was tested for effects on patient mortality, stability on arrival, and recommended therapy implementation. Method: The instrument was developed and pilot tested for 6 months to optimize function and applicability. Then, a before-and-after quasi-experimental study tested this instrument by assessing several key outcomes. Outcomes measured included 48-hour mortality, ICU mortality, hospital mortality, emergent intubation, emergent central venous catheter insertion, immediate change in antibiotics, and addition of vasopressors immediately on arrival. Patients were compared by age, gender, cause for admission, and Acute Physiology and Chronic Health Evaluation (APACHE) II score. A standardized mortality ratio was calculated using the patient’s APACHE II score. Pretransport recommendations to referring physicians and adherence to recommendations were also measured. Results: The preintervention group consisted of 134 patients collected continuously over 6 months. The postintervention group was collected continuously over a 6-month period and included 77 patients. The interhospital ICU transfer instrument was associated with fewer emergent central venous catheter insertions and fewer changes in antibiotics on arrival. Recommendations to transferring physicians were followed 90% of the time. Conclusions: The interhospital ICU transfer instrument is a tool that is effective in coordinating the transfer of medical ICU patients. Implementation leads to timely critical interventions and may reduce mortality.

Published
2014

7. Mutational Tail Loss Is an Evolutionary Mechanism for Liberating Marapsins and Other Type I Serine Proteases from Transmembrane Anchors

Author

Eric L. Schneider, Kavita Raman, Neil N. Trivedi, Wilfred W. Raymond, Daniel Kirchhofer, Shilpa Nimishakavi, Rajkumar Ganesan, George H. Caughey, George M. Verghese, and Charles S. Craik

Subjects
medicine.disease_cause, Medical and Health Sciences, Biochemistry, Serine, Mice, chemistry.chemical_compound, Cricetinae, 2.1 Biological and endogenous factors, Aetiology, Mutation, Serine Endopeptidases, food and beverages, Biological Sciences, Pan paniscus, Transmembrane protein, Mutant Strains, Biochemistry & Molecular Biology, Proteases, Pan troglodytes, Evolution, Guinea Pigs, Nonsense mutation, CHO Cells, Biology, Evolution, Molecular, Cricetulus, Species Specificity, medicine, Animals, Humans, Protease Inhibitors, Molecular Biology, Serine protease, Mole Rats, fungi, Leupeptin, Molecular, Membrane Proteins, Cell Biology, Mice, Mutant Strains, Rats, Solubility, Membrane protein, chemistry, Chemical Sciences, Enzymology, biology.protein, Cattle
Abstract

Human and mouse marapsins (Prss27) are serine proteases preferentially expressed by stratified squamous epithelia. However, mouse marapsin contains a transmembrane anchor absent from the human enzyme. To gain insights into physical forms, activities, inhibition, and roles in epithelial differentiation, we traced tail loss in human marapsin to a nonsense mutation in an ancestral ape, compared substrate preferences of mouse and human marapsins with those of the epithelial peptidase prostasin, designed a selective substrate and inhibitor, and generated Prss27-null mice. Phylogenetic analysis predicts that most marapsins are transmembrane proteins. However, nonsense mutations caused membrane anchor loss in three clades: human/bonobo/chimpanzee, guinea pig/degu/tuco-tuco/mole rat, and cattle/yak. Most marapsin-related proteases, including prostasins, are type I transmembrane proteins, but the closest relatives (prosemins) are not. Soluble mouse and human marapsins are tryptic with subsite preferences distinct from those of prostasin, lack general proteinase activity, and unlike prostasins resist antiproteases, including leupeptin, aprotinin, serpins, and α2-macroglobulin, suggesting the presence of non-canonical active sites. Prss27-null mice develop normally in barrier conditions and are fertile without overt epithelial defects, indicating that marapsin does not play critical, non-redundant roles in development, reproduction, or epithelial differentiation. In conclusion, marapsins are conserved, inhibitor-resistant, tryptic peptidases. Although marapsins are type I transmembrane proteins in their typical form, they mutated independently into anchorless forms in several mammalian clades, including one involving humans. Similar pathways appear to have been traversed by prosemins and tryptases, suggesting that mutational tail loss is an important means of evolving new functions of tryptic serine proteases from transmembrane ancestors.

Published
2013

8. Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor

Author

George M. Verghese, George H. Caughey, and Michael F. Gutknecht

Subjects
Male, Epithelial sodium channel, Glycosylation, Glycosylphosphatidylinositols, Physiology, Cell, Kidney, Cell junction, Exocytosis, Article, Cell Line, Mice, Phospholipase D, medicine, Animals, Secretion, Lung, Serine protease, Tight junction, biology, Serine Endopeptidases, Epithelial Cells, Cell Biology, Epithelium, Cell biology, medicine.anatomical_structure, Biochemistry, Mutagenesis, Site-Directed, biology.protein
Abstract

Prostasin, a trypsinlike serine peptidase, is highly expressed in prostate, kidney, and lung epithelia, where it is bound to the cell surface, secreted, or both. Prostasin activates the epithelial sodium channel (ENaC) and suppresses invasion of prostate and breast cancer cells. The studies reported here establish mechanisms of membrane anchoring and secretion in kidney and lung epithelial cells and demonstrate a critical role for prostasin in regulating epithelial monolayer function. We report that endogenous mouse prostasin is glycosylphosphatidylinositol (GPI) anchored to the cell surface and is constitutively secreted from the apical surface of kidney cortical collecting duct cells. Using site-directed mutagenesis, detergent phase separation, and RNA interference approaches, we show that prostasin secretion depends on GPI anchor cleavage by endogenous GPI-specific phospholipase D1 (Gpld1). Secretion of prostasin by kidney and lung epithelial cells, in contrast to prostate epithelium, does not depend on COOH-terminal processing at conserved Arg322. Using stably transfected M-1 cells expressing wild-type, catalytically inactive, or chimeric transmembrane (not GPI)-anchored prostasins we establish that prostasin regulates transepithelial resistance, current, and paracellular permeability by GPI anchor- and protease activity-dependent mechanisms. These studies demonstrate a novel role for prostasin in regulating epithelial monolayer resistance and permeability in kidney epithelial cells and, furthermore, show specifically that prostasin is a critical regulator of transepithelial ion transport in M-1 cells. These functions depend on the GPI anchor as well as the peptidase activity of prostasin. These studies suggest that cell-specific Gpld1- or peptidase-dependent pathways for prostasin secretion may control prostasin functions in a tissue-specific manner.

Published
2006

9. S-Nitrosylating Agents: A Novel Class of Compounds That Increase Cystic Fibrosis Transmembrane Conductance Regulator Expression and Maturation in Epithelial Cells

Author

Elizabeth Lendermon, Mark M. Ross, Benjamin Gaston, Edward W. Park, Silvia Carraro, Lisa A. Palmer, Lei Liu, Molly A. Zigler, Allan Doctor, Jonathan S. Stamler, Edward M. Henderson, Khalequz Zaman, George M. Verghese, and Joseph Doherty

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Cystic Fibrosis Transmembrane Conductance Regulator, Endogeny, Endoplasmic Reticulum, Cell Line, symbols.namesake, Humans, Gene silencing, HSP70 Heat-Shock Proteins, Pharmacology, Regulation of gene expression, S-Nitrosothiols, Molecular Structure, biology, Endoplasmic reticulum, Membrane Proteins, Cell Differentiation, Epithelial Cells, HSP40 Heat-Shock Proteins, respiratory system, Golgi apparatus, digestive system diseases, Cystic fibrosis transmembrane conductance regulator, Transmembrane protein, respiratory tract diseases, Cell biology, Gene Expression Regulation, S-Nitrosoglutathione, symbols, biology.protein, Molecular Medicine, Protein Processing, Post-Translational, Intracellular
Abstract

The endogenous bronchodilator, S-nitrosoglutathione (GSNO), increases expression, maturation, and function of both the wild-type and the DeltaF508 mutant of the cystic fibrosis transmembrane conductance regulatory protein (CFTR). Though transcriptional mechanisms of action have been identified, GSNO seems also to have post-transcriptional effects on CFTR maturation. Here, we report that 1) GSNO is only one of a class of S-nitrosylating agents that, at low micromolar concentrations, increase DeltaF508 and wild-type CFTR expression and maturation; 2) NO itself (at these concentrations) and 8-bromocyclic GMP are minimally active on CFTR; 3) a novel agent, S-nitrosoglutathione diethyl ester, bypasses the need for GSNO bioactivation by gamma-glutamyl transpeptidase to increase CFTR maturation; 4) surprisingly, expression-but not S-nitrosylation-of cysteine string proteins (Csp) 1 and 2 is increased by GSNO; 5) the effect of GSNO to increase full maturation of wild-type CFTR is inhibited by Csp silencing (si)RNA; 6) proteins relevant to CFTR trafficking are SNO-modified, and SNO proteins traffic through the endoplasmic reticulum (ER) and Golgi after GSNO exposure; and 7) GSNO alters the interactions of DeltaF508 CFTR with Csp and Hsc70 in the ER and Golgi. These data suggest that GSNO is one of a class of S-nitrosylating agents that act independently of the classic NO radical/cyclic GMP pathway to increase CFTR expression and maturation. They also suggest that the effect of GSNO is dependent on Csp and on intracellular SNO trafficking. We speculate that these data will be of relevance to the development of NO donor-based therapies for CF.

Published
2006

10. Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line

Author

Zhenyue Tong, Vikash J. Bhagwandin, Beate Illek, George M. Verghese, and George H. Caughey

Subjects
Pulmonary and Respiratory Medicine, Epithelial sodium channel, medicine.medical_specialty, Cystic Fibrosis, Glycosylphosphatidylinositols, Physiology, medicine.medical_treatment, Xenopus, Respiratory Mucosa, Biology, Cystic fibrosis, Gene Expression Regulation, Enzymologic, Sodium Channels, Cell Line, Serine, Epitopes, Aprotinin, Physiology (medical), Internal medicine, Escherichia coli, medicine, Humans, Trypsin, Gene Silencing, Epithelial Sodium Channels, Kidney, Protease, Serine Endopeptidases, Sodium, Epithelial Cells, Cell Biology, respiratory system, medicine.disease, biology.organism_classification, Recombinant Proteins, Epithelium, Cell biology, medicine.anatomical_structure, Endocrinology, Solubility, Cell culture
Abstract

Prostasin is a tryptic peptidase expressed in prostate, kidney, lung, and airway. Mammalian prostasins are related to Xenopus channel-activating protease, which stimulates epithelial Na+channel (ENaC) activity in frogs. In human epithelia, prostasin is one of several membrane peptidases proposed to regulate ENaC. This study tests the hypothesis that prostasin can regulate ENaC in cystic fibrosis epithelia in which excessive Na+uptake contributes to salt and water imbalance. We show that prostasin mRNA and protein are strongly expressed by human airway epithelial cell lines, including immortalized JME/CF15 nasal epithelial cells homozygous for the ΔF508 cystic fibrosis mutation. Epithelial cells transfected with vectors encoding recombinant soluble prostasin secrete active, tryptic peptidase that is highly sensitive to inactivation by aprotinin. When studied as monolayers in Ussing chambers, JME/CF15 cells exhibit amiloride-sensitive, transepithelial Na+currents that are markedly diminished by aprotinin, suggesting regulation by serine-class peptidases. Overproduction of membrane-anchored prostasin in transfected JME/CF15 cells does not augment Na+currents, and trypsin-induced increases are small, suggesting that baseline serine peptidase-dependent ENaC activation is maximal in these cells. To probe prostasin’s involvement in basal ENaC activity, we silenced expression of prostasin using short interfering RNA targeting of prostasin mRNA’s 3′-untranslated region. This drops ENaC currents to 26 ± 9% of baseline. These data predict that prostasin is a major regulator of ENaC-mediated Na+current in ΔF508 cystic fibrosis epithelia and suggest that airway prostasin is a target for therapeutic inhibition to normalize ion current in cystic fibrosis airway.

Published
2004

12. Mouse prostasin gene structure, promoter analysis, and restricted expression in lung and kidney

Author

George M. Verghese, Vikash J. Bhagwandin, Z. Y. Tong, and George H. Caughey

Subjects
Pulmonary and Respiratory Medicine, Untranslated region, Male, 5' Flanking Region, Clinical Biochemistry, 5' flanking region, Molecular Sequence Data, Gene Expression, Biology, Kidney, Mice, Gene expression, Animals, Cloning, Molecular, Enhancer, Promoter Regions, Genetic, Molecular Biology, 3' Untranslated Regions, Lung, Regulation of gene expression, Reporter gene, Base Sequence, Three prime untranslated region, PRSS8, Serine Endopeptidases, Prostate, Chromosome Mapping, Gene Expression Regulation, Developmental, Epithelial Cells, Cell Biology, Molecular biology, Rats, Kidney Tubules, Organ Specificity
Abstract

Human prostasin is a membrane-anchored serine peptidase hypothesized to regulate lung epithelial sodium transport. It belongs to a unique family of genes on chromosome 16p11.2/13.3. Here we describe genomic cloning, promoter analysis, and expression of prostasin's mouse ortholog. The 4.3-kb mouse prostasin gene (prss8) has a six-exon organization identical to human prostasin. Prss8 spans two signal tagged-sites localized to chromosome 7. Multiple mRNA transcripts arise from two consensus initiator elements of a TATA-less promoter and an alternatively spliced, 5' untranslated region intron. Reporter assay establishes that the initiator elements and a GC-rich domain comprise the core promoter and identifies 5' flanking regions with strong enhancer and repressor activity. The 3' untranslated region overlaps the 3' untranslated region of the Myst1 gene oriented tail-to-tail at this locus. Prss8 is highly transcribed in pancreas, kidney, submaxillary gland, lung, thyroid, prostate, and epididymis, and is developmentally regulated. Using selective riboprobes and antibodies to mouse prostasin, we localized its expression to lung airway epithelial and alveolar type II cells and kidney cortical tubule epithelium. Mouse prostasin highly resembles its human ortholog in gene organization and tissue specificity, including strong expression in pulmonary epithelium, suggesting that mice will be useful for probing prostasin's functions in vivo.

Published
2003

13. Multifocal metachronous osteogenic sarcoma

Author

SUSHlL M. Chandi, G.D. Sundararaj, V. Sarada, and George M Verghese

Subjects
Male, Osteosarcoma, Adolescent, business.industry, Skull Neoplasms, Bone Neoplasms, Tarsal Bones, medicine.disease, Neoplasms, Multiple Primary, Text mining, Fibula, Sphenoid Bone, medicine, Cancer research, Humans, Radiology, Nuclear Medicine and imaging, Sarcoma, business
Published
1992

14. Outcomes and factors influencing outcomes of critically ill HIV-positive patients in a tertiary care center in South India

Author

I Ramya, Shubankar Mitra, Shilpa D'Sa, Sowmya Sathyendra, Anand Zachariah, C Vignesh Kumar, Ronald Albert Benton Carey, and George M Verghese

Subjects
HIV-positive patients, intensive care, mortality outcomes, Medicine
Abstract

The incidence of (Human immune deficiency) HIV in India has fallen by 58% since the onset of the HIV epidemic. As of 2016 there are 2.1 million people living in India with HIV and only 49% of the adults with HIV are on ART (1). The HIV infected individuals may require intensive care due to various reasons. This study attempts to look at the outcomes of these patients admitted in the intensive care unit and the predictors of these outcomes. Aims: 1. To assess the outcomes of critically ill HIV infected patients admitted in the medical intensive care unit. 2. Assessment of the factors that are likely to influence the outcome. Materials and Methods: it is a retrospective medical review of all the patient records available on our electronic database. The study period was January 2008 – October 2013. Results: in our study cohort the commonest reason for admission into the intensive care unit was sepsis associated with multi organ dysfunction (64%).A low CD 4 count, renal failure acute respiratory distress syndrome, and hypotension and multi organ dysfunction were predictive of a poor outcome in our study. Conclusion: The most common cause of admission of PLHIV in ours study cohort was Infections, ART associated side effects and low CD4 counts, presence of multi organ dysfunction, acute respiratory distress syndrome (ARDS), hypotension were associated with adverse outcomes.

Published
2019
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