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1. Kidney Recovery and Death in Critically Ill Patients With COVID-19-Associated Acute Kidney Injury Treated With Dialysis: The STOP-COVID Cohort Study

Author

Caroline M. Hsu, Shruti Gupta, Hocine Tighiouart, Nitender Goyal, Anthony J. Faugno, Asma Tariq, Ritesh Raichoudhury, Jill H. Sharma, Leah Meyer, Ravi K. Kshirsagar, Aju Jose, David E. Leaf, Daniel E. Weiner, Hsu Gupta, Goyal Faugno, Tariq Raichoudhury, Sharma Meyer, Kshirsagar Leaf, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Shahzad Shaefi, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Kenneth A. Bauer, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Ajiboye Oyintayo, Adam Green, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Alexandre M. Shehata, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino WilliamsSamantha K. Brenner, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Miguel A. Hernán, Amy M. Zhou, Ethan C. Kim, Rebecca Lisk, Lili Chan, Kusum S. Mathews, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Pattharawin Pattharanitima, Emily J. Gallagher, Allon N. Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Katherine J. Kelly, Chirag R. Parikh, Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, Samir C. Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddhartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Leon Boudourakis, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Kianoush Kashani, Shahrzad Tehranian, Yan Zhou, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Michal L. Melamed, Tanya S. Johns. Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Jyotsana Thakkar, Neelja Kumar, Michael J. Ross, Michael Chang, Akshay Athreya, Mohamed Farag, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Anand Srivastava, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner M.B. Mohamed, Rupali S. Avasare, David Zonies, Hanny Al-Samkari, Rebecca Karp Leaf, Rachel Rosovsky, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Roberta E. Redfern, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhani-Lovely, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Jared Radbel, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth S. Vatson, George Karp, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Moh’d A. Sharshir, Vadym V. Rusnak, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Arash Rashidi, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Carl E. Schulze, Etienne Macedo, Harin RheeKa, null thleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Stephanie M. Toth-Manikowski, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Madona Elias, Yahya Ahmad, Rajany Dy, Alfredo Iardino, Elizabeth H. Au, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Hayley B. Gershengorn, Alessia Fornoni, Salim S. Hayek, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’Hayer, Chelsea Meloche, Rafey Feroze, Kishan J. Padalia, Jeff Leya, John P. Donnelly, Andrew J. Admon, Jennifer E. Flythe, Matthew J. Tugman, Emily H. Chang, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Amar D. Bansal, Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, S. Susan Hedayati, Mridula V. Nadamuni, Shani Shastri, Duwayne L. Willett, Samuel A.P. Short, Amanda D. Renaghan, Kyle B. Enfield, Pavan K. Bhatraju, A. Bilal Malik, Matthew W. Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Savneek Chugh, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Adult, urogenital system, SARS-CoV-2, Critical Illness, Aftercare, COVID-19, Original Investigations, Acute Kidney Injury, urologic and male genital diseases, Kidney, Patient Discharge, Cohort Studies, critical care, Intensive Care Units, Nephrology, Renal Dialysis, Risk Factors, urine output, Humans, dialysis, chronic kidney disease, Retrospective Studies
Abstract

Rationale & Objective Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with COVID-19. We examined the clinical factors that determine kidney recovery in this population. Study Design Multicenter cohort study. Setting & Participants 4221 adults with COVID-19 not receiving kidney replacement therapy who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the “ICU cohort”). Among these, 876 developed AKI-KRT after admission to the ICU (the “AKI-KRT subcohort”). Exposure(s) The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of dialysis initiation. Outcome(s) The outcome for the ICU cohort was estimated glomerular filtration rate (GFR) at hospital discharge. A three-level outcome including death, kidney nonrecovery, and kidney recovery at discharge, was analyzed for the AKI-KRT subcohort. Analytical approach The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. Results Among a total of 4221 patients in the ICU cohort, 2361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower estimated GFR with odds ratios (ORs) of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for CKD GFR categories 3, 4, and 5, respectively, compared to estimated GFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (OR 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and, Critically ill patients with COVID-19 often develop acute kidney injury (AKI). This study of 4221 patients demonstrated that more severe AKI was associated with greater in-hospital mortality and poorer kidney function at hospital discharge. Among the 876 patients who required dialysis for AKI, almost two-thirds died. Among those who survived to discharge, about two-thirds recovered kidney function and were discharged without the need for dialysis. Lower baseline kidney function and reduced urine output were associated with non-recovery of kidney function. Identification of such predictors is important in assessing prognosis among these critically ill patients and has implications for clinical care of individuals critically ill with COVID-19.

Published
2021

2. Performance of crisis standards of care guidelines in a cohort of critically ill COVID-19 patients in the United States

Author

Huei Hsun Wen, Vishal Jaikaransingh, Ernie Yap, Matthew T. Scharf, Jiahua Li, Samir Gautam, Jeffery O. Boateng, John Guirguis, Timothy E. Albertson, Shuchi Anand, Kathleen D. Liu, Amar D. Bansal, Alessia Fornoni, Caroline M. Hsu, Simon Correa, Natalie C. Ernecoff, Chris Rowan, William Feldman, Rupali S. Avasare, Maureen Brogan, Etienne Macedo, Nourhan Chaaban, Sabrina Taldone, Ryan Mocerino, Nilam P. Patel, Christopher Meshberger, Muner Mb. Mohamed, Joy-Marie Hermes, Ritesh Raichoudhury, Jamuna Krishnan, Amy M. Zhou, Abbas Bitar, Danny Perry, Barbara A. Danek, Allon N. Friedman, Salim S. Hayek, Richard G. Wunderink, Duwayne L. Willett, Moh’d A. Sharshir, Luis G. Gomez-Escobar, Wei Wang, Nicholas S. Cairl, Lisa Shea, Miguel A. Hernán, Christa A. Schorr, Rubab F. Malik, Patricia F. Kao, John Wagner, Patrick O’ Hayer, Sonika Puri, Shreyak Sharma, Mariah Thaxton, Seble G. Kassaye, Sidharth Shankar, Paul A. Bergl, Hayley B. Gershengorn, Sanjeev Gupta, Ibrahim Mohamed, Sushrut S. Waikar, Dheeraj Reddy Sirganagari, Jill H. Sharma, Gohar Mosoyan, Kyle B. Enfield, Ian A. Strohbehn, Thuy-Duyen Nguyen, Suzanne M. Boyle, Brent Brown, Rebecca V. Levy, Vasantha K. Jotwani, Alexandre M. Shehata, Maria Plataki, Julia L. Jezmir, Valerie Allusson, Jennifer Griffiths, Chirag R. Parikh, Alfredo Iardino, Emily H. Chang, Sanjana Kapoor, Tanira Ferreira, Harin Rhee, Nicholas Sadovnikoff, Aquino Williams, Vivian S. Cruz, Jay L. Koyner, Kristen M. Hess, Leon Boudourakis, Shahzad Shaefi, Vasil Peev, Omer Kamal, Ugochukwu Ugwuowo, Aromma Kapoor, Anitha Vijayan, Jared Radbel, Husam Shadid, Vadym V. Rusnak, Pattharawin Pattharanitima, Aju Jose, Yohannes Adama Melaku, Jayanth S. Vatson, Tariq U. Azam, Yahya Ahmad, William Whalen, Meghan Lee, Shani Shastri, David De La Zerda, Goni Katz-Greenberg, Hanna Berlin, Todd A. Miano, Seth Goldberg, Jatan A. Shah, Frank Modersitzki, Jag Sunderram, Anna E. Hasty, Esha M. Kapania, Samantha K. Brenner, Pennelope K. Blakely, Elizabeth H. Au, Ronaldo C. Go, Keith M. Rose, Anand Srivastava, Kathleen F. Kopecky, Ilya Berim, Alexander Chaitoff, Danyell Hall, Jingjing Zhang, Michel Chonchol, Gabriel Naimy, Sejal B. Shah, Stephanie M. Toth-Manikowski, Christina Mariyam Joy, Deepa G. Lazarous, Matthew W. Semler, Mark Liotta, Mridula V. Nadamuni, Greg L. Schumaker, Patricia Walters, Joseph E. Levitt, Steven G. Coca, Rana Hejal, Stefi Lee, Pramod Guru, Noor ul aain Bhatti, Jennifer E. Flythe, Daniel L. Edmonston, Asma Tariq, John J. Byun, Jesus Rodriguez, Mrigank S. Gupta, Andrew Vissing, Michal L. Melamed, Howard Soh, Adam E. Green, Yorg Azzi, Ladan Golestaneh, Amee Patrawalla, Amber S. Podoll, Ryan C. Spiardi, Xiaoying Deng, Ishaan Vohra, Carl P. Walther, Michael Chang, John P. Donnelly, David M. Charytan, Anthony J. Faugno, Peter Hart, Ameeka Pannu, Sandeep P. Kishore, Roberta E. Redfern, Ambreen Azhar, Meghan E. Sise, Di Pan, Sang Hoon Woo, H. Bryant Nguyen, Pavan K. Bhatraju, Bradford Diephuis, Justin Arunthamakun, Kaltrina Sedaliu, Ajiboye Oyintayo, Aimee Milliken, Andrew J Admon, Elena Cervantes, Erik T. Newman, Heather Yang, Lili Chan, Nitender Goyal, Peter Cangialosi, Arash Rashidi, David Zonies, Juan D. Valencia, Rebecca Lisk, Zoe Post, Farah Madhani-Lovely, Benjamin M. Wu, Princy N. Kumar, Ethan C. Kim, Maheetha Bharadwaj, Chintan V. Shah, A. Bilal Malik, Siddartha Bajracharya, Gabriela Bambrick-Santoyo, Conor P. Crowley, Ellen L. Burnham, Kianoush Kashani, Ashley Macina, Diana Finkel, Rebecca M. Beutler, Sowminya Arikapudi, Ayesha Ahmed, Edward J. Schenck, Kishan Padalia, Aparna Saha, Alexander J. Hodakowski, Tanya S. Johns, Rayan Kaakati, James P. Lash, Bhavarth Shukla, Mary Mallappallil, Eboni G. Price-Haywood, Steven Menez, Samaya J. Anumudu, Christopher L. Mosher, Rajat Kapoor, Harkarandeep Singh, Amanda K. Leonberg-Yoo, Rui Song, Samah Abu Omar, Laura Latta, Siddharth Verma, Steven Y. Chang, Soo Jung Cho, Emily Leven, Denzel Zhu, Jing G. Wang, Katharine Senter, Bijal Mehta, Ariel Mueller, Peter A. McCullough, Alexander S. Leidner, Milagros Yunes, Akshay Athreya, Carlos Martinez, Muhammad Imran Ali, Matthew J. Tugman, Laura Bickley, Perry Wilson, Chanu Rhee, Ambarish M. Athavale, Shruti Gupta, Samuel A.P. Short, S. Susan Hedayati, Neelja Kumar, Abeer Abu-Saif, Jeffrey M. Paer, Sobaata Chaudhry, Louis T. Merriam, Jochen Reiser, Gabriel Contreras, Eric Judd, Isha Puri, Marta Christov, Afshin Ahoubim, Leslie F. Thomas, Tanima Arora, Eric Goralnick, Elizabeth Anderson, Csaba P. Kovesdy, Alanna L. Jacobs, Marie Anne Sosa, Ashita Tolwani, Ravi K. Kshirsagar, Jason Y. Adams, Tingting Li, Javier A. Neyra, Deena R. Altman, Anip Bansal, Katherine J. Kelly, Sunita Sharma, Jean-Sebastien Rachoin, Zoe A. Kibbelaar, Celia P. Corona-Villalobos, Juan Carlos Q. Velez, Tanveer Shaukat, Leah Meyer, Kalyan Prudhvi, Edy Y. Kim, Madona Elias, Brian T. Garibaldi, Miklos Z. Molnar, Megan L. Krajewski, Sabu John, Girish N. Nadkarni, Molly Fisher, Michael Pan, Zaza Cohen, Min J. Joo, Yumeng Wen, Kapil K. Pokharel, Kusum S. Mathews, Shristi Upadhyay, Charles R. Vasquez, Amanda DeMauro Renaghan, Sergio L. Alvarez-Mulett, Rafey Feroze, Jacqueline M. Kruser, Daniel E. Weiner, Anne Sutherland, Jie Ouyang, Mohamed Farag, Gregory P. Milligan, Meaghan S. Roche, Luis A. Matute-Trochez, Chelsea Meloche, Yan Zhou, Jyotsna Bhattacharya, Sonali Bose, and David E. Leaf

Subjects
Adult, Male, Medicine (General), medicine.medical_specialty, Exacerbation, Critical Care, Organ Dysfunction Scores, Critical Illness, Population, Comorbidity, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, R5-920, Intensive care, medicine, Humans, Hospital Mortality, Intensive care medicine, education, Pandemics, intensive care, Aged, Retrospective Studies, education.field_of_study, crisis standards of care, Receiver operating characteristic, business.industry, SARS-CoV-2, Crew Resource Management, Healthcare, COVID-19, Standard of Care, Middle Aged, medicine.disease, Triage, United States, medical ethics, Cohort, Practice Guidelines as Topic, SOFA score, Female, triage, business, Algorithms
Abstract

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Published
2021

3. Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19

Author

Hanny Al-Samkari, Shruti Gupta, Rebecca Karp Leaf, Wei Wang, Rachel P. Rosovsky, Samantha K. Brenner, Salim S. Hayek, Hanna Berlin, Rajat Kapoor, Shahzad Shaefi, Michal L. Melamed, Anne Sutherland, Jared Radbel, Adam Green, Brian T. Garibaldi, Anand Srivastava, Amanda Leonberg-Yoo, Alexandre M. Shehata, Jennifer E. Flythe, Arash Rashidi, Nitender Goyal, Lili Chan, Kusum S. Mathews, S. Susan Hedayati, Rajany Dy, Stephanie M. Toth-Manikowski, Jingjing Zhang, Mary Mallappallil, Roberta E. Redfern, Amar D. Bansal, Samuel A.P. Short, Mark G. Vangel, Andrew J. Admon, Matthew W. Semler, Kenneth A. Bauer, Miguel A. Hernán, David E. Leaf, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Ajiboye Oyintayo, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Amy M. Zhou, Ethan C. Kim, Rebecca Lisk, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Pattharawin Pattharanitima, Emily J. Gallagher, Allon N. Friedman, John Guirguis, Christopher Meshberger, Katherine J. Kelly, Chirag R. Parikh, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, Samir C. Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddhartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Leon Boudourakis, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Yan Zhou, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Jyotsana Thakkar, Neelja Kumar, Michael J. Ross, Michael Chang, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner M.B. Mohamed, Rupali S. Avasare, David Zonies, Rachel Rosovsky, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhani-Lovely, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth S. Vatson, George Karp, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Moh'd A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Carl E. Schulze, Etienne Macedo, Harin Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Madona Elias, Yahya Ahmad, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Hayley B. Gershengorn, Alessia Fornoni, Pennelope Blakely, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’Hayer, Chelsea Meloche, Rafey Feroze, Kishan J. Padalia, Jeff Leya, John P. Donnelly, Matthew J. Tugman, Emily H. Chang, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, Mridula V. Nadamuni, Shani Shastri, Duwayne L. Willett, Amanda D. Renaghan, Kyle B. Enfield, Pavan K. Bhatraju, A. Bilal Malik, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Daniel E. Weiner, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Savneek Chugh, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Male, medicine.medical_specialty, Critical Illness, Hemorrhage, 01 natural sciences, law.invention, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, law, Internal Medicine, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, Survival rate, Original Research, Aged, Proportional hazards model, business.industry, SARS-CoV-2, Incidence (epidemiology), 010102 general mathematics, Hazard ratio, Anticoagulants, COVID-19, General Medicine, Venous Thromboembolism, Blood Coagulation Disorders, Middle Aged, Intensive care unit, United States, Survival Rate, Intensive Care Units, Emergency medicine, Observational study, Female, business, Cohort study
Abstract

Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival. Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. Setting: 67 hospitals in the United States. Participants: Adults with COVID-19 admitted to a participating ICU. Measurements: Time to death, censored at hospital discharge, or date of last follow-up. Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Limitation: Observational design. Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. Primary Funding Source: None.

Published
2021

4. Self‐derived structure‐disrupting peptides targeting methionine aminopeptidase in pathogenic bacteria: a new strategy to generate antimicrobial peptides

Author

Kate L. Seib, Yaoqi Zhou, Freda E.-C. Jen, Amy M. Zhou, Michael P. Jennings, Evgeny A. Semchenko, Makrina Totsika, Qizhuang Ye, Yuedong Yang, Husen Jia, Yunqiang Bian, Thomas Haselhorst, Helen Blanchard, Sohinee Sarkar, Jihua Wang, Jian Zhan, and Zhixiu Li

Subjects
0301 basic medicine, medicine.drug_class, Antibiotics, Antimicrobial peptides, Peptide, Cervix Uteri, Microbial Sensitivity Tests, medicine.disease_cause, Aminopeptidases, Biochemistry, Microbiology, Gonorrhea, 03 medical and health sciences, Methionine, 0302 clinical medicine, Antibiotic resistance, Drug Resistance, Multiple, Bacterial, Genetics, medicine, Humans, Molecular Biology, Escherichia coli, Cells, Cultured, Cell Proliferation, chemistry.chemical_classification, biology, Chemistry, Research, Pathogenic bacteria, biology.organism_classification, Neisseria gonorrhoeae, Anti-Bacterial Agents, 030104 developmental biology, Female, 030217 neurology & neurosurgery, Bacteria, Antimicrobial Cationic Peptides, Biotechnology
Abstract

Bacterial infection is one of the leading causes of death in young, elderly, and immune-compromised patients. The rapid spread of multi-drug-resistant (MDR) bacteria is a global health emergency and there is a lack of new drugs to control MDR pathogens. We describe a heretofore-unexplored discovery pathway for novel antibiotics that is based on self-targeting, structure-disrupting peptides. We show that a helical peptide, KFF- EcH3, derived from the Escherichia coli methionine aminopeptidase can disrupt secondary and tertiary structure of this essential enzyme, thereby killing the bacterium (including MDR strains). Significantly, no detectable resistance developed against this peptide. Based on a computational analysis, our study predicted that peptide KFF- EcH3 has the strongest interaction with the structural core of the methionine aminopeptidase. We further used our approach to identify peptide KFF- NgH1 to target the same enzyme from Neisseria gonorrhoeae. This peptide inhibited bacterial growth and was able to treat a gonococcal infection in a human cervical epithelial cell model. These findings present an exciting new paradigm in antibiotic discovery using self-derived peptides that can be developed to target the structures of any essential bacterial proteins.-Zhan, J., Jia, H., Semchenko, E. A., Bian, Y., Zhou, A. M., Li, Z., Yang, Y., Wang, J., Sarkar, S., Totsika, M., Blanchard, H., Jen, F. E.-C., Ye, Q., Haselhorst, T., Jennings, M. P., Seib, K. L., Zhou, Y. Self-derived structure-disrupting peptides targeting methionine aminopeptidase in pathogenic bacteria: a new strategy to generate antimicrobial peptides.

Published
2018
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