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1. COVID-19 Survival and its impact on chronic kidney disease

Author

Ian A. Strohbehn, Meghan E. Sise, Roby P. Bhattacharyya, Rani Sawtell, and Joshua D. Long

Subjects
COVID-19 and Chronic Kidney Disease, medicine.medical_specialty, Kidney Glomerulus, Renal function, Physiology (medical), Internal medicine, Biopsy, Humans, Medicine, Renal Insufficiency, Chronic, Risk factor, Prospective cohort study, Kidney, medicine.diagnostic_test, SARS-CoV-2, urogenital system, business.industry, Incidence (epidemiology), Biochemistry (medical), Public Health, Environmental and Occupational Health, Acute kidney injury, COVID-19, General Medicine, medicine.disease, Survival Analysis, medicine.anatomical_structure, business, Kidney disease
Abstract

Up to 87% of patients hospitalized with coronavirus disease 2019 (COVID-19) experience chronic sequelae following infection. The long-term impact of COVID-19 infection on kidney function is largely unknown at this point in the COVID-19 pandemic. In this review, we highlight the current understanding of the pathophysiology of COVID-19-associated kidney injury and the impact COVID-19 may have on long-term kidney function. COVID-19-induced acute kidney injury may lead to tubular injury, endothelial injury, and glomerular injury. We highlight histopathologic correlates from large kidney biopsy and autopsy series. By conducting a comprehensive review of published literature to date, we summarize the rates of recovery from COVID-19-associated-AKI. Finally, we discuss how certain genetic differences, including APOL1 risk alleles (a risk factor for collapsing glomerulopathy), coupled with systemic healthcare disparities, may lead to a disproportionate burden of post-COVID-19-kidney function decline among racial and ethnic minority groups. We highlight the need for prospective studies to determine the true incidence of chronic kidney disease burden after COVID-19.

Published
2022

2. Association of donor hepatitis C virus infection status and risk of BK polyomavirus viremia after kidney transplantation

Author

Ambreen Azhar, Anshul Bhalla, Rachel C. Forbes, Beatrice P. Concepcion, Roy D. Bloom, Deirdre Sawinski, Miklos Z Molnar, Jennifer Trofe-Clark, Raymond T. Chung, Peter P. Reese, Vasanthi Balaraman, David Shaffer, Ian A. Strohbehn, Behdad Besharatian, Douglas E. Schaubel, Emily A. Blumberg, Mital Shah, David S. Goldberg, Manish Talwar, Laura A Binari, Nahel Elias, James D. Eason, Vishnu S. Potluri, and Meghan E. Sise

Subjects
Nephrology, medicine.medical_specialty, Hepatitis C virus, Viremia, Hepacivirus, medicine.disease_cause, Gastroenterology, Article, Nephropathy, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Kidney transplantation, Retrospective Studies, Polyomavirus Infections, Transplantation, Kidney, business.industry, Proportional hazards model, virus diseases, Retrospective cohort study, medicine.disease, Kidney Transplantation, Tumor Virus Infections, medicine.anatomical_structure, BK Virus, business
Abstract

Kidney transplantation (KT) from deceased donors with hepatitis C virus (HCV) into HCV-negative recipients has become more common. However, the risk of complications such as BK polyomavirus (BKPyV) remains unknown. We assembled a retrospective cohort at four centers. We matched recipients of HCV-viremic kidneys to highly similar recipients of HCV-aviremic kidneys on established risk factors for BKPyV. To limit bias, matches were within the same center. The primary outcome was BKPyV viremia ≥1000 copies/ml or biopsy-proven BKPyV nephropathy; a secondary outcome was BKPyV viremia ≥10 000 copies/ml or nephropathy. Outcomes were analyzed using weighted and stratified Cox regression. The median days to peak BKPyV viremia level was 119 (IQR 87-182). HCV-viremic KT was not associated with increased risk of the primary BKPyV outcome (HR 1.26, p = .22), but was significantly associated with the secondary outcome of BKPyV ≥10 000 copies/ml (HR 1.69, p = .03). One-year eGFR was similar between the matched groups. Only one HCV-viremic kidney recipient had primary graft loss. In summary, HCV-viremic KT was not significantly associated with the primary outcome of BKPyV viremia, but the data suggested that donor HCV might elevate the risk of more severe BKPyV viremia ≥10 000 copies/ml. Nonetheless, one-year graft function for HCV-viremic recipients was reassuring.

Published
2022

3. Immune-related adverse events and kidney function decline in patients with genitourinary cancers treated with immune checkpoint inhibitors

Author

Harish Seethapathy, Sarah Street, Xiao Wei, Shveta S. Motwani, Kerry L. Reynolds, Toni K. Choueiri, Nifasha Rusibamayila, Ian A. Strohbehn, Meghan Lee, M.D. Michaelson, Brad McGregor, Cristina Salabao, Guru Sonpavde, Meghan E. Sise, David E. Leaf, Shruti Gupta, Sophia H. Zhao, Donald F. Chute, Xin Gao, Marina D. Kaymakcalan, and Osama E. Rahma

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Renal function, Renal cell carcinoma, Internal medicine, medicine, Humans, Cumulative incidence, Adverse effect, Carcinoma, Renal Cell, Immune Checkpoint Inhibitors, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Acute kidney injury, Cancer, Retrospective cohort study, Acute Kidney Injury, Middle Aged, medicine.disease, Kidney Neoplasms, Urinary Bladder Neoplasms, Cohort, Female, business, Glomerular Filtration Rate
Abstract

Background In patients with genitourinary cancers, the effect of immune checkpoint inhibitors (ICIs) on kidney function is unknown. Patients and methods This is a retrospective cohort study of patients with renal cell carcinoma (RCC) and urothelial carcinoma who received ICIs at two major cancer centers between 2012 and 2018. Cumulative incidence and Fine and Gray subdistribution hazard models were performed to determine predictors of the co-primary outcomes, (1) acute kidney injury (AKI) and (2) sustained estimated glomerular filtration rate (eGFR) loss, defined as a >20% decline in eGFR sustained ≥90 days. We also determined the association between immune-related adverse events (irAE) and adverse kidney outcomes among patients surviving ≥1 year. Results 637 patients were included; 320 (50%) patients had RCC and 317 (50%) patients had urothelial carcinoma. Half of the cohort had eGFR Conclusion AKI and sustained eGFR loss are common in patients with genitourinary cancers receiving ICIs. irAEs may be a novel risk factor for kidney function decline among patients receiving ICIs.

Published
2021

4. Curative Therapies for Hepatitis C Virus Infection in Patients with Kidney Disease

Author

Ian A. Strohbehn, Meghan Lee, Rituvanthikaa Seethapathy, and Meghan E. Sise

Subjects
medicine.medical_specialty, Hepatitis C virus, 030232 urology & nephrology, Review Article, Hepacivirus, 030204 cardiovascular system & hematology, medicine.disease_cause, Dialysis patients, DIRECT ACTING ANTIVIRALS, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Internal medicine, Humans, Medicine, In patient, Renal Insufficiency, Chronic, Risk factor, Adverse effect, business.industry, General Medicine, Hepatitis C, Chronic, medicine.disease, Hepatitis C, Clinical trial, business, Kidney disease
Abstract

Through the discovery of direct-acting antiviral therapies over the last decade, Hepatitis C virus (HCV) has been transformed from a highly morbid and potentially fatal chronic viral infection to a curable illness. HCV is common in patients with kidney disease and is a risk factor for progression of chronic kidney disease, is associated with higher morbidity and mortality in dialysis patients and leads to worse allograft and patient outcomes in kidney transplant recipients. Clinical trial and real-world data of direct acting antivirals in patients with kidney disease demonstrate extremely high cure rates and favorable adverse event profiles. This review covers the transformative effects of curative HCV therapies on patients with kidney disease including patients with chronic kidney disease, end-stage kidney disease, and kidney transplant recipients.

Published
2021

5. Clinical features of acute kidney injury in patients receiving dabrafenib and trametinib

Author

Nifasha Rusibamayila, Harish Seethapathy, Riley Fadden, Ivy A. Rosales, Ian A. Strohbehn, Kenar D. Jhaveri, Meghan E. Sise, Ryan J. Sullivan, Kerry L. Reynolds, Robert B. Colvin, Howard L. Kaufman, Orhan Efe, Meghan Lee, and Donald F. Chute

Subjects
Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Pyridones, Pyrimidinones, urologic and male genital diseases, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Oximes, medicine, Humans, 030212 general & internal medicine, Melanoma, Retrospective Studies, Trametinib, Transplantation, urogenital system, business.industry, Incidence (epidemiology), Imidazoles, Acute kidney injury, Dabrafenib, Retrospective cohort study, Acute Kidney Injury, medicine.disease, female genital diseases and pregnancy complications, Nephrology, 030220 oncology & carcinogenesis, Mutation, Cohort, Original Article, Chills, medicine.symptom, business, medicine.drug
Abstract

Background Our objective was to characterize the incidence, risk factors and clinical features of acute kidney injury (AKI) in patients receiving dabrafenib and trametinib. Methods We performed a retrospective cohort study examining the kidney outcomes of patients in a large healthcare system who received dabrafenib/trametinib between 2010 and 2019. The primary outcome was AKI, defined as a 1.5-fold increase in serum creatinine from baseline within a 12-month study period. AKI severity and etiology was determined for each case by chart review. Logistic regression was used to evaluate baseline predictors of AKI. Results A total of 199 patients who received dabrafenib in our healthcare system from 2010 to 2019 were included in the analysis. Forty-two patients (21%) experienced AKI within 12 months; 10 patients (5% of the total cohort, 24% of AKI patients) experienced AKI occurring during a dabrafenib/trametinib-induced febrile syndrome characterized by fever, chills, gastrointestinal symptoms and elevated liver enzymes. Preexisting liver disease was the only significant predictor of AKI in the cohort. One patient had biopsy-proven granulomatous acute interstitial nephritis that resolved with corticosteroids. Conclusions Oncologists and nephrologists should be aware that AKI is common after dabrafenib/trametinib and a substantial number of cases occur in the setting of treatment-induced pyrexia.

Published
2020

6. Acute Kidney Injury After the CAR-T Therapy Tisagenlecleucel

Author

Meghan E. Sise, Meghan Lee, Matthew J. Frigault, Ian A. Strohbehn, Nifasha Rusibamayila, Keagan S Casey, David E. Leaf, Harish Seethapathy, and Shruti Gupta

Subjects
Adult, Male, medicine.medical_specialty, Receptors, Chimeric Antigen, business.industry, Receptors, Antigen, T-Cell, MEDLINE, Acute kidney injury, Acute Kidney Injury, Middle Aged, medicine.disease, Immunotherapy, Adoptive, Article, Text mining, Nephrology, Internal medicine, medicine, Humans, Female, Car t cells, business, Aged, Retrospective Studies
Published
2021

7. Acute Kidney Injury and Electrolyte Abnormalities After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Diffuse Large B-Cell Lymphoma

Author

Matthew J. Frigault, Ian A. Strohbehn, Gary C. Curhan, Harish Seethapathy, David E. Leaf, Samir M. Parikh, Meghan E. Sise, Shruti Gupta, Elizabeth O'Donnell, Shveta S. Motwani, Caron A. Jacobson, and Kerry L. Reynolds

Subjects
Male, medicine.medical_specialty, Water-Electrolyte Imbalance, 030232 urology & nephrology, Immunotherapy, Adoptive, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Acute tubular necrosis, Aged, business.industry, Acute kidney injury, Acute Kidney Injury, Middle Aged, Water-Electrolyte Balance, medicine.disease, Cytokine release syndrome, Nephrology, Female, Lymphoma, Large B-Cell, Diffuse, Hyponatremia, Complication, business, Diffuse large B-cell lymphoma, Hypophosphatemia, Kidney disease
Abstract

Rationale & Objective Cytokine release syndrome is a well-known complication of chimeric antigen receptor T-cell (CAR-T) therapy and can lead to multiorgan dysfunction. However, the nephrotoxicity of CAR-T therapy is unknown. We aimed to characterize the occurrence, cause, and outcomes of acute kidney injury (AKI), along with the occurrence of electrolyte abnormalities, among adults with diffuse large B-cell lymphoma receiving CAR-T therapy. Study Design Case series. Setting & Participants We reviewed the course of 78 adults receiving CAR-T therapy with axicabtagene ciloleucel or tisagenlecleucel at 2 major cancer centers between October 2017 and February 2019. Baseline demographics, comorbid conditions, medications, and laboratory values were obtained from electronic health records. AKI was defined using KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The cause, clinical course, and outcome of AKI events and electrolyte abnormalities in the first 30 days after CAR-T infusion were characterized using data contained in electronic health records. Results Among 78 patients receiving CAR-T therapy, cytokine release syndrome occurred in 85%, of whom 62% were treated with tocilizumab. AKI occurred in 15 patients (19%): 8 had decreased kidney perfusion, 6 developed acute tubular necrosis, and 1 patient had urinary obstruction related to disease progression. Those with acute tubular necrosis and obstruction had the longest lengths of stay and highest 60-day mortality. Electrolyte abnormalities were common; hypophosphatemia, hypokalemia, and hyponatremia occurred in 75%, 56%, and 51% of patients, respectively. Limitations Small sample size; AKI adjudicated by retrospective chart review; lack of biopsy data. Conclusions In this case series of patients with diffuse large B-cell lymphoma receiving CAR-T therapy, AKI and electrolyte abnormalities occurred commonly in the context of cytokine release syndrome.

Published
2020

8. Acute kidney injury in patients receiving pembrolizumab combination therapy versus pembrolizumab monotherapy for advanced lung cancer

Author

Shruti Gupta, Ian A. Strohbehn, Qiyu Wang, Paul E. Hanna, Rituvanthikaa Seethapathy, Jason M. Prosek, Sandra M. Herrmann, Ala Abudayyeh, A. Bilal Malik, Sebastian Loew, Christopher A. Carlos, Wei-Ting Chang, Pazit Beckerman, Zain Mithani, Chintan V. Shah, Amanda D. Renaghan, Sophie de Seigneux, Luca Campedel, Abhijat Kitchlu, Daniel Sanghoon Shin, Gaia Coppock, Nuttha Lumlertgul, Pablo Garcia, David I. Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, Karolina Benesova, Kenar D. Jhaveri, Frank B. Cortazar, Astrid Weins, Yiqin Zuo, Meghan J. Mooradian, Kerry L. Reynolds, David E. Leaf, Meghan E. Sise, Joe-Elie Salem, Corinne Isnard Bagnis, Harkarandeep Singh, Shveta S. Motwani, Naoka Murakami, Maria C. Tio, Suraj S. Mothi, Umut Selamet, Kai M. Schmidt-Ott, Weiting Chang, Rimda Wanchoo, Yuriy Khanin, Jamie S. Hirsch, Vipulbhai Sakhiya, Daniel Stalbow, Sylvia Wu, Marlies Ostermann, Nina Seylanova, Armando Cennamo, Anne Rigg, Nisha Shaunak, Zoe A. Kibbelaar, Priya Deshpande, Harish S. Seethapathy, Meghan Lee, Ian A. Strohbhen, Busra Isik, Ilya G. Glezerman, Sunandana Chandra, Sethu M. Madhavan, Dwight H. Owen, Marium Husain, Sharon Mini, Shuchi Anand, Aydin Kaghazchi, Sunil Rangarajan, Grace Cherry, Raymond K. Hsu, Andrey Kisel, Sheru K. Kansal, Nicole Albert, Katherine Carter, Vicki Donley, Tricia Young, Heather Cigoi, Sophie De Seigneux, Thibaud Koessler, Els Wauters, Mark Eijgelsheim, Javier A. Pagan, Jonathan J. Hogan, Omar Mamlouk, Jamie S. Lin, Valda Page, Samuel A.P. Short, Elizabeth M. Gaughan, Maria Jose Soler, Clara García-Carro, Sheila Bermejo, Enriqueta Felip, Eva Muñoz-Couselo, and Maria Josep Carreras

Subjects
Lung Neoplasms, Nephrology, Antineoplastic Combined Chemotherapy Protocols, Humans, Acute Kidney Injury, Antibodies, Monoclonal, Humanized
Published
2022

9. Association of Surge Conditions with Mortality Among Critically Ill Patients with COVID-19

Author

Adam B. Keene, Andrew J. Admon, Samantha K. Brenner, Shruti Gupta, Deepa Lazarous, David E. Leaf, Hayley B. Gershengorn, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Shahzad Shaefi, Brian P. O’Gara, Megan L. Krajewski, Sean M. Baskin, Sidharth Shankar, Juan D. Valencia, Ameeka Pannu, Margaret M. Hayes, E. Wilson Grandin, 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 Williams, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Miguel A. Hernán, 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, Girish N. Nadkarni, 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, Neelja Kumar, Michael Chang, Jyotsana Thakkar, 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, Sobaata Chaudhry, Benjamin Wu, Frank Modersitzki, 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 MB. Mohamed, Rupali S. Avasare, David Zonies, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Heather Yang, Jeffery O. Boateng, 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, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Ali Arif, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Katharine Senter, Moh’d A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Terri Peters, Kathy Hughes, 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 Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Alissa Kunczt, 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, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, 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, Abbas Bitar, Jeff Leya, John P. Donnelly, 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, Nitender Goyal, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Aju Jose, Daniel E. Weiner, Marta Christov, Savneek Chugh, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Adult, Cohort Studies, Male, Intensive Care Units, SARS-CoV-2, Critical Illness, COVID-19, Humans, Female, Hospital Mortality, Middle Aged, Critical Care and Intensive Care Medicine
Abstract

Objective To determine whether surge conditions were associated with increased mortality. Design Multicenter cohort study. Setting U.S. ICUs participating in STOP-COVID. Patients Consecutive adults with COVID-19 admitted to participating ICUs between March 4 and July 1, 2020. Interventions None Measurements and Main Results The main outcome was 28-day in-hospital mortality. To assess the association between admission to an ICU during a surge period and mortality, we used two different strategies: (1) an inverse probability weighted difference-in-differences model limited to appropriately matched surge and non-surge patients and (2) a meta-regression of 50 multivariable difference-in-differences models (each based on sets of randomly matched surge- and non-surge hospitals). In the first analysis, we considered a single surge period for the cohort (March 23 – May 6). In the second, each surge hospital had its own surge period (which was compared to the same time periods in matched non-surge hospitals). Our cohort consisted of 4342 ICU patients (average age 60.8 [sd 14.8], 63.5% men) in 53 U.S. hospitals. Of these, 13 hospitals encountered surge conditions. In analysis 1, the increase in mortality seen during surge was not statistically significant (odds ratio [95% CI]: 1.30 [0.47-3.58], p = .6). In analysis 2, surge was associated with an increased odds of death (odds ratio 1.39 [95% CI, 1.34-1.43], p Conclusions Admission to an ICU with COVID-19 in a hospital that is experiencing surge conditions may be associated with an increased odds of death. Given the high incidence of COVID-19, such increases would translate into substantial excess mortality.

Published
2021

10. A Propensity Score–Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney Disease

Author

Rituvanthikaa, Seethapathy, Sophia, Zhao, Joshua D, Long, Ian A, Strohbehn, and Meghan E, Sise

Subjects
Alanine, SARS-CoV-2, General Medicine, Kidney, Antiviral Agents, Adenosine Monophosphate, COVID-19 Drug Treatment, Renal Dialysis, Humans, Female, Renal Insufficiency, Propensity Score, Aged, Retrospective Studies, Original Investigation
Abstract

BACKGROUND: Remdesivir is not currently approved for patients with eGFR

Published
2021

11. Acute kidney injury in patients treated with immune checkpoint inhibitors

Author

Enriqueta Felip, Sophie Papa, Shuchi Anand, Karolina Benesova, Ala Abudayyeh, Omar Mamlouk, Umut Selamet, Grace Cherry, Sunandana Chandra, Sandra M Herrmann, Maria Jose Soler, Abhijat Kitchlu, Jamie S Lin, Kerry L Reynolds, Osama E Rahma, Elizabeth M Gaughan, Eva Muñoz-Couselo, Jamie S Hirsch, Pablo Garcia, Meghan D Lee, Harish Seethapathy, Ian A Strohbehn, Meghan E Sise, Wei-Ting Chang, Els Wauters, Lucy Flanders, Deborah Schrag, Thibaud Koessler, Mark Eijgelsheim, Shruti Gupta, Frank B Cortazar, Samuel A P Short, Jason M Prosek, Sethu M Madhavan, Ilya Glezerman, Shveta S Motwani, Naoka Murakami, Rimda Wanchoo, David I Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, A Bilal Malik, Sebastian Loew, Christopher A Carlos, Pazit Beckerman, Zain Mithani, Chintan V Shah, Amanda D Renaghan, Sophie De Seigneux, Luca Campedel, Daniel Sanghoon Shin, Sunil Rangarajan, Priya Deshpande, Gaia Coppock, Dwight H. Owen, Marium Husain, Clara Garcia-Carro, Sheila Bermejo, Nuttha Lumlertgul, Nina Seylanova, Busra Isik, Aydin Kaghazchi, Yuriy Khanin, Sheru K Kansal, Kai M Schmidt-Ott, Raymond K Hsu, Maria C Tio, Suraj Sarvode Mothi, Harkarandeep Singh, Kenar D Jhaveri, David E Leaf, Corinne Isnard Bagnis, Suraj S Mothi, Weiting Chang, Vipulbhai Sakhiya, Daniel Stalbow, Sylvia Wu, Armando Cennamo, Anne Rigg, Nisha Shaunak, Zoe A Kibbelaar, Harish S Seethapathy, Meghan Lee, Ian A Strohbhen, Ilya G Glezerman, Dwight H Owen, Sharon Mini, Andrey Kisel, Nicole Albert, Katherine Carter, Vicki Donley, Tricia Young, Heather Cigoi, Els Wauters Ben Sprangers, Javier A Pagan, Jonathan J Hogan, Valda Page, Samuel AP Short, Maria Josep Carreras, Institut Català de la Salut, [Gupta S] Division of Renal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA. [Short SAP] University of Vermont Larner College of Medicine, Burlington, Vermont, USA. [Sise ME] Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA. [Prosek JM, Madhavan SM] Division of Nephrology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, Ohio, USA. [Soler MJ, Bermejo S] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Ostermann M] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Nephrology Department, San Carlos Clinical University Hospital, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Cancer Research, ACUTE INTERSTITIAL NEPHRITIS, Immunoteràpia, Other subheadings::Other subheadings::/drug therapy [Other subheadings], urologic and male genital diseases, THERAPY, Gastroenterology, Cohort Studies, Risk Factors, Immunology and Allergy, Immune Checkpoint Inhibitors, RC254-282, RISK, Clinical/Translational Cancer Immunotherapy, Kidney, medicine.diagnostic_test, terapéutica::terapia biológica::inmunomodulación::inmunoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Acute kidney injury, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Acute Kidney Injury, Middle Aged, female genital diseases and pregnancy complications, medicine.anatomical_structure, Oncology, Molecular Medicine, Female, immunotherapy, Life Sciences & Biomedicine, CTLA-4 antigen, medicine.medical_specialty, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::insuficiencia renal::lesión renal aguda [ENFERMEDADES], medicine.drug_class, Immunology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Proton-pump inhibitor, Renal function, programmed cell death 1 receptor, EVENTS, Internal medicine, Biopsy, medicine, Humans, Adverse effect, Acute tubulointerstitial nephritis, Aged, Pharmacology, Science & Technology, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], urogenital system, business.industry, Proportional hazards model, CLINICAL-FEATURES, medicine.disease, Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Acute Kidney Injury [DISEASES], business, Ronyons - Malalties - Tractament
Abstract

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Published
2021

12. 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

13. Immune checkpoint inhibitor–induced thyroiditis is a risk factor for acute and chronic kidney dysfunction

Author

Donald F. Chute, Ian A. Strohbehn, Zsofia D. Drobni, Meghan Lee, Osama E. Rahma, Kerry L. Reynolds, Harish Seeethapathy, Sarah Street, Meghan E. Sise, Rituvanthikaa Seethapathy, Leyre Zubiri, and Tomas G. Neilan

Subjects
Transplantation, Thyroiditis, business.industry, Immune checkpoint inhibitors, Kidney dysfunction, medicine.disease, Kidney, Nephrology, Risk Factors, Immunology, Research Letter, Medicine, Humans, Risk factor, business, Immune Checkpoint Inhibitors
Published
2021

14. Balancing the risk and rewards of utilizing organs from hepatitis C viremic donors

Author

Jenna L. Gustafson, Meghan E. Sise, Raymond T. Chung, Emily D. Bethea, and Ian A. Strohbehn

Subjects
Transplantation, medicine.medical_specialty, Kidney, Tissue and Organ Procurement, Lung, Extramural, business.industry, MEDLINE, Hepatitis C, 030230 surgery, medicine.disease, Article, Tissue Donors, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Internal medicine, medicine, Humans, Immunology and Allergy, 030211 gastroenterology & hepatology, business
Abstract

PURPOSE OF REVIEW: Because of long waitlist times and high waitlist morbidity and mortality, strategies to increase utilization of Hepatitis C viremic deceased donor organs are under investigation in kidney, liver, heart and lung transplantation. RECENT FINDINGS: Direct-acting antiviral medications for Hepatitis C virus infection have high cure rates and are well tolerated. Small, single-center trials in kidney and heart transplant recipients have demonstrated that with early post-transplant direct-acting antiviral therapy, 100% of uninfected recipients of Hepatitis C viremic organs have been cured of infection after transplantation. SUMMARY: In this manuscript, we review the risks and rewards of utilizing Hepatitis C viremic organs for transplantation.

Published
2019

15. Hospital-Level Variation in Death for Critically Ill Patients with COVID-19

Author

Matthew M. Churpek, Shruti Gupta, Alexandra B. Spicer, William F. Parker, John Fahrenbach, Samantha K. Brenner, David E. 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, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, 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 Williams, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Miguel A. Hernán, 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, Girish N. Nadkarni, 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, Elena Cervantes, Samir Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddartha 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, Neelja Kumar, Michael Chang, Jyotsana Thakkar, 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, Sobaata Chaudhry, Benjamin Wu, Frank Modersitzki, 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, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Heather Yang, Jeffery O. Boateng, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Roberta Redfern, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhai-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, Jag Sunderram, Sonika Puri, Jayanth S. Vatson, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Ali Arif, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Katharine Senter, Moh’d A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Terri Peters, Kathy Hughes, 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, Santa Monica, Carl E. Schulze, Etienne Macedo, Harin Rhee, Kathleen 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, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Alessia Fornoni, Hayley B. Gershengorn, Salim S. Hayek, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’Hayer, Chelsea Meloche, Rafey Feroze, Rayan Kaakati, Danny Perry, Abbas Bitar, Elizabeth Anderson, Kishan J. Padalia, Christopher Launius, 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, Nitender Goyal, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Daniel E. Weiner, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, genetic structures, Coronavirus disease 2019 (COVID-19), Critical Illness, Disease, Comorbidity, Critical Care and Intensive Care Medicine, medicine.disease_cause, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Risk Factors, medicine, Humans, 030212 general & internal medicine, Hospital Mortality, Coronavirus, Aged, Retrospective Studies, Critically ill, business.industry, SARS-CoV-2, Incidence, Editorials, COVID-19, Hospital level, Middle Aged, Prognosis, Intensive care unit, Health equity, United States, Survival Rate, Intensive Care Units, Variation (linguistics), 030228 respiratory system, Emergency medicine, Female, business, Algorithms, Follow-Up Studies
Abstract

Variation in hospital mortality has been described for coronavirus disease 2019 (COVID-19), but the factors that explain these differences remain unclear.Our objective was to utilize a large, nationally representative dataset of critically ill adults with COVID-19 to determine which factors explain mortality variability.In this multicenter cohort study, we examined adults hospitalized in intensive care units with COVID-19 at 70 United States hospitals between March and June 2020. The primary outcome was 28-day mortality. We examined patient-level and hospital-level variables. Mixed-effects logistic regression was used to identify factors associated with interhospital variation. The median odds ratio (OR) was calculated to compare outcomes in higher- vs. lower-mortality hospitals. A gradient boosted machine algorithm was developed for individual-level mortality models.A total of 4,019 patients were included, 1537 (38%) of whom died by 28 days. Mortality varied considerably across hospitals (0-82%). After adjustment for patient- and hospital-level domains, interhospital variation was attenuated (OR decline from 2.06 [95% CI, 1.73-2.37] to 1.22 [95% CI, 1.00-1.38]), with the greatest changes occurring with adjustment for acute physiology, socioeconomic status, and strain. For individual patients, the relative contribution of each domain to mortality risk was: acute physiology (49%), demographics and comorbidities (20%), socioeconomic status (12%), strain (9%), hospital quality (8%), and treatments (3%).There is considerable interhospital variation in mortality for critically ill patients with COVID-19, which is mostly explained by hospital-level socioeconomic status, strain, and acute physiologic differences. Individual mortality is driven mostly by patient-level factors. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Published
2021

16. Rapid corticosteroid taper versus standard of care for immune checkpoint inhibitor induced nephritis: a single-center retrospective cohort study

Author

Ryan J. Sullivan, Meghan E. Sise, Genevieve M. Boland, Riley Fadden, Kerry L. Reynolds, Harish Seethapathy, Sophia H. Zhao, Meghan Lee, and Ian A. Strohbehn

Subjects
0301 basic medicine, Male, Cancer Research, Time Factors, Single Center, chemistry.chemical_compound, 0302 clinical medicine, Prednisone, Adrenal Cortex Hormones, Immunology and Allergy, Immune Checkpoint Inhibitors, RC254-282, Clinical/Translational Cancer Immunotherapy, Aged, 80 and over, Kidney, Nephritis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, medicine.anatomical_structure, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Anesthesia, Molecular Medicine, Corticosteroid, Female, immunotherapy, medicine.drug, medicine.drug_class, Immunology, Proton-pump inhibitor, 03 medical and health sciences, medicine, Humans, Aged, Retrospective Studies, Pharmacology, Creatinine, Drug Tapering, business.industry, Retrospective cohort study, Recovery of Function, medicine.disease, 030104 developmental biology, chemistry, business, Boston
Abstract

BackgroundCurrent guidelines for treatment of immune checkpoint inhibitor (ICI)-induced nephritis are not evidence based and may lead to excess corticosteroid exposure. We aimed to compare a rapid corticosteroid taper to standard of care.MethodsRetrospective cohort study in patients with ICI-induced nephritis comparing a rapid taper beginning with 60 mg/day prednisone and tapered to 10 mg within 3 weeks to a historical control group that began 60 mg/day tapered to 10 mg within 6 weeks (standard of care). Renal recovery was defined as creatinine returning to within 1.5-fold baseline. The log-rank test compared the differences in time to renal recovery between the groups. We report rates of renal recovery at 30, 60 and 90 days, and timing and outcomes of ICI rechallenge.ResultsThirteen patients received rapid corticosteroid taper and 14 patients received standard of care. Baseline characteristics were similar between groups. The median time to ≤10 mg/day prednisone was 20 days (IQR 15–25) in the rapid-taper group compared with 38 days (IQR 30–58) in the standard-of-care group. There was no significant difference in the time to renal recovery between the groups, though numerically higher numbers of patients recovered by 30 days, 11 (85%) in the rapid-taper arm versus 6 (46%) in the standard of care arm. Exposure to other nephritis-causing medications (proton pump inhibitor or trimethoprim-sulfamethoxazole) during the corticosteroid taper was more common in the standard of care group, 9 (64%) versus rapid-taper group, 2 (15%), and was associated with longer time to renal recovery, 20 days (IQR 14–101) versus 13 days (IQR 7–34) in those that discontinued nephritis-causing medications. Fifteen (56%) of patients were rechallenged with ICIs, and only two (13%) developed recurrent nephritis.ConclusionsPatients with ICI-induced nephritis have excellent kidney outcomes when treated with corticosteroids that are tapered over 3 weeks.

Published
2021

17. 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

18. 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

19. Incidence and Predictors of CKD and Estimated GFR Decline in Patients Receiving Immune Checkpoint Inhibitors

Author

Nifasha Rusibamayila, Kerry L. Reynolds, Osama E. Rahma, Harish Seethapathy, Zsofia D. Drobni, Ian A. Strohbehn, Tomas G. Neilan, Shruti Gupta, David E. Leaf, Sophia Zhao, Donald F. Chute, Meghan Lee, Leyre Zubiri, and Meghan E. Sise

Subjects
Oncology, medicine.medical_specialty, business.industry, Immune checkpoint inhibitors, Incidence (epidemiology), Incidence, MEDLINE, Renal function, Article, Text mining, Nephrology, Internal medicine, medicine, Humans, In patient, Renal Insufficiency, Chronic, business, Immune Checkpoint Inhibitors, Glomerular Filtration Rate
Published
2021

20. Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors

Author

Meghan E. Sise, Donald F. Chute, Harish Seethapathy, Kenar D. Jhaveri, Alexander T. Faje, Ian A. Strohbehn, Leyre Zubiri, Meghan Lee, Kerry L. Reynolds, and Nifasha Rusibamayila

Subjects
Male, medicine.medical_specialty, Hyperkalemia, medicine.medical_treatment, 030232 urology & nephrology, Hypokalemia, macromolecular substances, Gastroenterology, 03 medical and health sciences, Electrolytes, 0302 clinical medicine, Internal medicine, Adrenal insufficiency, Medicine, Humans, Adverse effect, Immune Checkpoint Inhibitors, Retrospective Studies, Transplantation, business.industry, Sodium, nutritional and metabolic diseases, Middle Aged, medicine.disease, Nephrology, 030220 oncology & carcinogenesis, Etiology, Original Article, Diuretic, medicine.symptom, business, Hyponatremia, Hypophosphatemia
Abstract

Background Hyponatremia due to endocrinopathies such as adrenal insufficiency and hypothyroidism has been reported in patients receiving immune checkpoint inhibitors (ICIs). We determined the risk and predictors of hyponatremia and other electrolyte abnormalities in a ‘real-world’ sample of patients receiving ICIs to treat advanced malignancies. Methods This was a retrospective observational study of all patients who received ICIs from a single cancer center between 2011 and 2018. Patients were followed for 12 months after initiation of ICIs or until death. Common Terminology for Cancer Adverse Events version 5.0 criteria were used to grade the severity of hyponatremia and other electrolyte abnormalities. The predictors of severe (Grade 3 or 4) hyponatremia were determined using a multivariable logistic regression model. The etiology of Grade 3 or 4 hyponatremia was determined by chart review. Results A total of 2458 patients were included. Their average age was 64 years [standard deviation (SD) 13], 58% were male and 90% were white. In the first year after starting ICIs, 62% experienced hyponatremia (sodium Conclusions Hyponatremia is common in cancer patients receiving ICIs. However, endocrinopathies are an uncommon cause of severe hyponatremia.

Published
2020

21. The positive effect of immune checkpoint inhibitor-induced thyroiditis on overall survival accounting for immortal time bias: a retrospective cohort study of 6596 patients

Author

Kerry L. Reynolds, Sarah Street, Michelle Rengarajan, Zsofia D. Drobni, Meghan E. Sise, Alexander T. Faje, Harish Seethapathy, Ryan J. Sullivan, Meghan Lee, Alexandra-Chloé Villani, Leyre Zubiri, Meghan J. Mooradian, Rituvanthikaa Seethapathy, Donald F. Chute, T Neilan, Sophia H. Zhao, Ian A. Strohbehn, and Osama E. Rahma

Subjects
Oncology, Thyroiditis, medicine.medical_specialty, business.industry, Immune checkpoint inhibitors, MEDLINE, Retrospective cohort study, Hematology, medicine.disease, Article, Text mining, Bias, Internal medicine, medicine, Overall survival, Humans, business, Immune Checkpoint Inhibitors, Retrospective Studies
Published
2021

22. Acute kidney injury after ruxolitinib: Common complication, uncommon cause

Author

Nifasha Rusibamayila, Harish Seethapathy, Kenar D. Jhaveri, Samuel Strohbehn, Ian A. Strohbehn, Meghan Lee, Meghan E. Sise, Gabriela S. Hobbs, and Alla Keyzner

Subjects
Adult, Male, Ruxolitinib, medicine.medical_specialty, MEDLINE, Graft vs Host Disease, Article, Text mining, Internal medicine, Nitriles, Humans, Medicine, Aged, Retrospective Studies, business.industry, Acute kidney injury, Hematology, Acute Kidney Injury, Middle Aged, medicine.disease, Pyrimidines, Hematologic Neoplasms, Pyrazoles, Female, business, Complication, medicine.drug
Published
2020

23. Safety and Efficacy of Immune Checkpoint Inhibitors in Patients on Dialysis: A Retrospective Case Series

Author

Harish Seethapathy, Osama E. Rahma, Ian A. Strohbehn, Donald F. Chute, Meghan Lee, Daniel Okin, Tomas G. Neilan, Amanda C. Guidon, Kerry L. Reynolds, Michelle Rengarajan, Daniel A. Zlotoff, and Meghan E. Sise

Subjects
Oncology, Male, medicine.medical_specialty, Lung Neoplasms, Skin Neoplasms, Immune checkpoint inhibitors, Programmed Cell Death 1 Receptor, MEDLINE, Adrenal Gland Diseases, B7-H1 Antigen, Article, Text mining, Antineoplastic Agents, Immunological, Hypothyroidism, Renal Dialysis, Internal medicine, Neoplasms, medicine, Humans, In patient, CTLA-4 Antigen, Melanoma, Aged, Retrospective Studies, Aged, 80 and over, Myositis, business.industry, Pneumonia, Middle Aged, Carcinoma, Merkel Cell, Myocarditis, Treatment Outcome, Nephrology, Head and Neck Neoplasms, Kidney Failure, Chronic, Female, business, Dialysis (biochemistry), Urogenital Neoplasms
Published
2019

24. Development of an Algorithm to Identify Cases of Nonalcoholic Steatohepatitis Cirrhosis in the Electronic Health Record

Author

Christopher J, Danford, Jennifer Y, Lee, Ian A, Strohbehn, Kathleen E, Corey, and Michelle, Lai

Subjects
Liver Cirrhosis, Male, Reproducibility of Results, Middle Aged, Non-alcoholic Fatty Liver Disease, Predictive Value of Tests, Data Mining, Electronic Health Records, Humans, Female, Genetic Predisposition to Disease, Diagnosis, Computer-Assisted, Algorithms, Aged
Abstract

Current genetic research of nonalcoholic steatohepatitis (NASH) cirrhosis is limited by our ability to accurately identify cases on a large scale. Our objective was to develop and validate an electronic health record (EHR) algorithm to accurately identify cases of NASH cirrhosis in the EHR.We used Clinical Query 2, a search tool at Beth Israel Deaconess Medical Center, to create a pool of potential NASH cirrhosis cases (n = 5415). We created a training set of 300 randomly selected patients for chart review to confirm cases of NASH cirrhosis. Test characteristics of different algorithms, consisting of diagnosis codes, laboratory values, anthropomorphic measurements, and medication records, were calculated. The algorithms with the highest positive predictive value (PPV) and the highest F score with a PPV ≥ 80% were selected for internal validation using a separate random set of 100 patients from the potential NASH cirrhosis pool. These were then externally validated in another random set of 100 individuals using the research patient data registry tool at Massachusetts General Hospital.The algorithm with the highest PPV of 100% on internal validation and 92% on external validation consisted of ≥ 3 counts of "cirrhosis, no mention of alcohol" (571.5, K74.6) and ≥ 3 counts of "nonalcoholic fatty liver" (571.8-571.9, K75.81, K76.0) codes in the absence of any diagnosis codes for other common causes of chronic liver disease.We developed and validated an EHR algorithm using diagnosis codes that accurately identifies patients with NASH cirrhosis.

Published
2019

25. The Incidence, Causes, and Risk Factors of Acute Kidney Injury in Patients Receiving Immune Checkpoint Inhibitors

Author

Sophia Zhao, Ian A. Strohbehn, Leyre Zubiri, Meghan J. Mooradian, Frank B. Cortazar, Donald F. Chute, Meghan E. Sise, Kerry L. Reynolds, Ryan J. Sullivan, David E. Leaf, Alexandra-Chloé Villani, Harish Seethapathy, and Yaa Oppong

Subjects
Nephrology, medicine.medical_specialty, Epidemiology, Population, Programmed Cell Death 1 Receptor, 030232 urology & nephrology, Renal function, urologic and male genital diseases, Critical Care and Intensive Care Medicine, B7-H1 Antigen, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Cumulative incidence, CTLA-4 Antigen, education, Aged, Retrospective Studies, Transplantation, education.field_of_study, Creatinine, business.industry, Incidence, Acute kidney injury, Editorials, Proton Pump Inhibitors, Acute Kidney Injury, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, chemistry, 030220 oncology & carcinogenesis, Onconephrology, business, Kidney disease, Glomerular Filtration Rate
Abstract

Background and objectives Immune checkpoint inhibitor use in oncology is increasing rapidly. We sought to determine the frequency, severity, cause, and predictors of AKI in a real-world population receiving checkpoint inhibitors. Design, setting, participants, & measurements We included all patients who received checkpoint inhibitor therapy from May 2011 to December 2016 at Massachusetts General Hospital. Baseline serum creatinine, averaged 6 months before checkpoint inhibitor start date, was compared with all subsequent creatinine values within 12 months of starting therapy. AKI was defined by Kidney Disease: Improving Global Outcomes criteria for fold changes in creatinine from baseline. Sustained AKI events lasted at least 3 days and was our primary outcome. The cause of sustained AKI was determined by chart review. Cumulative incidence and subdistribution hazard models were used to assess the relationship between baseline demographics, comorbidities, and medications, and sustained AKI and potential checkpoint inhibitor–related AKI. Results We included 1016 patients in the analysis. Average age was 63 (SD 13) years, 61% were men, and 91% were white. Mean baseline creatinine was 0.9 mg/dl (SD 0.4 mg/dl), and 169 (17%) had CKD (eGFR Conclusions AKI is common in patients receiving checkpoint inhibitor therapy. The causes of sustained AKI in this population are heterogenous and merit thorough evaluation. The role of PPI and other nephritis-inducing drugs in the development of sustained AKI needs to be better defined.

Published
2019

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