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1. The Changing Landscape of Treatment for Cystic Fibrosis Related Diabetes

Author

Mehdia Amini, Kevin Yu, Jessica Liebich, Vaishaliben Ahir, Emily Wood, Stewart Albert, and Sandeep Dhindsa

Subjects
Cystic fibrosis, Diabetes, Elexacaftor, Tezacaftor, Ivacaftor, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Objective: Patients with Cystic Fibrosis related diabetes [CFRD] are treated with insulin and high calorie diets to maintain body mass. The combined CFTR modulator elexacaftor/tezacaftor/ivacaftor [ETI] decreases pulmonary exacerbations and improves nutritional status. We reviewed the effects of ETI on BMI, HbA1c and diabetes regimen in patients with CFRD over a period of three years. Methods: Data of previously CFTR-modulator-naïve patients with CFRD and pancreatic insufficiency on ETI therapy were retrieved from an electronic health record database. Patients were followed for a mean duration of 2.7 ± 0.8 years after ETI initiation. Data pertaining to weight, BMI, HbA1c and diabetes regimen were collected at 6 months, 12 months, 2 years and at 3 years post-ETI initiation. Patients were then dichotomized based on their baseline BMI into a low BMI group and an “at target” BMI group. The effects of ETI on changes in weight, BMI, A1c and diabetes regimen were compared in both groups over a period of three years. Results: Twenty-seven patients with CFRD (15 men/12 women), age 30.6 ± 11.5 (SD) years, BMI 22.4 ± 4.0 kg/m2, were included. Fifteen patients had low BMI (

Published
2024
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15. ODP170 Check Point Inhibitor Associated Multi-Endocrine Dysfunction Presenting With Euglycemic Ketoacidosis

Author

Stewart Albert, Gouyu Ling, Srikanth Nadella, and Aparna Yeggalam

Subjects
Endocrinology, Diabetes and Metabolism
Abstract

Introduction Immune check point inhibitors have become breakthrough therapy for many types of cancers. They inhibit one of two immune regulatory pathways, the cytotoxic T-lymphocyte antigen 4 (CTLA-4), and 'programmed death-1' (PD-1) and (PD-L1) pathways. Removing immune regulation allows for anti-cancer immune responses. They also cause immune related endocrine dysfunction such as hypophysitis, thyroiditis, diabetes mellitus (DM) and primary adrenal insufficiency (AI). We describe a patient on Pembrolizumab (PEM) (an anti-PD-1 inhibitor) who presented with new onset DM, euglycemic diabetic ketoacidosis (DKA) with simultaneous secondary AI. Case report 54-year-old woman with stage 4 non-small cell carcinoma of the lung (NSCLC) with known brain metastasis, was under therapy with carboplastin, paclitaxel and PEM, presented with headache, blurry vision and altered mental status. She had past history of Graves’ disease s/p radioactive iodine therapy, currently on levothyroxine. For two weeks, she had decreased oral intake, and generalized weakness. Upon presentation, she was cachectic, BP 152/65, pulse 117 and confabulating. Laboratory evaluation showed: serum glucose 72 mg/dL, Na 139 mmol/L, K 3.2 mmol/L, Cl 113 mmol/L, HCO3 11 mmol/L, anion gap 15 mmol/L, beta-hydroxybutyrate 4.8 mmol/L, lactic acid 0.7 mmol/L, venous pH 7.2 and base excess -16.6 mmol/L. The delta-delta gap was 10 mmol/L, compatible with a mixed anion-gap and hyperchloremic acidosis (HCA). Antibodies to GAD-65, and Zinc transporter-8 were negative. To evaluate euglycemia despite DKA, levels were obtained for serum cortisol 1 mcg/dL, and ACTH 10 g/hour), stress doses of hydrocortisone (HC), and infusion of low chloride solute for HCA. Conclusion Awareness of the potential for multi-endocrine dysfunction, directed us towards the urgent institution of therapy for DKA with supplementation of stress dose HC for presumed AI, the latter as a cause of relative "hypoglycemia". Central AI was confirmed with undetectable levels of cortisol and ACTH. Although less frequent than with CTLA-4 inhibitors, PD-1 inhibitors are associated with hypophysitis even without abnormalities on pituitary MRI. The DM (associated with PD-1 inhibitors) although autoimmune is nature, is "antibody" positive approximately 50% of the time. Further therapy for both euglycemic DKA and HCA required adjustment of the conventional management for DKA. To our knowledge this is the first reported case of Euglycemic DKA and secondary AI due to PD-1 inhibitors per literature review. Reference: Walters AGB, BraatvedtG G. Endocrine adverse effects of immune check point inhibitors . Intern Med J. 2021Jul;51(7): 1016-1020. doi: 10.111/imj . 14992. PMID: 34278695. Hattersley R, Nana M,Lansdown AJ. Endocrine complications of immunopathies: a review . ClinMed(Lond).2021 Mar;21(2): e212-e222. doi: 10.7861/clinmed.2020-0827. PMID: 33762389;PMCID: PMC8002767 Presentation: No date and time listed

Published
2022
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44. Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library

Author

Kung, Pei-Pei, primary, Bingham, Patrick, additional, Burke, Benjamin J., additional, Chen, Qiuxia, additional, Cheng, Xuemin, additional, Deng, Ya-Li, additional, Dou, Dengfeng, additional, Feng, Junli, additional, Gallego, Gary M., additional, Gehring, Michael R., additional, Grant, Stephan K., additional, Greasley, Samantha, additional, Harris, Anthony R., additional, Maegley, Karen A., additional, Meier, Jordan, additional, Meng, Xiaoyun, additional, Montano, Jose L., additional, Morgan, Barry A., additional, Naughton, Brigitte S., additional, Palde, Prakash B., additional, Paul, Thomas A., additional, Richardson, Paul, additional, Sakata, Sylvie, additional, Shaginian, Alex, additional, Sonnenburg, William K., additional, Subramanyam, Chakrapani, additional, Timofeevski, Sergei, additional, Wan, Jinqiao, additional, Yan, Wen, additional, and Stewart, Albert E., additional

Published
2020
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46. SYNTAX Score and Long-Term Outcomes

Author

Fumiaki Ikeno, Maria Mori Brooks, Kaori Nakagawa, Min-Kyu Kim, Hideaki Kaneda, Yoshiaki Mitsutake, Helen A. Vlachos, Leonard Schwartz, Robert L. Frye, Sheryl F. Kelsey, Katsuhisa Waseda, Mark A. Hlatky, Katherine M. Detre, Trevor J. Orchard, Stephen B. Thomas, Kim Sutton Tyrrell, Jamal S. Rana, Frani Averbach, Joan M. MacGregor, Scott M. O’Neal, Kathleen Pitluga, Veronica Sansing, Mary Tranchine, Sharon W. Crow, Marianne (Marnie) Bertolet, Regina Hardison, Kevin Kip, Manuel Lombardero, Jiang Lu, Sue Janiszewski, Darina Protivnak, Sarah Reiser, Stephen Barton, Ping Guo, Yulia Kushner, Owen Michael, Jeffrey P. Martin, Christopher Kania, Michael Kania, Jeffrey O’Donnell, Rae Ann Maxwell, Suzanne Goldberg, Yves Rosenberg, Patrice Desvigne-Nickens, Abby Ershow, David Gordon, Dina Paltoo, Teresa L.Z. Jones, Whady Hueb, José Ramires, Neuza Lopes, Bernardo Léo Wajchenberg, Eulogio E. Martinez, Sergio A. Oliveira, Expedito E. Ribeiro, Marcos Perin, Roberto Betti, George Steiner, Alan Barolet, Yolanda Groenewoud, Lisa Mighton, Kathy Camelon, Robert O’Rourke, Janet Blodgett, Edward Sako, Judith Nicastro, Robin Prescott, Charanjit Rihal, Frank Kennedy, Gregory Barsness, Amanda Basu, Alfredo Clavell, Robert Frye, David R. Holmes, Amir Lerman, Charles Mullaney, Guy Reeder, Robert Rizza, Hartzell Schaff, Steven Smith, Virend Somers, Thoralf Sundt, Henry Ting, R. Scott Wright, Pam Helgemoe, Diane Lesmeister, Deborah Rolbiecki, Luis Lepe-Montoya, Jorge Escobedo, Rafael Barraza, Rubén Baleón, Arturo Campos, Paula García, Carlos Lezama, Carlos Miramontes, Salvador Ocampo, Joaquín V. Peñafiel, Aquiles Valdespino, Raúl Verdín, Héctor Albarrán, Fernando Ayala, Eduardo Chávez, Héctor Murillo, Luisa Virginia Buitrón, Beatriz Rico-Verdin, Fabiola Angulo, Dale Adler, Austin Arthur Halle, Faramarz Ismail-Beigi, Suvinay Paranjape, Stacey Mazzurco, Karen Ridley, Kodangudi Ramanathan, Solomon Solomon, Barry Wall, Darryl Weinman, Tammy Touchstone, Lillie Douglas, Martial Bourassa, Jean-Claude Tardif, Jean-Louis Chiasson, Marc Andre Lavoie, Rémi Rabasa-Lhoret, Hélène Langelier, Suzy Foucher, Johanne Trudel, Scott Monrad, Vankeepuram Srinivas, Joel Zonszein, Jill Crandall, Helena Duffy, Eugen Vartolomei, Spencer King, Carl Jacobs, David Robertson, Marty Porter, Melanie Eley, Emmalee Nichols, Jennifer LaCorte, Melinda Mock, William Rogers, Fernando Ovalle, David Bell, Vijay K. Misra, William B. Hillegass, Raed Aqel, Penny Pierce, Melanie Smith, Leah Saag, Ashley Vaughn, Dwight Smith, Tiffany Grimes, Susan Rolli, Roberta Hill, Beth Dean Barrett, Clarinda Morehead, Ken Doss, Charles J. Davidson, Mark Molitch, Nirat Beohar, Elaine Massaro, Lynne Goodreau, Fabiola Arroyo, Petr Neužil, Lenka Pavlickova, Štĕpánka Stehlíková, Jaroslav Benedik, Liz Coling, Richard Davies, Christopher Glover, Michel LeMay, Thierry Mesana, Teik Chye Ooi, Mark Silverman, Alexander Sorisky, Colette Favreau, Susan McClinton, Melvin Weiss, Irene Weiss, Leo Saulle, Harichandra Kannam, Joanne C. Kurylas, Lorraine Vasi, John Douglas, Ziyad Ghazzal, Laurence Sperling, Priya Dayamani, Suzanne Gebhart, Sabreena Basu, Tarek Helmy, Vin Tangpricha, Pamela Hyde, Margaret Jenkins, Barbara P. Grant, Kenneth Kent, William Suddath, Michelle Magee, Patricia Julien-Williams, Vida Reed, Carine Nassar, Gilles Dagenais, Claude Garceau, Dominique Auger, Christopher Buller, Tom Elliott, Krishnan Ramanathan, Donald Ricci, Rebecca Fox, Daniela Kolesniak, Michael Attubato, Frederick Feit, Stephen Richardson, Ivan Pena Sing, James Slater, Angela Amendola, Bernardo Vargas, Nicholas Tsapatsaris, Bartholomew Woods, Gary Cushing, Martin Rutter, Premranjan Singh, Gail DesRochers, Gail Woodhead, Deborah Gannon, Nancy Shinopulos Campbell, Michael Ragosta, Ian Sarembock, Eric Powers, Eugene Barrett, Linda Jahn, Karen Murie, Gladwin Das, Gardar Sigurdsson, Carl White, John Bantle, J. Bruce Redmon, Christine Kwong, Jacqueline Tamis-Holland, Jeanine Albu, Judith S. Hochman, James Wilentz, Sylvaine Frances, Deborah Tormey, Carl Pepine, Karen Smith, Laurence Kennedy, Karen Brezner, Tempa Curry, Frank Bleyer, Stewart Albert, Arshag Mooradian, Sharon Plummer, Francisco Fuentes, Roberto Robles, Victor Lavis, Jaime Gomez, Cesar Iliescu, Carol Underwood, Maria Selin Fulton, Julie Gomez Ramirez, Jennifer Merta, Glenna Scott, Ashok Krishnaswami, Lynn Dowdell, Sarah Berkheimer, Adam Greenbaum, Fred Whitehouse, Raquel Pangilinan, Kelly Mann, Alice K. Jacobs, Elliot Sternthal, Susana Ebner, Zoran Nedeljkovic, Paula Beardsley, David Schneider, Richard Pratley, William Cefalu, Joel Schnure, Michaelanne Rowen, Linda Tilton, Alan Niederman, Cristina Mata, Terri Kellerman, John Farmer, Alan J. Garber, Neal Kleiman, Nancy Howard, Debra Nichols, Madonna Pool, Christopher Granger, Mark Feinglos, George Adams, Jennifer Green, Bernadette Druken, Dani Underwood, J. Lawrence Stafford, Thomas Donner, Warren Laskey, Dana Beach, John Lopez, Andrew Davis, David Faxon, Sirimon Reutrakul, Emily Bayer, Oscar Marroquin, Howard Cohen, Mary Korytkowski, Glory Koerbel, Lisa Baxendell, Debbie Rosenfelder, Louise DeRiso, Carole Farrell, Tina Vita, Janet McGill, Ronald Krone, Richard Bach, Carol Recklein, Kristin M. Luepke, Mary Jane Clifton, Michael E. Farkouh, Michael C. Kim, Donald A. Smith, Ida Guzman, Arlene Travis, James O’Keefe, Alan Forker, William Isley, Richard Moe, Paul Kennedy, Margaret Rosson, Aimee Long, Eric Bates, William Herman, Rodica Pop-Busui, Claire Duvernoy, Martin Stevens, Ann Luciano, Cheryl Majors, Sheldon H. Gottlieb, Annabelle Rodriguez, Melanie Herr, David Williams, Robert J. Smith, J. Dawn Abbott, Marc J. Laufgraben, Mary Grogan, Janice Muratori, Gabriel Habib, Marco Marcelli, Issam Mikati, Emilia Cordero, Gina Caldwell, David Schechter, Daniel Lorber, Phyllis August, Maisie Brown, Patricia Depree, Kurt Huber, Ursula Hanusch-Enserer, Nelly Jordanova, Dilek Cilesiz, Birgit Vogel, Ben McCallister, Michael Kleerekoper, Kelly Mandagere, Robert Urbanic, James Bengston, Bobby K. Kong, Andrew Pruitt, Jeffrey Sanfield, Carol Carulli, Ruth Churley-Strom, Raymond Magorien, Kwame Osei, Cecilia Casey Boyer, Richard Lee, Pasquale Palumbo, Joyce Wisbey, Edwin Alderman, Anne Schwarzkopf Michael Steffes, Maren Nowicki, Jean Bucksa, Bernard Chaitman, Jane Eckstein, Karen Stocke, Derek B. Boothroyd, Kathryn A. Melsop, Burton E. Sobel, Dagnija Neimane, Ami E. Iskandrian, Mary Beth Schaaf, Saul Genuth, Theresa Bongarno, Richard Nesto, Karen Hultberg, Helene Rosenhouse-Romeo, Georgia Pambianco, Michael Mock, Sheryl Kelsey, Trevor Orchard, Thomas Ryan, Harold Lebovitz, Robert Brown, Gottlieb Friesinger, Edward Horton, Jay Mason, Renu Virmani, Lawrence Wechsler, C. Noel Bairey-Merz, J. Ward Kennedy, Elliott Antman, John Colwell, Sarah Fowler, Curt Furberg, Lee Goldman, Bruce Jennings, and Scott Rankin

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Hazard ratio, Percutaneous coronary intervention, 030204 cardiovascular system & hematology, medicine.disease, Revascularization, humanities, Cardiac surgery, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Angioplasty, Conventional PCI, medicine, Cardiology, 030212 general & internal medicine, Myocardial infarction, Cardiology and Cardiovascular Medicine, business, Stroke
Abstract

Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

Published
2017
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50. Letters to the Editors

Author

Hill, E. L., Goodman, Fred, Lévesque, Réjean, Stewart, Albert B., and Watson, Warren Z.

Published
1970

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