Discoveries & Impact (October 2020)

Discoveries & Impact highlights publications per section across the Department of Internal Medicine.

Cardiovascular Medicine

Members of the Yale Structural Heart and Valve program led research published in JAMA Cardiology showing early favorable results of transcatheter aortic valve replacement (TAVR) in low-risk patients with bicuspid aortic valve stenosis. Using a self-expanding valve resulted in low rates of death & stroke (1.3%) and high device success rate. Read “Transcatheter Aortic Valve Replacement in Low-risk Patients With Bicuspid Aortic Valve Stenosis.”

Forrest, John K.; Ramlawi, Basel; Deeb, G. Michael; Zahr, Firas; Song, Howard K.; Kleiman, Neal S.; Chetcuti, Stanley J.; Michelena, Hector I.; Mangi, Abeel A.; Skiles, Jeffrey A.; Huang, Jian; Popma, Jeffrey J.; Reardon, Michael J. Transcatheter Aortic Valve Replacement in Low-risk Patients With Bicuspid Aortic Valve Stenosis. JAMA Cardiol. doi:10.1001/jamacardio.2020.4738

Digestive Diseases

Yale researchers found that patients with reactive gastropathy (RG) had a higher incidence of intestinal metaplasia (IM) around the gastroesophageal junction (GEJ) and a diagnosis of Barrett’s esophagus in “Intestinal Metaplasia Around The Gastroesophageal Junction Is Frequently Associated With Antral Reactive Gastropathy: Implications For Carcinoma At The Gastroesophageal Junction.” The team looked at 1257 patients who underwent gastric antral or concurrent mucosal biopsies around the GEJ between 2013 – 2015. In addition to the higher incidence of IM, they showed that PPI-associated changes were also seen more in patients with antral RG. The results support a role for bile reflux causing mucosal injury and intestinal metaplasia around GEJ, including Barrett’s esophagus. Read the study in Human Pathology.

Vyas, Monika; Celli, Romulo; Singh, Manpreet; Patel; Aslanian, Harry R; Boffa, Daniel; Deng, Yanhong; Ciarleglio, Maria M; Laine, Loren; Jain, Dhanpat. Intestinal Metaplasia Around The Gastroesophageal Junction Is Frequently Associated With Antral Reactive Gastropathy: Implications For Carcinoma At The Gastroesophageal Junction. Hum Pathol. doi: 10.1016/j.humpath.2020.08.007.

Endocrinology & Metabolism

The generic and brand-name versions of levothyroxine are associated with similar rates of achieving normal/stable thyrotropin levels in patients with mild thyroid dysfunction, found a recent study published in JAMA Network Open. In “Comparative Effectiveness of Generic vs Brand-Name Levothyroxine in Achieving Normal Thyrotropin Levels,” researchers associated with the Yale-Mayo Clinic CERSI, an FDA-funded research center, data from 17598 patients between 2008 – 2017 who newly filled generic or brand-name levothyroxine prescriptions. The results of this study should “reassure physicians and patients” that the generic version of levothyroxine as initial therapy is as effective as the brand-name version.

Brito, Juan P; Ross, Joseph S; Sangaralingham, Lindsey; Dutcher, Sarah K; Graham, David J; Wang, Zhong; Wu, Yute; Yao, Xiaoxi; Smallridge, Robert C; Bernet, Victor; Shah, Nilay D; Lipska, Kasia J. Comparative Effectiveness of Generic vs Brand-Name Levothyroxine in Achieving Normal Thyrotropin Levels. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2020.17645. PMID: 32997127; PMCID: PMC7527873.

General Internal Medicine

Researchers in the Yale Program in Addiction Medicine showed that use of a buprenorphine buccal film assisted a patient to transition from a high dose full agonist opioid to sublingual buprenorphine/naloxone, a partial opioid agonist. The paper in the Journal of Addiction Medicine discusses a case of a 59-year old hospitalized patient with an opioid dependence and the novel buprenorphine induction method used. Read “Hospital-based Buprenorphine Micro-dose Initiation” to learn more.

Weimer, Melissa B; Guerra, Michael; Morrow, Gina; Adams, Kathleen. Hospital-based Buprenorphine Micro-dose Initiation. J Addict Med. doi: 10.1097/ADM.0000000000000745. PMID: 32960820.

Geriatrics

In the newly released data from the multicenter prospective cohort study, the SILVER-AMI team found that 1 in 8 patients described worsening difficult in performing daily activities six months after suffering a heart attack. The researchers developed a risk model to predict this decline which they hope will improve “treatment planning and shared decision-making” for these patients. Read “Risk Model for Decline in Activities of Daily Living Among Older Adults Hospitalized With Acute Myocardial Infarction: The SILVER-AMI Study” in the Journal of the American Heart Association.

Hajduk, Alexandra M; Dodson, John A; Murphy, Terrence E; Tsang, Sui; Geda, Mary; Ouellet, Gregory M; Gill, Thomas M; Brush, John E; Chaudhry, Sarwat I. Risk Model for Decline in Activities of Daily Living Among Older Adults Hospitalized With Acute Myocardial Infarction: The SILVER-AMI Study. J Am Heart Assoc. doi: 10.1161/JAHA.119.015555. PMID: 33000681.

Hematology

Researchers performed a systematic review and meta-analysis on 44 studies with 1359 regarding the use of interferon (IFN) in the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) in a study recently released in Leukemia. They concluded that interferon is a treatment option with a good response rate and a reasonable therapeutic for patients with ET or PV. Read the study in “Interferon alpha therapy in essential thrombocythemia and polycythemia vera—a systematic review and meta-analysis.”

Bewersdorf, Jan Philipp; Giri, Smith; Wang, Rong; Podoltsev, Nikolai; Williams, Robert T; Tallman, Martin S; Rampal, Raajit K; Zeidan, Amer M; Stahl, Maximilian. Interferon alpha therapy in essential thrombocythemia and polycythemia vera-a systematic review and meta-analysis. Leukemia. doi: 10.1038/s41375-020-01020-4.

Infectious Diseases

A team of researchers looked at the correlation between solid organ transplant patients, COVID-19, and mortality in the recently published paper, “Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study.” A total of 482 cases were studied in this multisite prospective study. They concluded that mortality was largely driven by the patient’s comorbidity and certain clinical features, rather than immunosuppression, but future studies are warranted. Read the paper in Clinical Infectious Diseases.

Kates, Olivia S; Haydel, Brandy M; Florman, S,ander S; Rana, Meenakshi M; Chaudhry, Zohra S; Ramesh, Mayur S; Safa, Kassem; Kotton, Camille Nelson; Blumberg, Emily A; Besharatian, Behdad D; Tanna, Sajal D; Ison, Michael G; Malinis, Maricar; Azar, Marwan M; Rakita, Robert M; Morilla, Jose A; ; Majeed, Aneela; Sait, Afrah S; Spaggiari, Mario; Hemmige, Vagish; Mehta, Sapna A; Neumann, Henry; Badami, Abbasali; Goldman, Jason D; Lala, Anuradha; Hemmersbach-Miller, Marion; McCort, Margaret E; Bajrovic, Valida; Ortiz-Bautista, Carlos; Friedman-Moraco, Rachel; Sehgal, Sameep; Lease, Erika D; Fisher, Cynthia E; Limaye, Ajit P; UW COVID-19 SOT Study Team. Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa1097

Medical Oncology

According to findings led by Yale Cancer Center researchers, treatment with the targeted therapy osimertinib following surgery significantly improves disease-free survival (DFS) in patients with early-stage, non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. The double-blind study followed 682 patients for three years. In patients with stage IB to IIIA EGFR mutation-positive NSCLC, those patients treated with osimertinib had significantly longer disease-free survival than those who received placebo. Additionally the emergence of brain metastasis were prevented. Read “Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer” in New England Journal of Medicine.

Wu, Yi-Long; Tsuboi, Masahiro; He, Jie; John, Thomas; Grohe, Christian; Majem, Margarita; Goldman, Jonathan W; Laktionov, Konstantin; Kim, Sang-We; Kato, Terufumi; Vu, Huu-Vinh; Lu, Shun; Lee, Kye-Young; Akewanlop, Charuwan; Yu, Chong-Jen; de Marinis, Filippo; Bonanno, Laura; Domine, Manuel; Shepherd, Francis A; Zeng, Lingmin; Hodge, Rachel; Atasoy, Ajlan; Rukazenkov, Yuri; Herbst, Roy S; ADAURA Investigators. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. doi: 10.1056/NEJMoa2027071. PMID: 32955177.

Nephrology

New research out of Yale Nephrology found that when adult mice lose the gene Pkhd1, they develop a cystic liver. This finding demonstrates that the gene for autosomal recessive polycystic kidney disease (ARPKD) continues to play a role in bile duct homeostasis after liver development. Further, the liver cysts which accompany ARPKD-associated congenital hepatic fibrosis do not require a developmental ductal plate malformation and could occur in heterozygous carriers for PKHD1 mutations. The findings may lead to better understanding of whether targeted therapies for autosomal dominant polycystic kidney disease (ADPKD) could be relevant for autosomal recessive polycystic kidney disease. Read “Adult inactivation of the recessive polycystic kidney disease gene causes polycystic liver disease” in Kidney360.

Besse, Whitney; Roosendaal, Charlotte E. J.; Tuccillo, Luigi; Ghosh Roy, Sounak; Gallagher, Anna-Rachel; Somlo, Stefan. Adult inactivation of the recessive polycystic kidney disease gene causes polycystic liver disease. Kidney360. 10.34067/KID.0002522020; DOI: 10.34067/KID.0002522020

Pulmonary, Critical Care & Sleep Medicine

In the new editorial, “The Idiopathic Pulmonary Fibrosis Cell Atlas,” a team of Yale researchers discuss the studies, design, features, uses, and future state of the IPF Cell Atlas. The IPF Cell Atlas was created to share scRNAseq data related to the incurable lung disease idiopathic pulmonary fibrosis (IPF). The team created a web interface (www.ipfcellatlas.com) which contains information from over 550,000 cells obtained from 134 individuals with advanced lung disease. The IPF Cell Atlas has so far 4000 unique users from five continents and 56 countries that performed over 100,000 searches of more than 7400 genes since its creation a year ago. The team encourages scientists from all disciplines to enter the portal and search in what cell type do their favorite genes express, and how do they change in disease. They plan to add more single-cell datasets and analytical tools as they become available and hopes that this tool is a significant step in the cure of IPF and other parenchymal lung diseases. Learn more in the American Journal of Physiology-Lung Cellular and Molecular Physiology.

Neumark, Nir; Cosme, Carlos Jr; Rose, Kadi-Ann; Kaminski, Naftali. The Idiopathic Pulmonary Fibrosis Cell Atlas. Am J Physiol Lung Cell Mol Physiol. doi: 10.1152/ajplung.00451.2020. PMID: 32996785.

Rheumatology, Allergy & Immunology

As part of the GO-ALIVE phase 3 clinical trial, 208 patients with ankylosing spondylitis (AS) were given either intravenous (IV) golimumab or placebo for first 12 weeks followed crossover to IV Golimumab for total 52 weeks. About 70% patients treated with IV golimumab demonstrated improvement in disease activity and physical function as well as commensurate improvement in the health-related quality of life (HRQoL) and work productivity. In “The effect of intravenous golimumab on health-related quality of life and work productivity in adult patients with active ankylosing spondylitis: results of the phase 3 GO-ALIVE trial,” researchers found that IV golimumab provided improvement as early as eight weeks and maintained improvement through one year. Read the study in Clinical Rheumatology.

Reveille, John D; Hwang, Mark C; Danve, Abhijeet; Kafka, Shelly; Peterson, Steven; Lo, Kim H; Kim, Lilianne; Hsia, Elizabeth C; Chan, Eric KH; Deodhar, Atul. The effect of intravenous golimumab on health-related quality of life and work productivity in adult patients with active ankylosing spondylitis: results of the phase 3 GO-ALIVE trial. Clin Rheumatol. doi: 10.1007/s10067-020-05342-7. PMID: 32926247.

VA Connecticut Healthcare System

Individuals from minority backgrounds in the United States are twice as likely to test positive for COVID-19 than their white counterparts, according to new research in PLOS Medicine. In “Patterns of Covid-19 testing and mortality by race and ethnicity among United States Veterans: a nationwide cohort study,” researchers looked at 5.8M patients who received care in the U.S. Department of Veterans Affairs and showed that this disparity for Black and Hispanic individuals was found even after accounting for factors such as underlying health conditions, where they live, and where they receive care. The researchers state the findings highlight the urgent need for improved strategies to contain and prevent further outbreaks in racial and ethnic minority communities in the U.S., principally focused on testing and getting individuals into care.

Rentsch, Christopher T; Kidwai-Khan, Farah; Tate, Janet P; Park, Lesley S; King, Joseph T Jr; Skanderson, Melissa; Hauser, Ronald G; Schultze, Anna; Jarvis, Christopher I; Holodniy, Mark; Lo Re, Vincent 3^rd; Akgün, Kathleen M; Crothers, Kristina; Taddei, Tamar H; Freiberg, Matthew S; Justice, Amy C. Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study. PLoS Med. doi: 10.1371/journal.pmed.1003379. PMID: 32960880; PMCID: PMC7508372.