Discoveries & Impact (November 2020)

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

Cardiovascular Medicine

A Yale-led study published in November in JAMA explores the relationship between physician payments from industry and the selection of implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices. According to the study, 96 percent of ICD or CRT-D implants were performed by physicians who had received at least one payment from device manufacturers.

Annapureddy, Amarnath R.; Henien, Shady; Wang, Yongfei; Minges, Karl E.; Ross, Joseph S.; Spatz, Erica S.; Desai, Nihar R.; Peterson, Pamela N.; Masoudi, Frederick A.; Curtis, Jeptha P. Association Between Industry Payments to Physicians and Device Selection in ICD Implantation. JAMA. 2020;324(17):1755–1764. doi:10.1001/jama.2020.17436

Digestive Diseases

Nonalcoholic fatty liver disease is the fastest growing chronic liver disease in the world, and its prevalence is expected to increase by 30% in the next 10 years. In “Drug development of nonalcoholic fatty liver disease: challenges in research, regulatory pathways, and study endpoints,” the authors detail difficulties with drug development, but outline a multifaceted approach in rapid drug development. Read the paper in Expert Opinion on Drug Discovery.

Do, Albert; Ilagan-Ying, Ysabel C; Mehal, Wajahat Z; Lim, Joseph K. Drug development of nonalcoholic fatty liver disease: challenges in research, regulatory pathways, and study endpoints. Expert Opin Drug Discov. 10.1080/17460441.2020.1811674. PMID: 33086894.

Endocrinology & Metabolism

In the new study, “The Impact of Empagliflozin on Obstructive Sleep Apnea, Cardiovascular, and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial,” researchers found that the SGLT2 inhibitor, empagliflozin, reduced body weight and improved cardiovascular and renal outcomes in patients with obstructive sleep apnea (OSA). Empagliflozin also appeared to reduce the risk of new-onset OSA – a novel finding involving this newer glucose lowering medication. 7020 patients with type 2 diabetes and cardiovascular disease were randomized to empagliflozin or placebo, in addition to the standard of care, and followed for an average of three years. To learn more, read the report in Diabetes Care.

Neeland, Ian J; Eliasson, Bjorn; Kasai, Takatoshi; Marx, Nikolaus; Zinman, Bernard; Inzucchi, Silvio E; Wanner, Christoph; Zwiener, Isabella; Wojeck, Brian S; Yaggi, Henry K; Johansen, Odd E; EMPA-REG OUTCOME Investigators. The Impact of Empagliflozin on Obstructive Sleep Apnea, Cardiovascular, and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care. doi: 10.2337/dc20-1096. PMID: 33004464.

General Internal Medicine

In “Racial and Ethnic Disparities in Population-Level Covid-19 Mortality,” the research team found that the availability of COVID-19 data across the country regarding race varied drastically. They performed a cross-sectional study which not only identified substantial racial and ethnic disparities in population-level COVID mortality, but they also demonstrated that accurate measurement of these disparities requires age-adjustment. These findings have had an impact on how some states are reporting their covid mortality data. Read the report in the Journal of General Internal Medicine.

Gross, Cary P; Essien, Utibe R; Pasha, Saamir; Gross, Jacob R; Wang, Shi-Yi; Nunez-Smith, Marcella. Racial and Ethnic Disparities in Population-Level Covid-19 Mortality. J Gen Intern Med. doi: 10.1007/s11606-020-06081-w. 32754782; PMCID: PMC7402388.

Geriatrics

In the recent study, “Functional Effects of Intervening Illnesses and Injuries After Hospitalization for Major Surgery in Community-living Older Persons,” Yale researchers looked at 754 people, 70 years or older, and evaluated their functional outcomes in the year after having a major surgery. They found that the adults who experienced an illness or injury in the year after their surgery were at the greatest risk for having poor functional outcomes. They urge more aggressive care to prevent and manage these intervening illnesses and injuries. Read the report in Annals of Surgery.

Gill, Thomas M; Han, Ling; Gahbauer, Evelyne A; Leo-Summers, Linda; Murphy, Terrance E; Becher, Robert D. Functional Effects of Intervening Illnesses and Injuries After Hospitalization for Major Surgery in Community-living Older Persons. Ann Surg. PMID: 33074902.

Hematology

For patients with relapsed/refractory acute myeloid leukemia, treatment options are limited. In “A phase 1b study of onvansertib, a novel oral PLK1 inhibitor, in combination therapy for patients with relapsed or refractory acute myeloid leukemia,” a multi-center study, researchers treated 40 such patients with onvansertib with either LDAC or decitabine. The team found that the combination of onvansertib and decitabine was well tolerated with preliminary evidence of clinical activity, but stressed the need for future studies.

Zeidan, Amer M.; Ridinger, Maya; Lin, Tara L; Becker, Pamela S.; Schiller, Gary; Patel, Prapti A.; Spira, Alexander I; Tsai, Michaela L.; Samuëlsz, Errin; Silberman, Sandra L.; Erlander, Mark; Wang, Eunice S. A phase 1b study of onvansertib, a novel oral PLK1 inhibitor, in combination therapy for patients with relapsed or refractory acute myeloid leukemia. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-20-2586.

Infectious Diseases

Progress can be made if a concentrated effort is made to increase diversity within the specialty of infectious diseases says Mahalia S. Desruisseaux, MD, associate professor in the Section of Infectious Diseases and author of a recent publication in The Journal of Infectious Diseases. Desruisseaux and her co-author, Tina Tan, MD, of Northwestern University, identify the benefits of diversity, equity, and inclusion in business organizations including medicine, and five focus areas identified by the Infectious Diseases Society of America’s Inclusion, Diversity, Access, and Equity task force. Learn more in “Inclusion, Diversity, Access, and Equity (IDA&E) Roadmap: Infectious Diseases Society of America’s Commitment to the Future.”

Desruisseaux, Mahalia S; Tan, Tina Q. Inclusion, Diversity, Access, and Equity (IDA&E) Roadmap: Infectious Diseases Society of America’s Commitment to the Future. The Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiaa153

Medical Oncology

In “Increasing accrual of minority patients in breast cancer clinical trials,” Yale Cancer Center authors were able to increase the number of minority patients who participated in clinical trials over a two-year span at the facility, but also note the participation rate among Black and Hispanic patients is likely low for a number of factors. They detailed the efforts and impact of the Oncology Welcomes New Haven into Trials (OWN IT) initiative and acknowledge patient education may play a role in low enrollment. Read the study in Breast Cancer Research and Treatment.

Trant, Amelia A.; Walz, Lucas; Allen, Whitney; DeJesus, Jose; Hatzis, Christos; Silber, Andrea. Increasing accrual of minority patients in breast cancer clinical trials. Breast Cancer Res Treat 184, 499–505 (2020). https://doi.org/10.1007/s10549-020-05873-2

Nephrology

Acute interstitial nephritis (AIN) is treated with immunosuppressive therapy but not all patients respond favorably. Researchers looked at 55 patients with AIN to determine kidney function at six month post-diagnosis and found that those with higher (IL)-9 levels were more likely to have higher kidney function with corticosteroid therapy than those with lower IL-9 levels. Researchers hope that this leads to better prediction of who should receive immunosuppressive therapy with AIN. Read “Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis,” in Nephrology Dialysis Transplantation.

Moledina, Dennis G; Wilson, F Perry; Kukova, Lidiya; Obeid, Wassim; Luciano, Randy; Kuperman, Michael; Moeckel, Gilbert W; Kashgarian, Michael; Perazella, Mark A; Cantley, Lloyd G; Parikh, Chirag R. Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis. Nephrol Dial Transplant. doi: 10.1093/ndt/gfaa169. PMID: 33125471.

Pulmonary, Critical Care & Sleep Medicine

A recent study published in the Journal of Leukocyte Biology may lead to an increased understanding of the varied clinical responses of asthmatic inflammation. Yale researchers analyzed sputum samples from healthy controls and asthmatic patients using single cell CyTOF to identify the distinct cellular phenotypes of each participant. Using the in-depth profiling, the authors of “Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF” identified differences in airway cells which may to future understanding of who may respond to a therapeutic asthma treatment.

Stewart, Emma; Wang, Xiaomei; Chupp, Geoffrey L; Montgomery, Ruth R. Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF. J Leukoc Biol. doi: 10.1002/JLB.5MA0720-770RR. PMID: 32911570.

Rheumatology, Allergy & Immunology

The COVID-19 related cytokine storm which drives disease severity is associated with increased levels of inflammatory cytokines and chemokines as well as specific biomarkers such as C-reactive protein, ferritin, and D-dimer, says a new study from Yale School of Medicine researchers in Expert Review of Molecular Diagnostics. Identifying the most significant upstream pathways that dictate systemic inflammatory responses will be critical in uncovering further biomarkers to assess COVID-19 severity. Learn more in “Diagnosis of SARS-CoV-2 infection in the setting of the cytokine release syndrome.”

Azar, Marwan M; Shin, Junghee J; Kang, Insoo; Landry, Marie. Diagnosis of SARS-CoV-2 infection in the setting of the cytokine release syndrome. Expert Rev Mol Diagn. doi: 10.1080/14737159.2020.1830760. PMID: 32990479.

VA Connecticut Healthcare System

In “Incidence and Presentation of Sarcoidosis With and Without HIV Infection,” researchers reviewed 173,194 patients with and without HIV and the incidence of sarcoidosis in each population using data from the Veterans Aging Cohort Study (VACS). They found that people with HIV had a lower risk of sarcoidosis, but despite the lower risk, the disease severity was similar across both populations. Read the complete report in Open Forum Infectious Diseases.

Hanberg, Jennifer S; Akgün, Kathleen M; Hsieh, Evelyn; Fraenkel, Liana; Justice, Amy C; VACS Project Team. Incidence and Presentation of Sarcoidosis With and Without HIV Infection. Open Forum Infectious Diseases. https://doi.org/10.1093/ofid/ofaa441