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Discoveries & Impact (September 2020)

September 17, 2020
by Julie Parry

Discoveries & Impact is a new D[IM]ensions column, highlighting publications per section across the Department of Internal Medicine.

Cardiovascular Medicine

Yale New Haven Hospital (YNHH) developed a system to determine which patients were in need of urgent cardiac procedures and which could be rescheduled to reduce possible exposure. In addition to delaying nonurgent cardiac procedures, YNHH leadership established mandatory protocols to limit contact between healthcare providers and patients. The use of masks, personal protective equipment, and pre-procedure testing were also recommended by the Heart Rhythm Society (HRS) COVID-19 task force and other professional cardiovascular societies. In “Risk of COVID-19 infection after cardiac electrophysiology procedures,” authors concluded that the infection-prevention strategies minimized the spread of COVID-19 for patients and staff. Read the publication in Heart Rhythm O2.

Workman, Virginia; Freeman, James V.; Obasare, Edinrin R.; Jain, Shashank; Ganeshan, Raj; Burr, Alicia; Blitzer, Mark; Akar, Joseph; Lampert, Rachel. Risk of COVID-19 infection after cardiac electrophysiology procedures. Heart Rhythm O2. doi: 10.1016/j.hroo.2020.08.00

Digestive Diseases

Yale Liver Center researchers looked at data from patients with confirmed COVID-19 within Yale New Haven Health and found that abnormal liver tests were common. Their data revealed that abnormal liver test rates were higher in the United States than the data released from China and called for future studies to determine the cause for disparity. Learn more about the study in Abnormal Liver Tests in COVID-19: A Retrospective Observational Cohort Study of 1827 Patients in a Major U.S. Hospital Network in Hepatology.

Hundt, Melanie A.; Deng, Yanhong; Ciarleglio, Maria M.; Nathanson, Michael H.; Lim, Joseph K. Abnormal Liver Tests in COVID‐19: A Retrospective Observational Cohort Study of 1827 Patients in a Major U.S. Hospital Network. Hepatology. doi:10.1002/hep.31487

Endocrinology & Metabolism

A new study published in Cell Metabolism provides new insights into the development of insulin resistance in the liver. In “A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance,” the team devised a subcellular fractionation method to measure diacylglycerol stereoisomers and ceramides in the endoplasmic reticulum (ER), mitochondria, plasma membrane, lipid droplets, and cytosol. These findings identify PM sn-1,2-DAGs as the key pool of lipids that activate the PKCϵ enzyme, and that this enzyme in the liver is necessary for the development of insulin resistance.

Lyu, Kun; Zhang, Ye; Zhang, Dongyan; Kahn, Mario; Ter Horst, Kasper W.; Rodrigues, Marcos; Gaspar, Rafael C.; Hirabara, Sandro M.; Luukkonen, Panu K.; Lee, Seohyuk; Bhanot, Sanjay; Rinehart, Jesse; Blume, Niels; Rasch, Morten G.; Serlie, Mireille J., Bogan, Jonathan S.; Cline, Gary W.; Samuel, Varman T.; Shulman, Gerald I. A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance. Cell Metab. 2020;S1550-4131(20)30414-9. doi:10.1016/j.cmet.2020.08.001

General Internal Medicine

In “Charting the Course for Online Physician Assistant Education,” published in Medical Science Educator, authors Jane McDaniel, MS, MLS, SC; and James Van Rhee, MS, PA-C; noted that the “move to online learning has become one of the most challenging events in physician assistant (PA) education.” Online curriculum started at Yale School of Medicine in 2018 with the debut of the Yale Physician Assistant Online Program. The 28-month curriculum blends the latest innovations in online technology with a problem-based learning (PBL) curriculum, and engages students using the Socratic method online while providing feedback in real time. While this novel approach to learning is still being evaluated as data is continually collected, preliminary results indicate online technology can be successfully implemented in a blended PA education curriculum.

McDaniel, M. Jane; Van Rhee, James A. Charting the Course for Online Physician Assistant Education. Med.Sci.Educ. (2020).


Researchers at Yale School of Medicine and the VA CT Healthcare System developed and internally validated a model to predict six-month risk of serious falls for middle-aged veterans. The team looked at data (demographics, laboratory results, pharmacy fill/refill, health factors, vital signs, clinical text notes) from Veterans aged 45 and 65 years from the Veterans Health Administration (VA) Birth Cohort. They identified 16 key predictors of serious falls and five interaction terms. Read “Serious Falls in Middle‐Aged Veterans: Development and Validation of a Predictive Risk Model” in the Journal of the American Geriatrics Society to learn more.

Womack, Julie A.; Murphy, Terrance E.; Bathulapalli, Harini; Smith, Alexandria; Bates, Jonathan; Jarad, Samah; Redeker, Nancy S.; Luther, Stephen L.; Gill, Thomas M.; Brandt, Cynthia A.; Justice, Amy C. Serious Falls in Middle-Aged Veterans: Development and Validation of a Predictive Risk Model. J Am Geriatr Soc. 2020;10.1111/jgs.16773. doi:10.1111/jgs.16773


The use of leukapheresis for hyperleukocytosis, a life-threatening complication of leukemia leading to an excess of white blood cells in the bloodstream, in acute myeloid leukemia (AML) patients did not provide a benefit, found researchers at Yale School of Medicine, University of Alabama School of Medicine, and Memorial Sloan Kettering Cancer Center. The team performed a systematic review and meta-analysis of 13 two-arm, retrospective studies including 1743 patients. They found that “leukapheresis did not improve the primary outcome of early mortality compared to treatment strategies in which leukapheresis was not used,” and concluded that the results argue against the use of leukapheresis for management of hyperleukocytosis in AML patients. Read “Leukapheresis for the management of hyperleukocytosis in acute myeloid leukemia—A systematic review and meta‐analysis” in Transfusion to learn more.

Bewersdorf, Jan P; Giri, Smith; Tallman, Martin S; Zeidan, Amer M; Stahl, Maxmilian. Leukapheresis for the management of hyperleukocytosis in acute myeloid leukemia-A systematic review and meta-analysis. Transfusion. 2020;10.1111/trf.15994. doi:10.1111/trf.15994

Infectious Diseases

In “Preventing COVID-19 Collateral Damage,” authors James Shepherd, MD, PhD; and Gerald Friedland, MD, outlined other diseases and patient populations that could be significantly negatively affected by the COVID-19 pandemic. Global programs assisting those with diseases such as tuberculosis and HIV and vaccinations for preventing measles and poliovirus and others have been suspended due to COVID-19, with dire consequences. The authors suggest that COVID-19 programs be integrated into already existing public health programs, healthcare workers be protected, and supply chains be maintained. Read “Preventing COVID-19 Collateral Damage” in Clinical Infectious Diseases.

Shepherd, James; Friedland, Gerald. Preventing COVID-19 Collateral Damage. Clinical Infectious Diseases.

Medical Oncology

The use of medical marijuana for pain led to fewer hospitalizations for patients with sickle cell disease (SCD) found a recent study published in Blood Advances. This retrospective study of 50 patients at the Adult Sickle Cell Program at Yale New Haven Hospital found a reduction in admission rates and an increase in edible product use, but many patients were unable to get medical marijuana due to varying state laws and out-of-pocket costs. Learn more in “Medical marijuana certification for patients with sickle cell disease: a report of a single center experience.”

Curtis, Susanna A; Lew, Dana; Spodick, Jonathan; Hendrickson, Jeanne E; Minniti, Caterina P; Roberts, John D. Medical marijuana certification for patients with sickle cell disease: a report of a single center experience. Blood Adv. 2020;4(16):3814-3821. doi:10.1182/bloodadvances.2020002325


The current kidney allocation policy may need revised, said authors of “Physician and Patient Acceptance of Policies to Reduce Kidney Discard,” a new study published in Clinical Transplantation. The kidney discard rate varies globally, but remains between 18 – 20 percent in the United States. Physicians and patients surveyed found the fast-tracking of kidneys at risk of discard and returning waiting time to patients with graft failure within the first 12 months were acceptable policy changes, but future research in the design and implementation of these policies are needed.

Mehrotra, Sanjay; Schantz, Karolina; Friedewald, John J.; Ladner, Daniela P.; Becker, Yolanda; Formica, Richard; Barah, Masoud; Gu, Jiayi; Gordon, Elisa J. Physician and Patient Acceptance of Policies to Reduce Kidney Discard. Clin Transplant. doi:10.1111/ctr.14054

Pulmonary, Critical Care & Sleep Medicine

In “Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia,” researchers found that the immune protein procalcitonin (PCT) rises during viral infection in proportion to disease severity, and in contrast to previous PCT regulation models, “is not suppressed by [virus-induced] interferon signaling.” These properties make it a poor biomarker for postviral bacterial pneumonia. The retrospective study looked at 2811 patients admitted to Yale New Haven Hospital with a positive test for a respiratory virus and at least one measurement of PCT during admission. Along with the human data, they also looked at murine and cellular models. The team suggests further studies to clarify PCT biology and its use as a diagnostic aid for respiratory infections. Read the complete study in Thorax.

Gautam, Samir; Cohen, Avi J; Stahl, Yannick; Valda Toro, Patricia; Young, Grant M; Datta, Rupak; Yan, Xiting; Ristic, Nicholas T; Bermejo, Santos D; Sharma, Lokesh; Restrepo, Marcos I; Dela Cruz, Charles S. Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia. Thorax. doi: 10.1136/thoraxjnl-2020-214896

Rheumatology, Allergy & Immunology

The new study “Antirheumatic Disease Therapies for the Treatment of COVID-19: A Systematic Review and Meta-analysis,” published in Arthritis & Rheumatology, found that the use of hydroxychloroquine in COVID-19 patients was found to be neither beneficial or harmful in terms of mortality. In “Antirheumatic Disease Therapies for the Treatment of COVID‐19: A Systematic Review and Meta‐analysis,” the team performed a systematic review and meta-analysis of 45 articles (4 randomized controlled trials, 29 cohort studies, and 12 case series) and looked at the use of hydroxychloroquine and other antirheumatic disease therapies, such as glucocorticoids, intravenous immunoglobulin and baricitinib. The group suggests further study and caution to physicians considering an off-label use of antirheumatic disease therapies in the treatment of COVID-19.

Putman, Michael; Chock, Yu Pei Eugenia; Tam, Herman; Kim, Alfred H.J.; Sattui, Sebastian E.; Berenbaum, Francis; Danila, Maria I.; Korsten, Peter; Sanchez-Alvarez, Catalina; Sparks, Jeffrey A.; Coates, Laura C.; Palmerlee, Candace; Peirce, Andrea; Jayatilleke, Arundathi; Johnson, Sindhu R.; Kilian, Adam; Liew, Jean; Prokop, Larry J.; Murad, M. Hassan; Grainger, Rebecca; Wallace, Zachary S.; Duarte-García, Alí. Antirheumatic Disease Therapies for the Treatment of COVID-19: A Systematic Review and Meta-analysis. Arthritis Rheumatol. 2020;10.1002/art.41469. doi:10.1002/art.41469

VA Connecticut Healthcare System

As COVID-19 spread across the United States, the VA Connecticut Healthcare System shifted its care model to virtual. In A Model for Rapid Transition to Virtual Care, VA Connecticut Primary Care Response to COVID-19 in the Journal of General Internal Medicine, the clinicians and primary care leaders describe their rapid deployment model to virtual care and found that, despite the dramatic conversion to virtual care over a short period of time, they were able to maintain provision of care. They found that nearly all patients were capable of virtual visits but barriers existed with video modalities. Spelman et al wrote that the “COVID-19 pandemic has forced a dramatic shift in how health care is delivered, and an important ‘silver lining’ of this crisis is that it has triggered a rethinking of the optimal balance of care-delivery modalities.”

Spelman, Juliette F.; Brienza, Rebecca; Walsh, Robert; Drost, Paul; Schwartz, Amy; Kravetz, Jeffrey; Pitkin, Patricia; Ruser, Christopher. A Model for Rapid Transition to Virtual Care, VA Connecticut Primary Care Response to COVID-19. J Gen Intern Med. (2020).

Submitted by Julie Parry on September 17, 2020