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Discoveries & Impact (August 2021)

August 11, 2021
by Elisabeth Reitman, Jane E. Dee and Julie Parry

Discoveries & Impact highlights select scientific discoveries per section across the Department of Internal Medicine.

Cardiovascular Medicine

This study published in Circulation: Cardiovascular Quality and Outcomes provides new insights about postoperative pain experiences for those undergoing cardiac surgery and underscores the variations among different sites. The authors explore the determinants of different experiences and possible interventions to mitigate pain.

Mori M, Brooks C, Dhruva SS, Lu Y, Spatz ES, Dey P, Zhang Y, Chaudhry SI, Geirsson A, Allore HG, Krumholz HM. Trajectories of Pain After Cardiac Surgery: Implications for Measurement, Reporting, and Individualized Treatment. Circ Cardiovasc Qual Outcomes. 2021 Jul 26:CIRCOUTCOMES120007781. doi: 10.1161/CIRCOUTCOMES.120.007781. Epub ahead of print. PMID: 34304586.

Digestive Diseases

Yale researchers evaluated whether SGLT2i can reduce the incidence of ascites and death over a period of 36 months in patients with cirrhosis and diabetes mellitus. Among 846 patients from Veterans Affairs hospitals in the United States, they found no significant difference in the risk for ascites but did find that SGLT2i users had a reduced risk for death. In comparison with dipeptidyl peptidase-4 inhibitors, SGLT2i may improve survival for patients with cirrhosis who require additional pharmacotherapy for diabetes mellitus beyond metformin, but additional studies are necessary. Read the report in Diabetes, Obesity and Metabolism.

Saffo S, Kaplan DE, Mahmud N, Serper M, John BV, Ross JS, Taddei T. Impact of SGLT2 inhibitors in comparison with DPP4 inhibitors on ascites and death in veterans with cirrhosis on metformin. Diabetes Obes Metab. 2021 Jul 6. doi: 10.1111/dom.14488. Epub ahead of print. PMID: 34227216.

Endocrinology & Metabolism and Pulmonary, Critical Care & Sleep Medicine

Although there’s a well-documented bidirectional connection between obesity and mood- and stress-related psychiatric disorders, molecular mechanisms altered in obesity have not been fully explained. Yale researchers investigated relationships between obesity and synaptic density using the radioligand [11C]UCB-J, which binds to synaptic glycoprotein SV2A, and positron emission tomography in individuals with obesity with or without stress-related psychiatric disorders. Read more in Nature.

Asch RH, Holmes SE, Jastreboff AM, Potenza MN, Baldassarri SR, Carson RE, Pietrzak RH, Esterlis I. Lower synaptic density is associated with psychiatric and cognitive alterations in obesity. Neuropsychopharmacology. 2021 Jul 22. doi: 10.1038/s41386-021-01111-5. Epub ahead of print. PMID: 34294874.

General Internal Medicine

Entrustment Decision-Making in the Core EPAs: Results of a Multi-Institutional Study published in Academic Medicine in July, reports that medical schools are able to gather and review student data longitudinally to make decisions regarding graduating students’ readiness for indirect supervision on key clinical activities during residency. The data also highlight the work still to be done, particularly regarding workplace assessments and availability of other data.

Brown DR, Moeller JJ, Grbic D, Biskobing DM, Crowe R, Cutrer WB, Green ML, Obeso VT, Wagner DP, Warren JB, Yingling SL, Andriole DA; Core Entrustable Professional Activities for Entering Residency Pilot. Entrustment Decision-Making in the Core EPAs: Results of a Multi-Institutional Study. Acad Med. 2021 Jul 13. doi: 10.1097/ACM.0000000000004242. Epub ahead of print. PMID: 34261864.


In this new study from Yale School of Medicine and Yale School of Public Health, researchers looked at nationally-representative data on 5,571 community-living older persons from the National Health and Aging Trends Study (NHATS) and found that an average of nearly 9 major surgeries were performed per year for every 100 persons ≥65 years. Over the 5 years of data analyzed, more than 1 in 7 Medicare beneficiaries had at least 1 major surgery; 40% of major surgeries were unplanned. These results have critical implications for health care in the U.S. Read more…

Becher RD, Wyk BV, Leo-Summers L, Desai MM, Gill TM. The Incidence and Cumulative Risk of Major Surgery in Older Persons in the United States. Ann Surg. 2021 Jul 14. doi: 10.1097/SLA.0000000000005077. Epub ahead of print. PMID: 34261884.


In the new publication, “Peri-transfusion quality-of-life assessment for patients with myelodysplastic syndromes,” researchers performed a prospective pilot study of 62 adults with myelodysplastic syndromes who received red blood cell transfusions due to anemia. They concluded that while peri-transfusion QOL assessment was possible, red cell transfusion may not improve quality of life for many patients. Learn more…

Abel GA, Klepin HD, Magnavita ES, Jaung T, Lu W, Shallis RM, Hantel A, Bahl NE, Dellinger-Johnson R, Winer ES, Zeidan AM. Peri-transfusion quality-of-life assessment for patients with myelodysplastic syndromes. Transfusion. 2021 Jul 12. doi: 10.1111/trf.16584. Epub ahead of print. PMID: 34251040.

Infectious Diseases

In “Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19,” scientists across Yale School of Medicine performed a cohort study looking at 151 patients hospitalized with moderate to severe COVID-19 who received COVID-19 convalescent plasma (CCP) to determine if when the CCP was administered made a difference in patient outcomes. They determined that the timing of administering CCP does matter, with those receiving the treatment within six days of admission having lower mortality and fewer days on a ventilator. Learn more…

Briggs N, Gormally MV, Li F, Browning SL, Treggiari MM, Morrison A, Laurent-Rolle M, Deng Y, Hendrickson JE, Tormey CA, Desruisseaux MS. Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19. PLoS One. 2021 Jul 28;16(7):e0254453. doi: 10.1371/journal.pone.0254453. PMID: 34320004; PMCID: PMC8318280.

Medical Oncology

In the United States, the incidence of hepatocellular carcinoma (HCC) is growing. This study looked at the neutrophil to lymphocyte ratio (NLR) in 581 patients with HCC, over 60% of whom had underlying hepatitis C virus (HCV) infection. Lower NLR was associated with improved overall survival, however the effect of NLR is decreased in patients with HCV. Future studies are needed to determine how HCV affects the immune response. Learn more…

Sellers CM, Uhlig J, Ludwig JM, Pollak JS, Taddei TH, Stein SM, Lim JK, Kim HS. The effect of chronic viral hepatitis on prognostic value of inflammatory biomarkers in hepatocellular carcinoma. Cancer Med. 2021 Jul 28. doi: 10.1002/cam4.3573. Epub ahead of print. PMID: 34318618.


In this new report out of Yale School of Medicine, the team looked at a patient with action myoclonus–renal failure syndrome (AMRF), a rare autosomal recessive progressive myoclonic epilepsy associated with progressive myoclonic epilepsy and kidney disease to see if using miglustat could improve neurologic symptoms. The work suggests that these symptoms can be improved by targeting glycosphingolipid metabolism with miglustat. Learn more…

Quraishi IH, Szekely AM, Shirali AC, Mistry PK, Hirsch LJ. Miglustat Therapy for SCARB2-Associated Action Myoclonus-Renal Failure Syndrome. Neurol Genet. 2021 Jul 28;7(5):e614. doi: 10.1212/NXG.0000000000000614. PMID: 34337151; PMCID: PMC8320328.

Pulmonary, Critical Care & Sleep Medicine

A mitochondrial molecule, nucleotide-binding domain and leucine-rich-repeat-containing protein X1 (NLRX1), represents the only NLR family member that targets this cellular location, implying that NLRX1 probably establishes a fundamental link between mitochondrial functions and cellular physiology. A recent study by Yale researchers provides evidence for NLRX1 as a crucial regulator of cellular senescence and in vivo lung aging.

Shin HJ, Kim SH, Park HJ, Shin MS, Kang I, Kang MJ. Nucleotide-binding domain and leucine-rich-repeat-containing protein X1 deficiency induces nicotinamide adenine dinucleotide decline, mechanistic target of rapamycin activation, and cellular senescence and accelerates aging lung-like changes. Aging Cell. 2021 Jul;20(7):e13410. doi: 10.1111/acel.13410. Epub 2021 Jun 4. PMID: 34087956; PMCID: PMC8282248.

Rheumatology, Allergy & Immunology

A study by Yale researchers published in The Journal of Rheumatology in July presents positron emission tomography-computed tomography (PET/CT) myocardial perfusion imaging study results. Patients with systemic sclerosis demonstrated impaired myocardial flow reserve, which may indicate coronary microvascular dysfunction compared to two control groups (healthy individuals and patient group matched for age, gender and comorbidities). Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Computed Tomography in Patients with Systemic Sclerosis

Feher A, Boutagy NE, Oikonomou EK, Thorn S, Liu YH, Miller EJ, Sinusas AJ, Hinchcliff M. Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Computed Tomography in Patients with Systemic Sclerosis. J Rheumatol. 2021 Jul 15:jrheum.210040. doi: 10.3899/jrheum.210040. Epub ahead of print. PMID: 34266986.

Submitted by Julie Parry on August 11, 2021