Discoveries & Impact (June 2021)

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

Cardiovascular Medicine

The root causes of symptoms associated with long-COVID are not well understood. A Yale-Duke research team evaluated over 100 proteins to see if any were linked with poor lung function. They found three proteins (lipocalin 2, matrix metalloproteinase 7, and hepatocyte growth factor) that were highly elevated in COVID-19 patients with persistently impaired lung function. The authors hope that future research targeting these proteins may provide patients with improved long-term outcomes.

Chun HJ, Coutavas E, Pine AB, Lee AI, Yu VL, Shallow MK, Giovacchini CX, Mathews AM, Stephenson B, Que LG, Lee PJ, Kraft BD. Immuno-fibrotic drivers of impaired lung function in post-acute sequelae of SARS-CoV-2. JCI Insight. 2021 Jun 10:148476. doi: 10.1172/jci.insight.148476. Epub ahead of print. PMID: 34111030.

Digestive Diseases

Patients with SARS-CoV-2 infection often have liver injury, but why this occurs remains unknown. High levels of interleukin-6 (IL-6), which may form a complex with the soluble form of its receptor to induce inflammatory signals, have been observed in COVID-19 patients. A recent paper in the Journal of Hepatology shows that the IL-6 signaling complex causes harmful changes to liver sinusoidal endothelial cells and may promote blood clotting and contribute to liver injury.

McConnell MJ, Kawaguchi N, Kondo R, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Lee A, Pine AB, Chun HJ, Zhang X, Fernandez-Hernando C, Qing H, Wang A, Price C, Sun Z, Utsumi T, Hwa J, Strazzabosco M, Iwakiri Y. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. J Hepatol. 2021 May 12:S0168-8278(21)00327-5. doi: 10.1016/j.jhep.2021.04.050. PMID: 33991637.

Endocrinology & Metabolism

Hospital admissions for severe hypoglycemia are associated with significant health care costs, decreased quality of life, and increased mortality, especially for older adults with diabetes. To better understand the reasons for hypoglycemia hospitalization, researchers interviewed older hospitalized patients with diabetes-related hypoglycemia. The findings revealed that health care providers need to shift from their general emphasis on the avoidance of hyperglycemia towards the prevention of hypoglycemia, and work with their patients to design treatment plans that accommodate the patients’ life demands and health care preferences. Read more in BMC Geriatrics.

Pasciak WE, Berg DN, Cherlin E, Fried T, Lipska KJ. Qualitative analysis of reasons for hospitalization for severe hypoglycemia among older adults with diabetes. BMC Geriatr. 2021 May 17;21(1):318. doi: 10.1186/s12877-021-02268-w. PMID: 34001014; PMCID: PMC8130109.

General Internal Medicine

In what is believed to be the first report specifically on the COVID-19 vaccination plans of Medicare recipients, Yale researchers sought to determine whether the vaccination plans of Medicare beneficiaries in the fall of 2020 mirrored patterns in vaccine uptake during the first month of vaccination, the reasons given by those who planned to decline, and whether sociodemographic differences exist among those who planned to decline and their reasons for saying so. Read more in the Journal of the American Geriatrics Society.

Holaday LW, Balasuriya L, Roy B, Ross JS, Oladele CR. Medicare Beneficiaries' Plans For the COVID-19 Vaccine in Fall 2020, and Why Some Planned to Decline. J Am Geriatr Soc. 2021 May 14. doi: 10.1111/jgs.17285. PMID: 33990945.

Geriatrics

A cross-sectional study that evaluates anticoagulation at the end of life among nursing home residents with advanced dementia and atrial fibrillation (AF) is described in a recent JAMA Internal Medicine article.

According to the authors, “while practice guidelines contain a well-defined threshold for starting anticoagulation for AF, there is no clear standard for stopping it.” The study points to the need for high-quality data to inform decision-making about the benefits and harms of anticoagulation for patients with dementia.

Ouellet GM, Fried TR, Gilstrap LG, O'Leary JR, Austin AM, Skinner JS, Cohen AB. Anticoagulant Use for Atrial Fibrillation Among Persons With Advanced Dementia at the End of Life. JAMA Intern Med. 2021 May 10:e211819. doi: 10.1001/jamainternmed.2021.1819. PMID: 33970197; PMCID: PMC8111560

Hematology

In a phase 1 study, mivebresib, a novel drug that influences the way cancer cells read genetic information, was tested together with venetoclax in patients with acute myeloid leukemia (AML) after standard medicines failed and the disease returned, or when standard medicine was unavailable. Adverse effects were described for different drug doses, and the dose that is tolerable was determined. In some patients, their leukemia improved for some time. More studies are necessary to determine whether mivebresib can be used to treat AML. Read more in Cancer journal.

Borthakur G, Odenike O, Aldoss I, Rizzieri DA, Prebet T, Chen C, Popovic R, Modi DA, Joshi RH, Wolff JE, Jonas BA. A phase 1 study of the pan-bromodomain and extraterminal inhibitor mivebresib (ABBV-075) alone or in combination with venetoclax in patients with relapsed/refractory acute myeloid leukemia. Cancer. 2021 May 2. doi: 10.1002/cncr.33590. PMID: 33934351.

Infectious Diseases

In the letter published in BMJ Supportive & Palliative Care, the authors urge caregivers to incorporate palliative care therapies for patients living with HIV and concurrently undergoing cancer therapies. Read more in “Palliation of Malignancies in HIV Infection."

Yasin F, Chow R, Emu B, Bui T, Prsic E. Palliation of malignancies in HIV infection. BMJ Support Palliat Care. 2021 May 18:bmjspcare-2021-003179. doi: 10.1136/bmjspcare-2021-003179. PMID: 34006512.

Medical Oncology

In this new publication in Cancer, researchers evaluated the safety and efficacy of adding TAS-102 to oxaliplatin (TAS-OX) for people with metastatic colorectal cancer. Through the phase 1b study, 41 patients were treated with TAS-OX, which was well-tolerated, with one patient having a partial response and 12 had tumor shrinkage. Learn more.

Cecchini M, Kortmansky JS, Cui C, Wei W, Thumar JR, Uboha NV, Hafez N, Lacy J, Fischbach NA, Sabbath KD, Gomez CM, Sporn JR, Stein S, Hochster HS. A phase 1b expansion study of TAS-102 with oxaliplatin for refractory metastatic colorectal cancer. Cancer. 2021 May 1;127(9):1417-1424. doi: 10.1002/cncr.33379. PMID: 33351187; PMCID: PMC8085021.

Nephrology

In this new study, researchers looked at markers of cell integrity and inflammation for kidney outcomes in post-cardiac surgery patients. They determined that urinary biomarkers EGF and monocyte chemoattractant protein-1 may serve as indicators of tubular damage. Learn more.

Menez S, Ju W, Menon R, Moledina DG, Thiessen Philbrook H, McArthur E, Jia Y, Obeid W, Mansour SG, Koyner JK, Shlipak MG, Coca SG, Garg AX, Kellum JA, Bomback AS, Kretzler M, Parikh CR. Urinary EGF and MCP-1 and risk of CKD after cardiac surgery. JCI Insight. 2021 May 11:147464. doi: 10.1172/jci.insight.147464. PMID: 33974569.

Pulmonary, Critical Care & Sleep Medicine

In this new Yale study, researchers looked at the correlation of stress and sleep disturbances in 153 heart failure patients. They found that perceived stress is related to insomnia in these patients, but it may vary between males and females, and urge more research.

Gaffey AE, Jeon S, Conley S, Jacoby D, Ash GI, Yaggi HK, O'Connell M, Linsky SJ, Redeker NS. Perceived Stress, Subjective, and Objective Symptoms of Disturbed Sleep in Men and Women with Stable Heart Failure. Behav Sleep Med. 2021 May-Jun;19(3):363-377. doi: 10.1080/15402002.2020.1762601. PMID: 32394733; PMCID: PMC7658015.

Rheumatology, Allergy & Immunology

In this new retrospective chart review, researchers looked at the cytokine profiles of 239 hospitalized COVID-19 patients and determined through cluster analysis, an associated between rates of admission, IL-6, sIL2R, and CRP levels and disease severity. Learn more.

Azmy V, Kaman K, Tang D, Zhao H, Dela Cruz C, Topal JE, Malinis M, Price CC. Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19. J Clin Immunol. 2021 May;41(4):738-747. doi: 10.1007/s10875-020-00949-6. PMID: 33459964; PMCID: PMC7812117.