Discoveries & Impact (February 2021)

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

Cardiovascular Medicine

Cardiac allograft vasculopathy is a leading cause of death among heart transplant recipients. In this review Albert Sinusas, MD, and Attila Feher, MD, PhD, discuss the value of PET in the evaluation of cardiac allograft vasculopathy.

Feher A, Sinusas AJ. Evaluation of cardiac allograft vasculopathy by positron emission tomography. J Nucl Cardiol. 2021 Jan 3. doi: 10.1007/s12350-020-02438-0. Epub ahead of print. PMID: 33389637.

Digestive Diseases

A multi-center observational study of 1,601 patients evaluated the long-term impact of hepatitis C virus (HCV) therapy with direct-acting oral antiviral drugs. A study published last month in Liver International reports on patient-reported outcomes (PROs) from pre-treatment to 12 months post-treatment. “On average, small improvements were observed at 3 months post‐treatment in all PROs and sustained at 12 months post‐treatment among patients with sustained virologic response (SVR),” the authors wrote. Clinically meaningful improvements were achieved in fatigue, sleep, abdominal pain, and functional well-being. The patients with cirrhosis had the greatest improvements in functional well-being, according to the authors.

Serper, M., Evon, D.M., Amador, J., Stewart, P.W., Sarkar, S., Lok, A.S., Sterling, R.K., Reeve, B.B., Golin, C.E., Reddy, K.R., Lim, J.K., Reau, N., Nelson, D.R., Di Bisceglie, A.M. and Fried, M.W. (2021), Patient‐Reported Outcomes 12 Months After Hepatitis C Treatment with Direct‐Acting Antivirals: Results from the PROP UP Study. Liver International. https://doi.org/10.1111/liv.14781

Endocrinology & Metabolism

In an abstract published this year, a team of investigators reports that a specific signaling pathway is activated by metabolic stress, promoting the development of metabolic syndrome, including hyperglycemia, hyperlipidemia, and insulin resistance. “This integrated physiological response involves cross-talk between different organs. Here we demonstrate that cJun NH₂-terminal kinase (JNK) signaling in adipocytes causes an increased circulating concentration of the hepatokine fibroblast growth factor 21 (FGF21) that regulates systemic metabolism,” the researchers wrote. Learn more in Genes & Development.

Han MS, Perry RJ, Camporez JP, Scherer PE, Shulman GI, Gao G, Davis RJ. A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21. Genes Dev. 2021 Jan 1;35(1-2):133-146. doi: 10.1101/gad.344556.120. PMID: 33334822.

General Internal Medicine

Applying a social ecological model (SEM) to describe the potential and observed range of effects of the COVID-19 pandemic on individuals with opioid use disorder (OUD) is discussed in a commentary published in January in Addiction Science & Clinical Practice. The pandemic “has posed unique and poorly characterized challenges” for individuals with OUD, the authors explained. Theoretical modes “can guide scientific inquiry, interventions, and public policy. Models also provide a visual image of the interplay of individual-, network-, community-, structural-, and pandemic-level factors that can lead to increased risks of infection and associated morbidity and mortality for individuals and populations.”

Cowan E, Khan MR, Shastry S, Edelman EJ. Conceptualizing the effects of the COVID-19 pandemic on people with opioid use disorder: an application of the social ecological model. Addict Sci Clin Pract. 2021 Jan 7;16(1):4. doi: 10.1186/s13722-020-00210-w. PMID: 33413619; PMCID: PMC7789072.

Geriatrics

Researchers developed a 180-day readmission risk model for older adults with acute myocardial infarction (AMI) that included a broad range of characteristics, including functional mobility and self-reported health status, neither of which have been previously considered in 180-day risk models, they said in Open Heart journal last month. The researchers concluded that over 40% of participants were readmitted within 180 days. They used data from the ComprehenSIVe Evaluation of Risk in Older Adults with AMI (SILVER-AMI), a prospective cohort study that enrolled patients 75 years of age or older, with data from 94 hospitals in the U.S.

Dodson JA, Hajduk AM, Murphy TE, Geda M, Krumholz HM, Tsang S, Nanna MG, Tinetti ME, Ouellet G, Sybrant D, Gill TM, Chaudhry SI. 180-day readmission risk model for older adults with acute myocardial infarction: the SILVER-AMI study. Open Heart. 2021 Jan;8(1):e001442. doi: 10.1136/openhrt-2020-001442. PMID: 33452007; PMCID: PMC7813425.

Hematology

In a new study in Transfusion and Apheresis Science, a team from Yale created institutional guidelines for repeat plerixafor dosing in stem cell mobilization for use in patients with multiple myeloma and lymphoma. The authors hope the algorithms will improve patient experience, along with improving resource utilization.

Gupta GK, Perreault S, Seropian SE, Tormey CA, Hendrickson JE. Optimization of repeat plerixafor dosing for autologous peripheral blood stem-cell collection. Transfus Apher Sci. 2021 Jan 27:103069. doi: 10.1016/j.transci.2021.103069. PMID: 33546988.

Infectious Diseases

Yale researchers looked at immune response and chronic inflammation of persons with and without HIV infection with an opioid use disorder who use methadone or buprenorphine. In this prospective, longitudinal study of 135 participants, this paper shares the recruitment, laboratory, and statistical methods of the study, in addition to protocol in hopes to determine whether methadone or buprenorphine is best for individuals with HIV and opioid use disorder.

Biondi BE, Mohanty S, Wyk BV, Montgomery RR, Shaw AC, Springer SA. Design and implementation of a prospective cohort study of persons living with and without HIV infection who are initiating medication treatment for opioid use disorder. Contemp Clin Trials Commun. 2021 Jan 6;21:100704. doi: 10.1016/j.conctc.2021.100704. PMID: 33490708; PMCID: PMC7807244.

Medical Oncology

In this editorial, Yale authors commend the work of Riaz et al. who, in JNCI, evaluated whether low tumor oxygen content predicts the need for full doses of radiation in human papillomavirus-related head and neck cancer. They urge more studies on treatment de-escalation in conjunction with other treatment approaches. Read more in JNCI.

Burtness, B, Contessa, J. Hypoxia-Guided Therapy for Human Papillomavirus-Associated Oropharynx Cancer. JNCI. https://doi.org/10.1093/jnci/djaa187

Nephrology

In this study, Yale researchers looked at the association of COVID-19 infection with acute kidney injury (AKI). They looked at 22,122 patients hospitalized from March to August of 2020, and found that patients with COVID-19 had more AKI, more severe AKI, and a lower recovery from the condition than other hospitalized patients. Future research is necessary to look at how COVID-19 may cause AKI. Learn more in the American Journal of Kidney Diseases.

Moledina DG, Simonov M, Yamamoto Y, Alausa J, Arora T, Biswas A, Cantley LG, Ghazi L, Greenberg JH, Hinchcliff M, Huang C, Mansour SG, Martin M, Peixoto A, Schulz W, Subair L, Testani JM, Ugwuowo U, Young P, Wilson FP. The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study. Am J Kidney Dis. 2021 Jan 7:S0272-6386(21)00003-2. doi: 10.1053/j.ajkd.2020.12.007. PMID: 33422598; PMCID: PMC7791318.

Pulmonary, Critical Care & Sleep Medicine

In a study that aimed to uncover potentially new disease mechanisms that can be easily treated, researchers discovered that macrophage-derived NTN1 drives the development of fibrosis through a mechanism involving remodeled adrenergic nerves, their secretory product noradrenaline, and α₁ adrenoreceptors. Further, the researchers recently stated in The Journal of Clinical Investigation, “this axis is at least partially intact in humans with Idiopathic pulmonary fibrosis (IPF) where it may be targeted with safe and well-tolerated α₁ adrenoreceptor antagonists that are already FDA approved.”

Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve-associated lung fibrosis. J Clin Invest. 2021 Jan 4;131(1):e136542. doi: 10.1172/JCI136542. PMID: 33393489; PMCID: PMC7773383.

Rheumatology, Allergy & Immunology

Dual-energy X-ray absorptiometry (DXA) is used to measure bone mineral density (BMD) in the diagnosis of osteoporosis, but technical aspects of DXA measurement, including selection of different scanning modes, may impact readings. Using the European Spine Phantom (ESP) to perform ex vivo measurements across 19 hospitals with Hologic DXA machines in China, significant differences were observed between average ESP BMD for the Array and Express Array scan modes, and between Fast Array and Express Array scan modes. However, no significant difference in average ESP BMD was observed between the Array and Fast Array scan modes. In the appropriate context, the Fast Array scanning mode may be a reasonable choice for Hologic DXA machines, said the researchers. Future in vivo studies can help guide the clinical application of these findings. Learn more in the Journal of Clinical Densitometry.

Yu W, Zhang Z, Pan W, Guan W, Lin Q, Xia W, Li T, Hsieh E. Comparison of Differences in Bone Mineral Density Measurement With 3 Hologic Dual-Energy X-Ray Absorptiometry Scan Modes. J Clin Densitom. 2021 Jan 9:S1094-6950(21)00003-2. doi: 10.1016/j.jocd.2021.01.003. PMID: 33504451.