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Discoveries & Impact (January 2022)

January 11, 2022
by Elisabeth Reitman, Jane E. Dee and Julie Parry

Discoveries & Impact highlights select scientific discoveries per section across the Department of Internal Medicine. The complete publications report can be viewed under Related Documents.

Cardiovascular Medicine

In BMJ Surgery, Interventions, & Health Technologies researchers at Mayo Clinic, University of California, University of Pennsylvania, Mercy, and the Yale School of Medicine demonstrated that informatics approaches can be feasibly used to capture safety and effectiveness outcomes in real-world data in the evaluation of cardiac ablation catheters. Lessons from this collaborative study can help future researchers use real-world health system data to evaluate medical device safety and effectiveness.

Jiang G, Dhruva SS, Chen J, Schulz WL, Doshi AA, Noseworthy PA, Zhang S, Yu Y, Patrick Young H, Brandt E, Ervin KR, Shah ND, Ross JS, Coplan P, Drozda JP. Feasibility of capturing real-world data from health information technology systems at multiple centers to assess cardiac ablation device outcomes: A fit-for-purpose informatics analysis report. J Am Med Inform Assoc. 2021 Sep 18;28(10):2241-2250. doi: 10.1093/jamia/ocab117. PMID: 34313748; PMCID: PMC8449615.

Digestive Diseases

In “The Use of Nondirected Donor Organs in Living Donor Liver Transplantation: Perspectives and Guidance,” the authors reviewed current transplant policy and emerging data to provide guidance in non-directed living liver donation. They outlined an algorithm designed to be equitable and derive the maximal benefit for the recipient. Learn more in Hepatology.

Fox AN, Liapakis A, Batra R, Bittermann T, Emamaullee J, Emre S, Genyk Y, Han H, Jackson W, Pomfret E, Raza M, Rodriguez-Davalos M, Rubman S, Samstein B, Shenoy A, Taner T, Roberts J. The Use of Nondirected Donor Organs in Living Donor Liver Transplantation: Perspectives and Guidance. Hepatology (Baltimore, Md.) 2021 doi: 10.1002/hep.32260. PMID: 34859474.

Endocrinology & Metabolism

In this Yale-led study, researchers found an opportunity to improve care for people with type 2 diabetes. They reviewed U.S. Medicare prescriber data from 2014 to 2018 for the use of metformin and sodium-glucose cotransporter-2 inhibitors (SGLT2i) and found that one in five clinicians prescribing antihyperglycemic therapies, prescribed any SGLT2i. In addition, only one in seven cardiologists prescribed SGLT2i in the same scenario. The team suggested that proactive investigation is necessary to improve the usage of SGLT2i. Read more in Circulation: Cardiovascular Quality and Outcomes.

Sangha V, Lipska K, Lin Z, Inzucchi SE, McGuire DK, Krumholz HM, Khera R. Patterns of Prescribing Sodium-Glucose Cotransporter-2 Inhibitors for Medicare Beneficiaries in the United States. Circulation. Cardiovascular Quality And Outcomes 2021, 14(12): e008381. doi: 10.1161/CIRCOUTCOMES.121.008381. PMID: 34779654.

General Internal Medicine

In this new study, the researchers conducted qualitative interviews of primary care physicians between July 2018 to March 2020 and evaluated using thematic analysis to evaluate career and life satisfaction. They evaluated the interviews by five themes applicable to physician thriving, and found that thriving is partly an internal process through which a person finds their life and work meaningful. Learn more in “Thriving among Primary Care Physicians: a Qualitative Study” in the Journal Of General Internal Medicine.

Gielissen KA, Taylor EP, Vermette D, Doolittle B. Thriving among Primary Care Physicians: a Qualitative Study. Journal Of General Internal Medicine 2021, 36(12): 3759-3765. doi: 10.1007/s11606-021-06883-6. PMID: 34047922. PMCID: PMC8642558.

Geriatrics

Older adults who have been hospitalized for a heart attack are at risk for falls post-discharge. New research published in the Journal Of The American Geriatrics Society found that 21.6% of study participants reported a fall, with 6.4% falls considered medically serious in the six months after hospitalization for heart attack. Researchers urge that fall risk and opportunities to prevent this risk be evaluated post-hospital discharge.

Goldstein DW,* Hajduk AM,* Song X, Tsang S, Geda M, McClurken JB, Tinetti ME, Krumholz HM, Chaudhry SI. Falls in older adults after hospitalization for acute myocardial infarction. Journal Of The American Geriatrics Society 2021, 69(12): 3476-3485. doi: 10.1111/jgs.17398. PMID: 34383963.

Hematology

In this new phase I study led by investigators at Yale, CC-90002, an anti-CD47 antibody, was given to patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). While CC-90002 was shown to be safe and important information on the drug’s pharmacological properties in mice and humans were collected, the clinical efficacy of CC-90002 among the 28 enrolled patients was modest and CC-90002 will not be developed further in AML and MDS. However, even “negative” studies such as this are important to gain a better understanding of the differences between anti-CD47 agents in preclinical and clinical settings. Learn more in Annals of Hematology.

Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, Burgess MR, Hege K, Stock W. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Ann Hematol. 2022 Jan 4. doi: 10.1007/s00277-021-04734-2. Online ahead of print.PMID: 34981142

Infectious Diseases

Although early-career researchers represent the foundation of public health infrastructure and are playing a major role in COVID-19 response, pandemic pressures are squeezing them out of public health and academic research. Read more about why postdoctoral fellows are in a precarious position.

Malik AA, Crookes DM, Sundaram M. Being an early career public health professional during the COVID-19 pandemic. Lancet Regional Health. Americas 2021, 4: 100087. doi: 10.1016/j.lana.2021.100087. PMID: 34642688. PMCID: PMC8497032.

Medical Oncology

Currently, there’s no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions on oncologic end points. A panel of experts, including David C. Madoff, MD, reached consensus on recommendations which they published in the journal Radiology. Clear definitions will ensure an objective and reliable interpretation of results, the authors argue. Find information about their report here, and read an accompanying editorial here.

Puijk RS, Ahmed M, Adam A, Arai Y, Arellano R, de Baère T, Bale R, Bellera C, Binkert CA, Brace CL, Breen DJ, Brountzos E, Callstrom MR, Carrafiello G, Chapiro J, de Cobelli F, Coupé VMH, Crocetti L, Denys A, Dupuy DE, Erinjeri JP, Filippiadis D, Gangi A, Gervais DA, Gillams AR, Greene T, Guiu B, Helmberger T, Iezzi R, Kang TW, Kelekis A, Kim HS, Kröncke T, Kwan S, Lee MW, Lee FT, Lee EW, Liang P, Lissenberg-Witte BI, Lu DS, Madoff DC, Mauri G, Meloni MF, Morgan R, Nadolski G, Narayanan G, Newton I, Nikolic B, Orsi F, Pereira PL, Pua U, Rhim H, Ricke J, Rilling W, Salem R, Scheffer HJ, Sofocleous CT, Solbiati LA, Solomon SB, Soulen MC, Sze D, Uberoi R, Vogl TJ, Wang DS, Wood BJ, Goldberg SN, Meijerink MR. Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative. Radiology 2021, 301(3): 533-540. doi: 10.1148/radiol.2021203715. PMID: 34581627.

Nephrology

APOL1 G1 and G2 variants are established risk factors for nondiabetic kidney disease. The presence of two APOL1 risk variants in donor kidneys negatively impacts kidney allograft survival. However, the role of APOL1-G1/G2 in kidney transplant recipients was not known. An important study led by Dr Madhav Menon from Yale nephrology and colleagues in The Journal of Clinical Investigation showed that these genetic variants when in recipients increase the rate of kidney rejection and lower transplant kidney life. The study is also featured in “Nature Reviews Nephrology” as a research highlight, and was the focus of a commentary in the American Journal of Kidney Diseases: “Compared to other populations, individuals with recent African ancestry have markedly higher incidence rates of end-stage kidney disease (ESKD) and faster progression of chronic kidney disease (CKD). Transplanted kidneys from deceased donors with recent African ancestry fail more rapidly…”

Read the study in The Journal of Clinical Investigation as well as an accompanying commentary. The paper was also named editor's pick in the JCI for December 2021.

Zhang Z, Sun Z, Fu J, Lin Q, Banu K, Chauhan K, Planoutene M, Wei C, Salem F, Yi Z, Liu R, Cravedi P, Cheng H, Hao K, O'Connell PJ, Ishibe S, Zhang W, Coca SG, Gibson IW, Colvin RB, He JC, Heeger PS, Murphy B, Menon MC. Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes. J Clin Invest. 2021 Nov 15;131(22):e146643. doi: 10.1172/JCI146643. PMID: 34499625; PMCID: PMC8592534.

Pulmonary, Critical Care & Sleep Medicine

Speaking invitations often lead to national and international recognition, collaborations, and academic promotion. However, women persistently remain underrepresented as invited speakers at conferences, including at the Society of Anesthesia and Sleep Medicine (SASM). The authors of a correspondence in the Journal of Clinical Anesthesia identified 183 speaker slots and 63 moderator slots at the SASM annual meeting between 2011 and 2020. Of the total number of speakers, 57 (31.2%) were women while 13 (20.6%) of moderators were women. “Reasons behind these disparities need to be rigorously investigated in order to effect transformative social change on a structural level as well as an interpersonal and personal level,” the authors said. Read more: https://pubmed.ncbi.nlm.nih.gov/34464769/

Lorello GR, Haider T, Rahman N, Won C, Ramachandran SK, Huszti E, Singh M. Amplifying women's voices and representation of women speakers and moderators at the Society of Anesthesia and Sleep Medicine: A retrospective analysis, 2011-2020. Journal Of Clinical Anesthesia 2021, 75: 110494. doi: 10.1016/j.jclinane.2021.110494. PMID: 34464769.

Rheumatology, Allergy & Immunology

Excessive inflammation drives the clinical progression from bacterial sepsis to lethal septic shock. A research article in The Journal of Clinical Investigation report on the inflammatory mediator macrophage migration inhibitory factor (MIF) is of interest because MIF genetic polymorphisms predict mortality in different infections, and anti-MIF therapies improve survival in experimental models when administered even many hours after then onset of infection. The recent discovery of a second MIF family member, called MIF-2, prompted closer investigation of MIF’s role in sepsis as anti-MIF directed therapies could be limited by the simultaneous action of MIF-2. In this study, the authors found that MIF-2 differed critically from MIF in not being able to recruit a lethal inflammatory macrophage population into sites of sepsis inflammation. This distinction was due to the absence of a small structural region in MIF-2 required for the activation of signals necessary for macrophage recruitment into sites of infection. This study is the first to reveal critical distinctions between MIF and MIF-2 that now may guide precision MIF-directed therapies, particularly in subjects who are high genotypic MIF expressers.

Tilstam PV, Schulte W, Holowka T, Kim BS, Nouws J, Sauler M, Piecychna M, Pantouris G, Lolis E, Leng L, Bernhagen J, Fingerle-Rowson G, Bucala R. MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model. The Journal Of Clinical Investigation 2021, 131(23) doi: 10.1172/JCI127171. PMID: 34850744. PMCID: PMC8631602.

Submitted by Julie Parry on January 11, 2022