1. < Message from the Chair

For many of us, summer time is the opportunity to sit down with a good book, while taking time off with family. I have not taken any personal time off as yet this summer, but I do see amazing reading opportunities each week, as colleagues in the UCLA Department of Medicine (DoM), are not slowing down in publishing influential papers in major journals. Some of these publications represent primary research and others represent perspectives and definitive position papers. I picked five publications to highlight this week, recognizing that these represent a mere fraction of the prolific body of work that our faculty publish each week. I encourage you to see the full list at DoM Connect.

Jason Hong, MD, PhD: “Charting the Cellular Landscape of Pulmonary Arterial Hypertension Through Single-Cell Omics” in Respiratory Research

Past traditional studies have not captured the complexity of PAH. However scRNAseq is providing a new perspective which details the cellular diversity within PAH. In this review, Hong discusses recent findings that identified unique cell subsets, gene networks, and molecular pathways driving PAH, and considers future research directions which can inform the development of new therapies.

Jason continues to build on this review with his most recent study, which he discussed in his DoM Grand Rounds lecture on August 8^th, which further advances our understanding of the mechanisms underlying PAH. In this study, Dr. Hong used integrative multiomics approaches on a large biobank of lung tissues and discovered that the protein asporin, which is encoded by the ASPN gene, has a protective role in PAH. Increasing asporin in the lungs and plasma of PAH patients correlates with reduced disease severity. Asporin does so by inhibiting the proliferation of pulmonary artery smooth muscle cells and TGF- β which are key factors in PAH progression. These new findings give us hope for developing new therapeutics in the future. With continued research, targeting asporin could lead to new therapies that may reduce the severity of PAH and improve the lives of those affected by this challenging condition. Keep an eye out for this study in an upcoming edition of Circulation.

Mina Ma, MD: “Factors Influencing Primary Care Career Choice: A Multi-Institutional Cross-sectional Survey of Internal Medicine Primary Care Residency Graduates” in Journal of General Internal Medicine

Across the country, there is growing concern of a shortage of primary care physicians. In order to ensure a robust and accessible healthcare system that can effectively serve the needs of our diverse communities, it is essential to understand how best to recruit skilled physicians to the primary care track.

These insights provide a better understanding of the factors that influence a resident’s decision to pursue a career in primary care. By addressing factors such as administrative burden and burnout, the appeal of a career in primary care may be enhanced, leading to greater retention of talented physicians, which is critical for addressing the shortage of primary care doctors. Expanding the pool of primary care physicians can potentially enhance overall health care access and improve health outcomes for patients within our health system and across the country. Thanks Mina for this study and for your leadership of our primary care training programs at UCLA.

Raphael Landovitz, MD: “Features of HIV Infection in the Context of Long-Acting Cabotegravir Preexposure Prophylaxis” in New England Journal of Medicine

Last month, Landovitz published a follow-up study in the New England Journal of Medicine, introducing us to long acting early viral inhibition (LEVI), which examines the novel biology seen in rare cases where injectable HIV prevention medication fails. Unlike the typical acute symptoms and rapid viral replication seen in HIV infection, LEVI’s viral replication is slow, and the infection is silent resulting in delayed biological responses that include fluctuating viral loads, often right at the lower limits of quantification, and delayed antibody production. These effects result in antibody tests that can fluctuate between positive and negative, delaying a diagnosis and treatment – sometimes over a period of years.

These findings have important implications for physicians. As long-acting injectable HIV medications for HIV prevention become more prevalent, recognizing and diagnosing rare cases of breakthrough infections and medication failure will be critical. Long-acting injectable PrEP is a superior treatment for HIV prevention, however the testing algorithms monitoring for PrEP failure are different for these medications and physicians should seek expert consultation when they receive confusing or discordant HIV test results if a patient is using a long-acting injectable.

Eric Yang, MD: “Cardiovascular Toxicities of Immune Therapies for Cancer – A Scientific Statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology” in European Journal of Heart Failure

Immune therapies, such as checkpoint inhibitors (ICIs) and chimeric antigen T cell (CAR-T) therapy, have made major advancements in how we treat cancer. While these therapies harness and reprogram the immune system to fight cancer cells, they have complex cardiovascular risks. The scientific statement provides valuable insight into various toxicities affecting the cardiovascular system such as ICI-related myocarditis, subclinical heart failure, acute coronary syndrome, and arrythmias associated with CAR-T therapy. Some of these disease processes can be difficult to detect and this scientific statement provides detailed strategies for diagnosis and treatment. The statement elaborates that for patients who recently initiated ICI treatment and presenting with cardiovascular complaints in clinic or in the hospital, myocarditis should be suspected with immediate multidisciplinary involvement with cardio-oncology related specialists. Steroids and immunomodulator therapies should be started as soon as possible. CAR-T can be associated with cytokine release syndrome and associated cardiovascular toxicities including arrhythmias, elevated cardiac biomarkers and cardiac dysfunction which can be associated with worse outcomes.

Currently, nearly half of cancer patients qualify for immune checkpoint therapy. With improved cancer survivorship, we may see more patients experiencing immediate and long-term cardiovascular effects from these therapies. It is critical for cardiovascular specialists to monitor and manage a cancer patient’s heart health to address risks such as myocarditis, increases in atherosclerosis, or other cardiovascular events. This scientific statement guides clinicians in addressing the complex challenges associated with these groundbreaking treatments.

Carolyn Crandall, MD: “Annals On Call - ACP Recommendation: Pharmacologic Treatment of Type 2 Diabetes” in Annals of Internal Medicine

According to the updated recommendations, when metformin and lifestyle modifications alone are not sufficient for managing type 2 diabetes, it is advised to add either a sodium-glucose cotransporter 2 (SGLT-2) inhibitor or a glucagon-like peptide-1 (GLP-1) agonist. Both medications have been shown to significantly reduce the risk of death in a population with inadequate glycemic control and increased risk for cardiovascular disease. Of note, SGLT-2i’s significantly reduce the risks for all-cause mortality, major cardiovascular events, stroke, progressive chronic kidney disease, and hospitalization for heart failure. GLP1RAs reduce major cardiovascular events, improve symptoms in patients with heart failure and induce durable weight loss. The new guidelines strongly advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors in patients at high risk for cardiovascular disease, as they do not reduce critical health risks such as heart attack, stroke, or chronic kidney disease.

As patients navigate the complex assortment of diabetes medication options, these guidelines provide evidence-based information for patients and clinicians to consider when selecting which treatment may help mitigate the risk for serious health conditions and/or death. As our focus shifts from solely managing blood sugar levels, patients can partner with clinicians to make better informed decisions about their diabetes management, ultimately enhancing their health outcomes.

I trust that you are as impressed as I am with the influence and leadership, that our faculty play in advancing diverse areas of medicine.

Dale

P.S.

My mother spent the last three weeks with us and is now visiting my brother in Seattle. She loves to walk and has made many friends in the neighborhood. On weekends, she walked along my running route, with me running ahead and returning to meet her. This is her at the 2.8-mile marker on our walk last weekend.

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