Year 4. February 24.
[Intro: This week’s edition features the inspiring work of our research faculty who have published in high-impact journals or recently made a mark in academic medicine. We also continue our celebration of Black History Month by highlighting Jasmine Marcelin, MD and Renee Williams, MD, Black physicians who recently shared their research at Grand Rounds.]
Science Monday
Our research faculty have been busy making groundbreaking discoveries and challenging assumptions to move medicine forward. For the first “Science Monday” of 2025, I would like to highlight a handful of recent standout publications that demonstrate our scholastic excellence.
Li Lab Cinnamon Study Makes Top 10 ASN Articles of 2024
First up is research led by Zhaoping Li, MD, PhD, professor of medicine and chief of the division of clinical nutrition. Dr. Li’s March 2024 publication in the American Journal of Clinical Nutrition on the anti-glycemic properties of cinnamon made the top 10 most popular articles within the journals of the American Society of Nutrition. They were ranked according to their Altmetric scores, a value that measures how much attention an article receives on social media, in news outlets, in policy documents and more.
“Cinnamon has been used in every ancient medicine, including Indian and Chinese medicine, and has been regarded as capable of regulating blood glucose across thousands of years of using this special tree bark,” Dr. Li explained. “Because of the prevalence of diabetes, particularly type 2 diabetes, is so high, there has been major public interest on whether this spice actually has this beneficial effect.”
Scientists for years have attempted to demonstrate that cinnamon can lower blood sugar, but results have been inconsistent. In this case, Dr. Li’s team recruited participants with prediabetes and used continuous glucose monitors to track their blood sugar levels; one group was assigned to season some foods with a standardized amount of cinnamon, while the other ate normally. The researchers found that while there was no statistically significant difference between individuals’ absolute glucose values, the glucose area under the curve — a measurement that represents average glucose levels over time — was lower for participants who seasoned their food with cinnamon.
“The single most important thing was that we focused on continuous glucose levels. It’s not taken at just one time point,” Dr. Li explained. “We really considered variation.”
Eighteen participants were involved in the study, which took place across four weeks. Future experiments will include more subjects larger as well as a segment that allows the team to assess whether people replace sugar with cinnamon in their diets.
“We want to see if the cinnamon not only has its own benefit, but also has the added benefit of reducing sugar intake,” Dr. Li said.
Please join me on congratulating Dr. Li on her team’s recognition and outstanding work! I look forward to seeing the results of the studies that spring from these results.
Amy Vandiver, MD, PhD, Identifies Aging-Linked Mutations in Mitochondrial DNA
Mitochondrial DNA is an important yet still-mysterious contributor to the aging process. Thanks to the work of Amy Vandiver, MD, PhD, a dermatologist and STAR program alumni, we are one step closer to understanding how mutations in the mitochondrial genome influence skin aging.
In a study published Dec. 16 in Aging Cell, Dr. Vandiver and her team in the lab of Michael Teitell, MD, PhD developed an induced pluripotent stem cell (iPSC) model to demonstrate that a phenomenon called heteroplasmy — genetic variation within a population of mitochondria in a cell — increases over time, with some genes taking on mutations that delete them entirely. Additionally, the team also found that the mutations were associated with age-related phenotypes and metabolic changes.
“There’s been kind of a longstanding question in the aging field as to if accumulating these large mitochondria deletion mutations like we study in the paper are just there or if they directly cause the problems we see in old cells,” Dr. Vandiver said. “This paper is our initial observations on this in a new system we developed.”
One of the challenges with mitochondrial DNA is that it cannot be edited with techniques like CRISPR the way that nuclear DNA can. To get around this, Dr. Vandiver’s team built off earlier evidence suggesting that reprogramming skin cells called fibroblasts to make iPSCs naturally led to heteroplasmy. They had expected to see random mutations but instead observed some a clear pattern.
“Essentially, the mitochondrial DNA either got rid of the mutation or accumulated it at a very high level,” Dr. Vandiver explained. Cells containing the mitochondrial DNA that didn’t clear the mutations showed altered growth dynamics and morphology.
“Typically, stem cells are all about division, not a lot of growth — they’re one of the most rapidly-dividing cell types there are, so they don’t have a lot of time to sit and grow big before they divide,” Dr. Vandiver said. “But in our cells with high levels of deletion, we saw a shift of that, where they were dividing much more slowly and spending more time accumulating mass.” This persisted even after the team differentiated the cells into other types, a finding that Dr. Vandiver described as “striking.”
“We were able to replicate a little bit of the growth pattern we see in aging stem cells just by altering the level of mitochondrial genome mutations,” she said. They also had metabolic changes that mirrored those seen in aging cells.
“It was exciting to us to see that,” Dr. Vandiver said.
Ultimately, while she cannot say definitively whether the genomic changes seen in the models are the cause of age-related skin diseases, Dr. Vandiver views these findings as a crucial first step to developing therapies that could potentially treat or prevent them. By understanding what and how these genomic and metabolic changes arise, it will be possible to come up with interventions that target them.
“We know that these mutations are there at high levels in older skin. By seeing that in the cell model those changes directly cause metabolic and growth changes, that gives us more impetus to try to use them as targets for intervention in aging skin and tissue,” she said. “This study gave us a lot of insight into the metabolic changes that are downstream of having high levels of bad mitochondrial DNA.”
Great work to Dr. Vandiver and all of her team!
Race and Gender Influence Spending on IBS Care, Study Led by Andrea Shin, MD, MSCR Finds
It’s well-known that people with irritable bowel syndrome (IBS) have greater healthcare spending than those who do not. However, until recently, it was unclear whether factors like race and gender influence spending amounts, or whether IBS patients from certain demographics have different experiences with the healthcare system. To tease out the answers to these questions, UCLA gastroenterologist Andrea Shin, MD, MSCR led a wide-ranging study involving data from more than 95,300 adults with IBS. An article about their findings was published Dec. 9 in Clinical Gastroenterology and Hepatology.
“We do know that IBS tends to be more prevalent in women, so we wanted to see if that also extends into healthcare utilization,” Dr. Shin said. “There’s little work on examining racial disparities in IBS. So that was another reason that we wanted to perform this study.”
Some trends the researchers observed included lower spending among Asian and Hispanic patients compared to white patients, and that certain costs — such as emergency room visits and prescriptions — were greater for Black patients. However, the results around interactions between different demographic factors were quite complicated, with no consistent patterns. However, it was clear that there are differences in spending between races and genders as well as interactions between them. For example, the impact of gender on spending differed by race; different spending patterns were observed for Asian men compared to Black women, for instance.
“This made us realize how these factors are actually not independent, and they do interact with each other in terms of how people are experiencing the healthcare system and how that impacts your spending,” Dr. Shin said.
The researchers also observed that overall healthcare spending — not IBS-specific spending — was greater for women than for men. More research will be required to understand why women with IBS spend more on healthcare overall. However, it could be that they have additional comorbidities that coexist with IBS, which translates into additional healthcare spending.
The results point to different avenues for research, such as exploring why some treatments, like endoscopies, might be costlier for men than for women even as healthcare spending overall was higher. The high cost of emergency department visits among some demographics will be fertile ground to explore as well.
“The next question to answer is why these differences are occurring,” Dr. Shin said. “Why is spending on care different between these different groups?”
Please join me in congratulating Dr. Shin and her team on this important study!
Joanna Schaenman, MD, PhD Characterizes Immune Response to COVID-19 in Organ Transplant Patients
COVID-19 is particularly dangerous for solid organ transplant (SOT) recipients, who must take lifelong, powerful immune-suppressive drugs to prevent their bodies from rejecting the transplanted organ. Joanna Schaenman, MD, PhD, an infectious diseases physician at UCLA, and a team of researchers from UCLA, the University of Texas at Austin, UCSF, Emory School of Medicine and more recently published a study that illuminates major differences in how the immune response of SOT patients differs from that of non-SOT patients with COVID-19, with implications for treatment.
“This data underlines the importance of vaccination of patients and their close contacts to try to bolster immune response and prevent infection transmission,” Schaenman said. “It also suggests that we may need to reconsider the standard approach to immunologic therapies for SOT patients with both mild and severe COVID-19 disease.”
The researchers analyzed a cross-section of data from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, a multicenter, systems immunology-based study on 1,100 hospitalized patients with COVID-19. They identified 86 SOT patients and matched them 2 to 1 with non-SOT patients from the same dataset according to age, sex and location.
The researchers found that SOT patients had higher and more persistent viral loads of SARS-CoV-2, the virus that causes COVID-19, in their nasal passages than non-SOT patients. As expected, they also found that the patients exhibited signs of an impaired immune response, such as increased levels of senescent T cells and a decreased presence of plasmablasts, transitional B cells and antibodies to SARS-CoV-2. However, they were surprised to find that SOT patients with mild disease responded more robustly to COVID-19 than non-SOT patients, though SOT patients with severe diseases had much lower responses compared with non-transplant controls.
These results present some major implications for treatment approaches. Some of you may recall that in the early days of COVID-19, clinicians observed that severe COVID-19 was accompanied by a “cytokine storm”. The standard treatment was to give these patients steroids and Janus kinase inhibitors. However, the findings by Dr. Schaenman and her team suggest a need for additional studies on immune-modulating treatments in transplant recipients.
Given the early observations that severe COVID-19 was accompanied by a ‘cytokine storm’ immune response in previously healthy individuals, standard treatments for hospitalized adults with severe COVID-19 target the immune system with steroids and Janus kinase inhibitors. The finding that immune response in SOT patients differs significantly from normal hosts calls this routine practice into question and suggests that additional studies for immune modulation-related therapies in transplant recipients should be performed to identify best treatment practices.
Dr. Schaeman noted that although the study applies to all SOT patients, it is most relevant for those who have had lung transplants. Furthermore, it has implications for future pandemics, as COVID-19 offered a unique opportunity to see how the immune responds to a pathogen it has never encountered before. Additionally, the study “also underlines the fact that as most initial therapy and vaccination studies exclude immunocompromised patients, this patient population would benefit from directed studies to identify optimal therapies,” she said.
Thank you to Dr. Schaeman and the rest of the team for their exceptional work!
For Open Heart Surgery, Referral Networks May Keep Black Patients Out of Top Hospitals, Study Led by Ioana Popescu, MD, MPH Finds
Despite living in areas with access to a wider selection of hospitals, on average, than white patients, Black patients are less likely to undergo elective coronary artery bypass grafting (CABG) surgery at top-quality hospitals — a possible consequence of subpar referral networks, a recent study led by Associate Professor of Medicine and internist Ioana Popescu, MD, MPH shows. The research was published Dec. 27 in Circulation: Cardiovascular Quality and Outcomes.
“The mind finding was that there are clear and significant effects of referral networks,” Dr. Popescu said. “This is the first time that somebody has quantified the effect of a referral network on admission to a high-quality hospital and shown that it varies by race.”
Dr. Popescu’s research is part of a larger initiative by the NIH to figure out how physician referral networks influence differences in outcomes for Black and white patients with coronary heart disease. An earlier study by Dr. Popescu and her team showed that proximity to high-quality hospitals was less influential than non-geographic factors in determining whether a Black patient’s CABG took place at a hospital with low mortality rates. Given that additional studies from other teams have demonstrated that primary care physicians treating Black and white patients have different access to hospitals and specialty services—and that cardiac care specialists who care for patients from communities of color are often isolated within their networks—it seemed that physician referral networks for CABG might contribute to the mortality difference between the two populations.
To find out, Dr. Popescu and her team analyzed anonymized data on 76,376 Black and white Medicare patients who underwent elective CABG procedures between 2017 and 2019. The researchers’ statistical framework was predicated on hospital choice models, which assume that patients and their physicians select one hospital over another based on location and hospital characteristics. They ranked the relative quality of the hospitals in their assessment according to Medicare-published 30-day CABG mortality data and measured the strength of ties between primary care physicians and hospitals by how many CABG patients they shared in the 12 months prior to a subject’s surgery.
Their results suggested that, on average, Black and white CABG patients are treated at hospitals with similar levels of mortality — an encouraging finding that differs from past research, the study authors noted. However, Black patients used low-mortality hospitals less often than white patients despite living closer to them. The researchers’ analysis found that this was partly explained by differences in physician-hospital referral networks.
In other words, “geography was more favorable to Black patients, but referral networks were more favorable to white patients,” Dr. Popescu said. “Black patients are in better geographical proximity to high-quality hospitals, but having a good hospital near you doesn’t necessarily mean you can have your open heart surgery there.”
Dr. Popescu stressed that the results do not indicate outright bias on the part of the PCPs who are referring patients. She and her team previously conducted qualitative research during which they spoke with physicians about how they make referral decisions and found that they consider language preference, care concordance, socioeconomic status and many other factors when deciding where to refer a patient.
“Decisions are very complicated, and all we observe is the end result,” she said. “I think these studies are an interesting starting point to begin to understand referrals. They are a central part of healthcare.”
Thank you to Dr. Popescu and her team for all their great work on this important topic!
Jasmine Marcelin, MD and Renee Williams, MD, MHPE Share Expertise on Pharmacoequity and Colorectal Cancer Screening at Grand Rounds
In continuation of our celebration of Black History Month, I would like to highlight two recent Grand Rounds presentations on issues that pertain to equity and inclusion in medicine.
The first was given Feb. 13 by Jasmine Marcelin, MD, vice chair for belonging and community engagement in the department of internal medicine at the University of Nebraska Medical Center. Her talk focused on disparities in antimicrobial prescribing between white patients and patients from communities of color, sharing data that showed how Hispanic and Black patients had higher rates of hospital-acquired infections than white patients, as well as greater rates of infections that are resistant to antibiotics. Additionally, she shared evidence that efforts to curb antibiotic use were disproportionately leading to Black and rural patients not getting the medicines they need to treat their infections.
She noted that these findings had nothing to do with any individual’s race or ethnicity but instead were a manifestation of structural racism. As a solution, she proposed ways to use pharmacoequity (a term coined by UCLA physician-scientist Utibe Essian, MD, MPH) to solve these challenges. Some ideas included reminding patients of their role in decision making around antibiotic prescribing, improving representation of patients from rural areas and communities of color in clinical trials, and advocating on behalf of underserved populations to elected officials.
The second talk was given by gastroenterologist Renee Williams, MD, MHPE, associate chair for health equity within the department of medicine at NYU Langone. Dr. Williams presented an update on non-invasive colorectal cancer (CRC) screening techniques, an essential topic in light of increasing rates of early-onset CRC among young people and high rates of mortality from the disease among Black men and Native American women. She reviewed the various non-invasive techniques used to screen for CRC, including new blood-based tests that are coming to market, and offered suggestions for reoffering tests to patients who had previously declined colonoscopies.
Thank you to Dr. Marcelin and Dr. Williams for their excellent talks!
Dale
P.S.
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