1. < Message from the Chair

DoM Scholarship Shines on Research Day

As I told the more than 300 faculty, post-docs, trainees and medical students who took part in the UCLA Department of Medicine (DoM) Research Day on Oct. 9, research represents the life blood of the department. The exceptional collection of posters and presentations shared during DoM Research Day support the conclusion that our department's research mission is healthy and strong.

I was delighted to see broad-based progress arising from every corner of our department. We are tackling big, complex questions here at UCLA, in the DoM in particular. The scholarship at every level — from undergraduates working in the DoM to our faculty LEADERS — is exceptional. The poster winners will be announced soon, and I am very grateful to our DoM Research Day judges who undertook the tough task of evaluating them. They had tough choices to make with nearly 400 abstracts showcasing the depth of innovation in our department!

Speaking of science communication, DoM Research Day attendees received a master class in talking about research in the form of the presentations from our plenary speakers. These faculty members are helping the DoM lead in innovation, and we are grateful for their many contributions to our success and the future of medicine. Read on to learn about some of their work!

Plant-Based Diets for CKD Patients

Chronic kidney disease (CKD) affects over 35 million people in the US. Each year around 125,000 individuals transition to end-stage kidney disease (ESKD), with the majority requiring dialysis. To prevent at-risk patients from developing CKD — or to keep existing CKD from worsening — the evidence is mounting that lifestyle medicine and choice of foods really, really matter.

Additional studies by Dr. Narasaki added even more nuance. She also found that higher dietary potassium and fiber, which are typically found in plant-based foods, are associated with greater survival in non-dialysis CKD patients, and that lower dietary potassium intake was associated with a higher risk of death in CKD patients who are on dialysis. While there are a variety of plant-based diets consumed in the non-CKD population, it is important to note that not all are low in protein, which is needed to reduce kidney disease progression.

These studies helped inform the development of what Dr. Rhee calls the “Plant-Dominant Low Protein Diet,” or PLADO diet, for CKD patients who aren’t on dialysis. The diet is comprised of 0.6 to 0.8 g/kg per day of protein, more than half of which comes from plant-based sources. It’s low in sodium, high in fiber and provides adequate calories for patients. Dr. Rhee also noted that multi-disciplinary collaboration is key to ensuring that nutritional recommendations can be translated into a diet that is practical, feasible, and palatable for CKD patients.

“It is heart-breaking when our patients lament, ‘There is nothing left to eat!” Dr. Rhee said. “Hence, it is critical that we partner with specialty-trained kidney dietitians to effectively and safely implement plant-based low-protein diets in non-dialysis CKD patients.” She noted that patients with non-dialysis CKD who have Medicare are covered for up to four consultations per year with a kidney dietitian.

Some questions about the best diet for CKD patients remain, especially with regards the many patients who have both diabetes and CKD. Dr. Rhee is working on addressing them as the co-principal investigator of an NIH R01 multi-center randomized controlled trial called the “Plant-Focused Nutrition in Patients with Diabetes and CKD”, or PLAFOND, study, which she is running alongside her co-principal investigator, Dr. Kamyar Kalantar-Zadeh, MD, MPH, PhD, who is a UCLA Professor of Medicine and Public Health and Harbor-UCLA chief of nephrology.

“We believe that these data will be critical for informing major knowledge gaps regarding dietary interventions in non-dialysis CKD patients with diabetes,” she said. She and Dr. Kalantar-Zadeh are also studying the mechanisms that could explain why plant-based, low-protein diets are linked with a lower incidence of CKD and progression, as well as fewer complications of kidney disease.

Ultimately, patients and their care partners are the motivation for Dr. Rhee’s research. Patients play an important role in the design of these studies, acting as the “critical experts” who inform the research questions, hypotheses and practical implementation of the investigations she carries out, she said.

“While there are a number of exciting pharmacotherapies that are being used to treat cardio-kidney-metabolic disease, at the foundation of a healthy lifestyle is optimal nutrition,” Dr. Rhee said. “We truly hope that the work we are pursuing in kidney nutrition will improve the health, survival, and well-being of the CKD community.”

Real-World Prevention Strategies for Type 2 Diabetes

Tannaz Moin, MD, MBA, MSHS and Kenrik Duru, MD, MS arrived at Research Day fresh off of a Centers for Disease Control and Prevention (CDC) meeting. Their plenary presentation focused on enhancing research translation for type 2 diabetes prevention, including the application of strategies that have been successful in randomized clinical trials (RCTs) to real-world clinical settings.

“RCTs test interventions or treatments under ideal conditions, often with dedicated resources and standardized approaches that are difficult to replicate in real world settings,” Dr. Moin said. “The real world is complex and messy, so translating the evidence from a RCT to real world practice requires adaptability and numerous iterations to address the needs of specific settings and populations.”

For instance, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-sponsored Diabetes Prevention Program (DPP) provided one-on-one lifestyle coaching to prediabetic patients for three years. The DPP was effective at helping patients lose weight and avoid developing diabetes — and has since been expanded into a wider program offered to Medicare beneficiaries in some states, including California — but research by led Dr. Duru and Dr. Moin suggests that it comes with logistical and financial pitfalls that should be ameliorated by restructuring and adjusting the reimbursement system for providers and suppliers. 

Dr. Duru, Dr. Moin and their multi-disciplinary research team have identified more practical strategies for diabetes prevention. One example is shared decision making (SDM), a clinical philosophy that gives patients a say in their clinical care — in other words, “no decision about me, without me.” Clinical trials at UCLA, such as the PRIDE trial, have found that SDM care delivery increases participation in diabetes prevention programs and is effective at helping patients sustainably lose weight for up to three years. 

Another approach that seems effective is electronic health records (EHR)-based risk estimation models that allow care providers, including pharmacists and nurses to initiate conversations with patients about their likelihood of developing diabetes. In a study funded by PCORI and run in conjunction with Intermountain Healthcare, the researchers demonstrated that SDM for type 2 diabetes prevention that included an EHR-based risk prediction model stratifying patient risk levels of diabetes was associated with greater participation in diabetes prevention initiatives. 

Dr. Moin and Dr. Duru are currently joint principal investigators on a CDC-funded multi-center network aiming to examine the real-world effectiveness and cost-effectiveness of DPP in real world settings which will include data on the thousands of adults at risk for diabetes across the U.S. The goal is to figure out whether the benefits observed in RCTs bear out in the real world. They are also continuing to co-lead their NIDDK-funded Gestational diabetes Risk Attenuation for New Diabetes (GRAND) study, which looks at the effectiveness of a tailored diabetes prevention SDM for women with a history of gestational diabetes, prediabetes and overweight/obesity at UCLA and Intermountain Healthcare. Additionally, they’re working closely with the University of California Office of the President to implement best practices for translating type 2 diabetes prevention strategies across all 10 campuses in the UC system.

“There’s a lot of work to be done, particularly for high-risk groups such as Medi-Cal patients,” Dr. Duru said. “We have had some important success in enhancing research translation for type 2 diabetes prevention with over 9 years of collaborative studies in this space, but there is still a long road ahead.”

Targeting Solid Tumors with T Cells

Adoptive T cell therapies like chimeric antigen receptor T cell (CAR-T) therapy have revolutionized outcomes for blood cancers, dramatically improving the survival rates for even some of the deadliest forms. But researchers have struggled to get these therapies to work in solid tumors on account of the hostile environment that surrounds them.

“We believe that this approach can overcome barriers related to delivering the T cells to the tumor and reduce the possibility of toxicities in other parts of the body,” he said.

Dr. Lee and collaborators from Fred Hutch Cancer Center are launching a first-in-human clinical trial of a CAR-T therapy that targets the protein STEAP1 in late-stage prostate cancer, with their first patient enrollment slated for this month. His team is also working on launching a trial of a CAR-T therapy with the same target against relapsed or refractory pediatric and adult bone cancer Ewing’s sarcoma. Additionally, they have filed an Investigational New Drug application with the FDA to see if a CAR-T therapy aimed at the protein L1CAM is effective against a highly aggressive, lethal subtype of prostate cancer.

Moving forward, Dr. Lee’s team will use what they learn from their work in the laboratory and clinical trials to learn more about resistance to adoptive T cell therapies in solid tumors and to make them safer and more effective.

A Humanized Monoclonal Antibody that Enhances Tissue Repair

Thank you!

The 2024 DoM Research Day was a tremendous success, and I would like to recognize and thank the faculty leaders and administrative staff who made this day possible. Their LEADERShip and vision created an afternoon filled with curiosity, inspiration, and future collaboration which take us one step closer to achieving our goals to lead in innovation, transform care, and advance health for all.

View Video Highlights

Research Day 2024 Overview, Featuring Basic Research:
An overview of the UCLA Department of Medicine Research Day 2024, featuring a basic research presentation from Lingyun (Ivy) Xiong, PhD.

Clinical Translational Research:
A brief look at the wonderful clinical translational research from Adrian Castillo, MD, Charlotte Jeong, and Karissa Britton, MD and why they enjoy research at UCLA DoM.

Health Services Research:
We talk to Xinjiang Chi, MD, PhD, Katherine Chen, MD, PhD, and Rebecca Tsevat, MD about their health services research and what it's like to conduct their research at UCLA DoM.

Yusuke Tsugawa, MD, PhD Finds Insurance Coverage Benefits Physical Health

In keeping with our research theme, I now highlight recent work by Yusuke Tsugawa, MD, PhD, whose study on the impact of insurance coverage on physical health was published Sept. 23 in the BMJ. Health care policymakers have debated for years whether insurance coverage can improve physical health. While there is still more work to be done to answer this critical question, Dr. Tsugawa’s new findings brings us much closer — and demonstrate the power of a new approach to data analysis that stands to improve the way we conduct biomedical and health policy research.

In his new BMJ publication, Dr. Tsugawa and collaborators from Stanford and the University of Chicago used machine learning to comb through data collected as part of the 2008 Oregon Health Insurance Experiment (OHIE), one of the landmark randomized controlled trials on the effect of Medicaid expansion on health care use, outcomes and well-being among those with low-income. While the original analysis of the OHIE data found that health insurance coverage improved subjects’ mental health, it did not find an impact on markers of physical health, like blood pressure and blood glucose levels.

“The causal forest model allows us to look at that in terms of more complicated interaction between variables, and that gives us a full picture of whether the heterogeneity exists, and if so, where it is coming from,” Dr. Tsugawa explained.

In the case of health insurance, the researchers’ algorithm suggested that earlier interpretations of the data had indeed failed to capture some nuance in the results. Blood pressure improved in people who had little or no health care spending in the year before they were enrolled in Medicaid, while those who already had been spending money on health care did not see improvements. That suggests that obtaining health insurance coverage — and, therefore, improved access to medical services — benefits people who previously were skipping care because they were uninsured.

“I think what our study contributes is that we now know that health insurance coverage not only improves financial risk protection, access to care and mental health, but it also improves physical health,” Dr. Tsugawa said. “Given that the life expectancy or health outcomes of American people lag behind other high-income countries, I think providing universal health coverage is likely to lead to better health.”

The causal forest model’s benefits could extend beyond health policy research into randomized clinical trials for therapies, and even for precision medicine, Dr. Tsugawa noted. He and some members of the team behind the new research in the BMJ have already applied the algorithm to investigating treatment approaches for lowering blood pressure. The results of a study published last August suggested that it’s more effective to prescribe blood pressure medicine to patients who stand to benefit from it the most — regardless of their blood pressure levels — than it is to reserve it for those who have high blood pressure and are at high risk of adverse outcomes.

“This is really useful in terms of coming up with a more targeted approach that will lead to, in my view, improved effectiveness of the medical interventions,” Dr. Tsugawa said. “It can be some drug, or it can be health insurance, but in any case, we can find out who will benefit the most, and why.”

Dr. Tsugawa anticipates that the causal forest model will be applied to drug trials to help researchers avoid concluding the treatments to be ineffective only based on their average effects and ensure that they’re not missing any important therapeutic benefits within subgroups of the treatment population. He also thinks researchers should consider revisiting previously conducted randomized controlled clinical trials to see if applying the algorithm to their data yields different results.

“Those studies that found no impact of the intervention on the average treatment effect might be missing out on treatments that are actually beneficial for some subgroup of the study population,” Dr. Tsugawa said.

The importance of Dr. Tsugawa’s findings cannot be overstated, and I am proud that progress toward more equitable utilization of health care system resources is being championed right here in the DoM. I would also like to add that Dr. Tsugawa was recently appointed as a Fellow of the American College of Physicians. Please join me in congratulating him on this achievement!

Kevin Ikuta, MD Demonstrates Dangers of Antimicrobial Resistance

Another body of work that has harnessed worldwide media attention is new research from Kevin Ikuta, MD, MPH, an infectious disease physician and epidemiologist in the DoM who recently co-led an extremely important investigation on the future of antimicrobial resistance (AMR). AMR is the process by which bacteria, viruses, fungi and other organisms evolve to the point that fewer and fewer drugs are effective against them, meaning patients could die from infections that were previously curable.

In a paper published Sept. 28 in The Lancet, Dr. Ikuta and other scientists at the University of Washington and Oxford-based Global Research on Antimicrobial Resistance (GRAM) Project described how they found that direct deaths from AMR are likely to rise almost 70% by 2050, when it could kill as many as 2 million people in a single year. The team also found that more than 1 million people have died annually due to AMR between 1990 and 2021, with a notable shift in deaths from children younger than 5 to people older than 70 over that period.

Dr. Ikuta said his colleagues have described this phenomenon as two different “phenotypes” of how AMR can cause health loss. One type is the sort we’re familiar with here in the U.S. — the kind where microbes develop defenses to increasingly stronger drugs — while the second arises in places without the diagnostic capacity to even tell what bug is causing an infection.

“In that second phenotype, providers aren’t able to test for the optimal antibiotic, so they’re left making an educated guess on how best to treat their patients,” Dr. Ikuta explained. “And even when that diagnostic capacity exists and there may be a ton of options theoretically available to treat the infection, but what’s stocked in the pharmacy or just available to the patient is very limited.” As a result, patients are treated with antibiotics that don’t treat their illness but do give microbes the opportunity to develop new forms of resistance.

Tackling AMR thus requires different tactics depending on where in the world you’re trying to solve the problem. In countries where there is robust availability to many different types of antibiotics, the best solution is avoiding antibiotic use when it isn’t absolutely warranted. But in places like Sub-Saharan Africa, the right approach is building healthcare capacity and increasing access to antibiotics.

“We often think about antimicrobial stewardship as policing antibiotics and restricting use, but a good steward is making sure that the right antibiotics are available to the right patient,” Dr. Ikuta said. “That means increasing access in a lot of locations and restricting access in others.”

Dr. Ikuta noted that there are some limitations to the study, like a dearth of data in some regions that forced them to make informed assumptions about antibiotic use and infection prevalence. This is a common problem in global epidemiology, he noted. 

“Some locations just have very, very limited capacity for data collection, and the surveillance systems are often very siloed or nonexistent,” Dr. Ikuta said.

Limitations aside, there are universal truths that Dr. Ikuta wants clinicians to keep in mind. First, antibiotic stewardship programs like the one at UCLA are a vital part of the healthcare system, and the work they do is incredibly important. Second, prevention is an underappreciated strategy in mitigating AMR.

“We often talk about drug development as the way to solve or get us out of the AMR crisis, but we rarely see discussion about how preventing infections in the first place and improving healthcare quality can be as impactful, if not more impactful, than developing novel drugs,” Dr. Ikuta said.

Applications Open for Biodesign Innovation Program

Dale

P.S.

As I mentioned above, Research Day represented an opportunity to make serendipitous connections. Let me share one of my unexpected encounters. At the reception, I met Dr. Tarek Karan, currently a second-year nephrology fellow at UCLA. Tarek, who graduated from the Carver College of Medicine at the University of Iowa, reminded me how mortified he was when he had to present a case to me during Chairman's rounds at the University of Iowa some 6 years ago. I would not have recognized Tarek, who seemed so grown up and confident now!

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