Year 3. February 12. Changing the Research Landscape One Publication at a Time.

Last week, I shared a number of impressive department of medicine (DoM) awards and conferences awarded to or held by DoM faculty and trainees that served as an example of how much progress we are already making towards reaching our strategic goals. This week, I'd like to build off last week's message by highlighting a number of recent publications from the DoM.

Choosing just a few proved to be a significant task as we boast an impressive publication portfolio department-wide at an average of about 50 publications per week with a mean impact factor of 12.11. In 2023, department co-authored publications totaled about 2,528 across the entire year, with 1,462 publications in journals with an impact factor greater than or equal to 5. Research success isn't specific just to our faculty, however, as our trainees over just a 6-month period (July to December 2023) put out 158 publications, 47 of which had an impact factor greater than or equal to 5. 71 of those publications came from fellows, 62 from residents, 4 from post-docs, and 32 from DGSOM students!

I want to be careful to caveat these numbers: they are not absolute; rather, they are just an estimate captured through a search query script we developed to run on PubMed that draws publications according to that script daily. Given this caveat, it's possible, if not plausible, that the numbers are even higher than we've captured. With that preface, let me highlight six groundbreaking studies (among hundreds of groundbreaking studies from the past months), below.

Arpan Patel, MD, PhD and Anne Walling, MD, PhD, Found Palliative Care Consultations are Under-Implemented in Cases of Acute-on-Chronic Liver Failure

Rates, patterns, and predictors of specialty palliative care consultation among patients with acute-on-chronic liver failure, JHEP Reports

Arpan Patel, MD, PhD, assistant professor of medicine in the Division of Digestive Diseases at UCLA and a staff transplant hepatologist at the VA Greater Los Angeles Healthcare System, led a retrospective cohort study, entitled "Rates, patterns, and predictors of specialty palliative care consultation among patients with acute-on-chronic liver failure" recently published in JHEP Reports: Innovation in Hepatology. The study examined how often specialty palliative care teams are involved in the care of patients with acute-on-chronic liver failure. The authors, which included DoM's Anne Walling, MD, PhD, examined the involvement of palliative care teams in acute-on-chronic liver failure, a condition associated with multi-organ failure that affects nearly one-third of hospitalized patients with cirrhosis, and is associated with a 90-day mortality rate of over 50%.  

Using VA data, the study team found that despite specialty palliative care teams being recommended in the care of patients with this condition, less than a third of patients actually received this consultation. In addition, they found that patients who had more organ failures received later consultation than people who had fewer organ failures -- demonstrating a dangerous paradox. Dr. Patel shared that his team "believes that these findings should further provoke clinicians to consider models for integrating hepatology and palliative care teams across both outpatient and inpatient settings." They are already well on their way to implementing the guidelines supported by their results, by coordinating shared meetings between the national organizations in the hepatology and palliative care space. In doing so, and through future research, Dr. Patel and his team hope to improve our understanding of specific provider and system-level barriers that impede the delivery of palliative care. The team is also working to analyze data to show whether specialty palliative care consultation is associated with any differences in consideration for liver transplantation and end of life outcomes. Under the leadership of Dr. Patel, Dr. Walling, and other palliative care experts, UCLA DoM has established itself as thought leaders in research and policy development for palliative care nationally for this population. This study exemplifies how their continued leadership has leveraged a body of their scholarly publications (see Clinical Gastroenterology and HepatologyJAMA Internal Medicine, and these guidelines in Hepatology) that have similarly shaped the field. 

Study Authored by Holly Middlekauff, MD Finds Evidence of Similar Cardiac Risk in use of Nicotine-Based E-Cigarettes and Nicotine-Based Tobacco Cigarettes

Acute Cardiovascular Effects of 4th Generation Electronic Cigarettes and Combusted Cigarettes: Implications for Harm Reduction, Journal of Applied Physiology

Holly Middlekauff, MD, professor of medicine in the division of cardiology and professor of physiology, assistant dean for student affairs at the David Geffen School of Medicine at UCLA, has been focusing her recent research on the cardiovascular effects of tobacco products -- especially electronic cigarettes (e-cigarettes). In studying the effect of e-cigarettes on humans, she hopes to understand the full scope of the role of e-cigarettes in reducing harm for people addicted to nicotine who are unable to quit smoking. In her team's most recent publication, "Acute Cardiovascular Effects of 4th Generation Electronic Cigarettes and Combusted Cigarettes: Implications for Harm Reduction," published in the Journal of Applied Physiology, they further this understanding by examining whether acutely using an e-cigarette is less harmful than acute smoking a tobacco cigarette by measuring heart rate (HR), blood pressure (BP), and heart rate variability (HRV) at baseline and after use of an e-cigarette with or without nicotine, a tobacco cigarette with or without nicotine, and a straw-control. 

Their findings demonstrated that in both groups (tobacco cigarette users and e-cigarette users), all exposures that contained nicotine significantly increased the heart rate and blood pressure when compared to non-nicotine exposures. Further, in people who exclusively used electronic cigarettes, acute electronic cigarette use produced a similar, harmful pattern in heart rate variability (variation in heart rate measured on the electrocardiogram) associated with heightened cardiac risk. Dr. Middlekauff shared that in terms of implications, these results call into question the use of electronic cigarettes for harm reduction. However, she also cautioned that we must put these findings in the broader context of tobacco and e-cigarette research comparing other acute effects of these tobacco products, including inflammation, blood vessel function, and oxidative stress. 

These prior studies have found overwhelming evidence that electronic cigarettes were less harmful than that of tobacco cigarettes. However, "E-cigarettes are not harmless," Dr. Middlekauff explains. "As such, if being used for harm reduction, e-cigarettes should be used for the shortest period of time in order to ensure smoking cessation, and then stopped." She is hoping that this research will be used to target smoking cessation in communities where traditional smoking cessation practices have fallen short, such as people living with HIV. Her team also hopes to apply these methodologies to other exposures on cardiac risk, such as marijuana use, which has increased among younger generations.

Orian Shirihai, MD, PhD, and team Present a Novel Method for Isolating Fat Droplets Associated with Mitochondria and Describes their Characteristics

“Mitochondria isolated from lipid droplets of white adipose tissue reveal functional differences based on lipid droplet size,” Life Science Alliance

Orian Shirihai, MD, PhD, recently helped lead an investigation that found mitochondria that build lipid droplets have different structure and function than other mitochondria. The finding led them to coin a new term for these types of mitochondria, known as "peri-droplet mitochondria," and set them on a path to studying how to better isolate peri-droplet mitochondria to better understand their characteristics. These efforts led to the publication of Dr. Shirihai and team's most recent study "Mitochondria isolated from lipid droplets of white adipose tissue reveal functional differences based on lipid droplet size," published in Life Science Alliance, which offers a newly developed method of isolating peri-droplet mitochondria by shaving the mitochondria from the lipid droplet while preserving its respiratory function.

In addition to offering a method of isolating such mitochondria, the study yielded several novel findings about peri-droplet mitochondria; one finding is that peri-droplet mitochondria from white adipose tissue (WAT) have different characteristics than those from brown adipose tissue (BAT). A second finding is that mitochondria that adhere to smaller lipid droplets have their own characteristics that likely serve different functions for small and large lipid droplets. Dr. Shirihai hopes that this study serves as a foundational piece for future mitochondrial research and helps to propel our understanding of peri-droplet mitochondria and their functions forward. 

Study Conducted by Albert Shieh, MD, and Team Makes Breakthrough on Understanding Bone Loss Across the Menopause Transition

"Changes in collagen type I C-telopeptide and procollagen type I N-terminal propeptide during the menopause transition," The Journal of Clinical Endocrinology and Metabolism

Albert Shieh, MD, is an endocrinologist and assistant professor in the Division of Geriatrics at UCLA. His research explores the possibility of preventing osteoporosis and fractures in later life among women by blocking menopause-related bone loss while women are still in their 40s and 50s. His latest study, "Changes in collagen type I C-telopeptide and procollagen type I N-terminal propeptide during the menopause transition," contributes to investigating this prevention possibility. 

The 18-year longitudinal analysis from the Study of Women's Health Across the Nation characterized, among 541 women, how blood levels of collagen type I C-telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP) change across the menopause transition. CTX is a marker of bone resorption (or breakdown), whereas PINP is a marker of bone formation. Through most of a woman's pre-menopausal life, bone breakdown and formation are in balance (meaning that the amount of bone removed is roughly the same as the amount of bone formed. This means that bone density is stable. Researchers have known that bone breakdown begins to exceed formation during menopause, but were uncertain to what degree and at what point this imbalance begins to occur. This study aimed to fill those gaps by following CTX and PINP measurements across menopause.

Dr. Shieh and his team found that bone breakdown (measured by CTX) begins accelerating approximately three years before a women's final menstrual period. Although bone formation (PINP) also increases, it does so more slowly than CTX, leading to “negative” balance. This imbalance begins three years before a woman's final menstrual period, and peaks about three years after a woman's final menstrual period. Specifically, during this six-year window, CTX increased 60%, but PINP increased only 40%. Thus, although both markers increased, bone breakdown increased proportionally more than formation, leading to bone loss. 

Building on these findings, Dr. Shieh and his team are testing whether researchers can use CTX and PINP to predict who will lose the most bone during the menopause transition. "CTX and PINP increasing so early suggests that we could potentially use these blood tests to pre-emptively identify women who will lose bone most rapidly, before substantial bone loss occurs. Once we can identify these high-risk individuals, we can then test whether it is possible to prevent this bone loss." Dr. Shieh shared. We are excited to see where this work could lead. 

Christopher Moriates, MD, Publishes Two Studies that Pave the Path for Reduction of Low-Value Care from an Equity Lens

  1. "“4 E’s” Ways That Clinicians Can Reduce Low-Value Care on Medical Wards," JAMA
  2. "Improving healthcare value: The need to explicitly address equity in high‐value care," Journal of Hospital Medicine

Christopher Moriates, MD, chief of hospital medicine at the VA Greater Los Angeles Healthcare System and professor of clinical medicine at UCLA, is dedicated to improving delivery of high-value care. Two of his recent publications aim to advance work on decreasing widespread overuse in hospitals and to ensure that these efforts explicitly address equity.  

The first article, “4 E’s” Ways That Clinicians Can Reduce Low-Value Care on Medical Wards," published in JAMA Internal Medicine, was written in collaboration with high-value care leaders in Canada. 

The authors begin the article by recognizing that despite more than a decade of the Choosing Wisely campaign, common areas of overuse persist in hospitals, including: 1) telemetry (continuous monitoring of patient cardiac rhythms), 2) routine bloodwork, and 3) urinary catheterization. Dr. Moriates shared that though these interventions are extraordinarily important when there's an indication, they are regularly ordered in circumstances where they are not necessary, often in around half or more of cases, in a manner that has the potential to do more harm in a patient's healing or recovery process. As a result, the article’s authors sought to summarize the relevant evidence and create a framework to overcome the common areas of overuse. The framework introduces the four E's: Enforce Stewardship, Empower Interprofessionals, Embed reminders, and Educate Clinicians. 

The second, related recent article co-authored by Dr. Moriates, "Improving healthcare value: The need to explicitly address equity in high‐value care," published in the Journal of Hospital Medicine, contextualizes the work of addressing medical overuse within the imperative to improve healthcare equity. In essence, the article explains how the need to make the delivery of high-value care interventions more equitable and accessible is well-established, but that the health disparities present within the receipt of certain low-value care services is less well understood. For example, the paper points out that "the overuse of certain low-value services has been disproportionately observed among patients who are publicly insured or uninsured," and that more care is not always better. As a result, Dr. Moriates and his coauthors argue that we have a dynamic where, at least at times, marginalized patients are less likely to receive high-value care, and more likely to receive low-value care. In response, the article suggests that we must take these nuanced dynamics into consideration when pushing forward interventions to mitigate low-value care, for instance by actually identifying the “optimal rate” of care delivery across populations rather than relying on assumptions. 

"Our hope is that individual physicians and hospitals will adopt the "Four E's" framework and work on system-wide practices to reduce common overuse at the hospital," shares Dr. Moriates. "Regarding equity, our hope is that researchers and implementation leaders integrate equity considerations when prioritizing high value care initiatives."

Research from Richard Leuchter, MD, Sheds Light on How to Mitigate Echocardiogram Overuse

"Evaluation of an Electronic Health Record Tool to Identify Echocardiograms That Do Not Change Clinical Care,” Journal of the American Society of Echocardiography

Richard Leuchter, MD, is a hospitalist at Ronald Reagan and Santa Monica UCLA Medical Centers, the VA, and Olive View-UCLA Medical Center. When he's not caring directly for patients, he's working on research to maximize the value of care for hospitalized patients, which, he shares, often involves "minimizing unnecessary tests or procedures that have the potential to harm patients." Dr. Leuchter and his colleagues primarily do so by using large electronic health records (EHR) and predictive models that allow for the identification of potentially harmful or wasteful practices. Upon identifying these low-value interventions or practices, they design interventions to be embedded into the EHR to prevent such practices at the point-of-care. 

This process is the premise of one of his recently coauthored papers "Evaluation of an Electronic Health Record Tool to Identify Echocardiograms That Do Not Change Clinical Care" in the Journal of the American Society of Echocardiography. According to Dr. Leuchter, we carry out MANY transthoracic echocardiograms (also known as TTEs) on hospitalized patients across the country -- including at UCLA at over 6,000 TTEs per year. While TTEs can be incredibly useful, there are many cases in which we repeat TTEs multiple times during a single admission without clear evidence of added value. This can drive up hospital bills, contribute to discharge delays, and make patients in greater need of TTEs wait while potentially less important TTEs get completed.

As a result, Dr. Leuchter and his team wanted to see if they could develop a set of criteria using EHR data to predict which TTEs were low-value -- which they defined as any TTE that resulted in no change in clinical care (any TTE that provided reassurance of the current treatment plan or changed the treatment plan was considered high-value). Ultimately, they identified 10 criteria that could pinpoint a low-value TTE with 89% accuracy, demonstrating that these criteria could be built into an automated system to classify thousands of TTEs in a matter of seconds. Given that the models they built only use data present at the time the clinician ordered the study, this model could be used in real-time to help prioritize the most important TTEs and discourage ordering low-value TTEs. Dr. Leuchter's hope is that this model, and similar models built into EHR systems -- such as predictions about which patients in the ED could be safely sent home instead of being admitted -- help to improve patient care and workflows at our hospitals.

Keep on innovating.



For those who celebrate, Happy Year of the Dragon!

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