Lab Notes

Summaries of late-breaking research and news from the scientists at UCLA Health and David Geffen School of Medicine

Women treated with thrombectomy for pulmonary embolism fare worse A new study led by UCLA researchers analyzed the different outcomes in men and women with a pulmonary embolism who are treated by a percutaneous pulmonary artery thrombectomy- a procedure in which a catheter is placed in a patient’s lung to dissolve or remove a blood clot. After analysis of a national cohort of US patients from an inpatient claims-based database, researchers reported that women had higher rates of procedural bleeding, vascular complications, and needed more blood transfusions compared to men. They also found that women had higher in-hospital death rates and were more likely to go a nursing home or an assisted living facility instead of returning home after discharge. Given these disparities in outcomes, study authors are calling for more sex-based research. Read the study in the January 1, 2023 issue of CHEST. 

A new clue about Parkinson’s progression The transmission of misfolded proteins in the brain is a key mechanism for the progression of various neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. Chao Peng, PhD, an assistant professor of neurology, found a novel mechanism that regulates the transmission of one of these pathological proteins, misfolded alpha-synuclein, which leads to disease progression in Parkinson’s. This mechanism is the discovery that many modifications that a cell makes in these proteins alter their ability for transmission in the brain and disease progression. This discovery not only provides critical insights into disease mechanism but also facilitates the development of novel therapy for neurodegenerative diseases. Read the study, published Jan. 23, in Nature Neuroscience.

Urban heat islands, redlining and kidney stones The persistent rise in kidney stone prevalence in recent decades has prompted much speculation as to the causes. There has been some discussion about the effect of heat on nephrolithiasis. A review of recent data suggests that heat may play a role in stone formation on a large scale and among African-Americans in particular. A new UCLA-led study led by Dr. Kymora B. Scotland states that African-Americans are the race/ancestry group with faster rates of increasing incidence and prevalence of kidney stones. Researchers also found that urban heat islands in the United States have resulted in part from the effects of redlining, a practice of systematic segregation and racism in housing that led to the development of neighborhoods with substantial disparities in environmental conditions. Dr. Scotland and her team hypothesize that the increased temperatures experienced by residents in redlined communities, many of whom are African American may contribute to the 150% increase in the prevalence of kidney stones in African Americans in recent decades. Read the study in the January 1, 2023 issue of Current Opinion in Nephrology and Hypertension.

Gender-affirming hormones tied to mental health for transgender youth Transgender and nonbinary teens who receive gender-affirming hormones experience improvement in body satisfaction, life satisfaction and less depression and anxiety than before treatment. These findings are according to newly-published research by a four-site prospective, observational study and co-authored by Marco A. Hidalgo, PhD. Dr. Hidalgo is a clinical psychologist and Associate Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA. Read the study published January 19, 2023 in the New England Journal of Medicine.

COVID outcomes among patients with COPD While chronic respiratory condition such as COPD - a disease that causes airway blockage and emphysema - increases risks of worse clinical outcomes in COVID-19, its impact on survival of patients treated in hospital settings has not been studied well enough, especially in the health systems with adequate resources and better COVID-19 pandemic control. In a newly published study reviewing the outcomes in patients with COPD who were hospitalized at UCLA Health with acute COVID-19 infection in the first year of the pandemic, COPD was found to be associated with a more severe disease course. However, the patients with COPD did not have a significantly higher rate of ICU admissions, mechanical ventilation, or in-hospital mortality once the contribution of other commonly seen comorbidities in this population was accounted for. Although the retrospective nature of this analysis and the fact that the findings were confined to a single hospital center limits the significance of these findings, it was also interesting to find that the chronic use of inhaled COPD therapies and aspirin prior to the hospitalization was associated with better outcomes.  Read the study in the International Journal of Chronic Obstructive Pulmonary Disease.

The link between obesity, the brain, and stroke. Obesity, a growing global problem, increases the risk for stroke and vascular brain injury with long-term consequences including the development of cognitive impairment and dementia. A new UCLA study focused on identifying molecular pathways induced by diet-induced obesity in the brain of mice and humans found that overweight mice had strokes in the deep brain white matter that were 30% larger than normal weight mice. The researchers, led by Dr. Jason D. Hinman, Associate Professor and Vice Chair of Research in Neurology and Stroke Program Director of the West Los Angeles VA Medical Center, also found that obesity induced a specific inflammatory pathway in brain blood vessels that limits the ability of the brain to repair after stroke. They also showed that because obesity damages brain blood vessels, this specific pathway can  be measured in patients’ bloodstream and may be a new biomarker to identify patients with silent brain vascular injury at risk for stroke, especially in those with obesity. Read the study in Cell Reports.

Reducing low value treatments in Alzheimer’s Disease and related dementias Physicians routinely prescribe antipsychotic medications to patients with dementia to control their behavioral disturbances, despite the fact that these low-value drugs are not considered first-line therapy and can even increase the risk for death. To help curb this trend, a UCLA-led team has designed a clinical trial aimed at steering physicians away from prescribing these drugs, or to reduce the dosages and number of pills in the bottle.  Under the one-year controlled randomized trial, participating physicians would either receive an electronic health record clinical decision support intervention or no intervention at all. The intervention will do three things: alert the physician that the drug can increase mortality risk, offer non-drug behavioral resources for caregivers, and default the prescription to the lowest dosage and number of pills and not include refills. The researchers believe that this would be the first such clinical trial to combine two behavioral economic principles – a desire for non-malfeasance (do no harm), and auto-defaulting to the lowest supply of the medications as possible. Read the full details about the clinical trial at the peer-reviewed journal PLOS ONE.

Opioids frequently prescribed in cirrhosis Using weighted data representing 12.3 million ambulatory visits in the US, researchers found that opioids were frequently prescribed to patients with cirrhosis, often without a documented pain diagnosis, raising concerns about appropriateness. Encounters involving older, male, Black patients and primary care physicians were associated with prescription risk. The authors say de-escalation efforts should be individualized towards these patient communities and prescribers, who may be less familiar with the patient population and should be educated on risks of their opioid use. Read the study in Clinical Gastroenterology and Hepatology.

Masks for COVID also prevented whooping cough A new analysis by researchers at UCLA Health finds public health prevention measures taken during the COVID pandemic led to a dramatic drop in whooping cough cases in their health system. Whooping cough, or pertussis, spreads rapidly through droplet transmission, impacting individuals of all ages. Whooping cough is vaccine preventable, however immunity wanes over time. When patients seek care, the risk of transmission to other patients and health care workers can be high. The researchers sought to evaluate the impact of COVID-19 mitigation measures, like masking and school closures, on the number of primary pertussis cases in patients and secondary cases in staff members at ambulatory clinics at their institution before and after the COVID-19 pandemic. Pertussis cases for 2019, 2020, and 2021 were 1,008, 87, and 0 respectively. There were no reported health care worker exposures after March 2020. The authors say their findings demonstrate that masking can impact respiratory disease transmission outside of COVID-19, and that the results are of clinical importance in health care as they show how wearing a mask with symptomatic respiratory patients can be beneficial in reducing exposure to health care workers. Read the study in the American Journal of Infection Control

Microbiome approaches to food allergies The prevalence of food allergies continues to rise, and with limited existing therapeutic options there is a growing need for new and innovative treatments. Food allergies are, in a large part, related to environmental influences on immune tolerance in early life, and represent a significant treatment challenge. This review, led by Dr. Diana Chernikova, pediatric allergy and immunology fellow at the David Geffen School of Medicine at UCLA, discusses the intersection between the gut microbiome and the development of food allergies, with particular focus on microbiome therapeutic strategies. These emerging microbiome approaches to food allergies are subject to continued investigation and include dietary interventions, pre- and probiotics, microbiota metabolism-based interventions, and targeted live biotherapeutics. Read about the findings in the Dec. 3, 2022 issue of Nutrients.

Medicaid expansion, increased access may reduce HIV infections Enacting Medicaid expansion and increasing the use of preventive and antiviral medications could result in a decline of new HIV infections among young Black gay, bisexual, and other men who have sex with men (MSM), reports a study co-authored by Dr. Nina Harawa, professor of Medicine and Epidemiology at the UCLA David Geffen School of Medicine and the Fielding School of Public Health. Led by Francis Lee, PhD, of the University of Chicago, the study used a technique called "agent-based network modeling" to simulate the effects of alternative Medicaid expansion strategies on HIV transmission among young Black gay, bisexual, and other MSM in Houston. Simulations projected the effects of Medicaid expansion alone and with the addition of two further strategies that have shown promise in increasing engagement with ART and PrEP. In the study models, all three scenarios were projected to lead to considerable declines in HIV transmission among young Black gay, bisexual, and other MSM. With Medicaid expansion alone, the HIV incidence rate (new cases per 100 uninfected) was projected to decrease by 17.5% by the tenth year, while the number of new infections would decrease by 14.9%. The most aggressive scenario modeled would nearly halve rates of new infections. Read the study in the journal Medical Care.

Hope for a highly lethal brain cancer A study led by Dr. Linda Liau of the Jonsson Comprehensive Cancer Center finds a cancer vaccine co-developed by Dr. Liau at UCLA led to meaningful increases in survival for patients with glioblastoma multiforme (GBM), a highly lethal brain cancer with a nearly 100% recurrence rate and dismal patient survival. Glioblastomas are aggressive and rapidly lethal; there is a pressing need for new treatments and for novel clinical trial designs to streamline their development. This phase 3 nonrandomized controlled trial of 331 patients found newly-diagnosed GBM patients who received DCVax-L had a median overall survival of 19.3 months after randomization (22.4 after from surgery) compared to 16.5 months survival among a group of external control patients treated with standard care.  For patients with recurrent GBM, median overall survival was 13.2 months from relapse in the DCVax-L group vs 7.8 months in the external control cohort. Meaningful increases in the long-term tails of the survival curves in both nGBM and rGBM were also observed. Read the study in JAMA Oncology and hear Dr. Liau discuss its results and implications in this JAMA podcast.

UCLA Health's response to unaccompanied children at the border A new report details the University of California Health (UCH) system-wide, rapid response to the humanitarian crisis of unaccompanied children crossing the southern U.S. border in the midst of the COVID-19 pandemic in 2021.  In collaboration with multiple federal, state, and local agencies, UCH mobilized a multidisciplinary team to deliver acute general and specialty pediatric care to unaccompanied children at two Californian emergency intake sites. The response, which did not disrupt normal UCH operations, mobilized the capacities of the system and resulted in a safe and developmentally appropriate environment that supported the physical and mental health of migrant children during this traumatic period. Overall, 260 physicians, 42 residents and fellows, four nurse practitioners participated as treating clinicians and were supported by hundreds of staff across the 2 sites. Over five months and across both sites, a total of 4,911 children aged 3–17 years were cared for. A total of 782 children had COVID-19, most infected prior to arrival. Most children (3,931) were reunified with family or sponsors. Read more in the Nov. 15, 2022 report in Academic Medicine.

When congenital heart disease patients get cancer: A new study of cancer outcomes in people with adult congenital heart disease (ACHD) indicates the need for more concerted efforts to appropriately screen and care for this unique population. This collaborative study from the UCLA Adult Congenital Heart Disease and cardio-oncology programs found that all cardiac events in this population were able to be addressed successfully without permanent discontinuation of cancer therapy. In this cohort of adults with both conditions, the median age of cancer diagnosis was only 43.5 years. Only 10% of cancers were detected through screening, and a quarter of all patients had metastatic disease at time of diagnosis. Despite predominantly moderate or great anatomic complexity of congenital heart disease and a high incidence of adverse cardiac events, most deaths occurred due to cancer rather than cardiovascular causes. The authors say the data shows that it is feasible to administer systemic cancer therapy to such a cohort and manage cardiotoxicity without prolonged discontinuation of therapy. Additionally, the authors underscore the need to better define cancer screening in this high-risk population to ensure timely diagnosis and improved outcomes. Read the study in Cardio-Oncology.

Diversity in Gastroenterology A new survey of more than 1,200 gastroenterology (GI) and hepatology professionals in the United States assessed current perspectives of racial and ethnic workforce diversity and health care disparities. It finds the most frequently reported barriers to increasing racial and ethnic diversity in GI and hepatology were insufficient representation of underrepresented racial and ethnic minority groups in the education and training pipeline (reported by 35.4% of respondents), in professional leadership (27.9%), and among practicing GI and hepatology professionals (26.6%). The survey also underscored the discrepancy in satisfaction with workplace diversity among GI and hepatology physicians by race and ethnicity. While 63% of Black physicians were very or somewhat unsatisfied with workplace diversity, 78% of white physicians were very or somewhat satisfied. Read the study in the December 2022 issue of Gastroenterology.

An unexpected Alzheimer’s discovery Little is known about how non-neuronal brain cells known as astrocytes – distinguished by their “bushy” star-like shape – differ in structure or function across the brain, or how these cells may contribute to neurological disease. In a new UCLA-led study aimed at better understanding the molecular similarities and differences between astrocytes, researchers found gene networks correlated with the cells’ shape unexpectedly contained Alzheimer’s disease risk genes. When researchers working with mice reduced the expression of key genes related to the cells’ shape in the hippocampus, making the astrocytes less complex, cognitive function was reduced. They also found the expression of the same genes was reduced in human brains of Alzheimer’s patients. The findings suggest that therapies restoring astrocyte structure may help fight Alzheimer’s. The study was led by Fumito Endo, a project scientist in the lab of UCLA professor of physiology and neurobiology Baljit Khakh. Read the Nov. 4, 2022 study in Science.

Environmental risk of neurodegeneration While scientists increasingly recognize long-term exposure to air pollution as contributing to the development of neurodegenerative diseases like Parkinson’s and Alzheimer’s, how this exposure increases the risk is not well understood. A new UCLA study of air pollution exposure in a novel animal model found that the exposure caused neuronal loss, which was at least partly due to a buildup of protein aggregates in the brain. The researchers, led by Dr. Jeff Bronstein, director of the Movement Disorders Program at UCLA, also found that pollution exposure activated inflammatory cells that can be both good and bad, indicating that any medications to combat inflammation should be highly targeted to cells that can damage neurons. Read the study in Scientific Reports

Housing & Health: It's complicated Previous evidence has shown that housing insecurity—that is, difficulty with housing affordability and stability—is prevalent and results in increased risk for both homelessness and poor health. But a new study finds weak evidence that interventions to boost housing affordability and stability make a difference in improving health. Led by Dr. Katherine Chen, health sciences clinical instructor at the David Geffen School of Medicine at UCLA, the authors conclude that existing strategies to prevent housing insecurity, while necessary, are not sufficient to achieve long-term health gains for vulnerable populations and may need to be both modified and partnered with other policies to redress social inequity, including racism in housing. Read the study in the Nov. 2, 2022 issue of JAMA Network Open

Immunotherapy attaching to cancer cells

New approach to bladder cancer A new UCLA-led study of 82 patients with a high-risk form of bladder cancer shows that 71% of the patients, all of whom had not responded to typical therapy, responded to an experimental immunotherapy drug called NAI, which works by activating the body’s natural killer cells. After two years, 90% of the patients who responded to the drug avoided surgery to remove the bladder and there were no deaths from bladder cancer among all 82 patients. The study was funded by ImmunityBio and the results appear in the Nov. 10, 2022 issue of  NEJM Evidence.

Handheld diagnostic tool

A lab in the palm of your hand Using swarms of pinhead-sized magnets inside a handheld, all-in-one lab kit, UCLA researchers have developed a technology that could significantly increase the speed and volume of disease testing, while reducing the costs and usage of scarce supplies. Read more in this Nov. 10, 2022 press release from the UCLA Samueli School of Engineering here.

Award winner Roni Haas

Young investigator award October 26, 2022: Roni Haas, PhD, postdoctoral scholar in the lab of Paul Boutros has received a 2022 Young Investigator Award from the Prostate Cancer Foundation. The award will support Haas’s prostate cancer research project, Associating Germline Variants with Prostate Tumor Evolution and Lethality, at total of $225,000 over three years. Read more about the PCF Young Investigator Awards here.

Do celebrity endorsements increase vaccination? In the year between October 2020 and October 2022, Americans’ willingness to be vaccinated (defined as being vaccinated or planning to be) increased from 47.6% to 81.1%. A new survey led by Arash Naeim at the Center for SMART Health at UCLA’s Clinical and Translational Science Institute looked at how much impact five strategies had on increasing the willingness of unvaccinated adults to get their shots. It found endorsements by members of the scientific community, healthcare professionals, or celebrities had no positive effect. What did? The chance to relax the need for masks and social distancing, financial incentives, and vaccine requirements for attending sporting events traveling and work. Read the study in Vaccine.