Heart disease

New noninvasive tests may help pediatric heart recipients

Nathan Kahl — Thu, 15 Feb 2024 15:08:18 +0000

New noninvasive tests may help pediatric heart recipients Nathan Kahl Thu, 02/15/2024 - 10:08

Each year, approximately 500 children in the U.S. undergo heart transplantation. These children face considerable stress.

Undergoing a biopsy—an invasive procedure using a catheter to remove a piece of the transplanted heart to test it—is just one way such patients are poked and prodded. Cardiac biopsies are a necessary evil, serving as the primary way doctors detect if a heart is likely to be rejected. But now ��ӽ紫ý and the Inova Health System are teaming up to develop ways to make that determination with noninvasive techniques.

Jason Goldberg. Photo provided

“On average, children pediatric heart transplant patients undergo approximately 10 biopsies within the first year of transplant…and more if they have rejection,” said Jason Goldberg, MD, MS, a pediatric cardiologist and research fellow at Mason. “That's a big deal, especially since taking a child to the hospital is no small thing. They have to go under anesthesia, they have to have needles stuck in them. It's quite traumatic, and diagnosing rejection in a noninvasive manner may help start treatment before the patient is sick and not feeling well.”

Cardiologist Palak Shah, MD, an adult heart-transplant specialist who serves as Goldberg’s research mentor at Inova, has worked with colleagues both at Inova and Mason to evaluate the potential of microRNA (miR) to provide clues on whether heart transplant recipients are at risk for rejection. miR are small, noncoding RNA molecules that impact the regulation of gene-expression.

Shah and his team published a paper in 2022 that was cause for optimism. The researchers found that “miRs are promising genomic biomarkers in cardiovascular medicine, have the potential ability to detect heart transplant rejection, and may provide mechanistic insights into molecular pathways modulated during rejection.”

“MicroRNA is a type of transcription factor, which is a protein that turns specific genes ‘on’ or ‘off’ by binding to nearby DNA,” explained Goldberg. “And it's encoded to a certain degree to do what the body needs, so when you measure the microRNA, you can get a sense of what the body is doing—essentially it's a molecular biomarker. What Palak and others found is that there are microRNA signatures correlating with heart transplant rejection.”

Goldberg is now using the technique to test children who have received new hearts. He and his colleagues at Mason and Inova received a grant from the Enduring Hearts Foundation, which includes collaboration with colleagues at the University of Pittsburgh Medical Center who have bio-banked blood samples taken at the time of biopsy. The biomarkers are validated by looking simultaneously at the microRNA taken at the same time as a rejection or nonrejection biopsy.

Testing microRNA allows doctors to determine the likelihood of a successful heart transplantation

The new pediatric developments are being supported by a partnership between Inova and the Mason Statistics Collaboration Core (SCC), which is providing the mircoRNA analysis. This and other collaborative projects require machine learning and other advanced statistical techniques utilized by Mason faculty and graduate students.

Goldberg said that the collaboration is mutually beneficial. “Mason has great research and science but no medical school, whereas Inova has great medicine but lacks significant biomedical academic partnership," said Goldberg. "With the two organizations working together it creates a lot of runway for research.”

Goldberg is one the first members of a postdoc program for Inova clinician-scientists interested in developing skills in statistics and data science. “I'm a pediatric heart transplant physician and I've been taking care of patients for nearly 15 years,” he said. “But I was at a point in my career where I really caught the research bug, and it hasn’t gone away."

Palak, Goldberg's mentor, has ongoing collaborations with Jiayang Sun, chair of Mason's Department of Statistics, and Carolyn Drews-Botsch, chair of the Department of Global and Community Health in Mason's College of Public Health. Sun is the Mason PI and Drews-Botsch is the Co-PI for this special joint postdoc program with Inova Health System.

“This pioneering program between Mason and Inova uniquely trains the next generation of medical research scientists in collaborative research and some essentials in data science, statistics, or epidemiology to address the challenges of the AI and information revolution," said Sun. The program features dedicated mentors from Mason in the fields of statistics, epidemiology, and global health, along with top physicians and researchers at Inova.

Goldberg is enthused about the new development, and most importantly, the increased longevity it may bring to young patients with critical heart disease. “When I was in my cardiology fellowship, we thought that the big change in heart transplantation would be that we wouldn't have to do it anymore, that there would be stem cells and other fancy machines that wouldn't require the use of donor organs. But time and time again, nothing has really worked to replace heart transplantation.

“It has become clear that the next frontier for our patients includes personalized medicine where molecular biomarkers and therapies can evaluate ongoing pathology and define specific treatments before significant illness develops. I am proud to be part of this work at Mason and Inova.”

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Jiayang Sun

Carolyn Drews-Botsch, PhD, MPH

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Study finds probiotics are not only good for the gut, they affect other organs too

Colleen Rich — Mon, 17 Apr 2023 15:03:47 +0000

Study finds probiotics are not only good for the gut, they affect other organs too Colleen Rich Mon, 04/17/2023 - 11:03

According to the Centers for Disease Control and Prevention, more than 40% of Americans are classified as obese, leading obesity to be considered a significant public health threat. High fat diets, which are often cited as a cause of obesity, can also result in the development of metabolic syndrome, a group of conditions that may promote the progression of serious health conditions, including cardiovascular disease and type 2 diabetes. With obesity rates still rising, the hunt is on for ways to combat the negative effects of a high fat diet. ��ӽ紫ý researchers now believe they have discovered a possible answer—probiotic supplementation.

Mason researchers Robin Couch and Allyson Dailey in the lab.
Photo by Evan Cantwell/Creative Services

Robin Couch and Allyson Dailey, researchers in Mason’s College of Science and the Institute for Biohealth Innovation, are interested in the correlations between dietary intake and overall health. In a recent study, Couch and Dailey partnered with the U.S. Department of Agriculture to explore the influence of probiotic supplementation on a higher fat diet, using pigs as model organisms.

The research team looked at four groups of pigs—two groups that were fed nutritionally balanced diets with and without probiotic supplementation, and two groups that were fed higher fat diets with and without probiotic supplementation. The probiotic that was tested is known as Lacticaseibacillus paracasei. After six months of dietary intake, organ tissue samples obtained from the pigs were examined, specifically looking at their molecular composition.

Couch and Dailey were looking at specifically at metabolites, substances that are produced or used during metabolism. They found that the kidneys and the brain were particularly sensitive to a high-fat diet and when certain metabolites were noted to be at harmful levels, the kidneys and the brain were the most susceptible.

In contrast, they also discovered that, with probiotic supplementation, many of the detrimental metabolite levels reverted to levels found in pigs that were fed a healthy diet. In other words, probiotic supplementation staved off the negative effects associated with a high-fat diet, illustrating how probiotics may play a key role in preventative health care.

“We’d like to see probiotic intake become a regular part of the dietary recommendations that a physician would give to a patient,” said Dailey.

The researchers are also aiming to investigate other probiotic strains.

“If different strains do have distinct effects on the body, then you could see individualized probiotics, or even probiotic cocktails, being used to treat specific diseases,” said Couch. “We think it’s likely that, alongside pharmaceuticals, prescribing probiotics that address various diseases will be more commonplace in the future.”

Additionally, Couch and Dailey view this study as a stepping stone to potential subsequent work on how other nutrients, such as protein and carbohydrates, affect tissue composition.

“We specifically looked at the influence of a high-fat diet in our research, but this opens up a whole world of nutritional investigation at the metabolic level,” said Couch.

For now, the researchers are hoping that their study, which was recently published in the journal Metabolites, serves to add scientific validity to the claims of the benefits of probiotics.

“This is progress towards providing new evidence that probiotics are good for you and that what you consume has a profound effect on your health,” said Dailey. “These findings can contribute to the creation of revolutionary solutions, and, in the end, that’s why I’m in this—to help people thrive.”

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Heart disease

New noninvasive tests may help pediatric heart recipients

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Study finds probiotics are not only good for the gut, they affect other organs too

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