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MIS-C, Heart Disease, Sleep Genes, Neonatal Resuscitation

Published on January 20, 2023 in Cornerstone Blog · Last updated 5 months 3 weeks ago


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In the News

In this week's news roundup, find out about a study funded by the National Institutes of Health to inform diagnosis of multisystem inflammatory syndrome in children (MIS-C).

Chief of Infectious Diseases Receives Additional NIH Funding for MIS-C Study

Audrey Odom John, MD, PhD, chief of the Division Infectious Diseases at Children's Hospital of Philadelphia, and her team received two more years of funding from the NIH for their study, "Diagnosis of MIS-C in Febrile Children." The initial 2020 award was part of an NIH initiative to study methods to diagnose children at high risk for MIS-C, a rare effect of SARS-CoV-2 infection or exposure in children. Dr. Odom John was one of eight grant recipients under the Rapid Acceleration of Diagnostics Radical (RADx-rad) program to identify new and reimagined tools to address gaps in COVID-19 testing and surveillance.

Audrey R. Odom John, MD, PhD
Audrey Odom John, MD, PhD

Dr. Odom John and Hamid Bassiri, MD, PhD, lead the research team, who are examining whether MIS-C causes changes in metabolites found in the breath, urine, or saliva of children. The goal is to integrate these findings with clinical and immunological profiling to develop diagnostics for MIS-C and distinguish it from other causes of fever. Fran Balamuth, MD, PhD; Ed Behrens, MD; Jeff Gerber, MD, PhD; Aaron Masino, PhD; David Teachey, MD; and Laura Vella, MD, PhD, are also part of the research team.

Read more about this research on Cornerstone.

Robert Levy, MD

Robert Levy, MD

Researchers Investigate How Serotonin Contributes to Heart Valve Disease Progression

The neurotransmitter serotonin can negatively affect the heart's mitral valve and lead to a heart disease called degenerative mitral valve regurgitation, according to data from a new study co-led by Robert J. Levy, MD, William J. Rashkind Endowed Chair in Pediatric Cardiology at CHOP and, and Giovanni Ferrari, PhD, of Columbia University.

In degenerative mitral valve regurgitation, the mitral valve becomes deformed and unable to completely close when the heart contracts, allowing blood to leak backwards into the left atrium. Though patients are initially asymptomatic, the heart needs to work harder and this extra work eventually leads to heart failure, and potentially surgery to repair the mitral valve. Dr. Levy and colleagues analyzed data from more than 9,000 patients who had surgery for degenerative mitral valve disease and evaluated disease models.

The researchers found that taking selective serotonin reuptake inhibitors (SSRIs) — commonly prescribed antidepressants — was associated with severe mitral regurgitation, which required surgery at a younger age than those not taking SSRIs. In animal models, high doses of SSRIs were associated with thickened mitral valves. The findings appear in Science Translational Medicine.

They also found that genetic variants in the serotonin transporter (SERT) gene 5HTTLPR may affect the influence of SSRIs on the mitral valves. Specifically, those that have two copies of a "long" variation of the gene were more likely to react to serotonin in a way that could change the shape of the mitral valve. The researchers noted that they did not find a negative effect with normal doses of SSRIs and that a healthy mitral valve may tolerate low SERT without deforming, as it is unlikely that low SERT can cause degeneration of the mitral valve by itself.

"Our study shows that taking SSRIs and having the 'long-long' SERT genetic variant lowers SERT activity in the mitral valve," said Dr. Levy, who is also a professor of Pediatrics at Perelman School of Medicine at the University of Pennsylvania. "We suggest that assessing patients with known degenerative mitral regurgitation for potential low SERT activity by genotyping them for 5HTTLPR may help identify patients who may need mitral valve surgery earlier."

Find out more about the study in the CHOP press release.

Struan Grant, PhD

Struan Grant, PhD

Researchers Identify Genetic Regulator of Sleep

A research collaboration between CHOP, Texas A&M University, and the Perelman School of Medicine at the University of Pennsylvania led to the identification of a genetic pathway involved in regulating sleep, which could help to develop new treatments for insomnia and other sleep disorders. Struan F.A. Grant, PhD, a director of the Center for Spatial and Functional Genomics, was one of the senior authors on the study, which appeared in Science Advances.

In this study working with fruit flies, the researchers used human genomics data to validate and test the function behind genes identified in previous large-scale studies. They further validated results in zebrafish, which led to the identification of the PIGQ gene and its role in sleep regulation. The researchers aim to study the role of a common form of protein modification on sleep regulation to see if other genes behave similarly.

"Our lab's three-dimensional genomics approach implicated causal genes responsible for human insomnia, and we were able to then perturb the comparable gene in a fruit fly model and observed sleep disturbance," Dr. Grant said. "This study shows how we're able to use such model organisms to validate human genetic leads that help get us closer to therapeutic discoveries that could benefit patients."

Learn more in the CHOP press release.

Elizabeth Foglia, MD, MA

Elizabeth Foglia, MD, MA

CHOP Leads Guideline Development for Neonatal Resuscitation Research

CHOP researchers led an international group of experts to develop new guidelines for neonatal resuscitation research. The guidelines, developed by the International Liaison Committee on Resuscitation Neonatal Life Support Task Force, will standardize data definitions for research in this area, which will allow for better comparisons across studies. Elizabeth E. Foglia, MD, MA, attending neonatologist in the Division of Neonatology, is first author of the guidelines, which appeared in Pediatrics.

A task force working group developed reporting guidelines for neonatal resuscitation based on similar guidelines developed for adults in 1990 in Utstein Abbey, Norway. The guidelines focus on resuscitation of newborns after birth for respiratory failure, bradycardia, severe bradycardia, or cardiac arrest. The researchers identified seven relevant domains, and then identified relevant data elements within each domain as core or supplemental. Core data elements should be collected and reported for all neonatal resuscitation studies.

"We hope the Neonatal Utstein reporting guidelines will assist investigators to engage in neonatal resuscitation research and facilitate data pooling in meta-analyses, enhancing the strength of neonatal resuscitation treatment recommendations and subsequent guidelines," Dr. Foglia said.

Read more about this in the CHOP press release.


Catch up on our headlines from our Jan. 6 In the News:

  • COVID-19 Vaccine Appears Safe for Children with History of MIS-C
  • Antibody Treatment Improves EoE Symptoms and Pathology in Young Adults
  • Strong CHOP Contribution and Presence at Premier Hematology Conference

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