COVID Testing, Immunometabolism, Autistic Drivers, Neighborhoods and Sleep

limjr [at] chop.edu (By Jillian Rose Lim)

From COVID-19 testing times to sleep outcomes for adolescents, this week's roundup features a number of ways Children's Hospital of Philadelphia researchers are working to improve outcomes and interventions in pediatrics. Learn whether testing for COVID-19 a few days before surgery yields discordant results than testing the day of surgery, why defects in mitochondria may cause autism spectrum disorder (ASD), how neighborhood conditions affect sleep, and more.

Study Assesses Concordance Between Preoperative SARS CoV-2 Testing and Surgery Day

Though testing a patient for COVID-19 immediately before surgery is ideal, a variety of factors make this a challenge, including the 24 to 48 hours it may take for test results to return and the logistical challenges of scheduling surgery. Learning about any discordance between preoperative test results and those from the day of surgery is critical to ensure the safety of patients and staff. In recent findings pre-published online in Pediatrics, Elaina Lin, MD, and a team of CHOP researchers reported that in a cohort of 241 CHOP patients, they found no discordance between preoperative test results (results from testing up to 72 hours before surgery) and those from the time of surgery. The findings in the study cohort validate the accuracy of CHOP's policy, which is to test within three calendar days of surgery.

"This is reassuring, at least within the study population," said Dr. Lin, an anesthesiologist in the Department of Anesthesiology and Critical Care Medicine at CHOP. "We do have the caveat that our sample period was from mid-July to mid-October, a time of relatively low community prevalence. However, within this population, our policy appears to be a reasonable strategy that balances the safety of patients and staff with the logistical challenges of testing and scheduling surgery. The goal of this work is to reassure clinicians, patients, and their families that testing within three calendar days is accurate."

The study will be published in print in Pediatrics in April 2021. You can read the pre-publication online.

Will Bailis, PhD, Recognized With Distinguished Investigator Award

Join us in congratulating Dr. Bailis, assistant professor in the Department of Pathology and Laboratory Medicine at CHOP, for his recent recognition by the Paul G. Allen Frontiers Group as an Allen Distinguished Investigator. In an effort to better understand the intersection of immunology and metabolism (an emerging field called immunometabolism), the Allen Frontiers Group announced their support for four research projects led by teams of two or three Distinguished Investigators. Each award provides $1.5 million in funding over three years.

Alongside his team, Chris Bennet, MD, from the University of Pennsylvania, and Ruaidhri Jackson, PhD, from Harvard University, Dr. Bailis' research project seeks to understand how immunity and metabolism are linked at the scale of individual cells, organs, and the entire body. Working with animal models, the team will examine how food affects energy production inside immune cells by genetically engineering cells to "ignore" changes in diet. The researchers will also examine how tissue-resident macrophages, a particular type of immune cell, use metabolism to govern the function of tissues and the entire body.

Defects in Mitochondria May Predispose Patients to Autism Spectrum Disorder

Autism spectrum disorder (ASD) may be caused by defects in the mitochondria of brain cells, according to new findings published in the Proceedings of the National Academy of Sciences. Previous research has laid the foundation for this finding, suggesting that deficiencies in mitochondria, the energy-generating power plants of our cells, may explain the many genetic mutations associated with ASD. Recent research also has shown variants of mitochondrial DNA (mtDNA) are associated with ASD. Now, researchers at CHOP set out to further explore these associations.

The team introduced a mild missense mutation in the mtDNA ND6 gene into an animal model, hypothesizing that if defects in mitochondria can predispose patients to ASD, introducing relevant mtDNA mutations should result in autism endophenotypes (measurable traits similar to those seen in patients). Indeed, the model exhibited common behavioral features associated with ASD as well as brain-region specific defects on mitochondrial function. Since the researchers found no clear change in brain anatomy, the findings suggest that mitochondrial energetic defects appear sufficient to cause autism.

"Our study shows that mild systemic mitochondrial defects can result in autism spectrum disorder without causing apparent neuroanatomical defects," said Douglas Wallace, PhD, director of the Center for Mitochondrial and Epigenomic Medicine at CHOP, co-senior author of the study. "These mutations appear to cause tissue-specific brain defects. While our findings warrant further study, there is reason to believe that this could lead to better diagnosis of autism and potentially treatments directed toward mitochondrial function."

Learn more.

New Study Finds Young Autistic Drivers Crash Less Than Non-autistic Peers

A new study from researchers in our Center for Injury Research Prevention (CIRP) and Center for Autism Research indicates that newly licensed young autistic drivers have similar to lower rates of crash involvement than their non-autistic peers. Despite prior driving simulator research that suggests young autistic drivers may be at heightened risk, this study revealed 33.5 percent were involved in a police-reported crash compared to 38.1 percent of other young drivers over the study period. Young autistic drivers also showed lower rates of moving violations and license suspensions than other young drivers. Dr. Curry and her team published the findings in the Journal of the American Academy of Child and Adolescent Psychiatry.

In a CIRP Research in Action blog, study author Allison Curry, PhD, wrote that the findings help to establish best practices for the development and refinement of tools, strategies, and interventions to help young autistic drivers learn to drive safely. They also point to the need to examine which of the observed crash patterns can be attributed to different driving patterns, active efforts by families to balance independence and driving risk, and a greater affinity to follow road rules.

"Our findings suggest licensed young autistic drivers may establish driving patterns that balance independent mobility and risk — thus bringing their probability of crash involvement in line with other young drivers," wrote Dr. Curry, who is director of Epidemiology and Biostatistics at CIRP.

Learn more.

Neighborhood Conditions Linked to Adolescent Sleep Loss

From street sound levels to the number of trees, specific neighborhood conditions can affect how much sleep an adolescent gets, according to a new study from CHOP researchers published in the journal Sleep. With more than 75 percent of high school students not getting the recommended amount of sleep (thus placing them at risk for future chronic disease), identifying the modifiable factors in a teen's environment can be crucial for developing interventions to improve sleep outcomes.

With support from the National Heart, Lung, and Blood Institute (NHLBI), researchers assessed 110 adolescents using actigraphy, in which a wrist device measures a person's cycles of activity and rest over several days or weeks. The team also examined participants' home addresses, particularly built environment exposures within them such as sound levels, tree canopy cover, street density, intersection density, population density, and housing density. They found that higher sound level was associated with lower odds of sufficient sleep, while more tree canopy cover was associated with more favorable sleep timing.

"For adolescents, the harms of insufficient sleep are wide-ranging and include impaired cognition and engagement in antisocial behavior," said study author Stephanie Mayne, PhD, assistant professor of Pediatrics at CHOP, in an NIH news release. "This makes identifying strategies to prevent and treat the problem critical. Our findings suggest that neighborhood noise and green space may be important targets for interventions."

Learn more.

ICYMI

Catch up on our headlines from our Jan. 22 In the News:

• Pfizer Approves Drug for Anaplastic Large Cell Lymphoma
• Nanoparticles Could Deliver mRNA in Fetal Therapy
• NTRK Fusions More Common in Pediatric Cancers Than Expected
• Article Highlights Implementing Infection Control Program at Alternate Care Site
• Autism, Epilepsy May Share Genetic Pathways
• Philanthropic Funding Support Children's Brain Tumor Network's Research

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