Cytokine Panels, mRNA Vaccines, LiBI Symposium, Firearm Safety, Concussion Recovery

 

In the News this week, researchers at Children's Hospital of Philadelphia investigate how mRNA vaccines could treat C. diff, and they develop a new understanding of CRISPR/Cas9 gene editing tools. Scientists presented cutting-edge psychosis research at the Lifespan Brain Institute (LiBI) Symposium, and a new grant equips nurses to administer firearm safety interventions.

Serum Cytokine Panels Inform Patient Management in Real Time

Researchers from CHOP are uncovering new ways to harness the information derived from serum cytokine panels to help improve the treatment and management of certain diseases.

Cytokines are signaling proteins that regulate inflammation and coordinate immune responses. Although typically panel results can be returned within five to seven days, researchers studied the impact of this biomarker information when received in real time within 24 hours. For diseases with symptoms that may present similarly, such as COVID-19 and multisystem inflammatory syndrome in children, a cytokine panel could reveal the difference more quickly and inform the appropriate course of treatment.

The team's study results published in the Journal of Allergy and Clinical Immunology found that cytokine panel analysis changed or informed diagnosis in 18.8% of reviewed cases, and it changed or informed management of the patient in 29.8% of cases.

"The results of a cytokine panel could potentially save lives, supporting antibiotics or immune suppression, but only if we have the results fast enough," said senior study author Michele Lambert, MD, Associate Clinical Director of the Frontier Program in Immune Dysregulation and an attending physician in the Division of Hematology at CHOP. "The evolution of our response time and our understanding of the value of these biomarkers demonstrates how important it is for clinicians and clinical laboratories to collaborate to provide the best care possible for patients."

Learn more in this CHOP news release.

Early Research Shows mRNA Vaccine Treats, Prevents C. diff in Disease Models

Successful results from a CHOP and Penn-led preclinical study that analyzed the efficacy of a mRNA-lipid nanoparticle vaccine to treat Clostridioides difficile (C. diff) will pave the way for clinical trials in humans.

"C. diff can persist in multiple forms in the gut, including in biofilms and as an incredibly hardy spore, making it uniquely difficult to treat," said Joseph Zackular, PhD, Co-director of the Center for Microbial Medicine at CHOP and an assistant professor of Pathology and Laboratory Medicine at CHOP and Penn. "This work represents how collaboration between vaccine researchers and basic scientists can transform new discoveries into potential therapeutics faster than ever before."

Antibiotics are not always effective when treating pathogens like C. diff, which can cause symptoms ranging from diarrhea to deadly colon damage. Thirty to 40% of patients will likely experience re-infection. The mRNA vaccine under development, in addition to promoting a strong immune response that eliminates existing C. diff bacteria in the gut, does not harm the healthy microbiota that co-exist alongside it.

The findings were published in Science. Find out more in this CHOP news release.

Lifespan Brain Institute's Annual Symposium Spotlights ‘Pathways to Psychosis'

Lifespan Brain Institute Director Raquel Gur, MD, PhD, and Michael Gandal, MD, PhD, highlighted how LiBI bridges the gap between pediatric and adult research.

The LiBI 2024 symposium, "Pathways to Psychosis", held this week at the University of Pennsylvania shed light on the breadth and depth of scientific inquiry across two research institutions. LiBI is a collaboration between CHOP and Penn's Perelman School of Medicine with a mission to bridge the gap between pediatric and adult research.

The partnership allows for researchers to begin studying participants at a young age and to continue to follow them into adulthood. LiBI's Philadelphia Neurodevelopmental Cohort includes a population-based sample of over 10,000 individuals from the greater Philadelphia area, ages 8 to 21 years old, who received medical care at CHOP's Pediatric Network. 

"Most of the mothers in our studies deliver at Penn, and their kids become patients at CHOP, so we have records of the mothers, the kids, and we follow them into adulthood," said LiBI Director Raquel Gur, MD, PhD. "This offers us a unique dataset, which doesn't exist at other institutions, and we are able to learn a lot."

Presenters at the symposium included:

Michael Gandal, MD, PhD, the William and Noreen Hetznecker Associate Professor at LiBI, who highlighted how genomics research is revealing new genetic and environmental risk factors for schizophrenia.

Daniel Wolf, MD, PhD, an Associate Professor at Penn, shed light on new functional neuroimaging techniques that are revealing the neural architecture of early psychosis.

Jorge Alvarez, PhD, an Associate Professor at Penn, explained how the blood-brain barrier — a layer of cells that defends the brain from toxins — is impacted during neuropsychiatric disorders.

Monica Calkins, PhD, a Professor at Penn, presented on the current and future directions in identifying and intervening psychosis in patients.

Study Reveals CRISPR/Cas9 Genome Editing Mechanics

CHOP researchers gained a deeper understanding of CRISPR/Cas9, a revolutionary genome editing tool, that could lead to improved CRISPR-based gene therapies in the future.

CRISPR/Cas9 scans the human genome for typos and uses "molecular scissors" to snip out and replace those errors with healthy DNA. However, a significant barrier in using CRISPR gene editing is off-target DNA cleavage, which occurs when the molecular scissor alters the wrong section of the genome.

"We always had a suspicion that the existing structures of Cas9 were not telling us the whole story, specifically with respect to on-target versus off-target DNA sequences," said senior study author Nikolaos Sgourakis, PhD, Associate Professor in the Center for Computational and Genomic Medicine at CHOP.

To address this problem, Dr. Sgourakis and a team of researchers used nuclear magnetic resonance spectroscopy to better understand the basis of on-target and off-target DNA recognition from a fundamental molecular standpoint.

The advanced imaging techniques allowed Dr. Sgourakis and his colleagues to directly visualize atoms, proteins, and their dynamics. Their analysis showed that there are multiple transitions that must happen for CRISPR to progress from an "inactive" to an "active" state, and these intermediate steps in the gene editing process serve as checkpoints to detect the presence of DNA mismatches.

The preclinical results were published in the journal Cell Chemical Biology. Read more in this CHOP news release.

New Grant to Promote Secure Firearm Storage Interventions

The National Institute of Nursing Research awarded researchers from the University of Pennsylvania School of Nursing $3.2 million over five years to fund research that will be conducted at CHOP to help keep children safer from firearm injury by promoting secure firearm storage.

"Children's hospitals are uniquely positioned to play a role in promoting firearm safety," said co-investigator Joel Fein, MD, MPH, Co-director of the Center for Violence Prevention. "Through the trusted relationship between nurses and our patients' families, we hope to make a positive impact on their safety and well-being."

The intervention, called S.A.F.E. Firearm, involves a brief discussion with parents about secure firearm storage and offers free cable locks. It will be adapted for nurses to deliver in a pediatric inpatient setting, and it includes topics such as firearm safety behaviors. The study team plans to collaborate with parents on the design of the implementation approach, and nurses will have the opportunity to share their perspectives on the intervention adaptation.

Twelve medical-surgical units at CHOP Philadelphia and King of Prussia campuses will be randomized to the adapted intervention or the usual care group to test the effectiveness of the intervention.

Read more in the Penn Almanac.

Identifying Healthcare Point of Entry Could Improve Concussion Recovery

Researchers investigated how individual-level and community-level characteristics may influence where a pediatric patient with a concussion enters the healthcare system: the emergency room, primary care, or specialty care.

Individual characteristics may include insurance type, whereas community-level characteristics are detailed in the Child Opportunity Index, which measures quality of access to safe housing and healthy foods among other factors.

The broad data published in JAMA Network Open indicates that 27.2% of patients were initially seen in the specialty care setting, 53% in the primary care setting, and 19% in the emergency department. Findings indicated that those with public insurance and non-Hispanic Black patients were significantly more likely to first seek care in the emergency department compared to specialty care.

"Being able to adequately describe the significant differences we found in this study is a critical first step to addressing health equity in pediatric concussion." said lead study author Daniel Corwin, MD, Associate Director and Emergency Department Lead of the Minds Matter Concussion Program at CHOP.

Individualized rehabilitation regimens have been shown to improve recovery when prescribed early, but it may be difficult for emergency department clinicians to provide personalized recommendations.

The study suggests equipping emergency medicine personnel with tools and training to better tailor concussion management to the individual could be the next step in improving health equity in pediatric concussion.

Learn more in this CHOP news release.

ICYMI

Catch up on our headlines from our Oct. 25 In The News:

• CHOP Hematology Chief Elected to National Academy of Medicine
• Accessible Entrepreneurship Training Critical to Patient-centered Innovation
• Study Highlights Genetic Links Between Childhood Speech and Language Disorders
• CHOP and Vanderbilt Scientists Lead Creation of Novel Kidney Disease Research Tool
• CHOP Researchers Highlight Role of Alternative Splicing in Chemotherapy Resistance
• Improving Risk Prediction During Adolescent Outpatient Screenings
• Mitigating the Effects of Climate Change on Pediatric Health
• Morgan Center Construction Highlighted in Trade Publication

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