Patellar Sleeve Fractures, Center of Excellence, Opioid Use, Foerderer Awardees

 

This week's news highlights innovative projects and collaborative spirits as we celebrate the awardees of the Foerderer Grants and CHOP's designation as a Center of Excellence for telomere biology disorders. A new study more accurately measures the impact of caregiver support on anxiety and depression in both LGBTQ+ and non-LGBTQ+ youths. Read on to find out more.

Surgery to Repair Patellar Sleeve Fractures Helps Restore Range of Motion

Brendan Williams, MD

Researchers from the Division of Orthopedics found that surgery was most effective for restoring full range of motion for pediatric patients with patellar sleeve fractures (PSFs), which occur when a piece of bone and cartilage separates from the kneecap. The results were published in the Journal of Pediatric Orthopedics.

"These observations help us to understand this unique type of injury and provide patients and families more accurate counseling about what to expect when undergoing treatment," said Brendan Williams, MD, an attending pediatric orthopedic surgeon with the Division of Orthopedics and Sports Medicine and Performance Center at CHOP. "We will continue to evaluate these issues in larger cohorts of pediatric patients to help patients and their families find the safest and most efficient means of restoring their normal knee function."

PSFs usually appear in developing male adolescents who participate in high-impact sports such as basketball, but can also result from accidents like falling off scooters. Researchers retrospectively reviewed 38 patients and determined that those who received surgery to treat their PSF regained the ability to straighten their legs and returned to their sport on average just over four months from surgery. Although more than a quarter of patients experienced a postoperative complication, most were minor, and 8% required unplanned surgery.

Learn more in this CHOP news release.

CHOP Designated as Center of Excellence for Telomere Biology Disorders

Team Telomere, an organization that provides community and support to people affected with dyskeratosis congenita and other telomere biology disorders (TBDs), designated CHOP as a Tier 1 Center of Excellence for TBDs, due to their outstanding contributions to advocacy, research, and comprehensive care for those living with TBDs.

"Telomere biology disorders present a multitude of devastating challenges to affected patients and families," said Timothy Olson, MD, PhD, director of Research for the Comprehensive Bone Marrow Failure Center. "These challenges transcend disciplines and cut across the age spectrum from infancy to adulthood. CHOP's designation as a first tier center of excellence for the treatment of patients with TBDs reflects the reality that we are one of only a few pediatric centers globally that has the necessary multispecialty expertise and dedication to help patients overcome these challenges."

TBDs result from a genetic mutation that causes premature or faster shortening of the caps on chromosomes, called telomeres. When a telomere is too short, it signals the cell to stop dividing and passing on genetic information. Patients with TBDs experience impaired organ function and failure over time, and the organ systems most affected include bone marrow, blood, and skin.

As part of the Team Telomere Centers for Excellence, CHOP will have access to and join a collaborative network of other centers dedicated to sharing best practices and improving patient care. With this designation, they are recognized as research leaders in the TBDs field.

Congratulations to Dr. Olson and his multidisciplinary team of expert physicians!

Study Reveals Some Youths May Take Opioids Months After Surgery

A new multi-institutional study underscored the need for establishing a standard of care for patients who undergo procedures that require an opioid prescription and identifying patient risk factors for persistent opioid use. The findings were published in JAMA Network Open.

"Our study found that patients are still filling prescriptions that are either not recommended or are in excess of what they may need," said first study author Tori Sutherland, MD, MPH, an attending anesthesiologist in the Department of Anesthesiology and Critical Care Medicine at CHOP. "They are also filling prescriptions up to two weeks before surgeries not associated with severe preoperative pain, putting young patients at risk for developing persistent use throughout their lives as they transition into adulthood."

Using a national insurance database of privately insured patients, researchers looked at patients between the ages of 11 and 20 who underwent 22 surgical procedures that were either common or associated with severe postoperative pain requiring opioids for initial pain management. Of more than 100,000 patients, 46.9% of patients filled a prescription for opioids, and 3% of patients were still filling opioid prescriptions three to six months after surgery.

Researchers also found severe pain following a surgical procedure was not associated with persistent opioid use. Patients with pre-existing chronic pain, who often underwent procedures associated with mild or moderate pain that could be managed with non-opioid medications, had increased odds of developing persistent opioid use.

Learn more in this CHOP news release.

Foerderer Grants to Fund 11 Innovative, Internal Projects

CHOP awarded Foerderer grants to 11 researchers to support ongoing basic, translational, and clinical research projects. The grants encourage collaboration between different groups across the institution with the goal of developing new and productive research avenues or applying novel techniques to existing investigations.

• Alicia Alcamo, MD, MPH, Department of Anesthesiology and Critical Care Medicine – "Identifying Anticholinergic Exposure as a Modifiable Risk Factor for Acute Brain Dysfunction During Sepsis"
• Marita Cooper, PhD, Department of Psychiatry – "Too much, not enough, or just right: Understanding feeling full in youth with ARFID or gastrointestinal conditions"
• Brian Dulmovits, MD, PhD, Division of Neonatology – "Multiomic and metabolic profiling of the hematopoietic niche in full term and preterm neonates"
• Kandace Gollomp, MD, Division of Hematology – "Targeting NETs to improve neurocognitive outcomes in sepsis"
• Valentina Graci, PhD, Department of Pediatrics – "Return to driving among teen drivers after ACL reconstruction surgery"
• Alex Holdaway, PhD, Department of Psychiatry – "Developing a Patient-Centered Preference Gathering Tool for Treatment Engagement Interventions"
• Guillem Pascual-Pasto, PhD, Division of Oncology – "Hijacking tumor-secreted immunosuppressive factors to enhance CAR T-cell therapy against retinoblastoma"
• Carlyn Patterson Gentile, MD, PhD, Division of Neurology – "Implications of restricted visual diet on symptom burden in youth with migraine"
• Muhammad Saleh, PhD, Division of Radiology – "Brain chemistry of individuals with Leigh Syndrome"
• Sesh Sundararaman, MD, PhD, Division of Infectious Diseases – "The effects of sickle cell disease modifying agents on malaria infection"
• Christopher Thom, MD, PhD, Division of Neonatology – "Enhancing blood formation with functional genomics."

The recipients may receive up to $50,000 in funding over one year. Their projects are designed to result in preliminary data that will support extramural funding applications.

Congratulations to all!

Antioxidants May Reduce Mitochondrial Damage From SARS-CoV-2 Virus

Preclinical findings published in Proceedings of the National Academy of Science suggest mitochondrially-targeted antioxidants could reduce the effects of the SARS-CoV-2 virus while avoiding viral gene mutation resistance.

Researchers from CHOP sought to inhibit mitochondrial reactive oxygen species (mROS) to see if they could block the metabolic processes required for viral synthesis. The SARS-CoV-2 virus disrupts how mitochondria generate cellular energy and increases mROS, which leads to a shift from energy production to viral substrate production. The increased mROS also damages the mitochondrial DNA (mtDNA) which is released into the cytosol to activate the inflammatory systems.

"We believe that reducing mROS represents a superior strategy for mitigating the pathogenicity of SARS-CoV-2," said senior study author Douglas Wallace, PhD, director of the Center for Mitochondrial and Epigenomic Medicine. "The virus is constantly mutating its 'S' protein gene to evade immunity induced by current anti-S vaccines. By modulating cmROS levels, we are rendering the host cell unfavorable for viral life cycle which the virus cannot change."

Studying an animal model expressing human ACE2 gene — which permits SARS-CoV-2 cell infection — researchers analyzed the effects of antioxidant enzymes, mitochondrially-targeted catalase, and the mitochondrially-targeted catalytic antioxidant compound EUK8. Results indicated that inhibiting mROS production reduced the negative effects of viral infection such as weight loss, clinical severity, and circulating levels of mtDNA, in addition to reduced lung levels of HIF-1α, viral proteins, and inflammatory cytokines. Mitochondrial oxidative phosphorylation increased in the lungs, a key process by which mitochondria generate cellular energy.

Learn more in this CHOP news release.

Penn Health-Tech Awards Accelerator Grants to Six CHOP Teams

Penn Health-Tech awarded six CHOP-based research teams with Health Tech Accelerator grants designed to empower innovators to develop transformative devices and technologies. The winning teams represent approximately 15 departments, divisions, and research programs at CHOP, demonstrating the success of multidisciplinary collaboration at the Research Institute.

The projects include:

• AMP-Vent: Rodrigo Menezes Forti, PhD; Todd Kilbaugh, MD; and Katie Weeks: "High-tech, low-cost ventilation for austere environments and underserved communities"
• Cranio Care: Alexander Tucker, MD; Shu Yang, MD; and Jordan Swanson, MD: "A single-stage bioresorbable craniofacial distractor"
• MENDing the Eardrum: Riccardo Gottardi, PhD; Narintadeach Charoensombut, PhD; John Germiller, MD, PhD; and Dana Ragbirsingh, MS: "Decellularized cartilage for tympanoplasty"
• NOM: Rodrigo Menezes Forti, PhD; Katie Weeks; Todd Kilbaugh, MD; Wesley B. Baker, PhD; and Tiffany S. Ko, PhD : "Noninvasive neurometabolic optical monitor to improve pediatric brain health"
• RadHawk: Janet Reid, MD, FRCPC, MSEd; Julian Lopez Rippe, MD, MSc; Ami Gokli, MD, MSEd; Michael Francavilla, MD; Manasa Ramanjana Reddy; Susan Sotardi, MD, MSEng; Michael Welsh, BSc: "RADHawk™: An AI-Based Radiology Expert Advisor"
• ZeoDrop: Stefanie Modri MSN, RNC-MNN, C-OB: "POC device to accurately and quickly determine birth blood loss."

The Penn Health-Tech Accelerator program is a year-long, cohort-based program that provides support through advising, funding, education, and resource connection to help innovators attract further financial support toward commercialization goals.

Congratulations to the winners!

Study Underscores Role of Caregiver Support in LGBTQ+ Youth Mental Health

Researchers from CHOP and the Perelman School of Medicine at the University of Pennsylvania conducted a study of 60,226 adolescents between the ages of 13 and 19 to measure the impact of family support on both LGBTQ+ and non LGBTQ+ adolescents with depression and anxiety. The findings were published in JAMA Pediatrics.

Researchers used The Adolescent Health Questionnaire — developed and piloted by the Possibilities Project consisting of pediatricians; researchers at Clinical Futures, a CHOP Research Institute Center of Emphasis, and technology experts at CHOP — to screen adolescents pre-visit. While most youth reported parent and caregiver support, fewer LGBTQ+ youth reported parental support. LGBTQ+ youth who did report parental support saw lower rates of depression and suicidal thoughts and significantly reduced rates of attempted suicide.

"This study builds upon our understanding of the prevalence of depression and suicide among LGBTQ+ youth," said senior study author Sarah Wood, MD, MSHP, an attending physician in the Division of Adolescent Medicine and member of Clinical Futures at CHOP. "As pediatric health systems, we need broader efforts to train pediatricians to provide affirming care and increase funding for nurse navigators and social workers to facilitate more frequent follow-up for youth with depression."

Read more about the study in this CHOP news brief.

ICYMI

Catch up on our headlines from our July 5 In The News:

• Key Clinical Trial Results Support New Treatment Option for Eosinophilic Esophagitis
• Ophthalmology Research Contributes to Image-based ROP Grading Scale
• Investigators Discover Molecule's Mechanistic Role in Insulin Regulation
• Improving Concussion Intervention and Treatment for Young Patients
• Researchers Develop Innovative Approach for Alpha Thalassemia
• CHOP Awarded AWS Grant to Accelerate Brain Tumor Research
• Research Experiences Program Mentors Future Injury Science Professionals

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