CHOC awarded $2.3-million grant to study how toxic stress and unpredictability in the early environment affects neurodevelopment

The state of California has awarded CHOC, in partnership with UC Irvine and Chapman University, a $2.3-million grant to screen patients for adverse childhood experiences (ACEs) and childhood unpredictability to assess how such high-stress events affect the brain and put kids at increased risk of later developing physical and mental illnesses.

In a novel aspect of the study, researchers also will determine if there are epigenetic markers on the DNA that predict whether any given child will be more adversely affected than another.

The team is among four awardees statewide that have been given a total of $9 million to assess which children are most vulnerable to the effects of ACEs and unpredictability in the home environment, and to design medical care to improve the outcomes for this particular group of patients – a model known as “precision medicine,” which eschews a one-therapy-fits-all approach to healthcare.

“The whole concept here is that kids who grow up in environments with frequent exposures to toxic levels of stress can have all kinds of internal things happen in their bodies related to prolonged or extensive stress hormone response – their brains can develop differently, and when they become adults, research has shown that they have a higher risk of developing medical conditions such as heart disease, asthma and cancer,  among other physical diseases, as well as mental disorders,” says Dr. Charles Golden, a co-investigator on the study and executive medical director of the CHOC Primary Care Network (PCN).

Dr. Charles Golden, executive medical director of the CHOC Primary Care Network (PCN)

The California Governor’s Office of Planning & Research, in partnership with the Office of the California Surgeon General, awarded the three-year research project as part of the California Initiative to Advance Precision Medicine (CIAPM). The other three recipients were Children’s Hospital Los Angeles, University of California, San Francisco, and Loma Linda University.

The CHOC-UCI-Chapman research project begins in July 2021, with screening expected to start in CHOC PCN clinics by November 2021. Lead principal investigator on the project is Dr. Tallie Baram, Bren Distinguished Professor and director of the Conte Center at UCI. The National Institute of Mental Health-funded Conte Center also addresses how early-life experiences influence the brain and contribute to mental illnesses.

Results of the study are expected by the end of 2024, says Laura Glynn, PhD, a Professor of Psychology and Associate Dean for Research at Chapman University and one of the principal investigators on the study.

CHOC’s PCN has been screening its Medi-Cal patient population for ACEs since February 2020, and expanded such screening – using a tool called PEARLS, for Pediatric ACEs and Related Life Events Screener – to all patients in November 2020, Dr. Golden says.

The 17-question PEARLS tool screens for such experiences as a parent being jailed, the prevalence of alcohol or drug abuse in the household, and whether the child has been a victim of violence in his or her neighborhood, in the community at large, or at school.

“This existing infrastructure at CHOC was a very important part of the application for this grant,” Glynn says.

The CHOC-UCI-Chapman study, “Using Precision Medicine to Tackle Impacts of Adverse and Unpredictable Experiences on Children’s Neurodevelopment,” will dig deeper than standard PEARLS screening.

The children will be asked an additional five questions to assess exposure to unpredictability in the social, emotional, and physical domains. Such questions are an attempt by researchers to develop an instrument that will predict this population of kids’ resilience to, or risk of developing, physical or mental illnesses. Children from low socioeconomic and racial/ethnic minority communities are at greater risk of exposure to ACEs.

“This study will involve looking at whether routine, or lack of routine, in a child’s life contribute as an ACE,” Dr. Golden explains. “In other words, do they eat dinner every night at 6 p.m., do they have a routine bedtime, do they have a stable household versus a family with no routine or little structure.”

Such factors of unpredictability potentially are amenable to intervention, Glynn notes.

Emerging evidence from experiments with rodents show that fragmented or unpredictable maternal signals influence the maturation of systems governing emotional and cognitive function in the developing brain. In preclinical work led by Dr. Baram, the group has shown that rats exhibited diminished memory function when exposed to unpredictable maternal signals early in life, as well as anhedonia (reduced ability to experience pleasure) beginning in adolescence.

Also, as part of the study, DNA swabs will be performed on a cohort of 120 children who experience high levels of ACEs to determine if genetic expression patterns indicate a vulnerability to chaos and unpredictability in their lives. The team also will be examining whether epigenetics – the process of how genes may be altered based on environmental events – may play a role in the development of ACE-related medical conditions.

“We think potentially we can look at these epigenetic profiles to predict neurodevelopmental outcomes,” Glynn says.

Dr. Michael Weiss, vice president of population health at CHOC and a primary investigator on the study, says such information may make it easier for doctors to identify a child who has a genetic predisposition to experiencing a bad outcome from being exposed to ACEs – thus leading to targeted interventions to kids who need them the most.

“This project is a great demonstration of a collaboration between CHOC and UCI and Chapman University involving primary care research,” Dr. Weiss says.

Other CHOC researchers who will participate in the research project are Dr. Dan Cooper, who treats kids with lung conditions at CHOC and who serves as director of UC Irvine’s Institute for Clinical & Translational Science; Dr. Candice Taylor Lucas, co-director of LEAD-ABC (Leadership Education to Advance Diversity–African, Black and Caribbean) at UCI/CHOC; Louis Ehwerhemuepa, PhD, a senior data scientist; and Dr. Mary Zupanc, co-medical director of the Neuroscience Institute.

CHOC-UCI Pediatric Urology study illustrates how COVID-19 delayed emergency care

CHOC’s pediatric urology team, in a partnership with UCI Health, has published the largest study of its kind on an emergency condition that afflicts young males, adding to the emerging body of data on how the COVID-19 pandemic has caused patients to delay seeking emergency treatment.

The CHOC/UCI-led study, recently published in the Journal of Pediatric Urology, also marks a first for the Western Pediatric Urology Consortium (WPUC), a group of several leading pediatric healthcare centers that CHOC was instrumental in founding in 2020.

“This study is a good example of CHOC leading the way and bringing together institutions to answer questions that haven’t been answered before,” says Carol Davis-Dao, PhD, a clinical epidemiologist in CHOC’s Department of Pediatric Urology who has a joint appointment in the UC Irvine Department of Urology.

Dr. Davis-Dao leads urology research efforts at CHOC to provide patients and their families with the most current, evidence-based diagnoses and treatments.

The lead author of “A Multicenter Study of Acute Testicular Torsion in the Time of COVID-10,” Dr. Sarah Holzman, a research fellow at UCI-CHOC, says the research paper is the only multicenter urology study and the largest one related to torsion and COVID-19. Most importantly, she adds, it’s the only study that shows patients were delaying presenting to the Emergency Department for testicular torsion.  

The study’s key finding: Patients significantly delayed seeking treatment in the Emergency Department following the onset of symptoms of a testicular torsion during the early months of the pandemic, and, as a result, more of them had to have a testicle removed compared to patients with the same condition who sought care before the pandemic.

“This is the largest study of testicular torsion during COVID-19 and the first to show a significantly longer time from symptom onset to presentation (in the Emergency Department),” the paper states.

“Low baseline awareness of torsion may contribute to delays in care that were present even before the pandemic, making patients and their families less likely to present for emergency care during the pandemic when there is concern for exposure to COVID-19.”

Also participating as authors of the study were CHOC pediatric urologists Dr. Heidi Stephany, Dr. Kai-wen Chuang, Dr. Elias Wehbi, and Dr. Antoine Khoury, chief of pediatric urology at both CHOC and UC Irvine Medical Center. 

Testicular torsion occurs when the spermatic cord that supplies blood to the testicle twists, cutting off the testicle’s blood supply. It presents as acute and severe scrotal pain that quickly worsens, as well as nausea and vomiting.

Testicular torsion occurs when the spermatic cord that supplies blood to the testicle twists, cutting off the blood supply.

It’s a relatively rare surgical emergency, with an incidence rate of around 4 per 100,000 males per year in the United States. It most frequently occurs in males between the ages of 10 and 19, with one peak in the neonatal period and the second peak around puberty.

Surgery is required for all patients with testicular torsion.

When torsion is caught early — typically within the first six hours — a detorsion orchiopexy can be performed. In the detorsion surgery, the spermatic cord is untwisted and the blood flow returns to the testicle. The surgeon then secures the testis to the inner scrotum so it can never twist again. However, if patients delay coming to the hospital and the testicle does not have blood supply for several hours, the testicle may have to be removed in a procedure called an orchiectomy.

The CHOC-UCI led study involved a total of 221 patients enrolled at one of seven hospitals in the WPUC (CHOC, Children’s Hospital Los Angeles, Seattle Children’s, UC San Francisco, UCLA, UC San Diego and Western University in Ontario, Canada).

A total of 84 patients with testicular torsion, ages 2 months to 18 years, made up the first cohort. They were studied from March 2020 through July 2020.

The second cohort totaled 137 patients who were treated from January 2019 through February 2020.

The median time it took patients in the COVID-19 cohort to show up at the Emergency Department from the onset of symptoms was 17.9 hours, the study found. This compares to 7.5 hours for patients in the pre-pandemic cohort.

A total of 42 percent of patients in the COVID-19 cohort underwent an orchiectomy (removal of the twisted testicle), compared to 29 percent in the pre-pandemic population.

Distribution of patterns in acute testicular torsion presentation by month of the COVID-19 pandemic. Blue bars represent rate of orchiectomy by month, while the navy-blue line represents median time from onset of symptoms to presentation by month.

Other studies have shown that COVID-19 has caused people to delay Emergency Department treatment, including one that examined acute appendicitis from the New York metropolitan region and another similar study in Virginia.

During the last week of June 2020, 41 percent of U.S. adults admitted to avoiding medical care because of COVID-19 exposure concerns and 12 percent avoided urgent or emergent care, according to the Morbidity and Mortality Weekly Report, an epidemiological digest for the United States published by the Centers for Disease Control and Prevention.

Drs. Holzman and Davis-Dao say they plan to continue the study as the pandemic progresses.

Read more about CHOC’s Department of Urology.

CHOC leads first ED study on adverse childhood experiences and prevalence of food and housing insecurity

In the only known hospital research project of its kind in the United States, CHOC’s Emergency Department is leading a study on how food and housing insecurity impacts children’s health and environment.

The project, being conducted in collaboration with departments at UC Irvine and Chapman University, involves surveying 7,000 CHOC ED patients by September 2021, with results expected by the end of the year, says Dr. Theodore Heyming, medical director of emergency medicine at CHOC and chief architect of the effort.

Dr. Theodore Heyming, medical director of emergency medicine at CHOC

The study, which to date already has enrolled some 2,500 CHOC patients, will assess ACEs, also known as adverse childhood experiences. Most ACEs studies conducted to date by other hospitals have been limited to the primary care setting. Since July 2020, CHOC’s ED has been screening for ACEs with particular attention to the following three areas: abuse, neglect, and/or household challenges. 

“To my knowledge, we’re the only pediatric hospital that has this kind of health research project implemented in an emergency department,” Dr. Heyming says. And that makes sense, he adds.

“People don’t usually think of an emergency room as a primary care setting,” Dr. Heyming says. “However, the opposite actually is true. A lot of patients use the ER as their primary care. EDs also have the ability to potentially intervene on patients even to a greater extent than in the primary care setting, given the availability of experienced social workers.”

The potential benefits of the study, which involves questioning patients in more depth than standard ACEs screenings, are numerous, as detailed in an abstract that Dr. Heyming and his collaborators have submitted to the American Public Health Association (APHA), a Washington, D.C.-based organization for public health professionals.

For example, ED-based research has yet to investigate the extent to which neighborhood-level factors such as fast-food accessibility and a lack of healthy food options contribute to poor pediatric health outcomes.

The CHOC-led study aims to identify such neighborhood-level factors and generate valuable information that could be leveraged for public policy and advocacy efforts to improve pediatric health. That, in turn, could lead to a reduction of ED overutilization and associated healthcare costs.

Disadvantaged kids hit hardest

Food and housing insecurity disproportionately impact children in disadvantaged communities, studies show.

And children living in so-called “food swamps” — areas with an abundance of fast-food restaurants, pharmacies and discount stores that sell cheap but unhealthy food — as well as “food deserts,” areas that lack affordable food that is fresh and nutritious, are more at risk of obesity, diabetes and other adverse health conditions, as well as mental and behavioral issues and trauma, the paper explains.

The study of 7,000 CHOC ED patients comes on the heels of a smaller CHOC ED study on the prevalence of ACEs in patients that was conducted between July 2020 and February 2021. Twenty-four CHOC ED doctors were certified in state-run ACEs modules and 1,861 patients participated – the biggest cross-sectional survey that CHOC has done to date, according to Dr. Heyming.

About 20 percent of respondents in that smaller-scale survey reported at least one ACE or more — a percentage consistent with national numbers, Dr. Heyming says. In addition, the survey found that the prevalence of food insecurity among CHOC patients is about 15 percent. 

Now, in partnering with Chapman University and UCI, CHOC is digging deeper into the prevalence of food and housing insecurity with its study of 7,000 patients — and the potential neighborhood-level factors that contribute to such insecurity.

Dr. Jason Douglas, an assistant professor of public health at Chapman University, specializes in investigating social and environmental determinants of public health disparities that disproportionately impact the Black and Latinx communities. 

Dr. Douglas, who has extensive experience connecting social and environmental factors to public health disparities in Los Angeles County as well as Northern California, New York and Jamaica, will use data from the 7,000 survey respondents to analyze neighborhood-level factors that contribute to poor pediatric health.

“The goal is to identify factors that are affecting community health and well-being and inform public policies to improve health in underserved communities,” Dr. Douglas says. “To be able to identify adverse childhood experiences and food and housing security within the clinical context and use that data to garner a better understanding of how social and environmental factors may be exacerbating health disparities will allow us to develop a more holistic understanding of the deleterious impacts of these challenges on children’s lives.”

At UCI, Dr. Victor Cisneros, an emergency medicine clinical instructor and current research fellow in population health and social emergency medicine, will lead a team of investigators who will participate in follow-up phone calls with the CHOC ED survey respondents. The follow-up interviews will be conducted three and six weeks after respondents complete the survey.

“These follow-up interviews are important to assess if interventions given in the ED are effective, and if not, what barriers our patients are facing,” Dr. Cisneros says.

All CHOC ED patients up to 18 years of age and their parents or guardians qualify as potential participants in the survey, which is available in English and Spanish. The survey includes 16 questions that take about 5 to 10 minutes to complete on iPads provided by CHOC.

Patients identified as experiencing food and/or housing insecurity are directed to passive food and housing resource materials in the form of informational pamphlets and flyers.

“We’re going to potentially be able to leverage this data to help cities and the county to make informed policy changes,” Dr. Heyming says. 

“Obtaining this information will not only be great for Orange County,” he adds. “I think we’ll be able to point to the fact that pediatric EDs are a great place to conduct these screenings because there’s a high incidence of either adverse childhood experiences or food or housing insecurity.”

Dr. Heyming says pediatric EDs in the future would be able to provide patients more active resources such as gift and food cards.

Dr. Douglas says the study ideally will serve as a model for pediatric and other emergency departments across the country.

The bottom line, Dr. Cisneros says, is getting people resources they need – for example, food that restaurants now dispose of that can be “recycled.”

The ED, he says, is a perfect microcosm of the community.

“One of the beauties of this study,” Dr. Cisneros says, “is we’ll be able to identify people with housing and food insecurity and be able to refer these people to the appropriate tailored resources. In addition, we will be able to further quantify what obstacles our patients face both at the individual and community level.”

CHOC surgeons thriving as productive researchers outside the operating room

CHOC surgeons are known for performing the latest procedures, no matter how complex, in areas including heart, trauma, gastrointestinal, urology and neurosurgery.

Outside the operating room, the seven physicians who make up CHOC’s pediatric general and thoracic surgery team also are excelling in another realm that is critical to CHOC’s mission of developing into one of the nation’s leading pediatric healthcare systems —

Research.

In the last five years, the surgery team has published some 35 papers, bolstered by recent new hires and a renewed commitment to dramatically transform CHOC from its roots as a community children’s hospital to an academic institution.

“It’s unprecedented in the history of pediatric surgery at CHOC – there’s no question about that,” pediatric surgeon Dr. Peter Yu says of the volume of research going on with his team.

“We are proud to be one of the most academically productive divisions at the hospital, and we have some impressive partners in other specialties here,” Dr. Yu says. He calls fellow pediatric surgeon Dr. Yigit S. Guner  the leader behind the recent flurry of research.

“The number of papers that we’ve published in the last several years would be something to be proud of at any children’s health system, even the ones that have a longstanding academic tradition,” Dr. Yu says.

Dr. Yu also cites two more recent hires as critical players: John Schomberg, PhD, a biostatistician in nursing administration and trauma, and Elizabeth Wallace, MPH, a clinical research coordinator in the trauma department in Research Administration.

Schomberg has been instrumental in the team’s research efforts, providing statistical expertise to help investigators, both experienced and new to research, formulate and refine their research questions, Wallace says.

“The research team’s accomplishments are due in large part to the progressive leadership of CHOC executives and the CHOC Research Institute for prioritizing research and providing support needed to make these research endeavors possible,” she adds.

“Though we rarely think of it when we’re waiting for our child to be seen by their physician, ultimately research is the foundation for providing our pediatric patients with leading, innovative and excellent care,” Wallace says. “This group’s research has potential to inform best practices, policy and advocacy that addresses the needs of our community and to advance pediatric care on a more global level. I’m excited to see what the future brings.”

Dr. Guner says conducting research is a central part of his effort to care for children. “We always strive to provide great care, but research raises the bar on what can be done to help our patients,” he says.

Three general areas

The research being conducted by doctors in CHOC’s pediatric general and thoracic surgery division falls into three general categories: general pediatric surgery, trauma and extracorporeal membrane oxygenation (ECMO), a critical care technology that can be used to bypass a failing heart or lungs.

One trauma study, expected to be submitted for publication in February 2021, looked at legal intervention — any injury sustained from an encounter with a law enforcement officer. While studies have been conducted in adults, none have focused on the pediatric population. Legal intervention as cause of traumatic injury in the pediatric trauma population is infrequent yet reported.

Schomberg, Wallace, Dr. Guner and Dr. Yu were among the researchers who examined the National Trauma Data Bank (NTDB) for health disparities related to legal intervention in the pediatric population.

The team’s key finding: Legal intervention in children disproportionately affects the African American population.

Of the 1,069,609 pediatric trauma patients identified in the NTDB, according to an abstract of their paper, 622 sustained injuries involving legal intervention. When these patients were compared to the general pediatric NTDB, they were more likely to be older, male and test positive for illegal drugs or alcohol.

They were more likely to be African American (44.37% vs 17%), Latino (22.82% vs 15.10%), or Native American (0.96% vs 0.94%).

Mortality was higher in trauma involving legal intervention than in the general pediatric trauma population (4.82% vs 1.11%,), particularly in African Americans (63.33% vs 36.66%). Understanding the issue can hopefully point to more effective strategies to minimize harm while protecting public safety.

Variety of research papers

Several of the pediatric general and thoracic surgery division’s research papers concern congenital diaphragmatic hernias (CDH), a rare birth defect in which a hole in the diaphragm allows the intestines, stomach, liver and other abdominal organs to enter the chest, impairing typical lung development.

In another research project in collaboration with St. Louis Children’s Hospital-Washington University and The Children’s Hospital of Philadelphia, Dr. Yu looked at the incidence and length of stay for pediatric appendicitis during the initial days of the COVID-19 pandemic.

Dr. Yu is also currently working on a model to predict a rare traumatic injury referred to as blunt cerebrovascular injury (BCVI) and an interactive web app that would allow a trauma team to better understand their patient’s risk for BCVI.

Dr. Mustafa Kabeer, a CHOC pediatric surgeon, has published work in trauma and neonatology as well as basic science research on the stress response following splenectomy in mice. Dr. Kabeer’s most notable work includes research on the pioneering use of newborn umbilical cords to repair congenital birth defects such as gastroschisis.

Dr. David Gibbs, director of trauma services at CHOC, has been a staunch advocate for research, pushing CHOC to become the leading institution for pediatric trauma research in Orange County while pursuing a Pediatric Level 1 Trauma Center designation.

Dr. Gibbs’ published work includes developing prediction models in the trauma population to better understand prolonged hospital stays and return visits to the emergency department, revisiting the practice of X-rays post chest tube removal, and trauma case reports.

A true team effort

Dr. Yu  says the surgeons in his division work as a team on many research projects.

“Just like you can be a great surgeon,” he explains, “if you go in to operate and you don’t have any anesthesiologists or a nurse or a scrub tech to hand you instruments, there’s only so much that you can do by yourself.”

Dr. Guner says he enjoys understanding as much as possible about the diseases that he treats, and that research is an ideal vehicle to deepen that understanding.

“I really respect people who come here to work and take care of patients – it’s a vital service that people need,” he says. “In addition, I’ve always felt that I really wanted to know about the diseases themselves. Conducting research allows me to contribute to my field and to society at large.”

Another important aspect of research, Dr. Guner adds, is that it helps residents.

“Part of their training is more than taking care of patients,” Dr. Guner explains. “Learning and research go hand in hand. Research makes residents more motivated to work with their mentors and gives them something to do in the early stages of their career by increasing the energy they devote to academia.”

Personalized medicine, surgical innovations advance pediatric brain tumor care

The Neuro-Oncology Treatment Program at the Hyundai Cancer Institute at CHOC is doing more than providing the most advanced care for pediatric brain tumors — it’s also helping to shape the future of personalized medicine and surgical innovations.

CHOC offers a full range of standard treatments for brain tumors, as well as personalized therapies for many tumor types, such as medulloblastomas, based on genetic subtyping. Experimental treatments are available through Children’s Oncology Group and other consortium and industry-driven clinical trials. Some of these studies — including a trial developed by a CHOC neuro-oncologist to investigate a vaccine for diffuse intrinsic pontine glioma — are part of CHOC’s robust early-phase clinical trials program, according to Dr. Chenue Abongwa, pediatric neuro-oncologist at CHOC.

Dr. Chenue Abongwa
Dr. Chenue Abongwa, pediatric neuro-oncologist at CHOC

CHOC also partners with some of the country’s foremost healthcare institutions, including Mayo Clinic, to apply the latest genomic sequencing and molecular studies in studying each individual tumor.

When a patient presents with a brain tumor, a wide range of specialists are involved from the beginning. “We have a multidisciplinary neuro-oncology tumor board that includes neurologists, neurosurgeons, neuroradiologists, radiation oncologists, pathologists and a neuro-oncologist, and we involve other specialists as needed,” says Dr. Abongwa. “This expertise allows us to select the treatment likely to be the best option for each child while minimizing the risk of side effects.”

Each patient at CHOC is treated via an individualized, precision medicine approach. When surgery is necessary, CHOC has four highly experienced, board-certified pediatric neurosurgeons who can apply some of the most advanced surgical capabilities. “We have the latest in surgical navigation, and we partner with neurologists at CHOC to offer surgical neuromonitoring to track certain nerve potentials during resections,” says Dr. Suresh Magge, medical director of neurosurgery at CHOC and co-medical director of the CHOC Neuroscience Institute. “If we’re operating near the brain stem, it’s important to know if there’s potential for damage in surrounding structures.”

Dr. Suresh Magge
Dr. Suresh Magge, medical director of neurosurgery at CHOC and co-medical director of the CHOC Neuroscience Institute

Several of the surgical therapies CHOC offers are minimally invasive alternatives to craniotomy. One example is endoscopic surgery, which may be appropriate for tumors located in the ventricles. Neurosurgeons can visualize and resect these tumors using an endoscope inserted through a small incision.

“Certain tumors, especially those located deep in the brain, are amenable to laser interstitial thermal therapy (laser ablation),” Dr. Magge says. “This has revolutionized the treatment of certain types of lesions. We can insert a catheter through a small incision down to the deep part of the brain and ablate the tumor without harming surrounding structures. A ROSA™ (robotic stereotactic assistance) robot allows us to insert the laser with a high degree of precision. Patients experience minimal blood loss and typically go home within a day.”

Once treatment concludes, patients ultimately enter the Neuro-Oncology Treatment Program’s longstanding late effects program. This multidisciplinary program provides long-term follow-up of patients and connects them with specialists who can treat endocrine, neurocognitive, psychosocial and other side effects of treatment.

“For some tumors, such as medulloblastomas, we’ve reached the point where we’re achieving good rates of cure, as high as 80% or more,” Dr. Abongwa says. “So now we’re focused on minimizing the long-term effects of treatment. Most institutions don’t have a strong, long-term follow-up program for pediatric patients. Over time, our program has become quite robust and multidisciplinary. That’s another area of benefit that we offer our patients. We’re a child- and family-focused institution. That focus is evident in all the programs and services that are available to our patients.”

Our Care and Commitment to Children Has Been Recognized

CHOC Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the cancer specialty.

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.

CHOC-UCI origami mask project gets some national attention

Back in the early days of the COVID-19 pandemic, in late March 2020, Jonathan Realmuto, a visiting scientist at CHOC and a postdoctoral researcher at UC Irvine, got a call from his lab leader, Dr. Terence Sanger.

Dr. Sanger, a physician, engineer, and computational neuroscientist who joined CHOC in January 2020 as its vice president of research and first chief scientific officer, was concerned about the possibility of CHOC running out of masks for its frontline healthcare workers.

“Could you please think about this problem and see if you can come up with a solution just in case the supply runs out?” Dr. Sanger asked Realmuto, who has a Ph.D. in mechanical engineering and whose expertise is wearable robotics, which help people regain and strengthen their movements.

Dr. Terence Sanger, chief scientific officer at CHOC

Since September 2017, the two had been working together after Realmuto earned his doctorate degree from the University of Washington.

Thus began the UCI Face Mask Project, a collaboration between Dr. Sanger and Realmuto that grew to a team of five that includes two other UCI professors, aerosol chemist Jim Smith and environmental toxologist Michael Kleinman, and Michael Lawler, an atmospheric chemist and assistant project scientist who works in Smith’s lab.

The work of the UCI Face Mask Project ultimately led to the creation of what experts call a mask for the masses — an inexpensive face covering that takes its cues from origami, the art of paper folding closely associated with Japanese culture.

No sewing is needed to make the origami mask – just a filter material that can be purchased at a craft or hardware store, a stapler, two elastic straps, and a nose clip fashioned from a metal wire such as a twist tie.

Illustrated directions for creating the origami mask

Realmuto was among several origami mask experts recently featured in a National Geographic story that highlights the inexpensive (less than $1 of materials per mask), disposal masks that can be made by anyone after a little practice. The story details how origami pleats and interlocking folds can result in better-fitting, more comfortable, and more stylish face coverings.

Dr. Sanger, who served in an advisory capacity on the UCI Face Mask Project, played a “very critical role” in developing the mask, which has not been mass produced but was designed in case there is a shortage of face coverings such as N95 masks, the gold standard at preventing expelled air leakage during coughing.

“CHOC and UCI were one of the first out of the gate to work on this,” says Realmuto, who with his colleagues has written a paper, “A Sew-Free Origami Mask for Improvised Respiratory Protection,” that details the research that went into the project.

The team put several masks through rigorous testing using a custom-made mannequin head equipped with a breathing tube and mounted inside a chamber.

The team concluded, in the paper they plan to get reviewed by peers and published, that origami masks combine high filtration efficiency with ease of breathing, minimal leakage that can dramatically reduce overall mask performance, and greater comfort compared to some commercial alternatives.

Because of this, origami face coverings are “likely to promote greater mask-wearing tolerance and acceptance,” the researchers concluded in their paper.

Says Realmuto: “Origami presents this really nice solution where you can use the folds as a way to make seams that won’t leak.”

The team produced a how-to video starring Realmuto, who shows how to construct the single-use masks. They tested a variety of materials that have an inner layer of non-woven polypropylene that can be easily and rapidly sourced locally from a hardware or craft store, in addition to a material made by Filti that can be purchased through the manufacturer.

“For a novice without prior experience,” they write, “construction takes approximately 10 minutes. In our experience, practice decreases assembly time to under five minutes.”

Dr. Sanger and Realmuto have collaborated on another unrelated project that earned them accolades. That project involved developing a non-rigid forearm orthosis – a brace to correct alignment or provide support – to help make it easier for people with movement disorders such as cerebral palsy to feed themselves, open doors, and complete other daily tasks. Their work made them finalists in the Best Paper category at the 2019 Institute of Electrical and Electronics Engineers (IEEE) Conference on Soft Robotics.

In July 2021, Realmuto will become a full-time assistant professor in the Department of Mechanical Engineering at UC Riverside. He says he hopes to maintain his collaboration with Dr. Sanger and CHOC on future projects.

“It’s been a great partnership,”Realmuto says.

For more information about the UCI Face Mask Project, click here.

CHOC clinicians pitch ideas for new medical devices to UCI students

In the neonatal intensive care unit (NICU) at CHOC, most pre-term babies are not able to take all their food through a bottle until they’re closer to term. They also must rely on a tube connected to a feeding pump.

In hospitals that have a centralized room where technicians prepare feedings for the nurse, the feeding is often delivered pre-drawn up in a syringe since it is unknown if all of the feeding will be given via the tube or if the baby will be able to take some by mouth.

If the baby is alert enough to eat by mouth, the nurse would need to transfer some of the feeding from the syringe to a bottle. If the baby did not take the full volume in the bottle, the nurse would need to draw any remaining milk back into the syringe to be able to deliver it via a tube.

Because of all these steps, there’s a risk of contamination, misadministration (giving the wrong milk to the wrong baby) and a loss of nutrients caused by milk adhering to the side of the containers.

Wouldn’t it be great to create a device that could solve those concerns and make feeding premature infants safer and more efficient?

That was the concept presented by Michelle Roberts, a registered nurse and lactation consultant, to UCI biomedical engineering graduates at the annual UCI BioENGINE Reverse Project Pitch Night.

Undergraduates students in the BioENGINE Program (Bioengineering Innovation & Entrepreneurship) obtain hands-on experience in the technical and business development aspects of biomedical engineering as they work in teams to further develop med-tech startups into marketable products.

Roberts was among several CHOC associates who gave two-minute presentations at the Fall 2020 Reverse Project Pitch Night, held online because of the COVID-19 pandemic. Kicking off the 90-minute session, which featured some 30 presenters, was Dr. Terence Sanger, a physician, engineer and computational neuroscientist who joined CHOC in January 2020 as its vice president of research and first chief scientific officer.

BioENGINE partners with the UCI School of Medicine, the Henry Samueli School of Engineering, the Donald Bren School of Information and Computer Sciences, the Beckman Laser Institute, UCI Athletics and UCI Applied Innovation. 

At Reverse Project Pitch Night, physicians, scientists, clinicians and industry representatives describe their concepts for new medical devices. Students are matched with projects that interest them and are mentored by the presenters to help develop healthcare solutions.

“Physicians and engineers need to work together,” said Dr. Sanger, a child neurologist who specializes in movement disorders. “The goal is to identify an important problem, marry it to a piece of technology, and create a device in a way that will have an impact. Different knowledges have to be brought together, and personally I find that very inspiring.”

In the final quarter of 2020, the CHOC Research Institute sponsored three pediatric-focused projects that were presented at Reverse Project Pitch Night.

One software project, presented by Sira Medical, involves the use of patient-specific, high fidelity 3D holograms to enable surgeons to better understand complicated anatomy, collaboratively plan an operation, and virtually size medical implants — all before stepping into the operating room.

Another project, presented by Adventure BioFeedback, is designed to deliver speech therapy anywhere, anytime. The company is producing a series of audio linguistic tools that can analyze and learn on-the-fly from the utterances of children performing vocal exercises using a smartphone. 

The third CHOC Research Institute-sponsored project, NeuroDetect, places a patient’s own stem cells on a computer chip to replicate the brain chemistry of the neurological disorder in a laboratory environment and facilitate rapid development of precision-guided therapeutics.  

Roberts offered to serve as a mentor on her project along with Caroline Steele, director of Clinical Nutrition and Lactation Services at CHOC. Edwards Lifesciences is involved in designing the device.

Kaitlin Hipp, another CHOC NICU nurse, introduced her project, Touche, at BioENGINE Reverse Project Pitch Night. It’s a hands-free communications system for nurses and healthcare workers that is especially relevant in the era of COVID-19. The Bluetooth device can communicate with several devices – phones, monitors, etc. — thereby reducing or eliminating the need for nurses to touch the surfaces of items.

“We need to be better about using touchless technology in the healthcare setting,” Hipp said. “Long term, think of this as Alexa for healthcare providers.”

Dr. Timothy Flannery, a pediatric endocrinologist at CHOC, introduced Cervos, a non-invasive device to address cervical incompetence, which affects 1 percent of all pregnancies. The goal is to get Cervos approved for clinical trials at medical schools, Dr. Flannery said.

Dr. Sanger, in his remarks, noted CHOC’s critical mission of ramping up research to better address unmet healthcare needs by marrying engineering with healthcare.

“Medicine is about decision making,” Dr. Sanger said. “Biology is so complicated we can’t hope to ever understand it fully. When you want to make decisions in healthcare, you need to take measurements and design interventions that will respond to those measurements. In medicine, the goal is always to make the next big decision. You don’t even need to know the diagnosis if you can make the right decisions.”

Innovating Toward a Cure: Smart Shunt Technology for Hydrocephalus

Shunts for hydrocephalus require an average of about 10 revisions during the patient’s lifetime. New innovations at CHOC aim to revolutionize shunt design to give patients more control in the management of this condition.

For the past few years, Dr. Michael Muhonen, pediatric neurosurgeon at CHOC, has been developing and refining a “smart shunt,” which allows families of children with hydrocephalus to measure intracranial pressure at home or determine if the shunt is failing. The shunt has a wireless sensor that communicates with a family’s smartphone-like device when held near their child’s head. If the sensor determines the pressure is too low, a magnet is used to manipulate the pressure. Another device within the valve allows the parent to potentially disocclude the shunt catheter if it’s plugged.

Dr. Michael Muhonen, pediatric neurosurgeon at CHOC

The technology received FDA approval last year, and it should be commercially available within one year.

“I have families who won’t go more than a few hours away from their pediatric neurosurgeon because of fear. If the shunt plugs up, what are they going to do?” Dr. Muhonen says. “Every neurosurgeon who treats hydrocephalus has a goal to make a simplified system for both the families and the doctor, and a system that saves future surgeries down the road. Having wireless technology so you can measure pressure with your smartphone would accomplish that. I’ll keep working on this until it happens.”

Smarter technology would also result in far fewer operations for patients.

“Some patients come in regularly with headaches, failures, broken and fractured shunts or calcium on the tubing; we follow them regularly and the chronically shunted patient has too many operations,” Dr. Muhonen says. “I am excited about the prospects that this new technology has to offer to many patients with hydrocephalus.”

The supportive culture at the CHOC Neuroscience Institute has aided Dr. Muhonen’s research and advancement of wireless technology in shunts.

“CHOC has been very supportive in morphing into a hospital that supports research and cure, rather than a purely clinical children’s hospital,” Dr. Muhonen says. “We’re also fortunate to have donors in the community who want to help. Together, we’re able to strengthen our focus on being a leading research and academic institution.”

Our Care and Commitment to Children Has Been Recognized

CHOC Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the neurology/neurosurgery specialty.

USNWR Neurology and Neurosurgery award

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

Three Common Challenges—and Solutions—for Bone Marrow Transplant Success

CHOC’s Blueprint for Achieving Successful Outcomes for Bone Marrow Transplant Patients

Long-term survivorship and improved quality of life among pediatric cancer patients undergoing bone marrow transplants is routinely threatened by three common challenges that all pediatric oncologists face: cancer relapse, infection and graft versus host disease (GVHD). The oncology team at the Hyundai Cancer Institute at CHOC is overcoming these challenges — and delivering survival outcomes better than the national average.

“What we want for bone marrow transplant patients is for them to go through transplant without getting any infections; to have a small, controlled amount of GVHD; and for their cancer to never return and their immune systems to work fine,” says Dr. Rishikesh Chavan, pediatric oncologist at CHOC. “That would be the best-case scenario, and our team at CHOC is constantly optimizing to that.”

Dr. Chavan says this best-case scenario can be difficult to achieve because of common challenges associated with bone marrow transplants: infections, GVHD and relapse. CHOC is innovating better solutions to defeat these challenges:

  1. Preventing infections: CHOC has a robust program that covers infection prevention, infection surveillance, and timely and appropriate treatment of infections if they arise. “Post-transplant, families receive a dedicated callback number and prompt follow-up to answer their questions and triage them appropriately,” says Dr. Chavan. “If a complication occurs such as fever, patients are seen within 15 minutes of arriving to our ED and their first dose of antibiotics is administered within 60 minutes of their ED visit.” CHOC routinely monitors for infections and underlying immune status, including surveillance labs to check for viral and fungal infections. There is also a keen focus on ensuring all post-transplant patients are re-immunized to prevent infections. With the COVID-19 pandemic, telehealth checks are frequently held to see how the patient is doing and avoid unnecessary hospital visits.
  2. Preventing GVHD: “A little bit of GVHD is not bad, because it tells us the new immune system from the donor is functional and responding,” Dr. Chavan says. “In fact, patients who have Grade I GVHD have better long-term survival outcomes than patients who have no GVHD at all.” Based on the use of post-transplant cyclophosphamide, CHOC has been successful in preventing GVHD in most patients despite having more mismatched/haplo transplants. To manage more serious grades of GVHD, Dr. Chavan is starting a new clinical approach at CHOC dedicated to treating GVHD. “The clinic will utilize our tumor board team-based approach for quickly recognizing GVHD based on clinical as well as laboratory data and using that information to match patients to appropriate GVHD treatments,” he says. “This design will allow us to review what is working, what isn’t and switch treatments quickly, if needed, to help patients get better. Having this ability at our clinic to respond quickly and offer very personalized treatments is the future solution to managing GVHD.”
  3. Preventing relapse: Patients’ bone marrow is checked for engraftment studies and minimal residual disease after transplant through monthly marrows, which is essentially surveillance for relapse. If a patient is likely to relapse because they are at a higher risk of leukemia to begin with or based on their surveillance marrows, they receive donor lymphocyte infusions to support their immature immune system as well as other regimens to prevent or treat relapse. Dr. Chavan is also involved in research projects to study and mitigate potential factors that affect relapse in leukemia patients undergoing stem cell transplant and cellular therapy with a focus on regulatory T lymphocytes.

For proof that CHOC’s efforts in preventing GVHD, infections and relapse is working, bolstered by both algorithm-influenced care and a concierge-medicine approach, Dr. Chavan references patient survival outcomes from 2018 and 2019 in reports by the Center for International Blood & Marrow Transplant Research (CIBMTR). Results showed CHOC well above the national average for survival outcomes and higher than most of its cohort of transplant programs.

“A great team consists of a group of kind-hearted people who can not only detect and treat complications but also anticipate potential problems and try to prevent them, and that’s what we have here at CHOC,” Dr. Chavan says.

Our Care and Commitment to Children Has Been Recognized

CHOC Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the cancer specialty.

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.

CHOC studies child maltreatment during COVID-19, adopts new tools to better recognize signs of abuse

With COVID-19 restrictions keeping more families at home, a critical question has emerged:

Are children suffering more physical and emotional maltreatment because they’re spending more time with parents who are dealing with extra stress in their lives?

A recently completed study by clinicians in the Julia and George Argyros Emergency Department at CHOC Hospital sheds some light on whether child abuse cases are rising because of stay-at-home orders. The study comes as CHOC ED personnel are using two new screening tools to help clinicians better recognize signs of abuse as well as victims of human sex trafficking.

COVID’s effect on child maltreatment

CHOC ED personnel studied whether the incidence of child maltreatment – which includes physical, sexual and emotional abuse, plus neglect – among patients being admitted to the emergency department has risen since the pandemic began in mid-March 2020.

They reviewed records of ED visits of patients up to 18 years old during a 3 ½-month period from March to July 2020 and reviewed the Child Protective Services database, then compared that period to the same time frame in 2019, 2018 and 2017.

Result: More reports of child mistreatment – 215 – were filed during the COVID-19 pandemic, compared to 204 during the same period in 2019, 199 in 2018 and 158 in 2017.

This is especially significant because CHOC’s ED has experienced a significantly lower ED patient census during the pandemic compared to pre-COVID days, says Dr. Mary Jane Piroutek, a CHOC ED attending physician.

Dr. Mary Jane Piroutek, CHOC ED attending physician

While sexual and physical abuse cases were down in the 3 ½-month period in 2020, cases of general neglect and medical neglect, as well as emotional abuse, were higher during COVID compared to the previous years.

Erika Jewell, manager of Case Management and Social Services at CHOC, put some of these numbers in context. In 2017, she reports, the rate of children in Orange County suffering abuse or neglect was 43.8 per 1,000, compared to 33.5 in 2012.

Of the 4,451 substantiated case of child abuse and neglect in Orange County in 2017, the vast majority – 3,204 – were cases of general neglect. Sexual abuse cases, in comparison, totaled 191.

“Our findings suggest the incidence of child neglect increased during the implementation of the stay-at-home guidelines,” says Dr. Piroutek, who spoke with Jewell and others on a panel on Research Day on Nov. 18, 2020.

Knowledge of such a trend, Dr. Piroutek explains, could help providers identify children at risk for maltreatment and, ultimately, provide an impetus to shape public policy and to improve the effectiveness with which resources are allocated to address the COVID-19 public health crisis.

Two new screening tools

Beginning in October 2019, the CHOC ED rolled out the first of two new screening tools aimed at making it easier for nurses and doctors to better identify patients at risk of abuse.

The first new screening tool being used in CHOC’s ED is TRAIN, for Timely Recognition of Abusive Injuries Collaborative. It is used to screen patients 6 months and younger.

The second screening tool, launched in July 2020, is CA-CDS, for Child Abuse – Clinical Decision Support. It is used to screen patients 11 years or younger. Components include a triage screen where nurses or doctors answer five questions, a pop-up computer alert that flags which patients may be at risk for physical abuse, a link to order sets and CHOC’s computerized suspected child abuse form.

With these two new tools, the CHOC ED estimates it can detect 50 percent more sentinel injuries than before. A sentinel injury is a seemingly trivial one that can be viewed as a “sentinel event” for much worse injuries in the future. Research shows that one-quarter of abused children had previous sentinel injuries.

The ED is collecting data through December 2021 to evaluate how well the new screening tools are helping healthcare workers detect cases of maltreatment, Dr. Piroutek says.

“It’s a more data-based and methodical approach; you have a computer that’s looking at data and flagging concerning patterns for you: ‘Hey, there’s something that might be abuse here,’” Dr. Piroutek explains.

The new screening tools will help CHOC better comply with treatment guidelines set forth by the American Academy of Pediatrics (AAP), Dr. Piroutek notes.

“CHOC is committed to research for the betterment of our patients and children,” Dr. Piroutek says. “With the implementation of these new screening tools I am confident we can provide the best care for our patients.”

Screening for human sex trafficking has also become an important part of CHOC nursing care.

Sheryl Riccardi, Emergency Department manager at CHOC, says a steering group of about 20 associates has been established to help healthcare workers better identify, intervene and advocate for these victims, many of whom are minors and most of whom come from the Unites States.

Santa Ana is the largest hub of human sex trafficking in the state, she notes. The ED has begun screening 12- to 18-year-olds – regardless of their chief complaint for possible further evaluation – if a child reports a complaint indicating a high risk of abuse, Riccardi says.

CHOC, she adds, recently became a partner with the Orange County Human Trafficking Task Force, a law enforcement-led coalition that is committed to combating all forms of human trafficking through the rescue and long-term support of victims, prosecution of offenders, training of fellow law enforcement professionals, community awareness and effective public/private partnerships.

According to Waymakers and the Salvation Army, in 2019 there were 415 identified victims of human trafficking in Orange County, with sex trafficking victims totaling 359. The other victims were trafficked for labor.

CHOC is determined to do what it can to find and help these victims.

“We’ve very passionate about this,” Riccardi says.

Learn more about how to identify child abuse.