NCC-PDI Finalists

Pediatric medical device competition names finalists

Five finalists have been named in the prestigious annual “Make Your Medical Device Pitch for Kids!” competition presented by the National Capital Consortium for Pediatric Device Innovation (NCC-PDI). Representing innovations in pediatric technologies that aim to address unmet medical needs for children, these five finalists now have access to a pediatric accelerator program led by MedTech Innovator and will compete for a share of $150,000 in grant funding from the U.S. Food and Drug Administration (FDA) in the final virtual pitch event in October 2022. The pediatric pitch event is part of the 10th Annual Symposium on Pediatric Device Innovation, co-located with the MedTech Conference, powered by AdvaMed.

“Addressing unmet needs across pediatric populations is critical to advancing children’s health and we are delighted to once again work with pioneering companies that seek to bridge this care gap,” says Kolaleh Eskandanian, Ph.D., M.B.A, P.M.P, vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. “As an FDA-funded consortium, NCC-PDI serves as a critical device development resource, bringing together individuals and institutions that support viable pediatric innovations and create faster pathways to commercialization. We congratulate this year’s finalists and look forward to seeing the progress made in the coming months as they navigate the accelerator program.”

The following are the five pediatric device innovations that judges selected for the final competition:

  • CorInnova – Houston, TX – Minimally invasive biventricular non-blood contacting cardiac assist device to treat heart failure.
  • Innovation Lab – La Palma, CA – Mechanical elbow brace stabilizes tremors for pediatric ataxic cerebral palsy to improve the performance of Activities of Daily Living (ADLs).
  • Prapela – Biddeford, ME – Prapela’s incubator pad is the first innovation to improve the treatment of apnea of prematurity in over twenty years.
  • Tympanogen – Richmond, VA – Perf-Fix replaces surgical eardrum repair with a nonsurgical clinic procedure
  • Xpan – Concord, Ont. – Xpan’s universal trocar enables safest and most dynamic access and effortless upsizing in conventional/mini/robotic procedures.

Beginning in June 2022, the five finalists will participate in a pediatric-focused track of the MedTech Innovator accelerator, the world’s largest accelerator of medical devices.

NCC-PDI is one of five consortia in the FDA’s Pediatric Device Consortia Grant Program created to support the development and commercialization of medical devices for children, which lags significantly behind the progress of adult medical devices. NCC-PDI is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National and the A. James Clark School of Engineering at the University of Maryland, with support from partners MedTech Innovator, BioHealth Innovation and design firm Archimedic.

To date, NCC-PDI has mentored nearly 200 medical device sponsors to help advance their pediatric innovations, with 16 devices having received either their FDA market clearance or CE marking.

The accelerator program is the consortium’s latest addition to a network of resources and experts that it provides in support of pediatric innovators.

Eskandanian adds that supporting the progress of pediatric innovators is a key focus of the new Children’s National Research & Innovation Campus, a one-of-its-kind ecosystem that drives discoveries that save and improve the lives of children. On a nearly 12-acre portion of the former, historic Walter Reed Army Medical Center in Northwest Washington, D.C., Children’s National has combined its strengths with those of public and private partners, including industry, universities, federal agencies, start-up companies and academic medical centers. The campus provides a rich environment of public and private partners which, like the NCC-PDI network, will help bolster pediatric innovation and commercialization.

NCC-PDI Finalists social card

illustration of the brain

LIFU successfully delivers targeted therapies past the blood-brain barrier

illustration of the brain

LIFU offers doctors the first opportunity to open the blood-brain barrier and treat the entire malignant brain tumor.

Children’s National Hospital will leverage low-intensity focused ultrasound (LIFU) to deliver therapy directly to a child’s high-grade glioma. The approach offers doctors the first opportunity to open the blood-brain barrier and treat the entire malignant brain tumor.

Children’s National will be the first hospital in the U.S. to treat high-grade pediatric brain tumors with LIFU to disrupt the blood-brain barrier. Crossing it has been a major hurdle for effective therapy. The barrier, a network of blood vessels and tissue, prevents harmful substances from reaching the brain but also stops molecular targeted therapy and immunotherapy from getting into the tumor site and staying there.

“LIFU gives us a way to potentially transiently open up the barrier, so we can deliver novel therapy directly to the tumor and improve the likelihood of survival,” said Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National. “It is the greatest breakthrough we’ve potentially had in the past 50 years or more for the management of these tumors. We made great strides in our understanding of molecular genetics and the molecular drivers of tumors, but we have not yet translated that knowledge into better therapies; this may be our most effective mechanism to overcome the barrier.”

In 2020, Children’s National was recognized as the first worldwide Center of Excellence by the Focused Ultrasound Foundation.

Focused ultrasound (FUS) is a non-invasive therapeutic technology with the potential to transform the treatment of many medical disorders by using ultrasonic thermal energy to specifically target tissue deep in the body. The technology can treat without incisions or the need of radiation.

How it works

Doctors at Children’s National will be using LIFU in two different types of procedures:

  • 5-ALA: Doctors will give the patient 5-aminolevulinic acid (5-ALA) with the LIFU treatment. 5-ALA enters rapidly dividing cells and is activated by the ultrasound to a state where it kills the dividing cells of the tumor. The surrounding normal brain cells around the tumor are not dividing, so they do not take up the 5-ALA and are left unharmed after ultrasound therapy.
  • Microbubbles: While receiving different doses of LIFU over a one- to two-hour period, the patient is given “microbubbles,” which are widely used in medical imaging and as carriers for targeted drug delivery. These microbubbles bounce around against the walls like seltzer, opening the blood vessels and transiently opening that space.

Both studies are the first in the world for pediatric gliomas of the brain stem, allowing experts to treat patients 4-6 weeks after radiotherapy. The patient then receives medication orally or intravenously as it passes through the bloodstream. It does not go at high levels anywhere within the brain except where the blood-brain-barrier was opened, allowing oral medication or immune therapies to rush into the tumor.

The launch of this program comes a few months after the hospital successfully performed the first-ever high-intensity focused ultrasound surgery on a pediatric patient with neurofibromatosis.

Watch this video to learn more.

crawling baby

Gene-targeting may help prevent or recover neonatal brain injuries

crawling baby

The findings of a new pre-clinical study published in The Journal of Neuroscience are helping pave the way toward better understanding, prevention and recovery of neonatal brain injuries.

The findings of a new pre-clinical study published in The Journal of Neuroscience are helping pave the way toward better understanding, prevention and recovery of neonatal brain injuries. During pregnancy, the fetus normally grows in low oxygen conditions. When babies are born preterm, there is an abrupt change into a high oxygen environment which may be higher than the baby can tolerate. These preterm babies often need support to breathe because their lungs are immature. If the oxygen they receive is too high, oxygen-free radicals can form and cause cell death.

Premature infants have underdeveloped antioxidant defenses that prevent or delay some types of cell damage under normal conditions. In a high oxygen environment, these underdeveloped defenses cannot fully protect against oxidative stress, damaging different brain regions without available treatments or preventative measures.

“I am thrilled that we identified a defect in a specific cell population in the hippocampus for memory development,” said Vittorio Gallo, Ph.D., interim chief academic officer and interim director of the Children’s National Research Institute, and principal investigator for the District of Columbia Intellectual and Developmental Disabilities Research Center. “I did not think we would be able to do it at a refined level, identifying cell populations sensitive to oxidative stress and its underlying signaling pathway and molecular mechanism.”

Vittorio Gallo

“I am thrilled that we identified a defect in a specific cell population in the hippocampus for memory development,” said Vittorio Gallo, Ph.D.

Children’s National Hospital experts found that oxidative stress over-activates a glucose metabolism enzyme, GSK3β, altering hippocampal interneuron development and impairing learning and memory, according to the pre-clinical study. The researchers also inhibited GSK3β in hippocampal interneurons, reversing these cellular and cognitive deficits.

The role of oxidative stress in the developing hippocampus, as well as GSK3β involvement in oxidative stress-induced neurodevelopmental disorders and cognitive deficits, have both been unexplored until now. Goldstein et al. suggest the study paves the way for the field as a viable approach to maximize functional recovery after neonatal brain injury.

To better understand the mechanisms underlying neonatal brain injury, the researchers mimicked the brain injury by inducing high oxygen levels in a pre-clinical model for a short time. This quest led to unlocking the underpinnings of the cognitive deficits, including the pathophysiology and molecular mechanisms of oxidative damage in the developing hippocampus.

Once they identified what caused cellular damage, the researchers used a gene-targeted approach to reduce GSK3β levels in POMC-expressing cells or Gad2-expressing interneurons. By regulating the levels of GSK3β in interneurons ⁠— but not in POMC-expressing cells — inhibitory neurotransmission was significantly improved and memory deficits due to high oxygen levels were reversed.

2022 Hackathon logo

Addressing health equity issues through an app innovation competition

Children’s National Hospital launches The Health Equity in Research Hackathon — a team-based collaborative competition that empowers researchers to address health equity issues in the community through innovative apps. A panel of expert judges will select winning app ideas for full development, including finding grant opportunities, access to mentors and collaborators.

The big picture

“This Hackathon is a great chance for our research community to address larger issues related to advancing health equity within translational and clinical research,” said Patrick O’Keefe, administrative director for the Clinical and Translational Science Institute at Children’s National (CTSI-CN). “We are thrilled to see how people collaborate to create solutions for big problems that have traditionally slowed research and contributed to the vast inequities in health we see today.”

Additional details

The 2022 hackathon will be a two-part event. During Part I, slated for June 17, participants will gather in diverse teams to discuss and refine the selected app ideas. They will learn from technical and scientific experts and brainstorm app-based approaches to address health equity.

Each team will pitch their ideas to a panel of judges, and the winning app(s) will advance to Part II of the hackathon planned for Fall 2022, where app developers will build the selected apps.

“We encourage anyone at Children’s or George Washington University to submit an app idea – even if it is not fully formed — as long as they think it would help reduce health disparities through improving the research process,” said Lisa Guay-Woodford, M.D., director for Clinical and Translational Science Institute and Center for Translational Research at Children’s National. “We also hope researchers, staff and students who don’t have app ideas at this time will consider attending anyway to participate in the lively development process of the Hackathon.”

Anyone within the Children’s National and George Washington University research communities can submit an app idea for consideration. No app development experience is necessary to enter.

Why it matters

Health equity also means bringing the community into the research process. Thus, in part II, Children’s National will partner with high schools and universities in the area to incorporate voices who are often under-represented in the science and technology field.

“Our community is home to brilliant young minds at our local high schools and universities,” said Chaya Merrill, Dr.P.H., director for Child Health Data Lab at Children’s National. “We are excited to create an opportunity for them to work alongside experienced app builders – at the intersection of health equity and technology – by engaging in Part II of the Hackathon to build the winning apps!”

The hackathon will take place at Children’s Research and Innovation Campus in partnership with CTSI-CN and the Center for Translational Research.

The app idea submission deadline is on May 20, 2022, by 5pm. You may apply here. If you have questions about completing this submission, please email Patrick O’Keefe at pokeefe@childrensnational.org.

2022 Hackathon logo

caspase molecule

Caspases may link brain cell degeneration and cardiac surgery

caspase molecule

The review summarizes both the known physiological roles of caspases as well as some of the well-characterized neurotoxic effects of anesthetics in pre-clinical models.

A review article in the journal Cell Press: Trends in Neuroscience outlines the wide variety of cellular signaling roles for caspase proteins — a type of cellular enzyme best known for its documented role in the natural process of cell death (apoptosis). The authors, including Nemanja Saric, Ph.D., Kazue Hashimoto-Torii, Ph.D., and Nobuyuki Ishibashi, M.D., all from Children’s National Research Institute, pay particular attention to what the scientific literature shows about caspases’ non-apoptotic roles in the neurons specifically. They also highlight research showing how, when activated during a cardiac surgery with anesthesia and cardiopulmonary bypass, these enzymes may contribute to the degeneration of brain cells seen in young children who undergo heart surgery for critical congenital heart defects (CHDs).

Why it matters

The review summarizes both the known physiological roles of caspases as well as some of the well-characterized neurotoxic effects of anesthetics in pre-clinical models.

The authors propose that these non-apoptotic activities of caspases may be behind some of the adverse effects on the developing brain related to cardiac surgery and anesthesia. Those adverse effects are known to increase risk of behavioral impairments in children with congenital heart disease who underwent cardiac surgery with both anesthesia and cardiopulmonary bypass at a very young age.

This work is the first to propose a possible link between developmental anesthesia neurotoxicity and caspase-dependent cellular responses.

The patient benefit

Better understanding of the time and dose-dependent effects of general anesthetics on the developing brain, particularly in children who have genetic predispositions to conditions such as CHDs, will help researchers understand their role (if any) in behavioral problems often encountered by these patients after surgery.

If found to be a contributing factor, perhaps new therapies to mitigate this caspase activity might be explored to alleviate some of these adverse effects on the developing brain.

What’s next?

The authors hope to stimulate more in-depth research into caspase signaling events, particularly related to how these signaling events change when an anesthetic is introduced. Deeper understanding of how anesthetics impact caspase activation in the developing brain will allow for better assessments of the risk for children who need major surgery early in life.

Children’s National leads the way

Children’s National Hospital leads studies funded by the U.S. Department of Defense to better understand how these other roles of caspases, which until now have not been well-documented, may contribute to brain cell degeneration when activated by prolonged anesthesia and cardiopulmonary bypass during cardiac surgery for congenital heart disease.

NCC-PDI announcement

Medical device pitch competition returns with $150K in FDA awards

Kolaleh-Eskandanian

“This pitch competition helps to recognize and support the advancement of innovations that can specifically address the needs of pediatric patients,” says Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI.

Recognizing the continued gap in the development and commercialization of medical devices for children versus adults, the National Capital Consortium for Pediatric Device Innovation (NCC-PDI), in collaboration with MedTech Innovator, is accepting applications through April 22, 2022, for its annual “Make Your Medical Device Pitch for Kids!” competition. Recognizing the wide range of unmet needs for diagnostic and therapeutic devices designed especially for children, this year’s competition is open to any innovation in medical technology that addresses a significant unmet need in pediatric medical care.

“As one of the five FDA Pediatric Device Consortia, NCC-PDI is focused on seeking out and addressing significant unmet needs in pediatric medical technology,” says Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. “While great advances are made in adult medical devices, children are often left behind because the pediatric market is small and there are not incentives to develop for pediatrics. This pitch competition helps to recognize and support the advancement of innovations that can specifically address the needs of pediatric patients.”

Using a virtual format, semi-finalists chosen from all submissions will make their first pitch on May 20, 2022. Up to six finalists selected from this first round will earn participation in a special pediatric-focused track of the MedTech Innovator accelerator program, the largest medical device accelerator in the world, beginning in June 2022. These innovators will then participate in the competition finals in the fall 2022 where judges will award up to $150,000 in FDA-sponsored grants to the devices selected as most impactful and commercially viable.

Unlike devices for adults, the development and commercialization of pediatric medical devices lags behind by approximately five to 10 years. Programs like the NCC-PDI pitch competition and MedTech Innovator accelerator program offer innovators access to expert insight and consultation to help overcome regulatory hurdles and advance the product’s development path.

NCC-PDI is one of five members in the FDA’s Pediatric Device Consortia Grant Program created to support the development and commercialization of medical devices for children. NCC-PDI is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National and the A. James Clark School of Engineering at the University of Maryland with support from partners MedTech Innovator, BioHealth Innovation and design firm Archimedic.

Eskandanian adds that supporting the progress of pediatric innovators is a key focus of the new Children’s National Research & Innovation Campus, a one-of-its-kind ecosystem that drives discoveries that save and improve the lives of children. On a nearly 12-acre portion of the former, historic Walter Reed Army Medical Center in Northwest Washington, D.C., Children’s National has combined its strengths with those of public and private partners, including industry, universities, federal agencies, start-up companies and academic medical centers. The campus provides a rich environment of public and private partners which, like the NCC-PDI network, will help bolster pediatric innovation and commercialization.

NCC-PDI announcement

Applications for the “Make Your Medical Device Pitch for Kids!” competition are open now through April 22 for innovations that address unmet pediatric needs.

 

parathyroid close-up

A new imaging device with AI may reduce complications during thyroid surgery

parathyroid close-upSurgeons perform approximately 150,000 thyroidectomies in the United States. Post-surgical complications from this procedure frequently occur due to the misidentification or accidental removal of healthy parathyroid glands. On average, 27% of these patients suffer from transient or permanent hypocalcemia, a condition in which the blood has too little calcium, leading to lifelong complications and socioeconomic burden.

To improve parathyroid detection during surgery, Children’s National Hospital experts developed a prototype equipped with a dual-sensor imaging device and a deep learning algorithm that accurately detects parathyroids, according to a new study published in the Journal of Biophotonics.

“What excited us in this study was that even deep-seated tissues were able to be imaged without light loss, and high resolution imaging was possible due to the unique optical design,” said Richard Jaepyeong Cha, Ph.D., council member of the International Society of Innovative Technologies for Endocrine Surgery and principal investigator for the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital. “Moreover, in several cases, parathyroid autofluorescence was detected even before the surgeon dissected the parathyroid gland, and while it was covered by fat and/or fascia.”

What’s unique

This is the first study that uses color RGB/NIR paired imaging-based parathyroid detection by incorporating multi-modal (both RGB light and near-infrared autofluorescence, or NIRAF, ground truth imaging) data into parathyroid identification using a deep learning algorithm.

The patient benefit

“We envision that our technology will open a new door for the digital imaging paradigm of dye-free, temporally unlimited, and precise parathyroid detection and preservation,” said Richard. “Successful translation of this technology will potentially reduce the risk of hypoparathyroidism after common thyroid surgery and improve the clinical outcomes.”

The results support the effectiveness of their novel approach despite the small sample size, which can potentially improve specificity in the identification of parathyroid glands during parathyroid and thyroid surgeries.

The hold-up in the field

It is often difficult for surgeons with naked eyes to identify parathyroid glands from thyroid tissue because of the small size, the variable position, and similar appearance to the surrounding tissues.

Since 2011, surgeons have benefited from using NIRAF, a non-invasive optical method for intraoperative real-time localization of parathyroids.

While the NIRAF technology has gained traction among endocrine surgery community, false negatives can occur with current devices that use the NIRAF technology in secondary hyperparathyroidism cases. According to Kim et al., the technology is still suboptimal, and a significant percentage of parathyroid is being missed.

Children’s National Hospital leads the way

Engineers in Children’s National are leading this field through several innovations:

  • Non-dye injected, label-free use in real-time in comparison to temporally limited ICG angiography. This technology was featured as the cover article in the journal Lasers in Surgery and Medicine 54(3), 2022.).
  • Simultaneous perfusion assessment from four glands at any time during operation.
  • Arterial flow detection from pulsatile information in well-perfused PG vasculature.
  • Quantified parathyroid detection and classification with prediction values using deep learning technique.

You can read the full study “A co-axial excitation, dual-RGB/NIR paired imaging system toward computer-aided detection (CAD) of parathyroid glands in situ and ex vivo” in the Journal of Biophotonics.

overview of parathyroid surgery procedure

colorful strands of DNA

Paving the way to activate a single gene in Angelman syndrome

colorful strands of DNA

Angelman syndrome (AS) is a rare disorder that causes neurodevelopmental issues such as intellectual disability, impaired speech and motor skills, epilepsy and sleep disruptions. This single gene disorder is caused by mutations or deletions in the maternal copy of the UBE3A gene.

Angelman syndrome (AS) is a rare disorder that causes neurodevelopmental issues such as intellectual disability, impaired speech and motor skills, epilepsy and sleep disruptions. This single gene disorder is caused by mutations or deletions in the maternal copy of the UBE3A gene. To date, there is no treatment for AS.

It is easier to treat this syndrome when the disrupted gene is present but repressed. If experts can figure out how to activate it in clinical trials, they believe patients could receive a treatment that tackles the root of the problem. Children’s National Hospital experts support this vision and the AS community by helping establish appropriate biomarkers for current and future clinical trials.

While the field is trying to figure out the best scientific method to quantify progress in clinical trials for AS, the Sidorov Laboratory found that overnight sleep testing is not necessary for detecting Angelman syndrome electroencephalography (EEG) biomarkers, according to the study published in Autism Research. The data further suggests that while sleep EEGs do not provide additional benefit for detecting delta EEG rhythms, sleep itself represents a valuable AS biomarker.

What this means

“It is encouraging to see that wake EEGs are sufficient, and perhaps ideal, for detecting delta waves in a clinical trial setting,” said Michael S. Sidorov, Ph.D., principal investigator with the Center for Neuroscience Research at Children’s National. “With this biomarker, researchers can measure how AS severity changes in children over the course of a clinical trial. This enables trials to test the efficacy of exciting new treatments.”

The hold-up in the field

In the past decade, the research community has focused on activating the dormant paternal copy of the UBE3A gene in pre-clinical models. Presently, there are three ongoing phase I clinical trials for AS in the U.S. These trials use antisense oligonucleotides (ASOs), which can modify gene expression to treat genetic disorders, and have been FDA approved for other disorders. These new compounds specifically target the gene activation to unleash the existing copy of UBE3A. However, there is a need for better and more accurate ways to know if the drug is working or not. The field has not reached a consensus yet on the appropriate biomarkers that can correctly measure success.

There are also challenges associated with performing overnight EEG studies in children with AS due to the severe sleeping problems, difficulty in tolerating the process and sample recruitment.

The patient benefit

Elizabeth R. Jalazo, M.D., assistant professor of pediatrics at the University of North Carolina in Chapel Hill, chief medical officer at the Angelman Syndrome Foundation, is also the parent of a child with Angelman syndrome. Dr. Jalazo, who was not part of the study, mentioned that her experience with a daughter with a rare disorder had brought challenges to their family over the last seven years. But, alas, she said the joy Evelyn has brought to their lives far outweighs the day-to-day challenges of special needs parenting.

“As a parent I’m thrilled that we can potentially capture as much meaningful EEG data in a short daytime EEG rather than subjecting our children to overnight EEG studies,” said Dr. Jalazo. “As a clinician this is equally exciting from a clinical trial feasibility standpoint.”

One of the greatest challenges facing Angelman syndrome and other neurodevelopmental disorder therapeutic development is the lack of appropriate endpoints to assess the efficacy of our interventions.

“I worry very much that without objective measures specific to Angelman syndrome, potentially beneficial therapeutics may fail to meet the mark and ultimately not reach the community,” she added.

The scientific community has transitioned from the hope of clinical trials to lessen those day-to-day challenges to witnessing first-in-human trials of potentially transformative therapeutics in just the last few years.

“It is a biomarker work like this that is critical as we delve into the exciting landscape of clinical trial design and advance therapeutics for Angelman syndrome,” said Dr. Jalazo.

You can read the full study “Evaluation of electroencephalography biomarkers for Angelman syndrome during overnight sleep” in Autism Research.

 

zika virus

Researcher to decipher how viruses affect the developing brain with nearly $1M NIH award

zika virus

Zika virus in blood with red blood cells, a virus which causes Zika fever found in Brazil and other tropical countries.

The National Institutes of Health (NIH) awarded Children’s National Hospital nearly $1M of research support toward uncovering the specific cellular response that happens inside a developing brain once it is infected with a virus, including how the neuron gets infected, and how it dies or survives. The research is expected to gather critical information that can inform prenatal neuro-precision therapies to prevent or attenuate the effects of endemic and pandemic viruses in the future.

“We need to use all of the information we have from ongoing and past pandemics to prevent tomorrow’s public health crisis,” said Youssef Kousa, MS, D.O., Ph.D., neonatal critical care neurologist and physician-scientist at Children’s National. “There is still here a whole lot to learn and discover. We could eventually — and this is the vision that’s inspiring us — prevent neurodevelopmental disorders before a baby is born by understanding more about the interaction between the virus, mother, fetus, and environment, among other factors.”

Different viruses, including HIV, CMV, Zika and rubella, injure the developing brain in very similar ways. This line of work was fostered first by the clinical research team led by Adre du Plessis, M.B.Ch.B., and Sarah Mulkey, M.D., supported by Catherine Limperopoulos, Ph.D., chief and director of the Developing Brain Institute at Children’s National.

The clinical research findings then led to the NIH support, which then inspired more basic science research. Fast forward to now, Kousa will study how Zika affects the human brain and extrapolate what is learned and discovered for a broader understanding of neurovirology.

The research program is supported by senior scientists and advisors, including Tarik Haydar, Ph.D., and Eric Vilain, M.D., Ph.D., both at Children’s National and Avindra Nath, M.D., at NIH, as well as other leading researchers at various U.S. centers.

“This is a team effort;” added Kousa, “I’m thankful to have a group of pioneering and seasoned researchers engaged with me throughout this process to provide invaluable guidance.”

Many viruses can harm the developing brain when they replicate in the absence of host defenses, including the gene regulatory networks responsible for the neuronal response. As a result, viral infections can lead to brain injury and neurodevelopmental delays and disorders such as intellectual disability, seizures that are difficult to treat, and vision or hearing loss.

The big picture

Youssef Kousa

Youssef Kousa, MS, D.O., Ph.D., neonatal critical care neurologist and physician-scientist at Children’s National.

The translational research supported by NIH with this award synergistically complements nationally recognized clinical research programs and ongoing prospective cohort studies at Children’s National to identify the full spectrum of neurodevelopmental clinical outcomes after prenatal Zika and other viral infections led by Dr. Mulkey and Roberta DeBiasi, M.D., M.S..

The award also builds upon strengths at the Children’s National Research & Innovation Campus, which is in proximity to federal science agencies. Children’s National experts from the Center for Genetic Medicine Research, known for pediatric genomic and precision medicine, joined forces with the Center of Neuroscience Research and the NIH-NINDS intramural research program to focus on examining prenatal and childhood neurological disorders.

Kousa received this competitive career development award from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number K08NS119882. The research content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The hold-up in the field

Many neurodevelopmental disorders are caused by endemic viruses, such as CMV, and by viral pandemics, including rubella as seen in the 1960s and Zika since 2015. By studying Zika and other prenatal viral infections, Kousa and team hope to gain deeper biological understanding of the viral effects toward developing therapies for anticipating, treating and preventing virally induced prenatal brain injury in the long-term future.

To date, little is known about how viruses affect developing neurons and, as a result, prenatal brain injury is not yet treatable. To bridge the gap towards prenatal neuro-precision therapies, the research explores how genes regulate neuronal developmental and viral clearance by innovatively integrating three systems:

  • Cerebral organoids, which illuminate how a neuron reacts to a viral infection
  • Pre-clinical models that link prenatal brain injury to postnatal neurodevelopmental outcomes
  • Populational genomics to identify human genetic risk or protective factors for prenatal brain injury

Given the scope and complexity of this issue, the international Zika Genetics Consortium, founded in 2015 by Kousa and a team of leading investigators across the world, provides critical samples and resources for the third arm of the research by performing comprehensive genomic analyses using sequencing data collected from diverse human populations throughout Central and South America, which are not as heavily sequenced as Western populations. Through partnerships with the Centers for Disease Control and Prevention and NIH, the consortium’s database and biorepository houses thousands of patient records and biospecimens for research studies to better understand how viruses affect the developing human brain.

“It is inspiring to imagine that, in the longer term, we could recognize early on the level of brain-injury risk faced by a developing fetus and have the tools to mitigate ensuing complications,” said Kousa. “What is driving this research is the vision that one day, brain injury could be prevented from happening before a baby is born.”

illustration of brain tumor

International initiative aims to find rare brain tumor treatments

illustration of brain tumor

Rare brain tumors are not as well characterized due to the paucity of biological and clinical data available.

Certain brain tumors can be hard to diagnose. And as such, that makes it complicated to find a treatment.

In an effort to identify and tailor treatments to patients with rare brain tumors, Children’s National is launching a rare brain tumor initiative. The hospital is collaborating with other hospitals in North America, South America and Europe to compile a registry of children diagnosed with rare brain tumors. The registry will collect biospecimens, clinical and radiological data from patients diagnosed with certain rare brain tumors.

The goal is to find a correlation between the molecular findings and the clinical findings to categorize them. This will help doctors get different prognosticators or different treatment approaches.

Here, Adriana Fonseca Sheridan, M.D., pediatric neuro-oncologist at Children’s National Hospital, tells us more about this international initiative.

What’s been the hold-up in the field?

The recent incorporation of molecular features as part of the diagnostic criteria and classification of brain tumors highlighted a high biological and molecular heterogeneity within previously histologically defined entities. The improvement in our diagnostic capabilities have been incredibly useful to stratify patients into different disease-specific risk groups and tailor therapeutic approaches accordingly in the most common brain tumors. In contrast, rare brain tumors are not as well characterized due to the paucity of biological and clinical data available. Additionally, newly molecularly defined entities lack specific clinical and therapeutic data and represent a major challenge to patients and doctors alike.

How does this work move the field forward?

The overarching objective of the international rare brain tumor registry is to deepen our understanding of the biological underpinnings of rare brain tumors. The registry also seeks to create infrastructure that allows for development of rational and personalized treatment strategies for children with rare entities.

What are you hoping to discover?

We hope to characterize the clinicopathological features and identify risk factors for survival and optimal therapeutic approaches of:

  • CNS sarcomas
  • BCOR-ITD tumors
  • Astroblastoma/MN1 altered tumors
  • Histologically ambiguous/unclassifiable brain tumors

How unique is this work?

Children’s National will spearhead the development of this initiative and lead an effort to prospectively collect biological specimens, radiological and clinical data that allow us to better understand the biologic mechanisms and therapeutic susceptibilities of these rare diseases.

We know that the best way to lead the advancement of the field in rare diseases is through collaboration. Therefore, we will synchronize efforts and collaborate with our European colleagues. They will be running a similar initiative. Our goal is to generate meaningful and robust data that will allow us to better understand how to successfully treat patients with these rare brain tumors across the globe.

girl hugging stuffed animal

Developing next-generation T cells to fight cancer

girl hugging stuffed animal

In the last decade, researchers have witnessed significant advances in the immunotherapy field. Most recently, a study in Nature claimed a novel CAR T-cell therapy “cured” a patient.

In the last decade, researchers have witnessed significant advances in the immunotherapy field. Most recently, a study in Nature claimed a novel CAR T-cell therapy “cured” a patient. Given the landmark scientific achievement for patients with different types of leukemia and lymphoma, Children’s National Hospital experts chimed in on the technology they have developed beyond CAR T cells.

Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, discusses the implications of this research, how it relates to the work she’s doing at Children’s National and the future of T-cell therapies.

Q: What did the research published in Nature find?

A: It reported a decade-long experience with this novel T-cell therapy called CD19 CAR T cells. These were used to treat patients with a type of leukemia or lymphoma that expresses the CD19 on its surface. While the article reported the experience of Children’s Hospital of Philadelphia and the University of Pennsylvania, multiple groups throughout the country did similar trials that have used these unique CD19 CAR T cells to treat children and adults with these refractory blood cancers.

Q: What are your thoughts on the implications of this research?

A: We now have three FDA-approved commercial CD19 CAR T-cell products developed by several academic institutions. This is revolutionary for our patients who have B-cell leukemias and lymphomas. It’s incredibly exciting for our T-cell therapy field in general because this was the first time the FDA approved a T-cell therapy. What it means now is the field is extremely excited to develop similar effective therapies for other patients with cancer.

Q: How does this relate to your work at Children’s National?

A: While CAR T cells have made tremendous progress for patients with B-cell leukemias, lymphomas and other blood cancers, the CAR T-cell field has not made the same impact for adult and pediatric solid tumors. We think the field is going to expand the type of T-cell therapies we’re generating beyond just CAR T cells. That’s where the work we’re doing comes in – not only by developing new T cells that don’t need gene engineering but also T cells that can be used as a platform for next-generation engineering approaches. We think the technology we’ve developed at Children’s National will help make an impact, especially in the solid tumor space. I hope in the next 10 years, we’ll be having a conversation not just about CAR T cells, but about other types of T cells that are now making an impact for solid tumors.

Q: How are the CAR T cells you develop different than those in the Nature article?

A: We think our multi-antigen specific T cells are complimentary and could have more potency than conventional CAR T cells for solid tumors especially when used in combination. This is in part because they can identify multiple targets on a tumor cell. Tumor cells are very clever and try to hide from T-cell therapies by down regulating the target that the T cell is directed towards. However, our novel T-cell therapies get around that escape by targeting multiple targets in a single product, making it much harder for the cancer cell to hide from the immune attack by the T cells.

Additionally, we’re excited by our approach because not all of our products require gene engineering, unlike CAR T cells. We have effectively used our T cells to target viruses in the “off-the-shelf” setting and we’re now about to start a first human clinical trial at Children’s National using an off the shelf T-cell product for children with solid tumors. It makes the T-cell therapy more like an “off-the-shelf” drug therapy that will allow us to treat many more children and adults nationally, as well as we hope, internationally.

mitochondria

Grant funds study of two maternally inherited mitochondrial diseases

mitochondria

The National Institutes of Health awarded George Washington University and Children’s National Hospital a grant to study two maternally inherited mitochondrial diseases.

The National Institutes of Health awarded George Washington University and Children’s National Hospital a grant to study two maternally inherited mitochondrial diseases. Andrea Gropman, M.D., division chief of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National, along with her co-investigator, Anne Chiaramello, M.D., from the George Washington University School of Medicine, will lead the study.

The proposed studies focus on two ultra-rare maternally inherited mitochondrial diseases:

  • Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS); and
  • Leber’s Hereditary Optic Neuropathy-Plus (LHON-Plus).

Both diseases are among those studied by the Rare Diseases Clinical Research Network.

“We are really pleased to be able to change the landscape for MELAS and LHON, two mitochondrial disorders with relentless progression and no treatment,” Dr. Gropman said. “This grant represents the fruition of an eight-year collaboration with my colleague Dr. Chiaramello and we are fortunate to be able to deliver this at Children’s National and serve our patients and community.”

Because patients currently do not have access to effective therapeutic intervention, this results in significant disability, morbidity and premature death. The UG3 phase of the study will focus on translational MELAS and LHON-Plus studies and submission of an IND protocol to the Food and Drug Administration. The UH3 phase will focus on a basket clinical trial with MELAS and LHON-Plus to:

  • Provide proof-of-concept that the basket design can be applied to divergent ultra-rare diseases.
  • Advance the dataset for safety and pharmacokinetics/pharmacodynamics of our lead compound for a larger number of patients than in a conventional clinical trial setting.
  • Gather outcomes and practical information for optimizing the design of future basket clinical trial.

“Dr. Gropman is dedicated to giving children with MELAS the very best care,” said Elizabeth Wells, M.D., vice president of Neuroscience and Behavioral Medicine Center at Children’s National. “This new research funding is exciting and means more patients can benefit from the expertise she has developed at Children’s National.”

doctor and cancer patient smiling

Manufactured leukemia-specific T cells may help increase survival rates

doctor and cancer patient smiling

Infusion of a novel, multi-targeted donor-derived T-cell therapy is safe and well-tolerated in patients with high-risk or relapsed leukemia after a donated bone marrow transplant, according to a new study published in Blood Advances.

Infusion of a novel, multi-targeted donor-derived T-cell therapy is safe and well-tolerated in patients with high-risk or relapsed leukemia after a donated bone marrow transplant, according to a new study published in Blood Advances. The findings suggest that this strategy may make a difference in these patients, as will be evaluated in later phase trials.

“A tumor cell is very clever because it tries to hide from T-cell therapies by deleting or down regulating targets that the T cell is directed towards,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital and co-senior author. “This novel cell therapy has the potential to get around that escape by targeting multiple proteins in a single product, making it much harder for the cancer cell to hide from the immune attack by the T cells.”

The tumor-associated antigen-specific T cell (TAA-T) product targets WT1, survivin and PRAME, which are proteins that play a role in cancer cell proliferation and survival. They are overexpressed in leukemia and many other human malignancies. The researchers chose to expand the T cells to target many malignancies through at least one expressed antigen. The manufactured TAA-T products are derived from peripheral blood mononuclear cells (PBMCs) obtained from the patient’s own BMT donor.

The hold-up in the field

Conventional therapies for patients with high-risk or relapsed malignancies often fail due to toxicity associated with additional chemotherapy and second transplant, particularly in those who relapse early after transplant. This novel cellular immunotherapy approach is shown to be safe and targets antigens that are found in CD19 positive and negative blood cancers, which may broaden the applicability to other cancer types, such as acute myeloid leukemia, that are currently lacking effective T cell therapy options.

What’s next

“Evaluation and tracking of unique T cell receptor clonotypes in patients following TAA-T cell infusion demonstrated expansion and persistence of some clonotypes up to 6 months to one-year post-infusion,” said Hannah Kinoshita, M.D., oncology fellow at Children’s National and co-lead author. “In future studies, we are hoping to identify and track unique target antigen-specific clonotypes from the T cell product infused to better understand the immunobiological effect of the infused T cells and how that can be translated into improved clinical outcomes.”

Children’s National Hospital leads the way

The Cell Enhancement and Technologies for Immunotherapy (CETI) program at Children’s National specializes in developing and analyzing novel cellular therapeutics such as this one.

You can read the full study “Outcome of Donor-derived TAA-T cell therapy in Patients with High-risk or Relapsed Acute Leukemia Post Allogeneic BMT,” in Blood Advances. Children’s National researchers worked in partnership with Rick Jones, M.D., co-senior author and Kenneth Cooke, M.D., Ph.D., co-lead author, both at Johns Hopkins Medicine.

aggrecan protein

Two new papers advance aggrecan deficiency research

aggrecan protein

Aggrecan (ACAN) is a large protein found in joint cartilage and growth plates.

Andrew Dauber, M.D., M.M.Sc., division chief of Endocrinology at Children’s National Hospital, and colleagues recently published two papers that describe the phenotypic spectrum of aggrecan deficiency and look at treating the condition with human growth hormone.

Aggrecan (ACAN) is a large protein found in joint cartilage and growth plates. It allows joints to move smoothly and without pain. Aggrecan deficiency — due to heterozygous mutations in the ACAN gene — causes dominantly inherited short stature and, in many patients, early-onset osteoarthritis and degenerative disc disease.

Clinical phenotype of patients with aggrecan deficiency

In 2017, Dr. Dauber led an international consortium of researchers that published a manuscript describing the phenotypic spectrum of 103 individuals – 70 adults and 33 children, including 57 females and 46 males – from 20 families with ACAN mutations. In the study, Dr. Dauber and his colleagues established that short stature and accelerated bone age is common among people with ACAN mutations.

In a new study published in the American Journal of Medical Genetics Part A, Dr. Dauber and colleagues further characterize the phenotypic spectrum of aggrecan deficiency, with an emphasis on musculoskeletal health.

Twenty-two individuals from nine families were enrolled in the study. Recorded histories and examinations focused on joint health, gait analysis, joint specific patient reported outcomes and imaging.

“We performed a detailed analysis of the musculoskeletal manifestations in patients with mutations in the aggrecan gene,” says Dr. Dauber. “We found that patients with mutations in this gene had significant short stature which worsened with age. There was a high prevalence of joint complaints and arthritis in adults, and we were able to detect pre-symptomatic joint damage in children using knee MRIs.”

Treating short stature in aggrecan-deficient patients with human growth hormone

Until now, it was unknown how to treat children with aggrecan deficiency. “Providing growth hormone therapy to children with ACAN gene mutations is relatively new in the field of pediatric endocrinology,” explains Dr. Dauber. “Previously, the assumption was that this was just short stature.”

In a new study, published in The Journal of Clinical Endocrinology and Metabolism, Dr. Dauber and colleagues reported the results of a trial that evaluated the efficacy and safety of recombinant human growth hormone (rhGH) therapy on linear growth in children with ACAN deficiency.

“This is the first prospective trial of growth hormone therapy in patients with mutations in the aggrecan gene,” says Dr. Dauber. “Mutations in the gene are the cause for short stature in approximately 2%  of individuals with idiopathic short stature.”

The open-label, single-arm, prospective study enrolled ten treatment-naïve patients with a confirmed heterozygous mutation in ACAN. Participants were treated with rhGH (50 µg/kg/day) over 1 year. Main outcomes measured were height velocity and change in height standard deviation score.

The authors found that growth hormone led to short term improvements in growth rate over the course of the year. The treated patients had their growth rate increase from 5.2 centimeters per year to 8.3 centimeters per year while on therapy.

In 2019, the researchers received the 2019 Human Growth Award at the Pediatric Endocrine Society’s Annual Meeting for an abstract related to this work, entitled “Clinical Characterization and Trial of Growth Hormone in Patients with Aggrecan Deficiency: 6 Month Data.”

Handrawn illustration of human Kidneys

Children’s National Nephrology team presents virtually at IPTA’s 11th Congress

Handrawn illustration of human KidneysThe International Pediatric Transplant Association (IPTA) is hosting their 11th Congress meeting March 26-29, 2022, and many Children’s National Hospital providers will be presenting throughout the conference. We hope you will join us!

Diversity, inequity and inclusivity in the practice of pediatric transplantation in the U.S.

Presenter: Marva Moxey-Mims, M.D., division chief, Nephrology

Dr. Moxey-Mims will review the trends in pediatric kidney transplantation over the past decade, focusing on differences by race and ethnicity, whether the gaps have narrowed over that time and steps that can be taken to increase equity.

Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study

Presenter: Asha Moudgil, M.D., medical director, Kidney Transplant

Mycophenolate mofetil (MMF) is a common maintenance immunosuppressant in children receiving kidney transplants but is often discontinued for various reasons. In this multi-center Pediatric Nephrology Research Consortium study, researchers sought to determine the prevalence and reasons for MMF discontinuation and its association with patient and allograft outcomes. They will be discussing their methodology and results from this study.

Additional Children’s National staff involved in the study include:

Changes in diastolic function and cardiac geometry after pediatric kidney transplantation: A longitudinal study

Presenter: Kristen Sgambat, Ph.D., clinical assistant professor

Children with end stage kidney disease are at high risk for cardiovascular morbidities. Indicators of systolic function, such as ejection fraction and fractional shortening, are often preserved and may not reveal cardiac dysfunction until it is severe. Longitudinal changes in diastolic function and cardiac geometry have not been well studied.

Additional Children’s National staff involved in the study include:

COVID19 in pediatric kidney transplant recipients: Incidence, outcomes, and response to vaccine

Presenter: Asha Moudgil, M.D., medical director, Kidney Transplant

At the start of the pandemic, no information was available on the outcomes of pediatric kidney transplant recipients with COVID-19. When the COVID-19 vaccine became available, response of immunosuppressed children to the vaccine was not known. While more information has become available in adult transplant recipients, information on pediatric transplant recipients remains limited.

The team will discuss their methodology of collecting information and their results and conclusions.

Additional Children’s National staff involved in the study include:

Poster presentation: Psychological functioning and adaptive behavior in pediatric patients awaiting renal transplantation.

Presenter: Kaushal Amatya, Ph.D., psychologist

Psychosocial functioning of children with chronic kidney disease (CKD) at pretransplant evaluation is associated with transplant readiness and post-transplant outcomes. Higher prevalence of emotional/behavioral issues is noted in children with CKD compared to healthy counterparts. Although issues with functional impairment is often reported, research on adaptive functioning using a validated measure is lacking. The study aimed to explore psychological and adaptive functioning in pediatric pre-transplant patients to identify areas in need of intervention.

Additional Children’s National staff involved in the study include:

  • Asha Moudgil, M.D., medical director, Kidney Transplant
  • Paige Johnson, Psychology resident

 

boy using a nebulizer

Algorithm for antibiotic use benefits patient care in cystic fibrosis

boy using a nebulizer

Despite national consensus guidelines for antibiotic treatment for pulmonary exacerbations in people with CF, prior research and systematic reviews have repeatedly demonstrated a longstanding lack of sufficient evidence for empiric antibiotic therapy recommendations, leading to a significant variation in how antibiotics are prescribed across CF care centers in the United States.

In a recent quality improvement project, researchers from Children’s National Hospital found that antimicrobial stewardship initiatives are beneficial in standardizing care and fostering positive working relationships between cystic fibrosis (CF) pulmonologists, infectious disease physicians and pharmacists.

Antimicrobial stewardship is a systematic effort to change prescribing attitudes that can provide benefit for people with CF. The objective of this effort was to decrease unwarranted use of broad-spectrum antibiotics for children and adolescents with CF. Through initiation of the empiric antibiotic algorithm, researchers found that the proportion of pulmonary exacerbations with antibiotic use consistent with the algorithm increased from 46.2% to 79.5%.

“This work will provide people with CF the expectation of a more consistent approach in their care, as well as the benefits of care from a multidisciplinary team of experts,” said Andrea Hahn, M.D., an infectious diseases specialist at Children’s National and co-author. “Implementing antimicrobial stewardship in the context of care to persons with CF provides benefit in this complex patient population.”

Despite national consensus guidelines for antibiotic treatment for pulmonary exacerbations in people with CF, prior research and systematic reviews have repeatedly demonstrated a longstanding lack of sufficient evidence for empiric antibiotic therapy recommendations, leading to a significant variation in how antibiotics are prescribed across CF care centers in the United States.

The researchers found that implementing antimicrobial stewardship when caring for people with CF provides benefit in this complex patient population.

“We would encourage other CF centers to explore their own trends in practice to determine whether a similar intervention may be both feasible and beneficial in the treatment of pulmonary exacerbations in persons with CF,” said Dr. Hahn.

doctor listening to patients heart

Children’s National leads patient-centered study of adult congenital heart disease

doctor listening to patients heart

The team will work with the 14 research institutions across the United States to collect data and then examine rates of complications or associated illnesses, as well as how adult patients have accessed health care throughout their lives.

Investigators at Children’s National Hospital and the Louisiana Public Health Institute are leading a $4.9 million research effort to study how gaps in health care affect the health and well-being of adults with congenital heart disease (CHD), supported by the Patient-Centered Outcomes Research Institute (PCORI).

The research is led by Anitha John, M.D., Ph.D., medical director of the Washington Adult Congenital Heart Program at Children’s National Hospital and Thomas Carton, Ph.D., chief data officer at the Louisiana Public Health Institute, as well as two patient co-investigators, Ruth Phillippi and Scott Leezer. The study leads also include representatives from the Adult Congenital Heart Association and Anu Agarwal, M.D., who represents the University of California – San Francisco (UCSF).

“With the increasing number of adult patients with CHD, it is important for us to understand how current recommended practices influence patient outcomes,” says Dr. John. “This project will guide us on how to best care for our patients, not just through childhood, but across their entire lifespans. Most importantly, this project will involve direct outreach to patients, incorporating patient reported outcomes as a measure of long-term outcomes.”

Together, the team will work with the 14 research institutions across the United States to collect data and then examine rates of complications or associated illnesses, as well as how adult patients have accessed health care throughout their lives. The findings may help predict which patients are at greater risk of falling out of routine health care, and when these gaps in care are likely to occur across a patient’s lifespan. The study will also correlate findings with how patients are actually feeling in their everyday lives.

The 14 participating institutions are:

  • Ochsner Health
  • Children’s Hospital of Philadelphia
  • Icahn School of Medicine at Mount Sinai
  • University of California – San Francisco
  • Nationwide Children’s Hospital
  • Duke University Health System
  • NYU Grossman School of Medicine
  • Nicklaus Children’s Hospital
  • Children’s Hospital Colorado
  • University of Miami
  • Columbia University Irving Medical Center
  • Cincinnati Children’s Hospital Medical Center
  • Weill Cornell Medical College
  • University of Florida

“This unprecedented look at the health of adults living with congenital heart disease allows us to get a full spectrum view by combining clinical data with patient-reported health data,” says Dr. Carton.

The first patient-powered registry for adults with CHD — the Congenital Heart Initiative (CHI) is a key component of this research. Launched with seed funding from Children’s National and the Heart Research Alliance at UCSF, the CHI is led by Dr. John and her team at Children’s National in addition to a broad multi-stakeholder advisory board, including patients. The CHI was co-developed with input from patients, clinicians and researchers and continues to involve these voices in the advancement of the registry. Patients who are recruited for this research will participate via enrollment in the registry, which will allow researchers to ask patients directly about health, wellness and any specific barriers to care. Learn more about CHI’s progress in their first annual report.

“Patients, like myself, are charting a new course and we desire answers to significant questions, as do our providers, about impact of lifelong specialized care, along with improved understanding of the quality-of-life patients experience,” says Leezer. “This project represents a huge step forward towards obtaining answers for the adult CHD community.”

The study also draws on the vast health data resources of PCORnet®, the National Patient-Centered Clinical Research Institute, to conduct this study more efficiently. With health records for 66 million patients available for observational studies, the PCORI-funded PCORnet provides vast scale to power research on conditions affecting even small numbers of people.

“We are confident that this research will yield critical learnings that will empower the community, align resources and spur future innovation to better meet the specialized care needs of this emerging population,” says Mark Roeder, president and chief executive officer for the Adult Congenital Heart Association.

PCORI is an independent, nonprofit organization authorized by Congress in 2010 to fund research that will provide patients, their caregivers and clinicians and other health care decision makers with the evidence-based information needed to make better-informed health care choices.

brain network illustration

Changing the surgical evaluation of epilepsy

brain network illustrationThe choice between stereoelectroencephalography (SEEG) and subdural evaluation is not mutually exclusive, according to a new opinion piece published in JAMA Neurology.

In their article, Chima Oluigbo, M.D., pediatric epilepsy neurosurgeon, William D. Gaillard, M.D., division chief of Epilepsy and Neurophysiology and Neurology, both at Children’s National Hospital, and Mohamad Z. Koubeissi, M.D., M.A., from The George Washington University Hospital, discuss how the practicing epileptologist requires a profound understanding of the roles of different technologies. It also looks at how to integrate both traditional and emerging paradigms to optimize seizure control. This issue is particularly relevant to choosing the best method of invasive intracranial electroencephalography monitoring in individual cases.

Noting that despite the dramatic increase in SEEG use in recent years, the authors talk about how many patients still benefit from invasive monitoring using subdural grids. Therefore, it is important to define the considerations that should guide decision-making on the choice of SEEG versus subdural monitoring in each patient. The authors expand on their statement explaining that it is critical to define the roles of SEEG vs subdural grid investigation in each patient as subdural grid evaluations are still indicated in specific circumstances.

Additionally combined hybrid deployment of both techniques may be indicated in specific situations. Accommodation should be made to allow customization of the technique chosen to available technical expertise and equipment as well as patient preference.

Med Games Logo

Continuing medical education through online games

Med Games LogoAndrew Dauber, M.D., MMSc., chief of Endocrinology at Children’s National Hospital, participated as the faculty chair of a Med Games CME educational online activity, to provide continuing medical education for physicians. This game-based activity is intended to meet the educational needs of endocrinologists, endocrine fellows, primary care physicians, physician assistants, nurse practitioners and health care professionals who diagnose and manage children with growth hormone deficiency (CGHD). This CME educational program is provided by Med Learning Group and supported by an educational grant from Novo Nordisk Inc.

Learn more about the program and test your knowledge: ‘Accurate Diagnosis and Effective Management of Children with Growth Hormone Deficiency: What Can You Do to Improve Patient Outcomes in Your Clinical Practice?’

Jacob Smith

Q&A with Pediatric Surgical Innovation Fellow Jacob Smith, M.D.

Jacob Smith

Jacob Smith, M.D.

Jacob Smith, M.D. is currently a fellow with The Joseph E. Robert, Jr. Fellowship in Pediatric Surgical Innovation at Children’s National Hospital. The fellowship provides is an exciting and dynamic post-graduate research experience focused on biomedical innovation. Participants can focus their work on specific areas of interest. Here, Dr. Smith shares some information on his work with the Urology Department.

Q: How has the Joseph E. Robert, Jr., Fellows in Pediatric Surgical Innovation program allowed you to expand your experience in pediatric urology?

A: The Roberts Fellow program has provided me the ability to work with Michael Hsieh, M.D., who has years of experience in UTI and schistosomiasis research. The UTI research has been a focus of mine and we are working on ways to diagnosis and treat UTI faster in patients. One population that this can benefit are those that deal with recurrent UTIs, such as patients in our spina bifida population.

Q: Talk a little about your work on spina bifida and areas of opportunity for research.

A: Briony Varda, M.D. is heavily involved in our spina bifida program here at Children’s National. I am working with Dr. Varda to develop a database that looks at the use of the emergency department (ED) by children with spina bifida in the Washington, D.C. area. We are also conducting interviews with families and other stakeholders in this population to better understand the factors that drive this population to utilize the ED. We hope that this research can give us a better understanding of the spina bifida care in our area and inform us to provide improvement in care.

Q: How will your work to develop methods to diagnose urinary tract infections faster and how will this benefit our patient population?

A: As mentioned before, a common patient population that deals with recurrent UTIs is the spina bifida population. The protocol that we are attempting to develop would provide us quicker results than the standard urine culture and sensitivity testing that can take anywhere between 48-72 hours to result on average. We hope by providing a quicker result, we can better identify the necessary treatment these patients need to treat their infections. Another scenario that we hope this can be utilized in is for those patients that have recurrent UTI symptoms but negative urine cultures. We hope we can determine if there are viable cells that may be too few to culture but still could cause these symptoms.

Q: What are you currently working on that you are most excited about?

A: As you can tell, a lot of my research is conducted around the spina bifida population. I am excited to dive into the data we have collected on this population and determine if there are ways we could improve the care of these patients.

Q: What made you interested in specializing in pediatric urology?

A: Pediatric urology is a great field. It has a very diverse patient population. There are a multitude of problems that could arise from multiple congenital malformations to stones and voiding dysfunctions. There is also a range of cases from minor and major reconstruction, robotics, endourology and laparoscopy. One thing that does differentiate pediatric urology is that many of the problems that we repair are congenital and it is a privilege to be able to help these children and families. In fact, I was a patient myself as a child with a ureteral malformation which required surgery. The concept of helping other children with urology concerns brings an obvious “pay-it-forward” mentality that also attracted me to the field. I am excited to obtain the knowledge and skills necessary to treat my future patients.