Epstein-Barr virus

Study with largest cohort in the Western world sheds light on Epstein-Barr virus

Epstein-Barr virus

Epstein-Barr virus is a member of the herpes family and it spreads primarily through saliva.

Children’s National Hospital experts provided a contemporary description of the epidemiology, clinical presentation and management of chronic active Epstein-Barr virus (CAEBV), shedding light on this very rare disease. The paper, published in Blood Advances, assessed 57 patients outside of Asia — the biggest international retrospective cohort study published in the Western world.

Epstein-Barr virus is a member of the herpes family and it spreads primarily through saliva. Once a person is infected with Epstein-Barr virus, the immune system will control the infections, but the virus lies in a dormant state in the patient’s B Cells. However, in some patients, there is a failure of the body to control the infection, and the virus is found inside the patient’s T and/or NK cells. These rare patients are diagnosed with CAEBV. The hallmark of the disease is proliferation of Epstein-Barr virus-infected T or NK cells that infiltrate tissues, leading to end-organ damage. Patients most often experience fevers, hepatosplenomegaly, liver inflammation, cytopenias and lymphoproliferation that may progress to lymphoma.

Given it is most prevalent in Asia, little is known about the disease in the Western world. There has only been one published paper regarding the outcomes of patients in the U.S., which included 19 patients amassed over 28 years, and was published a decade ago.

Multiple treatments have been attempted to control the disease, but none have resulted in consistent remission. Historically, the consensus is to use steroids and/or antiviral drug in combination with proteasome inhibitor agents. In some cases, clinicians also use cytotoxic chemotherapy to reduce disease burden and improve the patient’s condition before HSCT. Still, this approach is limited because most patients die due to the progression of their disease despite these interventions.

Ultimately, most of these patients are referred for allogeneic hematopoietic stem cell transplantation (HSCT), which is the only known curative therapy for CAEBV. However, the best approach to control disease prior to HSCT, as well as the optimal conditioning regimen, are unknown.

“For the first time in many years, we provide insight on contemporary treatment options to consider for patients with CAEBV, as well as identifying risk factors for worse outcomes,” said Blachy Dávila Saldaña, M.D., blood and marrow transplant specialist at Children’s National and lead author of the study. “HSCT is curative, but patients need to be considered prior to the evolution of more advanced disease, particularly lymphoma. We also provide a new platform that will inform research on new interventions and therapies for this population.”

“CAEBV remains a challenging disorder to treat, especially once severe complications develop,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National. “However, our data suggests that T cell modulating therapies may enhance disease control, and future studies should address this question in a controlled setting.”

Future steps also include performing genetic studies to identify those at risk of developing the disease, and developing new platforms for treatment, including checkpoint inhibitors and cytotoxic lymphocyte therapies (CTL’s), which is a form of adoptive immunotherapy that employs virus-specific T cells.

The cohort includes patients treated in CNH and multiple institutions around the world, including Texas Children’s and the National Institutes of Health. “This work was only possible through our collaborative research in anti-EBV cellular therapies,” said Dr. Dávila.

Kristen Sgambat, Ph.D., and Asha Moudgil, M.D.

Kristen Sgambat, Ph.D., R.D. and Asha Moudgil, M.D. receive Editors’ Choice Award

Kristen Sgambat, Ph.D., and Asha Moudgil, M.D.

Children’s National Hospital researchers Kristen Sgambat, Ph.D., and Asha Moudgil, M.D., were presented with the 2021 AJKD Editors’ Choice Award.

The American Journal of Kidney Disease (AJKD) announced the selection of the 2021 AJKD Editors’ Choice Award, recognizing outstanding articles published in their journal this year.

Children’s National Hospital researchers Kristen Sgambat, Ph.D., and Asha Moudgil, M.D., were presented with the 2021 AJKD Editors’ Choice Award for their July 2021 study, Social determinants of cardiovascular health in African American children with chronic kidney disease: An analysis of the chronic kidney disease in children.

The study is the first to investigate the relationship between race, socioeconomic factors and cardiovascular health in children with chronic kidney disease. Dr. Sgambat, Dr. Moudgil and their collaborators found that African American children with chronic kidney disease had increased evidence of socioeconomic challenges, including food insecurity, reliance on public insurance, lower household incomes and lower levels of maternal education. These children had worse cardiovascular outcomes than Caucasian children with the same chronic kidney conditions. Notably, the cardiovascular outcomes of the two groups became more alike when statistical analysis was applied to equalize their socioeconomic factors. This suggests that these socioeconomic indicators do play a role in adverse cardiovascular health outcomes observed among African American children with chronic kidney disease.

“The findings of this study are important because they highlight the urgent need to shift the clinical research paradigm to investigate how social, rather than biological, factors contribute to racial differences in health outcomes,” said Dr. Sgambat. “Future studies should focus on the impact of systemic racism on cardiovascular health among children with chronic kidney disease, an area not well-studied so far.”

doctor taking blood sample from child

Study shows increase in diabetes cases during COVID-19 pandemic

doctor taking blood sample from child

A retrospective study found pediatric Type 1 diabetes cases rose 15.2% and Type 2 diabetes cases increased by 182% during the first year of the COVID-19 pandemic compared to the prior two years— affecting non-Hispanic Black youth the most.

While the effects of COVID-19 on diabetes-related outcomes are extensively studied in adults, data about the incidence and severity of presentation of pediatric new-onset Type 1 diabetes (T1D) and Type 2 diabetes (T2D) is limited. A new retrospective study of 737 youth diagnosed with diabetes at Children’s National Hospital between March 11, 2018 and March 10, 2021 found pediatric T1D cases rose 15.2% and T2D cases increased by 182% during the first year of the COVID-19 pandemic compared to the prior two years — affecting non-Hispanic Black youth the most.

The study, published in Hormone Research in Paediatrics, compared T1D and T2D cases during the first 12 months of the pandemic, between March 11, 2020 and March 10, 2021, to the same time in the previous two years. This increase in cases was accompanied by a nearly six-fold rise in diabetic ketoacidosis (DKA) and a 9.2% incidence of hyperosmolar DKA during the pandemic as compared to no cases in the two years prior.

“A better understanding of the impact of the COVID-19 pandemic is crucial for raising public awareness, shaping policy and guiding appropriate health screenings,” said Brynn Marks, M.D., M.S.H.P.Ed., endocrinologist at Children’s National and lead author of the study.

Children’s National provides clinical care to approximately 1,800 youth with T1D and 600 youth with T2D annually. In the two years before the pandemic, cases of T2D accounted for 25.1% of all newly diagnosed diabetes at Children’s National compared to 43.7% during the pandemic. Before the pandemic, females accounted for 59.6% of youth with new-onset T2D but 58.9% of new-onset T2D cases were among males during the pandemic.

The researchers noted that the rise in cases of T2D and severity of presentation of both T1D and T2D during the pandemic disproportionately impacted non-Hispanic Black youth (NHB). NHB youth accounted for 58% of cases of T2D pre-pandemic, which further increased to 77% during the pandemic. The findings also showed that cases of DKA among NHB youth newly diagnosed with T1D increased during the pandemic compared to the two years before (62.7% vs. 45.8%, p=0.02).  Before the pandemic, there was no significant difference in A1c at T1D diagnosis between racial and ethnic groups. However, during the pandemic, hemoglobin A1c levels were higher among NHB youth.

“Future studies are needed to understand the root cause of the disproportionate impact of the COVID-19 pandemic on non-Hispanic Black youth with newly diagnosed diabetes,” said Dr. Marks. “These outcomes during the pandemic will likely worsen pre-existing health care disparities among youth with diabetes.  In understanding the indirect effects of our response to the pandemic, we can better inform future emergency responses and develop strategies to improve outcomes for all youth living with diabetes.”

Neuronal network with electrical activity

Neonatal hypoxia-ischemia causes damage to the cholinergic system

Neuronal network with electrical activity

Study suggests permanent injury to the cholinergic system after neonatal hypoxia-ischemia is responsible for the poor executive functions and difficulties in learning and memory.

Newborn babies who go through periods of low oxygen — also known as hypoxic-ischemic encephalopathy — during their first hours of life often experience difficulties in learning, memory and executive functions later on. Even when treated with therapeutic hypothermia, memory deficits and executive functions remain severely affected. These functions are linked to a neurotransmitter network called the cholinergic system.

“Complications from hypoxic-ischemic brain injury contribute to one-quarter of neonatal deaths worldwide and cause significant long-term neurological morbidity,” explains Panagiotis Kratimenos, M.D., Ph.D., neonatologist at Children’s National Hospital and Assistant Professor of Pediatrics at the George Washington University School of Medicine and Health Sciences.

In a study published in the Journal of Comparative Neurology led by Frances Northington, M.D., co-director of Neurosciences Intensive Care Nursery at Johns Hopkins and Professor of Pediatrics at Johns Hopkins University School of Medicine, with contributions from Dr. Kratimenos, the authors found significant injury to the neurons of the cholinergic systems in specific parts of the brain after exposure to low oxygen and restricted blood flow. These areas included the ipsilateral medial septal nucleus (MSN), the ipsilateral nucleus basalis of Meynert (nbM) and striatum. Within the injured part of the cortex at the site of injury, acetylcholine — the neurotransmitter found in cholinergic systems — was abnormally overactivated.

The authors hypothesize that permanent injury to the cholinergic system after neonatal hypoxia-ischemia is responsible for the poor executive functions and difficulties in learning and memory.

“Because cholinergic systems can easily be manipulated pharmacologically with already established treatments that have been used in other areas of medicine, they could be a good a target for therapeutic interventions for neonates with hypoxic-ischemic encephalopathy,” says Dr. Kratimenos.

Read the full article in the Journal of Comparative Neurology.

t cells fighting cancer cell

Personalized T cell immunotherapy for brain tumors closer to becoming reality

t cells fighting cancer cell

Children’s National Hospital experts developed a new approach that discovered unique proteins in an individual tumor’s cells, which then helped scientists generate personalized T cells to target and kill tumors.

Children’s National Hospital experts developed a new approach that discovered unique proteins in an individual tumor’s cells, which then helped scientists generate personalized T cells to target and kill tumors, according to a pre-clinical study published in Nature Communications.

This effort is the first to create a new workflow for neoantigen identification that incorporates both genetic sequencing and protein identification to create a personalized treatment for medulloblastoma in children, a common malignant brain tumor. Given these promising findings, the researchers are now designing a phase I clinical trial slated to open in 12-18 months.

“This work is an incredibly exciting advancement in personalized medicine. It will allow us to treat patients with a novel T cell therapy that is developed for each individual patient to specifically attack and kill their tumor,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National and co-senior author on the paper. “This treatment will offer a potential option for children with hard-to-treat brain tumors for which all other therapeutic options have been exhausted.”

Catherine Bollard

Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National and co-senior author on the paper.

First, the researchers sequenced the DNA of small tissue samples while studying its complete set of proteins that influence cancer biology — also named a “low-input proteogenomic approach” by the authors. After analyzing the empirical data, which shies away from the commonly used predictive models, the researchers developed a T cell immunotherapy that targets the tumor’s unique proteins and allows the T cells to distinguish between healthy cells and tumor cells. This means that Rivero-Hinojosa et al. managed to merge two research fields, proteogenomics and immunotherapy, and lay the groundwork for personalized, targeted T cell therapies to treat children with brain tumors.

“Neoantigen discovery techniques have either been dependent upon in silico prediction algorithms or have required a significant amount of tumor tissue, making them inappropriate for most brain tumors,” said Brian Rood, M.D., medical director of Neuro-oncology and the Brain Tumor Institute at Children’s National. “This neoantigen identification pipeline creates a new opportunity to expand the repertoire of T cell-based immunotherapies.”

Samuel Rivero-Hinojosa

Samuel Rivero-Hinojosa, Ph.D., staff scientist at Children’s National and first author of the study.

Tumor cells have damaged DNA that create mutations during the repair process because they do not do a good job at maintaining their DNA fidelity. The repairs therefore create aberrant DNA that codes for proteins that were never intended by the genetic code and, consequently, they are unique to the individual’s tumor cells.

“We developed a new filtering pipeline to remove non-annotated normal peptides. Targeting antigens that are completely specific to the tumor, and expressed nowhere else in the body, will potentially increase the strength of tumor antigen-specific T cell products while decreasing the toxicity,” said Samuel Rivero-Hinojosa, Ph.D., staff scientist at Children’s National and first author of the study.

Once the experts identified these unique peptides, they used them to select and expand T cells, which showed specificity for the tumor specific neoantigens and the ability to kill tumor cells. The next step is to conduct a clinical trial in which a patient’s own T cells are trained to recognize their tumor’s unique neoantigens and then reinfused back into the patient.

Brian Rood

Brian Rood, M.D., medical director of Neuro-oncology and the Brain Tumor Institute at Children’s National and co-senior author on the paper.

From an immunotherapy standpoint, tumor specificity is important because when clinicians treat patients with T cell therapies, they want to make sure that the T cells directly target and kill the tumor and will not cause devastating harm to healthy cells. This paper demonstrated that it may be possible to create a better efficacy and safety margin with this new approach.

In the past five years, under the leadership of Dr. Bollard, the Center for Cancer and Immunology Research at Children’s National has advanced the scientific knowledge in preclinical and clinical settings. The center discovered a signaling pathway that can be hijacked to prevent brain tumor development, and further advanced translational research with several key first-in-human studies that utilized novel cell therapies to treat cancer and life-threatening viral infections.

Blood sample tube for anti-Müllerian hormone

A look at the clinical utility of anti-Mullerian hormone

Blood sample tube for anti-Müllerian hormone

Anti-Mullerian hormone (AMH), also known as Mullerian inhibiting substance (MIS), is a hormone produced exclusively in the gonads. It was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females.

In a mini-review published in The Journal of Clinical Endocrinology and Metabolism, Roopa Kanakatti Shankar, M.D., pediatric endocrinologist at Children’s National Hospital and an associate professor of pediatrics at the George Washington University School of Medicine and Health Sciences, and co-authors offer an updated synopsis on AMH and its clinical utility in pediatric patients.

The authors performed a systematic search for studies related to the physiology of AMH, normative data and clinical role in pediatrics. After reviewing 70 clinical studies and systematic reviews, they conclude that, “AMH has widespread clinical diagnostic utility in pediatrics but interpretation is often challenging and should be undertaken in the context of not only age and sex but also developmental and pubertal stage of the child.”

Other authors from Children’s National Hospital include Andrew Dauber, M.D., MMSc, Tazim Dowlut-Mcelroy, M.D., and Veronica Gomez-Lobo, M.D.

Read the full review in The Journal of Clinical Endocrinology and Metabolism.

Dr. Sable performing an echocardiogram in Uganda

Penicillin slows impacts of rheumatic heart disease in Ugandan children

Dr. Sable performing an echocardiogram in Uganda

“We know from previous studies that though it is not always well-documented, sub-Saharan Africa continues to have some of the highest numbers of people with rheumatic heart disease and the highest numbers of people dying from it,” said Craig Sable, M.D., associate chief of Cardiology at Children’s National Hospital and co-senior author of the study. “This study is the first large-scale clinical trial to show that early detection coupled with prophylactic treatment of penicillin is feasible and can prevent rheumatic heart disease from progressing and causing further damage to a child’s heart.”

Penicillin, a widely available and affordable antibiotic, may be one key to turning the tide on the deadly impacts of rheumatic heart disease (RHD) for children in developing nations. This according to the new findings of a large-scale, randomized controlled trial completed in Uganda and published in the New England Journal of Medicine.

The most devastating feature of RHD is severe heart valve damage that is caused by rheumatic fever — a condition that results from the body’s immune system trying to fight poorly treated, repeat infections from streptococcus bacteria, also known as strep throat. Though widely eradicated in nations such as the United States due to the swift detection and treatment of strep throat, rheumatic fever remains prevalent in developing countries including those in sub-Saharan Africa. Current estimates are that 40.5 million people worldwide live with rheumatic heart disease, and that it kills 306,000 people every year. Most of those affected are children, adolescents and young adults under age 25.

“We know from previous studies that though it is not always well-documented, sub-Saharan Africa continues to have some of the highest numbers of people with rheumatic heart disease and the highest numbers of people dying from it,” said Craig Sable, M.D., associate chief of Cardiology at Children’s National Hospital and co-senior author of the study. “This study is the first large-scale clinical trial to show that early detection coupled with prophylactic treatment of penicillin is feasible and can prevent rheumatic heart disease from progressing and causing further damage to a child’s heart.”

The study was led by an international panel of pediatric cardiac experts from institutions including Children’s National, Cincinnati Children’s Medical Center, the Uganda Heart Institute and Murdoch Children’s Research Institute in Melbourne, Australia.

“Our study found a cheap and easily available penicillin can prevent progression of latent rheumatic heart disease into more severe, irreversible valve damage that is commonly seen in our hospitals with little or no access to valve surgery,” said co-lead author Emmy Okello, M.D., chief of Cardiology at the Uganda Heart Institute.

To Andrea Beaton, M.D., associate professor of Cardiology at Cincinnati Children’s and co-lead author, this is the first contemporary randomized controlled trial in rheumatic heart disease. “The results are incredibly important on their own, but also demonstrate that high-quality clinical trials are feasible to address this neglected cardiovascular disease,” she said.

Beaton et al. named the trial Gwoko Adunu pa Lutino (GOAL), which means “protect the heart of a child.” The study enrolled 818 Ugandan children and adolescents ages 5 to 17 years old who were diagnosed with latent rheumatic heart disease to see if an injection of penicillin was effective at preventing their heart condition from worsening.

“There are many challenges with recruitment and retention of trial participants in areas like our study region in Uganda,” said Dr. Sable. “But it is critical to work together and overcome barriers, because we must study these treatments in the people most affected by the condition to understand how they, and others like them, may benefit from the findings.”

Of the 799 participants who completed the trial, the group receiving a prophylactic injection of penicillin (399 volunteers) had three participants show evidence of worsened rheumatic heart disease on repeat echocardiogram after two years. In contrast, 33 of the 400 volunteers in the control group, who received no treatment, showed similar progression on echocardiogram results.

Professor Andrew Steer, who is theme director of Infection and Immunity at Murdoch Children’s Research Institute in Melbourne and who served as senior author of the study, said screening for latent rheumatic heart disease was critical to stop progression because heart valve damage was largely untreatable. “Most patients are diagnosed when the disease is advanced and complications have already developed. If patients can be identified early, there is an opportunity for intervention and improved health outcomes.”

The results were shared in a special presentation at the American Heart Association’s Scientific Sessions on the same day that the findings were published in the New England Journal of Medicine.

The trial was supported by the Thrasher Pediatric Research Fund, Gift of Life International, Children’s National Hospital Foundation: Zachary Blumenfeld Fund, Children’s National Hospital Race for Every Child: Team Jocelyn, the Elias/Ginsburg Family, Wiley-Rein LLP, Phillips Foundation, AT&T Foundation, Heart Healers International, the Karp Family Foundation, Huron Philanthropies and the Cincinnati Children’s Hospital Heart Institute Research Core.

Learn more about the challenges of rheumatic heart disease in sub-Saharan Africa and other developing parts of the world through the Rheumatic Heart Disease microdocumentary series:

sick child in palliative care hospital bed

New study compares first and second wave of MIS-C

sick child in palliative care hospital bed

When comparing the first and second wave of patients diagnosed with multi-system inflammatory syndrome in children (MIS-C), the second wave patients had more severe illness, according to a new prospective cohort study at Children’s National Hospital in Washington, D.C.

When comparing the first and second wave of patients diagnosed with multi-system inflammatory syndrome in children (MIS-C), the second wave patients had more severe illness, according to a new prospective cohort study of 106 patients at Children’s National Hospital in Washington, D.C. The results, published in The Pediatric Infectious Disease Journal, show that despite increased severity in the second wave cohort, both cohorts had similarities in cardiac outcomes and length of stay. Researchers are still working to better understand the exact immunologic mechanisms that trigger MIS-C and the specific factors accounting for its rare occurrence.

“We’ve now seen three distinct waves of MIS-C since the beginning of the pandemic, each wave following national spikes in cases,” said Roberta DeBiasi, M.D., chief of the Division of Pediatric Infectious Diseases at Children’s National and co-author of the study. “Kids in the second wave cohort had potentially experienced intermittent and/or repeated exposures to the virus circulating in their communities. In turn, this may have served as repeated triggers for their immune system which created the more severe inflammatory response.”

In this new study, key demographic features Children’s National researchers previously identified held true across both waves – including the fact that Black and Latino children are significantly more affected than white children.  Of the 106 patients, 54% were Black and 39% were Hispanic. The authors also noted that 75% of the patients were otherwise healthy children with no underlying medical conditions.

“While we believe the most recent third wave associated with the delta variant surge is tapering off, the findings from the first two waves provide important baseline information and are highly relevant for clinicians across the country that are evaluating and treating kids with MIS-C,” said Dr. DeBiasi.

Children’s National has cared for more than 4,200 symptomatic patients with SAR-CoV-2 infection and more than 185 MIS-C patients since the pandemic began. The first wave of MIS-C patients were hospitalized between March 2020 and October 2020. Second wave patients were hospitalized between November 2020 and April 2021. Each wave came 4-6 weeks following periods of COVID-19 surges in the community.

In the study, researchers compared patient demographics, clinical features, laboratory results, radiographic images, therapies and outcomes. The second wave cohort had a higher proportion of children 15 years of age or older. Patients also presented more frequently with shortness of breath and required more advanced respiratory and inotropic support. Researchers also found that patients in the second wave were less likely to test positive for SARS-CoV-2 on a PCR test.

Dr. DeBiasi and her team hope to unlock even more insights as they now analyze data from the third wave associated with the delta variant, which currently appears to have affected less children than the previous two. Children’s National is also working in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) to study the long-term effects of MIS-C and COVID-19 on the pediatric population after recovery. This is among the largest and longest studies being conducted, and researchers are hopeful the findings will help improve treatment of COVID-19 and MIS-C in the pediatric population both nationally and around the world.

“Our timely established multidisciplinary MIS-C task force here at Children’s National allowed us to reduce the learning curve,” said Ashraf S. Harahsheh, M.D., F.A.A.P., F.A.C.C., director of Quality Outcomes in Cardiology and co-first author of the study. “Experience from other centers showed that immunotherapy was utilized more frequently in recent MIS-C cohorts leading to reduction in percentage of cardiac complications. On the other hand, and despite having increased illness severity in the second cohort, our approach with prompt immunotherapy helped stabilize the rate of cardiac complications.”

Rare Diseases Institute sign

Children’s National Rare Disease Institute named a Center of Excellence

Rare Diseases Institute sign

RDI, which includes the largest clinical group of pediatric geneticists in the nation, focuses on developing the clinical care field of more than 8,000 rare diseases currently recognized and advancing the best possible treatments for children with these diseases.

The Rare Disease Institute (RDI) at Children’s National Hospital announced its designation as a NORD Rare Disease Center of Excellence, joining a highly select group of 31 medical centers nationwide. This new, innovative network seeks to expand access and advance care and research for rare disease patients in the United States. The program is being led by the National Organization for Rare Disorders (NORD), with a goal to foster knowledge sharing between experts across the country, connect patients to appropriate specialists regardless of disease or geography, and to improve the pace of progress in rare disease diagnosis, treatment and research.

“Children’s National has worked closely with NORD to move this program forward and is very proud to be amongst the first group of recognized centers,” said Marshall Summar, M.D., chief of the Division of Genetics and Metabolism and the director of RDI at Children’s National. “This is a recognition of the institutional efforts, as we take care of patients with the rare disease and help set the standard for the field.”

RDI, which includes the largest clinical group of pediatric geneticists in the nation, focuses on developing the clinical care field of more than 8,000 rare diseases currently recognized and advancing the best possible treatments for children with these diseases.

In February 2021, RDI became the first occupant of the new Children’s National Research & Innovation Campus, a first-of-its-kind pediatric research and innovation hub. The campus now also houses the Center for Genetic Medicine Research, and together researchers are constantly pursuing high-impact opportunities in pediatric genomic and precision medicine. Both centers combine its strengths with public and private partners, including industry, universities, federal agencies, start-up companies and academic medical centers. They also serve as an international referral site for rare disorders.

People living with rare diseases frequently face many challenges in finding a diagnosis and quality clinical care. In establishing the Centers of Excellence program, NORD has designated clinical centers across the U.S. that provide exceptional rare disease care and have demonstrated a deep commitment to serving rare disease patients and their families using a holistic, state of the art approach.

“Right now, far too many rare diseases are without an established standard of care. The Centers of Excellence program will help set that standard – for patients, clinicians, and medical centers alike,” said Ed Neilan, chief scientific and medical officer of NORD. “We are proud to announce Children’s National as a NORD Rare Disease Center of Excellence and look forward to their many further contributions as we collectively seek to improve health equity, care and research to support all individuals with rare diseases.”

Each center was selected by NORD in a competitive application process requiring evidence of staffing with experts across multiple specialties to meet the needs of rare disease patients and significant contributions to rare disease patient education, physician training and research.

Dr. Javad Nazarian

Q&A with Dr. Javad Nazarian on his upcoming work on low-grade gliomas

Dr. Javad Nazarian

Supported by the Gilbert Family Foundation, Dr. Nazarian’s return is part of a special research program within the Gilbert Family Neurofibromatosis Institute that focuses on NF1 research.

Javad Nazarian, Ph.D., M.Sc., associate professor of Pediatrics at George Washington University and professor at the University of Zurich, has expanded his research group at Children’s National to focus on Neurofibromatosis type 1 (NF1) transformed low-grade gliomas (LGGs). Dr. Nazarian will apply his expertise from establishing a successful DIPG (diffuse intrinsic pontine glioma) and DMG (diffuse midline glioma) program in Zurich Switzerland and previously at Children’s National.

In addition to his continued research in Zurich, as a principal investigator at the Department of Genomics and Precision Medicine at Children’s National Dr. Nazarian plans on aggregating his knowledge to the new research and work spearheaded at Children’s National. As one of the first research teams to move to the Children’s National Research & Innovation Campus, Dr. Nazarian’s group is excited to use the opportunity to establish cutting-edge and clinically translational platforms.

Supported by the Gilbert Family Foundation, Dr. Nazarian’s return is part of a special research program within the Gilbert Family Neurofibromatosis Institute that focuses on NF1 research. This research includes associated gliomas with a special emphasis on NF1-associated transformed anaplastic LGGs. His team will develop new avenues of research into childhood and young adult NF-associated LGGs with a special emphasis on transformed high-grade gliomas.

Dr. Nazarian is excited for what’s to come and his goals are clear and set. Here, Dr. Nazarian tells us more about his main objectives and what it means for the future of pediatric neuro-oncology care at Children’s National.

  1. What excites you most about being back at Children’s National?

I have received most of my training at Children’s National, so this is home for me. Being one of the nation’s top children’s hospitals gives a unique advantage and ability to advocate for childhood diseases and cancers. It is always exciting to play a part in the vision of Children’s National.

  1. What are some of the lessons learned during your time working in Zurich? And how do you think these will compliment your work at Children’s National?

We developed a focused group with basic research activities intertwined with clinical needs.  The result was the launch of two clinical trials. I also helped in developing the Diffuse Midline Glioma-Adaptive Combinatory Trial (DMG-ACT) working group that spans across the world with over 18-member institutions that will help to design the next generation clinical trials. I will continue leading the research component of these efforts, which will have a positive impact on our research activities at Children’s National.

  1. How does your work focusing on low-grade gliomas formulating into high-grade gliomas expand and place Children’s National as a leader in the field?

Scientifically speaking, transformed LLGs are very intriguing. I became interested in the field because these tumors share molecular signatures similar to high-grade gliomas (HGGs). Our team has done a great job at Children’s National to develop tools – including biorepositories, avatar models, drug screening platforms, focused working groups, etc. – for HGGs. We will apply the same model to transformed LGGs with the goal of developing biology-derived clinical therapeutics for this patient population.

  1. How will this work support families and patients seeking specific neuro-oncology care?

We will develop new and high thruput tools so that we can better study cancer formation or transformation. These tools and platforms will allow us to screen candidate drugs that will be clinically effective. The main focus is to accelerate discovery, push drugs to the clinic, feed information back to the lab from clinical and subsequently design better therapies.

  1. You are one of the first scientists to move to the Children’s National Research & Innovation Campus. What are some of the valuable changes or advancements you hope to see as a result of the move?

The campus will provide high-end facilities, including cutting-edge preclinical space, and allow for team expansion. The close proximity to Virginia Tech will also provide an environment for cross-discipline interactions.

  1. Anything else you think peers in your field should know about you, the field or our program?

The team at Children’s National includes Drs. Roger Packer and Miriam Bornhorst. Both have provided constant clinical support, innovation and clinical translation of our findings. I look forward to working with them.

group of teenagers sitting on a wall

Assessing the pandemic’s impact on adolescents with and without ADHD

group of teenagers sitting on a wall

Understanding factors that foster resilience and buffer against the negative psychological impact of COVID-19 is critical to inform efforts to promote adjustment, reduce risk and improve care, particularly for adolescents with neurodevelopmental disorders.

In a new prospective longitudinal study, Melissa Dvorsky, Ph.D., director of the ADHD & Learning Differences Program at Children’s National Hospital and lead author, and others address this gap by investigating the impact of the COVID-19 pandemic on adolescents’ mental health and substance use, and by assessing specific positive coping strategies among adolescents with and without attention-deficit/hyperactivity disorder (ADHD).

Read the full study in Research on Child and Adolescent Psychopathology.

brain network illustration

Cardiopulmonary bypass may cause significant changes to developing brain and nerve cells

brain network illustration

Cardiopulmonary bypass, more commonly known as heart-and-lung bypass, has some unique impacts on the creation and growth of brain cells in the area of a child’s brain called the subventricular zone (SVZ), according to a study in the Annals of Neurology. The SVZ is a critical area for the growth and migration of neurons and nerve cells called neuroblasts, both of which ultimately contribute to the proper development of key brain structures and functions during the early years of life.

The findings, from a study conducted in the Cardiac Surgery Research Laboratory at Children’s National Hospital, provide new insight into the cellular impacts of the cardiopulmonary bypass machine on brain growth and development for newborn infants with congenital heart disease. They will have an important role in the refinement of strategies to help protect the fragile brains of children who require lifesaving cardiac surgery with cardiopulmonary bypass immediately after birth.

Specifically, the research team found that during cardiopulmonary bypass:

  • Creation of neurons (neurogenesis) in the neonatal and infant subventricular zone is altered.
  • Migration of nerve cells, called neuroblasts, to the frontal lobe is potentially disrupted.
  • Changes to the growth and movement of neurons in the SVZ are prolonged.
  • Cortical development and expansion is impaired.
  • Specific types of neurons found only in the brain and spinal cord, called interneurons, are also affected.

The study uses an innovative pre-clinical model of the developing brain that is more anatomically and physiologically similar to human neonates and infants than those used in prior studies and in most neurological laboratory-based research.

Cardiopulmonary bypass is one of several key factors thought to cause children with congenital heart disease to sometimes demonstrate delays in the development of cognitive and motor skills. These disabilities often persist into adolescence and adulthood and can ultimately represent long-term neurocognitive disabilities. It is also believed that genetic factors, abnormal blood flow to the brain while in utero or low cardiac output after surgical procedures on the heart may contribute to these challenges.

“Unraveling cellular and molecular events during surgery using this preclinical model will allow us to design therapeutic approaches that can be restorative or reparative to the neurogenic potential of the neuronal stem precursor cells found in the subventricular zone of the neonatal or infant brain,” says Nobuyuki Ishibashi. M.D., Foglia-Hills Professor of Pediatric Cardiac Research, director of the Cardiac Surgery Research Laboratory at Children’s National and senior author on the study. “In particular, previous studies in our laboratory have shown improvement in the neurogenic activities of these precursor cells when they are treated with mesenchymal stromal cells (MSCs).”

The findings from this study further support the work already underway in the NIH-funded MeDCaP clinical trial for neonates and infants undergoing cardiac surgery using the cardiopulmonary bypass machine. That trial uses the heart and lung machine itself to deliver MSCs directly into the main arteries that carry blood to the brain.

Denver Brown

New grant to conduct single center pilot trial of alkali therapy in children with CKD

Denver Brown

Denver D. Brown, M.D., recipient of the Child Health Research Career Development Award.

Linear growth (i.e., height) impairment is commonly observed in children with chronic kidney disease (CKD). Several studies have suggested metabolic acidosis, a frequent consequence of mild to moderate CKD in children, as a contributing factor to linear growth failure in these patients. Grant awardee Denver D. Brown, M.D., aims to conduct a pilot trial in children with mild metabolic acidosis and CKD, comparing differences in linear growth between an observation period versus a period of supplementation with alkali therapy (i.e., treatment for metabolic acidosis).

“This grant is so important because there has never been a clinical trial of alkali therapy in children with CKD despite its frequent use in this population” says Dr. Brown. “This research has the potential to better inform treatment practices with the aim of improving the care of our young, vulnerable patients.”

The Child Health Research Career Development Award (CHRCDA) of $125,000 will support Dr. Brown in her efforts to carry out this pilot trial.

“Funding for this pilot study could lay the groundwork for a large, randomized controlled clinical trial, which would help fill a major gap in knowledge as to the precise benefits of alkali therapy, especially regarding growth in children with impaired kidney function.”

Maria Susana Rueda Altez

Maria Susana Rueda Altez, M.D., to lead as Junior Section President-Elect

Maria Susana Rueda Altez

Maria Susana Rueda Altez, M.D., junior section president-elect for the Society for Pediatric Research (SPR).

Maria Susana Rueda Altez, M.D., was selected as junior section president-elect for the Society for Pediatric Research (SPR). During her tenure, Dr. Rueda Altez will ensure more trainees benefit from networking opportunities and leverage her online communications experience to increase awareness, membership and participation in SPR among students, residents and fellows.

The president of the junior section is a fellow who is elected by other junior member peers and is in-charge of managing and enhancing the junior section, by participating in SPR council meetings, promoting membership among trainees and reinforcing the pipeline from junior to active members.

“I am so honored, not only as a Peruvian physician, but as an international medical graduate (IMG), to have been elected for this position,” said Dr. Rueda Altez. “As an IMG, there are special challenges to conducting research, so I plan to raise awareness and provide support to my fellow IMG junior members.”

To Beth A. Tarini, M.D., M.S., SPR president and associate director for the Center for Translational Research at Children’s National Hospital, it is an honor for the hospital to have representatives in the roles of SPR president and SPR junior section president-elect simultaneously.

Dr. Rueda Altez added that there is an urgent need for increased funding in pediatric research, especially for minority and health disparities research. Through her participation in SPR, she will also have the opportunity to advocate for increases in child health research funding.

“I encourage all the trainees and junior faculty in our institution to join the SPR junior section,” said Dr. Rueda Altez. “It provides wonderful resources for career development and guidance, grant writing courses and invaluable mentorship.”

Her research interest is newborn infections, and her overall goal is to reduce the unnecessary use of antibiotics in this population.

“I am currently working on a quality improvement project to reduce the number of days NICU infants are exposed to antibiotics,” said Dr. Rueda Altez. “I have developed a project to ascertain the utility of microbial cell-free DNA next generation sequencing, a novel microbiologic diagnostic tool, for the diagnosis of neonatal infections.”

Dr. Rueda Altez’s work on neonatal sepsis will help scientists better distinguish between neonates who do and don’t have serious bacterial infections.

“Right now, when in doubt we tend to treat it as bacterial infections, which can lead to unnecessary medical treatment and worsen resistance to antibiotics,” said Tarini.

Dr. Rueda Altez also serves as an independent reviewer of investigational manuscripts for The Journal of Pediatrics and Pediatrics and guest editor for The Journal of Pediatrics. Her passion for the peer-review process also shows in her long list of published research.

Dr. Tarini also foresees multiple research trends in the next five years that might appear in peer-reviewed publications.

“We have so much to tackle in child health research, both ongoing and new challenges,” said Dr. Tarini.  “Some issues that come to mind are the mental health crisis in children and teens, continuing to make strides on treating and preventing childhood obesity, the effect of poverty on children’s health, and the pandemic’s effect on all of these issues and its direct effect on health outcomes.”

masked kids giving thumbs up in front of school bus

Pediatricians and public health officials should unite against controversial school masking bans

masked kids giving thumbs up in front of school bus

To keep in-person learning and protect students in schools, pediatricians and public health officials must advocate for evidence-based mitigation strategies that can reduce COVID-19 transmission — especially the Delta variant, which overwhelmed pediatric emergency rooms and hospitals, argued Yang et al. in a Perspective published in the journal Pediatrics.

To keep in-person learning and protect students in schools, pediatricians and public health officials must advocate for evidence-based mitigation strategies that can reduce COVID-19 transmission — especially the Delta variant, which overwhelmed pediatric emergency rooms and hospitals, argued Yang et al. in a Perspective published in the journal Pediatrics.

The authors propose that pediatricians and their associated institutions actively advocate for masking in schools and debunk myths and misinformation during well and sick visits. In addition, they encourage doctors to develop and disseminate behavioral strategies to support children’s compliance with masking based on individual abilities and needs. Finally, providers can partner with educators at the local, district, state and national levels to advocate for evidence-based masking policies.

“As pediatricians, it is our responsibility to advocate for universal masking to facilitate safe in-person schooling for all children,” said Sarah Schaffer DeRoo, M.D., pediatrician at Children’s National Hospital and co-author of the Perspective. “Children have readily adapted to masking during the pandemic and continuing this practice in schools is not a significant change from their recent experience.”

To date, nine states have enacted policies to prohibit school masking mandates, disregarding evidence that masking is a crucial COVID-19 preventive measure, Yang et al. wrote. The court overturned these mandates in four states out of the nine because they either exceeded the governor’s executive authority or did not comply with the law granting the executive order’s authority. In other instances, judges have only placed a temporary block.

“Despite politically charged rhetoric and headline-grabbing lawsuits, evidence shows that schools without mask mandates are more likely to have COVID-19 outbreaks,” said Y. Tony Yang, Sc.D., endowed professor of health policy and executive director of the Center for Health Policy and Media Engagement at the George Washington University, and lead author of the Perspective. “Pediatricians have generally commanded a heightened level of public trust, which suggests that pediatricians who make the case for policies that advance sound medical and public health science may have a greater chance than other advocates of generating the public and political will needed to make evidence-based policy ideas, such as school mask mandates, a reality.”

Some localities have found creative ways to circumvent state mask mandate bans by altering the school dress code to include face coverings and finding loopholes that do not apply to individual cities. Parents have also tried to challenge the policies in court, asserting that mask mandate bans violate federal anti-discrimination laws.

“Continued efforts are needed to ensure schools are able to promote reasonable, evidence-based strategies to promote the health of their students, teachers and communities, and we, as advocates for children, are obligated to emphatically support these efforts,” said Yang et al.

illustration of lungs with coronavirus inside

Study compares outcomes of SARS-CoV-2 versus other respiratory viruses

illustration of lungs with coronavirus inside

Until now, little was known about the incidence and virus-specific patient outcome of SARS-CoV-2 compared to common seasonal respiratory viruses in children — including respiratory syncytial virus (RSV), human parainfluenza (hPIV), human metapneumovirus (hMPV), respiratory adenovirus and human rhinovirus (hHRV) and respiratory enterovirus (rENT).

Common respiratory viral infections were associated with a higher proportion of inpatient admissions but were similar in intensive care unit (ICU) admissions and death rates in hospitalized pediatric patients when compared to SARS-CoV-2, according to Children’s National Hospital researchers that led a study published in Infection Control & Hospital Epidemiology.

Until now, little was known about the incidence and virus-specific patient outcome of SARS-CoV-2 compared to common seasonal respiratory viruses in children — including respiratory syncytial virus (RSV), human parainfluenza (hPIV), human metapneumovirus (hMPV), respiratory adenovirus and human rhinovirus (hHRV) and respiratory enterovirus (rENT).

The researchers also noted that there was an overall substantial decrease in seasonal respiratory viral infections, especially the severe forms that require hospitalization. They believe that this correlation might be associated with the adoption of COVID-19 public health mitigation efforts, which played a major role in the reduction of these viruses that often circulate in fall and winter. The retrospective cross-sectional cohort study analyzed over 55,000 patient admissions between Match 15 and December 31, 2020. The findings shed light on the incidences of eight common seasonal respiratory viral infections before and during the COVID-19 pandemic. It also compared patient outcomes associated with COVID-19 and these other viral infections among pediatric patients at Children’s National.

Xiaoyan Song, Ph.D., M.Sc., chief infection control officer at Children’s National, spoke to us about the study.

Q: Why is this important work?

A: This is the first study to date that has described and compared hospitalization rates, ICU admission rates and death associated with COVID-19, RSV, seasonal influenza, rhinovirus, enterovirus and other common respiratory viral infections in children in one study. Previously, studies have compared one or two viruses at a time. This study compared 8 viruses, including the most detected ones – COVID-19, RSV, seasonal flu, rhinovirus and enterovirus.

Q: How will this work benefit patients?

A: This study will inform patients, families and the public that preventative measures like masking, hand hygiene, avoiding crowds and avoiding people who are ill are good practices that work to protect children from getting COVID-19 but also from getting infected with RSV, influenza and other viruses. Any of these respiratory viruses could harm a patient to a point where the child may have to be hospitalized or receive ICU care.

You can read the full study published in Infection Control & Hospital Epidemiology.

microglia cells damage the myelin sheath of neuron axons

Katrina Adams, Ph.D., awarded fellowship to help restore functions in MS patients

microglia cells damage the myelin sheath of neuron axons

Multiple sclerosis is a demyelinating disease in which the insulating covers of nerve cells are damaged. Microglia cells (orange) attack the oligodendrocytes that form the insulating myelin sheath around neuron axons, leading to the destruction of the myelin sheath and to the loss of nerve function.

For her contributions to Multiple Sclerosis (MS) research, Katrina Adams, Ph.D., postdoctoral researcher at Children’s National Hospital, received the career transition fellowship from The National Multiple Sclerosis Society. The $600,000 fellowship will support a two-year period of advanced postdoctoral training in MS research and the first three years of research support in a new faculty appointment.

MS symptoms, including vision loss, pain, fatigue and reduced motor coordination, result from the demyelination of neuronal axons that transport critical information across the brain and spinal cord. Demyelination is the loss of myelin protein, which is normally produced by oligodendrocyte cells.

In the healthy brain, oligodendrocytes repair demyelinated areas by replacing damaged or lost myelin in a process called remyelination. Recent evidence has shown that oligodendrocytes display differences in their molecular and functional properties. One source of new oligodendrocytes in the adult brain is neural stem cells, which have been shown to generate oligodendrocytes that contribute to remyelination.

“The goal of this project is to determine whether neural stem cell-derived oligodendrocytes are distinct from other oligodendrocytes, both in the healthy brain and in MS,” said Adams. “I aim to understand the molecular mechanisms that regulate generation of oligodendrocytes from neural stem cells, with the goal of identifying signals that could be targeted in MS patients to promote remyelination.”

Remyelination is very limited in MS patients and current therapies for MS have very little impact on promoting remyelination.

This study will take advantage of the state-of-the-art facilities for single-cell analysis, transcriptomics, microscopy, and animal research in Children’s Research Institute at Children’s National. Adams also added that her postdoctoral mentor, Vittorio Gallo, Ph.D., interim chief academic officer and interim director of the Children’s National Research Institute, and principal investigator for the DC-IDDRC, has renowned expertise in glial biology, animal models of MS and white matter injury.

“This research will be the first to directly compare neural stem cell-derived oligodendrocytes with other resident oligodendrocytes in MS brain samples,” said Adams. “The results of this study will provide critical insight into the role that neural stem cells play in repair of MS demyelinated lesions.”

Adams received her doctorate in molecular biology from the University of California, Los Angeles where she used pluripotent stem cells to study motor neuron development. She currently investigates signaling pathways that regulate neural stem and progenitor cell maintenance and differentiation in the developing postnatal and adult brain, with a focus on the Endothelin-1 pathway. She is interested in understanding how stem and progenitor cells respond to disease or injury, such as in Multiple Sclerosis, with the hope of identifying new therapeutic targets.

Matthew Oetgen

Matthew Oetgen, M.D., M.B.A, lauded for paper on treating Compartment Syndrome

Matthew Oetgen

For his work in advancing the care for children with complex orthopaedic needs, Matthew Oetgen, M.D., M.B.A., chief of Orthopaedics at Children’s National Hospital, recently accepted the award for Best Basic Science Paper at the 2021 Pediatric Orthopaedic Society of North America (POSNA) annual meeting. Dr. Oetgen co-authored the paper titled “Activation of A Central Immunosuppressive Cascade Prevents Ischemia Reperfusion Injury after Acute Compartment Syndrome in a Murine Model.”

Compartment Syndrome is rare and often difficult to diagnose. It occurs when interstitial pressure exceeds perfusion pressure and results in warm ischemia and cell death due to impaired aerobic metabolism. Following surgical decompression and reperfusion of the extremity, a robust innate inflammatory response results in further tissue injury due to the production of reactive oxygen species and local capillary dysfunction.

The authors described using varenicline, an FDA-approved medication for smoking cessation, to mitigate inflammation after ischemia reperfusion injury in murine models. Twenty-four hours after reperfusion, the treatment reduced acute leukocyte infiltrate, 7 days following reperfusion, the expression of pro-fibrotic genes was reduced and 14 days following treatment, histologic evidence of collagen deposition was also significantly reduced.

“The promising results of this study show that this medication may have the potential to blunt the immune response resulting in better outcomes for children with compartment syndrome,” says Dr. Oetgen.

Watch Dr. Oetgen’s presentation here.

Drs. Wernovsky and Martin

Cardiac care leaders recognized for mentorship and innovation at AAP

Two Children’s National Hospital cardiac care leaders received prestigious recognition awards from the American Academy of Pediatrics (AAP) during that organization’s virtual National Conference and Exhibition in October 2021.

  • Gil Wernovsky, M.D., cardiac critical care specialist at Children’s National Hospital, received the 2021 Maria Serratto Master Educator Award from AAP Section on Pediatric Cardiology and Cardiac Surgery, celebrating his 30-plus-years as a clinician, educator, mentor and leader in the field.
  • Gerard Martin, M.D., FAAP, FACC, FAHA, C. Richard Beyda Professor of Cardiology, Children’s National Hospital, received the AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award, in recognition of his work to establish the use of pulse oximetry to screen newborn infants for critical congenital heart disease in the first 24 hours of life.

Dr. Wernovsky: 2021 Maria Serratto Master Educator Award, AAP Section on Pediatric Cardiology and Cardiac Surgery

Gil Wernovsky

Gil Wernovsky, M.D., received the 2021 Maria Serratto Master Educator Award from AAP Section on Pediatric Cardiology and Cardiac Surgery.

The Master Educator Award is presented each year to a pediatric cardiologist or cardiothoracic surgeon who exemplifies excellence as an educator, mentor and/or leader in the field.

A practicing cardiac critical care specialist with more than 30 years’ experience in pediatric cardiology, Dr. Wernovsky trained and mentored more than 300 fellows in pediatric cardiology, cardiac surgery, neonatology, critical care medicine and cardiac anesthesia, in addition to countless residents and fellows. He also organizes national and international symposia to share expertise around the world. During the COVID-19 public health emergency, for example, he co-founded the Congenital Heart Academy (CHA). The CHA provides content from an international faculty of cardiac care to more than 26,000 practitioners in 112 countries and includes a thriving YouTube channel.

Dr. Wernovsky is also a founding member of several international societies focused on bringing together clinicians, researchers and students across sub-specialties of pediatric cardiology and cardiac surgery for knowledge exchange and best practice sharing. These include: the Pediatric Cardiac Intensive Care Society, World Society for Pediatric and Congenital Heart Surgery, the International Society of Pediatric Mechanical Circulatory Support and the Cardiac Neurodevelopmental Outcome Collaborative.

Dr. Wernovsky received the award on October 10 at the virtual Scientific Sessions of the 2021 American Academy of Pediatrics National Conference and Exhibition.

Dr. Martin: AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award

Gerard Martin

Gerard Martin, M.D., FAAP, FACC, FAHA, C. Richard Beyda Professor of Cardiology, Children’s National Hospital, received the AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award.

The Section on Advances in Therapeutics and Technology (SOATT) educates physicians, stimulates research and development and consults on therapeutics and technology-related matters for the AAP. The Achievement Award recognizes someone who has shown leadership in applying innovative approaches to solve pressing problems.

Dr. Martin is the C. Richard Beyda Professor of Cardiology and has cared for children at Children’s National for more than 30 years. As an advocate for congenital heart disease efforts nationally and internationally, he played an integral role in the development of an innovative use of existing hospital technology—the pulse oximeter—to detect critical congenital heart disease in newborn babies.

Today, Dr. Martin and colleagues across the United States and around the world have worked to make this screening method a standard of care for newborns everywhere. It is a part of the Health Resources and Services Administration (HRSA) Recommended Uniform Screening Panel and has become law in every state. They continue to conduct research to refine the recommendations and hone-in on the most effective ways to harness these tools.

Dr. Martin was selected for this award in 2020. He accepted it and offered remarks during the 2021 virtual AAP National Conference and Exhibition on Monday, October 11, 2021.

doctor checking boy for concussion

NINDS awards $10 million for pediatric concussion research

doctor checking boy for concussion

Every year, more than 3 million Americans are diagnosed with concussions. Symptoms continue to plague 30 percent of patients three months after injury — adolescents face an even higher risk of delayed recovery.

The National Institute of Neurological Disorders and Stroke has awarded a $10-million grant to the Four Corners Youth Consortium, a group of academic medical centers studying concussions in school-aged children. Led in part by the Safe Concussion Outcome Recovery and Education (SCORE) program at Children’s National Hospital, the project is named Concussion Assessment, Research and Education for Kids, or CARE4Kids.

Researchers will use advanced brain imaging and blood tests to explore biological markers—changes in blood pressure, heart rate and pupil reactivity—that could predict which children will develop persistent symptoms after concussion. The five-year CARE4Kids study will enroll more than 1,300 children ages 11-18 nationwide.

The five-year study will be led by Gerard Gioia, Ph.D., division chief of Neuropsychology at Children’s National Hospital, Frederick Rivara, M.D., M.P.H., at Seattle Children’s Center for Child Health, Behavior and Development and University of Washington’s Medicine’s Department of Pediatrics, and Dr. Chris Giza at University of California, Los Angeles (UCLA).

“We will be gathering innovative data to help answer the critical question asked by every patient: ‘When can I expect to recover from this concussion?’” said Dr. Gioia. “We have a great team and are excited to have been selected to study this important issue.”

Christopher G. Vaughan, Psy.D., neuropsychologist, and Raquel Langdon, M.D., neurologist, both at Children’s National, will join Dr. Gioia as principal investigators of the study at this site.

Every year, more than 3 million Americans are diagnosed with concussions. Symptoms continue to plague 30 percent of patients three months after injury—adolescents face an even higher risk of delayed recovery. Chronic migraine headaches, learning and memory problems, exercise intolerance, sleep disturbances, anxiety and depressed mood are common.

“Providing individualized symptom-specific treatments for youth with a concussion has been a longstanding aim of the SCORE program,”Dr. Vaughan said. “This project will lead to a better understanding of the specific markers for which children may have a longer recovery. With this knowledge, we can start individualized treatments earlier in the process and ultimately help to reduce the number of children who experienced prolonged effects after concussion.”

The grant was announced on September 9, 2021.

In Washington, D.C., an estimated 240 children ages 11 to 18, will participate in the study.

The study will unfold in two phases. The first part will evaluate children with concussion to identify a set of biomarkers predictive of persistent post-concussion symptoms. To validate the findings, the next stage will confirm that these biomarkers accurately predict prolonged symptoms in a second group of children who have been diagnosed with concussion. The goal is to develop a practical algorithm for use in general clinical practice for doctors and other health professionals caring for pediatric patients.

Institutions currently recruiting patients for the study include Children’s National Hospital, UCLA Mattel Children’s Hospital, Seattle Children’s, the University of Washington, University of Rochester, University of Texas Southwestern Medical Center and Wake Forest School of Medicine. Indiana University, the National Institute of Nursing Research, University of Arkansas, University of Southern California and the data coordinating center at the University of Utah are also involved in the project.

Earlier research conducted by the Four Corners Youth Consortium that led to this project was funded by private donations from Stan and Patti Silver, the UCLA Steve Tisch BrainSPORT Program and the UCLA Easton Clinic for Brain Health; Children’s National Research Institute; as well as from the Satterberg Foundation to Seattle Children’s Research Institute; and an investment from the Sports Institute at UW Medicine.