Public Health

Research & Innovation Campus

Children’s National welcomes Virginia Tech to its new campus

Children’s National Hospital and Virginia Tech create formal partnership that includes the launch of a Virginia Tech biomedical research facility within the new Children’s National Research & Innovation Campus.

Children’s National Hospital and Virginia Tech recently announced a formal partnership that will include the launch of a 12,000-square-foot Virginia Tech biomedical research facility within the new Children’s National Research & Innovation Campus. The campus is an expansion of Children’s National that is located on a nearly 12-acre portion of the former Walter Reed Army Medical Center in Washington, D.C. and is set to open its first phase in December 2020. This new collaboration brings together Virginia Tech, a top tier academic research institution, with Children’s National, a U.S. News and World Report top 10 children’s hospital, on what will be the nation’s first innovation campus focused on pediatric research.

Research & Innovation Campus

“Virginia Tech is an ideal partner to help us deliver on what we promised for the Children’s National Research & Innovation Campus – an ecosystem that enables us to accelerate the translation of potential breakthrough discoveries into new treatments and technologies,” says Kurt Newman, M.D., president and CEO, Children’s National. “Our clinical expertise combined with Virginia Tech’s leadership in engineering and technology, and its growing emphasis on biomedical research, will be a significant advance in developing much needed treatment and cures to save children’s lives.”

Earlier this year, Children’s National announced a collaboration with Johnson & Johnson Innovation LLC to launch JLABS @ Washington, DC at the Research & Innovation Campus. The JLABS @ Washington, DC site will be open to pharmaceutical, medical device, consumer and health technology companies that are aiming to advance the development of new drugs, medical devices, precision diagnostics and health technologies, including applications in pediatrics.

“We are proud to welcome Virginia Tech to our historic Walter Reed campus – a campus that is shaping up to host some of the top minds, talent and innovation incubators in the world,” says Washington, D.C. Mayor Muriel Bowser. “The new Children’s National Research & Innovation Campus will exemplify why D.C. is the capital of inclusive innovation – because we are a city committed to building the public and private partnerships necessary to drive discoveries, create jobs, promote economic growth and keep D.C. at the forefront of innovation and change.”

Faculty from the Children’s National Research Institute and the Fralin Biomedical Research Institute at Virginia Tech Carilion (VTC) have worked together for more than a decade, already resulting in shared research grants, collaborative publications and shared intellectual property. Together, the two institutions will now expand their collaborations to develop new drugs, medical devices, software applications and other novel treatments for cancer, rare diseases and other disorders.

“Joining with Children’s National in the nation’s capital positions Virginia Tech to improve the health and well-being of infants and children around the world,” says Virginia Tech President Tim Sands, Ph.D. “This partnership resonates with our land-grant mission to solve big problems and create new opportunities in Virginia and D.C. through education, technology and research.”

The partnership with Children’s National adds to Virginia Tech’s growing footprint in the Washington D.C. region, which includes plans for a new graduate campus in Alexandria, Va. with a human-centered approach to technological innovation. Sands said the proximity of the two locations – just across the Potomac – will enable researchers to leverage resources, and will also create opportunities with the Virginia Tech campus in Blacksburg, Va. and the Virginia Tech Carilion Health Science and Technology campus in Roanoke, Va.

Carilion Clinic and Children’s National have an existing collaboration for provision of certain specialized pediatric clinical services. The more formalized partnership between Virginia Tech and Children’s National will drive the already strong Virginia Tech-Carilion Clinic partnership, particularly for children’s health initiatives and facilitate collaborations between all three institutions in the pediatric research and clinical service domains.

Children’s National and Virginia Tech will engage in joint faculty recruiting, joint intellectual property, joint training of students and fellows, and collaborative research projects and programs according to Michael Friedlander, Ph.D., Virginia Tech’s vice president for health sciences and technology, and executive director of the Fralin Biomedical Research Institute at VTC.

“The expansion and formalization of our partnership with Children’s National is extremely timely and vital for pediatric research innovation and for translating these innovations into practice to prevent, treat and ultimately cure nervous system cancer in children,” says Friedlander, who has collaborated with Children’s National leaders and researchers for more than 20 years. “Both Virginia Tech and Children’s National have similar values and cultures with a firm commitment to discovery and innovation in the service of society.”

“Brain and other nervous system cancers are among the most common cancers in children (alongside leukemia),” says Friedlander. “With our strength in neurobiology including adult brain cancer research in both humans and companion animals at Virginia Tech and the strength of Children’s National research in pediatric cancer, developmental neuroscience and intellectual disabilities, this is a perfect match.”

The design of the Children’s National Research & Innovation Campus not only makes it conducive for the hospital to strengthen its prestigious partnerships with Virginia Tech and Johnson & Johnson, it also fosters synergies with federal agencies like the Biomedical Advanced Research and Development Authority, which will collaborate with JLABS @ Washington, DC to establish a specialized innovation zone to develop responses to health security threats. As more partners sign on, this convergence of key public and private institutions will accelerate discoveries and bring them to market faster for the benefit of children and adults.

“The Children’s National Research & Innovation Campus pairs an inspirational mission to find new treatments for childhood illness and disease with the ideal environment for early stage companies. I am confident the campus will be a magnet for big ideas and will be an economic boost for Washington DC and the region,” says Jeff Zients, who was appointed chair of the Children’s National Board of Directors effective October 1, 2019. As a CEO and the former director of President Obama’s National Economic Council, Zients says that “When you bring together business, academia, health care and government in the right setting, you create a hotbed for innovation.”

Ranked 7th in National Institutes of Health research funding among pediatric hospitals, Children’s National continues to foster collaborations as it prepares to open its first 158,000-square-foot phase of its Research & Innovation Campus. These key partnerships will enable the hospital to fulfill its mission of keeping children top of mind for healthcare innovation and research while also contributing to Washington D.C.’s thriving innovation economy.

t-cells

Tailored T-cell therapies neutralize viruses that threaten kids with PID

t-cells

Tailored T-cells specially designed to combat a half dozen viruses are safe and may be effective in preventing and treating multiple viral infections, according to research led by Children’s National Hospital faculty.

Catherine Bollard, M.B.Ch.B., M.D., director of the Center for Cancer and Immunology Research at Children’s National and the study’s senior author, presented the teams’ findings Nov. 8, 2019, during a second-annual symposium jointly held by Children’s National and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Children’s National and NIAID formed a research partnership in 2017 to develop and conduct collaborative clinical research studies focused on young children with allergic, immunologic, infectious and inflammatory diseases. Each year, they co-host a symposium to exchange their latest research findings.

According to the NIH, more than 200 forms of primary immune deficiency diseases impact about 500,000 people in the U.S. These rare, genetic diseases so impair the person’s immune system that they experience repeated and sometimes rare infections that can be life threatening. After a hematopoietic stem cell transplantation, brand new stem cells can rebuild the person’s missing or impaired immune system. However, during the window in which the immune system rebuilds, patients can be vulnerable to a host of viral infections.

Because viral infections can be controlled by T-cells, the body’s infection-fighting white blood cells, the Children’s National first-in-humans Phase 1 dose escalation trial aimed to determine the safety of T-cells with antiviral activity against a half dozen opportunistic viruses: adenovirus, BK virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human Herpesvirus 6 and human parainfluenza-3 (HPIV3).

Eight patients received the hexa-valent, virus-specific T-cells after their stem cell transplants:

  • Three patients were treated for active CMV, and the T-cells resolved their viremia.
  • Two patients treated for active BK virus had complete symptom resolution, while one had hemorrhagic cystitis resolved but had fluctuating viral loads in their blood and urine.
  • Of two patients treated prophylactically, one developed EBV viremia that was treated with rituximab.

Two additional patients received the T-cell treatments under expanded access for emergency treatment, one for disseminated adenoviremia and the other for HPIV3 pneumonia. While these critically ill patients had partial clinical improvement, they were being treated with steroids which may have dampened their antiviral responses.

“These preliminary results show that hexaviral-specific, virus-specific T-cells are safe and may be effective in preventing and treating multiple viral infections,” says Michael Keller, M.D., a pediatric immunologist at Children’s National and the lead study author. “Of note, enzyme-linked immune absorbent spot assays showed evidence of antiviral T-cell activity by three months post infusion in three of four patients who could be evaluated and expansion was detectable in two patients.”

In addition to Drs. Bollard and Keller, additional study authors include Katherine Harris M.D.; Patrick J. Hanley Ph.D., assistant research professor in the Center for Cancer and Immunology; Allistair Abraham, M.D., a blood and marrow transplantation specialist; Blachy J. Dávila Saldaña, M.D., Division of Blood and Marrow Transplantation; Nan Zhang Ph.D.; Gelina Sani BS; Haili Lang MS; Richard Childs M.D.; and Richard Jones M.D.

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Children’s National-NIAID 2019 symposium presentations

“Welcome and introduction”
H. Clifford Lane, M.D., director of NIAID’s Division of Clinical Research

“Lessons and benefits from collaboration between the NIH and a free-standing children’s hospital”
Marshall L. Summar, M.D., director, Rare Disease Institute, Children’s National

“The hereditary disorders of PropionylCoA and Cobalamin Metabolism – past, present and future”
Charles P. Venditti, M.D., Ph.D., National Human Genome Research Institute Collaboration

“The road(s) to genetic precision therapeutics in pediatric neuromuscular disease: opportunities and challenges”
Carsten G. Bönnemann, M.D., National Institute of Neurological Disorders and Stroke

“Genomic diagnostics in immunologic diseases”
Helen Su, M.D., Ph.D., National Institute of Allergy and Infectious Diseases

“Update on outcomes of gene therapy clinical trials for X-SCID and X-CGD and plans for future trials”
Harry Malech, M.D., National Institute of Allergy and Infectious Diseases

“Virus-specific T-cell therapies: broadening applicability for PID patients”
Catherine Bollard, M.D., Children’s National 

“Using genetic testing to guide therapeutic decisions in Primary Immune Deficiency Disease”
Vanessa Bundy, M.D., Ph.D., Children’s National 

Panel discussion moderated by Lisa M. Guay-Woodford, M.D.
Drs. Su, Malech, Bollard and Bundy
Morgan Similuk, S.C.M., NIAID
Maren Chamorro, Parent Advocate

“Underlying mechanisms of pediatric food allergy: focus on B cells
Adora Lin, M.D., Ph.D., Children’s National 

“Pediatric Lyme outcomes study – interim update”
Roberta L. DeBiasi, M.D., MS, Children’s National 

“Molecular drivers and opportunities in neuroimmune conditions of pediatric onset”
Elizabeth Wells, M.D., Children’s National 

 

kidneys with cysts on them

$6M gift powers new PKD clinical and research activities

kidneys with cysts on them

PKD is a genetic disorder characterized by clusters of fluid-filled sacs (cysts) multiplying and interfering with the kidneys’ ability to filter waste from the blood.

When Lisa M. Guay-Woodford, M.D., McGehee Joyce Professor of Pediatrics at Children’s National Hospital, considers a brand-new gift, she likens it to 6 million gallons of “rocket fuel” that will power new research to better understand polycystic kidney disease.

Dr. Guay-Woodford received a $5.7 million dollar gift to support PKD clinical and research activities. PKD is a genetic disorder characterized by clusters of fluid-filled sacs (cysts) multiplying and interfering with the kidneys’ ability to filter waste from the blood. The kidneys’ smooth surface transforms to a bumpy texture as the essential organs grow oversized and riddled with cysts.

The extraordinary generosity got its start in an ordinary clinical visit.

Dr. Guay-Woodford saw a young patient in her clinic at Children’s National a few times in 2015. The child’s diagnosis sparked a voyage of discovery for the patient’s extended family and, ultimately, they attended a presentation she gave during a regional meeting about PKD. That led to a telephone conversation and in-person meeting as they invited her to describe “the white space” between what was being done at the time to better understand PKD and what could be done.

“It’s the power of the art and science of medicine. They come to see people like me because of the science. If we can convey to patients and families that who they are and their unique concerns are really important to researchers, that becomes a powerful connection,” she says. “The art plus the science equals hope. That is what these families are looking for: We give people the latest insights about their disease because information is power.”

The infusion of new funding will strengthen the global initiative’s four pillars:

  • Coordinated care for children and families impacted by renal cystic disease. The Inherited and Polycystic Kidney Disease (IPKD) program, launched September 2019, includes a cadre of experts working together as a team in the medical home so that “in a single, one-stop visit, Children’s National can address the myriad concerns they have,” she explains. A multi-disciplinary team that includes nephrologists, hepatologists and endocrinology experts meets weekly to ensure the Center of Excellence provides the highest-caliber patient care. The team includes genetic counselors to empower families with knowledge about genetic risks and testing opportunities. A nurse helps families navigate the maze of who to call about which issue. Psychologists help to ease anxiety. “There is stress. There is fear. There is pain that can be associated with this set of diseases. The good news is we can control their medical issues. The bad news is some children have difficulty coping. Our psychologists help children cope so they can be a child and do the normal things that children do,” she says.
  • Strengthening global databases to capture PKD variations. The team will expand its outreach to other centers located around the world – including Australia, Europe, India and Latin America – caring for patients with both the recessive and dominant forms of polycystic kidney disease, to better understand the variety of ways the disease can manifest in children. “We really don’t know a lot about kids with the dominant form of the disease. How hard should we push to control their blood pressure, knowing that could ease symptoms? What are the ramifications of experiencing acute pain compared with chronic pain? How much do these pain flareups interfere with daily life and a child’s sense of self,” she asks. Capturing the nuances of the worldwide experience offers the power of harnessing even more data. And ensuring that teams collect data in a consistent way means each group would have the potential to extract the most useful information from database queries.
  • Filling a ‘desperate need’ for biomarkers. Developing clinical trials for new therapies requires having biomarkers that indicate the disease course. Such biomarkers have been instrumental in personalizing care for patients with other chronic conditions. “We are in desperate need for such biomarkers, and this new funding will underwrite pilot studies to identify and validate these disease markers. The first bite at the apple will leverage our imaging data to identify promising biomarkers,” she says.
  • Genetic mechanisms that trigger kidney disease. About 500,000 people in the U.S. have PKD. In many cases, children inherit a genetic mutation but, often, their genetic mutation develops spontaneously. Dr. Guay-Woodford’s research about the mechanisms that make certain inherited renal disorders lethal, such as autosomal recessive polycystic kidney disease, is recognized around the world. The fourth pillar of the new project provides funding to continue her lab’s research efforts to improve the mechanistic understanding of what triggers PKD.
baby with tubes

BPA analogues may be less likely to disrupt heart rhythm

Some chemical alternatives to plastic bisphenol-a (BPA), which is still commonly used in medical settings such as operating rooms and intensive care units, may be less disruptive to heart electrical function than BPA.

A poster at the AHA Scientific Sessions suggests bisphenol-s (BPS) and bisphenol-f (BPF) may have less impact on heart function than bisphenol-a (BPA).

Some chemical alternatives to plastic bisphenol-a (BPA), which is still commonly used in medical settings such as operating rooms and intensive care units, may be less disruptive to heart electrical function than BPA, according to a pre-clinical study that explored how the structural analogues bisphenol-s (BPS) and bisphenol-f (BPF) interact with the chemical and electrical functions of heart cells.

The findings suggest that in terms of toxicity for heart function, these chemicals that are similar in structure to BPA may actually be safer for medically fragile heart cells, such as those in children with congenital heart disease. Previous research has found a high likelihood that BPA exposure may impact the heart’s electrical conductivity and disrupt heart rhythm, and patients are often exposed to the plastic via clinical equipment found in intensive care and in the operating room.

“There are still many questions that need to be answered about the safety and efficacy of using chemicals that look and act like BPA in medical settings, especially in terms of their potential contribution to endocrine disruption,” says Nikki Gillum Posnack, Ph.D., the poster’s senior author and a principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital. “What we can say is that, in this initial pre-clinical investigation, it appears that these structural analogues have less of an impact on the electrical activity within the heart and therefore, may be less likely to contribute to dysrhythmias.”

Future studies will seek to quantify the risk that these alternative chemicals pose in vulnerable populations, including pediatric cardiology and cardiac surgery patients. Since pediatric patients’ hearts are still growing and developing, the interactions may be different than what was seen in this pilot study.

Learn more the impacts of exposure to plastics such as bisphenol-A and plasticizers such as DEHP and MEHP that are commonly used in medical devices:

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Bisphenol-a Analogues May Be Safer Alternatives For Plastic Medical Products
Rafael Jaimes, Damon McCullough, Luther M Swift, Marissa Reilly, Morgan Burke, Jiansong Sheng, Javier Saiz, Nikki G Posnack
Poster Presentation by senior author Nikki G Posnack
CH.APS.01 – Translational Research in Congenital Heart Disease
AHA Scientific Sessions
November 16, 2019
1:30 p.m. – 2:00 p.m.

Marva Moxey-Mims in her office at Children's National.

Kidney disease outcomes differ between severely obese kids vs. adults after bariatric surgery

Marva Moxey-Mims in her office at Children's National.

“We know that bariatric surgery improves markers of kidney health in severely obese adults and adolescents,” says Marva Moxey-Mims, M.D. “This research helps to elucidate possible differences in kidney disease outcomes between children and adults post-surgery.”

Adolescents with Type 2 diabetes experienced more hyperfiltration and earlier attenuation of their elevated urine albumin-to-creatinine ratio (UACR) after gastric bypass surgery compared with adults. This finding contrasts with adolescents or adults who did not have diabetes prior to surgery, according to research presented Nov. 8, 2019, during the American Society of Nephrology’s Kidney Week 2019, the world’s largest gathering of kidney researchers.

“Findings from this work support a recent policy statement by the American Academy of Pediatrics (AAP) that advocates for increasing severely obese youths’ access to bariatric surgery,” says Marva Moxey-Mims, M.D., Chief of the Division of Nephrology at Children’s National Hospital and a study co-author.  “We know that bariatric surgery improves markers of kidney health in severely obese adults and adolescents. This research helps to elucidate possible differences in kidney disease outcomes between children and adults post-surgery.”

According to the AAP, the prevalence of severe obesity in youth aged 12 to 19 has nearly doubled since 1999. Now, 4.5 million U.S. children are affected by severe obesity, defined as having a body mass index ≥35 or ≥120% of the 95th percentile for age and sex.

In a Roux-en-Y gastric bypass, the surgeon staples the stomach to make it smaller, so people eat less. Then, they attach the lower part of the small intestine in a way that bypasses most of the stomach so the body takes in fewer calories.

The multi-institutional study team examined the health effects of such gastric bypass surgeries by comparing 161 adolescents with 396 adults enrolled in related studies. They compared their estimated glomerular filtration rates by serum creatinine and cystatin C. UACR was also compared at various time periods, up till five years after surgery.

Across the board, adolescents had higher UACR – a key marker for chronic kidney disease – than adults. However, for kids who had Type 2 diabetes prior to surgery, the prevalence of elevated UACR levels dip from 29% pre-surgery to 6% one year post-surgery. By contrast, adults who had diabetes prior to surgery and elevated UACR did not see a significant reduction in UACR until five years post-surgery.

While hyperfiltration prevalence was similar in study participants who did not have Type 2 diabetes, adolescents who had Type 2 diabetes prior to surgery had an increased prevalence of hyperfiltration for the duration of the study period.

Financial support for research described in this post was provided by the National Institute of Diabetes and Digestive and Kidney Diseases.

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ASN Kidney Week 2019 presentation

“Five-year kidney outcomes of bariatric surgery in adolescents compared with adults”
Friday, Nov. 8, 2019, 10 a.m. to noon (EST)
Petter Bjornstad, University of Colorado School of Medicine; Todd Jenkins, Edward Nehus and Mark Mitsnefes, all of Cincinnati Children’s Hospital; Marva M. Moxey-Mims, Children’s National Hospital; and Thomas H. Inge, Children’s Hospital Colorado.

 

2019 National Maternal & Infant Health Summit

Children’s National Hospital participated in the second annual National Maternal & Infant Health Summit which highlights the District’s approaches to ensure the health of women, babies and families. From L to R are: Sahira Long, M.D., Jessica Nash, M.D., Hope Rhodes, M.D., and Kofi Essel, M.D.

Children’s National Hospital participated in the second annual National Maternal & Infant Health Summit hosted by Mayor Muriel Bowser. The summit was built upon highlighting the District’s approaches to ensure the health of women, babies and families, while also seeking to increase public awareness and interest on these topics.

“I enjoyed the summit as a mother, parent, physician and presenter,” said Jessica Nash, M.D., a pediatrician at Children’s National. “I am excited about the future conversations about infant and maternal mortality and the strides needed in the District.”

Nash led a panel titled “Maternal and Infant Mental Health Landscape: Taking Steps to Improve Practice and Policy,” with Hope Rhodes, MD, MPH, Dominique Charlot-Swilley, Ph.D., Leandra Godoy, Ph.D. and Sarah Barclay Hoffman. The discussion identified infant and early childhood mental health resources available in the District, the current state of infant and early childhood mental health, future potential policy changes and the collaborative model that places HealthySteps DC within a child’s primary care medical home.

Children’s National Hospital’s Saharia Long, M.D., discusses the local efforts to improve healthy food access for families.

The day-long summit covered many topics including The Role of Food Policy, Access, and Nutrition in Supporting Positive Outcomes for Families, which focused on national and local efforts to improve healthy food access for families, breastfeeding and babies’ first foods. The discussion was a direct response to feedback on the absence of information about breastfeeding and nutrition during last year’s summit. Sahira Long, M.D., and Kofi Essel, M.D.  served as panelists.

“According to the Centers for Disease Control and Prevention (CDC), low rates of breastfeeding add $3 billion a year to medical costs for mothers and children in the U.S.” said Dr. Long. “Breastfeeding is more than an infant feeding choice, it’s a public health decision due to its impact on maternal and infant health.”

The Maternal and Infant Health Summit brings together residents of the District, elected officials, health and education officials and community-based partners to collaborate and explore strategies that will improve perinatal health and address racial disparities in birth outcomes.

Mother receives bad news from pediatrician

All in the family: How to run an effective family meeting

Mother receives bad news from pediatrician

Tessie October, M.D., M.P.H., led a qualitative study that discovered an increase in important information shared from families to the physician when physicians had openly responded with empathy and made time for families to share.

When critically ill children are in the intensive care unit (ICU), physicians must often lead difficult discussions with their families about the direction of care. These family conferences can be challenging for both the doctors leading them and for the families, who are unsure of their options, are under emotional strain and who may feel pressured to make decisions.

“We have patients with serious illnesses discussing major decisions and we don’t do a great job thinking about how to structure those meetings,” says Tessie October, M.D., M.P.H., a critical care specialist at Children’s National Hospital.

Dr. October seeks to help doctors better bridge the gap between themselves and families with her presentation entitled “All in the family: How to run an effective family meeting,” which she presented during the American Academy of Pediatrics (AAP) National Conference and Exhibition in New Orleans on October 28th.

During her session, Dr. October role-played a family conference scenario and allowed the audience to experience key skills needed to successfully facilitate them. “Many people think family conferences are about being nice and assume that physicians know how to do this well,” says October. “There is a skill to navigating the conversation where you ensure that the family hears what you’re saying and you respond to the emotions that follow.”

Dr. October led a qualitative study that discovered an increase in important information shared from families to the physician when physicians had openly responded with empathy and made time for families to share. “Families experience increased satisfaction, physicians become more confident in leading these family conferences and the time needed to make medical decisions is shortened because the family heard the information clearly enough for them to make the decision,” says Dr. October.

Within her study, the 68 recorded conferences that took place at Children’s National pediatric ICU (PICU) showed that physicians missed opportunities to respond to the emotions expressed by a patient’s family in 26% of their interactions. “Families want a doctor to be professional caregiver, to be honest with them, and to present clear information that allows the family to make an informed decision.”

Dr. October and her colleagues intend to help physicians learn to communicate better, starting at Children’s National. “My goal is to expand the program hospital-wide, starting with hematology, neonatology, emergency medicine and cardiology fellows, all of whom will most likely have these difficult treatment and end-of-life discussions with families at some point.”

mitochondria

Molecular gatekeepers that regulate calcium ions key to muscle function

mitochondria

Controlled entry of calcium ions into the mitochondria, the cell’s energy powerhouses, makes the difference between whether muscles grow strong or easily tire and perish from injury, according to research published in Cell Reports.

Calcium ions are essential to how muscles work effectively, playing a starring role in how and when muscles contract, tap energy stores to keep working and self-repair damage. Not only are calcium ions vital for the repair of injured muscle fibers, their controlled entry into the mitochondria, the cell’s energy powerhouses, spells the difference between whether muscles will be healthy or if they will easily tire and perish following an injury, according to research published Oct. 29, 2019, in Cell Reports.

“Lack of the protein mitochondrial calcium uptake1 (MICU1) lowers the activation threshold for calcium uptake mediated by the mitochondrial calcium uniporter in both, muscle fibers from an experimental model and fibroblast of  a patient lacking MICU1,” says Jyoti K. Jaiswal, MSc, Ph.D., a principal investigator in the Center for Genetic Medicine Research at Children’s National Hospital and one of the paper’s corresponding authors. “Missing MICU1 also tips the calcium ion balance in the mitochondria when muscles contract or are injured, leading to more pronounced muscle weakness and myofiber death.”

Five years ago, patients with a very rare disease linked to mutations in the mitochondrial gene MICU1 were described to suffer from a neuromuscular disease with signs of muscle weakness and damage that could not be fully explained.

To determine what was going awry, the multi-institutional research team used a comprehensive approach that included fibroblasts donated by a patient lacking MICU1 and an experimental model whose MICU1 gene was deleted in the muscles.

Loss of MICU1 in skeletal muscle fibers leads to less contractile force, increased fatigue and diminished capacity to repair damage to their cell membrane, called the sarcolemma. Just like human patients, the experimental model suffers more pronounced muscle weakness, increased numbers of dead myofibers, with greater loss of muscle mass in certain muscles, like the quadriceps and triceps, the research team writes.

“What was happening to the patient’s muscles was a big riddle that our research addressed,” Jaiswal adds. “Lacking this protein is not supposed to make the muscle fiber die, like we see in patients with this rare disease. The missing protein is just supposed to cause atrophy and weakness.”

Patients with this rare disease show early muscle weakness, fluctuating levels of fatigue and lethargy, muscle aches after exercise, and elevated creatine kinase in their bloodstream, an indication of cell damage due to physical stress.

“One by one, we investigated these specific features in experimental models that look normal and have normal body weight, but also show lost muscle mass in the quadriceps and triceps,” explains Adam Horn, Ph.D., the lead researcher in Jaiswal’s lab who conducted this study. “Our experimental model lacking MICU1 only in skeletal muscles responded to muscle deficits so similar to humans that it suggests that some of the symptoms we see in patients can be attributed to MICU1 loss in skeletal muscles.”

Future research will aim to explore the details of how the impact of MICU1 deficit in muscles may be addressed therapeutically and possible implications of lacking MICU1 or its paralog in other organs.

In addition to Jaiswal and Horn, Children’s National Hospital Center for Genetic Medicine Research co-authors include Marshall W. Hogarth and Davi A. Mazala. Additional co-authors include Lead Author Valentina Debattisti, Raghavendra Singh, Erin L. Seifert, Kai Ting Huang, and Senior Author György Hajnóczky, all from Thomas Jefferson University; and Rita Horvath, from Newcastle University.

Financial support for research described in this post was provided by the National Institutes of Health under award numbers R01AR55686, U54HD090257 and RO1 GM102724; National Institute of Arthritis and Musculoskeletal and Skin Diseases under award number T32AR056993; and Foundation Leducq.

doctor checking pregnant woman's belly

Novel approach to detect fetal growth restriction

doctor checking pregnant woman's belly

Morphometric and textural analyses of magnetic resonance imaging can point out subtle architectural deviations associated with fetal growth restriction during the second half of pregnancy, a first-time finding that has the promise to lead to earlier intervention.

Morphometric and textural analyses of magnetic resonance imaging (MRI) can point out subtle architectural deviations that are associated with fetal growth restriction (FGR) during the second half of pregnancy. The first-time finding hints at the potential to spot otherwise hidden placental woes earlier and intervene in a more timely fashion, a research team led by Children’s National Hospital faculty reports in Pediatric Research.

“We found reduced placental size, as expected, but also determined that the textural metrics are accelerated in FGR when factoring in gestational age, suggesting premature placental aging in FGR,” says Nickie Andescavage, M.D., a neonatologist at Children’s National and the study’s lead author. “While morphometric and textural features can discriminate placental differences between FGR cases with and without Doppler abnormalities, the pattern of affected features differs between these sub-groups. Of note, placental insufficiency with abnormal Doppler findings have significant differences in the signal-intensity metrics, perhaps related to differences of water content within the placenta.”

The placenta, an organ shared by the pregnant woman and the developing fetus, delivers oxygen and nutrients to the developing fetus and ferries away waste products. Placental insufficiency is characterized by a placenta that develops poorly or is damaged, impairing blood flow, and can result in still birth or death shortly after birth. Surviving infants may be born preterm or suffer early brain injury; later in life, they may experience cardiovascular, metabolic or neuropsychiatric problems.

Because there are no available tools to help clinicians identify small but critical changes in placental architecture during pregnancy, placental insufficiency often is found after some damage is already done. Typically, it is discovered when FGR is diagnosed, when a fetus weighs less than 9 of 10 fetuses of the same gestational age.

“There is a growing appreciation for the prenatal origin of some neuropsychiatric disorders that manifest years to decades later. Those nine months of gestation very much define the breath of who we later become as adults,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National and the study’s senior author. “By identifying better biomarkers of fetal distress at an earlier stage in pregnancy and refining our imaging toolkit to detect them, we set the stage to be able to intervene earlier and improve children’s overall outcomes.”

The research team studied 32 healthy pregnancies and compared them with 34 pregnancies complicated by FGR. These women underwent up to two MRIs between 20 weeks to 40 weeks gestation. They also had abdominal circumference, fetal head circumference and fetal femur length measured as well as fetal weight estimated.

In pregnancies complicated by FGR, placentas were smaller, thinner and shorter than uncomplicated pregnancies and had decreased placental volume. Ten of 13 textural and morphometric features that differed between the two groups were associated with absolute birth weight.

“Interestingly, when FGR is diagnosed in the second trimester, placental volume, elongation and thickness are significantly reduced compared with healthy pregnancies, whereas the late-onset of FGR only affects placental volume,” Limperopoulos adds. “We believe with early-onset FGR there is a more significant reduction in the developing placental units that is detected by gross measures of size and shape. By the third trimester, the overall shape of the placenta seems to have been well defined so that primarily volume is affected in late-onset FGR.”

In addition to Dr. Andescavage and Limperopoulos, study co-authors include Sonia Dahdouh, Sayali Yewale, Dorothy Bulas, M.D., chief of the Division of Diagnostic Imaging and Radiology, and Biostatistician, Marni Jacobs, Ph.D., MPH, all of Children’s National; Sara Iqbal, of MedStar Washington Hospital Center; and Ahmet Baschat, of Johns Hopkins Center for Fetal Therapy.

Financial support for research described in this post was provided by the National Institutes of Health under award number 1U54HD090257, R01-HL116585, UL1TR000075 and KL2TR000076, and the Clinical-Translational Science Institute-Children’s National.

little girl reaching for gun

Empowering pediatricians to reduce preventable firearm injuries and deaths

little girl reaching for gun

Lenore Jarvis, M.D., MEd, FAAP, will participate in a symposium of surgeons, neurosurgeons and emergency medicine doctors during the American Academy of Pediatrics National Conference and Exhibition – the first time these groups have come together to help reduce the number of kids hurt or killed by firearms.

Lenore Jarvis, M.D., MEd, FAAP, remembers feeling fatigue and frustration when, despite her team’s herculean efforts, a 5-year-old died from accidental gunshot wounds. The preschooler had been feeling playful: He surprised a family member who mistook him for an intruder and fired, fatally wounding the child.

As an Emergency Medicine and Trauma Services specialist at Children’s National Hospital, Dr. Jarvis has cared for kids with a range of firearm-related injuries from accidental shootings, intentional acts of violence or suicide attempts. Even when children survive such traumatic injuries, their lives are indelibly altered.

“We’re trained to save lives, but we also want to prevent childhood injuries, if possible. As I considered this young child’s life ending so prematurely and so tragically, I thought I should do more. I could do more,” recalls Dr. Jarvis, the division’s director of advocacy and health policy.

To that end, in addition to advocacy at the regional and national level, on Oct. 26, 2019, Dr. Jarvis will participate in a four-hour symposium of surgeons, neurosurgeons and emergency medicine doctors during the American Academy of Pediatrics (AAP) National Conference and Exhibition – the first time these groups have come together to explore ways they can help to reduce the number of kids hurt or killed by firearms.

Dr. Jarvis will set the stage for the day’s collective call to action when she counsels pediatricians about how they can advocate within the clinic by simple actions such as:

  • Asking families if there are firearms in the home
  • Making time for such conversations during routine care, including well-child visits
  • Paying special attention to warning signs of suicide and depression
  • Having frank conversations with parents about curious toddlers

“The safest home is a home without a firearm. If that’s not possible, the firearm should be stored in a locked cabinet with the ammunition stored separately,” she says. “Toddlers are especially curious and they actively explore their environment. An unsecured firearm can be a tragic accident waiting to happen with curious young children in the home. And if teenagers happen upon the weapon, it could be used in a homicide or suicide.”

In addition to empowering clinicians to have these conversations routinely, symposium speakers will emphasize empowering parents to ask other families: “Is there an unlocked gun in your house?”

“It’s no different than a parent of a child with a life-threatening sensitivity to peanuts asking if there are peanuts in any home that child may visit,” she adds. “As one of the leading causes of death among children and youth, unsecured firearms are even more dangerous than peanuts. And families should feel comfortable making informed decisions about whether their children will be safe as they play and socialize with friends.”

***
AAP National Conference and Exhibition presentation
Saturday, Oct. 26, 2:15 p.m. to 6:15 p.m. (ET)
“AAP NCE Section on Emergency Medicine/Section on Surgery/Section on Neurosurgery gun advocacy joint program”

doctor giving girl checkup

Decision support tool reduces unneeded referrals of low-risk patients with chest pain

doctor giving girl checkup

A simple evidence-based change to standard practice could avert needless referrals of low-risk patients to cardiac specialists, potentially saving nearly $4 million in annual health care spending while also easing worried parents’ minds.

Few events strike more fear in parents than hearing their child’s heart “hurts.”

When primary care pediatricians – who are on the frontline of triaging such distressing doctor visits – access a digital helping hand tucked into the patient’s electronic health record to help them make assessments, they are more likely to refer only the patients whose chest pain is rooted in a cardiac problem to a specialist.

That simple evidence-based change to standard practice could avert needless referrals of low-risk patients to cardiac specialists according to a quality-improvement project presented during the American Academy of Pediatrics (AAP) National Conference and Exhibition. This has the potential to save nearly $4 million in annual health care spending while also easing worried parents’ minds.

“Our decision support tool incorporates the know-how of providers and helps them to accurately capture the type of red flags that point to a cardiac origin for chest pain,” says Ashraf Harahsheh, M.D., FACC, FAAP, pediatric and preventive cardiologist and director of Resident Education in Cardiology at Children’s National Hospital. Those red flags include:

  • Abnormal personal medical history
    • Chest pain with exertion
    • Exertional syncope
    • Chest pain that radiates to the back, jaw, left arm or left shoulder
    • Chest pain that increases with supine position
    • Chest pain temporarily associated with a fever (>38.4°C)
  • A worrisome family history, including sudden unexplained death and cardiomyopathy.

“We know that evidence-based tools can be very effective in guiding physician behavior and reducing unnecessary testing and referrals which saves both the health care system in dollars and families in time and anxiety,” Dr. Harahsheh adds.

The abstract builds on a multi-institutional study published in Clinical Pediatrics in 2017 for which Dr. Harahsheh was lead author. More than 620,000 office-based visits (1.3%) to pediatricians in 2012 were for chest pain, he and co-authors wrote at the time. While children often complain of having chest pain, most of the time it is not due to an actual heart problem.

Over recent years, momentum has built for creating an evidence-based approach for determining which children with chest pain to refer to cardiac specialists. In response, the team’s quality-improvement tool, first introduced at two local primary pediatric offices, was expanded to the entire Children’s Pediatricians & Associates network of providers who offer pediatric primary care in Washington, D.C., and Maryland.

One daunting challenge: How to ensure that busy clinicians actually use the tool. To improve adoption, the project team embedded the decision support tool within the patient’s electronic medical record.  Now, they seek to make sure the tool gets used by more pediatricians around the country.

“If the chest pain decision support tool/medical red-flags criteria were adopted nationwide, we expect to save a minimum of $3.8 million in health care charges each year,” Dr. Harahsheh says. “That figure is very likely an underestimate of the true potential savings, because we did not calculate the value of lost productivity and other direct costs to families who shuttle from one appointment to the next.”

To ensure the changes stick, the team plans to train fledgling physicians poised to embrace the quality-improvement approach as they first launch their careers, and also look for evangelists within outpatient cardiology and pediatric clinics who can catalyze change.

“These types of quality-improvement projects require a change to the status quo. In order to be successful, we need members of the care team – including frontline clinicians and nurse practitioners – to champion change at the clinic level. With their help, we can continue to refine this tool and move toward nationwide implementation,” he explains.

***

AAP National Conference and Exhibition presentation
Saturday, Oct. 26, 9 a.m. to 2 p.m. (ET)
H2086 Council on Quality Improvement and Patient Safety Program

Saturday, Oct. 26, noon to 1 p.m. (ET)
Poster viewing
“Reducing low-probability cardiology referrals for chest pain from primary care: a quality improvement initiative”
Ashraf Harahsheh, M.D., FACC, FAAP; Ellen Hamburger, M.D.; Lexi Crawford, M.D.; Christina Driskill, MPH, RN, CPN; Anusha Rao, MHSA; Deena Berkowitz, M.D., MPH

***

Additional AAP 2019 activities featuring cardiology faculty at Children’s National Hospital include:

    • Rohan Kumthekar, M.D., recipient of the “Trainee Pediatric Cardiology Research Award” sponsored by the Children’s Heart Foundation
    • “Motion-corrected cardiac MRI limits anesthesia exposure and healthcare costs in children,” Adam B. Christopher, M.D.; Rachel Quinn, M.D.; Sara Zoulfagharian; Andrew Matisoff, M.D.; Russell Cross, M.D.; Adrienne Campbell-Washburn, Ph.D.; Laura Olivieri, M.D.
    • “Prevalence of abnormal echocardiograms in healthy, asymptomatic adolescents with Down syndrome,” Sarah B. Clauss, M.D.; Samuel S. Gidding M.D.; Claire I. Cochrane, BA; Rachel Walega, MS; Babette S. Zemel, Ph.D.; Mary E. Pipan, M.D.; Sheela N. Magge, M.D., MSCE;  Andrea Kelly, M.D., MSCE; Meryl S. Cohen, M.D.
    • “American College of Cardiology body mass index measurement and counseling quality improvement initiative,” Ashraf Harahsheh, M.D., FACC, FAAP; Arash Sabati, M.D., FACC; Jeffrey Anderson, M.D.; Clara Fitzgerald; Kathy Jenkins, M.D., MPH; Carolyn M. Wilhelm, M.D., MS, FACC, FAAP; Roy Jedeikin, M.D. FACC, MBA; Devyani Chowdhury, M.D.
Andrea Gropman

$5M in federal funding to help patients with urea cycle disorders

Andrea Gropman

Andrea L. Gropman, M.D.: We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.

An international research consortium co-led by Andrea L. Gropman, M.D., at Children’s National Hospital has received $5 million in federal funding as part of an overall effort to better understand rare diseases and accelerate potential treatments to patients.

Urea cycle disorder, one such rare disease, is a hiccup in a series of biochemical reactions that transform nitrogen into a non-toxic compound, urea. The six enzymes and two carrier/transport molecules that accomplish this essential task reside primarily in the liver and, to a lesser degree, in other organs.

The majority of patients have the recessive form of the disorder, meaning it has skipped a generation. These kids inherit one copy of an abnormal gene from each parent, while the parents themselves were not affected, says Dr. Gropman, chief of the Division of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National. Another more common version of the disease is carried on the X chromosome and affects boys more seriously that girls, given that boys have only one X chromosome.

Regardless of the type of urea cycle disorder, when the urea cycle breaks down, nitrogen converts into toxic ammonia that builds up in the body (hyperammonemia), particularly in the brain. As a result, the person may feel lethargic; if the ammonia in the bloodstream reaches the brain in high concentrations, the person can experience seizures, behavior changes and lapse into a coma.

Improvements in clinical care and the advent of effective medicines have transformed this once deadly disease into a more manageable chronic ailment.

“It’s gratifying that patients diagnosed with urea cycle disorder now are surviving, growing up, becoming young adults and starting families themselves. Twenty to 30 years ago, this never would have seemed conceivable,” Dr. Gropman says. “We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.”

In early October 2019, the National Institutes of Health (NIH) awarded the Urea Cycle Disorders Consortium for which Dr. Gropman is co-principal investigator a five-year grant. This is the fourth time that the international Consortium of physicians, scientists, neuropsychologists, nurses, genetic counselors and researchers has received NIH funding to study this group of conditions.

Dr. Gropman says the current urea cycle research program builds on a sturdy foundation built by previous principal investigators Mendel Tuchman, M.D., and Mark Batshaw, M.D., also funded by the NIH. While previous rounds of NIH funding powered research about patients’ long-term survival prospects and cognitive dysfunction, this next phase of research will explore patients’ long-term health.

Among the topics they will study:

Long-term organ damage. Magnetic resonance elastrography (MRE) is a state-of-the-art imaging technique that combines the sharp images from MRI with a visual map that shows body tissue stiffness. The research team will use MRE to look for early changes in the liver – before patients show any symptoms – that could be associated with long-term health impacts. Their aim is spot the earliest signs of potential liver dysfunction in order to intervene before the patient develops liver fibrosis.

Academic achievement. The research team will examine gaps in academic achievement for patients who appear to be underperforming to determine what is triggering the discrepancy between their potential and actual scholastics. If they uncover issues such as learning difficulties or mental health concerns like anxiety, there are opportunities to intervene to boost academic achievement.

“And if we find many of the patients meet the criteria for depression or anxiety disorders, there are potential opportunities to intervene.  It’s tricky: We need to balance their existing medications with any new ones to ensure that we don’t increase their hyperammonemia risk,” Dr. Gropman explains.

Neurologic complications. The researchers will tap continuous, bedside electroencephalogram, which measures the brain’s electrical activity, to detect silent seizures and otherwise undetectable changes in the brain in an effort to stave off epilepsy, a brain disorder that causes seizures.

“This is really the first time we will examine babies’ brains,” she adds. “Our previous imaging studies looked at kids and adults who were 6 years and older. Now, we’re lowering that age range down to infants. By tracking such images over time, the field has described the trajectory of what normal brain development should look like. We can use that as a background and comparison point.”

In the future, newborns may be screened for urea cycle disorder shortly after birth. Because it is not possible to diagnose it in the womb in cases where there is no family history, the team aims to better counsel families contemplating pregnancy about their possible risks.

Research described in this post was underwritten by the NIH through its Rare Diseases Clinical Research Network.

allopregnanolone molecule

Autism spectrum disorder risk linked to insufficient placental steroid

allopregnanolone molecule

A study led by Children’s National Hospital and presented during Neuroscience 2019 finds that loss of allopregnanolone, a key hormone supplied by the placenta, leads to long-term structural alterations of the cerebellum – a brain region essential for smooth motor coordination, balance and social cognition – and increases the risk of developing autism.

An experimental model study suggests that allopregnanolone, one of many hormones produced by the placenta during pregnancy, is so essential to normal fetal brain development that when provision of that hormone decreases – as occurs with premature birth – offspring are more likely to develop autism-like behaviors, a Children’s National Hospital research team reports at the Neuroscience 2019 annual meeting.

“To our knowledge, no other research team has studied how placental allopregnanolone (ALLO) contributes to brain development and long-term behaviors,” says Claire-Marie Vacher, Ph.D., lead author. “Our study finds that targeted loss of ALLO in the womb leads to long-term structural alterations of the cerebellum – a brain region that is essential for motor coordination, balance and social cognition ­– and increases the risk of developing autism,” Vacher says.

According to the Centers for Disease Control and Prevention, about 1 in 10 infants is born preterm, before 37 weeks gestation; and 1 in 59 children has autism spectrum disorder.

In addition to presenting the abstract, on Monday, Oct. 21, Anna Penn, M.D., Ph.D., the abstract’s senior author, will discuss the research with reporters during a Neuroscience 2019 news conference. This Children’s National abstract is among 14,000 abstracts submitted for the meeting, the world’s largest source of emerging news about brain science and health.

ALLO production by the placenta rises in the second trimester of pregnancy, and levels of the neurosteroid peak as fetuses approach full term.

To investigate what happens when ALLO supplies are disrupted, a research team led by Children’s National created a novel transgenic preclinical model in which they deleted a gene essential in ALLO synthesis. When production of ALLO in the placentas of these experimental models declines, offspring had permanent neurodevelopmental changes in a sex- and region-specific manner.

“From a structural perspective, the most pronounced cerebellar abnormalities appeared in the cerebellum’s white matter,” Vacher adds. “We found increased thickness of the myelin, a lipid-rich insulating layer that protects nerve fibers. From a behavioral perspective, male offspring whose ALLO supply was abruptly reduced exhibited increased repetitive behavior and sociability deficits – two hallmarks in humans of autism spectrum disorder.”

On a positive note, providing a single ALLO injection during pregnancy was enough to avert both the cerebellar abnormalities and the aberrant social behaviors.

The research team is now launching a new area of research focus they call “neuroplacentology” to better understand the role of placenta function on fetal and newborn brain development.

“Our team’s data provide exciting new evidence that underscores the importance of placental hormones on shaping and programming the developing fetal brain,” Vacher notes.

  • Neuroscience 2019 presentation
    Sunday, Oct. 20, 9:30 a.m. (CDT)
    “Preterm ASD risk linked to cerebellar white matter changes”
    Claire-Marie Vacher, lead author; Sonia Sebaoui, co-author; Helene Lacaille, co-author; Jackie Salzbank, co-author; Jiaqi O’Reilly, co-author; Diana Bakalar, co-author; Panagiotis Kratimenos, M.D., neonatologist and co-author; and Anna Penn, M.D., clinical neonatologist and developmental neuroscientist and senior author.
Bella when she was sick

Preserving brain function by purposely inducing strokes

Bella when she was sick

Born to young parents, no prenatal testing had suggested any problems with Bella’s brain. But just a few hours after birth, Bella suffered her first seizure – one of many that would follow in the ensuing days. After brain imaging, her doctors in Iowa diagnosed her with hemimegalencephaly.

Strokes are neurologically devastating events, cutting off life-sustaining oxygen to regions of the brain. If these brain tissues are deprived of oxygen long enough, they die, leading to critical loss of function – and sometimes loss of life.

“As physicians, we’re taught to prevent or treat stroke. We’re never taught to inflict it,” says Taeun Chang, M.D., director of the Neonatal Neurology and Neonatal Neurocritical Care Program at Children’s National Hospital.

That’s why a treatment developed at Children’s National for a rare brain condition called hemimegalencephaly is so surprising, Dr. Chang explains. By inflicting controlled, targeted strokes, Children’s National physician-researchers have treated five newborns born with intractable seizures due to hemimegalencephaly before they’re eligible for epilepsy surgery, the standard of care. In the four surviving infants, the procedures drastically reduced or completely relieved the infants of hemimegalencephaly’s characteristic, uncontrollable seizures.

The most recent patient to receive this life-changing procedure is Bella, a 13-month-old from Iowa whose treatment at Children’s National began within her second week of life. Born to young parents, no prenatal testing had suggested any problems with Bella’s brain. But just a few hours after birth, Bella suffered her first seizure – one of many that would follow in the ensuing days. After brain imaging, her doctors in Iowa diagnosed her with hemimegalencephaly.

A congenital condition occurring in just a handful of children born worldwide each year, hemimegalencephaly is marked by one brain hemisphere growing strikingly larger and dysplastic than the other, Dr. Chang explains. This abnormal half of the brain is highly vascularized, rippled with blood vessels needed to support the seizing brain. The most conspicuous symptoms of hemimegalencephaly are the numerous seizures that it causes, sometimes several in the course of an hour, which also may prevent the normal half of the brain from developing and learning.

Prior studies suggest early surgery achieves better developmental outcomes with one study reporting as much as a drop of 10-20 IQ points with every month delay in epilepsy surgery.

The standard treatment for unilateral megalencephaly is a dramatic procedure called a hemispherectomy, in which surgeons remove and disconnect the affected half of the brain, allowing the remaining half to take over its neurological duties. However, Dr. Chang says, implementing this procedure in infants younger than 3 months of age is highly dangerous.  Excessive, potentially fatal blood loss is likely in infants younger than 3 months who have a highly vascularized brain in the setting of an immature coagulation system. That leaves their doctors with no choice but to wait until these infants are at least 3 months old, when they are more likely to survive the surgery.

However, five years ago, Dr. Chang and her colleagues came up with a different idea when a newborn continued to have several seizures per hour despite multiple IV seizure medications: Because strokes cause irreversible tissue death, it might be possible to effectively incapacitate the enlarged hemisphere from within by inflicting a stroke on purpose. At the very least, this “functional embolization” might buy time for a traditional hemispherectomy, and slow or halt ongoing brain damage until the infants are able to withstand surgery. Ideally, this procedure may be all some children need, knocking out the offending hemisphere completely so they’d never need a hemispherectomy, which has late complications, such as hydrocephalus.

A pediatrician friend of Bella’s paternal grandparents read a story on Children’s National website about Darcy, another baby who’d received functional embolization a year earlier and was doing well. She contacted Dr. Chang to see if the procedure would be appropriate for Bella.

Within days, Bella and her family headed to Washington, D.C., to prepare for functional embolization herself. Within the first weeks of life, Bella underwent three separate procedures, each three to four hours long. Under real-time fluoroscopic and angiographic guidance, interventional neuroradiologist Monica Pearl, M.D., threaded a micro-catheter up from the baby’s femoral artery through the complex network of blood vessels all the way to her brain. There, in targeted branches of her cerebral arteries, Dr. Pearl strategically placed liquid embolic agent to obstruct blood flow to the abnormal half of Bella’s brain.

Immediately after the first procedure, the team had to contend with the same consequences that come after any stroke: brain swelling that can cause bleeding and herniation, complicated further by the already enlarged hemisphere of Bella’s brain. Using neuroprotective strategies learned from treating hundreds of brain-injured newborns, the neonatal neurocritical care team and the neonatal intensive care unit (NICU) minimized the brain swelling and protected the normal half of the brain by tightly controlling the brain temperature, her sugar and electrolyte levels, her blood pressure and coagulation system.

As the brain tissue in the oversized hemisphere died, so did the seizures that had plagued Bella since birth. She has not had a seizure since she left Children’s National more than one year ago. Her adoptive parents report that Bella is hitting many of the typical developmental milestones for her age: She’s getting ready to walk, blowing kisses and saying a few words. Physical, speech and occupational therapy will keep her moving in the right direction, Dr. Chang says.

“We believe that Children’s National is the only place in the world that’s treating newborns in this way to preserve their futures,” Dr. Chang says. “We’re privileged to be able to care for Bella and other kids with this rare condition.”

Bella’s transfer and successful procedures required the support and collective efforts of many within the hospital organization including William D. Gaillard, M.D., and his surgical epilepsy team; interventional neuroradiology with Dr. Monica Pearl; Neurosurgery; Neonatology and the NICU; social work; and even approval from Robin Steinhorn, M.D., senior vice president of the Center for Hospital-Based Specialties, and David Wessel, M.D., executive vice president and Chief Medical Officer.

“While obvious credit goes to the medical team who saved Bella’s future and the neonatal intensive care nurses who provided exceptional, intensive, one-on-one care, Bella’s team of supporters extend to all levels within our hospital,” Dr. Chang adds.

Also read:

Bella's brain scan

Born with hemimegalencephaly, Bella now has a bright future

bella's brain scans

PDF Version

Bella was born with a rare condition (hemimegalencephaly) in which one half of the brain developed abnormally, causing seizures. The textbook approach is to let babies grow big enough for a dramatic surgery. But Bella’s left hemisphere was triggering so many seizures each hour that waiting would mean her life would be defined by severe disability. Children’s National Hospital is believed to be the only center in the world that calms these seizures through controlled strokes.

Procedure one occurred five days after Bella came to Children’s National Hospital from Iowa, when she was 13 days old. The team first optimized control of her seizures and obtained special magnetic resonance images to plan their approach. They glued up the branches of the left posterior cerebral artery and branches of the left middle cerebral artery. Bella had a tiny bleed that was controlled immediately in the angio suite and afterwards in the Children’s National neonatal intensive care unit.

Procedure two occurred 10 days later when Bella was 23 days old. The team waited until brain swelling had subsided and brain tissue loss had occurred from the first procedure. This time, they glued up the remaining branches of the left posterior cerebral artery and some branches of the left anterior cerebral artery.

The third and final procedure was done nine days later when Bella was 29 days old.  This time the team glued and coiled, placing little wire coils where it was unsafe to use glue, getting at the remaining small and numerous branches that remained of the left anterior cerebral artery.

Also read:
nurse checking boy's hearbeat

Children’s National launches telehealth collaboration with Whittle School & Studios

nurse checking boy's hearbeat

The School-Based Telehealth Program provides students quick access to medical care, rapid diagnosis of medical conditions, and better management of chronic conditions like asthma and diabetes, while minimizing time away from school for children – and from work for parents.

Children’s National Hospital and Whittle School & Studios announced a collaboration to provide students at the Whittle School’s D.C. campus with on-site video connectivity to health professionals at the hospital throughout the 2019-20 school year.

“We are thrilled to collaborate with Children’s National to offer our students world-class medical care from compassionate providers,” said Dennis Bisgaard, head of Whittle’s D.C. campus. “The health and safety of our students is our top priority, and this new collaboration ensures that they’ll be in excellent hands.”

A registered nurse from Children’s National will work on-site at Whittle’s D.C. campus to provide acute care, first aid, immunization record-keeping, medication management, EpiPen storage and training and more.

Children’s National’s School-Based Telehealth Program will also be available at the Whittle School. The on-site nurse will have the ability to use secure video-conferencing technology to connect students with board-certified physicians from Children’s National, if necessary.

The School-Based Telehealth Program provides students quick access to medical care, rapid diagnosis of medical conditions, and better management of chronic conditions like asthma and diabetes, while minimizing time away from school for children – and from work for parents. The program will complement existing care the student may already receive from their medical home or primary care provider.

“We are excited to collaborate with the Whittle School to design a program centered on our shared vision of helping children,” said Denice Cora-Bramble, M.D., executive vice president and chief medical officer, ambulatory and community health services at Children’s National. “Our goal is that this new collaboration will provide access to highly-specialized health care expertise to patients and families and our hope is that school-based nursing services, coupled with telehealth technology, will improve students’ health and education outcomes.”

Mihailo Kaplarevic

Extracting actionable research data faster, with fewer hassles

Mihailo Kaplarevic

Mihailo Kaplarevic, Ph.D., the newly minted Chief Research Information Officer at Children’s National Hospital and Bioinformatics Division Chief at Children’s National Research Institute, will provide computational support, advice, informational guidance, expertise in big data and data analyses for researchers and clinicians.

Kaplarevic’s new job is much like the role he played most recently at the National Heart, Lung and Blood Institute (NHLBI), assembling a team of researchers and scientists skilled in computing and statistical analyses to assist as in-house experts for other researchers and scientists.

NHLBI was the first institute within the National Institutes of Health (NIH) family to set up a scientific information office. During his tenure, a half-dozen other NIH institutions followed, setting up the same entity to help bridge the enormous gap between basic and clinical science and everything related to IT.

“There is a difference compared with traditional IT support at Children’s National – which will remain in place and still do the same sort of things they have been doing so far,” he says of The Bear Institute for Health Innovation. “The difference is this office has experience in research because every single one of us was a researcher at a certain point in our career: We are published. We applied for grants. We lived the life of a typical scientist. On top of that, we’re coming from the computational world. That helps us bridge the gaps between research and clinical worlds and IT.”

Ultimately, he aims to foster groundbreaking science by recognizing the potential to enhance research projects by bringing expertise acquired over his career and powerful computing tools to help teams achieve their goals in a less expensive and more efficient way.

“I have lived the life of a typical scientist. I know exactly how painful and frustrating it can be to want to do something quickly and efficiently but be slowed by technological barriers,” he adds.

As just one example, his office will design the high-performance computing cluster for the hospital to help teams extract more useful clinical and research data with fewer headaches.

Right now, the hospital has three independent clinical systems storing patient data; all serve a different purpose. (And there are also a couple of research information systems, also used for different purposes.) Since databases are his expertise, he will be involved in consolidating data resources, finding the best way to infuse the project with the bigger-picture mission – especially for translational science – and creating meaningful, actionable reports.

“It’s not only about running fewer queries,” he explains. “One needs to know how to design the right question. One needs to know how to design that question in a way that the systems could understand. And, once you get the data back, it’s a big set of things that you need to further filter and carefully shape. Only then will you get the essence that has clinical or scientific value. It’s a long process.”

As he was introduced during a Children’s National Research Institute faculty meeting in late-September 2019, Kaplarevic joked that his move away from pure computer science into a health care and clinical research domain was triggered by his parents: “When my mom would introduce me, she would say ‘My son is a doctor, but not the kind of doctor who helps other people.’ ”

Some of that know-how will play out by applying tools and methodology to analyze big data to pluck out the wheat (useful data) from the chaff in an efficient and useful way. On projects that involve leveraging cloud computing for storing massive amounts of data, it could entail analyzing the data wisely to reduce its size when it comes back from the cloud – when the real storage costs come in. “You can save a lot of money by being smart about how you analyze data,” he says.

While he expects his first few months will be spent getting the lay of the land, understanding research project portfolios, key principal investigators and the pediatric hospital’s biggest users in the computational domain, he has ambitious longer-term goals.

“Three years from now, I would like this institution to say that the researchers are feeling confident that their research is not affected by limitations related to computer science in general. I would like this place to become a very attractive environment for up-and-coming researchers as well as for established researchers because we are offering cutting-edge technological efficiencies; we are following the trends; we are a secure place; and we foster science in the best possible way by making computational services accessible, affordable and reliable.”

Lee Beers

Getting to know Lee Beers, M.D., FAAP, future president-elect of AAP

Lee Beers

Lee Savio Beers, M.D., FAAP, Medical Director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital carved out a Monday morning in late-September 2019, as she knew the American Academy of Pediatrics (AAP) would announce the results of its presidential election, first by telephone call, then by an email to all of its members.  Her husband blocked off the morning as well to wait with her for the results.  She soon got the call that she was elected by her peers to become AAP president-elect, beginning Jan. 1, 2020. Dr. Beers will then serve as AAP president in 2021 for a one-year term.

That day swept by in a rush, and then the next day she was back in clinic, caring for her patients, some of them teenagers whom she had taken care of since birth. Seeing children and families she had known for such a long time, some of whom had complex medical needs, was a perfect reminder of what originally motivated Dr. Beers to be considered as a candidate in the election.

“When we all work together – with our colleagues, other professionals, communities and families – we can make a real difference in the lives of children.  So many people have reached out to share their congratulations, and offer their support or help. There is a real sense of collaboration and commitment to child health,” Dr. Beers says.

That sense of excitement ripples through Children’s National.

“Dr. Beers has devoted her career to helping children. She has developed a national advocacy platform for children. I can think of no better selection for the president-elect role of the AAP. She will be of tremendous service to children within AAP national leadership,” says Kurt Newman, M.D., Children’s National Hospital President and CEO.

AAP comprises 67​,000 pediatricians, and its mission is to promote and safeguard the health and well-being of all children – from infancy to adulthood.

The daughter of a nuclear engineer and a schoolteacher, Dr. Beers knew by age 5 that she would become a doctor. Trained as a chemist, she entered the Emory University School of Medicine after graduation. After completing residency at the Naval Medical Center, she became the only pediatrician assigned to the Guantanamo Bay Naval Station.

That assignment to Cuba, occurring so early in her career, turned out to be a defining moment that shapes how she partners with families and other members of the team to provide comprehensive care.

“I was a brand-new physician, straight out of residency, and was the only pediatrician there so I was responsible for the health of all of the kids on the base. I didn’t know it would be this way at the time, but it was formative. It taught me to take a comprehensive public health approach to taking care of kids and their families,” she recalls.

On the isolated base, where she also ran the immunization clinic and the nursery, she quickly learned she had to judiciously use resources and work together as a team.

“It meant that I had to learn how to lead a multi-disciplinary team and think about how our health care systems support or get in the way of good care,” she says.

One common thread that unites her past and present is helping families build resiliency to shrug off adversity and stress.

“The base was a difficult and isolated place for some families and individuals, so I thought a lot about how to support them. One way is finding strong relationships where you are, which was important for patients and families miles away from their support systems. Another way is to find things you could do that were meaningful to you.”

Cuba sits where the Atlantic Ocean, Caribbean Sea and Gulf of Mexico meet. Dr. Beers learned how to scuba dive there – something she never would have done otherwise – finding it restful and restorative to appreciate the underwater beauty.

“I do think these lessons about resilience are universal. There are actually a lot of similarities between the families I take care of now, many of whom are in socioeconomically vulnerable situations, and military families when you think about the level of stress they are exposed to,” she adds.

Back stateside in 2001, Dr. Beers worked as a staff pediatrician at the National Naval Medical Center in Bethesda, Maryland, and Walter Reed Army Medical Center in Washington, D.C. In 2003, Dr. Beers joined Children’s National Hospital as a general pediatrician in the Goldberg Center for Community Pediatric Health. Currently, she oversees the DC Collaborative for Mental Health in Pediatric Primary Care, a public-private coalition that elevates the standards of mental health care for all children, and is Co-Director of the Early Childhood Innovation Network. She received the Academic Pediatric Association’s 2019 Public Policy and Advocacy Award.

As a candidate, Dr. Beers pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns
  • Tackling physician burnout by supporting pediatricians through office-based education and systems reforms
  • Expanding community-based prevention and treatment

“I am humbled and honored to have the support of my peers in taking on this newest leadership role,” says Dr. Beers. “AAP has been a part of my life since I first became a pediatrician, and my many leadership roles in the DC chapter and national AAP have given me a glimpse of the collective good that pediatricians can accomplish by working together toward common strategic goals.”

AAP isn’t just an integral part of her life, it’s where she met her future husband, Nathaniel Beers, M.D., MPA, FAAP, President of The HSC Health Care System. The couple’s children regularly attended AAP meetings with them when they were young.

Just take a glimpse at Lee Beers’ Twitter news feed. There’s a steady stream of images of her jogging before AAP meetings to amazing sunrises, jogging after AAP meetings to stellar sunsets and always, always, images of the entire family, once collectively costumed as The Incredibles.

“I really do believe that we have to set an example: If we are talking about supporting children and families in our work, we have to set that example in our own lives. That looks different for everyone, but as pediatricians and health professionals, we can model prioritizing our families while still being committed to our work,” she explains.

“Being together in the midst of the craziness is just part of what we do as a family. We travel a lot, and our kids have gone with us to AAP meetings since they were infants. My husband even brought our infant son to a meeting at the mayor’s office when he was on paternity leave. Recognizing that not everyone is in a position to be able to do things like that, it’s important for us to do it – to continue to change the conversation and make it normal to have your family to be part of your whole life, not have a separate work life and a separate family life.”

Tania Ahluwalia

Simulation curriculum for emergency medicine trainees in India

Tania Ahluwalia

“It is essential to equip emergency physicians in India with these necessary skills so they can provide the best acute care for children and help the country overcome its burden of pediatric illness. This project focuses on simulation training because it is a very effective way to practice clinical and communication skills,” says Tania Ahluwalia, M.D., FAAP.

India has a high burden of pediatric illness, and close to 1 million children die each year.

Despite those staggering public health challenges, pediatric emergency medicine training remains in its infancy in India. Tania Ahluwalia, M.D., FAAP, associate director of Global Health Programs, Division of Emergency Medicine and Trauma Services at Children’s National Hospital has been working with the Ronald Reagan Institute of Emergency Medicine to help address that training gap.

“It is essential to equip emergency physicians in India with these necessary skills so they can provide the best acute care for children and help the country overcome its burden of pediatric illness. This project focuses on simulation training because it is a very effective way to practice clinical and communication skills,” Dr. Ahluwalia says.

Each October a team led by Dr. Ahluwalia teaches Pediatric Emergency Medicine modules in India based on a three-year curriculum.  In October 2019, they will focus on neonatology. And thanks to a 2019-2020 Global Health Initiative Exploration in Global Health Award presented during Research and Education Week at Children’s National, over two weeks Dr. Ahluwalia will visit various cities in India with a team that includes:

  • Kaitlyn Boggs, M.D., a second-year pediatric resident at Children’s National
  • Camilo Gutierrez, M.D., Children’s National Emergency Medicine and Trauma Services
  • Simone Lawson, M.D., Children’s National Emergency Medicine and Trauma Services
  • Shobhit Jain, Kansas City
  • Shiva Kalidindi, Nemours Children’s Hospital
  • Manu Madhok, Minneapolis

For the study, about 80 trainees participating in postgraduate emergency medicine training programs in India will practice skills, such as intubating a patient, using the same medical equipment and mannequins of the same size as pediatric patients. The trainees will review several pediatric emergency medicine cases that were developed based on a needs assessment at partner programs in India. First, visiting faculty members will watch videos developed by Dr. Ahluwalia, Michael Hrdy, M.D., and Rachael Batabyal, M.D., and will review literature on how to conduct simulation in a developing country.

Faculty teaching neonatology, use of simulation modules and other pediatric emergency medicine training topics will visit Bangalore, Bhubaneswar, Dehradun, Delhi, Kochi, Kolkata, Kozhikhode, Madurai and Mumbai. (Kate Douglass, M.D., of the George Washington University and Serkan Toy, Ph.D., an educational psychologist at John Hopkins University, have been heavily involved in this project but will not travel to India in October.)

“My passion is global education so, for me, this project will be a success if we improve the trainees’ comfort, knowledge and skill at providing patient care after undergoing this simulation-based curriculum. We also want to improve our faculty’s capacity to teach through these simulation modules, so there are definitely learning opportunities for both U.S. teachers and Indian trainees,” she adds.

WATCH: Introduction to simulation training
WATCH: Performing a simulation learning event
WATCH: Debriefing tools

Financial support for research described in this post was provided by the 2019-2020 Global Health Initiative Exploration in Global Health Award.

gut bacteria

Understanding gut bacteria: forces for good (and sometimes evil)

gut bacteria

In a paper published Sept. 11, 2019, in PLOS ONE, a multi-institutional research team led by George Washington University (GW) faculty found 157 different types of organisms (eight phyla, 18 classes, 23 orders, 38 families, 59 genera and 109 species) living inside the guts of healthy volunteers.

Back in 2015, an interdisciplinary group of research scientists made their case during a business pitch competition: They want to create a subscription-based service, much like 23andMe, through which people could send in samples for detailed analyses. The researchers would crunch that big data fast, using a speedy algorithm, and would send the consumer a detailed report.

But rather than ancestry testing via cheek swab, the team sought to determine the plethora of diverse bacterial species that reside inside an individual’s gut in their ultimate aim to improve public health.

Hiroki Morizono, Ph.D., a member of that team, contributed detailed knowledge of Bacteroides, a key organism amid the diverse array of bacterial species that co-exist with humans, living inside our guts. These symbiotic bacteria convert the food we eat into elements that ensure their well-being as well as ours.

“Trillions of bacteria live in the gut. Bacteroides is one of the major bacterial species,” says Morizono, a principal investigator in the Center for Genetic Medicine Research at Children’s National in Washington, D.C. “In our guts they are usually good citizens. But if they enter our bloodstream, they turn evil; they’re in the wrong place. If you have a bacteroides infection, the mortality rate is 19%, and they resist most antibiotic treatments.”

The starting point for their project – as well as step one for better characterizing the relationship between gut bacteria and human disease – is taking an accurate census count of bacteria residing there.

In a paper published Sept. 11, 2019, in PLOS ONE, a multi-institutional research team led by George Washington University (GW) faculty did just that, finding 157 different types of organisms (eight phyla, 18 classes, 23 orders, 38 families, 59 genera and 109 species) living inside the guts of healthy volunteers.

The study participants were recruited through flyers on the GW Foggy Bottom campus and via emails.  They jotted down what they ate and drank daily, including the brand, type and portion size. They complemented that food journal by providing fecal samples from which DNA was extracted. Fifty fecal metagenomics samples randomly selected from the Human Microbiome Project Phase I research were used for comparison purposes.

“The gut microbiome inherently is really, really cool. In the process of gathering this data, we are building a knowledge base. In this paper, we’re saying that by looking at healthy people, we should be able to establish a baseline about what a normal, healthy gut microbiome should look like and how things may change under different conditions,” Morizono adds.

And they picked a really, really cool name for their bacteria abundance profile: GutFeelingKB.

“KB is knowledge base. Our idea, it’s a gut feeling. It’s a bad joke,” he admits. “Drosophila researchers have the best names for their genes. No other biology group can compete. We, at least, tried.”

Next, the team will continue to collect samples to build out their bacteria baseline, associate it with clinical data, and then will start looking at the health implications for patients.

“One thing we could use this for is to understand how the bacterial population in the gut changes after antibiotic treatment. It’s like watching a forest regrow after a massive fire,” he says. “With probiotics, can we do things to encourage the right bacteria to grow?”

In addition to Morizono, study co-authors include Lead Author Charles H. King, and co-authors Hiral Desai, Allison C. Sylvetsky, Jonathan LoTempio, Shant Ayanyan, Jill Carrie, Keith A. Crandall, Brian C. Fochtman, Lusine Gasparyan, Naila Gulzar, Najy Issa, Lopa Mishra, Shuyun Rao, Yao Ren, Vahan Simonyan, Krista Smith and Senior Author, Raja Mazumder, all of George Washington University; Paul Howell and Sharanjit VedBrat, of KamTek Inc.; Konstantinos Krampis, of City University of New York; Joseph R. Pisegna, of VA Greater Los Angeles Healthcare System; and Michael D. Yao, of Washington DC VA Medical Center.

Financial support for research described in this post was provided by the National Science Foundation under award number 1546491 and the National Institutes of Health National Center for Advancing Translational Sciences under award number UL1TR000075.