Public Health

Catherine Limperopoulos

Breastfeeding boosts metabolites important for brain growth

Catherine Limperopoulos

“Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites that may play a critical role for growth and explain what makes breastfeeding beneficial for newborns’ developing brains,” says Catherine Limperopoulos, Ph.D.

Micro-preemies who primarily consume breast milk have significantly higher levels of metabolites important for brain growth and development, according to sophisticated imaging conducted by an interdisciplinary research team at Children’s National.

“Our previous research established that vulnerable preterm infants who are fed breast milk early in life have improved brain growth and neurodevelopmental outcomes. It was unclear what makes breastfeeding so beneficial for newborns’ developing brains,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National. “Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites essential for growth and answer that lingering question.”

According to the Centers for Disease Control and Prevention, about 1 in 10 U.S. infants is born preterm. The Children’s research team presented their findings during the Pediatric Academic Societies 2019 Annual Meeting.

The research-clinicians enrolled babies who were very low birthweight (less than 1,500 grams) and 32 weeks gestational age or younger at birth when they were admitted to Children’s neonatal intensive care unit in the first week of life. The team gathered data from the right frontal white matter and the cerebellum – a brain region that enables people to maintain balance and proper muscle coordination and that supports high-order cognitive functions.

Each chemical has its own a unique spectral fingerprint. The team generated light signatures for key metabolites and calculated the quantity of each metabolite. Of note:

  • Cerebral white matter spectra showed significantly greater levels of inositol (a molecule similar to glucose) for babies fed breast milk, compared with babies fed formula.
  • Cerebellar spectra had significantly greater creatine levels for breastfed babies compared with infants fed formula.
  • And the percentage of days infants were fed breast milk was associated with significantly greater levels of both creatine and choline, a water soluble nutrient.

“Key metabolite levels ramp up during the times babies’ brains experience exponential growth,” says Katherine M. Ottolini, the study’s lead author. “Creatine facilitates recycling of ATP, the cell’s energy currency. Seeing greater quantities of this metabolite denotes more rapid changes and higher cellular maturation. Choline is a marker of cell membrane turnover; when new cells are generated, we see choline levels rise.”

Already, Children’s National leverages an array of imaging options that describe normal brain growth, which makes it easier to spot when fetal or neonatal brain development goes awry, enabling earlier intervention and more effective treatment. “Proton magnetic resonance spectroscopy may serve as an important additional tool to advance our understanding of how breastfeeding boosts neurodevelopment for preterm infants,” Limperopoulos adds.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Improved cerebral and cerebellar metabolism in breast milk-fed VLBW infants.”
    • Monday, April 29, 2019, 3:30–3:45 p.m. (EST)

Katherine M. Ottolini, lead author; Nickie Andescavage, M.D., Attending, Neonatal-Perinatal Medicine and co-author; Kushal Kapse, research and development staff engineer and co-author; Sudeepta Basu, M.D., neonatologist and co-author; and Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain and senior author, all of Children’s National.

An-Massaro

Looking for ‘help’ signals in the blood of newborns with HIE

An Massaro

“This data support our hypothesis that a panel of biomarkers – not a one-time test for a single biomarker – is needed to adequately determine the risk and timing of brain injury for babies with HIE,” says An N. Massaro, M.D.

Measuring a number of biomarkers over time that are produced as the body responds to inflammation and injury may help to pinpoint newborns who are more vulnerable to suffering lasting brain injury due to disrupted oxygen delivery and blood flow, according to research presented during the Pediatric Academic Societies 2019 Annual Meeting.

Hypoxic-ischemic encephalopathy (HIE) happens when blood and oxygen flow are disrupted around the time of birth and is a serious birth complication for full-term infants. To lessen the chance of these newborns suffering permanent brain injury, affected infants undergo therapeutic cooling, which temporarily lowers their body temperatures.

“Several candidate blood biomarkers have been investigated in HIE but we still don’t have one in clinical use.  We need to understand how these markers change over time before we can use them to direct care in patients,” says An N. Massaro, M.D., co-director of the Neonatal Neurocritical Care Program at Children’s National and the study’s senior author. “The newborns’ bodies sent out different ‘help’ signals that we detected in their bloodstream, and the markers had strikingly different time courses. A panel of plasma biomarkers has the potential to help us identify infants most in need of additional interventions, and to help us understand the most optimal timing for those interventions.”

Past research has keyed in on inflammatory cytokines and Tau protein as potential biomarkers of brain injury for infants with HIE who are undergoing therapeutic cooling. The research team led by Children’s faculty wanted to gauge which time periods to measure such biomarkers circulating in newborns’ bloodstreams. They enrolled 85 infants with moderate or severe HIE and tapped unused blood specimens that had been collected as cooling began, as well as 12, 24, 72 and 96 hours later. The infants’ mean gestational age was 38.7 weeks, their mean birth weight was about 7 pounds (3.2 kilograms), and 19% had severe brain disease (encephalopathy).

Cytokines – chemicals like Interleukin (IL) 6, 8 and 10 that regulate how the body responds to infection, inflammation and trauma – peaked in the first 24 hours of cooling for most of the newborns. However, the highest measure of Tau protein for the majority of newborns was during or after the baby’s temperature was restored to normal.

“After adjusting for clinical severity of encephalopathy and five-minute Apgar scores, IL-6, IL-8 and IL-10 predicted adverse outcomes, like severe brain injury or death, as therapeutic hypothermia began. By contrast, Tau protein measurements predicted adverse outcomes during and after the infants were rewarmed,” Dr. Massaro says.

IL-6 and IL-8 proteins are pro-inflammatory cytokines while IL-10 is considered anti-inflammatory.  These chemicals are released as a part of the immune response to brain injury. Tau proteins are abundant in nerve cells and stabilize microtubules.

“This data support our hypothesis that a panel of biomarkers – not a one-time test for a single biomarker – is needed to adequately determine the risk and timing of brain injury for babies with HIE,” she adds.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Serial plasma biomarkers of brain injury in infants with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH).”
    • Saturday, April 27, 2019, 6 p.m. (EST)

Meaghan McGowan, lead author; Alexandra C. O’Kane, co-author; Gilbert Vezina, M.D.,  director, Neuroradiology Program and co-author; Tae Chang, M.D., director, Neonatal Neurology Program and co-author; and An N. Massaro, M.D., co-director of the Neonatal Neurocritical Care Program and senior author; all of Children’s National; and co-author Allen Everett, of Johns Hopkins School of Medicine.

Ololade Okito

Parents of older, healthier newborns with less social support less resilient

Ololade Okito

“We know that having a child hospitalized in the NICU can be a high-stress time for families,” says Ololade Okito, M.D., lead author of the cross-sectional study. “The good news is that as parental resiliency scores rise, we see a correlation with fewer symptoms of depression and anxiety.

Parents of older, healthier newborns who had less social support were less resilient during their child’s hospitalization in the neonatal intensive care unit (NICU), a finding that correlates with more symptoms of depression and anxiety, according to Children’s research presented during the Pediatric Academic Societies 2019 Annual Meeting.

Resiliency is the natural born, yet adaptable ability of people to bounce back in the face of significant adversity. Published research indicates that higher resilience is associated with reduced psychological distress, but the phenomenon had not been studied extensively in parents of children hospitalized in a NICU.

“We know that having a child hospitalized in the NICU can be a high-stress time for families,” says Ololade Okito, M.D., lead author of the cross-sectional study. “The good news is that as parental resiliency scores rise, we see a correlation with fewer symptoms of depression and anxiety. Parents who feel they have good family support also have higher resilience scores.”

The project is an offshoot of a larger study examining the impact of peer mentoring by other NICU parents who have experienced the same emotional rollercoaster ride as their tiny infants sometimes thrived and other times struggled.

The research team enrolled 35 parents whose newborns were 34 weeks gestation and younger and administered a battery of validated surveys, including:

Forty percent of these parents had high resilience scores; parents whose infants were a mean of 27.3 gestational weeks and who had more severe health challenges reported higher resilience. Another 40% of these parents had elevated depressive symptoms, while 31% screened positive for anxiety. Parental distress impairs the quality of parent-child interactions and long-term child development, the research team writes.

“Higher NICU-related stress correlates with greater symptoms of depression and anxiety in parents,” says Lamia Soghier, M.D., MEd, medical director of Children’s neonatal intensive care unit and the study’s senior author. “Specifically targeting interventions to these parents may help to improve their resilience, decrease the stress of parenting a child in the NICU and give these kids a healthier start to life.”

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Parental resilience and psychological distress in the neonatal intensive care unit (PARENT) study”
    • Tuesday, April 30, 2019, 7:30 a.m. (EST)

Ololade Okito, M.D., lead author; Yvonne Yui, M.D., co-author; Nicole Herrera, MPH, co-author; Randi Streisand, Ph.D., chief, Division of Psychology and Behavioral Health, and co-author; Carrie Tully, Ph.D., clinical psychologist and co-author; Karen Fratantoni, M.D., MPH, medical director, Complex Care Program, and co-author; and Lamia Soghier, M.D., MEd, medical unit director, neonatal intensive care unit, and senior author; all of Children’s National.

DNA Molecule

Decoding cellular signals linked to hypospadias

DNA Molecule

“By advancing our understanding of the genetic causes and the anatomic differences among patients, the real goal of this research is to generate knowledge that will allow us to take better care of children with hypospadias,” Daniel Casella, M.D. says.

Daniel Casella, M.D., a urologist at Children’s National, was honored with an AUA Mid-Atlantic Section William D. Steers, M.D. Award, which provides two years of dedicated research funding that he will use to better understand the genetic causes for hypospadias.

With over 7,000 new cases a year in the U.S., hypospadias is a common birth defect that occurs when the urethra, the tube that transports urine out of the body, does not form completely in males.

Dr. Casella has identified a unique subset of cells in the developing urethra that have stopped dividing but remain metabolically active and are thought to represent a novel signaling center. He likens them to doing the work of a construction foreman. “If you’re constructing a building, you need to make sure that everyone follows the blueprints.  We believe that these developmentally senescent cells are sending important signals that define how the urethra is formed,” he says.

His project also will help to standardize the characterization of hypospadias. Hypospadias is classically associated with a downward bend to the penis, a urethra that does not extend to the head of the penis and incomplete formation of the foreskin. Still, there is significant variability among patients’ anatomy and to date, no standardized method for documenting hypospadias anatomy.

“Some surgeons take measurements in the operating room, but without a standardized classification system, there is no definitive way to compare measurements among providers or standardize diagnoses from measurements that every surgeon makes,” he adds. “What one surgeon may call ‘distal’ may be called ‘midshaft’ by another.” (With distal hypospadias, the urethra opening is near the penis head; with midshaft hypospadias, the urethra opening occurs along the penis shaft.)

“By advancing our understanding of the genetic causes and the anatomic differences among patients, the real goal of this research is to generate knowledge that will allow us to take better care of children with hypospadias,” he says.

Parents worry about lingering social stigma, since some boys with hypospadias are unable to urinate while standing, and in older children the condition can be associated with difficulties having sex. Surgical correction of hypospadias traditionally is performed when children are between 6 months to 1 year old.

When reviewing treatment options with family, “discussing the surgery and postoperative care is straight forward. The hard part of our discussion is not having good answers to questions about long-term outcomes,” he says.

Dr. Casella’s study hopes to build the framework to enable that basic research to be done.

“Say we wanted to do a study to see how patients are doing 15-20 years after their surgery.  If we go to their charts now, often we can’t accurately describe their anatomy prior to surgery.  By establishing uniform measurement baselines, we can accurately track long-term outcomes since we’ll know what condition that child started with and where they ended up,” he says.

Dr. Casella’s research project will be conducted at Children’s National under the mentorship of Eric Vilain, M.D., Ph.D., an international expert in sex and genitalia development; Dolores J. Lamb, Ph.D., HCLD, an established leader in urology based at Weill Cornell Medicine; and Marius George Linguraru, DPhil, MA, MSc, an expert in image processing and artificial intelligence.

Mark Batshaw

40 years, 8 editions: Writing “Children With Disabilities”

Mark Batshaw

Forty years ago, Mark L. Batshaw, M.D., almost singlehandedly wrote a 23-chapter first edition that ran about 300 pages. Now Dr. Batshaw’s tome, “Children With Disabilities,” is in its eighth edition, and this new volume is almost 1,000 pages, with 42 chapters, two co-editors and over 35 authors from Children’s National.

Back in 1978, Mark L. Batshaw, M.D., was a junior faculty member at John’s Hopkins University School of Medicine. In the evenings he taught a course in the university’s School of Education  titled “The Medical and Physical Aspects of the Handicapped Child,” for Master’s level special education students. Because no textbook at that time focused on that specific topic, Batshaw developed his own slide set.

“At the end of the first year of teaching the course my students said ‘You really ought to consider writing a text book based on your slides to help us move forward,’ ” Dr. Batshaw recalls. The father of three carved out time by writing on weekends and at night, cutting back on sleep.

His first goal was to create a textbook that would serve as a curriculum for a series of courses that would be taught at universities to specialists who work with children with disabilities, including social workers, physical and occupational therapists, speech and language pathologists, special education teachers, nurses, doctors and dentists.

“I wanted to cover the whole range of disabilities and divided the book initially into a series of sections, including embryology, to help students understand what can go wrong in fetal development to lead to a developmental disability; and chapters on each developmental disability, including autism, attention-deficit/hyperactivity disorder (ADHD), cerebral palsy, learning disabilities and traumatic brain injury,” he says. “The third section was devoted to available treatments, including occupational and physical therapy, speech language therapy, nutrition and medications. The final section focused on outcomes.”

His second aim was for the book to serve as a reference text for professionals in the field. The 33-year-old contacted a brand-new new publisher, Paul H. Brookes Publishing Co., that focused on special education. “They took a chance on me, and I took a chance on them,” he says.

Forty years ago, he almost singlehandedly produced a 23-chapter first edition that ran about 300 pages. Now Dr. Batshaw’s tome is in its eighth edition, and this new volume is almost 1,000 pages. And, rather than being its sole author, Dr. Batshaw enlisted two co-editors and at least five dozen authors who contributed specialty expertise in genetic counseling, social work, physical and occupational therapy, medicine and nursing. His daughter, Elissa, a special education teacher and school psychologist, authored a chapter about special education services, and his son, Drew, an executive at a start-up company, contributed autobiographical letters about the effect ADHD has had on his life.

The book, “Children With Disabilities,” also includes:

  • A glossary of medical terms so that as the reader reviews patient reports they can easily look up an unfamiliar term
  • An appendix on commonly used drugs to treat children with disabilities in order to look up the medicine by name and see the range of doses
  • An appendix devoted to different syndromes children might have
  • A reference section with organizations and foundations that help children with disabilities
  • A web site with sections designed for students and other content designed for teachers with thought questions to guide practical use of information in each chapter and more than 450 customizable PowerPoint slides for download
  • Call-out boxes for interdisciplinary team members, such as genetic counselors, explaining the roles they serve and their educational background, and
  • Excerpts of recent research articles.

“The students say they don’t sell the book. Usually when students have a textbook, they try to sell it second hand after the course ends,” explains Dr. Batshaw, now Executive Vice President, Physician-in-Chief and Chief Academic Officer at Children’s National. “Instead, students keep it and use it as a practical reference as they become professionals in their field. It has had the impact I had hoped for both as a textbook and a reference book: They say they refer to it when they have patients with a particular disorder they’re not used to treating to read up on it.”

Now a bestseller, there are more than 200,000 copies in print, including Portuguese and Ukrainian translations. “It didn’t start that way. It grew organically,” he says.

In addition to Dr. Batshaw, Children’s contributors to “Children With Disabilities” include Nicholas Ah Mew, M.D., pediatric geneticist; Nickie N. Andescavage, M.D., neonatologist; Mackenzie E. Brown, D.O., fellow in Pediatric Rehabilitation Medicine; Justin M. Burton, M.D., chief, Division of Pediatric Rehabilitation Medicine; Gabrielle Sky Cardwell, BA, clinical research assistant; Catherine Larsen Coley, PT, DPT, PCS, physical therapist; Laurie S. Conklin, M.D., pediatric gastroenterologist; Denice Cora-Bramble, M.D., MBA, executive vice president and chief medical officer; Heather de Beaufort, M.D., pediatric ophthalmologist; Dewi Frances T. Depositario-Cabacar, M.D., pediatric neurologist; Lina Diaz-Calderon, M.D., fellow in Pediatric Gastroenterology; Olanrewaju O. Falusi, M.D., associate medical director of municipal and regional affairs, Child Health Advocacy Institute; Melissa Fleming, M.D., pediatric rehabilitation specialist; William Davis Gaillard, M.D., chief Division of Epilepsy, Neurophysiology and Critical Care; Satvika Garg, Ph.D., occupational therapist; Virginia C. Gebus, R.N., MSN, APN, CNSC, nutritionist; Monika K. Goyal, M.D., MSCE, assistant chief, Division of Emergency Medicine; Andrea Gropman, M.D., chief, Division of Neurodevelopmental Pediatrics and Neurogenetics, geneticist and Neurodevelopmental pediatrician; Mary A. Hadley, BS, senior executive assistant; Susan Keller, MLS., MS-HIT, research librarian; Lauren Kenworthy, Ph.D., director, Center for Autism Spectrum Disorders; Monisha S. Kisling, MS, CGC, genetic counselor; Eyby Leon, M.D., pediatric geneticist; Erin MacLeod, Ph.D., RD, LD, director, Metabolic Nutrition; Margaret B. Menzel, MS, CGC, genetic counselor; Shogo John Miyagi, Ph.D., PharmD, BCPPS, Pediatric Clinical Pharmacology fellow; Mitali Y. Patel, DDS, program director, Pediatric Dentistry; Deborah Potvin, Ph.D., neuropsychologist; Cara E. Pugliese, Ph.D., clinical psychologist; Khodayar Rais-Bahrami, M.D., neonatologist and director, Neonatal-Perinatal Medicine Fellowship Program; Allison B. Ratto, Ph.D., clinical psychologist; Adelaide S. Robb, M.D., chief, Division of Psychiatry and Behavioral Sciences; Joseph Scafidi, D.O., neonatal neurologist; Erik Scheifele, D.M.D., chief, Division of Oral Health; Rhonda L. Schonberg, MS, CGC, genetic counselor; Billie Lou Short, M.D., chief, Division of Neonatology; Kara L. Simpson, MS, CGC, genetic counselor; Anupama Rao Tate, D.M.D., MPH, pediatric dentist; Lisa Tuchman, M.D., chief, Division of Adolescent and Young Adult Medicine; Johannes N. van den Anker, M.D., Ph.D., FCP, chief, Division of Clinical Pharmacology, Vice Chair of Experimental Therapeutics; Miriam Weiss, CPNP-PC, nurse practitioner; and Tesfaye Getaneh Zelleke, M.D., pediatric neurologist.

Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty:
Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents:
Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students:
Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty:
Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students:
Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty:
Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents:
Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students:
Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty:
Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff:
Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents:
Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students:
Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty:
Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff:
Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents:
Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students:
Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.

Beth Tarini

Getting to know SPR’s future President, Beth Tarini, M.D., MS

Beth Tarini

Quick. Name four pillar pediatric organizations on the vanguard of advancing pediatric research.

Most researchers and clinicians can rattle off the names of the Academic Pediatric Association, the American Academy of Pediatrics and the American Pediatric Society. But that fourth one, the Society for Pediatric Research (SPR), is a little trickier. While many know SPR, a lot of research-clinicians simply do not.

Over the next few years, Beth A. Tarini, M.D., MS, will make it her personal mission to ensure that more pediatric researchers get to know SPR and are so excited about the organization that they become active members. In May 2019 Dr. Tarini becomes Vice President of the society that aims to stitch together an international network of interdisciplinary researchers to improve kids’ health. Four-year SPR leadership terms begin with Vice President before transitioning to President-Elect, President and Past-President, each for one year.

Dr. Tarini says she looks forward to working with other SPR leaders to find ways to build more productive, collaborative professional networks among faculty, especially emerging junior faculty. “Facilitating ways to network for research and professional reasons across pediatric research is vital – albeit easier said than done. I have been told I’m a connector, so I hope to leverage that skill in this new role,” says Dr. Tarini, associate director for Children’s Center for Translational Research.

“I’m delighted that Dr. Tarini was elected to this leadership position, and I am impressed by her vision of improving SPR’s outreach efforts,” says Mark Batshaw, M.D., Executive Vice President, Chief Academic Officer and Physician-in-Chief at Children’s National. “Her goal of engaging potential members in networking through a variety of ways – face-to-face as well as leveraging digital platforms like Twitter, Facebook and LinkedIn – and her focus on engaging junior faculty will help strengthen SPR membership in the near term and long term.”

Dr. Tarini adds: “Success to me would be leaving after four years with more faculty – especially junior faculty – approaching membership in SPR with the knowledge and enthusiasm that they bring to membership in other pediatric societies.”

SPR requires that its members not simply conduct research, but move the needle in their chosen discipline. In her research, Dr. Tarini has focused on ensuring that population-based newborn screening programs function efficiently and effectively with fewer hiccups at any place along the process.

Thanks to a heel stick to draw blood, an oxygen measurement, and a hearing test, U.S. babies are screened for select inherited health conditions, expediting treatment for infants and reducing the chances they’ll experience long-term health consequences.

“The complexity of this program that is able to test nearly all 4 million babies in the U.S. each year is nothing short of astounding. You have to know the child is born – anywhere in the state – and then between 24 and 48 hours of birth you have to do testing onsite, obtain a specific type of blood sample, send the blood sample to an off-site lab quickly, test the sample, find the child if the test is out of range, get the child evaluated and tested for the condition, then send them for treatment. Given the time pressures as well as the coordination of numerous people and organizations, the fact that this happens routinely is amazing. And like any complex process, there is always room for improvement,” she says.

Dr. Tarini’s research efforts have focused on those process improvements.

As just one example, the Advisory Committee on Heritable Disorders in Newborns and Children, a federal advisory committee on which she serves, was discussing how to eliminate delays in specimen processing to provide speedier results to families. One possible solution floated was to open labs all seven days, rather than just five days a week. Dr. Tarini advocated for partnering with health care engineers who could help model ways to make the specimen transport process more efficient, just like airlines and mail delivery services. A more efficient and effective solution was to match the specimen pick-up and delivery times more closely with the lab’s operational times – which maximizes lab resources and shortens wait times for parents.

Conceptual modeling comes so easily for her that she often leaps out of her seat mid-sentence, underscoring a point by jotting thoughts on a white board, doing it so often that her pens have run dry.

“It’s like a bus schedule: You want to find a bus that not only takes you to your destination but gets you there on time,” she says.

Dr. Tarini’s current observational study looks for opportunities to improve how parents in Minnesota and Iowa are given out-of-range newborn screening test results – especially false positives – and how that experience might shake their confidence in their child’s health as well as heighten their own stress level.

“After a false positive test result, are there parents who walk away from newborn screening with lingering stress about their child’s health? Can we predict who those parents might be and help them?” she asks.

Among the challenges is the newborn screening occurs so quickly after delivery that some emotionally and physically exhausted parents may not remember it was done. Then they get a call from the state with ominous results. Another challenge is standardizing communication approaches across dozens of birthing centers and hospitals.

“We know parents are concerned after receiving a false positive result, and some worry their infant remains vulnerable,” she says. “Can we change how we communicate – not just what we say, but how we say it – to alleviate those concerns?”

Nickie Andescavage

To understand the preterm brain, start with the fetal brain

Nickie Andescavage

“My best advice to future clinician-scientists is to stay curious and open-minded; I doubt I could have predicted my current research interest or described the path between the study of early oligodendrocyte maturation to in vivo placental development, but each experience along the way – both academic and clinical – has led me to where I am today,” Nickie Andescavage, M.D., writes.

Too often, medical institutions erect an artificial boundary between caring for the developing fetus inside the womb and caring for the newborn whose critical brain development continues outside the womb.

“To improve neonatal outcomes, we must transform our current clinical paradigms to begin treatment in the intrauterine period and continue care through the perinatal transition through strong collaborations with obstetricians and fetal-medicine specialists,” writes Nickie Andescavage, M.D., an attending in Neonatal-Perinatal Medicine at Children’s National.

Dr. Andescavage’s commentary was published online March 25, 2019, in Pediatrics Research and accompanies recently published Children’s research about differences in placental development in the setting of placental insufficiency. Her commentary is part of a new effort by Nature Publishing Group to spotlight research contributions from early career investigators.

The placenta, an organ shared by a pregnant woman and the developing fetus, plays a critical but underappreciated role in the infant’s overall health. Under the mentorship of Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain, and Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine, Dr. Andescavage works with interdisciplinary research teams at Children’s National to help expand that evidence base. She has contributed to myriad published works, including:

While attending Cornell University as an undergraduate, Dr. Andescavage had an early interest in neuroscience and neurobehavior. As she continued her education by attending medical school at Columbia University, she corroborated an early instinct to work in pediatrics.

It wasn’t until the New Jersey native began pediatric residency at Children’s National that those complementary interests coalesced into a focus on brain autoregulation and autonomic function in full-term and preterm infants and imaging the brains of both groups. In normal, healthy babies the autonomic nervous system regulates heart rate, blood pressure, digestion, breathing and other involuntary activities. When these essential controls go awry, babies can struggle to survive and thrive.

“My best advice to future clinician-scientists is to stay curious and open-minded; I doubt I could have predicted my current research interest or described the path between the study of early oligodendrocyte maturation to in vivo placental development, but each experience along the way – both academic and clinical – has led me to where I am today,” Dr. Andescavage writes in the commentary.

Assorted foods

Tamp down food allergy anxieties with this quiz


Asthma is associated with severe obstructive sleep apnea in children

Pulmonologists have often observed a link between asthma and the need for continuous positive airway pressure treatment (CPAP) among children with severe obstructive sleep apnea syndrome (OSAS).

Now, research published in the March 2019 issue of the journal Pediatric Pulmonology confirms the correlation.

Four-hundred eligible children with severe OSAS were included in a randomized, controlled study that took place at Children’s National Health System between September 2015 and June 2017. The mean age among study participants, ages 0 to 20, was 7.

Out of the 400 severe OSAS study participants, 113 children, about one-third, had asthma. Those with asthma were 29% more likely to require CPAP, compared to 14% of study participants without asthma. This association was independent of demographics, OSAS severity, obesity and a history of adenotonsillectomy, an operation to remove the tonsils.

“This is the first randomized, controlled study to test the association between asthma and CPAP among children with severe sleep apnea,” says Gustavo Nino, M.D., a corresponding study author, a pediatric pulmonologist and the director of sleep medicine at Children’s National Health System. “We’ve seen similar patterns in adults, but we needed to confirm the link in children to provide preventive screenings and personalized treatment.”

Dr. Nino mentions the goal now is to detect symptoms earlier, whether this occurs at an annual wellness exam with a pediatrician or at the first visit with a sleep medicine specialist.

“The next step for our research team, or for others interested in this topic, is to explore how these factors influence each other,” adds Dr. Nino. “Asthma itself is worse when you sleep. This leads us to wonder if obstructive sleep apnea exacerbates symptoms of asthma. Or could controlling asthma decrease the risk for CPAP therapy among children with severe obstructive sleep apnea?”

Until these questions have answers, Dr. Nino encourages pediatricians and specialists to keep the association in mind, especially since 7 million children nationwide have asthma, including 13,981 children in the District.

Parents should know that children who have severe obstructive sleep apnea and asthma are more likely to need extensive treatment, like CPAP, to maintain a positive flow of air to the nasal passages to keep the airway open.

Managing symptoms of asthma is also something parents can do at home, especially with the onset of spring asthma triggers, such as pollen, dust, dander, mold and smoke.

For help creating an asthma action plan, visit the Centers for Disease Control and Prevention.

Kofi Essel, M.D., M.P.H. and Ankoor Shah, M.D., M.B.A., M.P.H., named among 40 Under 40 Leaders in Minority Health

Ankoor Shah and Kofi Essel

Ankoor Shah, M.D., M.B.A., M.P.H., and Kofi Essel, M.D., M.P.H., were named 40 Under 40 Leaders in Minority Health.

Two doctors from Children’s National Health System are among the recipients of the 40 Under 40 Leaders in Minority Health award by the National Minority Quality Forum (NMQF) for 2019. Kofi Essel, M.D., M.P.H., is a pediatrician, Ankoor Shah, M.D., M.B.A., M.P.H., is the medical director of the IMPACT DC Asthma Clinic and also a pediatrician at Children’s National.

Founded in 1998, the NMFQ is dedicated to ensuring that high-risk racial and ethnic populations and communities receive optimal health care. The 40 individuals selected for this award represent the next generation of thought leaders in reducing health disparities.

Dr. Kofi Essel is a pediatrician at the Children’s Health Center Anacostia.  His focus and research has been around health equity, obesity, food insecurity and nutrition.

“Hunger strikes so many of our families,” says Dr. Essel, “In D.C., we were number one in the nation for having the highest rate of food hardship in households with children.”

Dr. Essel is involved with many organizations and initiatives that raise awareness about hunger and how much of an issue it is.  He strives to be a partner for the families that he serves, many of whom are in the fight against obesity, and works alongside them to improve their overall health.

“It’s a huge honor to receive recognition from this national organization,” says Dr. Kofi Essel, “Ultimately, it allows us to have a bit more of a platform to continue to advance some of the great work we’re doing with health disparities.”

Dr. Ankoor Shah is the medical director for IMPACT DC asthma clinic and a pediatrician at the Children’s Health Center at THEARC.  His focus includes improving pediatric population health and reducing child health asthma disparities.

“Through the coordination of the best in class care at Children’s National with amazing on the ground community partners, we have been able to transform the lives of the most at-risk children with asthma” says Dr. Shah.

Dr. Shah collaborates with organizations to improve the outcomes of kids with asthma by targeting intervention in high-risk areas.

“This award is recognition of the great work we’re doing in terms of improving asthma health in high-risk child populations throughout the District of Columbia.”

Both Dr. Essel and Dr. Shah are from Arkansas, attended Emory University and they did their residency together at Children’s National.

Congratulations to these wonderful doctors and leaders for receiving this award.

The 40 Under 40 recipients received their awards at the 2019 NMQF Leadership Summit on Health Disparities and CBC Spring Health Braintrust Gala Dinner on April 9.

Thurlow Evans Tibbs, Jr. Award

Community-based AIDS prevention organization recognizes Children’s National Health System

Thurlow Evans Tibbs, Jr. Award

Credit: Don Bon Photography

The Division of Adolescent and Young Adult Medicine at Children’s National Health System was honored with the Thurlow Evans Tibbs, Jr. Award for outstanding service in HIV prevention by Us Helping Us, People Into Living, a community-based AIDS service organization committed to reducing HIV infection in the African American community on April 2, 2019 in Washington, D.C.

“We are so honored to receive the Thurlow Evans Tibbs, Jr. Award from our colleagues and friends, Us Helping Us, People Into Living,” said Dr. Lawrence D’Angelo, director of the Youth Pride Clinic and Burgess Clinics, a division of Adolescent and Young Adult Medicine at Children’s National. “We have always considered Us Helping Us as an essential partner in this struggle and so it’s ingrained as a part of the community. It has been our honor to work with them, and an equal honor to be recognized in this way by them. We are so grateful and so proud!”

Dr. Lawrence D’Angelo and his team at the Burgess Clinic have cared for over 750 HIV infected youth, many who have gone on to live long and productive lives since the clinic opened its doors in 1988. The clinic started the Washington Area Consortium on HIV infection in Youth (WACHIVY) which later became MetroTeenAIDS Metro TeenAIDS, one of the largest and most successful prevention education programs for youth in the country. The Burgess Clinic is the home of over a dozen NIH and foundation grants that supported the diagnosis and treatment of HIV infected youth, accounting for over $55M in support.

“Receiving the Thurlow Evans Tibbs, Jr. Award from Us Helping Us, People Into Living is an honor beyond anything we could have hoped for,” says Dr. D’Angelo. “Our programs were started at the same time to meet similar needs and for years we have worked together and appreciated each other’s efforts in serving our community. D.C. could not have attained the progress it has made in the struggle against HIV without Us Helping Us, People Into Living and knowing that makes this award all the more special.”

Us Helping Us, People Into Living was incorporated in 1988 as a support group for HIV-positive black gay men.

The Rare Disease Institute staff on Rare Disease Day

Genetics 101: Rare diseases aren’t rare

The Rare Disease Institute staff on Rare Disease Day

Children’s National Health System is home to the Rare Disease Institute, the National Organization for Rare Disease’s first Center of Excellence, the largest clinical genetics program in the United States.

With the advent of DNA databanks, informatics, new technology, pediatric consortiums and global partnerships, clinical researchers have never been in a better position to diagnose and treat rare diseases. A rare disease is categorically defined as a condition that affects less than 200,000 people. However, 25 to 30 million Americans, about one in 10, have a rare disease.

Accelerations in genetic research and diagnostic criteria remain one of the most significant accomplishments in medicine, but these breakthroughs invite new challenges: How will researchers provide ongoing care and treatment for patients navigating a rare disease? How can doctors and researchers multiply themselves to ensure everyone has the latest information and resources they need? How can researchers use existing trials to augment other fields? How can we diagnose, catalogue and treat hundreds of new rare diseases each year, while accelerating the research and care of 7,000 existing rare conditions?

If these questions intrigue you, excite you and make you want to collaborate with scientific peers, welcome to the field of genetics. A common theme researchers and families talk about is that rare diseases affect a small proportion of the population, but have a huge impact.

On April 10, 1,200 international researchers, lawmakers, scientists and drug developers from 50 countries will meet in Oxon Hill, Md., 10 miles south of Washington, for a three-day summit, the World Orphan Drug Congress USA, to discuss how to unify efforts to enhance and maximize care for rare disease patients.

Here are eight themes to keep in mind:

  1. Rare diseases are chronic diseases. The human genome project has enabled the molecular mapping of 8,000 diseases with genetic underpinnings. Of these diseases, 600 diseases have therapies. A child born with a urea cycle disorder had a 5% chance of surviving the disease 40 years ago. Now the survival rate is 95%. Helping children survive is essential, but we need to think about the best treatments and standards for long-term care.
  2. Rare diseases are expensive. In Western Australia, according to the 2010 Western Australia Population Cohort, rare diseases account for less than 5% of hospital visits but for 10% of hospital costs. Similar data from Cleveland finds one-third of pediatric hospital visits have a genetic link but account for half of hospital costs.
  3. Rare diseases share common links. We’ve diagnosed 7,000 rare diseases but there are more to unravel. For example, breast cancer has over 30 molecular subtypes – some of which turn into rare diseases. By better understanding these molecular pathways, we may be able to inform common fields of medicine.
  4. Marshall Summar's Rare Disease 101 presentation

    Dr. Marshall Summar, a medical geneticist, speaks about the future of rare disease research and treatment at a Rare Disease 101 lecture hosted by the Rare Disease Congressional Caucus on Capitol Hill on Feb. 27. To sustain discoveries, Dr. Summar mentions a digital-first, flexible mindset is essential. Standard language and scalable, universal reference structures are required.

  5. Global partnerships create research repositories. Gold-standard research models – double blind, controlled studies with numerous participants – aren’t possible if five people in the world share the same disease. To increase the number of study participants, global partnerships and longitudinal registries are essential.
  6. Standard language helps. To avoid replicating existing research and to help teams quickly reference findings, we need to adopt standardized language to quantify measurements. Researchers from Berlin and Brazil may help inform the etiology of and future treatments for PKU, but they need to manage, store, access and share their collective findings, while remaining flexible.
  7. The science is here. The FDA is approving more drugs for rare diseases than ever before including gene therapy and micro organs, or Rare Diseases-on-chip models. The challenge with treating so many rare diseases isn’t developing new research, but creating therapies and studies to accommodate this patient volume. About 250 rare disease discoveries happen each year. At the current rate, it will take 2,000 years to treat them all.
  8. Progress is here. The Orphan Drug Act fast-tracked approval for rare disease treatments and therapies, and nearly half of all drugs coming in for FDA approval are for rare diseases. However, only 5% of rare diseases have FDA-approved drugs.
  9. We need to replicate geneticists. To provide optimal care, doctors need to standardize education models and use new forms of technology, such as artificial intelligence and deep learning, to share resources faster via patient education portals, resources for families, CME courses and virtual connections with pediatricians or families.

If you would like to learn more or get involved, watch this international summit, the Rare Disease Day Policy Event, which took place at the United Nations Headquarters in New York on Feb. 21. (Some of these issues are covered in video 4.)

If you are a patient, download this patient toolkit from the National Center for Advanced Translational Sciences.

If you live in Washington, D.C., follow the genetics team and consider working with us as we move into a new home, the Children’s National Research and Innovation Campus, in 2020.

Jeffrey Lukish

Pediatric Surgeon receives ACS/APSA Health Policy Scholarship

Jeffrey Lukish

Jeffrey Lukish, M.D., a pediatric surgeon at Children’s National Health System, has been named a 2019 American College of Surgeons (ACS) and American Pediatric Surgical Association (APSA) Health Policy Scholar for 2019.

The scholarship supports Dr. Lukish’s attendance at the Executive Leadership Program in Health Policy and Management at Brandeis University, which teaches knowledge and skills essential for participating in health care policy and equips health leaders with tools to create innovative and sustainable ways to improve health care service delivery. As a 2019 scholar, he will also provide health policy-related assistance to the ACS and the APSA as requested, and will have opportunities to build relationships with local, state and federal lawmakers.

Dr. Lukish is a nationally recognized expert in advanced minimally invasive surgery in infants and children, as well as pediatric surgical innovation. He has been voted a Baltimore Top Doctor by his peers for five of the last eight years. He holds academic appointments as a professor of surgery from the Uniformed Services University and associate professor of surgery at the George Washington University.

Dr. Lukish is a fellow of the American College of Surgeons and the American Academy of Pediatrics, and member of several prominent professional societies, including the American Pediatric Surgical Society, the Pediatric Cancer Oncology Group and the International Pediatric Endosurgery Group.  He has authored over 100 publications.

Zhe Han

$2M NIH grant for treating disease linked to APOL1

Zhe Han

Children’s researcher Zhe Han, Ph.D., has received a $2 million award from the National Institutes of Health (NIH) to study new approaches to treat kidney disease linked to inheriting Apolipoprotein L1 (APOL1) risk alleles. These risk alleles are particularly common among persons of recent African descent, and African Americans are disproportionately affected by the increased risk in kidney disease associated with these risk alleles.

Han, an associate professor in Children’s Center for Genetic Medicine Research, has established a leading research program that uses the fruit fly Drosophila as a model system to study how genetic mutations lead to disease.

Drosophila is a very basic model, but studies in the fly have led to major breakthroughs in understanding fundamental biological processes that underlie health and disease in humans,” Han says. “Since coming to Children’s National five years ago, I have focused a significant part of my research studying particular fly cells called nephrocytes that carry out many of the important roles of human kidney glomeruli, units within the kidney where blood is cleaned. Working together with clinician colleagues here, we have demonstrated that these Drosophila cells can be used to very efficiently study different types of renal disease caused by genetic mutations.”

The APOL1 risk alleles are genetic variants, termed G1 and G2, found almost exclusively in people of African ancestry and can lead to a four-fold higher risk of end-stage kidney disease, the last of five stages of chronic kidney disease. Exactly how inheriting these risk alleles increases the risk of kidney disease remains an unanswered question and the focus of considerable research activity. Han’s laboratory has developed a Drosophila model of APOL1-linked renal disease by producing the G1 and G2 forms of APOL1 specifically in nephrocytes. This led to defects in fly renal cells that strikingly overlap with disease-associated changes in experimental model and human kidney cells expressing APOL1 risk alleles.

The new NIH award will fund large-scale screening and functional testing to identify new treatment targets and new drugs to treat kidney disease linked to APOL1. Using a genetic screening approach, Han’s lab will identify nephrocyte “modifier” genes that interact with APOL1 proteins and counter the toxic effects of risk-associated G1 and G2 variants.

The team also will identify nephrocyte genes that are turned on or off in the presence of APOL1 risk alleles, and confirm that such “downstream” APOL1-regulated genes are similarly affected in experimental model and human kidney cells. The potential of the newly identified “modifier” and “downstream” genes to serve as targets of novel therapeutic interventions will be experimentally tested in fly nephrocytes in vivo and in cultured mammalian kidney cells.

Finally, the Drosophila model will be used as a drug screening platform for in vivo evaluation of positive “hits” from a cell-based APOL1 drug screening study in order to identify compounds that are most effective with the fewest side effects.

“These types of studies can be most efficiently performed in Drosophila,” Han adds.  “They take advantage of the speed and low cost of the fly model system and the amazing array of well-established, sophisticated genetic tools available for the fly. Using this model to elucidate human disease mechanisms and to identify new effective therapies has truly become my research passion.”

ACC19 attendees from Children's National

ACC.19: A focus on pediatric cardiology

ACC19 attendees from Children's National

Dr. Gerard Martin, center, accepts an award before delivering the 2019 Dan G. McNamara Keynote lecture at ACC.19.

“Innovation meets tradition,” is how many attendees and journalists described the American College of Cardiology’s 68th Scientific Sessions (ACC.19), which took place March 16-18, 2019 in New Orleans, La.

Gerard Martin, M.D., F.A.A.P., F.A.C.C., F.A.H.A., a pediatric cardiologist and the medical director of Global Services at Children’s National, supported this narrative by referencing both themes in his 2019 Dan G. McNamara keynote lecture, entitled “Improved Outcomes in Congenital Heart Disease through Advocacy and Collaboration.” Dr. Martin highlighted advancements in the field of pediatric cardiology that took place over the past 15 years, while touting modern advancements – such as pulse oximetry screenings for critical congenital heart disease – that were a result of physician-led advocacy and collaboration.

Dr. Martin’s message was to continue to invest in research and technology that leads to medical breakthroughs, but to remember the power of partnerships, such as those formed by the National Pediatric Cardiology Quality Improvement Collaborative. These alliances, which generated shared protocols and infrastructure among health systems, improved interstage mortality rates between surgeries for babies born with hypolastic left heart syndrome.

A dozen cardiologists and clinicians from the Children’s National Heart Institute also participated in CME panel discussions or delivered poster presentations to support future versions of this template, touching on early-stage innovations and multi-institution research collaborations. The themes among Children’s National Heart Institute faculty, presented to a diverse crowd of 12,000-plus professional attendees representing 108 countries, included:

Personalized guidelines:

  • Sarah Clauss, M.D., F.A.C.C., a cardiologist, presented “Unique Pediatric Differences from Adult Cholesterol Guidelines: Lipids and Preventive Cardiology,” before Charles Berul, M.D., division chief of cardiology and co-director of the Children’s National Heart Institute, presented “Unique Pediatric Differences from Adult Guidelines: Arrhythmias in Adults with Congenital Heart Disease,” in a joint symposium with the American Heart Association and the American College of Cardiology.
  • Berul, who specializes in electrophysiology, co-chaired a congenital heart disease pathway session, entitled “Rhythm and Blues: Electrophysiology Progress and Controversies in Congenital Heart Disease,” featuring components of pediatric electrophysiology, including heart block, surgical treatment of arrhythmias and sudden death risk.

Early detection:

  • Anita Krishnan, M.D., associate director of the echocardiography lab, presented “Identifying Socioeconomic and Geographic Barriers to Prenatal Detection of Hypoplastic Left Heart Syndrome and Transposition of the Great Arteries” as a moderated poster in Fetal Cardiology: Quickening Discoveries.
  • Jennifer Romanowicz, M.D., a cardiology fellow, and Russell Cross, M.D., director of cardiac MRI, presented the “Neonatal Supraventricular Tachycardia as a Presentation of Critical Aortic Coarctation” poster in FIT Clinical Decision Making: Congenital Heart Disease 2.
  • Pranava Sinha, M.D., a cardiac surgeon, presented the poster “Neuroprotective Effects of Vitamin D Supplementation in Children with Cyanotic Heart Defects: Insights from a Rodent Hypoxia Model” in Congenital Heart Disease: Therapy 2.

Coordinated care:

  • Ashraf Harahsheh, M.D., F.A.C.C., F.A.A.P., a cardiologist with a focus on hyperlipidemia and preventive cardiology, co-presented an update about BMI quality improvement (Q1) activity from the American College of Cardiology’s Adult Congenital and Pediatric Quality Network – BMI Q1 leadership panel.
  • Niti Dham, M.D., director of the cardio-oncology program, and Deepa Mokshagundam, M.D., cardiology fellow, presented the poster “Cardiac Changes in Pediatric Cancer Survivors” in Heart Failure and Cardiomyopathies: Clinical 3.
  • Nancy Klein, B.S.N., R.N., C.P.N., clinical program coordinator of the Washington Adult Congenital Heart program at Children’s National, presented the poster “Improving Completion of Advanced Directives in Adults with Congenital Heart Disease” in Risks and Rewards in Adult Congenital Heart Disease.

Innovation:

  • Jai Nahar, M.D., a cardiologist, moderated “Future Hub: Augmented Cardiovascular Practitioner: Giving Doctors and Patients a New Voice.” The session focused on technical aspects of artificial intelligence, such as language processing and conversational artificial intelligence, as well as how applications are used in patient-physician interactions.
  • Nahar also participated in a key event on the Heart-to-Heart stage, entitled “Rise of Intelligent Machines: The Potential of Artificial Intelligence in Cardiovascular Care.”

“While I enjoyed the significant representation of Children’s National faculty at the meeting and all of the presentations this year, one research finding that I found particularly compelling was Dr. Krishnan’s poster about geographical disparities in detecting congenital heart disease,” says Dr. Berul. “Her research finds obstetricians providing care to women in the lowest quartile of socioeconomic areas were twice as likely to miss a diagnosis for a critical congenital heart defect during a fetal ultrasound, compared to obstetricians providing care for women in the highest quartiles.”

Dr. Krishnan’s study was the collaborative effort of 21 centers in the United States and Canada, and investigated how socioeconomic and geographic factors affect prenatal detection of hypoplastic left heart syndrome and transposition of the great arteries.

“We studied over 1,800 patients, and chose these diseases because they require early stabilization by a specialized team at a tertiary care center,” says Dr. Krishnan, who led the research in conjunction with the Fetal Heart Society Research Collaborative. “We hope that by understanding what the barriers are, we can reduce disparities in care through education and community-based outreach.”

DNA strands on teal background

NUP160 genetic mutation linked to steroid-resistant nephrotic syndrome

DNA strands on teal background

Mutations in the NUP160 gene, which encodes one protein component of the nuclear pore complex nucleoporin 160 kD, are implicated in steroid-resistant nephrotic syndrome, an international team reports March 25, 2019, in the Journal of the American Society of Nephrology. Mutations in this gene have not been associated with steroid-resistant nephrotic syndrome previously.

“Our findings indicate that NUP160 should be included in the gene panel used to diagnose steroid-resistant nephrotic syndrome to identify additional patients with homozygous or compound-heterozygous NUP160 mutations,” says Zhe Han, Ph.D., an associate professor in the Center for Genetic Medicine Research at Children’s National and the study’s senior author.

The kidneys filter blood and ferry waste out of the body via urine. Nephrotic syndrome is a kidney disease caused by disruption of the glomerular filtration barrier, permitting a significant amount of protein to leak into the urine. While some types of nephrotic syndrome can be treated with steroids, the form of the disease that is triggered by genetic mutations does not respond to steroids.

The patient covered in the JASN article had experienced persistently high levels of protein in the urine (proteinuria) from the time she was 7. By age 10, she was admitted to a Shanghai hospital and underwent her first renal biopsy, which showed some kidney damage. Three years later, she had a second renal biopsy showing more pronounced kidney disease. Treatment with the steroid prednisone; cyclophosphamide, a chemotherapy drug; and tripterygium wilfordii glycoside, a traditional therapy, all failed. By age 15, the girl’s condition had worsened and she had end stage renal disease, the last of five stages of chronic kidney disease.

An older brother and older sister had steroid-resistant nephrotic syndrome as well and both died from end stage kidney disease before reaching 17. When she was 16, the girl was able to receive a kidney transplant that saved her life.

Han learned about the family while presenting research findings in China. An attendee of his session said that he suspected an unknown mutation might be responsible for steroid-resistant nephrotic syndrome in this family, and he invited Han to work in collaboration to solve the genetic mystery.

By conducting whole exome sequencing of surviving family members, the research team found that the mother and father each carry one mutated copy of NUP160 and one good copy. Their children inherited one mutated copy from either parent, the variant E803K from the father and the variant R1173X, which causes truncated proteins, from the mother. The woman (now 29) did not have any mutations in genes known to be associated with steroid-resistant nephrotic syndrome.

Some 50 different genes that serve vital roles – including encoding components of the slit diaphragm, actin cytoskeleton proteins and nucleoporins, building blocks of the nuclear pore complex – can trigger steroid-resistant nephrotic syndrome when mutated.

With dozens of possible suspects, they narrowed the list to six variant genes by analyzing minor allele frequency, mutation type, clinical characteristics and other factors.

The NUP160 gene is highly conserved from flies to humans. To prove that NUP160 was the true culprit, Dr. Han’s group silenced the Nup160 gene in nephrocytes, the filtration kidney cells in flies. Nephrocytes share molecular, cellular, structural and functional similarities with human podocytes. Without Nup160, nephrocytes had reduced nuclear volume, nuclear pore complex components were dispersed and nuclear lamin localization was irregular. Adult flies with silenced Nup160 lacked nephrocytes entirely and lived dramatically shorter lifespans.

Significantly, the dramatic structural and functional defects caused by silencing of fly Nup160 gene in nephrocytes could be completely rescued by expressing the wild-type human NUP160 gene, but not by expressing the human NUP160 gene carrying the E803K or R1173X mutation identified from the girl’s  family.

“This study identified new genetic mutations that could lead to steroid-resistant nephrotic syndrome,” Han notes. “In addition, it demonstrates a highly efficient Drosophila-based disease variant functional study system. We call it the ‘Gene Replacement’ system since it replaces a fly gene with a human gene. By comparing the function of the wild-type human gene versus mutant alleles from patients, we could determine exactly how a specific mutation affects the function of a human gene in the context of relevant tissues or cell types. Because of the low cost and high efficiency of the Drosophila system, we can quickly provide much-needed functional data for novel disease-causing genetic variants using this approach.”

In addition to Han, Children’s co-authors include Co-Lead Author Feng Zhao, Co-Lead Author Jun-yi Zhu, Adam Richman, Yulong Fu and Wen Huang, all of the Center for Genetic Medicine Research; Nan Chen and Xiaoxia Pan, Shanghai Jiaotong University School of Medicine; and Cuili Yi, Xiaohua Ding, Si Wang, Ping Wang, Xiaojing Nie, Jun Huang, Yonghui Yang and Zihua Yu, all of Fuzhou Dongfang Hospital.

Financial support for research described in this post was provided by the Nature Science Foundation of Fujian Province of China, under grant 2015J01407; National Nature Science Foundation of China, under grant 81270766; Key Project of Social Development of Fujian Province of China, under grant 2013Y0072; and the National Institutes of Health, under grants DK098410 and HL134940.

Nichole Jefferson and Patrick Gee

African American stakeholders help to perfect the APOLLO study

Nichole Jefferson and Patrick Gee

Nichole Jefferson and Patrick O. Gee

African Americans who either donated a kidney, received a kidney donation, are on dialysis awaiting a kidney transplant or have a close relative in one of those categories are helping to perfect a new study that aims to improve outcomes after kidney transplantation.

The study is called APOLLO, short for APOL1 Long-Term Kidney Transplantation Outcomes Network. Soon, the observational study will begin to enroll people who access transplant centers around the nation to genotype deceased and living African American kidney donors and transplant recipients to assess whether they carry a high-risk APOL1 gene variant.

The study’s Community Advisory Council – African American stakeholders who know the ins and outs of kidney donation, transplantation and dialysis because they’ve either given or  received an organ or are awaiting transplant – are opening the eyes of researchers about the unique views of patients and families.

Already, they’ve sensitized researchers that patients may not be at the same academic level as their clinicians, underscoring the importance of informed consent language that is understandable, approachable and respectful so people aren’t overwhelmed. They have encouraged the use of images and color to explain the apolipoprotein L1 (APOL1) gene. The APOL1 gene is found almost exclusively in people of recent African descent, however only 13 percent of these people carry the high-risk APOL1 variant that might cause kidney problems.

One issue arose early, during one of the group’s first monthly meetings, as they discussed when to tell patients and living donors about the APOLLO study. Someone suggested the day of the transplant.

“The Community Advisory Council told them that would not be appropriate. These conversations should occur well before the day of the transplant,” recalls Nichole Jefferson.

“The person is all ready to give a kidney. If you’re told the day of transplant ‘we’re going to include you in this study,’ that could possibly stop them from giving the organ,” Jefferson says. “We still remember the Tuskegee experiments. We still remember Henrietta Lacks. That is what we are trying to avoid.”

Patrick O. Gee, Ph.D., JLC, another Community Advisory Council member, adds that it’s important to consider “the mental state of the patient and the donor. As a patient, you know you are able to endure a five- to eight-hour surgery. The donor is the recipient’s hero. As the donor, you want to do what is right. But if you get this information; it’s going to cause doubt.”

Gee received his kidney transplant on April 21, 2017, and spent 33 days in the hospital undergoing four surgeries. His new kidney took 47 days to wake up, which he describes as a “very interesting journey.” Jefferson received her first transplant on June 12, 2008. Because that kidney is in failure, she is on the wait list for a new kidney.

“All I’ve ever known before APOLLO was diabetes and cardiovascular issues. Nobody had ever talked about genetics,” Gee adds. “When I tell people, I tread very light. I try to stay in my lane and not to come off as a researcher or a scientist. I just find out information and just share it with them.”

As he spoke during a church function, people began to search for information on their smart phones. He jotted down questions “above his pay grade” to refer to the study’s principal investigator. “When you start talking about genetics and a mutated gene, people really want to find out. That was probably one of the best things I liked about this committee: It allows you to learn, so you can pass it on.”

Jefferson’s encounters are more unstructured, informing people who she meets about her situation and kidney disease. When she traveled from her Des Moines, Iowa, home to Nebraska for a transplant evaluation, the nephrologist there was not aware of the APOL1 gene.

And during a meeting at the Mayo Clinic with a possible living donor, she asked if they would test for the APOL1 gene. “They stopped, looked at me and asked: ‘How do you know about that gene?’ Well, I’m a black woman with kidney failure.”

Patrick O. Gee received his kidney transplant on April 21, 2017, and spent 33 days in the hospital undergoing four surgeries. His new kidney took 47 days to wake up, which he describes as a “very interesting journey.”

About 100,000 U.S. children and adults await a kidney transplant. APOLLO study researchers believe that clarifying the role that the APOL1 gene plays in kidney-transplant failure could lead to fewer discarded kidneys, which could boost the number of available kidneys for patients awaiting transplant.

Gee advocates for other patients and families to volunteer to join the APOLLO Community Advisory Council. He’s still impressed that during the very first in-person gathering, all researchers were asked to leave the table. Only patients and families remained.

“They wanted to hear our voices. You rarely find that level of patient engagement. Normally, you sit there and listen to conversations that are over your head. They have definitely kept us engaged,” he says. “We have spoken the truth, and Dr. Kimmel is forever saying ‘who would want to listen to me about a genotype that doesn’t affect me? We want to hear your voice.’ ”

(Paul L. Kimmel, M.D., MACP, a program director at the National Institute of Diabetes and Digestive and Kidney Diseases, is one of the people overseeing the APOLLO study.)

Jefferson encourages other people personally impacted by kidney disease to participate in the APOLLO study.

“Something Dr. Kimmel always says is ‘You’re in the room.’ We’re in the room while it’s happening. It’s a line from Hamilton. That’s a good feeling,” she says. “I knew right off, these are not necessarily improvements I will see in my lifetime. I am OK with that. With kidney disease, we have not had advances in a long time. As long as my descendants don’t have to go through the same things I have gone through, I figure I have done my part. I have done my job.”

Dr. Kurt Newman in front of the capitol building

Kurt Newman, M.D., shares journey as a pediatric surgeon in TEDx Talk

Kurt Newman, M.D., president and chief executive officer of Children’s National, shares his poignant journey as a pediatric surgeon, offering a new perspective for approaching the most chronic and debilitating health conditions. In this independently-organized TEDx event, Dr. Newman also shares his passion for Children’s National and the need to increase pediatric innovations in medicine.

Robin Steinhorn in the NICU

Coming together as a team for the good of the baby

Robin Steinhorn in the NICU

Children’s National has a new program to care for children who have severe bronchopulmonary dysplasia, a serious complication of preterm birth.

Around the 1-year-old’s crib is a tight circle of smiling adults, and at the foot of his bed is a menagerie of plush animals, each a different color and texture and shape to spark his curiosity and sharpen his intellect.

Gone are the days a newborn with extremely complex medical needs like Elijah would transfer from the neonatal intensive care unit (NICU) to the pediatric intensive care unit and transition through a couple of other hospital units by the time he was discharged. Gone are the days when he’d see a variety of new physician faces at every stop. And gone are the days he’d be confined to his room, divorced from the sights and sounds and scents of the outside world, stimulation that helps little baby’s neural networks grow stronger.

Children’s National has a new program designed to meet the unique needs of children like Elijah who have severe bronchopulmonary dysplasia (BPD), a common complication of preterm birth.

“It’s more forward-thinking – and I mean thinking for the future of each individual baby, and it’s allowing the baby to have one team and one location to take advantage of a deep knowledge of and relationship with that baby and family,” says Robin Steinhorn, M.D. Dr. Steinhorn is senior vice president of the Center for Hospital-Based Specialties and one of Children’s multidisciplinary team members who visited Elijah’s bed twice weekly during his lengthy hospitalization and who continues to see him regularly during outpatient visits.

“The pulmonologist, the neonatologist, the respiratory therapist, the physical therapist, the dietitian, the cardiologist – we all come as a team to work together for the good of the baby,” Dr. Steinhorn adds. “We stick with these babies through thick and thin. We will stick with that baby with this team and this location until they are ready to go home – and beyond.”

BPD, a serious lung condition, mostly affects extremely low birthweight preterm babies whose lungs were designed to continue developing inside the womb until the pregnancy reaches full term. Often born months before their due dates, these extremely vulnerable newborns have immature organs, including the lungs, which are not ready for the task of breathing air. Children’s program targets infants who experience respiratory failure from BPD. The respiratory support required for these infants ranges from oxygen delivered through a nasal cannula to mechanical ventilators.

Robin Steinhorn and Colleague

“It’s more forward-thinking – and I mean thinking for the future of each individual baby, and it’s allowing the baby to have one team and one location to take advantage of a deep knowledge of and relationship with that baby and family,” says Robin Steinhorn, M.D.

About 1 percent of all preterm births are extremely low birthweight, or less than 1,500 grams. Within that group, up to 40 percent will develop BPD. While they represent a small percentage of overall births, these very sick babies need comprehensive, focused care for the first few years of their lives. And some infants with severe BPD also have pulmonary hypertension which, at Children’s National, is co-managed by cardiology and pulmonary specialists.

Children’s BPD team not only focuses on the child’s survival and medical care, they focus on the neurodevelopmental and social care that a baby needs to thrive. From enhanced nutrition to occupational and physical therapy to a regular sleep cycle, the goal is to help these babies achieve their full potential.

“These babies are at tremendous risk for long-term developmental issues. Everything we do is geared to alleviate that,” adds John T. Berger III, M.D., director of Children’s Pulmonary Hypertension Program.

“Our NICU care is more focused, comprehensive and consistent,” agrees Mariam Said, M.D., a neonatologist on the team. “We’re also optimizing the timing of care and diagnostic testing that will directly impact health outcomes.”

Leaving no detail overlooked, the team also ensures that infants have age-appropriate developmental stimuli, like toys, and push for early mobility by getting children up and out of bed and into a chair or riding in a wagon.

“The standard approach is to keep the baby in a room with limited physical or occupational therapy and a lack of appropriate stimulation,” says Geovanny Perez, M.D., a pulmonologist on the team. “A normal baby interacts with their environment inside the home and outside the home. We aim to mimic that within the hospital environment.”

Dr. Steinhorn, who had long dreamed of creating this comprehensive team care approach adds that “it’s been so gratifying to see it adopted and embraced so quickly by Children’s NICU caregivers.”