telemedicine control room

Telehealth connects pediatric heart experts about critical COVID-19 details

telemedicine control room

Telehealth is more than a doctor-to-patient tool during COVID-19. Experts in congenital heart disease meet weekly to share details about how it affects their vulnerable patients.

During the COVID-19 pandemic, telehealth has been crucial in allowing doctors to maintain safe contact with patients who require ongoing medical care without an office visit. Just as important is the role that telehealth is playing to connect care providers with each other to ensure that everyone around the world has the information they need to provide the best care possible for this swift-moving disease.

One good example of this specialist-to-specialist thought leadership connection is the ongoing weekly meeting hosted by the Children’s National Hospital cardiac critical care specialists. Since early in the spread of COVID-19, the Cardiac-ICU team, led by cardiovascular specialists including Ricardo Munoz, M.D., chief of cardiac critical care medicine and executive director of telehealth at Children’s National, have connected pediatric clinicians around the world to discuss how best to care for particularly vulnerable patients with pre-existing heart diseases, and to discuss breaking news in epidemiology of the disease and the effectiveness of various treatment approaches.

The video conference attracts hundreds of physicians and nurses who specialize in pediatric cardiac care from countries all over the world. In the last week of April, the meeting featured a late-breaking session to discuss new pediatric intensive care observations of inflammatory symptoms similar to Kawasaki disease, which were being detected in the United Kingdom, Paris and the United States. While more information is needed about this discovery, the ability of these experts to gather and compare disease phenotypes from country to country facilitates both the additional classification of pediatric-related symptoms and improves how all centers, no matter their location, can prepare to treat children who present locally with these symptoms.

In recent weeks, cardiac physicians and nurses from some of the world’s hardest hit regions, including Italy and Spain, have shared detailed information about their on-the-ground experiences to help colleagues in the U.S. and elsewhere better prepare for new developments.

“This new disease is a moving target, especially when it comes to understanding how it might impact children and adults with existing cardiac disease, particularly those with congenital heart disease,” says Dr. Munoz. “It is extremely important that we learn from each other, especially when we are able to connect with our colleagues in the epicenters of the most serious outbreaks of COVID-19. We are happy to host this important weekly meeting with the goal of helping every specialist keep as many patients with cardiac diseases as safe as possible throughout the global health emergency.”

If you would like to join these weekly telehealth meetings, please send your request to COVIDMultiCICUResponse@childrensnational.org.

bacterial extracellular vesicle

Once overlooked cellular messengers could combat antibiotic resistance

bacterial extracellular vesicle

Children’s National Hospital researchers for the first time have isolated bacterial extracellular vesicles from the blood of healthy donors. The team theorizes that the solar eclipse lookalikes contain important signaling proteins and chromatin, DNA from the human host.

Children’s National Hospital researchers for the first time have isolated bacterial extracellular vesicles from the blood of healthy donors, a critical step to better understanding the way gut bacteria communicate with the rest of the body via the bloodstream.

For decades, researchers considered circulating bacterial extracellular vesicles as bothersome flotsam to be jettisoned as they sought to tease out how bacteria that reside in the gut whisper messages to the brain.

There is a growing appreciation that extracellular vesicles – particles that cells naturally release – actually facilitate intracellular communication.

“In the past, we thought they were garbage or noise,” says Robert J. Freishtat, M.D., MPH, associate director, Center for Genetic Medicine Research at Children’s National Research Institute. “It turns out what we throw away is not trash.”

Kylie Krohmaly, a graduate student in Dr. Freishtat’s laboratory, has isolated from blood, extracellular vesicles from Escherichia coli and Haemophilus influenzae, common bacteria that colonize the gut, and validated the results via electron microscopy.

“The images are interesting because they look like they have a bit of a halo around them or penumbra,” Krohmaly says.

The team theorizes that the solar eclipse lookalikes contain important signaling proteins and chromatin, DNA from the human host.

“It’s the first time anyone has pulled them out of blood. Detecting them is one thing. Pulling them out is a critical step to understanding the language the microbiome uses as it speaks with its human host,” Dr. Freishtat adds.

Krohmaly’s technique is so promising that the Children’s National team filed a provisional patent.

The Children’s research team has devised a way to gum up the cellular works so that bacteria no longer become antibiotic resistant. Targeted bacteria retain the ability to make antibiotic-resistance RNA, but like a relay runner dropping rather than passing a baton, the bacteria are thwarted from advancing beyond that step. And, because that gene is turned off, the bacteria are newly sensitive to antibiotics – instead of resistant bacteria multiplying like clockwork these bacteria get killed.

“Our plan is to hijack this process in order to turn off antibiotic-resistance genes in bacteria,” Dr. Freishtat says. “Ultimately, if a child who has an ear infection can no longer take amoxicillin, the antibiotic would be given in tandem with the bacteria-derived booster to turn off bacteria’s ability to become antibiotic resistant. This one-two punch could become a novel way of addressing the antibiotic resistance process.”

ISEV2020 Annual Meeting presentation
(Timing may be subject to change due to COVID-19 safety precautions)
Oral with poster session 3: Neurological & ID
Saturday May 23, 2020, 5 p.m. to 5:05 p.m. (ET)
“Detection of bacterial extracellular vesicles in blood from healthy volunteers”
Kylie Krohmaly, lead author; Claire Hoptay, co-author; Andrea Hahn, M.D., MS, infectious disease specialist and co-author; Robert J. Freishtat, M.D., MPH, associate director, Center for Genetic Medicine Research at Children’s National Research Institute and senior author.

electronic cigarette dispenser with different flavors of nicotine

Extreme difficulty breathing and swallowing linked to teen’s vaping?

electronic cigarette dispenser with different flavors of nicotine

After a teen was transferred to Children’s National Hospital suffering from severe difficulty breathing and swallowing, a multidisciplinary team continued the detective work and surmises that vaping was to blame for her unusual symptoms.

A teenage girl with no hint of prior asthma or respiratory illness began to feel hoarseness in her throat and a feeling that she needed to clear her throat frequently. Within a few weeks, her hoarseness and throat-clearing worsened with early morning voice loss and feeling as if food were lodged in her throat. She started having trouble swallowing and began to avoid food all together.

Her pediatrician prescribed loratadine for suspected allergies to no avail. Days later, an urgent care center prescribed a three-day course of prednisone. For a few days, she felt a little better, but went back to feeling like she was breathing “through a straw.” After going to an emergency room with acute respiratory distress and severe difficulty swallowing, staff tried intravenous dexamethasone, ampicillin/sulbactam, and inhaled racemic epinephrine and arranged for transfer.

When she arrived at Children’s National Hospital, a multidisciplinary team continued the detective work with additional testing, imaging and bloodwork.

Examining her throat confirmed moderate swelling and a partially obstructed airway draped with thick chartreuse-colored mucus. The teen had no history of an autoimmune disorder, no international travel and no exposure to animals. She had no fever and had received all her scheduled immunizations.

“With epiglottitis – an inflammation of the flap found at the base of the tongue that prevents food from entering the trachea – our first concern is that an underlying infection is to blame,” says Michael Jason Bozzella, D.O., MS, a third-year infectious diseases fellow and lead author of the case report published Feb. 5, 2020, in Pediatrics. “We tested her specimens in a number of ways for a host of respiratory pathogens, including human rhino/enterovirus, respiratory syncytial virus, influenza, Epstein-Barr virus, Streptococcus and more. All negative. We also looked for more atypical infections with bacteria, like Arcanobacterium, Mycoplasma and Gonorrhea. Those were all negative as well,” Dr. Bozzella adds.

She slowly improved during a seven-day initial hospital stay, though soon returned for another six-day hospital stay after it again became excruciatingly painful for her to swallow.

Every throat culture and biopsy result showed no evidence of fungal, bacterial or viral infection, acid-fast bacilli or other malignancy. But in speaking with doctors, the teen had admitted to using candy-and fruit-flavored e-cigarettes three to five times with her friends over the two months preceding her symptoms. The last time she vaped was two weeks before her unusual symptoms began.

According to the Centers for Disease Control and Prevention, 2,668 people in the U.S. have been hospitalized for e-cigarette or vaping product use-associated lung injury, as of Jan. 14, 2020. The Children’s National case report’s authors say the increasing use of vaping products by teenagers highlights the potential for unknown health risks to continue to grow.

“This teenager’s use of e-cigarettes is the most plausible reason for this subacute epiglottitis diagnosis, a condition that can become life-threatening,” says Kathleen Ferrer, M.D., a hospitalist at Children’s National and the case report’s senior author. “This unusual case adds to a growing list of toxic effects attributable to vaping. While we normally investigate infectious triggers, like Streptococci, Staphylococci and Haemophilus, we and other health care providers should also consider e-cigarettes as we evaluate oro-respiratory complaints.”

In addition to Drs. Bozzella and Ferrer, Children’s National case report co-authors include Matthew Allen Magyar, M.D., a hospitalist; and Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases.

people sitting in a circle holding hands

Religiousness linked to improved quality of life for people with HIV

people sitting in a circle holding hands

Adults living with HIV in Washington, D.C., were more likely to feel higher levels of emotional and physical well-being if they attended religious services regularly, prayed daily, felt “God’s presence,” and self-identified as religious or spiritual.

Adults living with HIV in Washington, D.C., were more likely to feel higher levels of emotional and physical well-being if they attended religious services regularly, prayed daily, felt “God’s presence,” and self-identified as religious or spiritual, according to research published online Jan. 29, 2020, in Psychology of Religion and Spirituality. By contrast, patients living with HIV who had the lowest levels of quality of life and more mental health challenges were privately religious, potentially eschewing organized religion due to fears about being stigmatized or ostracized.

“These findings are significant because they point to the untapped potential of encouraging patients living with HIV who are already religious to attend religious services regularly.  Scientific evidence suggests that religions that present God as all-powerful, personal, responsive, loving, just and forgiving make a difference in health-related quality of life. By contrast, belief systems and religions that see God as punishing, angry, vengeful and distant and isolate members from their families and the larger community do not have health benefits or contribute to health-related quality of life. People who identify as spiritual also benefit from improved overall health-related quality of life,” says Maureen E. Lyon, Ph.D., FABPP, a clinical health psychologist at Children’s National Hospital, and senior study author.

“In general, patients living with HIV have reported that they wished their health care providers acknowledged their religious beliefs and spiritual struggles. Additional research is needed to gauge whether developing faith-based interventions or routine referrals to faith-based programs that welcome racial and sexual minorities improve satisfaction with treatment and health outcomes,” Lyon adds.

More than 1 million people in the U.S. live with HIV, and in 2018, 37,832 people received an HIV diagnosis in the U.S., according to the Centers for Disease Control and Prevention (CDC). In 2017, the Washington, D.C., region recorded one of nation’s highest rates of new cases of HIV: 46.3 diagnoses per 100,000 people, according to the CDC.

A research team that includes current and former Children’s National faculty wanted to learn more about the degree of religiousness and spirituality reported by people living with HIV and the interplay between religion and health-related quality of life. They recruited patients to participate in a clinical trial about family-centered advance care planning and enrolled 223 patient/family dyads in this study.

Fifty-six percent of patients were male. Eighty-six percent were African American, and their mean age was 50.8. Seventy-five percent were Christian.

The researchers identified three distinct classes of religious beliefs:

  • Class 1, the highest level of religiousness/spirituality, applied to people more likely to attend religious services in person each week, to pray daily, to “feel God’s presence” and to self-identify as religious and spiritual. Thirty-five percent of study participants were Class 1 and tended to be older than 40.
  • Class 2 applied to privately religious people who engaged in religious activities at home, like praying, and did not attend services regularly. Forty-seven percent of study participants were Class 2.
  • Class 3 participants self-identified as spiritual but were not involved in organized religion. Nearly 18 percent of study participants were Class 3, the lowest overall level of religiousness/spirituality.

Class 1 religiousness/spirituality was associated with increased quality of life, mental health and improved health status.

“Being committed to a welcoming religious group provides social support, a sense of identity and a way to cope with stress experienced by people living with HIV,” Lyon says. “We encourage clinicians to capitalize on patients’ spiritual beliefs that improve health – such as prayer, meditation, reading spiritual texts and attending community events – by including them in holistic treatment programs in a non-judgmental way.”

What’s more, the research team encourages clinicians to appoint a member of the team who is responsible for handling religiousness/spirituality screening and providing referrals to welcoming hospital-based chaplaincy programs or community-based religious groups.

“This is particularly challenging for HIV-positive African American men who have sex with men, as this group faces discrimination related to race and sexual orientation. Because HIV infection rates are increasing for this group, this additional outreach is all the more important,” she adds.

In addition to Lyon, study co-authors include Biostatistician Jichuan Wang, Ph.D., and Yao I. Cheng, MS., both of Children’s National; and Lead Author Katherine B. Grill, Ph.D., the former clinical coordinator for this randomized clinical trial who is currently an adjunct professor at the California Institute of Integral Studies.

Financial support for research described in this post was provided by the National Institutes of Health under award Nos. R01NR014-052-05 and UL1RR031988.

 

sleeping baby

False negatives: Delayed Zika effects in babies who appeared normal at birth

sleeping baby

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants.

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants, according to a cohort study published online Jan. 6, 2020, in JAMA Pediatrics.

“These infants had no evidence of Zika deficits or microcephaly at birth. Neurodevelopmental deficits, including declines in mobility and social cognition, emerged in their first year of life even as their head circumference remained normal,” says Sarah B. Mulkey, M.D. Ph.D., a fetal/neonatal neurologist at Children’s National Hospital and the study’s first author. “About one-third of these newborns who underwent postnatal head ultrasound had nonspecific imaging results, which we believe are the first published results finding a link between subtle brain injuries and impaired neuromotor development in Zika-exposed children.”

The multi-institutional research group led by Children’s National enrolled pregnant women in Atlántico Department, which hugs the Caribbean coast of Colombia, who had been exposed to Zika, and performed a series of fetal magnetic resonance images (MRI) and ultrasounds as their pregnancies progressed.

Even though their mothers had laboratory-confirmed Zika infections, 77 out of 82 of their offspring were born with no sign of congenital Zika syndrome, a constellation of birth defects that includes severe brain abnormalities, eye problems and congenital contractures, and 70 underwent additional testing of neurodevelopment during infancy. These apparently normal newborns were born between Aug. 1, 2016, and Nov. 30, 2017, at the height of the Zika epidemic, and had normal head circumference.

When they were 4 to 8 months or 9 to 18 months of age, the infants’ neurodevelopment was evaluated using two validated tools, the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (a 50-item test of such skills as self-care, mobility, communication and social cognition) and the Alberta Infant Motor Scale (a motor examination of infants in prone, supine, sitting and standing positions). Some infants were assessed during each time point.

Women participating in the study were highly motivated, with 91% following up with appointments, even if it meant traveling hours by bus. In addition to Children’s National faculty traveling to Colombia to train staff how to administer the screening instruments, videotaped assessments, MRIs and ultrasounds were read, analyzed and scored at Children’s National. According to the study team, the U.S. scoring of Alberta Infant Motor Scale tests administered in Colombia is also unprecedented for a research study and offers the potential of remote scoring of infants’ motor skill maturity in regions of the world where pediatric specialists, like child neurologists, are lacking.

“Normally, neurodevelopment in infants and toddlers continues for years, building a sturdy neural network that they later use to carry out complex neurologic and cognitive functions as children enter school,” Dr. Mulkey adds. “Our findings underscore the recommendations by the Centers for Disease Control and Prevention (CDC) that all infants exposed to Zika in the womb undergo long-term follow-up, providing an opportunity to intervene earlier.”

An accompanying editorial by CDC staffers concurs, saying the study reported “intriguing data” that add “to the growing evidence of the need for long-term follow-up for all children with Zika virus exposure in utero to ensure they receive the recommended clinical evaluations even when no structural defects are identified at birth.”

In addition to Dr. Mulkey, study co-authors include Margarita Arroyave-Wessel, MPH, Dorothy I. Bulas, M.D., chief of Diagnostic Imaging and Radiology, JiJi Jiang, MS, Stephanie Russo, BS, Robert McCarter, ScD, research section head, design and biostatistics,  Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine, and co-Senior Author, Roberta L. DeBiasi, MD, MS, chief of the Division of Pediatric Infectious Diseases, all of Children’s National; Colleen Peyton, PT, DPT, of Northwestern University; Yamil Fourzali, M.D., of Sabbag Radiologos, Barranquilla, Colombia; Michael E. Msall, M.D., of University of Chicago Comer Children’s Hospital; and co-Senior Author, Carlos Cure, M.D., BIOMELab, Barranquilla, Colombia.

Funding for the research described in this post was provided by the Thrasher Research Fund, the National Institutes of Health under award Nos. UL1TR001876 and KL2TR001877, and the Leadership Education in Neurodevelopmental and Related Disorders Training Program under grant HRSA/MCHB T73 MC11047.

Dr. Kurt Newman in front of the capitol building

Making healthcare innovation for children a priority

Dr. Kurt Newman in front of the capitol building

Recently, Kurt Newman, M.D., president and CEO of Children’s National Hospital, authored an opinion piece for the popular political website, The Hill. In the article, he called upon stakeholders from across the landscape to address the significant innovation gap in children’s healthcare versus adults.

As Chair of the Board of Trustees of the Children’s Hospital Association,  Dr. Newman knows the importance of raising awareness among policy makers at the federal and state level about the healthcare needs of children. Dr. Newman believes that children’s health should be a national priority that is addressed comprehensively. With years of experience as a pediatric surgeon, he is concerned by the major inequities in the advancements of children’s medical devices and technologies versus those for adults. That’s why Children’s National is working to create collaborations, influence policies and facilitate changes that will accelerate the pace of pediatric healthcare innovation for the benefit of children everywhere. One way that the hospital is tackling this challenge is by developing the Children’s National Research & Innovation Campus, which will be the nation’s first innovation campus focused on pediatric research.

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.

###

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 

 

Dr. Wiedermann's pyramid for determining study type

The five easy pieces of literature appraisal for busy front-line providers

Dr. Wiedermann's pyramid for determining study type

To help practitioners appraise medical literature, Bernhard Wiedermann, M.D., MA, suggests determining where it fits on this pyramid.

Practitioners often read journal articles to help inform them about best clinical practices and policies, but some may not feel comfortable changing their clinical practice in the absence of published practice guidelines.

During this year’s American Academy of Pediatrics National Conference and Exhibition, Bernhard Wiedermann, M.D., MA, an infectious disease specialist at Children’s National Hospital, spoke to a room full of pediatric providers about how to stay current with medical literature, quickly analyze the material and decide whether to apply it to their practice. “This interactive session served to help primary care pediatric providers understand how to critically appraise what they are reading in medical literature,” says Dr. Wiedermann. “Practitioners need to be able to critically read journal articles to better decide when to apply new studies or recommendations to their clinical practice.”

Dr. Wiedermann’s presentation, entitled “Should that new article change your practice? The five easy pieces of literature appraisal for busy front-line providers,” covered:

  • Techniques that providers should use when searching and browsing for literature
  • How to review abstracts for relevant content
  • How to determine the type of study (Where does it fit on the pyramid?)
  • Whether or not your patient fits the study population
  • How to explain findings to parents and patients

At the session, attendees gained the ability to develop a streamlined plan to keep current with the medical literature, apply simple strategies to select and appraise potentially worthwhile articles and discuss new management options with patients and families.

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.”

rabies virus illustration

Critters bugging! Test your infectious disease knowledge


Dengue virus

Children’s National/NIH team competes in #IDbugbowl

Dengue virus

IDBugBowl team member Maria Susana Rueda-Altez, M.D., hopes her knowledge of infectious diseases common to Peru, like dengue virus, will give her team an advantage.

It’s a bird. It’s a plane. No, it’s an infectious agent that zipped past country borders, infecting international passengers who shared the same commercial aircraft as a person who had symptomatic illness.

The buzzer rings. And the correct answer is: What is severe acute respiratory syndrome?

This fall, a combined team from Children’s National in Washington, D.C. and the National Institutes of Health (NIH) will compete against three other teams testing their collective infectious disease knowledge through IDBugBowl, a Jeopardy-style quiz geared toward fellows, residents and medical students. The competition is held during IDWeek2019. “From anaplasmosis to Zika, any topic is fair game,” according to organizers.

“BugBowl has become so popular that the IDWeek 2019 program committee carved out a separate time for the contest to ensure it would not conflict with any other symposia,” says Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases at Children’s National. “On a day-to-day basis, we all contend with serious infectious diseases that have the potential to jeopardize human health. However, this event helps to expand knowledge among the general public in a fun and engaging way.”

The Children’s National/NIH team participating in the Oct. 5 trivia contest includes:

  • Kevin Lloyd, M.D., third-year pediatrics resident
  • Maria Susana Rueda-Altez, M.D., third-year pediatrics resident
  • Kanal Singh, M.D., fellow, adult infectious diseases at the National Institutes of Health (NIH) and
  • Alexandra Yonts, M.D., fellow, pediatric infectious diseases at Children’s National

Even though she has little formal training in infectious diseases, team member Dr. Rueda-Altez says: “One thing I have in my favor is that I’m from Peru. We’re used to seeing infectious diseases that are less common elsewhere, including tuberculosis and hantavirus.”

And while disease-carrying mosquitoes aren’t abundant at Peru’s higher altitudes, closer to sea level and in its rain forests, infected mosquitoes spread chikungunya, dengue, malaria and Zika, she adds.

Take this quiz to test your infectious disease knowledge.

little boy using asthma inhaler

Searching for the molecular underpinnings of asthma exacerbations

little boy using asthma inhaler

It’s long been known that colds, flu and other respiratory illnesses are major triggers for asthma exacerbations, says asthma expert Stephen J. Teach, M.D., MPH. Consequently, a significant body of research has focused on trying to figure out what’s happening on the cellular or molecular level as these illnesses progress to exacerbations.

People with asthma can be indistinguishable from people who don’t have this chronic airway disease – until they have an asthma attack, also known as an exacerbation. During these events, their airways become inflamed and swollen and produce an abundance of mucus, causing dangerous narrowing of the bronchial tubes that leads to coughing, wheezing and trouble breathing. These events are a major cause of morbidity and mortality, leading to the deaths of 10 U.S. residents every day, according to the Centers for Disease Control and Prevention.

It’s long been known that colds, flu and other respiratory illnesses are major triggers for asthma exacerbations, says Children’s National in Washington, D.C., asthma expert Stephen J. Teach, M.D., MPH. Consequently, a significant body of research has focused on trying to figure out what’s happening on the cellular or molecular level as these illnesses progress to exacerbations. Targeted searches have identified several different molecular pathways that appear to be key players in this phenomenon. However, Dr. Teach says researchers have been missing a complete and unbiased snapshot of all the important pathways in illness-triggered exacerbations and how they interrelate.

To develop this big picture view, Dr. Teach and  Inner-City Asthma Consortium colleagues recruited 208 children ages 6-17 years old with severe asthma – marked by the need for daily doses of inhaled corticosteroids, two hospitalizations or systemic corticosteroid treatments over the past year, and a high concentration of asthma-associated immune cells – from nine pediatric medical centers across the country, including Children’s National. (Inhaled corticosteroids are a class of medicine that calms inflamed airways.) The researchers collected samples of nasal secretions and blood from these patients at baseline, when all of them were healthy.

Then, they waited for these children to show symptoms of respiratory illnesses. Within six days of cold symptoms, the researchers took two more samples of nasal secretions and blood. They also administered breathing tests to determine whether these respiratory illnesses led to asthma exacerbations and recorded whether these patients were treated with systemic corticosteroids to stem the associated respiratory inflammation.

The researchers examined nasal fluid samples for evidence of viral infection during illness and used analytical methods to identify the causative virus. They analyzed all the samples they collected for changes in concentrations of various immune cells. They also looked globally in these samples for changes in gene expression compared with baseline and between the two collection periods during respiratory illness.

Together, this information told the molecular story about what took place after these children got sick and after some of them developed exacerbations. Of the 208 patients recruited, 106 got respiratory illnesses during the six-month study period, leading to a total of 154 illness events. Of those, 47 caused exacerbations, and 107 didn’t.

About half the exacerbations appeared to have been triggered by a rhinovirus, a cause of common colds, the research team reports in a study published online April 8, 2019, in Nature Immunology. The other children’s cold-like symptoms could have been triggered by pollution, allergens or other irritants.

In most exacerbations, virally triggered or not, the researchers saw early activation of a network of genes that appeared to be associated with SMAD3, a signaling molecule already known to be involved in airway inflammation. At the same time, genes that control a set of immune cells known as lymphocytes were turned down. However, as the exacerbation progressed and worsened, the researchers saw gene networks turned on that related to airway narrowing, mucus hypersecretion and activation of other immune cells.

Exacerbations triggered by viruses were associated with multiple inflammatory pathways, in contrast to those in which viruses weren’t found, which were associated with molecular pathways that affected cells in the airway lining.

The researchers validated these findings in 19 patients who each got respiratory illnesses at least twice during the study period but only developed an exacerbation during one of these episodes, finding the same upregulated and downregulated molecular pathways in these patients as in the study population as a whole. They also identified a set of molecular risk factors in patients at baseline – signatures of gene activation that appeared to put patients at risk for exacerbations when they got sick. When patients were treated with systemic corticosteroids during exacerbations, these medicines appeared to restore only some of the affected molecular pathways to normal, healthy levels. Other molecular pathways remained markedly changed.

Each finding could represent a new target for drugs that could prevent or more effectively treat exacerbations, keeping more patients with asthma healthy and out of the hospital.

“Our consortium study found increased gene expression of enzymes that produce molecules that contribute to narrowed airways and dilated blood vessels,” Dr. Teach adds. “This is especially intriguing because drugs that target kallikreins or bradykinin may help treat asthma attacks that aren’t caused by viruses.”

In addition to Dr. Teach, study co-authors include Lead Author Matthew C. Altman, University of Washington; Michelle A. Gill, Baomei Shao and Rebecca S. Gruchalla, all of University of Texas Southwestern Medical Center; Elizabeth Whalen and Scott Presnell of Benaroya Research Institute; Denise C. Babineau and Brett Jepson of Rho, Inc.; Andrew H. Liu, Children’s Hospital Colorado; George T. O’Connor, Boston University School of Medicine; Jacqueline A. Pongracic, Ann Robert H. Lurie Children’s Hospital of Chicago; Carolyn M. Kercsmar and Gurjit K. Khurana Hershey, , Cincinnati Children’s Hospital; Edward M. Zoratti and Christine C. Johnson, Henry Ford Health System; Meyer Kattan, Columbia University College of Physicians and Surgeons; Leonard B. Bacharier and Avraham Beigelman, Washington University, St. Louis; Steve M. Sigelman, Peter J. Gergen, Lisa M. Wheatley and Alkis Togias, National Institute of Allergy and Infectious Diseases; and James E. Gern, William W. Busse and Senior author Daniel J. Jackson, University of Wisconsin School of Medicine and Public Health.

Funding for research described in this post was provided by the National Institute of Allergy and Infectious Diseases under award numbers 1UM1AI114271 and UM2AI117870; CTSA under award numbers UL1TR000150, UL1TR001422 and 5UL1TR001425; the National Institutes of Health under award number UL1TR000451;  CTSI under award number 1UL1TR001430; CCTSI under award numbers UL1TR001082 and 5UM1AI114271; and NCATS under award numbers UL1 TR001876 and UL1TR002345.

Dr. DeBiasi

Staying one step ahead of deadly Ebola

Dr. DeBiasi

An ongoing outbreak of Ebola virus since 2018 in the Democratic Republic of the Congo that has resulted in millions of travelers being screened at checkpoints, hundreds of thousands of vaccinations and thousands of deaths is a stark reminder of the need to remain one step ahead of the deadly disease.

To that end, one-half dozen personnel from Children’s National in Washington, D.C., including infectious diseases experts, critical care nurses and laboratory personnel traveled to New York in mid-August for an interactive workshop sponsored by the National Ebola Training and Education Center. They covered how to correctly don and doff protective gear, safely collect, handle and process specimens and discuss the special circumstances that arise when caring for pediatric patients, among other topics.

“Since 2014, Children’s National has evaluated 6 children with exposure as Persons Under Investigation of  Ebola virus disease, 4 of  whom required extended inpatient hospitalization under full isolation precautions,” says Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases. “As a designated Ebola Treatment Center, we must continue our preparedness to care for additional patients with suspected and proven Ebola infection.

“Hands-on training and  drilling offer Children’s National personnel an opportunity to continue to test, evaluate and optimize our institutional Ebola response plan and procedures to maintain our preparedness for the needs of future patients,” adds Dr. DeBiasi.

In addition to Dr. DeBiasi, members of the Children’s National Special Pathogens Isolation Unit team who attended the Emerging Infectious Disease Workshop included:

  • Zohreh Hojjati, Laboratory Medicine.
  • Kristin Elizabeth Mullins, Clinical Lab Director, Laboratory Medicine.
  • Daniel Schroeder, Registered Nurse II, Pediatric Intensive Care Unit (PICU).
  • Melissa Taylor, Registered Nurse II, PICU.
  • Heather Wellman, Registered Nurse II, PICU.

“Among the keys to Children’s National serving as a national exemplar for pediatric Ebola care, is the stability of our multidisciplinary care team and our institutional commitment to ongoing training,” Dr. DeBiasi adds.

During a Grand Rounds presentation at Children’s National in mid-August, Dr. DeBiasi provided updates about recent global infectious disease outbreaks affecting pediatric patients including Ebola, measles, acute flaccid myelitis and Zika Virus. An interdisciplinary panel of Children’s National experts, including nurses, transport specialists, infectious disease and intensive care experts directly involved in caring for Ebola Persons Under Investigation, demonstrated personal protective equipment and fielded questions from staff. The overview also outlined Children’s National institutional expertise and response, including the Congenital Zika Virus Program, the Acute Flaccid Myelitis Task Force, the Special Isolation Unit for Ebola and other highly contagious infectious diseases.

View Ebola preparedness photo gallery.

Paradoxical outcomes for Zika-exposed tots

In the midst of an unprecedented Zika crisis in Brazil, there were a few flickers of hope: Some babies appeared to be normal at birth, free of devastating birth defects that affected other Brazilian children exposed to the virus in utero.

In the midst of an unprecedented Zika crisis in Brazil, there were a few flickers of hope: Some babies appeared to be normal at birth, free of devastating birth defects that affected other Brazilian children exposed to the virus in utero. But according to a study published online July 8, 2019, in Nature Medicine and an accompanying commentary co-written by a Children’s National clinician-researcher, the reality for Zika-exposed infants is much more complicated.

Study authors led by Karin Nielsen-Saines at David Geffen UCLA School of Medicine followed 216 infants in Rio de Janeiro who had been exposed to the Zika virus during pregnancy, performing neurodevelopmental testing when the babies ranged in age from 7 to 32 months. These infants’ mothers had had Zika-related symptoms themselves, including rash.

Although many children had normal assessments, 29% scored below average in at least one domain of neurological development, including cognitive performance, fine and gross motor skills and expressive language, Sarah B. Mulkey, M.D., Ph.D., and a colleague write in a companion commentary published online by Nature Medicine July 29, 2019.

The study authors found progressively higher risks for developmental, hearing and eye abnormality depending on how early the pregnancy was at the time the infants were exposed. Because Zika virus has an affinity for immature neurons, even babies who were not born with microcephaly remained at continued risk for suffering abnormalities.

Of note, 24 of 49 (49%) infants who had abnormalities at birth went on to have normal test results in the second or third year of life. By contrast, 17 of 68 infants (25%) who had normal assessments at birth had below-average developmental testing or had abnormalities in hearing or vision by age 32 months.

“This work follows babies who were born in 2015 and 2016. It’s heartening that some babies born with abnormalities tested in the normal range later in life, though it’s unclear whether any specific interventions help to deliver these positive findings,” says Dr. Mulkey, a fetal–neonatal neurologist in the Division of Fetal and Transitional Medicine at Children’s National in Washington, D.C. “And it’s quite sobering that babies who appeared normal at birth went on to develop abnormalities due to that early Zika exposure.”

It’s unclear how closely the findings apply to the vast majority of U.S. women whose Zika infections were asymptomatic.

“This study adds to the growing body of research that argues in favor of ongoing follow-up for Zika-exposed children, even if their neurologic exams were reassuring at birth,” Dr. Mulkey adds. “As Zika-exposed children approach school age, it’s critical to better characterize the potential implications for the education system and public health.”

In addition to Dr. Mulkey, the perspective’s senior author, William J. Muller, Northwestern University, was the commentary’s lead author.

Autonomic nervous system appears to function well regardless of mode of childbirth

Late in pregnancy, the human body carefully prepares fetuses for the rigors of life outside the protection of the womb. Levels of cortisol, a stress hormone, ramp up and spike during labor. Catecholamines, another stress hormone, also rise at birth, helping to kick start the necessary functions that the baby will need to regulate breathing, heartbeat, blood pressure and energy metabolism levels at delivery. Oxytocin surges, promoting contractions for the mother during labor and stimulating milk production after the infant is born.

These processes also can play a role in preparing the fetal brain during the transition to life outside the womb by readying the autonomic nervous system and adapting its cerebral connections. The autonomic nervous system acts like the body’s autopilot, taking in information it needs to ensure that internal organs run steadily without willful action, such as ensuring the heart beats and eyelids blink at steady intervals. Its yin, the sympathetic division, stimulates body processes while its yang, the parasympathetic division, inhibits them.

Infants born preterm have reduced autonomic function compared with their full-term peers and also face possible serious neurodevelopmental impairment later in life. But is there a difference in autonomic nervous system function for full-term babies after undergoing labor compared with infants delivered via cesarean section (C-section)?

A team from the Children’s National Inova Collaborative Research Program (CNICA) – a research collaboration between Children’s National in Washington, D.C., and Inova Women’s and Children’s Hospital in Virginia – set out to answer that question in a paper published online July 30, 2019, in Scientific Reports.

They enrolled newborns who had experienced normal, full-term pregnancies and recorded their brain function and heart performance when they were about 2 days old. Infants whose conditions were fragile enough to require observation in the neonatal intensive care unit were excluded from the study. Of 167 infants recruited for the prospective cohort study, 118 newborns had sufficiently robust data to include them in the research.  Of these newborns:

  • 62 (52.5%) were born by vaginal delivery
  • 22 (18.6%) started out with vaginal delivery but ultimately switched to C-section based on failure to progress, failed labor induction or fetal intolerance to labor
  • And 34 (28.8%) were born by elective C-section.

The CNICA research team swaddled infants for comfort and slipped electrode nets over their tiny heads to simultaneously measure heart rate variability and electrocortical function through non-invasive techniques. The team hypothesized that infants who had been exposed to labor would have enhanced autonomic tone and higher cortical electroencephalogram (EEG) power than babies born via C-section.

“In a low-risk group of babies born full-term, the autonomic nervous system and cortical systems appear to function well regardless of whether infants were exposed to labor prior to birth,” says Sarah B. Mulkey, M.D., Ph.D., a fetal–neonatal neurologist in the Division of Fetal and Transitional Medicine at Children’s National and the study’s lead author.

However, infants born by C-section following a period of labor had significantly increased accelerations in their heart rates. And the infants born by C-section during labor had significantly lower relative gamma frequency EEG at 25.2 hours old compared with the other two groups studied.

“Together these findings point to a possible increased stress response and arousal difference in infants who started with vaginal delivery and finished delivery with C-section,” Dr. Mulkey says. “There is so little published research about the neurologic impacts of the mode of delivery, so our work helps to provide a normal reference point for future studies looking at high-risk infants, including babies born preterm.”

Because the research team saw little differences in autonomic tone or other EEG frequencies when the infants were 1 day old, future research will explore these measures at different points in the newborns’ early life as well as the role of the sleep-wake cycle on heart rate variability.

In addition to Dr. Mulkey, study co-authors include Srinivas Kota, Ph.D., Rathinaswamy B. Govindan, Ph.D., Tareq Al-Shargabi, MSc, Christopher B. Swisher, BS, Laura Hitchings, BScM, Stephanie Russo, BS, Nicole Herrera, MPH, Robert McCarter, ScD, and Senior Author Adré  J. du Plessis, M.B.Ch.B., MPH, all of Children’s National; and Augustine Eze Jr., MS, G. Larry Maxwell, M.D., and Robin Baker, M.D., all of Inova Women’s and Children’s Hospital.

Financial support for research described in this post was provided by the National Institutes of Health National Center for Advancing Translational Sciences under award numbers UL1TR001876 and KL2TR001877.

Children’s National ranked No. 6 overall and No. 1 for newborn care by U.S. News

Children’s National in Washington, D.C., is the nation’s No. 6 children’s hospital and, for the third year in a row, its neonatology program is No.1 among all children’s hospitals providing newborn intensive care, according to the U.S. News Best Children’s Hospitals annual rankings for 2019-20.

This is also the third year in a row that Children’s National has been in the top 10 of these national rankings. It is the ninth straight year it has ranked in all 10 specialty services, with five specialty service areas ranked among the top 10.

“I’m proud that our rankings continue to cement our standing as among the best children’s hospitals in the nation,” says Kurt Newman, M.D., President and CEO for Children’s National. “In addition to these service lines, today’s recognition honors countless specialists and support staff who provide unparalleled, multidisciplinary patient care. Quality care is a function of every team member performing their role well, so I credit every member of the Children’s National team for this continued high performance.”

The annual rankings recognize the nation’s top 50 pediatric facilities based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

“The top 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver outstanding care across a range of specialties and deserve to be nationally recognized,” says Ben Harder, chief of health analysis at U.S. News. “According to our analysis, these Honor Roll hospitals provide state-of-the-art medical expertise to children with rare or complex conditions. Their rankings reflect U.S. News’ assessment of their commitment to providing high-quality, compassionate care to young patients and their families day in and day out.”

The bulk of the score for each specialty is based on quality and outcomes data. The process also includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with challenging conditions.

Below are links to the five specialty services that U.S. News ranked in the top 10 nationally:

The other five specialties ranked among the top 50 were cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastro-intestinal surgery, orthopedics, and urology.

pill bottles and pills

Fewer than 60% of young women diagnosed with STIs in emergency departments fill scripts

Fewer than 60% of young women diagnosed with sexually transmitted infections (STIs) in the emergency department fill prescriptions for antimicrobial therapy to treat these conditions, according to a research letter published online May 28, 2019, by JAMA Pediatrics.

Adolescents make up nearly half of the people diagnosed with sexually transmitted infections each year. According to the Centers for Disease Control and Prevention, untreated sexually transmitted diseases in women can cause pelvic inflammatory disease (PID), an infection of the reproductive organs that can complicate getting pregnant in the future.

“We were astonished to find that teenagers’ rates of filling STI prescriptions were so low,” says Monika K. Goyal, M.D., MSCE, assistant chief of Children’s Division of Emergency Medicine and Trauma Services and the study’s senior author. “Our findings demonstrate the imperative need to identify innovative methods to improve treatment adherence for this high-risk population.”

The retrospective cohort study, conducted at two emergency departments affiliated with a large, urban, tertiary care children’s hospital, enrolled adolescents aged 13 to 19 who were prescribed antimicrobial treatment from Jan. 1, 2016, to Dec. 31, 2017, after being diagnosed with PID or testing positive for chlamydia.

Of 696 emergency department visits for diagnosed STIs, 208 teenagers received outpatient prescriptions for antimicrobial treatments. Only 54.1% of those prescriptions were filled.

“Teenagers may face a number of hurdles when it comes to STI treatment, including out-of-pocket cost, access to transportation and confidentiality concerns,” Dr. Goyal adds.

Future studies will attempt to identify barriers to filling prescriptions in order to inform development of targeted interventions based in the emergency department that promote adherence to STI treatment.

In addition to Dr. Goyal, study co-authors include Lead Author, Alexandra Lieberman, BA, The George Washington University School of Medicine & Health Sciences; and co-authors Gia M. Badolato, MPH, and Jennifer Tran, PA-C, MPH, both of Children’s National.

Alexandra M. Sim

Alexandra M. Sims, M.D., FAAP, counsels grads to know their who, how and why

Alexandra M. Sim

Alexandra M. Sims, M.D., FAAP, general academic pediatrics fellow at Children’s National, tells newly minted George Mason social sciences graduates the concrete and abstract skills they learned during their collegiate experience are exceedingly valuable.

As a 10-year-old growing up in the suburbs of Richmond, Virginia, lip syncing with friends as they pretended to be Destiny’s Child, Alexandra M. Sims, M.D., FAAP, predicted her future: She would become a doctor.

“Ten is a really funny age,” Dr. Sims told members of the 2019 graduating class from George Mason University College of Humanities and Social Sciences, the school and department from which she received her undergraduate degree in Anthropology. “I was old enough to feel compelled to contribute to the world meaningfully, but too young to know the weight of this undertaking. I was old enough to be intrigued by the science of the human body, but too young to be intimidated by the fact that there were no doctors in my family.”

Dr. Sims’ youngest sister, Bria, was born four weeks premature and died a few weeks after birth. The sting of that tragedy instilled in her a commitment to serve others and informed a lifelong passion to help society’s most marginalized.

Ten years after graduating George Mason herself, she invited this year’s newly minted graduates to distill their college experience into three terms: who, how and why:

  • Who means the family members and mentors who helped them enter college and persevere toward graduation.
  • How is their plan to change the world. The general academics pediatrics fellow at Children’s National asks kids about their unique superpower during visits to the primary care clinic at Children’s Health Center Anacostia. “I get a range of responses, and some of them are quite funny,” she told 800 social sciences graduates gathered for their degree celebration. “Some really surprise me in other ways. ‘I want to be kind.’ ‘I want to help people.’ ‘I want to take care of my parents.’ ”
  • Why is the reason they continue to do what they’re doing. For Dr. Sims, that’s service and mitigating health disparities, a mission that has led her to travel around the globe conducting HIV/AIDS outreach and building coalitions near and far. Her current work is domestic, as she seeks advocates for at-risk communities through health services research.

“So, come back to these when you’re feeling unsure or uneasy: your WHO, your HOW and your WHY. Know that your time here at Mason is time well spent, and that the skills that you’ve gained, both the concrete and the abstract, are exceedingly valuable,” she advised the group.