Meetings

happy children running with kite

Spurring innovation to support pediatric preparedness

happy children running with kite

There are many lessons to be learned from the response to the COVID-19 pandemic, but one that is at the forefront is to be prepared for anything and to strengthen readiness even in the unlikeliest circumstances.

This was the focus of a recent panel discussion featuring Lee Beers, M.D., F.A.A.P, medical director of Community Health and Advocacy within the Goldberg Center for Community Pediatric Health and Child Health Advocacy Institute at Children’s National Hospital. Dr. Beers is also president of the American Academy of Pediatrics.

The webinar entitled, “Protecting Our Future: Spurring Innovation to Support Pediatric Preparedness,” was hosted by Johnson & Johnson Innovation – JLABS (JLABS) as a product of BLUE KNIGHT™, a collaboration between JLABS and the Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services.

This event focused on what innovators can do to develop therapeutics, diagnostics, vaccines and other technologies that may protect our future, our children. Experts shared what has been done to develop groundbreaking medical countermeasures that aim to prepare and protect pediatric populations from the health threats of today and those of tomorrow. The main discussions were on ecosystems readiness, adaptations for the pediatric population and the way forward in 2021.

“One size does not fit all for pediatrics when it comes to treatments and personal protective equipment,” said Dr. Beers “We need to know the need and how to do the roll-out.” Fellow panelists agreed.

Dr. Beers went on to say that mental health is the pandemic within the pandemic for our nation’s youth. There are increased cases and severity now for children who struggle to cope with the lockdowns. “We cannot have our children bear the burdens of our challenges.”

After robust questions and answers from everything from the role of artificial intelligence in preparing for future pandemics to the inclusion of families in research and decisions, the panelists walked away with a good feeling about the future with the unprecedented speed of vaccines aimed to counter the effects of the 2020 virus crisis.

The consensus priorities of 2021 should be to develop specifics for children and not just adaptations from adults, with the aim to advance equity, diversity and inclusion in treatment goals, and to build on the success of telemedicine.

Nationally, funding for pediatric research continues to trail efforts targeted for adults. That’s why Children’s National is creating a one-of-a-kind pediatric research and innovation hub. The Children’s National Research & Innovation Campus is set to open in 2021, located on a nearly 12-acre portion of the former Walter Reed Army Medical Center campus. The campus will combine the strengths of Children’s National with those of public and private partners who share the vision of accelerating new discoveries that save and improve the lives of children. At the new campus, breakthrough innovations can more quickly be translated into new treatments and technologies benefitting kids.

Sally Allain, Head of Johnson & Johnson Innovation – JLABS @ Washington, D.C., highlighted the opening of a 32,000 square-foot facility on the Research & Innovation Campus with a residency capacity for up to 50 companies. This will be the first JLABS site anchored with a children’s hospital and research institute working to bring recognition to the need for more early-stage research and innovation in pediatrics for our smallest patients.

The new site will serve as an incubator for pharmaceutical, medical device, consumer and health technology companies, and serve as the hub for BLUE KNIGHT™. BLUE KNIGHT™ aims to stimulate innovation and incubation of technologies that improve health security and response through companies focused on public health threats and emerging infectious diseases. At JLABS @ Washington, DC, companies selected for BLUE KNIGHT™ will have access to the JLABS ecosystem and being a part of the Research & Innovation Campus, as well as fee assistance for certain costs associated with access, mentorship for BARDA, and dedicated equipment for BLUE KNIGHT™ companies.

global connectedness concept illustration

Research partnerships and capacity building in the time of COVID-19

global connectedness concept illustration

“COVID infection anywhere in the world is COVID infection everywhere in the world,” said John Nkengasong, M.Sc., Ph.D., director of the Africa Centers for Disease Control (Africa CDC), during his remarks on the importance of shared science, innovation and diplomacy. Leading experts in global health met virtually on November 13, 2020, to discuss updates in the COVID-19 crisis and lessons learned in Africa. Children’s National Hospital, along with the George Washington University (GW) Institute for Africa Studies and the CNRS-EpiDaPo Lab, sponsored the half-day conference that captured the interest of international attendees committed to examining how best to expand strong and enduring partnerships between U.S. and African scientists, health professionals and research institutes to meet global challenges.

Trust, transparency and communication were common themes of expert panelists that included Elizabeth Bukusi, Ph.D., M.P.H., Kenya Medical Research Institute; Maryam DeLoffre, Ph.D., GW Humanitarian Action Initiative; Peter Kilmarx, M.D., National Institutes of Health (NIH) Fogarty International Center; Enock Motavu, Ph.D., Makerere University in Uganda; Jennifer Troyer, Ph.D., Human Health and Heredity in Africa Program (H3Africa) at NIH; Désiré Tshala-Katumbay, M.D., Ph.D., National Institute of Biomedical Research in Kinshasa; Eric Vilain, M.D., Ph.D., Center for Genetic Medicine Research at Children’s National, with Institute for African Studies Director Jennifer Cooke, and Jonathan LoTempio Jr and D’Andre Spencer of Children’s National as moderators and co-conveners. Read more about the panelists.

The keynote speaker, Nkengasong, updated the group on the massive efforts in bending the COVID-19 disease curve on the African continent which at present has two million cases and 46,000 deaths. This is fewer than many other regions, and Nkengasong attributes this in part to health systems strengthening and capacity building that already occurred with past pandemics like Ebola. He stressed the importance of focusing on the “4 Ps” — population, pathogen, politics and policy — in fighting the pandemic, and the need to ensure that citizens trust their leaders and the public health measures they advance. New endeavors by the Africa CDC include the Pathogen Genomic Initiative, which will help inform research and responses to COVID-19 and other emergent disease threats, and the African COVID-19 Vaccine Development and Access Strategy, which aims to ensure widespread access, delivery and uptake of effective vaccines across Africa. Africa CDC is surging to hotspots as lockdowns ease or shift, and is empowering universities to invest in proactive and, which has helped with the active response success. “Rising tides raise all boats in the sea,” said Nkengasong. He went on to say that there is great power in coordination and cooperation, and science diplomacy and technology are critical to winning the novel coronavirus war.

In a panel on research partnerships, speakers Motavu, Tshala-Katumbay, and Vilain emphasized the global benefits of scientific collaborations in Africa. Africa contains more human genetic variation than any other region of the world, and capturing that diversity in global understanding of the human genome — which is still heavily skewed toward individuals of European ancestry — will be a major factor in global medical advances of the future. And research into relatively localized diseases can lead to breakthroughs in broader understanding on connections between climate variation, environment, nutrition and child health. “The simplistic, localized, nationalist, way of doing science is over,” said Tshala-Katumbay, “and there is no way to go back.” The discipline of science diplomacy will take time for people to grasp, he added, “but it will be crucial for the future generation of scientists to go back.”

A recurring conference theme was that collaboration between countries is crucial for development of better care. Kilmarx told the event participants that in 2019, the National Institutes of Health supported some 1,668 collaborations with African research institutions. Investments in capacity building have yielded impressive results, and today some of Africa’s foremost leaders in science research and public health have received NIH training and support, stating: “If you plant acorns over the decades, you have some mighty oaks.” Bukusi, once such NIH trainee, now is engaged in training a new generation of African researchers and U.S. researchers based in Africa and expanding research partnerships at the Kenya Medical Research Institute.

Troyer showed the successes of the Human Heredity and Health in Africa Initiative, a large consortium that supports a pan-continental network of laboratories that aims to determine disease susceptibility and drug responses. Finally, DeLoffre underscored the need for long-term investments and the value of building local capacities to respond to current crises and anticipate future challenges.

Overall, there was optimism that innovative coalitions are a long-term strength in fighting pandemics and promoting reciprocal learning that will last after the crisis. Science can be a neutral platform that, combined with diplomacy and technology, builds bridges between peoples.

a telehealth video visit with a patient family

Steady rates of patient satisfaction, reimbursement for cardiac telehealth during COVID-19

a telehealth video visit with a patient family

In the first two weeks of COVID-19’s major impact on the U.S., Children’s National Hospital moved most of its subspecialty in-person day-to-day clinics to virtual care. Children’s National Heart Institute was one of the first divisions to offer telehealth visits — in part because the team was an early adopter of telehealth in cardiology for both physician-to-physician consultations and direct-to-patient care, and stood poised to widely implement it.

A poster presentation at the American Heart Association Scientific Sessions 2020 quantified how the rapid transition to direct-to-consumer telehealth services impacted families with children who have congenital heart disease. The findings were presented by first author Kristine Mehrtens, M.S., B.S.N., R.N., C.P.N., clinical manager for the Heart Institute’s Ambulatory Services.

The team found that though in-person cardiology visits decreased during the COVID-19 pandemic, direct-to-patient telehealth visits were able to partially compensate for the sudden drop.

Additionally, payer reimbursement rates for these direct-to-consumer telehealth visits were similar to in-person clinic visits.

”This is exciting as prior to COVID-19  we have seen a lower reimbursement rates for these cardiology direct-to-consumer telehealth visits compared to in-person cardiology clinic visits,” said Ashraf S. Harahsheh, M.D., a pediatric cardiologist at Children’s National Hospital who has utilized direct-to-consumer telehealth visits since 2016 and is a senior author on the new study.

Patient satisfaction scores for care providers, including the likelihood of recommending a care provider from Children’s National Hospital, was the same for telehealth follow-up visits as it was for in-person clinic visits before the pandemic.

“As a multidisciplinary team, we agreed that diagnostic studies such as echocardiograms were important to include with follow-up visits,” says Mehrtens. “Together we developed a strategy to ensure we could meet the needs of the patients and also safely conduct in-person visits when necessary.”

Why is this important?

The pandemic and the resulting temporary halt to in-person, non-urgent/emergent visits earlier this year put the most vulnerable people with congenital heart disease at high risk for complications or worsening of their existing heart disease because they are unable to follow the recommended schedule for follow-ups.

The readiness of the Children’s Heart Institute team to quickly move to a telehealth platform successfully bridged the gap between in-person visits for some patients, allowing cardiology surveillance to continue safely.

“I am proud of our team of physicians and advanced care providers,” Harahsheh concludes. “We went from three providers (8%) pre-COVID 19 to 31 (79%) providers offering direct-to-consumer telehealth visits during the pandemic.”

What’s next?

Building on previous, smaller studies of telehealth before the pandemic began, the team will continue to conduct research to assess the safety and efficacy of these telehealth visits over time. The increase in patients who are continuing to see their providers for routine follow-ups via telehealth will allow a larger sample for effective study of this care model.

American Heart Association Scientific Sessions 2020
Impact of Telemedicine on Pediatric Cardiac Center’s Ambulatory Response to the 2019 Novel Coronavirus Disease (covid-19) Pandemic
P1692
9:00am – 10:00am
Fri, Nov 13  (CST)

Read additional news stories about cardiology telehealth:

newborn in ICU

Cardiac technology advances show promise for kids but only if right-sized

newborn in ICU

“Smaller patients, and those with congenital heart disease, can benefit from minimally-invasive methods of delivering pacemakers and defibrillators without the need for open-chest surgery,” says Charles Berul, M.D.

How to address the growing need for child-sized pacemakers and defibrillators, and finding better surgical techniques to place them, is the topic of an invited session called The Future is Now (or Coming Soon): Updates on New Technologies in Congenital Heart Care at the 2020 American Heart Association Scientific Sessions.

“Smaller patients, and those with congenital heart disease, can benefit from minimally-invasive methods of delivering pacemakers and defibrillators without the need for open-chest surgery,” says Charles Berul, M.D., co-director of the Children’s National Heart Institute and chief of Cardiology at Children’s National Hospital, who presented at the session.

“This unmet need can only be met by innovative pediatric research, geared towards miniaturization technologies for use in the smallest of children,” he says.

His presentation focused on the devices and approaches that have caught the attention of pediatric cardiology, such as pacemakers and subcutaneous defibrillators designed without lead wires, as well as less-invasive surgical approaches that may reduce recovery time for children with congenital heart disease who require these assist devices.

Using them in kids comes with added challenges, however. Often pediatric cardiologists have to be creative in how to make them work for smaller patients, Dr. Berul notes. This reiterates the important point that simply applying an adult technology to a child isn’t the right approach. The subcutaneous defibrillator, for example, is still pretty large for a child’s body. Some studies also show these devices may not be as accurate in children as in adults.

Investigators in the Sheikh Zayed Institute working together with the cardiologists at Children’s National Hospital are focused on product development and commercialization of tools and techniques to allow percutaneous minimally-invasive placement of devices, taking advantage of the newest devices and surgical techniques as they develop.

In his presentation, Dr. Berul stressed that as the technology for adults advances, it creates an opportunity for pediatric cardiology, but only if the devices, and the techniques to place them, are specifically redesigned for pediatric application.

American Heart Association Scientific Sessions 2020
The Future is Now (or Coming Soon): Updates on New Technologies in Congenital Heart Care – On Demand Session
CH.CVS.715
9:00am – 10:00am
Fri, Nov 13  (CST)

coronavirus

Single institution study finds high rates of cardiac complications in MIS-C

coronavirus

At this year’s AHA Scientific Sessions, cardiologists from Children’s National Hospital presented a poster about an interesting finding in children with MIS-C.

During the height of the pandemic, researchers at Children’s National Hospital discovered that as many as one half of children diagnosed with multisystem inflammatory disease in children (MIS-C) at the hospital developed cardiac complications including coronary artery abnormalities, even when diagnosed and treated promptly.

The data was shared as part of a poster presentation at the American Heart Association Scientific Sessions in November 2020. Though analysis was limited to the data from one institution’s confirmed MIS-C cases, the findings are significant enough to warrant further study.

Interestingly, the authors noted that the high rate of cardiac complications far exceeds the rate of similar issues in children with Kawasaki disease — another pediatric inflammatory syndrome that shares many common symptoms with MIS-C. The two are so similar that immunomodulation therapies successfully deployed in children with MIS-C were based on those developed to treat Kawasaki disease.

Knowledge of common cardiac complications in Kawasaki disease also flagged the need for routine echocardiograms in patients with MIS-C, which helped identify the higher rates of cardiac complications seen in the MIS-C patient population.

“This finding, however, is another data point that shows how MIS-C and Kawasaki disease have some specific differences needing further study,” says Ashraf Harahsheh, M.D., a pediatric cardiologist at Children’s National Hospital who studies Kawasaki disease and the first author on the new study.

“Previous clinical advancements made in Kawasaki disease set the stage for our response to MIS-C early on,” he said. ”Now we also need to understand MIS-C as its own syndrome so we can better address what we are seeing in this patient population,” he says.

While most of the cardiac findings resolved during follow up, long-term studies are needed to determine if the cardiac abnormalities are associated with major cardiac events later.

“This work will help inform the community of the importance of diagnosing children with MIS-C promptly and following clinical guidelines for necessary tests and treatments once MIS-C is diagnosed,” Harahsheh concludes.

Next, the research team plans to take a deep dive into patient demographics as well as findings from clinical, laboratory and electrocardiogram data for children who developed cardiac complications with MIS-C. The goal will be to refine treatment algorithms and potentially identify a subgroup of patients who may require different or more intense therapy to prevent cardiac complications.

American Heart Association Scientific Sessions 2020 Poster Session
Cardiac Complications of SARS CoV-2 Associated Multi-System Inflammatory Syndrome in Children (MIS-C)
P1306
9:00am – 10:00am
Fri, Nov 13 (CST)

Dr. Laura Tosi talks to a patient

Refining criteria for childhood skeletal fragility and osteoporosis

Dr. Laura Tosi talks to a patient

Orthopaedic surgeon Laura Tosi, M.D., presented information about bone fractures and skeletal fragility in children at this year’s POSNA Annual Meeting.

It’s true that broken bones are often a typical part of childhood, says international bone health expert Laura Tosi, M.D., an orthopaedic surgeon at Children’s National Hospital. But for some children, a single bone fracture under the right circumstances may be a signal that a child needs a closer look to rule out underlying skeletal fragility.

Dr. Tosi presented on this topic as part of the Pediatric Orthopaedic Society of North America’s (POSNA) 2020 Annual Meeting. The presentations were conducted virtually this year due to COVID-19.

“We know that between 27 and 40% of girls, and 42 to 51 percent of boys will have at least one fracture during childhood,” she says. “What we have also seen over time is that almost 40 percent of children who have one fracture will have more. How do we tell which children with a fracture may need our help to avoid future ones?”

During her session, Dr. Tosi discussed how adding more nuance to clinical evaluation criteria for childhood fractures can help identify which children should be evaluated for conditions affecting bone density.

To widen the scope and make sure an underlying bone density issue is detected and treated as early as possible, Dr. Tosi says there are some specific findings that should suggest the need for further exploration:

  • Does the child have an a priori risk for a fragility fracture due to a genetic bone disorder(such as osteogenesis imperfects (aka brittle bone disease) or immobility caused by a disorder such as spina bifida, cerebral palsy or muscular dystrophy?
  • Is there a mismatch between the fracture severity and level of trauma that led to the injury?
  • Does the child’s history include any of four factors known to be associated with increased fracture risk: early age at the time of the first fracture, intolerance to cow’s milk, low dietary calcium intake or high BMI values.
  • Does the child have a vertebral compression fracture?
  • Is there a family history of frequent fractures (which may indicate a previously unidentified genetic condition)

Dr. Tosi also laid out specific evaluation steps for a skeletal fragility condition when a child’s fracture meets criteria, including:

  • Family, nutrition and exercise histories
  • A detailed physical exam
  • Complete radiograph review, including previously existing films and bone densitometry
  • Rule out rickets and child abuse
  • A complete lab work up

“It can be extremely challenging to identify if a child’s first bone fracture is a result of typical childhood activity or something else,” says Dr. Tosi. “But the risks of waiting to evaluate a fracture that meets some of the criteria above may mean we are delaying a treatment that might improve bone density and prevent a future fracture altogether — which is always what we’d hope to do.”

In the past, bone health experts felt that the word “osteoporosis” should not be used in children and pushed for the term “low bone density for age.”  That perspective has begun to change thanks to important advances in our understanding of the genetic basis of bone fragility, the important role of chronic conditions and how the use of bone-active medications can significantly reduce fracture risk and improve function in certain conditions.

She then spoke about the benefits of early detection for conditions causing skeletal fragility by presenting compelling evidence of the resiliency of a child’s bones when they are managed appropriately.

She noted that she’s seen significant bone remodeling in patients with serious bone degeneration due to osteogenesis imperfecta and leukemia, for example, thanks to early detection and treatment.

“Our knowledge of bone density and bone health is improving, but is still imperfect,” she concluded. “But as we learn more, and are able to appropriately identify and treat kids with skeletal fragility or osteoporosis earlier, we can continue to refine how we evaluate and care for all of them.”

coronavirus

COVID-19 Pandemic: 3rd Annual CN – NIAID Virtual Symposium

The CN-NIAID Virtual Symposium highlighted work being done to fight the COVID-19 pandemic globally.

Matt Oetgen and patient

Periop procedures improve scoliosis surgery infection rates

Matt Oetgen and patient

Matthew Oetgen, M.D., MBA, chief of orthopaedics and sports medicine at Children’s National Hospital, presented findings from a study aimed at improving quality and safety for pediatric spinal fusion procedures by reducing surgical site infection rates.

Pediatric orthopaedic surgery as a field is focused on improving quality and value in pediatric spine surgery, especially when it comes to eliminating surgical site infections (SSI). Many studies have documented how and why surgical site infections occur in pediatric spinal fusion patients, however, there is very little data about what approaches are most effective at reducing SSIs for these patients in a sustainable way.

At the Pediatric Orthopaedic Society of North America’s 2020 Annual Meeting, Matthew Oetgen, M.D., MBA, chief of orthopaedic surgery and sports medicine at Children’s National Hospital, presented findings from a long-term single institution study of acute SSI prevention measures.

“These findings give us specific insight into the tactics that are truly preventing, and in our case sometimes even eliminating, SSIs for pediatric scoliosis surgery,” says Dr. Oetgen, who also served on the annual meeting program committee. “By analyzing patient records across more than a decade, we were able to see that some strategies are quite effective, and others, that we thought would move the needle, just don’t.”

The team reviewed medical records and radiographs dating back to 2008 for 1,195 patients who had spinal fusion for scoliosis, including idiopathic scoliosis as well as other forms such as neuromuscular or syndromic scoliosis. Over that period of time, the division of orthopaedics and sports medicine at Children’s National was collaborating with the hospital’s infection control team to achieve several programmatic implementation milestones, including:

  • January 2012: Standardized infection surveillance program
  • July 2013: Standardized perioperative infection control protocols including those for pre-operative surgical site wash, surgical site preparation and administration of antibiotics before and after surgery
  • March 2015: Standardized comprehensive spinal care pathway including protocols for patient temperature control, fluid and blood management, and drain and catheter management

Over the study time period, the team found that SSIs did decrease, but interestingly, the rate did not progressively decrease with each subsequent intervention.

“Instead, we found that the rate went down and was even eliminated for some subgroups when the perioperative infection control protocols were implemented in 2013 and sustained through the study period end,” says Dr. Oetgen. “The other programmatic efforts that started in 2012 and 2015 had no impact on infection rates.”

He also notes that the study’s findings have identified a crucial component in the process for infection control in pediatric spinal surgery—perioperative protocols. “A relatively uncomplicated perioperative infection control protocol did the best job decreasing SSI in spinal fusion. Future efforts to optimize this particular protocol may help improve the rates even further.”

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.

Andrew Dauber

Andrew Dauber, M.D., MMSc, caps off research success with award and reception

Andrew Dauber

Unfortunately, we’ve been notified that the ENDO2020 conference has been canceled due to concerns of COVID-19. Because of this, we will not be hosting our reception in honor of Andrew Dauber, M.D., on Sunday, March 29.

We hope to see you at a future Endocrinology or Pediatric Endocrinology event.

Children’s National Hospital is incredibly proud of the work Dr. Dauber has done in the endocrinology community.

Andrew Dauber, M.D., MMSc, division chief of Endocrinology at Children’s National Hospital, will be awarded the 2020 Richard E. Weitzman Outstanding Early Career Investigator Award at ENDO 2020. The prestigious award will be presented at the annual meeting of the Endocrine Society in recognition of Dauber’s work in understanding the regulation of growth and puberty, and applying innovative genetic technologies to studying pediatric endocrinology. Dauber credits many collaborators throughout the world, as well as the team at Children’s National for the award.

With a five-year grant from the National Institutes of Health (NIH), Dauber and colleagues from the Cincinnati Children’s Hospital Medical Center, Boston Children’s Hospital and the Children’s Hospital of Philadelphia are using electronic health records to identify children who likely have rare genetic growth disorders. Using cutting-edge DNA sequencing technologies, including whole exome sequencing, the researchers are aiming to identify novel genetic causes of severe growth disorders. The first paper describing genetic findings in patients with high IGF-1 levels was published in Hormone Research in Paediatrics in December 2019.

Dauber and researchers at Cincinnati Children’s Hospital Medical Center are exploring how to treat patients with mutations in the PAPPA2 gene. In 2016, the group described the first patients with mutations in this gene who had decreased the bioavailability of IGF-1, stunting their growth and development. In their current phase of research, findings are emphasizing the importance of this gene in regulating IGF-1 bioavailability throughout childhood. The ultimate aim is to create therapies to increase IGF-1 bioavailability, thereby supporting healthy growth and development in children. Their first study to track PAPPA2 and intact IBGBP-3 concentrations throughout childhood was published in the European Journal of Endocrinology in January 2020.

Dauber is particularly interested in studying children with dominantly inherited forms of short stature. Along with collaborators in Cincinnati, he currently has an ongoing treatment trial using growth hormone in patients with Aggrecan gene mutations.  Dauber hopes to announce soon a new clinical trial for children with all forms of dominantly inherited short stature.

Study upon study has shown us that there are many factors that affect an individual’s height and growth. As these studies and the conversation around how to identify and address genomic anomalies become more prevalent, the team at Children’s National is increasingly interested in engaging with other centers around the country. In the coming months, the Children’s National Research & Innovation Campus will open on the grounds of the former Walter Reed Army Medical Center, which will serve as a one-of-a-kind pediatric research and innovation hub. A critical component to this campus is the co-location of Children’s National research with key partners and incubator space.

Nadia Merchant

Working to improve the management of endocrine related conditions

Nadia Merchant

This past fall, Nadia Merchant, M.D., joined Children’s National Hospital as an endocrinologist in the Endocrinology and Diabetes Department. Dr. Merchant received her undergraduate and medical education at Weill Cornell Medical College in Qatar. She completed her pediatric residency at Wright State Boonshoft School of Medicine. She then completed her genetics residency and pediatric endocrine fellowship at Baylor College of Medicine/Texas Children’s Hospital.

Dr. Merchant was born with acromesomelic dysplasia, a rare genetic disorder, but that hasn’t stopped her from pursuing her medical career. While at Baylor College of Medicine, Dr. Merchant was very active in quality improvement projects, research and organizations that raise awareness of endocrine related conditions. For several years, she was a moderator at Baylor College of Medicine for “From Stress to Strength,” at a course for parents of children with genetic disorders and autism. Dr. Merchant also served as an endocrine fellow representative on the American Academy of Pediatrics Section on Endocrinology (SOEn) for the last two years and also served on the committee for a Bone and Mineral special interest group within the Pediatric Endocrine Society (PES). During medical school, she worked with Positive Exposure, an organization that uses visual arts to celebrate human diversity for individuals living with genetic, physical, behavioral and intellectual differences.

During the 2019 Endocrine Society Annual Meeting, Dr. Merchant won the Presidential Poster Award for her poster presentation: Assessing Metacarpal Cortical Thickness as a Tool to Evaluate Bone Density Compared to DXA in Osteogenesis Imperfecta a research project assessing whether hand film is an additional tool to detect low bone mineral density in children.

Dr. Nadia Merchant is currently one of the endocrinologists in the multidisciplinary bone health clinic at Children’s National, a clinic dedicated to addressing and improving bone health in children. Dr. Merchant also manages endocrine manifestations in children with rare genetic disorders.

The Endocrinology department at Children’s National is ranked among the best in the nation by “U.S. News & World Report”.

Schistosoma

Parasitic eggs trigger upregulation in genes associated with inflammation

Schistosoma

Of the 200 million people around the globe infected with Schistosomiasis, about 100 million of them were sickened by the parasite Schistosoma haematobium.

Of the 200 million people around the globe infected with Schistosomiasis, about 100 million of them were sickened by the parasite Schistosoma haematobium. As the body reacts to millions of eggs laid by the blood flukes, people can develop fever, cough and abdominal pain, according to the Centers for Disease Control and Prevention. Schistosomiasis triggered by S. haematobium can also include hematuria, bladder calcification and bladder cancer.

Despite the prevalence of this disease, there are few experimental models specifically designed to study it, and some tried-and-true preclinical models don’t display the full array of symptoms seen in humans. It’s also unclear how S. haematobium eggs deposited in the host bladder modulate local tissue gene expression.

To better understand the interplay between the parasite and its human host, a team led by Children’s National Hospital injected 6,000 S. haematobium eggs into the bladder wall of seven-week-old experimental models.

After four days, they isolated RNA for analysis, comparing differences in gene expression in various treatment groups, including those that had received the egg injection and experimental models whose bladders were not exposed to surgical intervention.

Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) – a tool that helps researchers understand the biological meaning of a long list of genes – the team identified commonalities with other pathways, including malaria, rheumatoid arthritis and the p53 signaling pathway, the team recently presented during the American Society of Tropical Medicine and Hygiene 2019 annual meeting. Some 325 genes were differentially expressed, including 34 genes in common with previous microarray data.

“Of particular importance, we found upregulation in genes associated with inflammation and fibrosis. We also now know that the body may send it strongest response on the first day it encounters a bolus of eggs,” says Michael Hsieh, M.D., Ph.D., director of transitional urology at Children’s National, and the research project’s senior author. “Next, we need to repeat these experiments and further narrow the list of candidate genes to key genes associated with immunomodulation and bladder cancer.”

In addition to Dr. Hsieh, presentation co-authors include Lead Author Kenji Ishida, Children’s National; Evaristus Mbanefo and Nirad Banskota, National Institutes of Health; James Cody, Vigene Biosciences; Loc Le, Texas Tech University; and Neil Young, University of Melbourne.

Financial support for research described in this post was provided by the National Institutes of Health under award No. R01-DK113504.

clatharin cage viewed by electron microscopy

IPSE infiltrates nuclei through clathrin-mediated endocytosis

clatharin cage viewed by electron microscopy

IPSE, one of the important proteins excreted by the parasite Schistosoma mansoni, infiltrates human cellular nuclei through clathrin-coated vesicles, like this one.

IPSE, one of the important proteins excreted by the parasite Schistosoma mansoni infiltrates human cellular nuclei through clathrin-mediated endocytosis (a process by which cells absorb metabolites, hormones and proteins), a research team led by Children’s National Hospital reported during the American Society of Tropical Medicine and Hygiene 2019 annual meeting.

Because the public health toll from the disease this parasite causes, Schistosomiasis, is second only to malaria in global impact, research teams have been studying its inner workings to help create the next generation of therapies.

In susceptible host cells – like urothelial cells, which line the urinary tract – IPSE modulates gene expression, increasing cell proliferation and angiogenesis (formation of new blood vessels). On a positive note, neurons appear better able to fend off its nucleus-infiltrating ways.

“We know that IPSE contributes to the severity of symptoms in Schistosomiasis, which leads some patients to develop bladder cancer, which develops from the urothelial lining of the bladder. Our team’s carefully designed experiments reveal IPSE’s function in the urothelium and point to the potential of IPSE playing a therapeutic role outside of the bladder,” says Michael Hsieh, M.D., Ph.D., director of transitional urology at Children’s National and the research project’s senior author.

In addition to Dr. Hsieh, research co-authors include Evaristus Mbanefo, Ph.D.; Kenji Ishida, Ph.D.; Austin Hester, M.D.; Catherine Forster, M.D.; Rebecca Zee, M.D., Ph.D.; and Christina Ho, M.D., all of Children’s National; Franco Falcone, Ph.D., University of Nottingham; and Theodore Jardetzky, Ph.D., and Luke Pennington, M.D., Ph.D., candidate, both of Stanford University.

Financial support for research described in this post was provided by the National Institutes of Health under award No. R01-DK113504.

Albert Oh

Albert Oh, M.D., receives 2020 Emerging Leader Award from the ACPA

Albert Oh

Albert Oh, M.D., Director of the Cleft and Craniofacial Program at Children’s National Hospital.

The American Cleft Palate-Craniofacial Association (ACPA) recognized Albert Oh, M.D., with the 2020 Emerging Leader Award. This award is given to professionals who have been members of ACPA between three to 15 years, and who exhibit exemplary accomplishments and dedication to the issues affecting people with cleft and craniofacial conditions.

The ACPA is an association consisting of professionals who treat and/or perform research on cleft and craniofacial conditions. The nonprofit organization also supports those affected through education and resources through its ACPA Family Services program.

As the director of the Cleft and Craniofacial Program at Children’s National Hospital, Dr. Oh is a leader in the research, surgical treatment and holistic care of cleft and craniofacial patients. He has published over 75 peer-reviewed scientific articles and book chapters. Dr. Oh’s current research interests include the outcomes and safety of cleft and craniofacial procedures, 3-D analysis of craniofacial morphology, Pierre Robin sequence and vascular anomalies.

Dr. Oh says that “It is an honor to be recognized by the ACPA and to share their mission of advancing research and improving outcomes for all those affected by cleft and craniofacial conditions.”

Dr. Oh will be presented with his award during the ACPA’s 77th Annual Meeting in Portland, Or.

Gilbert Vezina

Gilbert Vezina, M.D., recognized with American Society of Pediatric Neuroradiology Gold Medal Award

Gilbert Vezina

Gilbert Vezina, M.D., Director of Neuroradiology in the Division of Diagnostic Imaging and Radiology at Children’s National Hospital, is being recognized at the 2020 American Society of Pediatric Neuroradiology 2nd Annual Meeting with the society’s most distinguished honor, the Gold Medal Award.

The American Society of Pediatric Neuroradiology (ASPNR) Gold Medal is awarded for both professional and personal excellence, honoring individuals who are superb pediatric neuroradiologists, scientists, and/or physicians, and mentors and who also are truly outstanding people. Recipients have consistently extended themselves beyond self-interest to make contributions to the field of pediatric neuroradiology and as such, have elevated the subspecialty. This medal recognizes the exceptional service and achievements of these individuals.

Dr. Vezina completed his undergraduate degree at the Collège Jean-de-Brébeuf, Montréal, Canada and medical school at McGill Medical School, Montréal, Canada. He completed a mixed internship at Montreal General Hospital, Montreal, Canada; residency in Diagnostic Radiology, Massachusetts General Hospital, Boston, Massachusetts followed by a fellowship in Neuroradiology, Boston, Massachusetts.

He began his career at Children’s National Hospital in 1990. He is currently the Director of the Neuroradiology Program at Children’s National Hospital and Professor of Radiology and Pediatrics at George Washington University School of Medicine and Health Sciences, Washington DC. He created the Neuroradiology Fellowship Program in 1993 where he impacted medical students, residents and fellows from around the world. He served as president of ASPNR from 2001-2002 and past President from 2002-2005. He also served as the Interim Chief, Diagnostic Imaging and Radiology at Children’s National for a brief period in 2017.

Congratulations, Dr. Vezina!

4th International Symposium on hypothalamic hamartomas

Children’s National co-hosts the 4th International Symposium on hypothalamic hamartomas

The Children’s National Hospital’s Comprehensive Pediatric Epilepsy Program co-hosted the 4th International Symposium on Hypothalamic Hamartomas held in September 2019 in Washington, D.C.

The 2019 Symposium focused on the psychiatric, neuropsychological, neurological and endocrinological comorbidities of Hypothalamic Hamartomas (HH). The participants also looked at treating the whole person – in addition to the tumor – covering the cognitive, physical, emotional and intellectual impacts of HH.

4th International Symposium on hypothalamic hamartomas

Attendees at the 4th International Symposium on Hypothalamic Hamartomas.

Presenters at the Symposium included experts from around the world, such as Children’s National’s Chief of the Divisions of Child Neurology and of Epilepsy and Neurophysiology,, William D. Gaillard, M.D., who moderated the entire event and served as the HH Symposium Chair on the Symposium Steering Committee.  Dr. Gaillard also facilitated a presentation titledDeveloping a New Paradigm for Assessing, Surveilling, & Treating HH Comorbidities” and another presentation titled, “Set 3 Year Research Roadmap & Top Priorities.”

Senior Vice President for the Center for Neuroscience & Behavioral Health, Roger Packer, M.D., also presented at the event on treatments being used in other hypothalamic hamartoma syndromes which may possibly have opportunities for success with treatment of HH.

Dr. Sean Tabaie at the Limb Deformity Course

Orthopaedic surgeon shares expertise at Baltimore Limb Deformity Course

Dr. Sean Tabaie at the Limb Deformity Course

Dr. Tabaie oversees a hands-on lab session focused on teaching orthopaedic surgeons and other allied health professionals proper assessment and placement of corrective hardware for limb deformities.

Sean Tabaie served as a lab instructor to guide hands-on applications of the latest devices for treatment of limb deformities.

Earlier this year, Children’s National orthopaedic surgeon Sean Tabaie, M.D., served as a faculty member for one of the most highly regarded courses focused on limb deformities, the 29th Annual Baltimore Limb Deformity Course. The course is presented each year by the International Center for Limb Lengthening.

The event brings together nearly 400 orthopaedic physicians, podiatrists and allied health professionals from 36 countries and 33 states to learn from pre-eminent surgical experts in these conditions. The three-day meeting provides lecture content as well as hands-on opportunities to practice care and treatment of limb deformities in both adults and children.

Dr. Tabaie served as a lab instructor, sharing expertise and in-depth knowledge from the pediatric perspective about how to assess limb alignment and plan corrections for specific deformities. The faculty teams also outlined current best practices for correction of several specific deformities, including Blount’s deformity, using internal and external devices.

“It was an honor to be asked to serve as faculty alongside these pre-eminent leaders in the field of limb deformity,” he says. “It is workshops like these that give us the opportunity to share what we know and also learn from the experience of others. And ultimately, lending expertise to these courses helps everyone more effectively assess and treat limb deformities in children and adults around the world.”

Read more about the course’s esteemed history and its 2020 schedule.

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 

###

Also read: Johan’s story
View: Safeguarding Johan’s future

doctor's stethescope coming out of a computer

Virtual cardiology follow-ups may save families time and money

doctor's stethescope coming out of a computer

Virtual cardiology follow-ups via computer or smartphone are a feasible alternative to in-person patient follow-ups for some pediatric cardiac conditions.

A poster presentation at the AHA Scientific Sessions shows successful implementation of virtual care delivered directly to patients and families via technology.

Health provider follow-ups delivered via computer or smartphone is a feasible alternative to in-person patient follow-ups for some pediatric cardiac conditions, according to the findings of a pilot study presented at the AHA Scientific Sessions this week.

“We’ve used telemedicine in pediatric cardiology for physician-to-physician communications for years at Children’s National, thanks to cardiologists like Dr. Craig Sable,” says Ashraf Harahsheh, M.D., cardiologist at Children’s National Hospital and senior author of the study. “But this is the first time we’ve really had the appropriate technology to speak directly to patients and their families in their homes instead of requiring an in-person visit.”

“We developed it [telemedicine] into a primary every day component of reading echocardiograms around the region and the globe,” says Craig Sable, M.D., associate chief of cardiology at Children’s National. “Telemedicine has enabled doctors at Children’s National to extend our reach to improve the care of children and avoid unnecessary transport, family travel and lost time from work.”

Participants in the virtual visit pilot study were previously established patients with hyperlipidemia, hypercholesterolemia, syncope, or who needed to discuss cardiac testing results. The retrospective sample included 18 families who met the criteria and were open to the virtual visit/telehealth follow up option between 2016 and 2019. Six months after their virtual visit, none of the participants had presented urgently with a cardiology issue. While many (39%) had additional visits with cardiology scheduled as in person, none of those subsequent in-person visits were a result of a deficiency related to the virtual visit.

“There are many more questions to be answered about how best to appropriately use technology advances that allow us to see and hear our patients without requiring them to travel a great distance,” adds Dr. Harahsheh. “But my team and I were encouraged by the results of our small study, and by the anecdotal positive reviews from families who participated. We’re looking forward to determining how we can successfully and cost-effectively implement these approaches as additional options for our families to get the care they need.”

The project was supported by the Research, Education, Advocacy, and Child Health Care (REACH) program within the Children’s National Hospital Pediatric Residency Program.

###

Direct-to-Consumer Cardiology Telemedicine: A Single Large Academic Pediatric Center Experience
Aaron A. Phillips, M.D., Craig A. Sable, M.D., FAAP; Christina Waggaman, M.S.; and Ashraf S. Harahsheh, M.D., F.A.C.C., F.A.A.P.
Poster Presentation by first author Aaron Phillips, M.D., a third-year resident at Children’s National
CH.APS.12 – Man vs. Machine: Tech in Kids
AHA Scientific Sessions 2019
November 17, 2019
12:30 -1:00 p.m.