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Stat Madness 2019

Vote for Children’s National in STAT Madness

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Stat Madness 2019

Children’s National Health System has been selected to compete in STAT Madness for the second consecutive year. Our entry for the bracket-style competition is “Sensitive liquid biopsy platform to detect tumor-released mutated DNA using patient blood and CSF,” a new technique that will allow kids to get better treatment for an aggressive type of pediatric brain tumor.

In 2018, Children’s first-ever STAT Madness entry advanced through five brackets in the national competition and, in the championship round, finished second. That innovation, which enables more timely diagnoses of rare diseases and common genetic disorders, helping to improve kids’ health outcomes around the world, also was among four “Editor’s Pick” finalists, entries that spanned a diverse range of scientific disciplines.

“Children’s National researchers collaboratively work across divisions and departments to ensure that innovations discovered in our laboratories reach clinicians in order to improve patient care,” says Mark Batshaw, M.D., Children’s Executive Vice President, Chief Academic Officer and Physician-in-Chief. “It’s gratifying that Children’s multidisciplinary approach to improving the lives of children with brain tumors has been included in this year’s STAT Madness competition.”

Pediatric brain cancers are the leading cause of cancer-related death in children younger than 14. Children with tumors in their midline brain structures have the worst outcomes, and kids diagnosed with diffuse midline gliomas, including diffuse intrinsic pontine glioma, have a median survival of just 12 months.

“We heard from our clinician colleagues that many kids were coming in and their magnetic resonance imaging (MRI) suggested a particular type of tumor. But it was always problematic to identify the tumor’s molecular subtype,” says Javad Nazarian, Ph.D., MSC, a principal investigator in Children’s Center for Genetic Medicine Research. “Our colleagues wanted a more accurate measure than MRI to find the molecular subtype. That raised the question of whether we could actually look at their blood to determine the tumor subtype.”

Children’s liquid biopsy, which remains at the research phase, starts with a simple blood draw using the same type of needle as is used when people donate blood. When patients with brain tumors provide blood for other laboratory testing, a portion of it is used for the DNA detective work. Just as a criminal leaves behind fingerprints, tumors shed telltale clues in the blood. The Children’s team searches for the histone 3.3K27M (H3K27M), a mutation associated with worse clinical outcomes.

“With liquid biopsy, we were able to detect a few copies of tumor DNA that were hiding behind a million copies of healthy DNA,” Nazarian says. “The blood draw and liquid biopsy complement the MRI. The MRI gives the brain tumor’s ZIP code. Liquid biopsy gives you the demographics within that ZIP code.”

Working with collaborators around the nation, Children’s National continues to refine the technology to improve its accuracy. The multi-institutional team published findings online Oct. 15, 2018, in Clinical Cancer Research.

Even though this research technique is in its infancy, the rapid, cheap and sensitive technology already is being used by people around the globe.

“People around the world are sending blood to us, looking for this particular mutation, H3K27M, ” says Lindsay B. Kilburn, M.D., a Children’s neuro–oncologist, principal investigator at Children’s National for the Pacific Pediatric Neuro-Oncology Consortium, and study co-author. “In many countries or centers, children do not have access to teams experienced in taking a biopsy of tumors in the brainstem, they can perform a simple blood draw and have that blood processed and analyzed by us. In only a few days, we can provide important molecular information on the tumor subtype previously only available to patients that had undergone a tumor biopsy.”

“With that DNA finding, physicians can make more educated therapeutic decisions, including prescribing medications that could not have been given previously,” Nazarian adds.

The STAT Madness round of 64 brackets opened March 4, 2019, and the championship round voting concludes April 5 at 5 p.m. (EST).

In addition to Nazarian and Dr. Kilburn, study co-authors include Eshini Panditharatna, Madhuri Kambhampati, Heather Gordish-Dressman, Ph.D., Suresh N. Magge, M.D., John S. Myseros, M.D., Eugene I. Hwang, M.D. and Roger J. Packer, M.D., all of Children’s National; Mariam S. Aboian, Nalin Gupta, Soonmee Cha, Michael Prados and Co-Senior Author Sabine Mueller, all of University of California, San Francisco; Cassie Kline, UCSF Benioff Children’s Hospital; John R. Crawford, UC San Diego; Katherine E. Warren, National Cancer Institute; Winnie S. Liang and Michael E. Berens, Translational Genomics Research Institute; and Adam C. Resnick, Children’s Hospital of Philadelphia.

Financial support for the research described in the report was provided by the V Foundation for Cancer Research, Goldwin Foundation, Pediatric Brain Tumor Foundation, Smashing Walnuts Foundation, The Gabriella Miller Kids First Data Resource Center, Zickler Family Foundation, Clinical and Translational Science Institute at Children’s National under award 5UL1TR001876-03, Piedmont Community Foundation, Musella Foundation for Brain Tumor Research, Matthew Larson Foundation, The Lilabean Foundation for Pediatric Brain Cancer Research, The Childhood Brain Tumor Foundation, the National Institutes of Health and American Society of Neuroradiology.

Chima Oluigbo examines a patient

Eradicating epilepsy with Visualase

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Chima Oluigbo examines a patient

Chima Oluigbo, M.D., and his team are using Visualase to identify and eliminate seizure foci and provide patients with a minimally invasive procedure for treating epilepsy.

About one in 26 people will be diagnosed with epilepsy in their lifetime. That adds up to about 3.4 million people in the U.S., or about 1 percent of the population nationwide. This condition can have huge consequences on quality of life, affecting whether children will learn well in school, eventually drive a car, hold down a job or even survive into adulthood.

For most of those that develop epilepsy, medications can keep seizures in check. However, for about a third of patients, this strategy doesn’t work, says Chima Oluigbo, M.D., an attending neurosurgeon at Children’s National Health System. That’s when he and his team offer a surgical fix.

Epilepsy surgery has come a long way, Dr. Oluigbo explains. When he first began practicing in the early 2000s, most surgeries were open, he says – they involved making a long incision in the scalp that can span half a foot or more. After drilling out a window of skull that can be as long as five inches, surgeons had to dig through healthy brain to find the abnormal tissue and remove it.

Each part of this “maximally invasive” procedure can be traumatic on a patient, Dr. Oluigbo says. That leads to significant pain after the procedure, extended hospital stays of at least a week followed by a long recovery. There are also significant risks for neurological complications including stroke, weakness, paralysis, speech problems and more.

However, open surgery isn’t the only option for epilepsy surgery anymore. Several new minimally invasive alternatives are now available to patients and the most promising, Dr. Oluigbo says, is called Visualase. He and his team are the only surgeons in the region who perform this procedure.

In Visualase surgeries, Dr. Oluigbo and his colleagues start by making a tiny incision, about 5 millimeters, on the scalp. Through this opening, they bore an even tinier hole into the skull and thread a needle inside that’s about 1.6 millimeters wide. “The brain barely notices that it’s there,” he says.

The tip of this wire holds a laser. Once this tip is placed directly at the seizure foci – the cluster of nerve cells responsible for generating a seizure – the patient is placed in an intraoperative magnetic resonance imaging (MRI) device. There, after checking the tip’s precise placement, the surgeons turn the laser on. Heat from the laser eradicates the foci, which the surgeons can see in real time using MRI thermography technology. The margins of the destroyed tissue are well-defined, largely sparing healthy tissue.

After the wire is removed, the incision is closed with a single stitch, and patients go home the next day. The majority of patients are seizure free, with rates as high as 90 percent for some types of epilepsy, Dr. Oluigbo says. Although seizure-free rates are also high for open procedures, he adds, Visualase spares them many of open surgeries’ painful and difficult consequences.

“Having done both open surgeries and Visualase,” Dr. Oluigbo says, “I can tell you the difference is night and day.”

Although open procedures will still be necessary for some patients with particularly large foci that are close to the surface, Dr. Oluigbo says that Visualase is ideal for treating medication-resistant cases in which the foci are buried deep within the brain. A typical example is a condition called hypothalamic hamartoma, in which tumors on the hypothalamus lead to gelastic seizures, an unusual seizure type characterized by uncontrollable laughing. He also uses Visualase for another condition called tuberous sclerosis, in which waxy growths called tubers develop in the brain, and for cancerous and benign brain tumors.

It’s gratifying to be able to help these children become seizure-free for the rest of their lives, says Dr. Oluigbo – even more so with the numerous updates he receives from families telling him how much this procedure has improved their children’s lifestyle.

“Visualase has completely changed the way that we approach these patients,” Dr. Oluigbo says. “It’s extraordinary to see the effects that this one procedure can have on the quality of life for patients here at Children’s National.”

newborn in incubator

Tracking oxygen saturation with vital signs to identify vulnerable preemies

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Khodayar-Rais-Bahrami

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What’s known

Critically ill infants in neonatal intensive care units (NICU) require constant monitoring of their vital signs. Invasive methods, such as using umbilical arterial catheters to check blood pressure, are the gold standard but pose significant health risks. Low-risk noninvasive monitoring, such as continuous cardiorespiratory monitors, can measure heart rate, respiratory rate and blood oxygenation. A noninvasive technique called near-infrared spectroscopy (NIRS) can gauge how well tissues, including the brain, are oxygenated. While NIRS long has been used to monitor oxygenation in conditions in which blood flow is altered, such as bleeding in the brain, how NIRS values relate to other vital sign measures in NICU babies was unknown.

What’s new

A research team led by Khodayar Rais-Bahrami, M.D., a neonatologist at Children’s National Health System, investigated this question in 27 babies admitted to Children’s NICU. The researchers separated these subjects into two groups: Low birth weight (LBW, less than 1.5 kg or 3.3 pounds) and moderate birth weight (MBW, more than 1.5 kg). Then, they looked for correlations between information extracted from NIRS, such as tissue oxygenation (specific tissue oxygen saturation, StO2) and the balance between oxygen supply and consumption (fractional tissue oxygen extraction, FTOE), and various vital signs. They found that StO2 increased with blood pressure for LBW babies but decreased with blood pressure for MBW babies. Brain and body FTOE in LBW babies decreased with blood pressure. In babies with abnormal brain scans, brain StO2 increased with blood pressure and brain FTOE decreased with blood pressure. Together, the researchers suggest, these measures could give a more complete picture of critically ill babies’ health.

Questions for future research

Q: Can NIRS data be used as a surrogate for other forms of monitoring?

Q: How could NIRS data help health care professionals intervene to improve the health of critically ill infants in the NICU?

Source: “Significant correlation between regional tissue oxygen saturation and vital signs of critically ill infants.” B. Massa-Buck, V. Amendola, R. McCloskey and K. Rais-Bahrami. Published by Frontiers in Pediatrics Dec. 21, 2017.

Children’s National Fetal Medicine Institute hosts 2nd annual International Symposium on the Fetal Brain

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The Children’s National Health System Fetal Medicine Institute hosted the 2nd annual International Symposium on the Fetal Brain in August 2017 in Washington, D.C.

Speakers at this year’s symposium focused on the following four areas:

  • Brain Development in an Unsupportive In Utero Environment – Diagnosis and Consequences
  • Supporting Brain Development in the Ex Utero Fetus: How Far Are We From Optimal?
  • Genomic and Epigenomic Mechanisms Underlying Differences in Brain Development
  • The Emergence of Consciousness and Pain Sensation

Adré J. du Plessis, M.B.Ch.B., M.P.H., Director of the Fetal Medicine Institute and Division Chief of Fetal and Transitional Medicine hosted the conference. In his opening remarks Dr. du Plessis noted “Our goal has been to gather together a diverse group from across the spectrum of disciplines focused on the well-being of the fetal brain and to engage all disciplines together.”

Diana-Bianchi-at-ISFB

Diana Bianchi, MD gives her keynote presentation on non-invasive fetal testing at the second annual International Symposium on the Fetal Brain.

Invited, internationally renowned speakers presented on diverse topics, including Diana Bianchi, Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development who spoke on the “Non-Invasive Fetal Testing Beyond Karyotype: What’s in it for the Fetal Brain?”

A new component to the symposium was the clinically-focused breakfast breakout sessions, created based on feedback from attendees of the 2016 Symposium. Sessions covered varied topics such as “Fetal Ultrasound: the Cornerstone of Fetal Neurodiagnosis,” “The Essentials of Neurogenetic Testing,” “Developing a Transitional Fetal-Neonatal Program” and “Using MRI to Advance Fetal Neurodiagnosis.”

The conference started with an exciting discussion by Alistair Gunn, M.B.Ch.B., Head of the Department of Physiology at the University of Auckland. His presentation “Fetal Heart Rate: What It Does and Does Not Tell Us” explored the considerable body of evidence that essentially all decelerations are mediated by chemoreflex responses to repeated hypoxia and that the parasympathetic autonomic nervous system is the critical regulator of both fetal heart rate and heart rate variation in labor.

Following a voting process from the symposium’s external speakers, the inaugural Andrea Poretti Abstract Award was presented to Katherine Ottolini for her poster titled: Breastmilk Feeds Improve Brain Microstructural Development in Very Premature Infants.

For more information about the sessions and speakers at the 2017 Symposium, please visit our website.