Surgical Innovation

Kinsley and Dr. Timothy Kane

Case study: Diagnosing a choledochal cyst in utero

Kinsley and Dr. Timothy Kane

The Feigel family worked with Timothy Kane, M.D., the division chief of general and thoracic surgery at Children’s National, to ensure an accurate diagnosis, coordinate a corrective procedure and support a strong recovery for Kinsley, who just celebrated a 5-month milestone.

On Sept. 30, 2018, Elizabeth Feigel gave birth to a healthy baby girl, Kinsley Feigel. Thirty-two days later, Elizabeth and her husband, Steven Feigel, delighted in another hospital moment: Kinsley, who developed a choledochal cyst in utero, was recovering from a surgical procedure to remove an abnormal bile duct cyst, which also required the removal of her gallbladder.

While the series of events, interspersed with multiple hospital visits, would likely create uneasiness in new parents, the Feigel family worked with Vahe Badalyan, M.D., a gastroenterologist at Children’s National Health System, and with Timothy Kane, M.D., the division chief of general and thoracic surgery at Children’s National, to ensure an accurate diagnosis, coordinate a corrective procedure and support a strong recovery for Kinsley, who just celebrated a 5-month milestone.

One of the keys to Kinsley’s success was close communication between her parents and providers.

Dr. Badalyan and Dr. Kane listened to Elizabeth and Steven’s concerns, explained complex medical terms in lay language, and provided background about Kinsley’s presenting symptoms, risk factors and procedures. Instead of second-guessing the diagnosis, Elizabeth and Steven put their trust into and remained in contact with the medical team, sharing updates about Kinsley at home. This parent-physician partnership helped ensure an accurate diagnosis and tailored treatment for Kinsley.

Here is her story.

An early diagnosis

During a 12-week prenatal ultrasound, Elizabeth discovered that Kinsley had an intra-abdominal cyst. Before Elizabeth came to Children’s National for an MRI, she met with several fetal medicine specialists and had a variety of tests, including an amniocentesis to rule out chromosomal abnormalities, such as Down syndrome.

The team at Children’s National didn’t want to prematurely confirm Kinsley’s choledochal cyst in utero, but additional ultrasounds and an MRI helped narrow the diagnosis to a few conditions.

After Kinsley was born, and despite looking like a healthy, full-term baby, she was transported to the neonatal intensive care unit (NICU) at Children’s National. Dr. Badalyan and Dr. Kane analyzed Kinsley’s postnatal sonogram and found the cyst was bigger than they previously thought. Over a five-day period, the medical team kept Kinsley under their close watch, running additional tests, including an additional sonogram. They then followed up with Kinsley on an outpatient basis to better understand and diagnose her cyst.

Outpatient care

Over the next few weeks, Kinsley, Elizabeth and Steven returned to Children’s National to coordinate multiple exams, ranging from an MRI to a HIDA scan. During this period, Elizabeth and Steven remained in contact with Dr. Badalyan. They heard about Kinsley’s lab results and sent updates about her symptoms, including her stool, which helped the medical team monitor her status.

Meanwhile, Dr. Badalyan and Dr. Kane worked closely with the lab to measure Kinsley’s bilirubin levels. Her presenting symptoms and risk factors, she had jaundice and is a female baby of Asian descent, are associated with both choledochal cysts and biliary atresia.

Over time and with the help of Elizabeth, Steven and the pediatric radiologists, Dr. Badalyan and Dr. Kane confirmed Kinsley had a type 1 choledochal cyst, the most common. Originally, the plan was to operate at three to six months, but Dr. Kane needed to expedite the procedure and operate on Kinsley at one month due to a rise in her bilirubin, a sign of progressive liver disease.

Higher bilirubin levels are common in newborns and remain elevated at about 5 mg/dL after the first few days of birth, but Kinsley’s levels peaked and remained elevated. Instead of her bile flowing into her intestine, her choledochal cyst reduced the flow of bile, which accumulated and started to pour back into her liver. The timing of the surgery was as important as the procedure.

The surgery

On Oct. 31, Halloween, Kinsley had laparoscopic surgery to remove the choledochal cyst. Approximately five to seven patients per year undergo choledochal cyst removal at Children’s National. Smaller infants typically undergo removal of a choledochal cyst using a large incision (or open procedure). Kinsley was the smallest baby at Children’s National to have this type of surgery performed by minimally invasive laparoscopic surgery, which required a few 3-mm incisions – the size of coriander seeds.

Some hospitals use the da Vinci robot, which starts at 8-mm incisions, the size of a small pearl, to conduct this procedure on infants, but this method cannot effectively be done in very small infants. Instead, Dr. Kane prefers to stitch sutures by hand. This technique keeps the incisions small and is technically demanding, but Dr. Kane doesn’t mind (he views this as an advanced technical skill). The goal for this surgery was to cut out the abnormal piece of Kinsley’s common bile duct, comprised of the cyst, remove  this and then sew the bile duct to the small intestine (duodenum), creating a digestive pathway. The new digestive tube allows for bile to flow from her liver through the common hepatic duct, in place of the pathway where the cyst formed, and into her intestine.

Like other surgeries, Dr. Kane needed to adapt the procedure, especially with Kinsley’s size: Taking too much from the bile duct would create a tight space, and could create obstruction, blocking bile, while leaving too much room could create leakage and spilling of the bile, requiring a follow-up surgical procedure within a week or two of the original operation.

Dr. Kane had a few options in mind before he operated. He didn’t know which would be most suitable until the operation, but he remained open and prepared for all three. Adopting this mindset, instead of having one procedure in mind, has helped Dr. Kane with precise and tailored surgeries, which often result in the best procedure and a stronger recovery period for young patients.

After 4.5 hours, the surgery, a two-part procedure – removing the cyst and recreating a functional bile duct – was complete.

Kinsley moved into the recovery unit, where she rested and recovered under close medical supervision for five days. During the first few days, she didn’t have liquids or milk, but she did have two bedside nurses monitoring her status in addition to surgeons making regular rounds. Elizabeth and Steven were relieved: The diagnosis and surgery were over.

Managing risk factors

Before Kinsley left the hospital, Elizabeth and Steven scheduled a follow-up visit to ensure Kinsley was recovering well and avoided risk of infection, such as cholangitis, which can occur suddenly and become chronic.

Following Kinsley’s post-surgical bloodwork in early November, Dr. Badalyan noticed Kinsley’s white blood count was high, signaling infection, and he immediately brought the family back to the hospital. To help her body fight the infection, Kinsley received antibiotics and intravenous fluids. She stayed in the hospital for five days. Fortunately, cholangitis is easy to treat with antibiotics; the key is to detect it early.

Kinsley returned home in time for Thanksgiving. She came back to the hospital for biweekly visits. At this point, she was filling out, reaching a 2-month milestone and nearing a full recovery. She returned for follow-up visits in December and January – and has been healthy ever since. She will continue to make routine visits during her first year to ensure her white blood count remains in a healthy range.

Investing in youth resilience

Dr. Badalyan and Dr. Kane envision a healthy future for Kinsley. They don’t expect she’ll need additional operations. Her parents are also looking on the bright side: Since gallbladders aren’t essential for survival or long-term health outcomes, and since many people can easily live without them, Kinsley may be at an advantage. Elizabeth thinks Kinsley may be more cautious about lifestyle choices to support living without a gallbladder, which also support longevity.

Another perspective noted by Dr. Badalyan and Dr. Kane is Kinsley’s resilience factor. Having the surgery earlier brought unique challenges, but her age makes it easier for Kinsley to bounce back as her body rapidly develops. Her tissues were healthy, compared to adult patients undergoing surgery with chronic liver problems or heart disease, which puts her at an advantage for a faster healing process. Dr. Badalyan also mentions that while it’s good for her Kinsley and her family to continue to monitor risks for infections, she won’t have gallstones.

Elizabeth also started to notice something that Kinsley’s doctors likely wouldn’t pick up on: Her personality seems to be a result of her hospital experience and stay. Kinsley’s an easy baby. She eats well and sleeps well, which Elizabeth credits to being around clinicians and to learning the art of self-soothing, a skill she likely acquired while recovering from surgery.

This month, Kinsley has another adventure. She’ll travel with her parents to visit extended family in Seattle, Napa Valley, Calif. and West Virginia. She has several relatives and family friends, all of whom are looking forward to meeting her.

Dr. Kurt Newman in front of the capitol building

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

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

The traction sisters

Spinal-halo-gravity traction times three

The traction sisters

Three girls received spinal-halo-gravity traction at the same time at Children’s National prior to surgery for acute idiopathic scoliosis.

Washington, D.C.’s ABC affiliate, WJLA, recently featured a story about three girls who received treatment for acute idiopathic scoliosis through the Children’s National Spinal Fusion Surgical Home, a comprehensive and effective program that has demonstrated reductions in pain medication usage and medical stays following posterior spinal fusion surgery.

All three girls had extremely severe curvatures of the spine requiring a month long inpatient stay for spinal halo-gravity traction prior to surgical intervention. Spinal curves severe enough to require traction are rare, and often impede a child’s quality of life just as severely – eating, breathing and moving are difficult. Given the long hospital stay required and the challenges of asking a child to stay in a traction frame 23 hours out of every day, the orthopaedic surgery team tries to coordinate cases so that when possible, patients can support each other throughout the process. This was the first time, however, that the team had three traction patients on similar trajectories on the unit at the same time.

Spinal halo-gravity traction can reduce the degree of surgical intervention necessary by accomplishing some pre-operative gradual straightening of the spine prior to spinal fusion procedures. For severe spinal deformities this has been shown to improve the safety and effectiveness of the final surgical procedure.

Prescription for a healthy heart: pediatric-driven partnerships

Dr. Martin and a patient share a smile after a visit at Children’s National Health System.

For pediatric cardiologists, February, National Heart Month, is a special time. We share health tips in the hospital and talk about heart health with those looking for advice, especially with patients and families impacted by congenital heart disease (CHD). It’s also a time to look back at what’s worked well in the field, while accelerating advancements for CHD treatment.

To start, congenital heart disease, a structural abnormality of the heart or of the blood vessels surrounding it, is the most common birth defect and occurs in about one in every 100 live births, affecting 40,000 babies born in the U.S. each year. One million children and 1.4 million adults in the U.S. have CHD. Over the past 15 years, pediatric cardiologists have cut mortality rates for CHD in half. Gratefully, now instead of saving children’s lives, the emphasis is on improving them. The catalyst for this paradigm shift isn’t simply due to a medical breakthrough, but is also the result of collaboration and advocacy.

Pediatric cardiologists worked together with other stakeholders – nurses, neonatologists, parents, state and federal agencies – to implement newborn screening methods in hospitals, with the introduction pulse oximetry screenings for critical congenital heart defects (CCHD). The screening, which measures blood oxygen levels in newborns, focuses on screening babies for CCHD before they leave the hospital. The concept and a national protocol for screening began with a small project in 2002, was endorsed by medical associations by 2012 and required by all states in 2018. The impact of CCHD screening of newborns is remarkable. Data published in JAMA showed a 33 percent reduction in CCHD infant deaths associated with states that required CCHD screening.

The pulse oximetry screening’s impact on the number of lives saved goes beyond identifying newborns with CCHD. Worldwide, though the detection of secondary conditions, such as hypothermia, pneumonia, and sepsis, the pulse oximetry screening is estimated to save roughly 772,000 lives by 2030.

In addition to newborn screening recommendations for CCHD, a group of cardiologists, including myself, worked for the Joint Council on Congenital Heart Disease (JCCHD) to form and support the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC). We developed measures to see how we could improve survival rates between surgeries for infants born with hypoplastic left heart syndrome (HLHS), one of the most common and severe forms of CCHD.

Babies born with HLHS require two heart surgeries within the baby’s first six months. Babies that survived the first operation had a significant mortality rate (15 percent) and frequent growth failure, while waiting for the second operation. Our focused aims were to both decrease the death rate and improve growth in these children. We analyzed data from medical centers, utilized quality improvement principals from the Institute for Health Care Improvement, talked with doctors and families, and invited teams from across the U.S. to partner with us to put quality and safety measures into place.

We emphasized the following points:

  1. Clear communication. Parents leaving the hospital received consistent messages about CHD, the type of surgery their baby had, next steps and how to care for their child at home.
  2. Improved nutrient intake. Parents received clear guidelines about how many calories babies needed to consume, were asked to weigh their baby each day, and taught how to augment feeding.
  3. Warning signs.Parents received a list of typical infant behaviors and HLHS red flags to watch out for, such as if a baby isn’t gaining a certain amount of weight. They received monitors to measure oxygen saturation levels at home. If oxygen saturation dropped significantly or if parents noticed a problem, they called their doctor immediately.

The implementation of these procedures reduced interstage mortality rates and the number of growth failures for HLHS patients. In 2008, six centers participated in the NPC-QIC pilot. By 2018, 65 medical centers in the U.S. and Canada used these methods. Similar to the pulse oximetry screening guidelines, this new method wasn’t the result of a medical breakthrough, but the result of shared learning and shared infrastructure.

Now, we’re referring more adult congenital heart patients to board-certified adult congenital heart disease (ACHD) specialists, a better fit than internists or pediatric cardiologists. Adults with congenital heart defects should have their heart examined at least once by a specialist and those with complex needs should meet with a specialist at least every two years. More than 300 board-certified ACHD specialists practice in the U.S. and the field is growing. The third ACHD board exam takes place this year.

Over the next few decades, I hope we’ll make even more progress with understanding, diagnosing and treating CHD.

Emerging research examines genetic clues for congenital heart defects, which were once thought to account for 8 percent of cases and may now account for 30 percent of conditions. We’re working with neurologists to examine the timing and pathway of potential oxygen inefficiencies that occur as the brain develops in utero, infancy, and after neonatal surgery. We’ve come a long way, but we continue looking at new frontiers and for innovative solutions.

Fortunately, as cardiologists, we’re good at fixing problems. We work with surgeons and medical teams to repair holes in hearts, or replace them, and reroute blood from an underdeveloped left ventricle to improve circulation. For almost every heart defect, we have evidence-based solutions. However, to continue to help children worldwide, it’s imperative that we don’t forget about what works well: good science, tracking data, sharing best practices, active listening, transparency and constant collaboration.

Gerard Martin, M.D., F.A.A.P., F.A.C.C., F.A.H.A., is a cardiologist and the medical director of global services at Children’s National Health System. Dr. Martin has practiced pediatric cardiology for 34 years and is the Dan G. McNamara keynote speaker at the American College of Cardiology’s 2019 Scientific Sessions. Follow Dr. Martin on Twitter @Gerard_MD.

This article first appeared on KevinMD.com.

Nikki Gillum Posnack

What are the health effects of plastics?

Nikki Gillum Posnack

Nikki Posnack, Ph.D., assistant professor at the Children’s National Heart Institute, is an early-stage investigator examining the impact plastic chemical exposure has on the developing hearts of newborns and young children.

For newborns or children in the pediatric intensive care unit, plastic tubing is part of daily life. It delivers life-sustaining blood transfusions, liquid nutrition and air to breathe. But small amounts of the chemicals in the plastic of this tubing and other medical devices can leak into the patient’s bloodstream. The potential effects of these chemicals on the developing hearts of newborns and very young children are not well understood.

One researcher, Nikki Posnack, Ph.D., an assistant professor at the Children’s National Heart Institute, aims to change that and shares her early insights, funded by the National Center for Advancing Translation Science (NCATS), in an NCATS news feature.

“While plastics have revolutionized the medical field, we know chemicals in plastics leach into the body and may have unintended effects,” Posnack said. “The heart is sensitive to toxins, so we want to look at the effect of these plastics on the most sensitive patient population: kids who are recovering from heart surgery and already prone to cardiac complications.”

Dr. Michael Hsieh's clay shield

Innovative urologist Michael Hsieh takes unbeaten path

Dr. Michael Hsieh's clay shield

For an elementary school art project, Michael H. Hsieh, M.D., Ph.D., was instructed to fashion a coat of arms out of clay. In addition to panels for truth, justice and Taiwan, in the shield’s M.D. panel, a snake twists around a rod, like the staff for Asclepius, a Greek god associated with healing.

Children’s urologist Michael H. Hsieh, M.D., Ph.D., knew from age 10 that he would become a doctor. Proof is at his parents’ home. For an elementary school art project, students were instructed to fashion a coat of arms out of clay. In addition to panels for truth, justice and Taiwan, in the shield’s M.D. panel, a snake twists around a rod, like the staff for Asclepius, a Greek god associated with healing.

“I liked science. When I can use it to help patients, that is very rewarding,” says Dr. Hsieh, the first doctor in his family.

These days, Dr. Hsieh’s Twitter profile serves as a digital coat of arms, describing him as “tinker, tailor,” #UTI #biologist, epithelial #immunologist, helminthologist and #urologist.

Tinker/tailor is shorthand for the mystery drama, “Tinker Tailor Solider Spy,” he explains, adding that the “tinker” part also refers “to the fact that I am always questioning things, and science is about experimentation, trying to seek answers to questions.”

While still in medical school during a rotation Dr. Hsieh saw a bladder operation on a young child and thought it was “amazing.” That experience in part inspired Dr. Hsieh to become a urologist and bladder scientist. His training in immunology and study of the bladder naturally led him to study urinary tract infections and parasitic worms that affect the urinary tract. In addition, thanks to R01 funding from the National Institutes of Health (NIH), Dr. Hsieh is co-principal investigator with Axel Krieger, University of Maryland, and Jin U. Kang, Johns Hopkins, on a project to develop imaging robots for supervised autonomous surgery on soft tissue.

The $1 million in NIH funding pushes the boundaries on amazing by using multi-spectral imaging technology and improved techniques to reduce surgical complications.

Anastomosis is a technique used by surgeons to join one thing to another, whether it’s a vascular surgeon suturing blood vessels, an orthopedic surgeon joining muscles or a urologist stitching healthy parts of the urinary tract back together. Complications can set in if their stitching is too tight, prompting scar tissue to form, or too loose, letting fluid seep out.

“The human eye can see a narrow spectrum of electromagnetic radiation. These multi-spectral imaging cameras would see across greater set of wavelengths,” he says.

The project has three aims: figuring out the best way to place sutures using multi-spectral imaging, accurately tracking soft tissue as they model suturing and comparing the handicraft of a robot against anastomosis hand-sewn by surgeons.

“I like challenges, and I like new things. I am definitely not interested in doing permutations of other people’s work,” Dr. Hsieh explains. “I would much rather go on a path that hasn’t been tread. It is more difficult in some ways, but on a day-to-day basis, I know I am making a contribution.”

In another innovative research project, Dr. Hsieh leveraged a protein secreted by a parasitic worm, Schistosoma haematobium, that suppresses inflammation in hosts as a new therapeutic approach for chemotherapy-induced hemorrhagic cystitis, a form of inflammation of the bladder.

Watching his first surgery nearly 30 years ago, he had no idea robots might one day vie to take over some part of that complicated procedure, or that parasite proteins could be harnessed as drugs. However, he has a clear idea which innovations could be on the horizon for urology in the next three decades.

“My hope is 30 years from now, we will have a solid UTI vaccine and more non-antibiotic therapies. UTIs are the second-most common bacterial infection in childhood and, in severe cases, can contribute to kidney failure,” he says.

Globally, parasitic worms pose an ongoing challenge, affecting more than 1 billion worldwide – second only to malaria. People persistently infected by schistosome worms fail to reach their growth potential, struggle academically and lack sufficient energy for exercise or work.


“There is a feeling that the infection prevalence might be decreasing globally, but not as quickly as everyone hopes. In 30 years perhaps with more mass drug administration and additional drugs – including a vaccine – we’ll have it close to eliminated globally. It would become more like polio, casting a slim shadow with small pockets of infection here or there, rather than consigning millions to perpetual poverty.”

Pedbot video game

Pedbot’s next step – Home-based therapy

Pedbot video game

Pedbot’s home version adapts the same airplane-themed video game to a smaller therapeutic platform that is more affordable to build.

The novel ankle rehabilitation robot built at Children’s National to help children with cerebral palsy build ankle strength and control through video gaming is taking a big step forward. Engineers have created a smaller, more affordable version of the robotic platform using 3D printed parts, to explore the effectiveness of a home-based therapy program.

“We’re seeing preliminary success in our trial for in clinic use of the Pedbot. Now we’re hoping to see if making the technology accessible at home means that 1) Kids use it more often and 2) More frequent, regular use over time leads to better range of motion,” says Kevin Cleary, Ph.D., the Sheikh Zayed Institute for Pediatric Surgical Innovation’s bioengineering technical director and engineering lead for Pedbot.

Pedbot’s video game, designed by software engineer Hadi Fooladi, M.S., allows kids to pilot an airplane through a series of hoops at varying speeds as determined by the therapist and programmer. The game isn’t the only thing that’s unique about this therapeutic robot, however.

Just like the clinic version, the home model moves in three translational directions (x, y and z) and rotates about three axes (the x, y and z axes), similar to the movement of a flight simulator. The result is a robot that helps the patient exercise across a greater range of motion and build muscle strength in a way that more closely mimics real-life ankle function.

Pedbot Home potentially eliminates an additional major therapeutic barrier – the clinic appointment.

“The great thing about Pedbot is you’re constantly working to reach a moving target, and the therapist can vary the movement type as much or as little as needed for each patient,” says Catherine Coley, DPT, a physical therapist at Children’s National who is a member of the Pedbot development team. “We think the home version might make it easier for the child to succeed with a long term therapy program by removing the need for repeat clinic visits.”

“What if a child could come home from school and do their therapy at home after dinner? Would doing it every day for 20 minutes benefit the child more than just coming to see us once or twice a week for an hour? Can we make it easier for our patients to cooperate and follow through with therapy homework? These are some of the questions that we hope we can answer during our trial for the home version,” says Sally Evans, M.D., division chief of Pediatric Rehabilitation Medicine at Children’s National and clinical lead for the project.

The cross-functional Pedbot team includes engineers Reza Monfaredi Ph.D. and Tyler Salvador, B.S., as well as additional physical therapists, Stacey Kovelman, P.T. and Justine Belchner, P.T., and Sara Alyamani, B.A. Future expansions will include the addition of electromyography measurements in collaboration with Paola Pergami, M.D., Ph.D. and incorporation of other patient populations with Beth Wells, M.D.

Pedbot Home is currently being piloted in the home setting, with the goal of enrolling additional families to participate in a trial within the next year. The work is supported by a $500,000 federal grant from the Department of Health and Human Services’ National Institute on Disability, Independent Living, and Rehabilitation Research.

surgical theater

Virtual reality allows surgical planning from every angle

surgical theater

The virtual reality surgical system projects images into the operating room, allowing neurosurgeons to revisit the surgical plan in real time.

Neurosurgeons at Children’s National Health System are getting a new three-dimensional (3D) perspective on their cases thanks to an FDA-approved breakthrough virtual reality surgical system.

Children’s National is the first pediatric health system in metropolitan Washington, D.C., to use this state-of-the art system, created by Surgical Theater. It seamlessly integrates patient-specific surgical planning and navigation, professional education and rehearsal.

The technology acquisition was made possible through a generous gift from Sidney & Phyllis Bresler, in honor of their children Alex, Jonathan and Amanda and grandson Theo Charles Bresler, and in loving memory of Joshua Stouck.

“Virtual reality modeling enables us to further explore, analyze and find the best approach for each unique surgical procedure,” said Children’s National President and CEO Kurt Newman, M.D. “This generous gift from Sidney & Phyllis Bresler should translate into better outcomes for many of the more than 17,500 patients who receive surgery at our hospital each year, and will benefit generations to come. We are deeply grateful for the Breslers’ commitment to pediatric innovation.”

The 3D, 360-degree view gives surgeons a cutting-edge digital tool to plan procedures in depth using an accurate capture of the patient’s unique anatomy, and also allows the surgeon to illustrate the surgical path in greater detail than ever before for patients and their families.

“Technology such as Surgical Theater’s represents a quantum leap for neurosurgeons, both in and out of the operating room,” said Robert Keating, M.D., chief of Neurosurgery at Children’s National, in a press release from the company. “It allows us to marry state-of-the-art 3D simulation to the real world; for the patient and family as well as doctors in training, and ultimately offers a new tool for the neurosurgical armamentarium in approaching complex lesions in the brain, such as AVM’s, tumors, epilepsy and functional cases.”

Karun-Sharma-and-kids-MR-HIFU

Clinical Trial Spotlight: Treating tumors with ThermoDox® and MR-HIFU

Karun Sharma, M.D., is working with AeRang Kim, M.D., Ph.D., to evaluate the use of ThermoDox®, a heat-activated chemotherapy drug, in combination with noninvasive magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) to treat refractory or relapsed solid tumors in children and young adults.

A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®) and Magnetic Resonance-Guided High Intensity Focused Ultrasound for Relapsed or Refractory Solid Tumors in Children, Adolescents, and Young Adults.

This study is looking to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lyso-thermosensitive liposomal doxorubicin (LTLD), a heat-activated formulation of liposomal doxorubicin with unique property of heat-activated release of doxorubicin, administered in combination with magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) in children with relapsed/refractory solid tumors.

MR-HIFU is an innovative device that provides precise and controlled delivery of heat inside a tumor using an external applicator. Unlike other heating systems used in local therapy, MR-HIFU is entirely non-invasive and does not use any radiation. Integration of MR imaging allows for real-time temperature monitoring for accurate and precise targeting of tumors. LTLD is a novel formulation of doxorubicin with the unique property of heat-activated release. This selective drug delivery mechanism allows for local and rapid release of doxorubicin in high concentrations in tumors when heated. This novel combination may potentiate known effective therapy to improve local control and drug delivery without increasing toxicity.

Children’s National Health System and Celsion Corp, a leading oncology drug-development company, were the first to launch a clinical study in the U.S. that evaluates the use of ThermoDox® with MR-HIFU. Learn more about the clinical trial.

For more information about this trial or other trials available at Children’s National, contact:

Melissa Salerno
Clinical Research Program Manager
202-476-2142
msalerno@childrensnational.org

View more open phase 1 and phase 2 cancer clinical trials at Children’s National.

The Children’s National Center for Cancer and Blood Disorders is committed to providing the best care for pediatric patients. Our experts play an active role in innovative clinical trials to advance pediatric cancer care. We offer access to novel trials and therapies, some of which are only available here at Children’s National. With research interests covering nearly aspect of pediatric cancer care, our work is making great advancements in childhood cancer.

Nobuyuki Ishibashi

Cortical dysmaturation in congenital heart disease

Nobuyuki Ishibashi

On Jan. 4, 2019, Nobuyuki Ishibashi, M.D., the director of the Cardiac Surgery Research Laboratory and an investigator with the Center for Neuroscience Research at Children’s National Health System, published a review in Trends in Neurosciences about the mechanisms of cortical dysmaturation, or disturbances in cortical development, that can occur in children born with congenital heart disease (CHD). By understanding the early-life impact and relationship between cardiac abnormalities and cortical neuronal development, Dr. Ishibashi and the study authors hope to influence strategies for neonatal neuroprotection, mitigating the risk for developmental delays among CHD patients.

Dr. Ishibashi answers questions about this review and CHD-neurodevelopmental research:

  1. Tell us more about your research. Why did you choose to study these interactions in this patient population?

My research focuses on studying how CHD and neonatal cardiac surgery affect the rapidly-developing brain. Many children with CHD, particularly the most complex anomalies, suffer from important behavioral anomalies and neurodevelopmental delays after cardiac surgery. As a surgeon scientist, I want to optimize treatment strategy and develop a new standard of care that will reduce neurodevelopmental impairment in our patients.

  1. How does this study fit into your larger body of work? What are a few take-home messages from this paper?

Our team and other laboratories have recently identified a persistent perinatal neurogenesis that targets the frontal cortex – the brain area responsible for higher-order cognitive functions. The main message from this article is that further understanding of the cellular and molecular mechanisms underlying cortical development and dysmaturation will likely help to identify novel strategies to treat and improve outcomes in our patients suffering from intellectual and behavioral disabilities.

  1. What do you want pediatricians and researchers to know about this study? Why is it important right now?

Although the hospital mortality risk is greatly reduced, children with complex CHD frequently display subsequent neurological disabilities affecting intellectual function, memory, executive function, speech and language, gross and fine motor skills and visuospatial functions. In addition to the impact of the neurological morbidity on the patients themselves, the toll on families and society is immense. Therefore it is crucial to determine the causes of altered brain maturation in CHD.

  1. How do you envision this research influencing future studies and pediatric health outcomes? As a researcher, how will you proceed?

In this article we placed special emphasis on the need for well-designed preclinical studies to define disturbances in cortical neurogenesis due to perinatal brain injury. I believe that further study of the impact of hypoxemia on brain development is of broad relevance — not just for children with congenital heart disease, but for other populations where intellectual and behavioral dysfunctions are a source of chronic morbidity, such as survivors of premature birth.

  1. What discoveries do you envision being at the forefront of this field?

One of the important questions is: During which developmental period, prenatal or postnatal, is the brain most sensitive to developmental and behavioral disabilities associated with hypoxemia? Future experimental models will help us study key effects of congenital cortical development anomalies on brain development in children with CHD.

  1. What impact could this research make? What’s the most striking finding and how do you think it will influence the field?

Although cortical neurogenesis at fetal and adult stages has been widely studied, the development of the human frontal cortex during the perinatal period has only recently received greater attention as a result of new identification of ongoing postnatal neurogenesis in the region responsible for important intellectual and behavioral functions. Children’s National is very excited with the discoveries because it has opened new opportunities that may lead to regeneration and repair of the dysmature cortex. If researchers identify ways to restore endogenous neurogenic abilities after birth, the risk of neurodevelopment disabilities and limitations could be greatly reduced.

  1. Is there anything else you would like to add that we didn’t ask you about? What excites you about this research?

In this article we highlight an urgent need to create a truly translational area of research in CHD-induced brain injury through further exploration and integration of preclinical models. I’m very excited about the highly productive partnerships we developed within the Center for Neuroscience Research at Children’s National, led by an internationally-renowned developmental neuroscientist, Vittorio Gallo, Ph.D., who is a co-senior author of this article. Because of our collaboration, my team has successfully utilized sophisticated and cutting-edge neuroscience techniques to study brain development in children born with CHD. To determine the causes of altered brain maturation in congenital heart disease and ultimately improve neurological function, we believe that a strong unity between cardiovascular and neuroscience research must be established.

Additional study authors include Camille Leonetti, Ph.D., a postdoctoral research fellow with the Center for Neuroscience Research and Children’s National Heart Institute, and Stephen Back, M.D., Ph.D., a professor of pediatrics at Oregon Health and Science University.

The research was supported by multiple grants and awards from the National Institutes of Health, inclusive of the National Heart Lung and Blood Institute (RO1HL139712), the National Institute of Neurological Disorders and Stroke (1RO1NS054044, R37NS045737, R37NS109478), the National Institute on Aging (1RO1AG031892-01) and the National Institute of Child Health and Human Development (U54HD090257).

Additional support for this review was awarded by the American Heart Association (17GRNT33370058) and the District of Columbia Intellectual and Developmental Disabilities Research Center, which is supported through the Eunice Kennedy Shriver National Institute of Child Health and Human Development program grant 1U54HD090257.

AlgometRX

Breakthrough device objectively measures pain type, intensity and drug effects

AlgometRX

Clinical Research Assistant Kevin Jackson uses AlgometRx Platform Technology on Sarah Taylor’s eyes to measure her degree of pain. Children’s National Medical Center is testing an experimental device that aims to measure pain according to how pupils react to certain stimuli. (AP Photo/Manuel Balce Ceneta)

Pediatric anesthesiologist Julia C. Finkel, M.D., of Children’s National Health System, gazed into the eyes of a newborn patient determined to find a better way to measure the effectiveness of pain treatment on one so tiny and unable to verbalize. Then she realized the answer was staring back at her.

Armed with the knowledge that pain and analgesic drugs produce an involuntary response from the pupil, Dr. Finkel developed AlgometRx, a first-of-its-kind handheld device that measures a patient’s pupillary response and, using proprietary algorithms, provides a diagnostic measurement of pain intensity, pain type and, after treatment is administered, monitors efficacy. Her initial goal was to improve the care of premature infants. She now has a device that can be used with children of any age and adults.

“Pain is very complex and it is currently the only vital sign that is not objectively measured,” says Dr. Finkel, who has more than 25 years of experience as a pain specialist. “The systematic problem we are facing today is that healthcare providers prescribe pain medicine based on subjective self-reporting, which can often be inaccurate, rather than based on an objective measure of pain type and intensity.” To illustrate her point, Dr. Finkel continues, “A clinician would never prescribe blood pressure medicine without first taking a patient’s blood pressure.”

The current standard of care for measuring pain is the 0-to-10 pain scale, which is based on subjective, observational and self-reporting techniques. Patients indicate their level of pain, with zero being no pain and ten being highest or most severe pain. This subjective system increases the likelihood of inaccuracy, with the problem being most acute with pediatric and non-verbal patients. Moreover, Dr. Finkel points out that subjective pain scores cannot be standardized, heightening the potential for misdiagnosis, over-treatment or under-treatment.

Dr. Finkel, who serves as director of Research and Development for Pain Medicine at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, says that a key step in addressing the opioid crisis is providing physicians with objective, real-time data on a patient’s pain level and type, to safely prescribe the right drug and dosage or an alternate treatment.,

She notes that opioids are prescribed for patients who report high pain scores and are sometimes prescribed in cases where they are not appropriate. Dr. Finkel points to the example of sciatica, a neuropathic pain sensation felt in the lower back, legs and buttocks. Sciatica pain is carried by touch fibers that do not have opioid receptors, which makes opioids an inappropriate choice for treating that type of pain.

A pain biomarker could rapidly advance both clinical practice and pain research, Dr. Finkel adds. For clinicians, the power to identify the type and magnitude of a patient’s nociception (detection of pain stimuli) would provide a much-needed scientific foundation for approaching pain treatment. Nociception could be monitored through the course of treatment so that dosing is targeted and personalized to ensure patients receive adequate pain relief while reducing side effects.

“A validated measure to show whether or not an opioid is indicated for a given patient could ease the health care system’s transition from overreliance on opioids to a more comprehensive and less harmful approach to pain management,” says Dr. Finkel.

She also notes that objective pain measurement can provide much needed help in validating complementary approaches to pain management, such as acupuncture, physical therapy, virtual reality and other non-pharmacological interventions.

Dr. Finkel’s technology, called AlgometRx, has been selected by the U.S. Food and Drug Administration (FDA) to participate in its “Innovation Challenge: Devices to Prevent and Treat Opioid Use Disorder.” She is also the recipient of Small Business Innovation Research (SBIR) grant from the National Institute on Drug Abuse.

Photo of nurses in the cardiac intensive care unit at Children's National

Can pyruvate support metabolic function following heart surgery?

Photo of nurses in the cardiac intensive care unit at Children's National

Nurses rush a child to the cardiac intensive care unit at Children’s National Health System.

Can pyruvate, the end product of glycolysis, help improve cardiovascular function in children who have cardiopulmonary bypass surgery and suffer from low cardiac output syndrome (LCOS)? This question is one that Rafael Jaimes, Ph.D., a staff scientist at Children’s National Heart Institute, a division of Children’s National Health System, is studying, thanks to a two-year grant from the American Heart Association.

The competitive grant awards Dr. Jaimes with $110,000 to study how pyruvate may help improve cardiac output among pediatric patients with LCOS. The compound aims to stimulate metabolic function, now treated by inotropic agents, such as dobutamine and milrinone. These agents ensure optimal delivery of oxygen from the heart to the brain, as well as to other organs in the body, following heart surgery. While these agents help patients with cardiac dysfunction, there is still a critical need for safe and effective therapies.

“If there’s any detriment in cardiac output, the heart’s function begins to degrade,” explains Dr. Jaimes. “You see a downward spiral effect with reduced cardiac output because the heart is dependent on its own perfusion. It needs to pump blood throughout the body to survive.”

This is where the pyruvate study, and the grant, will be applied: Can pyruvate target the essential muscle of the heart and reverse this cardiac destabilization – and as soon as possible?

“By increasing the metabolic output of the heart’s local muscle, cardiac output increases,” Dr. Jaimes explains. “That’s going to lead to better recovery.”

Better recovery could be measured by how fast a child recovers from heart surgery as well as how much time they spend in the hospital, clinically referred to as throughput. A faster recovery could also influence a child’s quality of life and reduce overall health care costs.

Based on preliminary data that shows pyruvate improves cardiac function in experimental models after ischemic insult, which is what happens when pediatric patients undergo cardiac surgery, Dr. Jaimes believes the results will likely replicate themselves in his preclinical models.

To start, he’ll test pyruvate using 100 blood samples and discarded tissue from patients. The blood samples will be tested for metabolic markers, including measured pyruvate levels.

Part of what encouraged Dr. Jaimes to study how this compound could complement or replace standard therapies was the encouragement he received from his mentors in the field.

“Nobody has looked into using pyruvate for almost 30 years,” says Dr. Jaimes. “It’s not commercially favorable, there’s no patent on it, it doesn’t have a lot of marketability and there are no financial incentives, so it’s been put aside.”

As part of a discussion with cardiologists at a medical conference in Washington, Dr. Jaimes brought up the idea of using pyruvate for pediatric heart surgeries and received positive feedback.

“Once everyone’s eyes lit up, I knew I was on to something,” says Dr. Jaimes about the encouragement he received to pursue this study.

“You put lactate and glucose in your IV solutions,” adds Dr. Jaimes. “Pyruvate is an essential nutrient. It’s almost an essential sugar so there’s no reason not to put it in. If these cardiologists are intrigued by the project, maybe the American Heart Association will be, too.”

In addition to funding the study, which could support future research about how metabolic makers in the blood can be stimulated to fast-track recovery following heart surgery, the American Heart Association grant is specific to pediatric health outcomes.

“The current state of pharmaceutical treatment for patients recovering from cardiac surgery is designed and created for adults,” says Dr. Jaimes. “From our research in pediatrics, we know that children aren’t small adults.”

Dr. Jaimes explains that children are different on an anatomical and physiological level. Their cells even look and function different, compared to adult cells, because they haven’t matured yet.

While congenital heart defects are rare, they affect 1 percent, or 40,000 births worldwide, they often require multiple surgeries throughout a child’s lifespan. LCOS impacts 25 percent of patients following cardiopulmonary bypass and the timing of treatment is important. In severe cases, insufficient cardiac output following surgery could impact a child’s long-term development, ranging from reasoning, learning, attention and executive function, to developing age-appropriate language and social skills.

“The metabolic insufficiencies I’m looking at, which may help improve the muscle function of the heart, are just one piece of a bigger puzzle in pediatric cardiology,” notes Dr. Jaimes about ongoing research at Children’s National Heart Institute. “We already know pyruvate is safe. We just have to see if it’s effective in supporting a patient’s recovery in the intensive care unit.”

Dr. Jaimes will work with his research mentor Nikki Posnack, Ph.D., assistant professor at the Children’s National Heart Institute, on this preclinical study throughout the grant’s lifecycle, which starts in early January 2019 and ends in late December 2020.

ChildrensSV_Seal

Surgery team attains prestigious level 1 verification

ChildrensSV_Seal

Children’s National Health System has been verified as a Level 1 Children’s Surgery Center by the American College of Surgeons Children’s Surgery Verification Quality Improvement Program (ACS CSV). This distinction recognizes surgery centers whose quality improvement programs have measurably improved pediatric surgical quality, prevented complications, reduced costs and saved lives.

“We are extremely proud to achieve the prestigious Level 1 Surgery Verification,” says Anthony Sandler, M.D., senior vice president and surgeon-in-chief of the Joseph E. Robert, Jr., Center for Surgical Care at Children’s National. “The rigorous standards and focus on meeting the unique needs of each patient make this distinction particularly meaningful to us.”

The CSV program was developed to improve the safety and quality of children’s surgical care. Level 1 designation is given to hospitals who meet the standards for care outlined in Optimal Resources for Children’s Surgical Care 2015. These standards help to ensure children facing surgery receive care under a multidisciplinary program with quality improvement and safety processes, data collection and appropriate pediatric resources.

Children’s National is one of just twelve children’s hospitals nationwide to have earned this verification. To become a verified center, Children’s National met the essential criteria for staffing, training, facility infrastructure and protocols for care, ensuring its ability to appropriately care for pediatric surgical patients.

Shriprasad Deshpande

Accelerating advanced cardiac treatments for tiny patients

Shriprasad Deshpande

Shriprasad Deshpande, M.B.B.S., M.S., a pediatric cardiologist, joins Children’s National Health System as the director of the advanced cardiac therapies and heart transplant program.

Shriprasad Deshpande, M.B.B.S., M.S., a pediatric cardiologist, has joined Children’s National Health System as the director of the advanced cardiac therapies and heart transplant program.

Dr. Deshpande, an intensivist and heart failure and transplant cardiologist, will work within the Children’s National Heart Institute (the Division of Cardiology and the Division of Cardiac Intensive Care) to guide the diagnosis and treatment of pediatric heart failure. He will also work with researchers, surgeons and engineers to accelerate the field of biomedical research and make it easy for patients to receive advanced therapies, such as mechanical pumps to support circulation, and, if necessary, heart transplant.

“Subspecializing in personalized care is critical for all patients right now, not just adults,” says Dr. Deshpande. “This is one of the reasons I’m looking forward to working with Children’s National, a leader in the many subdivisions of pediatric medicine and research.

“Our priority is to recognize the special needs of infants and children as they relate to heart failure,” he adds. “We want to provide the best care and advance science at the same time.”

As an example, a grant from the National Institutes of Health enabled Dr. Deshpande to test ventricular assist devices for infants. Through another NIH grant, he analyzed the safety of organ transplants by testing a donor’s DNA, instead of conducting invasive biopsies in children.

“The field of cardiology is in a unique position now to take advantage of discoveries happening in science, technology and engineering,” says Dr. Deshpande. “In addition to thinking about the logistics of heart transplants, we’re thinking about how we can delay the need for a heart transplant, understand how to grow tissue better and utilize technology to improve these outcomes. We’re investing in a child’s quality of life.”

As the medical director of Mechanical Circulatory Support Program at Children’s Healthcare of Atlanta, Dr. Deshpande led the mechanical circulatory support program and created a subspecialty clinic to provide treatment for pediatric heart failure patients. He started the Muscular Dystrophy Cardiomyopathy clinic, which analyzes and treats cardiovascular comorbidities associated with muscular dystrophy. While he was an assistant professor of pediatrics at Emory University School of Medicine, he created a curriculum for pediatric cardiologists and for nurses training in the cardiac intensive critical care unit.

Dr. Deshpande has published more than 70 studies and abstracts and will oversee clinical practice models, subspecialty clinics and academic research efforts at Children’s. His current research portfolio, inclusive of grants from the NIH and other funding agencies, is robust and varied: He’s studying how to improve mechanical support for complex heart disease patients, how to improve the performance of current pumps and how to develop new algorithms for these devices. Improving the diagnosis of transplant rejection, using technology to improve compliance and using new technologies to diagnose rejection, without invasive biopsies, are his other research interests.

Dr. Deshpande serves as the chair of the scientific committee at the nonprofit Enduring Hearts and is on the American Heart Association’s Strategically Focused Research Network committee.

neuron

Children’s National to host 29th Annual Pediatric Neurology Update

neuron

The Children’s National Health System Center for Neuroscience and Behavioral Medicine is proud to host the 29th Annual Pediatric Neurology Update course.

This year’s course will focus on three critical areas in pediatric neuroscience and neurodevelopment: epilepsy with focuses on innovations in epilepsy surgery and new therapeutics; tuberous sclerosis including neurosurgical advances and transition to adulthood; and autism spectrum disorder with emphasis on new understandings and pre-requisites for an “Autism Friendly Hospital.”

We invite you to join us for presentations from renowned experts in the field in this full-day, CME accredited event on April 11, 2019 at the Bethesda North Marriott Hotel & Conference Center in Rockville, MD.

For more information and to register, visit ChildrensNational.org/NeurologyUpdate.

Charles Berul and Rohan Kumthekar demonstrate tiny pacemaker

A new prototype for tiny pacemakers, faster surgery

Charles Berul and Rohan Kumthekar demonstrate tiny pacemaker

Charles Berul, M.D., chief of cardiology at Children’s National, and Rohan Kumthekar, M.D., a cardiology fellow working in Dr. Berul’s bioengineering lab at the Sheikh Zayed Institute for Pediatric Surgical Innovation, explore ways to make surgical procedures for infants and children less invasive.

Rohan Kumthekar, M.D., a cardiology fellow working in Dr. Charles Berul’s bioengineering lab at the Sheikh Zayed Institute for Pediatric Surgical Innovation, part of Children’s National Health System, presented a prototype for a miniature pacemaker at the American Heart Association’s Scientific Sessions 2018  on Sunday, Nov. 11. The prototype, approximately 1 cc, the size of an almond, is designed to make pacemaker procedures for infants less invasive, less painful and more efficient, measured by shorter surgeries, faster recovery times and reduced medical costs.

Kumthekar, a Cardiovascular Disease in the Young Travel Award recipient, delivered his oral abstract, entitled “Minimally Invasive Percutaneous Epicardial Placement of a Custom Miniature Pacemaker with Leadlet under Direct Visualization,” as part of the Top Translational Science Abstracts in Pediatric Cardiology session.

“As cardiologists and pediatric surgeons, our goal is to put a child’s health and comfort first,” says Kumthekar. “Advancements in surgical fields are tending toward procedures that are less and less invasive. There are many laparoscopic surgeries in adults and children that used to be open surgeries, such as appendix and gall bladder removals. However, placing pacemaker leads on infants’ hearts has always been an open surgery. We are trying to bring those surgical advances into our field of pediatric cardiology to benefit our patients.”

Instead of using open-chest surgery, the current standard for implanting pacemakers in children, doctors could implant the tiny pacemakers by making a relatively tiny 1-cm incision just below the ribcage.

“The advantage is that the entire surgery is contained within a tiny 1-cm incision, which is what we find groundbreaking,” says Kumthekar.

With the help of a patented two-channel, self-anchoring access port previously developed by Berul’ s research group, the operator can insert a camera into the chest to directly visualize the entire procedure. They can then insert a sheath (narrow tube) through the second channel to access the pericardial sac, the plastic-like cover around the heart. The leadlet, the short extension of the miniature pacemaker, can be affixed onto the surface of the heart under direct visualization. The final step is to insert the pacemaker into the incision and close the skin, leaving a tiny scar instead of two large suture lines.

The median time from incision to implantation in this thoracoscopic surgery study was 21 minutes, and the entire procedure took less than an hour on average. In contrast, pediatric open-heart surgery could take up to several hours, depending on the child’s medical complexities.

“Placing a pacemaker in a small child is different than operating on an adult, due to their small chest cavity and narrow blood vessels,” says Kumthekar. “By eliminating the need to cut through the sternum or the ribs and fully open the chest to implant a pacemaker, the current model, we can cut down on surgical time and help alleviate pain.”

The miniature pacemakers and surgical approach may also work well for adult patients with limited vascular access, such as those born with congenital heart disease, or for patients who have had open-heart surgery or multiple previous cardiovascular procedures.

The miniature pacemakers passed a proof-of-concept simulation and the experimental model is now ready for a second phase of testing, which will analyze how the tailored devices hold up over time, prior to clinical testing and availability for infants.

“The concept of inserting a pacemaker with a 1-cm incision in less than an hour demonstrates the power of working with multidisciplinary research teams to quickly solve complex clinical challenges,” says Charles Berul, M.D., a guiding study author, electrophysiologist and the chief of cardiology at Children’s National.

Berul’s team from Children’s National collaborated with Medtronic PLC, developers of the first implantable pacemakers, to develop the prototype and provide resources and technical support to test the minimally-invasive surgery.

The National Institutes of Health provided a grant to Berul’s research team to develop the PeriPath, the all-in-one 1-cm access port, which cut down on the number of incisions by enabling the camera, needle, leadlet and pacemaker to be inserted into one port, through one tiny incision.

Other study authors listed on the abstract presented at Scientific Sessions 2018 include Justin Opfermann, M.S., Paige Mass, B.S., Jeffrey P. Moak, M.D., and Elizabeth Sherwin, M.D., from Children’s National, and Mark Marshall, M.S., and Teri Whitman, Ph.D., from Medtronic PLC.

Nikki Gillum Posnack

Do plastic chemicals contribute to the sudden death of patients on dialysis?

Nikki Gillum Posnack

Nikki Posnack, Ph.D., assistant professor with the Children’s National Heart Institute, continues to explore how repeat chemical exposure from medical devices influences cardiovascular function.

In a review published in HeartRhythmNikki Posnack, Ph.D., an assistant professor at the Children’s National Heart Institute, and Larisa Tereshchenko, M.D., Ph.D., FHRS, a researcher with the Knight Cardiovascular Institute at Oregon Health and Science University, establish a strong foundation for a running hypothesis: Replacing BPA- and DEHP- leaching plastics for alternative materials used to create medical devices may help patients on dialysis, and others with impaired immune function, live longer.

While Drs. Tereshchenko and Posnack note clinical studies and randomized controlled trials are needed to test this theory, they gather a compelling argument by examining the impact exposure to chemicals from plastics used in dialysis have on a patient’s short- and long-term health outcomes, including sudden cardiac death (SCD).

“As our society modifies our exposure to plastics to mitigate health risks, we should think about overexposure to plastics in a medical setting,” says Posnack. “The purpose of the review in HeartRhythm is to gather data about the impact chemical compounds, leached from plastic devices, have on cardiovascular outcomes for patients spending prolonged periods of time in the hospital.”

In this review, the authors explore chemical risk exposures in a medical setting, starting with factors that influence sudden cardiac death (SCD) among dialysis patients.

Why study dialysis patients?

SCD in dialysis patients accounts for one-third of deaths in this population. This prompts a need to develop prevention strategies, especially among patients with end-stage renal disease (ESRD).

The highest mortality rate observed among dialysis patients is during the first year of hemodialysis, a dialysis process that requires a machine to take the place of the kidneys and remove waste from the bloodstream and replenish it with minerals, such as potassium, sodium and calcium. During this year, mortality during hemodialysis is observed more frequently during the first three months of treatment, especially among older patients.

Possible reasons for an increased risk of an earlier death include chemical exposure, which is casually associated with altered cardiac function, as well as genetic risks for irregular heart rhythms and heart failure. In the HeartRhythm review, Drs. Tereshchenko and Posnack analyze factors that influence mortality:

Hemodialysis treatment, dialysis, is associated with plastic chemical exposure

Drs. Tereshchenko and Posnack note that dialysis tubing and catheters are commonly manufactured using polyvinyl chloride (PVC) polymers. The phthalate plastics used to soften PVC can easily leech if exposed to lipid-like substances, like blood. Research shows phthalate chemical concentrations increase during a four-hour dialysis.

Di(2-ethylhexyl) phthalate (DEHP) is a common plastic used to manufacture dialysis tubes, thanks to its structure and economy.

Bisphenol-A (BPA) is another common material used in medical device manufacturing. From the membranes of medical tools to resins, or external coatings and adhesives, BPA leaves behind a chemical residue on PVC medical devices.

In reviewing the research, the authors find dialysis patients are often exposed to high levels of DEHP and BPA. The amount of exposure to these chemicals varies in regards to room temperature, time of contact, other circuit coatings and the flow rate of dialysis. A faster flow rate correlates with reductions in chemical leaching and lower mortality rates.

Plastic chemical exposure is casually associated with altered cardiac function

Drs. Tereshchenko and Posnack note a causal relationship already exists between chemicals absorbed from plastics and cardiovascular outcomes.

Dr. Posnack’s previous research found BPA concentrations impaired electrical conduction in neonatal cardiomyocytes – young, developing heart cells – potentially altering the heart’s normal rhythm and function.

To the best of their knowledge, no clinical research has been conducted on DEHP exposure and SCD. However, proof-of-concept models find in vivo phthalate exposure alters autonomic regulation, which can slow down natural heart-rate rhythm and create a lag in recovery time to stressful stimuli. For humans, this type of stressful stimulation would be equivalent to recovering from a bike ride, car accident, or in this case, ongoing dialysis treatment with impaired immune function.

In other models, BPA exposure has been shown to cause bradycardia, or a delayed heart rate. In excised whole heart models, BPA has also been shown to alter cardiac electrical activity.

Abnormal electrophysiological substrate in end-stage renal disease

Since the heart and kidneys work in tandem to transport blood throughout the body, and manage vital functions, such as our heart rate, blood flow and breathing, the authors cite additional factors that lead to ongoing heart and kidney problems, with a look at end-stage renal disease (ESRD).

General heart-function kidney risks include abnormal electrophysiological (EP) substrate, the underlying electrical activity of the cardiac tissue, and genetic risk factors, including the TBX3 gene, a gene associated with a unique positioning of the heart and SCD.

“We don’t want to cite alarm about having a medical procedure or about relying on external help, such as dialysis, for proper kidney function,” says Posnack. “Especially since dialysis is a life-saving medical intervention for patients with inadequate kidney function.”

Pre-existing abnormal EP substrate interacts with plastic chemical exposure in incident dialysis, which increases risk of SCD in genetically predisposed ESRD patients

To summarize their findings, Drs. Tereshchenko and Posnack list a handful of support areas, starting with observations about reductions in cardiovascular mortality and SCD following kidney transplants. They note hemodialysis catheters are associated with larger DEHP exposure and a higher risk of SCD, compared to arteriovenous fistulas, highways surgically created to connect blood from the artery to the vein.

Drs. Posnack and Tereshchenko also note a correlative observation about higher SCD rates observed six hours after hemodialysis, when peak levels of DEHP and BPA are circulating in the bloodstream.

To compare and control for these factors among dialysis patients, the researchers cite different mortality patterns with hemodialysis and peritoneal dialysis. Patients on hemodialysis experience higher mortality during the first year of treatment, compared to peritoneal dialysis, who have higher mortality rates after the second year of treatment. Hemodialysis relies on a machine to take the place of kidney function, while peritoneal dialysis relies on a catheter, a small tube surgically inserted into the stomach.

“Our goal is to build on our previous research findings by analyzing variables that have yet to be studied before, and to update the field of medicine in the process,” says Dr. Posnack. “This includes investigating the cardiovascular risks of using BPA- and DEHP-materials to construct medical devices. Ultimately, we hope to determine whether plastic materials contribute to cardiovascular risks, and investigate whether patients might benefit from the use of alternative materials for medical devices.

Drs. Tereshchenko and Posnack note that despite the associations between chemical exposure from medical devices and increased cardiovascular risks, there are no restrictions in the United States on the use of phthalates and BPA chemicals used to manufacture medical devices.

Their future research will explore how replacing BPA- and DEHP-leaching plastics influence mortality and morbidity rates of ESRD patients on dialysis, as well as other patients exposed to repeat chemical exposure, such as patients having cardiac surgery.

“We want to make sure we identify and then work to minimize any potential risks of plastic exposure in a medical setting,” adds Dr. Posnack. “Our goal is to put the health and safety of patients first.”

Dr. Posnack’s research is funded by two grants (R01HL139472, R00ES023477) from the National Institutes of Health.

Dr.-Jonas.-WSPCHS

Snapshot: The Sixth Scientific Meeting of the World Society for Pediatric and Congenital Heart Surgery

Dr.-Jonas.-WSPCHS

Dr. Richard Jonas shows surgical advancements using 3D heart models, which participants could bring back to their host institutions.

On July 22, 2018, more than 700 cardiac specialists met in Orlando, Fla. for the Sixth Scientific Meeting of the World Society for Pediatric and Congenital Heart Surgery (WSPCHS 2018).

The five-day conference hosted a mix of specialists, ranging from cardiothoracic surgeons, cardiologists and cardiac intensivists, to anesthesiologists, physician assistants and nurse practitioners, representing 49 countries and six continents.

To advance the vision of WSPCHS – that every child born with a congenital heart defect should have access to appropriate medical and surgical care – the conference was divided into eight tracks: cardiac surgery, cardiology, anesthesia, critical care, nursing, perfusion, administration and training.

Richard Jonas, M.D., outgoing president of WSPCHS and the division chief of cardiac surgery at Children’s National Health System, provided the outgoing presidential address, delivered the keynote lecture on Transposition of the Great Arteries (TGA) and guided a surgical skills lab with printed 3-D heart models.

Other speakers from Children’s National include:

  • Gil Wernovsky, M.D., a cardiac critical care specialist, presented on the complex physiology of TGA, as well as long-term consequences in survivors of neonatal heart surgery, including TGA and single ventricle.
  • Mary Donofrio, M.D., a cardiologist and director of the Fetal Heart Program, presented “Prenatal Diagnosis: Improving Accuracy and Planning Delivery for babies with TGA,” “Systemic Venous Abnormalities in the Fetus,” “Intervention for Fetal Lesions Causing High Output Heart Failure” and “Fetal Cardiac Care – Can We Improve Outcomes by Altering the Natural History of Disease?”
  • Gerard Martin, M.D., a cardiologist and medical director of global services, presented “Is the Arterial Switch as Good as We Thought It Would Be?” and “Impact, MAPIT, NCPQIC – How and Why We Should All Embrace Quality Metrics.”
  • Pranava Sinha, M.D., a cardiac surgeon, presented the abstract “Cryopreserved Valved Femoral Vein Homografts for Right Ventricular Outflow Tract Reconstruction in Infants.”

Participants left with knowledge about how to diagnose and treat complex congenital heart disease, and an understanding of the long-term consequences of surgical management into adulthood. In addition, they received training regarding standardized practice models, new strategies in telemedicine and collaborative, multi-institutional research.

“It was an amazing experience for me to bring my expertise to a conference which historically concentrated on surgical and interventional care and long-term follow-up,” says Dr. Donofrio. “The collaboration between the fetal and postnatal care teams including surgeons, interventionalists and intensive care doctors enables new strategies to be developed to care for babies with CHD before birth. Our hope is that by intervening when possible in utero and by planning for specialized care in the delivery room, we can improve outcomes for our most complex patients”.

The Johns Hopkins University School of Medicine, Florida Board of Nursing, American Academy of Nurse Practitioners National Certification Program, American Nurses Credentialing Center and the American Board of Cardiovascular Perfusion provided continuing medical credits for eligible providers.

“I was so proud to be a member of the Children’s National team at this international conference,” notes Dr. Wernovsky. “We had to the opportunity to share our experience in fetal cardiology, outpatient cardiology, cardiac critical care, cardiac nursing and cardiac surgery with a worldwide audience, including surgical trainees, senior cardiovascular surgeons and the rest of the team members necessary to optimally care for babies and children with complex CHD. In addition, members of the nursing staff shared their research about advancements in the field. It was quite a success – both for our team and for all of the participants.”

Graph showing magnesium reduces arrhythmia risk

Magnesium helps prevent postsurgical arrhythmias in pediatric patients

Graph showing magnesium reduces arrhythmia risk

Magnesium (Mg) helps reduce arrhythmias, irregular heart rhythms, in adults. It also helps alleviate the symptoms of postoperative atrial fibrillation, or AFib, which can lead to blood clots, stroke and heart failure. Can it help prevent postsurgical arrhythmias in pediatric patients with congenital heart disease?

New research from Children’s National Health System finds a 25- or 50-mg dose of Mg used during congenital heart surgery (CHS) helps prevent arrhythmias, especially junctional ectopic tachycardia (JET) and atrial tachycardia (AT), common arrhythmias following CHS, according to a study published in the August 2018 edition of The Journal of Thoracic and Cardiovascular Surgery.

To reach this conclusion, the researchers separated 1,871 CHS patients from Children’s National into three groups: a control group of 750 patients who had surgery without Mg, a group of 338 patients receiving a 25-mg /kg dose of Mg during surgery and a group of 783 patients receiving a 50-mg/kg dose of Mg during surgery. The data looked at CHS cases over eight years, from 2005 to 2013, to determine if Mg administration during surgery alleviates postoperative arrhythmias and if the amount, measured by a 25- or 50-mg/kg dose, makes a difference.

“This study, the first conducted in pediatric patients, finds administering magnesium during congenital heart surgery reduces the likelihood of postsurgical arrhythmias,” says Charles Berul, M.D., a study author and the chief of cardiology at Children’s National. “We don’t detect a dose-dependent relationship, which means a small or larger amount of magnesium is equally effective at preventing arrhythmias following surgery.”

The researchers found that up to one-third of CHS patients experience postoperative arrhythmias, with JET and AT accounting for more than two-thirds of arrhythmias following CHS. They note that despite the administration of Mg during surgery, there continues to be a high incidence of postoperative arrhythmias – affecting 18 percent or about one in five CHS patients.

“We hope this study guides future research to see if adding new or additional agents to magnesium eliminates, or further reduces, postoperative arrhythmias,” notes Dr. Berul. “For now, we’re happy to find an algorithm to put into practice and to share with other medical centers, as a way to help pediatric patients recover from congenital heart surgery—stronger, faster and with a reduced risk of complications.”

The researchers note that postoperative arrhythmias impact the recovery period of CHS, increase the duration of intubation and CICU stay and prolong hospital stay.

Making the grade: Children’s National is nation’s Top 5 children’s hospital

Children’s National rose in rankings to become the nation’s Top 5 children’s hospital according to the 2018-19 Best Children’s Hospitals Honor Roll released June 26, 2018, by U.S. News & World Report. Additionally, for the second straight year, Children’s Neonatology division led by Billie Lou Short, M.D., ranked No. 1 among 50 neonatal intensive care units ranked across the nation.

Children’s National also ranked in the Top 10 in six additional services:

For the eighth year running, Children’s National ranked in all 10 specialty services, which underscores its unwavering commitment to excellence, continuous quality improvement and unmatched pediatric expertise throughout the organization.

“It’s a distinct honor for Children’s physicians, nurses and employees to be recognized as the nation’s Top 5 pediatric hospital. Children’s National provides the nation’s best care for kids and our dedicated physicians, neonatologists, surgeons, neuroscientists and other specialists, nurses and other clinical support teams are the reason why,” says Kurt Newman, M.D., Children’s President and CEO. “All of the Children’s staff is committed to ensuring that our kids and families enjoy the very best health outcomes today and for the rest of their lives.”

The excellence of Children’s care is made possible by our research insights and clinical innovations. In addition to being named to the U.S. News Honor Roll, a distinction awarded to just 10 children’s centers around the nation, Children’s National is a two-time Magnet® designated hospital for excellence in nursing and is a Leapfrog Group Top Hospital. Children’s ranks seventh among pediatric hospitals in funding from the National Institutes of Health, with a combined $40 million in direct and indirect funding, and transfers the latest research insights from the bench to patients’ bedsides.

“The 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver exceptional care across a range of specialties and deserve to be highlighted,” says Ben Harder, chief of health analysis at U.S. News. “Day after day, these hospitals provide state-of-the-art medical expertise to children with complex conditions. Their U.S. News’ rankings reflect their commitment to providing high-quality care.”

The 12th annual rankings recognize the top 50 pediatric facilities across the U.S. in 10 pediatric specialties: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology and urology. Hospitals received points for being ranked in a specialty, and higher-ranking hospitals receive more points. The Best Children’s Hospitals Honor Roll recognizes the 10 hospitals that received the most points overall.

This year’s rankings will be published in the U.S. News & World Report’s “Best Hospitals 2019” guidebook, available for purchase in late September.