Critical Care

AI: The “single greatest tool” for improving access to pediatric healthcare

Attendees at the inaugural symposium on AI in Pediatric Health and Rare Diseases

The daylong event drew experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere to start building a community aimed at using data for the advancement of pediatric medicine.

The future of pediatric medicine holds the promise of artificial intelligence (AI) that can help diagnose rare diseases, provide roadmaps for safer surgeries, tap into predictive technologies to guide individual treatment plans and shrink the distance between patients in rural areas and specialty care providers.

These and dozens of other innovations were contemplated as scientists came together at the inaugural symposium on AI in Pediatric Health and Rare Diseases, hosted by Children’s National Hospital and the Fralin Biomedical Research Institute at Virginia Tech. The daylong event drew experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere to start building a community aimed at using data for the advancement of pediatric medicine.

“AI is the single greatest tool for improving equity and access to health care,” said symposium host Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator at the Sheikh Zayed Institute for Pediatric Surgical Innovation. “As a population, kids are vastly underrepresented in scientific research and resulting treatments, but pediatric specialties can use AI to provide medical care to kids more efficiently, more quickly and more effectively.”

What they’re saying

Scientists shared their progress in building digital twins to predict surgical outcomes, enhancing visualization to increase the precision of delicate interventions, establishing data command centers to anticipate risks for fragile patients and more. Over two dozen speakers shared their vision for the future of medicine, augmented by the power of AI:

  • Keynote speaker Subha Madhavan, Ph.D., vice president and head of AI and machine learning at Pfizer, discussed various use cases and the potential to bring drugs to market faster using real-world evidence and AI. She saw promise for pediatrics. “This is probably the most engaging mission: children’s health and rare diseases,” she said. “It’s hard to find another mission that’s as compelling.”
  • Brandon J. Nelson, Ph.D., staff fellow in the Division of Imaging, Diagnostics and Software Reliability at the Food and Drug Administration, shared ways AI will improve diagnostic imaging and reduce radiation exposure to patients, using more advanced image reconstruction and denoising techniques. “That is really our key take-home message,” he said. “We can get what … appear as higher dose images, but with less dose.”
  • Daniel Donoho, M.D., a neurosurgeon at Children’s National, introduced the audience to the potential of “Smart ORs”: operating rooms where systems can ingest surgery video and provide feedback and skill assessments. “We have to transform the art of surgery into a measurable and improvable scientific practice,” he said.
  • Debra Regier, M.D., chief of Genetics and Metabolism at Children’s National, discussed how AI could be used to diagnose and treat rare diseases by conducting deep dives into genetics and studying dysmorphisms in patients’ faces. Already, Children’s National has designed an app – mGene – that measures facial features and provides a risk score to help anyone in general practice determine if a child has a genetic condition. “The untrained eye can stay the untrained eye, and the family can continue to have faith in their provider,” she said.

What’s next

Linguraru and others stressed the need to design AI for kids, rather than borrow it from adults, to ensure medicine meets their unique needs. He noted that scientists will need to solve challenges, such as the lack of data inherent in rare pediatric disorders and the simple fact that children grow. “Children are not mini-adults,” Linguraru said. “There are big changes in a child’s life.”

The landscape will require thoughtfulness. Naren Ramakrishnan, Ph.D., director of the Sanghani Center for Artificial Intelligence & Analytics at Virginia Tech and symposium co-host, said that scientists are heading into an era with a new incarnation of public-private partnerships, but many questions remain about how data will be shared and organizations will connect. “It is not going to be business as usual, but what is this new business?” he asked.

Children’s National Hospital ranked #5 in the nation on U.S. News & World Report’s Best Children’s Hospitals Honor Roll

U.S. News BadgesChildren’s National Hospital in Washington, D.C., was ranked #5 in the nation on the U.S. News & World Report 2023-24 Best Children’s Hospitals annual rankings. This marks the seventh straight year Children’s National has made the Honor Roll list. The Honor Roll is a distinction awarded to only 10 children’s hospitals nationwide.

For the thirteenth straight year, Children’s National also ranked in all 10 specialty services, with eight specialties ranked in the top 10 nationally. In addition, the hospital was ranked best in the Mid-Atlantic for neonatology, cancer, neurology and neurosurgery.

“Even from a team that is now a fixture on the list of the very best children’s hospitals in the nation, these results are phenomenal,” said Kurt Newman, M.D., president and chief executive officer of Children’s National. “It takes a ton of dedication and sacrifice to provide the best care anywhere and I could not be prouder of the team. Their commitment to excellence is in their DNA and will continue long after I retire as CEO later this month.”

“Congratulations to the entire Children’s National team on these truly incredible results. They leave me further humbled by the opportunity to lead this exceptional organization and contribute to its continued success,” said Michelle Riley-Brown, MHA, FACHE, who becomes the new president and CEO of Children’s National on July 1. “I am deeply committed to fostering a culture of collaboration, empowering our talented teams and charting a bold path forward to provide best in class pediatric care. Our focus will always remain on the kids.”

“I am incredibly proud of Kurt and the entire team. These rankings help families know that when they come to Children’s National, they’re receiving the best care available in the country,” said Horacio Rozanski, chair of the board of directors of Children’s National. “I’m confident that the organization’s next leader, Michelle Riley-Brown, will continue to ensure Children’s National is always a destination for excellent care.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals and recognizes the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News.

“For 17 years, U.S. News has provided information to help parents of sick children and their doctors find the best children’s hospital to treat their illness or condition,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “Children’s hospitals that are on the Honor Roll transcend in providing exceptional specialized care.”

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

The eight Children’s National specialty services that U.S. News ranked in the top 10 nationally are:

The other two specialties ranked among the top 50 were cardiology and heart surgery, and urology.

CN-NIAID Symposium seeks ways to promote child health amid challenges

Panel members at the NIAID symposium

More than 30 million children seek emergency care each year, but 80 percent of these visits happen at hospitals that aren’t designed for pediatrics — a daunting figure during pandemics and other crises in healthcare. This considerable hurdle is one of many challenges that leaders in pediatric health came to discuss during a two-day symposium on promoting child health, hosted by Children’s National Hospital, the National Institute of Allergy and Infectious Diseases and the Pediatric Pandemic Network (PPN).

The symposium laid out a multitude of issues facing children and their doctors: growing mental health diagnoses, shrinking access to care in rural areas, asthma and eczema, winter respiratory surges and more.

Joelle Simpson, M.D., chief of emergency medicine at Children’s National and PPN principal investigator, said the network is drawing on expertise from 10 pediatric hospitals to ensure communities are better prepared for whatever challenges lie ahead, through training and support, collaboration among pediatric specialists, education on best practices and the promotion of equity and inclusion.

Built on a Health Resources and Services Administration grant, the network is focusing on four key areas: infectious disease and disease outbreaks, emergency and disaster management, mental and behavioral health, and health equity and community engagement. “This year, we know we are boiling the ocean as we come together,” Simpson said.

Miss the symposium? Check out the recordings available on YouTube, including the closing Q&A with many of the panelists and Sheryl Gay Stolberg, health policy reporter with the New York Times.

Day 1 of the 6th Annual Children’s National Hospital – NIAID Symposium

Day 2 of the 6th Annual Children’s National Hospital – NIAID Symposium

 

In the News: Regenerative brain cells and the circadian clock

Screen grab of Dr. Terry Dean and Dr. Vittorio Gallo webinar

“I am a pediatric intensivist, and I am very interested in some of the pathologies and conditions that I come across in the ICU. We hatched this question that revolved around the idea: what can we do for TBI (traumatic brain injury) patients to enhance their cellular regeneration? …  We looked at NG2-glia in particular, otherwise known as oligodendrocyte precursor cells. They are about 2-8% of the brain…. Do these cells respond to sleep and circadian rhythm? Is it a factor? Does it help? Does it hurt?”

Find out more about what Terry Dean, M.D., Ph.D., says he has learned about these and other questions through his recent research with interim Chief Academic Officer Vittorio Gallo, Ph.D. They join the Society for Neuroscience in a webinar on the circadian rhythms of these important brain cells and how their regeneration may be used someday to promote healing after brain injuries.

Future TBI treatments may hinge on understanding a new cell type

glial cells

Only recently have investigators begun to understand how a cell type – the NG2-glia – may respond to injuries, offering clues into the brain’s healing and regeneration.

Traumatic brain injury (TBI) afflicts 69 million people, including 630,000 children, worldwide each year. Yet only recently have investigators begun to understand how a cell type – the NG2-glia – may respond to injuries, offering clues into the brain’s healing and regeneration.

In a new paper published in GLIA, investigators from Children’s National Hospital reviewed 25 years of neuroscience research to lay out what’s known about the molecular response of these NG2-glia cells after TBI. Researchers said they see “a seductive possibility” that tapping into the regenerative potential of NG2-glia cells after neurotrauma could lead to therapies in the future. The impact could be profound, given that TBI is the leading cause of death among all people ages 1-44 and the global cost of this ‘silent epidemic’ is estimated to top $102 billion annually.

What they’re saying

“Our review lays out what’s known about these fascinating cells,” said Terry Dean, M.D., Ph.D., critical care specialist at Children’s National and investigator at the Center for Neuroscience Research (CNR). “NG2-glia are found throughout the brain, and we know that these cells undergo several dynamic changes in the hours, days and weeks after TBI. They are unique, and we want to understand their molecular characteristics to eventually enhance patients’ cellular recovery after TBI.”

Although only encompassing 4% to 8% of brain cells, these NG2-glia cells make up the largest population of regenerative cells in the adult central nervous system. In their article, Dean and Vittorio Gallo, Ph.D., Children’s National Research Institute interim director, lay out a number of unique features of these cells:

  • They proliferate, or multiply, and can form different cell types, especially after brain injuries.
  • They are structurally dynamic and can move and migrate throughout the cortex, including toward injury sites.
  • They appear to play a role in cell-to-cell signaling, which may prove vital after injuries.

The big picture

“As we study the brain after injuries, we hope our work will reveal the role these NG2-glia cells play in recovery, driving us to possible therapies,” Gallo said. “We believe the big answers will come through understanding the brain on a molecular level. This type of deep investigation is the foundation of our bench-to-bedside approach and positions researchers like Dr. Dean to find answers for our patients.”

Moving the field forward

Researchers have only begun to unlock how NG2-glia respond to injury, making this a fruitful area for research. Gallo, Dean and others at CNR hope to build on their knowledge about what happens to the brain immediately after an injury to learn more about what happens months after a debilitating impact. They are also considering new types of research models to expand their knowledge about cellular destruction, immune interaction and blood vessel compromise after different types of brain injuries.

“We look forward to the day when we have a truly targeted therapy for TBI patients,” Dean said. “Imagine the relief this could provide patients suffering from the persistent physical, cognitive and psychological disabilities that often accompany these brain injuries.”

President Biden, First Lady tour cardiac telehealth command center

President Joe Biden and First Lady Jill Biden paid a recent visit to the Cardiac Intensive Care Unit (CICU) at Children’s National Hospital, where leaders of our cardiology services toured them through the state-of-the-art telehealth command center embedded on the unit.

The big picture

Children’s National is pioneering the integration of telemedicine into CICU care. It’s one of the few pediatric hospitals in the world to do this.

Experts liken the telehealth command center to an ‘air traffic control tower’ for the most vulnerable patients with critical heart disease. The President and First Lady saw how complex the environment is, with real-time monitoring of all 26 high-risk patients in the CICU. The system combines traditional remote monitoring, video surveillance and artificial intelligence tools.

What this means

“With this technology, we’re helping to predict and prevent major adverse events,” said Ricardo Munoz, M.D., executive director of the Telemedicine Program and chief of the Division of Critical Care Medicine at Children’s National. “For example, our neuromonitoring system can help signal an impending brain injury before it happens.”

Dr. Munoz says President Biden expressed interest in the prevention strategy of adverse events and this new approach to caring for children with critical cardiac illness.

What they’re saying

  • “It was important to share with the Biden’s that caring for these kids is a long-term endeavor, not simply a single surgery or procedure to fix their heart abnormality,” said Yves d’Udekem, M.D., Ph.D., chief of Cardiac Surgery at Children’s National. “That means making sure they have the earliest diagnoses, the best treatments from surgeons and others who truly understand their condition, and a technologically advanced, attentive place to recover and heal as safely as possible.”
  • “Many people don’t believe that ‘pediatrics’ and ‘innovation’ can co-exist,” said Annette Ansong, M.D., medical director of Outpatient Cardiology at Children’s National. “During the Biden’s visit, they were at the crux of a novel way to closely monitor some of our sickest children with the added ability to predict bad events before they happen.”

Dr. Ansong hopes bringing awareness of these cardiac capabilities to the President and First Lady is the first of many steps in seeking support for children with congenital and acquired heart disease.

The best of 2022 from Innovation District

Abstract Happy 2022 New Year greeting card with light bulbA clinical trial testing a new drug to increase growth in children with short stature. The first ever high-intensity focused ultrasound procedure on a pediatric patient with neurofibromatosis. A low dose gene therapy vector that restores the ability of injured muscle fibers to repair. These were among the most popular articles we published on Innovation District in 2022. Read on for our full top 10 list.

1. Vosoritide shows promise for children with certain genetic growth disorders

Preliminary results from a phase II clinical trial at Children’s National Hospital showed that a new drug, vosoritide, can increase growth in children with certain growth disorders. This was the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature.
(2 min. read)

2. Children’s National uses HIFU to perform first ever non-invasive brain tumor procedure

Children’s National Hospital successfully performed the first ever high-intensity focused ultrasound (HIFU) non-invasive procedure on a pediatric patient with neurofibromatosis. This was the youngest patient to undergo HIFU treatment in the world.
(3 min. read)

3. Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Using a single injection of a low dose gene therapy vector, researchers at Children’s National restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle.
(3 min. read)

4. Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, was selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children.
(4 min. read)

5. New telehealth command center redefines hospital care

Children’s National opened a new telehealth command center that uses cutting-edge technology to keep continuous watch over children with critical heart disease. The center offers improved collaborative communication to better help predict and prevent major events, like cardiac arrest.
(2 min. read)

6. Monika Goyal, M.D., recognized as the first endowed chair of Women in Science and Health

Children’s National named Monika Goyal, M.D., M.S.C.E., associate chief of Emergency Medicine, as the first endowed chair of Women in Science and Health (WISH) for her outstanding contributions in biomedical research.
(2 min. read)

7. Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient

A team at Children’s National performed the first treatment with sonodynamic therapy utilizing low intensity focused ultrasound (LIFU) and 5-aminolevulinic acid (5-ALA) medication on a pediatric patient. The treatment was done noninvasively through an intact skull.
(3 min. read)

8. COVID-19’s impact on pregnant women and their babies

In an editorial, Roberta L. DeBiasi, M.D., M.S., provided a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field.
(2 min. read)

9. Staged surgical hybrid strategy changes outcome for baby born with HLHS

Doctors at Children’s National used a staged, hybrid cardiac surgical strategy to care for a patient who was born with hypoplastic left heart syndrome (HLHS) at 28-weeks-old. Hybrid heart procedures blend traditional surgery and a minimally invasive interventional, or catheter-based, procedure.
(4 min. read)

10. 2022: Pediatric colorectal and pelvic reconstructive surgery today

In a review article in Seminars in Pediatric Surgery, Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National, discussed the history of pediatric colorectal and pelvic reconstructive surgery and described the key advances that have improved patients’ lives.
(11 min. read)

Healthcare leaders join to advance pediatric innovation

RFP collage of logosChildren’s National Hospital and the National Capital Consortium for Pediatric Device Innovation (NCC-PDI) have opened a request for proposal to solicit companies interested in obtaining pediatric labeling for medical devices that may address an unmet need in the pediatric population and that already have clearance or approval for adult use by the U.S. Food & Drug Administration (FDA). The objective of this program is to generate the real-world evidence (RWE) needed to facilitate the pediatric regulatory pathway for U.S. market clearance. The deadline to apply is 5 p.m. EST on Feb. 9. To learn more and apply, visit http://www.innovate4kids.org.

Instead of assessing medical devices based on data derived from clinical trials, this pioneering initiative is focused on leveraging real-world data (RWD) that can be translated into RWE to gain FDA clearance or approval for use with children.

Convening a coalition of healthcare leaders

The new partnership aims to address the significant gap that exists between devices labeled for adults and children. Additional coalition partners include:

  • CobiCure
  • MedStar Health Research Institute
  • Center for Technology Innovation in Pediatrics (CTIP)
  • UCSF-Stanford Pediatric Device Consortium
  • Pennsylvania Pediatric Device Consortium
  • Southwest National Pediatric Device Consortium

Funded by the FDA and facilitated through NCC-PDI and the Office of Innovation Ventures at Children’s National, this program will provide winning companies with technical expertise, including but not limited to regulatory, study design and data science services.

“We are delighted to partner with this coalition of trusted healthcare leaders that share our vision for advancing pediatric health. We know all too well that pediatric device development presents several unique challenges and that children have medical device needs that are considerably different from adults,” says Kolaleh Eskandanian, Ph.D., M.B.A, P.M.P, vice president and chief innovation officer at Children’s National and principal investigator of NCC-PDI. “There are already a number of medical devices on the market that have been FDA cleared or approved and proven viable, and this partnership will help provide important evidence generation and other wraparound services to guide device creators through the regulatory path for pediatric labeling.”

Using RWE to facilitate the regulatory pathway

While Randomized Clinical Trials (RCT) have traditionally been the gold standard when investigating a medical product’s efficacy and safety, many important populations, including children, are excluded from RCTs for ethical reasons. This means that pediatric researchers must make safety and efficacy decisions in the absence of data from such trials. RWE, including data from electronic health records (EHRs), healthcare claims data, disease registries and data gathered through other health applications, can close this gap in pediatric studies. She said that MedStar Health’s capabilities in applying RWE will be a formidable asset to the chosen applicants.

Proposals for companies seeking pediatric labeling for their medical device will be reviewed by an esteemed panel of judges specializing in data science, medical device development, evidence generation, post-market surveillance and the FDA’s regulatory pathway. Children’s National and members of the coalition will provide selected companies with technical expertise in support of their effort to achieve pediatric labeling. This will include:

  • Access to mentors
  • A design study protocol implementing RWE generation best practices
  • Facilitation of IRB submission and study implementation
  • Data science support
  • Regulatory, reimbursement and supply chain consultation

About NCC-PDI

NCC-PDI is one of five consortia in the FDA’s Pediatric Device Consortia Grant Program created to support the development and commercialization of medical devices for children. NCC-PDI is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National and the A. James Clark School of Engineering at the University of Maryland, with support from partners MedTech Innovator and design firm Archimedic.

Case study: COVID-19 patient with autoimmune adrenal insufficiency and hypothyroidism

coronavirus and DNA

This is the first report of a pediatric patient with COVID-19 who developed autoimmune thyroid and cortisol deficiency, although not confirmed that it was related or triggered by the COVID-19 infection.

There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link has been established. In a case study, published in Hormone Research in Paediatrics, researchers at Children’s National Hospital report a 14-year-old girl admitted with COVID-19 and symptoms of MIS-C who was then recognized to have autoimmune polyglandular syndrome (APS2). This is the first report of a pediatric patient with COVID-19 who developed autoimmune thyroid and cortisol deficiency, although not confirmed that it was related or triggered by the COVID-19 infection.

What this means

APS2 is rare in children and has an incidence of 1 in 20,000. Until now, there have only been reports of autoimmune thyroiditis and adrenal insufficiency in adults post-COVID-19.

“The role of COVID-19 in the etiopathogenesis of APS2 in this case remains unclear,” says Myrto Flokas, M.D., endocrinology fellow at Children’s National Hospital and first author of the case study. “But we suspect that it may have contributed to the rapid progression and severe clinical manifestations of both adrenal insufficiency and hypothyroidism leading to the presentation akin to MIS-C.”

The hold-up in the field

COVID-19 has been reported to affect the immune system and may serve as a trigger for autoimmune diseases similar to other viral infections.

“This is a case-report and while we cannot draw any mechanistic conclusions or infer causality, it is the first pediatric report of an association,” says Roopa Kanakatti Shankar, M.D., endocrinologist at Children’s National and one of the authors of the case study.  “We hope it will contribute to this novel field as our understanding of COVID-19 and its myriad effects on the immune system is still evolving.”

Why it matters

This case will alert clinicians to be mindful of the association and similarities in presentation of adrenal insufficiency to MIS-C and consider adrenal crisis in the differential diagnosis of such a presentation.

You can read the full case study, New-Onset Primary Adrenal Insufficiency and Autoimmune Hypothyroidism in a Pediatric Patient Presenting with MIS-C, in Hormone Research in Paediatrics.

Children’s National receives Platinum ELSO Award of Excellence

Platinum ELSO Award logoIn 1984, Children’s National Hospital became the first children’s hospital to offer Extracorporeal Membrane Oxygenation (ECMO) and remains one of the largest ECMO programs in the nation, led by Billie Lou Short, M.D., chief of the Division of Neonatology at Children’s National. This year, the Children’s National ECMO Program was recognized by the Extracorporeal Life Support Organization (ELSO) with the Platinum ELSO Award of Excellence in Extracorporeal Life Support. This award recognizes centers that demonstrate an exceptional commitment to evidence-based processes and quality measures, staff training and continuing education, patient satisfaction and ongoing clinical care.

By being designated as a Center of Excellence with ELSO, Children’s National has demonstrated extraordinary achievement in the following three categories:

  • Excellence in promoting the mission, activities and vision of ELSO
  • Excellence in patient care by using the highest quality measures, processes and structures based upon evidence
  • Excellence in training, education, collaboration and communication supporting ELSO guidelines that contributes to a healing environment for families, patients and staff

“As a member of the Founding Steering Committee of the ELSO organization which started in 1989, the goal was to bring critical care providers doing this highly technical therapy together to develop quality outcome data and standards of care,” says Dr. Short. “ELSO is now the international organization that most programs — neonatal, pediatric and adult — around the world belong to. So, it is an honor this year to have received the ELSO Award of Excellence at the platinum level representing the amazing Extracorporeal Life Support Team we have at Children’s National, caring for patients in all three ICUs.”

Join Children’s National at our 39th annual symposium, ECMO and the Advanced Therapies for Cardiovascular and Respiratory Failure, on February 26-March 1, 2023. Learn more at ecmomeeting.com.

How the circadian clock could help the brain recover after injury

illustration of the brain

A type of brain cell that can renew itself is regulated by circadian rhythms, providing significant insights into how the body’s internal clock may promote healing after traumatic brain injuries (TBI).

A type of brain cell that can renew itself is regulated by circadian rhythms, providing significant insights into how the body’s internal clock may promote healing after traumatic brain injuries (TBI), according to new research from Children’s National Hospital.

Released in the latest issue of eNeuro, the findings open new avenues of investigation for future TBI therapies. These injuries are currently managed only with supportive care and rehabilitation, rather than targeted drug treatment options. The findings also underscore the importance of addressing circadian disturbances to help injured brains heal.

Many of the body’s cells follow a 24-hour rhythm driven by their genes known as the circadian clock. The Children’s National research team found that a relatively newly discovered type of brain cell ­– known as NG2-glia, or oligodendrocyte precursor cells ­– also follow a circadian rhythm. This cell type is one of the few that continually self-renews throughout adulthood and is notably proliferative in the first week after brain injuries.

“We have found evidence for the role of this well-known molecular pathway – the molecular circadian clock – in regulating the ability for these NG2-glia to proliferate, both at rest and after injury,” said Terry Dean, M.D., Ph.D., critical care specialist at Children’s National and the lead author of the paper. “This will serve as a starting point to further investigate the pathways to controlling cellular regeneration and optimize recovery after injury.”

Sometimes called “the silent epidemic,” TBI afflicts an estimated 69 million people worldwide each year, with injuries ranging from mild concussions to severe injuries that cause mortality or lifelong disability. In the United States alone, approximately 2.8 million people sustain TBI annually, including 630,000 children. TBI is the leading cause of death in people under age 45, and those who survive are often left with persistent physical, cognitive and psychological disabilities.

Yet no targeted therapies exist for TBI, creating a critical need to uncover the mechanisms that could unlock the regeneration of these NG2-glia cells, which are the most common type of brain cell known to proliferate and self-renew in adult brains.

“It is essential for researchers to know that cell renewal is coordinated with the time of day,” said Vittorio Gallo, Ph.D., interim chief academic officer and interim director of the Children’s National Research Institute. “With this knowledge, we can dig deeper into the body’s genetic healing process to understand how cells regulate and regenerate themselves.”

JAMA study shows no benefit to nitric oxide in cardiopulmonary bypass for young children

Baby on ventilator

An international clinical trial showed that nitric oxide doesn’t help kids recover faster from cardiac surgery with cardiopulmonary bypass.

A study published in JAMA finds that the practice of introducing nitric oxide into the gas flow of the cardiopulmonary bypass oxygenator does not improve recovery or reduce the amount of time a child under age 2 needs to be on a ventilator after cardiac surgery.

Children’s National Cardiac Surgery Chief Yves d’Udekem, M.D., Ph.D., co-authored the international study, which is already leading to changes in how hospitals around the world care for children with congenital heart disease (CHD).

The results are from a double-blind, randomized controlled trial with more than 1,200 participants across six centers in Australia, New Zealand and the Netherlands. The research team found that children under age 2 who had cardiac surgery with cardiopulmonary bypass spent about the same number of days on ventilators after surgery, whether nitric oxide was used during surgery or not.

“These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery,” the authors conclude.

What this means

Previous smaller, single center studies had shown early indications that nitric oxide delivered during heart surgery could possibly improve recovery and shorten the need for respiratory support after surgery by reducing the occurrence of low cardiac output syndrome in children under age 2.

This large-scale international trial showed that this is not the case.

Why it matters

Based on these earlier studies, many hospitals in the United States and around the world who perform critical heart surgery on young children with congenital heart disease had already started to incorporate nitric oxide into cardiopulmonary bypass. This new, more robust data is helping hospitals reassess this practice. Many are stopping it altogether based on the findings.

This work is an important reminder of how valuable well-designed, large-scale, double-blind, randomized, controlled trials are to defining, improving and refining best practices in clinical care.

Also, trials of this size and significance in pediatrics generally, and CHD specifically, take a very long time to complete, if they are ever able to be completed at all. That’s because the number of children with these conditions is relatively small and spread out, even though CHD is the most common birth defect in the world. The authors say it is a major accomplishment to have completed a trial of this size and  in such a short time. Even better, the data gathered from this sample of patients from across international borders can be used to provide even more insights into how best to care for these children as they continue to grow and develop.

Ricardo Munoz, M.D., named MacCutcheon Family Professor in Cardiac Critical Care Medicine

Ricardo MunozChildren’s National Hospital named Ricardo Munoz, M.D., the MacCutcheon Family Professor in Cardiac Critical Care Medicine at Children’s National Hospital.

Dr. Munoz serves as chief of the Division of Cardiac Critical Care Medicine, executive director of Telehealth, and co-director of Children’s National Heart Institute at Children’s National Hospital. He is professor of pediatrics at the George Washington University School of Medicine and the main editor of several books in pediatric cardiac critical care medicine.

About the award

Dr. Munoz joins a distinguished group of 42 Children’s National physicians and scientists who hold an endowed chair. Professorships at Children’s National support groundbreaking work on behalf of children and their families and foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect the recipient’s achievements and donor’s forethought to advance and sustain knowledge.

As chief of the Division of Cardiac Critical Care Medicine, Dr. Munoz leads a multidisciplinary team of specially trained physicians in providing intensive pediatric cardiac critical care. Dr. Munoz is credited as pioneering telemedicine for pediatric critical care, dedicated to increasing access and quality care for children with special hearts in the nation’s capital and across the world.

The MacCutcheon Family Foundation, through their vision and generosity, are ensuring that Dr. Munoz and future holders of this professorship will launch bold, new initiatives to rapidly advance the field of pediatric cardiac critical care, elevate our leadership and improve the lifetimes of children with special hearts.

About the donors

Jim MacCutcheon’s involvement with Children’s National dates back to 1983. He has served in many leadership positions, most notably on the Children’s National and Children’s National Hospital Foundation board of directors. Jim and his daughters, Megan MacCutcheon, Candice Kessler and Colleen Crowley have supported Children’s National Heart Institute by funding the development of the MacCutcheon Cardiovascular Operating Suite and the Halle MacCutcheon Playroom on the heart and kidney unit. They have also provided support for the Peter Holbrook Endowed Lecture in Critical Care Medicine, the mobile health clinic and various events and capital improvement projects.

The MacCutcheon family’s investment to establish the MacCutcheon Family Professorship in Cardiac Critical Care Medicine allows Dr. Munoz and his team to provide innovative care utilizing telemedicine and artificial intelligence in support of our patients with special hearts.

Caspases may link brain cell degeneration and cardiac surgery

caspase molecule

The review summarizes both the known physiological roles of caspases as well as some of the well-characterized neurotoxic effects of anesthetics in pre-clinical models.

A review article in the journal Cell Press: Trends in Neuroscience outlines the wide variety of cellular signaling roles for caspase proteins — a type of cellular enzyme best known for its documented role in the natural process of cell death (apoptosis). The authors, including Nemanja Saric, Ph.D., Kazue Hashimoto-Torii, Ph.D., and Nobuyuki Ishibashi, M.D., all from Children’s National Research Institute, pay particular attention to what the scientific literature shows about caspases’ non-apoptotic roles in the neurons specifically. They also highlight research showing how, when activated during a cardiac surgery with anesthesia and cardiopulmonary bypass, these enzymes may contribute to the degeneration of brain cells seen in young children who undergo heart surgery for critical congenital heart defects (CHDs).

Why it matters

The review summarizes both the known physiological roles of caspases as well as some of the well-characterized neurotoxic effects of anesthetics in pre-clinical models.

The authors propose that these non-apoptotic activities of caspases may be behind some of the adverse effects on the developing brain related to cardiac surgery and anesthesia. Those adverse effects are known to increase risk of behavioral impairments in children with congenital heart disease who underwent cardiac surgery with both anesthesia and cardiopulmonary bypass at a very young age.

This work is the first to propose a possible link between developmental anesthesia neurotoxicity and caspase-dependent cellular responses.

The patient benefit

Better understanding of the time and dose-dependent effects of general anesthetics on the developing brain, particularly in children who have genetic predispositions to conditions such as CHDs, will help researchers understand their role (if any) in behavioral problems often encountered by these patients after surgery.

If found to be a contributing factor, perhaps new therapies to mitigate this caspase activity might be explored to alleviate some of these adverse effects on the developing brain.

What’s next?

The authors hope to stimulate more in-depth research into caspase signaling events, particularly related to how these signaling events change when an anesthetic is introduced. Deeper understanding of how anesthetics impact caspase activation in the developing brain will allow for better assessments of the risk for children who need major surgery early in life.

Children’s National leads the way

Children’s National Hospital leads studies funded by the U.S. Department of Defense to better understand how these other roles of caspases, which until now have not been well-documented, may contribute to brain cell degeneration when activated by prolonged anesthesia and cardiopulmonary bypass during cardiac surgery for congenital heart disease.

IV acetaminophen administration reduces duration of opioid use

little boy in hospital bed

The study led by Children’s National Hospital experts further suggested that administering IV acetaminophen prior to IV opioid should be considered earlier in multimodal pain regimens because it may reduce the overall use of IV opioids.

A new study published in JAMA Network Open used a diverse, national pediatric inpatient sample, which showed that intravenous (IV) acetaminophen can effectively reduce IV opioid requirements by 15.5% compared to IV opioids use alone. The study led by Children’s National Hospital experts further suggested that administering IV acetaminophen prior to IV opioid should be considered earlier in multimodal pain regimens because it may reduce the overall use of IV opioids.

“The information shared through this research study has the potential to reduce inpatient pediatric IV opioid utilization and therefore reduce opioid related complications such as addiction, withdrawal, respiratory depression and delayed gut motility,” said Anita Patel, M.D., critical care specialist at Children’s National.

The multidisciplinary team of clinicians, data scientists and statisticians came together under the overall guidance of Murray Pollack, M.D., M.B.A., professor of pediatrics at Children’s National and senior author, coupled with the unique access to the Health Facts database that made this study possible. This is the first assessment of the opioid sparing association of IV acetaminophen in a general, real-world pediatric inpatient population.

“This study will help us reduce the hospital use of opioids in infants, children and adolescents,” said Dr. Pollack. “Reducing opioid use is especially important for patients needing prolonged pain relief and will help care-givers minimize the risks of opioids including addiction and withdrawal.”

Non-opioid analgesic medications have yet to be effectively adopted with the goal of minimizing opioid medications to hospitalized pediatric inpatients. Studies with a sufficient sample size have also been difficult to perform in pediatrics to study non-opioid medications on a large scale until now.

“This work was a necessary first step in what I plan on being my lifelong goal of optimizing pediatric pain while minimizing the adverse effects related to many opioid derived pain medications,” said Dr. Patel.

Patel et al. performed a comparative effectiveness research of data collected from 274 U.S. hospitals between January 2011 and June 2016 with 893,293 hospitalized children who received IV acetaminophen prior to IV opioids. These were associated with a significant 15.5% reduction in total IV opioid duration when compared to patients who received IV opioids alone.

Patel plans on applying the skills and knowledge gained through this research to address how we can minimize the opioid related side effect of Iatrogenic withdrawal in critically ill children.

New study compares first and second wave of MIS-C

sick child in palliative care hospital bed

When comparing the first and second wave of patients diagnosed with multi-system inflammatory syndrome in children (MIS-C), the second wave patients had more severe illness, according to a new prospective cohort study at Children’s National Hospital in Washington, D.C.

When comparing the first and second wave of patients diagnosed with multi-system inflammatory syndrome in children (MIS-C), the second wave patients had more severe illness, according to a new prospective cohort study of 106 patients at Children’s National Hospital in Washington, D.C. The results, published in The Pediatric Infectious Disease Journal, show that despite increased severity in the second wave cohort, both cohorts had similarities in cardiac outcomes and length of stay. Researchers are still working to better understand the exact immunologic mechanisms that trigger MIS-C and the specific factors accounting for its rare occurrence.

“We’ve now seen three distinct waves of MIS-C since the beginning of the pandemic, each wave following national spikes in cases,” said Roberta DeBiasi, M.D., chief of the Division of Pediatric Infectious Diseases at Children’s National and co-author of the study. “Kids in the second wave cohort had potentially experienced intermittent and/or repeated exposures to the virus circulating in their communities. In turn, this may have served as repeated triggers for their immune system which created the more severe inflammatory response.”

In this new study, key demographic features Children’s National researchers previously identified held true across both waves – including the fact that Black and Latino children are significantly more affected than white children.  Of the 106 patients, 54% were Black and 39% were Hispanic. The authors also noted that 75% of the patients were otherwise healthy children with no underlying medical conditions.

“While we believe the most recent third wave associated with the delta variant surge is tapering off, the findings from the first two waves provide important baseline information and are highly relevant for clinicians across the country that are evaluating and treating kids with MIS-C,” said Dr. DeBiasi.

Children’s National has cared for more than 4,200 symptomatic patients with SAR-CoV-2 infection and more than 185 MIS-C patients since the pandemic began. The first wave of MIS-C patients were hospitalized between March 2020 and October 2020. Second wave patients were hospitalized between November 2020 and April 2021. Each wave came 4-6 weeks following periods of COVID-19 surges in the community.

In the study, researchers compared patient demographics, clinical features, laboratory results, radiographic images, therapies and outcomes. The second wave cohort had a higher proportion of children 15 years of age or older. Patients also presented more frequently with shortness of breath and required more advanced respiratory and inotropic support. Researchers also found that patients in the second wave were less likely to test positive for SARS-CoV-2 on a PCR test.

Dr. DeBiasi and her team hope to unlock even more insights as they now analyze data from the third wave associated with the delta variant, which currently appears to have affected less children than the previous two. Children’s National is also working in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) to study the long-term effects of MIS-C and COVID-19 on the pediatric population after recovery. This is among the largest and longest studies being conducted, and researchers are hopeful the findings will help improve treatment of COVID-19 and MIS-C in the pediatric population both nationally and around the world.

“Our timely established multidisciplinary MIS-C task force here at Children’s National allowed us to reduce the learning curve,” said Ashraf S. Harahsheh, M.D., F.A.A.P., F.A.C.C., director of Quality Outcomes in Cardiology and co-first author of the study. “Experience from other centers showed that immunotherapy was utilized more frequently in recent MIS-C cohorts leading to reduction in percentage of cardiac complications. On the other hand, and despite having increased illness severity in the second cohort, our approach with prompt immunotherapy helped stabilize the rate of cardiac complications.”

Children’s National Hospital Simulation Program receives SSH accreditation

Children's National simulation team

In this picture are L-R- Kellee Humphries, Clinical Simulation Technician; Rosalyn Manuel, Simulation Education Specialist; Simmy King, Chief Nursing Informatics and Education Officer; Laura Nicholson, Simulation Education Specialist; Heather Walsh, Simulation Program Manager; Kaitlin Moran, Clinical Simulation Technician; Nina Brown, Simulation Education Specialist.

A peer-reviewed organization of healthcare simulation, known as The Society for Simulation in Healthcare (SSH), accredited the Children’s National Hospital Simulation Program in the areas of Teaching/Education and Systems Integration.

“The accreditation is the culmination of years of hard work and recognition of our best practices in simulation education,” said Heather Walsh, M.S.N., R.N., P.C.N.S.-B.C., C.H.S.E., simulation program manager at Children’s National. “It’s been exciting to see simulation integrated into so many facets of care and processes throughout the organization. It makes our work fun and incredibly rewarding.”

The accreditation recognizes the program’s development and standardization of simulation operations, policies and procedures that guided the educational practices.

In teaching and education, the program provided examples of curriculum development, implementation and evaluation. Adaptive response training (the previous hospital-wide simulation-based training), hospitalist simulations and interprofessional nurse-resident simulations served as exemplars.

“Most of our simulations focus on improving teamwork and communication, safety events that have occurred on a particular unit, proper documentation or introducing new equipment or equipment that is not frequently used,” said Nina Brown, M.S., R.N.C.-O.B., simulation education specialist at Children’s National. “The simulation environment allows learners to practice the skills and communication that would be carried out in the real world.”

Gregory Yurasek, M.D., C.H.S.E., critical care simulation director at Children’s National, mentioned that they offered fellows virtual reality (VR) in pediatric cardiac critical care simulations.

“We piloted scenarios with six attending pediatric cardiac critical care physicians this summer to test the feasibility of VR for educational and practice improvement efforts in this highly specialized clinical environment,” said Dr. Yurasek.

The program uses a multidisciplinary approach that increases the possibilities to save a patient’s life in the real clinical environment.

“We can bring doctors and nurses together to practice assessment, management, escalation, teamwork and safety communication in a safe environment where each discipline can practice safety techniques such as shared mental model, closed-loop communication and peer coaching,” said Laura Nicholson M.S.N., R.N., C.P.N., C.H.S.E.

The collaboration also includes working with nearly every department, inpatient and outpatient, radiology, pharmacy, dialysis and others.

“I am really proud to join the team knowing that my colleagues are so committed to the work,” said Rosalyn Manuel, M.S.N., B.S.N., R.N., simulation education specialist at Children’s National. “I feel inspired by their commitment and want my own work to rise to the high bar that has been set.”

Study compares outcomes of SARS-CoV-2 versus other respiratory viruses

illustration of lungs with coronavirus inside

Until now, little was known about the incidence and virus-specific patient outcome of SARS-CoV-2 compared to common seasonal respiratory viruses in children — including respiratory syncytial virus (RSV), human parainfluenza (hPIV), human metapneumovirus (hMPV), respiratory adenovirus and human rhinovirus (hHRV) and respiratory enterovirus (rENT).

Common respiratory viral infections were associated with a higher proportion of inpatient admissions but were similar in intensive care unit (ICU) admissions and death rates in hospitalized pediatric patients when compared to SARS-CoV-2, according to Children’s National Hospital researchers that led a study published in Infection Control & Hospital Epidemiology.

Until now, little was known about the incidence and virus-specific patient outcome of SARS-CoV-2 compared to common seasonal respiratory viruses in children — including respiratory syncytial virus (RSV), human parainfluenza (hPIV), human metapneumovirus (hMPV), respiratory adenovirus and human rhinovirus (hHRV) and respiratory enterovirus (rENT).

The researchers also noted that there was an overall substantial decrease in seasonal respiratory viral infections, especially the severe forms that require hospitalization. They believe that this correlation might be associated with the adoption of COVID-19 public health mitigation efforts, which played a major role in the reduction of these viruses that often circulate in fall and winter. The retrospective cross-sectional cohort study analyzed over 55,000 patient admissions between Match 15 and December 31, 2020. The findings shed light on the incidences of eight common seasonal respiratory viral infections before and during the COVID-19 pandemic. It also compared patient outcomes associated with COVID-19 and these other viral infections among pediatric patients at Children’s National.

Xiaoyan Song, Ph.D., M.Sc., chief infection control officer at Children’s National, spoke to us about the study.

Q: Why is this important work?

A: This is the first study to date that has described and compared hospitalization rates, ICU admission rates and death associated with COVID-19, RSV, seasonal influenza, rhinovirus, enterovirus and other common respiratory viral infections in children in one study. Previously, studies have compared one or two viruses at a time. This study compared 8 viruses, including the most detected ones – COVID-19, RSV, seasonal flu, rhinovirus and enterovirus.

Q: How will this work benefit patients?

A: This study will inform patients, families and the public that preventative measures like masking, hand hygiene, avoiding crowds and avoiding people who are ill are good practices that work to protect children from getting COVID-19 but also from getting infected with RSV, influenza and other viruses. Any of these respiratory viruses could harm a patient to a point where the child may have to be hospitalized or receive ICU care.

You can read the full study published in Infection Control & Hospital Epidemiology.

Cardiac care leaders recognized for mentorship and innovation at AAP

Two Children’s National Hospital cardiac care leaders received prestigious recognition awards from the American Academy of Pediatrics (AAP) during that organization’s virtual National Conference and Exhibition in October 2021.

  • Gil Wernovsky, M.D., cardiac critical care specialist at Children’s National Hospital, received the 2021 Maria Serratto Master Educator Award from AAP Section on Pediatric Cardiology and Cardiac Surgery, celebrating his 30-plus-years as a clinician, educator, mentor and leader in the field.
  • Gerard Martin, M.D., FAAP, FACC, FAHA, C. Richard Beyda Professor of Cardiology, Children’s National Hospital, received the AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award, in recognition of his work to establish the use of pulse oximetry to screen newborn infants for critical congenital heart disease in the first 24 hours of life.

Dr. Wernovsky: 2021 Maria Serratto Master Educator Award, AAP Section on Pediatric Cardiology and Cardiac Surgery

Gil Wernovsky

Gil Wernovsky, M.D., received the 2021 Maria Serratto Master Educator Award from AAP Section on Pediatric Cardiology and Cardiac Surgery.

The Master Educator Award is presented each year to a pediatric cardiologist or cardiothoracic surgeon who exemplifies excellence as an educator, mentor and/or leader in the field.

A practicing cardiac critical care specialist with more than 30 years’ experience in pediatric cardiology, Dr. Wernovsky trained and mentored more than 300 fellows in pediatric cardiology, cardiac surgery, neonatology, critical care medicine and cardiac anesthesia, in addition to countless residents and fellows. He also organizes national and international symposia to share expertise around the world. During the COVID-19 public health emergency, for example, he co-founded the Congenital Heart Academy (CHA). The CHA provides content from an international faculty of cardiac care to more than 26,000 practitioners in 112 countries and includes a thriving YouTube channel.

Dr. Wernovsky is also a founding member of several international societies focused on bringing together clinicians, researchers and students across sub-specialties of pediatric cardiology and cardiac surgery for knowledge exchange and best practice sharing. These include: the Pediatric Cardiac Intensive Care Society, World Society for Pediatric and Congenital Heart Surgery, the International Society of Pediatric Mechanical Circulatory Support and the Cardiac Neurodevelopmental Outcome Collaborative.

Dr. Wernovsky received the award on October 10 at the virtual Scientific Sessions of the 2021 American Academy of Pediatrics National Conference and Exhibition.

Dr. Martin: AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award

Gerard Martin

Gerard Martin, M.D., FAAP, FACC, FAHA, C. Richard Beyda Professor of Cardiology, Children’s National Hospital, received the AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award.

The Section on Advances in Therapeutics and Technology (SOATT) educates physicians, stimulates research and development and consults on therapeutics and technology-related matters for the AAP. The Achievement Award recognizes someone who has shown leadership in applying innovative approaches to solve pressing problems.

Dr. Martin is the C. Richard Beyda Professor of Cardiology and has cared for children at Children’s National for more than 30 years. As an advocate for congenital heart disease efforts nationally and internationally, he played an integral role in the development of an innovative use of existing hospital technology—the pulse oximeter—to detect critical congenital heart disease in newborn babies.

Today, Dr. Martin and colleagues across the United States and around the world have worked to make this screening method a standard of care for newborns everywhere. It is a part of the Health Resources and Services Administration (HRSA) Recommended Uniform Screening Panel and has become law in every state. They continue to conduct research to refine the recommendations and hone-in on the most effective ways to harness these tools.

Dr. Martin was selected for this award in 2020. He accepted it and offered remarks during the 2021 virtual AAP National Conference and Exhibition on Monday, October 11, 2021.

One-half of MIS-C patients at a single center experienced heart complications

coronavirus

A single center study of patients with multisystem inflammatory disease in children (MIS-C) found that half of children diagnosed with MIS-C had a heart complication as part of the disease. The study collected and analyzed data from 39 cases of MIS-C at Children’s National Hospital in 2020. MIS-C is a pediatric disease that has been linked to SARS-CoV-2, the virus that causes COVID-19.

The study’s findings appear in the journal Cardiology of the Young. The authors aimed to describe the type and frequency of cardiac complications in children with MIS-C while also outlining the disease’s short-term progression. They also hoped to better understand the demographics, clinical and laboratory findings, as well as the therapeutic successes for children with cardiac complications from MIS-C.

“While half of all children at our hospital diagnosed with MIS-C did experience a cardiac complication, it’s important to note that almost all of them (84%) also fully recovered from that cardiac complication within 50 days of diagnosis,” says Ashraf Harahsheh, M.D., director of Quality Outcomes in Cardiology at Children’s National Hospital, who led the study. “We were also able to identify a few common factors among those with cardiac complications that, with further research, may help us identify earlier the children with MIS-C who are at greater risk for heart problems.”

The study found that children with cardiac complications had higher levels of natriuretic peptides, which appear in greater numbers when the heart isn’t pumping enough blood to the rest of the body. Additionally, children who developed heart complications also had higher initial white blood cell counts. MIS-C cardiac complications ranged from mild systolic dysfunction to coronary artery abnormalities and/or artery dilation.

This was a retrospective, observational study of 39 patients admitted to Children’s National Hospital from March 2020 to September 2020 who met the Centers for Disease Control and Prevention MIS-C case definition. Patient demographics, clinical features, laboratory values, diagnostic investigations, including echocardiograms, and therapies were extracted from the electronic medical records.

“This syndrome has some similarities to Kawasaki disease, another inflammatory syndrome that is known to cause cardiac complications,” says Dr. Harahsheh. “Thankfully what we’ve learned from studying and treating Kawasaki disease in children has helped us collaborate with partners around the world to find treatments for MIS-C that seem to minimize the impact of these complications, at least in the short term.”