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Hematology and Oncology, Inside Pediatrics

Bench-to-Bedside: Translational Focus Moves Sickle Cell Research into Clinic Faster 

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Jeffrey Lebensburger, D.O., is a pediatric hematologist at Children’s of Alabama and an associate professor in the Division of Hematology/Oncology in the Department of Pediatrics at the University of Alabama at Birmingham.

Basic research is conducted in labs and on animal models, and clinical research is conducted in humans. Traditionally, the two don’t mix, with the basic happening before the clinical. Translational research, a mix of the two, is designed to get new discoveries and treatments to patients faster. “Translational research is a vital component to making breakthroughs in clinical care,” said Jeffrey D. Lebensburger, D.O., who directs the pediatric hematology section of Children’s of Alabama’s Department of Hematology and Oncology. 

Dr. Lebensburger and his research partner, University of Alabama at Birmingham assistant professor Malgorzata Kasztan, Ph.D., are using this approach to find better ways to prevent early kidney disease in children with sickle cell disease. Between 20 percent and 30 percent of children with the disease already demonstrate kidney injury before they hit their teens, and up to 70 percent will develop chronic kidney disease by the time they’re middle-aged. Many will require dialysis or transplantation, often beginning in their 20s. However, the most commonly used test for kidney problems rarely identifies early signs. 

“While we may think that the kidneys are doing okay in childhood based on the tests, there may be severe damage that leads to this early dialysis, which is why we greatly need this bench-to-bedside approach to prevent progression early in adulthood,” Dr. Lebensburger said.  

“We are particularly interested in looking at which patients are at risk for kidney disease and if there is a way to identify those patients early in the process, so they can get better care,” said Dr. Kasztan. 

Tracking the progression from childhood through adulthood, however, would take too long and cost too much. Yet mice genetically engineered to have sickle cell disease fully mature in just a few months, making them a perfect model for exploring kidney disease progression. 

Using these mice, coupled with a biobank of patient blood and urine samples and a sophisticated assay for kidney damage available only in the research setting, Drs. Lebensburger and Kasztan identified high levels of the protein endothelin-1 (ET), which binds to two receptors, ETA and ETB, as a key contributor to early kidney damage. Blocking the ETA receptors with an already-FDA-approved drug, however, protected the mouse kidneys. 

“That allows us to bring back to the patient what we’re seeing in the mouse model and understand if it will continue into adulthood,” Dr. Kasztan said. “Then we could potentially intervene earlier.” 

At the same time, biomarkers of early damage they find in the human blood and urine samples can be “mirrored” in the mouse model to confirm the results, she said. Then interventions that work in the animal model can be tested in patients.  

This type of bidirectional work provides the foundation for clinical trials in humans, said Dr. Lebensburger. “That’s an example of this bench-to-bedside approach: It works in the mouse model of sickle cell, so we can lobby the FDA to start a clinical trial in humans.” 

Hematology and Oncology, Inside Pediatrics

Children’s of Alabama Welcomes Pediatric Neuropsychologist Specializing in Neuro-Oncology 

Emily A. H. Warren, Ph.D., is a pediatric neuropsychologist at Children’s of Alabama and an assistant professor in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

Emily A. H. Warren, Ph.D., is a pediatric neuropsychologist at Children’s of Alabama and an assistant professor in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

With or without cancer, childhood is a very important time for brain development. Yet the experience of cancer itself, as well as the cognitive effects of many cancer treatments, can derail that development, leaving kids at risk for long-lasting social, psychological, and cognitive challenges.  

“The great thing is that with the wonderful advancements in medical treatments and the comprehensive care these children receive, most will survive,” said Emily A.H. Warren, Ph.D., who came to Children’s of Alabama in the fall of 2021 as its first neuropsychologist dedicated specifically to caring for pediatric brain tumor patients. “Now there can be much more attention focused on quality of life, neurocognitive development, and long-term outcomes like educational attainment.” 

Children’s diagnoses and treats more than 60 new central nervous system tumors a year. Dr. Warren uses her expertise in brain development and neuroanatomy to evaluate cognitive development in children with brain tumors. “My main goal is to provide families with a high-quality neuropsychological evaluation, so I can help them understand the potential impact of their child’s brain tumor diagnosis and treatments on cognitive and psychosocial outcomes and support their child in pursuing their goals,” she said. 

Her work begins with a comprehensive neuropsychological assessment covering everything from intellectual functioning to learning, memory, attention, executive functioning, processing speed, visual motor skills, and psychosocial adjustment. 

“With that data, I can help families understand how a diagnosis like a brain tumor and treatments like surgical resection, radiation, and chemotherapy can affect brain development and cognitive abilities,” she said. The goal of the assessment is to carefully evaluate a child’s cognitive strengths and weaknesses to promote the development of age-appropriate skills. Once she knows each child’s unique cognitive profile, Dr. Warren helps families identify ways to support their child. Supports could include developing an individualized education program (IEP) and other school-based or community interventions such as physical therapy, social skills training, or psychological therapies. 

“These children are going through so many complex challenges,” she said. “There are the social and emotional aspects of the diagnosis and treatment, which can be very hard on families. We also need to support their school reintegration because some of these children have been out of school for a while.” Additionally, children may have new functional deficits. They might be in a wheelchair, have visual or hearing impairment, “or just feel that their thinking is slower than it used to be, or they are having trouble getting their words out,” Dr. Warren added. 

“I like to spend a lot of time helping families understand the relationship between their child’s cognitive abilities and their academic achievements and social interactions. It is also important to help families understand the social and emotional impact of being a cancer survivor.”  

Dr. Warren’s research focuses on cognitive and social outcomes following radiation therapies for brain tumor survivors. “With advances in radiation technology, such as proton radiation, children tend to have better neurocognitive and developmental outcomes than we saw in the past,” she said.  “Even so, we still routinely see challenges with skills such as attention, executive functions, and processing speed. Children who receive more intensive therapies might be at greater risk for cognitive challenges. This is why it’s important to individually tailor each neuropsychological evaluation to meet the needs of each child.” 

Dr. Warren hopes to collaborate with her colleagues in pediatric oncology and radiation oncology to continue this research and is currently a co-investigator for a clinical trial exploring whether memantine, a drug used in Alzheimer’s disease, is neuroprotective in children receiving brain radiation.  

Hematology and Oncology, Inside Pediatrics

Hematology/Oncology Fellowship Programs on a Growth Spurt  

Left to right, Katie Metrock, M.D., Hilary Haines, M.D., and Kimberly Whelan, M.D. All are pediatric oncologists at Children’s of Alabama and faculty members in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

Left to right, Katie Metrock, M.D., Hilary Haines, M.D., and Kimberly Whelan, M.D. All are pediatric oncologists at Children’s of Alabama and faculty members in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

Every year, two pediatric residents are accepted to Children’s of Alabama’s three-year, ACGME-accredited program. Their first year is a whirlwind of rotations through the inpatient, stem cell transplant, and outpatient clinics, said Kimberly F. Whelan, M.D., who completed the fellowship herself and now directs the program. “I think of it as being a very rewarding but steep learning curve year,” she said. In the second and third years, the fellows develop an area of research or scholarly focus that serves as the foundation for their first faculty position.  

“We send our fellows out to institutions all across the country,” Dr. Whelan said. “And as that number has grown, it’s been wonderful to see the opportunities for networking and collaboration and the impact our fellows are having on the field — not only here in Birmingham, but across the country.” 

The program typically gets about 40 applicants a year and interviews between 20 and 25. With COVID, of course, interviews have gone virtual, which has pros and cons, Dr. Whelan said. “The upside is it’s more convenient for the applicants since they don’t have to take as much time off to travel. And in the virtual interview you’re able to talk with them and get a good sense of what their interest is, where their passion lies, what they’re looking for in the program.” 

The downside, however, “is that we don’t get to show off Birmingham and the beautiful Children’s of Alabama, which is such a wonderful institution.” 

Recently, the Hematology/Oncology Program added two additional fellowships for hematology/oncology fellowship graduates who want additional training: one in bone marrow transplantation and one in neuro-oncology.  

Bone Marrow Transplant Fellowship 

While hematology/oncology fellows receive training in bone marrow transplant, the field has become very subspecialized, requiring specialized education, said Hilary Haines, M.D., who directs the bone marrow transplant fellowship. “The field as a whole is moving away from general hematology/oncology [and] into subspecialities, so the need to have dedicated training in these fields is definitely evolving,” she said. 

That’s why the division created the one-year fellowship program focused entirely on bone marrow transplantation. It’s one that interests many hematology/oncology fellows, said Dr. Haines, given the complexity of the field. “You get to care for a variety of patients and be involved with cutting-edge technology and new therapies.”  

Indeed, bone marrow transplants are not just for blood cancers. Today they are an option — even a cure — for other blood disorders like sickle cell anemia and severe combined immunodeficiency, bone marrow failure, and some neurological diseases. “We’ve identified more diseases that are curable via bone marrow transplant, and our outcomes have improved for the procedure, so we’re more willing to pursue transplant for diseases that we may not have in the past,” Dr. Haines said. 

Several large children’s hospitals already offer bone marrow transplant fellowships, she said, so having the option at Children’s of Alabama serves as a good recruitment tool for hematology/oncology fellows who may eventually want to focus on bone marrow transplantation.  

The first participant, who completed her hematology/oncology fellowship at Children’s, should finish her training in May. 

Neuro-oncology Fellowship 

Like Dr. Haines, Children’s neuro-oncologist Katie Metrock, M.D., points to the continued subspecialization in hematology/oncology as the reason for the new, one-year neuro-oncology fellowship she just launched. “The year is meant to submerge you into the field of neuro-oncology,” she said, which is vastly different from hematology/oncology overall. “Fellows get significant exposure to leukemia and lymphoma and other solid tumors during the general hematology/oncology fellowship, but not as much in-depth experience with neuro-oncology because the program operates slightly differently,” she said.  

Since patients often require comprehensive care from multiple medical specialties, the extra year is designed to enhance a fellow’s knowledge of pediatric brain tumors, including diagnosis, biology, clinical course, treatment options, outcomes, and areas of research. 

“In addition,” Dr. Metrock said, “the field is rapidly evolving as we learn more and more information about these tumors. This gives the fellow extra time to learn the details of the complex care required to help these children succeed.” 

Brain tumors are the most common pediatric tumors and the one with the highest mortality rate. In brain tumors, the neuro-oncologist coordinates the team of specialists required to care for these children, including neurosurgeons, neuropathologists, radiation-oncologists, neurologists, ophthalmologists, and others. The fellow will start by watching the neurosurgeon operate, then follow the tissue sample in the pathology lab, learn to discuss a neuro-ophthalmology exam with the ophthalmologist, understand the dosage and design behind radiation-oncology plans, and meet with palliative care, among other rotations — a deep dive they don’t get during their hematology/oncology fellowship.  

That experience is different from just meeting the patient and family after the surgery and diagnosis. “We feel we can better understand what’s going on with them — to the extent that’s possible — by following them from the beginning,” Dr. Metrock said. 

“My favorite year in all my training was my neuro-oncology fellowship,” she said. “It was a year when I was able to do what I loved most and ask every question I wanted to ask. I’m excited to offer that to other people.” 

The first neuro-oncology fellow starts in July 2022. 

Hematology and Oncology, Inside Pediatrics

Children’s Pediatric Oncologists Spearhead Registry of Children with Cancer, COVID 

Left, Julie Wolfson, M.D., and right, Emily Johnston, M.D., are pediatric oncologists at Children’s of Alabama and assistant professors in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics. Left, Julie Wolfson, M.D., and right, Emily Johnston, M.D., are pediatric oncologists at Children’s of Alabama and assistant professors in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

Left, Julie Wolfson, M.D., and right, Emily Johnston, M.D., are pediatric oncologists at Children’s of Alabama and assistant professors in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

What started as a conversation among a Facebook group of pediatric oncologists at the pandemic’s start has now grown into the largest registry of children with cancer and COVID-19 in the country, providing invaluable information for healthcare providers grappling with the effects of the virus on their patients. 

“People started posting in the Facebook group about caring for children with cancer and COVID-19, asking what they should do,” said Children’s of Alabama pediatric oncologist Emily Johnston, M.D., who, with her colleagues Julie Wolfson, M.D., and Jenn Levine, M.D., of Cornell Medical Center in New York, helped found the Pediatric COVID-19 Cancer Case (POCC) Report. “There were no data, no guidelines, nothing,” Dr. Johnston said. The registry, which is now housed at the University of Alabama at Birmingham, is led by Drs. Johnston and Wolfson.  

The growth has been “miraculous,” Dr. Johnston said. “We started these conversations in March 2020 and had our first patients entered by the end of April, representing an incredible pace.” Today, the registry has data on more than 1,400 children from more than 100 sites. “The other hospitals are participating in the registry because it’s the right thing to do for our community and our patients,” she said. “The national collaboration has been really impressive.” 

One goal of the registry is to provide real-time information to pediatric oncologists. The team sends regular data briefs to every pediatric cancer site in the country with updated summaries. 

In December 2021, the group published its findings on 917 children from 94 U.S. hospitals in the prestigious Journal of Clinical OncologyThey found these children had a high risk of severe infection, with one-third admitted to the hospital and 9 percent to the ICU. They also found nearly half (45 percent) had their cancer therapy changed because of the infection. Fourteen (1.5 percent) died from COVID-19.  

The children most likely to develop severe disease with COVID-19 infections were age 11 or older; those with health conditions in addition to their cancer; and those with neutropenia (low white blood cell count) or hematologic cancers. Hispanic children were most likely to be infected and to have their cancer therapy modified, even though they didn’t have more severe illness. This, Dr. Johnston said, mirrors the racial and ethnic disparities seen in the wider population with COVID-19.  

She and her colleagues are working on understanding why Hispanic children were more likely to have their treatment changed. “This may reflect a combination of systemic issues, biological issues, and even our innate biases. It’s probably a combination of all these, and definitely something we need to tease apart to figure out why this is happening.” 

Dr. Johnston and her team are now collecting data on the vaccination status of all patients, including those in the registry, and the impact of vaccination on infection. They also have a small grant to delve deeper into the data, including to assess how COVID-19 in children with cancer has changed over the course of the pandemic and determine the impact of the virus on long-term health. 

An important area they hope to research focuses on the impact of treatment changes. “We’ve had such incredible improvements in survival in the last several decades in part because we’ve gotten more treatments and escalated treatment, including giving more intense, frequent chemotherapy,” Dr. Johnston said. “That’s led to improved survival. We get very nervous when we have to hold or modify chemotherapy.” 

The two Drs. Johnston and Wolfson said they feel a calling for the work. “We felt it was our duty to use our research infrastructure for this public health purpose,” said Dr. Wolfson. “Hopefully, we’ll be able to help patients and clinicians as much as possible.” 

Inside Pediatrics, Neurology & Neurosurgery

Stopping Tics in Their Tracks 

Emily Gantz, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics.

Emily Gantz, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics.

The hallmark of Tourette syndrome is an array of tics, ranging from eye blinking and rolling to head and neck movements to verbal sounds. “It’s like feeling that you need to cough in a meeting, so you try to suppress it. But the more you try not to cough, the bigger the itch gets, so you just have to cough,” said Children’s of Alabama pediatric neurologist Emily Gantz, D.O. “Then [Tourette syndrome patients’] brains learn that when they do the movement or make the sounds, the urge goes away, and they feel better.” 

Those tics, however, can lead to bullying, academic issues, and social isolation. But just a few hours spent with the occupational therapists and neurologists at the Comprehensive Behavioral Intervention for Tics, or CBIT, clinic at Children’s of Alabama, can be lifechanging. 

The multidisciplinary program began in 2010. Since then, thousands of children have passed through, and 95 percent have significantly reduced or eliminated their tics. “It’s very doable,” said Jan Rowe, M.D., OT, who started the clinic“While it is hard work, the kids see it as a very easy way to manage their tics.” 

The children first meet with Dr. Gantz or Pediatric Neurology Director Leon S. Dure IV, M.D., who makes or confirms a diagnosis of Tourette syndrome, tic disorder, or other functional movement disorder. Then patients spend about one hour a week for eight weeks with a CBIT-trained occupational therapist in the clinic, where they learn competing responses to interrupt the tics, which minimizes and/or extinguishes them. 

For instance, someone with a head or neck tic, such as flipping their head back, is taught to push their head straight back, like leaning into a headrest. “When you do that, your chin automatically comes down just a bit and the front neck muscles are activated, which holds the head still,” Dr. Rowe said. An eye-rolling tic might be managed by looking down and out. And shoulder shrugs can be headed off by pushing and holding the shoulders down with the arms against the sides. 

“Having a competing response or strategy to block the tic allows the child to do something instead of just trying to suppress it, which takes a tremendous amount of physical and mental energy,” Dr. Rowe said. “This therapy can be really life-changing for these kids, especially those facing teasing or bullying in school or in their social life,” she said. And it only takes a handful of sessions. 

The clinic has been particularly busy the past 18 months with a pandemic-related phenomenon called “TikTok tics.” It primarily affects teenage girls with no previous history of tics. Time spent watching people with Tourette syndrome on the social media platform TikTok, combined with anxiety and stress, seem to trigger abnormal vocalizations and movements. 

The problem is global, Dr. Rowe said. Girls come into the clinic with a diagnosis of Tourette syndrome from their primary care clinician, but it’s clear something else is going on since they didn’t have the tics before, something Dr. Gantz confirms during a Zoom visit. The teens are invited into the CBIT program but must also work with a therapist to deal with their anxiety, stress, or trauma. “Let’s face it, these kids have had tremendous loss in the past two years,” Dr. Rowe said. “Many of them are on overload.”  

Dr. Rowe, who has tics herself, has been running the clinic for 12 years. “I just absolutely love it,” she said. “It is so life-changing.” 

Inside Pediatrics, Neurology & Neurosurgery

License Plates and Safer Schools: Advocacy in Action in Epilepsy 

Kathryn Lalor, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics.

Kathryn Lalor, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics.

When you think about epilepsy and Children’s of Alabama, you think about the epilepsy clinic, groundbreaking research, and state-of-the-art treatments and surgeries. You probably don’t think about license plates and training school staff to give life-saving emergency treatments. Yet that’s just what the pediatric neurology division has been doing as part of its advocacy efforts in the epilepsy field.  

Together with the Epilepsy Foundation AlabamaChildren’s of Alabama pediatric neurologists Monisha Goyal, M.D., Kathryn Lalor, M.D., and other staff designed the first epilepsy license plate in the country. The state approved the “Help End Epilepsy” car tag in March 2020, but it couldn’t be produced until at least 1,000 people committed to buying it. The team hit that milestone in 2021 thanks to the help of a generous donation that made the first 1,000 tags free.

“That was a big, big deal,” Dr. Lalor said. Each plate costs $50, $41.25 of which goes to the pediatric epilepsy program at Children’s. “We want to use some of that money to help educate future epilepsy specialists,” she said, citing a shortage of specialists in the region. In fact, while Children’s has a fellowship slot in epilepsy, it hasn’t had the funding to fill it.

The second major advocacy effort in 2021 revolved around improving the school environment for children with epilepsy by training school personnel other than nurses to administer seizure-rescue medications. That’s important for the 7,500 Alabama students with epilepsy. If there isn’t a nurse nearby, they can’t participate in activities like sports and field trips. Yet just 70 to 75 percent of Alabama public schools have access to a nurse, often sharing that nurse among several schools. 

Dr. Lalor and her colleagues, along with the Epilepsy Foundation Alabama, lobbied state legislators to pass the Seizure Safe Schools Act, including testifying in front of the House and Senate committees.  

It wasn’t as easy as they expected it to be, with opposition coming from the school nurses association and some legislators concerned that allowing non-medical volunteers to administer emergency medicine would hinder efforts to hire more nurses. That was never the intention, Dr. Lalor said. “We would love for school nurses to be everywhere,” she said. “The school systems just can’t afford that.” And there’s a national shortage of school nurses. Nonetheless, the legislature added an amendment to the act calling for more efforts to put school nurses in every school. “We fully support this,” said Dr. Lalor. “This is crucial for the safety of students.” 

A statewide task force composed of Epilepsy Foundation and Children’s representatives, school nurses, and public health officials is working to implement the new law and hopes to roll out education in early spring 2022. 

Inside Pediatrics, Neurology & Neurosurgery

Epilepsy Transition Clinic Helps Adolescents Move to Adult Care 

At right, Kathryn Lalor, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics. At left is epilepsy specialist Quynh Vo, M.D., of the University of Alabama at Birmingham.

At right, Kathryn Lalor, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics. At left is epilepsy specialist Quynh Vo, M.D., of the University of Alabama at Birmingham.

Adolescents are not known for self-discipline. Yet that’s exactly what teens with epilepsy need in order to avoid seizure triggers, like lack of sleep and alcohol consumption. They also must be vigilant about taking their medication. However, as young people become young adults and start to manage their care independently, “these are the hardest things to do,” said Children’s of Alabama pediatric neurologist Kathryn Lalor, M.D. 

Which is why young adulthood carries a high risk of recurrent seizures, particularly as epilepsy patients transition from pediatric to adult neurology. “Many of these patients have had epilepsy for a long time, and they’ve been diagnosed and cared for by the same neurologist for a long time. It can be very scary and disconcerting to change that, especially as you’re coping with so many other things,” Dr. Lalor said. 

Then there are the difficulties on the medical side, such as electronic medical record systems that don’t talk to each other, making transitioning between providers difficult. “We were hearing from our adult colleagues that they just didn’t have the information they needed,” Dr. Lalor said. “It was like starting over with the medical history.” 

Which is why Dr. Lalor and her team started one of the first epilepsy transition clinics in the country. “We really wanted to improve the process from a logistical and informational perspective but also help guide these patients through the process.” That’s particularly important given the impact of epilepsy on daily life. “It affects school, being able to drive, your job,” she said. “And we really wanted to be a place where we could help young adults gain their footing in their life.” 

Now when the pediatric neurologist refers the patient to the adult provider, they gather all the pertinent data and meet together with the patient. 

The young person also completes a transition-readiness assessment questionnaire, a validated tool specifically for epilepsy, to determine how ready they are to independently manage their disease. “And if there are any places where they’re still behind, still not doing things quite on their own, we set ‘homework’ goals for them for the next visit,” said Dr. Lalor. Clinic staff follow patients until they are fully managing their own care or until the staff feels they’re stable and ready to transition, at which point most patients continue with epilepsy specialist Quynh Vo, M.D., of the University of Alabama at Birmingham. 

The clinic is so busy that in December 2021, staff added a second day a month. The next step, Dr. Lalor said, is to implement national guidelines that recommend beginning transition at age 12 and add case management and social workers to the team.  

Cardiology, Inside Pediatrics

Improving Quality and Outcomes in Cardiology

Ashley Moellinger, RN, CRNP, Cardiovascular Services, Children's of Alabama

Ashley Moellinger, RN, CRNP, Cardiovascular Services, Children’s of Alabama

Children’s of Alabama is deeply committed to continual improvement in every part of the care pathway. Two quality-improvement projects in cardiology are already showing the results.

Handoff of Care

Medical errors are the third-leading cause of death in the United States.[1] The Joint Commission reports that two-thirds of serious medical errors, or “sentinel events,” are tied to poor communication, and half involve communication during care handoff, such as when a patient is transferred from the intensive care unit (ICU) to surgery or back.[2]

The handoff is an important faultline for miscommunication that can lead to patient harm, said Children’s of Alabama cardiovascular intensivist Hayden Zaccagni, M.D. It’s not just communication between the intensivist and the surgeon; it involves the pediatric anesthesiologist, bedside and surgical nurses, advanced practice practitioners, and respiratory therapists.

“It’s a big team that cares for these patients,” Dr. Zaccagni said. Research shows that standardizing the handoff from the ICU to the operating room increases communication without delaying surgery and increased provider satisfaction and patient readiness for surgery while reducing errors.[3],[4]

The cardiology service didn’t have standardized protocol for handoffs, so Dr. Zaccagni, together with Ashley Moellinger, RN, CRNP, leda quality-improvement (QI) project to develop a process that prioritized clear, concise, and consistent communication from the cardiac ICU to the operating room or catheterization lab.

They started with a survey of 82 staff members, which found that 69 percent had experienced a safety event related to inadequate handoff. The survey also showed that communication was the primary barrier to transition followed by organizational barriers.

The team developed a tool and process for handoffs that involved all clinicians who interacted with the patient. “This multidisciplinary approach is so important,” said Moellinger.

Now, the night prior to surgery, the nurse practitioner, bedside nurse, and respiratory therapist complete a data form on the patient. The next day, the entire team meets at the bedside to review the form and bring up any concerns. “A big part of this is around situational awareness, or concerns we have about the patient that might not be obvious from reading through the chart or notes,” said Moellinger.When the patient is transferred, the team verbally goes through the tool again to ensure there are no outstanding questions or changes in condition.

The team is also tracking what it calls “moments of clarity”—when the process unveiled a potentially problematic issue such as a difficult airway, unavailability of vasoactive drip, patient cardiac arrest the prior night, or airway management for a patient with worsening oxygen levels.

The goal, or “smart aim,” was to demonstrate a standardized handoff in 80 percent of transition interactions, with 80 percent completion of patient data points by December 2021, and 95 percent compliance by July 2022.

Reintervention Reduction

This reintervention reduction QI project focuses on the most complex cardiothoracic surgery performed in newborns. Called the Norwood procedure, the surgery involves constructing a new, larger aorta for babies born with hypoplastic left heart syndrome. Nationally, patients who don’t require an intervention after their surgery have a mortality rate of about 6 percent compared to the 26 percent mortality rate in those who require another surgery or catheterization procedure.

The project, which is part of the National Pediatric Cardiac Quality Improvement Collaborative, was designed to understand why reinterventions occurred and identify opportunities to recognize the warning signs early in the post-operative period.

The Children’s team first performed a root-cause analysis of the 69 patients who required additional interventions between January 2015 and June 2020. That involved identifying what triggered the complication and how it could have been prevented. Of the 69 patients, 23 (34 percent) required an unplanned cardiac surgery or catheterization while hospitalized after the first-stage operation. Half of the surgical interventions were to explore unexplained bleeding, and half of the catheterization interventions were for conduit stenting to improve pulmonary blood flow. Fewer than five patients (12.5 percent) who required a reintervention died compared to none in the other group.

Reviewing the entire care pathway from the cardiovascular ICU to the operating room and back, including rates of post-operative bleeding and the timing for administering blood products, “we were essentially able to come up with a solution that we should communicate more effectively between team members in the operating room,” said Dr. Zaccagni. One way to improve communication is to wait at least 30 minutes in the operating room after closing the sternum to estimate chest tube output. Another is to standardize blood work when a patient is bleeding in case it’s due to a rebound effect of blood thinners given during the surgery. In addition, the team developed a standardized tool for the post-operative debriefing with the entire team.

The efforts are already paying off, said Moellinger, with fewer reinterventions since they began in 2020. “Standardization and, thus, reducing variation in everything we do is an important component for the best outcomes,” she said.


[1] Makary MA, Daniel M. Medical error—the third leading cause of death in the US. BMJ. 2016;353:i2139.

[2] The Joint Commission. Inadequate hand-off communication. Sentinel Event Alert. September 12, 2017. Issue 58.

[3] Caruso TJ, Marquez S, ,Luis J, et al. Standardized ICU to OR handoff increases communication without delaying surgery. Int J Health Care Qual. 2017;30(4):304-311.

[4] Joy BF, Elliott E, Hardy C, Sullivan C, Backer CL, Kane JM. Standardized multidisciplinary protocol improves handover of cardiac surgery patients to the intensive care unit. Pediatr Crit Care Med. 2011 May;12(3):304-8.

Inside Pediatrics, Nephrology

Childhood Household Dysfunction Predicts Hypertension, Vascular Injury in Adolescents 

Dan Feig, M.D., Ph.D., is a pediatric nephrologist at Children’s of Alabama and a professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

Dan Feig, M.D., Ph.D., is a pediatric nephrologist at Children’s of Alabama and a professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

Verbal and physical abuse; neglect; and household dysfunction such as divorce, domestic violence, and poverty in early childhood (called adverse childhood experiences, or ACEs) affect approximately 25 percent to 30 percent of children in the United States. They also put those children at significantly increased risk for health issues like hypertension and cardiovascular disease as adults.  

“Ideally, we would like to prevent neglect, maltreatment, abuse, and household dysfunction,” said Children’s of Alabama pediatric nephrologist Daniel Feig, M.D., Ph.D. “But until that can be achieved, we need to work on mitigating their long-term effects.” Dr. Feig’s work looks at whether experiences have already changed the vascular function of individuals exposed to ACEs and whether those changes are reversible.  

“We want to see if there’s a detectable signal, something that puts them in the risk category for future disease and identify those who would benefit from intervention or therapy,” he said. 

Dr. Feig and his team used validated questionnaires to screen 78 teens for the three types of ACEs: abuse, neglect, and household dysfunction. Nearly 70 percent had been exposed to at least one ACE. The investigators also tracked the adolescents’ blood pressure with a 24-hour continuous ambulatory blood pressure monitor; measured their pulse wave velocity (a marker of blood vessel elasticity and reactivity); and looked for markers of inflammation and increased vascular tone in their bloodwork. 

They found that compared to teens with no exposure or with exposure to abuse and neglect, individuals exposed to household dysfunction had a significantly higher 24-hour diastolic blood pressure without the normal drop that occurs at night. They also found a significantly increased baseline inflammatory state. Those who experienced sexual abuse had substantially altered pulse wave velocity, which meant their blood vessels were stiffer. Despite these changes, the children had normal blood pressure. 

“This tells us that even as early as 10 to 12 years after exposure there are detectable alterations in vascular biology associated with the ACEs,” Dr. Feig said. “These individuals might benefit from interventions to reverse or slow those changes to prevent the progression of hypertension and the later risk of cardiovascular disease.” 

The team expected to see more changes in children with a history of exposure to abuse. Dr. Feig hypothesizes that the chronic nature of household dysfunction may be behind the vascular changes. “Things that reset the biology of the vessels are slow and steady effectors,” he said. “That can be dietary, that can be obesity, that can be emotional stressors, or chronic inflammation. I think that the household dysfunction category might have a greater continuous effect as opposed to episodes of horrific injury.” 

The next step is to intervene with medications to try and reduce inflammation and prevent the progression of vascular dysfunction.  

The group is currently following the study participants and hope to secure funding for larger longitudinal studies. 

Inside Pediatrics, Nephrology

Tracking Kidney Transplant Rejection in the Blood and Urine 

Michael Seifert, M.D., is a pediatric nephrologist at Children’s of Alabama and an associate professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

Michael Seifert, M.D., is a pediatric nephrologist at Children’s of Alabama and an associate professor in the Division of Nephrology in the University of Alabama at Birmingham Department of Pediatrics.

Children who receive kidney transplants at Children’s of Alabama undergo a routine biopsy six months after the procedure to look for signs of rejection. In about 20 percent of patients, those signs are there, even if their blood and urine tests look normal. “On the flip side,” said Children’s pediatric nephrologist Michael E. Seifert, M.D., “that means about 80 percent of our patients are getting biopsies that are normal.” 

The holy grail, then, would be a non-invasive biomarker test using blood or urine that can identify kidney transplant injury without needing a biopsy — which is exactly what Dr. Seifert and his lab are working on. Their research relies on a biorepository of patients’ blood, urine, and kidney biopsy tissue collected throughout and after the transplant process. 

One of the blood tests they’re working on uses technology originally developed to screen maternal blood for signs of fetal abnormalities. The test looks for cell-free DNA, or cfDNA, which comes from the fetus and differs from maternal DNA. Since transplanted kidneys also have DNA different from the patient’s own kidney, “you can look in the bloodstream for the proportion of the DNA coming from the transplant versus the normal background from the recipient’s non-transplant cells,” Dr. Seifert said. High levels of cfDNA is a sign of acute kidney injury that could be due to rejection.  

Studies in adults validate this as a good method to detect rejection. “But the problem is, those are done in adults whose native kidneys would be roughly similar in size to the transplant they’re carrying,” Dr. Seifert said. Children often have a much larger, adult-sized transplant compared to the size of their native kidneys, so the cutoff levels used for diagnosing rejection in adults may not work in children. “We’re trying to make these existing diagnostic tests more pediatric specific,” he said. 

The story is different for urinary biomarkers. It’s been known for years that the kidney releases certain proteins when it’s injured. Tests to detect those proteins, however, can take days. But a new device called SimplePlex, currently available only in the research setting, can measure several of these proteins at one time in a single sample in less than an hour.   

“We’re looking at ways to get this technology closer to the clinic, so you’re not just profiling kidney transplant patients’ risk for injury based on their standard blood tests like creatinine, but you’re also adding these additional biomarkers that can tell you more information about what’s happening inside the organ,” Dr. Seifert said.  

Being able to determine via blood and urine tests who needs a biopsy and who doesn’t would have a huge impact for pediatrics, particularly at Children’s, where these biopsies are done on a universal basis, he said. Ideally, the tests could also provide information on the underlying cause of the rejection. For instance, the cfDNA test is good at picking up antibody-mediated rejection, but not as good at recognizing cell-mediated rejection. The urine biomarkers are good at identifying both rejection types, but not at identifying rejection related to viral infections. 

“Once we understand more about the clinical scenarios in which the biomarkers perform well,” said Dr. Seifert, “we’ll be able to design interventional trials to treat the patient based on the biomarker changes rather than just the standard clinical tests such as creatinine.”