Inside Pediatrics, Neonatology

Generous Donation to NeuroNICU B.R.A.I.N. Program Helps Reduce Risk of Brain Injury in Premature Infants

NICU_WEB

Through a generous donation by Robert and Kathleen Israel, Children’s of Alabama is now home to new technology that helps dramatically prevent brain injury and improve brain development and function in its sickest patients.

Children’s of Alabama is thrilled to announce a very generous gift of a cutting-edge technology designed to help reduce the risk of brain injury in preterm infants. The gift was donated by Robert and Kathleen Israel in honor of the care their daughter, Ivy, received in the Neonatal Intensive Care Unit (NICU) in 2018. Ivy is home and doing very well. “The NICU team at Children’s of Alabama saved our daughter’s life,” said Robert Israel, “and we are forever grateful.”

“This new technology made possible by the Israel family is helping us  dramatically prevent brain injury and improve brain development and function in our sickest patients,” said Manimaran Ramani, M.D., director of the NeuroNICU program.

Preterm infants born at 30 weeks or earlier are at higher risk for developing intraventricular hemorrhage (IVH), which is associated with long-term neurocognitive and motor deficits. The risk for neurocognitive and motor deficits is also higher for term infants with hypoxic-ischemic encephalopathy (HIE), seizures, metabolic disorders, or stroke, and those undergoing ECMO therapy.

However, a multidisciplinary initiative in the NICU at Children’s of Alabama and the University of Alabama at Birmingham (UAB) called NeuroNICU B.R.A.I.N. (Brain Rescue and Avoidance of Injury in Neonates) aims to prevent and reduce neurocognitive and motor deficits in high-risk neonates.  

The objective of the B.R.A.I.N. program is to identify and prevent brain injury early in high-risk neonates through state-of-the-art diagnostic techniques and neuroprotective care. An interdisciplinary team of medical professionals meets every week to strategize individualized comprehensive neuroprotective plans for infants enrolled in B.R.A.I.N.

Though standard vital monitoring techniques used in NICUs such as blood pressure, heart rate and pulse oximetry provide valuable information about the infant’s hemodynamic status, such standard monitoring techniques don’t provide real-time information regarding the brain’s oxygenation saturation, oxygenation extraction and perfusion status of a sick neonate.

This is where infrared spectroscopy (NIRS) monitoring comes in. “This technology allows us to monitor cerebral oxygenation in very sick infants,” Ramani said. It is a non-invasive method that can be used continually at the bedside as well as during surgery to monitor the health of the brain. It can also be combined with amplitude-integrated electroencephalography (aEEG) to monitor cerebral electrical activity and to diagnose seizures in sick neonates in real-time.

“With the two NIRS devices donated by the Israel family, we are now able to monitor the brain health and adjust our therapies and strategies in real-time on our patients,” Ramani said.

 

 

Cardiology, Inside Pediatrics

Children’s of Alabama Receives Prestigious Accreditation from Children’s Cardiomyopathy Foundation

Cardiomyopathy_WEB

Livie Wheeler of Pell City, Alabama was diagnosed with dilated cardiomyopathy and underwent a successful heart transplant at Children’s of Alabama. Livie was discharged home just in time for her second birthday.

Children’s of Alabama was recently named an accredited center of care by the Children’s Cardiomyopathy Foundation (CCF), a national nonprofit committed to improving the health outcomes and quality of life for children with cardiomyopathy.

“We’re glad to be able to participate,” said F. Bennett Pearce, M.D., outgoing medical director of the Pediatric Advanced Heart Failure and Transplant Program at Children’s of Alabama. “CCF promotes education and helps families connect and choose centers with experience in these kinds of patients.”

The Pediatric and Congenital Heart Center of Alabama at Children’s of Alabama is one of the largest pediatric cardiovascular programs in the Southeast. In 2018, its team of 250 dedicated professionals treated more than 230 patients with pediatric cardiomyopathy. The team includes surgeons, intensivists, cardiologists and many others, including nurses, social workers, child life specialists, genetic counselors, nutritionists, occupational and physical therapists, and chaplains.

“We have traditionally had very strong clinical abilities and success with treating a variety of these conditions,” Pearce said. “Over the 25 years that I’ve worked in the program, I feel we have been among the finest centers, but we have not been quite so active in getting the word out. That needs to change because we want to make families aware that there’s a good resource for them here.”

The CCF offers a plethora of educational and supportive programs for families, as well as a research grant program for basic, clinical, population/epidemiologic, or translational studies focused on primary pediatric cardiomyopathy.

Its accreditation program was established in 2017 to recognize excellence in diagnosing and treating pediatric cardiomyopathy and provide families with standardized center information to help them find an expert treatment center in their area. To date, 39 centers in the U.S. and Canada, including Children’s of Alabama, have been accredited.

The CCF has very strict criteria for accreditation. Centers must:

  • Manage 30 or more cardiomyopathy patients up to age 18 annually or 60 pediatric cardiomyopathy patient visits a year.
  • Have at least one pediatric cardiologist who treats patients with dilated, hypertrophic, restrictive arrhythmogenic and right ventricular or left ventricular non-compaction cardiomyopathy.
  • Be part of a teaching hospital affiliated with a medical school.
  • Offer the following:
    • Prenatal or fetal echocardiography
    • High quality imaging (echocardiogram, cardiac magnetic resonance imaging)
    • Interventional cardiology (catheterization, endomyocardial biopsy)
    • Pediatric cardiac electrophysiology
    • Cardiac surgical services (septal myectomy, cardiac device implantation)
    • Genetic testing and counseling
    • Pediatric neurology
    • Social work
    • Child life services
  • Centers must also have at least one of the following (Children’s of Alabama meets all four):
    • A specialized clinic or program focused on pediatric cardiomyopathy or familial hypertrophic cardiomyopathy with a dedicated team of professionals.
    • Involvement with the North American Pediatric Cardiomyopathy Registry, Pediatric Cardiomyopathy Repository or Pediatric Heart Transplant Study Group.
    • Engagement in pediatric cardiomyopathy research.
    • Advanced heart failure management and transplantation.

“We have everything needed to offer to this group of patients,” Pearce said. “And we want to make sure that when a family confronts this difficult diagnosis, they can easily find our program and be assured that it is a good resource.”

 

Inside Pediatrics, Neurology & Neurosurgery

Children’s of Alabama Clinicians Bring Expertise and Training to Vietnam

Global Surgery NEW_WEB

Children’s of Alabama physicians review a brain scan at a hospital in Vietnam. Neurosurgeons, neurologists and other medical staff travel to Vietnam at least once a year to provide lectures and hands-on training at hospitals in Hanoi and Ho Chi Minh City as part of Children’s of Alabama’s Global Surgery Program.

Surgical interventions to reduce the burden of drug-resistant epilepsy in children have become an integral part of the field in the past 20 years. In low- or middle-income countries like Vietnam, however, it typically remains a vision, not a reality. Vietnam, for instance, has just two adult and two pediatric neurosurgery training programs for a country of 95 million people, and just four pediatric neurosurgeons serving a population of more than 50 million in the northern part of the country.

Enter Children’s of Alabama’s Global Surgery Program, which is designed to form strong, collaborative relationships with large pediatric hospitals in low- and middle-income countries and provide subspecialty fellowship training at Children’s. The hospital’s relationship with Vietnam began in 2013, with an initial visit to neurosurgeons in Ho Chi Minh City. Since then, a team from Children’s, including pediatric neurosurgeon Brandon Rocque, M.D., MS, FAANS, Pediatric Epilepsy Surgery Director Pongkiat Kankirawatana, M.D., Clinical Neurophysiology and Pediatric Epilepsy Program Director Monisha Goyal, M.D., and Director of Neuromonitoring Trei King, R.EEG.T, C.N.I.M., among others, has traveled the nearly 9,000 miles to Vietnam at least once a year to provide lectures and hands-on training at hospitals in Hanoi and Ho Chi Minh City. Their efforts have helped create premier epilepsy programs that draw children from throughout southeast Asia.

“We started with the corpus callosotomy,” Rocque said, a procedure performed on children with generalized epilepsy prone to drop attacks. It involves splitting the main connection pathway between the two cerebral hemispheres to prevent the attacks. The Vietnamese team, led by a neurosurgeon who specialized in brain tumors, performed two such surgeries with the Children’s of Alabama neurosurgeons, then went on to complete 10 themselves over the next six months, all with good long-term results.

Epilepsy surgery is not possible without advanced EEG monitoring, which is where King came in. His job was to teach EEG technologists how to use an EEG in the operating room, including electrode placements, and the most appropriate test for the child’s condition. “We started with the basics and now we’re going much deeper,” he said.

“The people there are extremely hard working and very, very smart,” King said. “They just didn’t have the opportunity and education. The training with our staff allows them to see the entire gamut of what we do in the field and, hopefully, grow to do what we do.”

The Children’s of Alabama team usually spends a week in each city, giving lectures and assisting with the more complex surgeries. “We’re not trying to hammer out a bunch of cases,” Rocque stressed. “The model is not missionary surgery; it’s teaching and working on the patients they asked us to assist with in order to reach a goal of improving specific techniques for the neurologists and surgeons.”

In addition to building the team’s skills in epilepsy surgery, the team hopes to improve how pediatric neurosurgeons are trained in Vietnam, Rocque said. Currently, residents are trained in neurosurgery but don’t receive any formal pediatric training. “There is a really big opportunity to improve the way pediatric neurosurgery is taught in this region,” Rocque said. To help in that goal, Vietnamese physicians and EEG nurses now come to Alabama for several months for focused training on various procedures.

The partnership has continued to grow, with the Vietnamese doctors sending PowerPoint presentations on difficult cases for discussion at Children’s of Alabama’s weekly multidisciplinary meeting, during which the neurology team develops treatment plans. Now the team also discusses the Vietnamese patients. “When we started, we often had to ask for more information and make some changes to the treatment plan,” Rocque said. “But over the last year, their own recommendations have been spot on.”

The experience has been eye opening for the Children’s of Alabama clinicians. “I found a pediatric neurology and neurosurgery program making a valiant effort in diagnosing and treating one child after another with minimal resources,” said Goyal, who visited City Children’s Hospital in Ho Chi Minh City. The children slept on cots that spilled out into the adjacent roofed but open courtyards and hallways, she said. “There were no fans and in September temperatures in Ho Chi Minh were far from balmy.” She was also struck by the fact that the government does not allow the use of benzodiazepines, one of the most common medications used to control seizures in the U.S.

However, Goyal said, “the small number of clinicians do an admirable job with limited resources. They learn from textbooks, not from mentors, even though they have much fewer technical and pharmacological resources.”

“As a physician, this has been a very rewarding experience,” Goyal said. She, Rocque and King are planning another trip this spring to Ho Chi Minh City to continue helping the hospital develop of its own pediatric surgical epilepsy program.

King echoed Goyal’s comments. “It’s been one of the most rewarding things I’ve experienced in my career,” he said. “You see the big difference you make not only in the training, but in the impact on the patients receiving care that they would not get unless we’re there.”

“The patients and families are so appreciative,” King said. “I’ve never experienced that level of appreciation before. I think a lot of it has to do with realizing that without the partnership and collaboration we wouldn’t be able to do the surgeries.”

For instance, he recalls one family whose child was operated on returning to the hospital a year later with a picture of the child to express their thanks. “Those are the things they make this so rewarding,” he said. “When we see the difference it makes in the life of the patients and families and the joy that continues long after the surgery.”

Inside Pediatrics, Neurology & Neurosurgery

At Children’s of Alabama, Transitioning Spina Bifida Patients to Adult Care Begins at Age 13

Spina Bifida_WEB

Professional heavyweight boxer Deontay Wilder greets a patient while touring Children’s of Alabama’s Comprehensive Spina Bifida Program space in this 2015 photo. The multidisciplinary program treats about 500 patients a year.

Before the 1970s, about one in four infants born with spina bifida died. Today, thanks to advances in neurosurgery, genitourinary surgery, gastroenterology and physical medicine and rehabilitation, between 75 and 80 percent now survive into adulthood.[1]

But surviving doesn’t mean thriving. That’s what clinicians from Children’s of Alabama’s multidisciplinary Comprehensive Spina Bifida Program, which treats about 500 patients a year, learned when they joined specialists at the University of Alabama at Birmingham (UAB) to develop an adult spina bifida clinic. While there is a greater awareness in the pediatric community about the overall need for transitional programs, said Jeffrey P. Blount, M.D., FAANS, chief of pediatric neurosurgery at Children’s of Alabama, more is needed than simply transferring a patient’s medical records.

“Our patients were arriving unprepared not just for adult health care, but for adult life in general,” said Spina Bifida Program Coordinator Betsy Hopson, MSHA, who assists patients in the transition from pediatric to adult care.  “We’d watch them grow up and hear about their dreams but every year it seemed like the light inside them was becoming dimmer and their opportunities fading away.” By the time they arrived at the adult clinic, she said, many patients were depressed and their childhood dreams seemed to have disappeared.

“We thought, ‘We’ve got to do better with this next generation,’” Hopson said.

They, along with Children’s of Alabama neurosurgeon Brandon Rocque M.D., MS, FAANS, started with data, surveying 188 patients in the adult clinic about their perceptions of their own disability. More than half (56.4 percent) identified as permanently disabled, with the most important predictors of disability being poor bowel continence and low education.[2]

They also found that 70 percent of those surveyed were not working and, again, poor bowel continence and low education were determining factors, as well as diagnosis (open versus closed spinal dysraphism). Rocque emphasized that patients with daily bowel accidents were six times more likely to be unemployed, while those with weekly accidents were three times more likely to be unemployed.

Thus was born the Individualized Transitional Plan (ITP), which starts at age 13. The objective is to ready the child for adulthood by developing and achieving five goals, including bowel management and educational achievement. Goals also include transitional readiness (ie, do they know their medical history, can they make their own appointments and see the doctor without a parent present); meeting a parent-initiated goal (ie, showering without being told or learning how to cook); and a personal goal, such as learning to eat healthier. Hopson individualizes care to transform each goal into a measurable task and the results become a contract and framework for the next few years.

They also receive a transition binder that includes a career interest survey. “They complete it before they see me and then I help guide them,” Hopson said. She also ensures their career  goals are realistic. For instance, one patient said he wanted to be the Marines, which she knew wasn’t possible. Instead, she suggested a meeting with a recruiter to discuss civilian jobs in the military.

About 45 percent of patients fall into the age group for the ITP, which is part of the clinic’s Lifetime Care Model (LCM). The LCM begins prenatally and continues throughout the adult years.[3] Hopson developed the ITP, which has generated great interest from other clinics in North America who are struggling with the challenges of implementing a meaningful transition program.

Since starting the program, Blount said, clinicians from throughout the country have contacted the team at Children’s to learn how to start their own program. “There’s such a need for a supportive multidisciplinary clinic to support these patients,” he said.

“This model could be replicated for other children with chronic conditions,” Hopson said. “If we’re doing our jobs well, our children are going to be adults. So we have some obligation to get them there in a way that provides a good quality of life.”

Bowel Management Program

Children with spina bifida are born with neurogenic bladder and bowel issues. While urination can be managed through catheterization, with children as young as 3 years old learning to catheterize themselves, “bowel management is much trickier,” Hopson said. Gastrointestinal motility slows and constipation becomes a chronic issue. Unfortunately, she said, many families prefer constipation to regular movements because it’s easier to handle. But “once you set up that pattern it’s hard to break,” she said.  And bowel management, she said, “becomes the most important issue in whether they are able to get a job.”

Today, the children in the spina bifida clinic benefit from working with pediatric gastroenterologist Mitchell B. Cohen, M.D., and members of the Division of Physical Medicine and Rehabilitation. Cohen chairs the UAB Department of Pediatrics and is physician-in-chief at Children’s of Alabama. He became interested in the program after hearing Hopson speak. He developed a protocol beginning at age 4 to help families understand the importance of a bowel management program and try to end their reliance on constipation.

Nonetheless, it remains an “extraordinarily difficult problem,” Roque said. “There is no magic bullet.” Still, “with Cohen’s help we’re making inroads on this extraordinarily difficult problem that has profound impact that echoes through rest of a child’s care, including issues of self-image and self-worth.”


[1] Talamonti G, D’Aliberti G, Collice M. Myelomeningocele: Long-term neurosurgical treatment and follow-up in 202 patients. J Neurosurg 2007; 107: 368-86.

[2] Davis MC, Hopson BD, Blount J, et al. Predictors of permanent disability among adults with spinal dysraphism. J Neurosurg Spine. 2017 August ; 27(2): 169–177.

[3] Hopson B, Rocque BG, Joseph DB, et al. The development of a lifetime care model in comprehensive spina bifida care. J Ped Rehab Med. 2018; 11:323–334

 

Cardiology, Inside Pediatrics, Nephrology

Children’s of Alabama Leads Consortium Dedicated to Improving Outcomes in Cardiac Surgery-Acute Kidney Injury

NEPHRON_WEB

Children’s of Alabama is one of 22 hospitals in the U.S. that is a member of the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON).

Neonatal acute kidney injury (AKI) occurs in 52 to 64 percent of patients undergoing cardiac surgery (CS) and is associated with increased morbidity and mortality.

However, because CS-AKI rates vary widely between centers, it appears that interventions to prevent or mitigate the condition could reduce the overall rate.

Yet, noted Santiago Borasino, M.D., medical director of Children’s of Alabama’s Cardiovascular Intensive Care Unit (CVICU), “there are critical gaps in our understanding as to how to best define CS-AKI, who is at risk, and which patients could best benefit from interventions to prevent or  mitigate the effects of CS-AKI.”

To improve understanding of CS-AKI in this population, Borasino is one of the leaders of the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON), composed of 22 children’s hospitals around the country. The consortium’s goals are to describe neonatal kidney injury epidemiology, evaluate variability in diagnosis and management, identify risk factors, investigate the impact of fluid overload and explore associations with outcomes. It involves multidisciplinary teams including clinicians from cardiac critical care, cardiology, nephrology, and cardiac surgery.

“NEPHRON is providing multicenter data on CS-AKI for the first time,” Borasino said. “The large size of the cohort will enable us to look at details that are not possible with single-center studies.”

NEPHRON published its preliminary results in April 2019, reporting an overall incidence of 54 percent among 2,240 patients in its database.[1] In November 2019, NEPHRON presented additional results during the American Heart Association’s annual meeting, showing a threefold variation in rates among centers, from 27 percent to 86 percent, with significant variations in KDIGO stage (adult AKI definition) to identify AKI (65 percent by oligo oligo-anuria versus 35 percent by creatinine).

The results also showed that the use of cardiopulmonary bypass, but not time spent on bypass, increased the odds of CS-AKI, and that only KDIGO Stage 3 was associated with mortality. There was no impact of CS-AKI on the duration of mechanical ventilation or hospital length of stay.[2]

“NEPHRON preliminary results highlight the limitations of the KDIGO definition and the need to better understand CS-AKI as it occurs with incredible variability among centers, opening the door for future quality improvement intervention,” Borasino said.

The next step is to develop an algorithm to predict which patients are more likely to develop AKI so physicians can intervene earlier. “Early recognition and proper management of AKI are at the forefront of critical care medicine,” said Children’s of Alabama pediatric nephrologist Tennille Webb, M.D. “However, most pediatric hospitals that perform cardiac surgeries do not have protocols in place for managing severe AKI post-operatively.” Webb is now working on developing a clinical pathway to identify patients at increased risk of AKI based on specific patient characteristics. “An advantage to developing this algorithm in the CVICU is that we are able to determine the exact timing and etiology of AKI development in individuals undergoing cardiopulmonary bypass,” she said. “If we can proactively identify risk factors that place these individuals at increased risk for AKI, we can provide earlier intervention, such as early initiation of renal replacement therapy, in an effort to mitigate some of the known severe consequences of AKI.”

“The work that we are doing is very important because we know that AKI post-cardiac surgery leads to worse outcomes and is associated with chronic kidney disease,” Webb said. “It’s great, and yet rare in other institutions, that we have been able to develop a strong relationship between the CVICU and nephrology to work as a cohesive team early AKI detection and prevention.”


[1] Gist KM, Blinder JJ, Bailly D, Neonatal and Paediatric Heart and Renal Outcomes Network: design of a multi-centre retrospective cohort study. Cardiol Young. 2019;29(4):511-518.

[2] Alten J, Cooper DS, Gist KM, et al. , Abstract 13177: Epidemiology of Neonatal Cardiac Surgery Induced Acute Kidney Injury From the Neonatal and Pediatric Heart and Renal Outcomes Network. Circulation. 2019;140(Suppl1).

 

Inside Pediatrics, Pulmonology

Children’s of Alabama Muscular Dystrophy Care Center Offers Life-Saving Treatment for Rare, Fatal Disease

MDA_WEB

Brad Troxler, M.D., director of the Muscular Dystrophy Care Center (MDA) at Children’s of Alabama, chats with a patient. The MDA Care Center is the only MDA clinic in Alabama and one of only a few in the region.

The Muscular Dystrophy Care Center (MDA) at Children’s of Alabama sees about 280 patients a year with a wide variety of neuromuscular conditions. They require multidisciplinary care from neuromuscular specialists, neurologists, pulmonologists, genetic counselors and cardiologists, among others. They also need respiratory, physical and occupational therapies, nutritional counseling and social work support.

One of the most devastating conditions the clinic sees is spinal muscular atrophy (SMA), a rare autosomal recessive genetic disorder that is the leading cause genetic cause of death in infants. It is characterized by degeneration and loss of lower motor neurons, leading to muscle atrophy. Infants with the most serious form of the disease, Type 0, can be diagnosed prenatally and typically die before 6 months, while those with Type 1 begin showing symptoms around 6 months, require ventilation and typically die before age 2. Other types of SMA may not manifest until childhood or even adulthood and are less severe, although all of those affected experience some neuromuscular effects.

Until recently, SMA was primarily treated with supportive care. Today, however, there are two groundbreaking treatments and Children’s is the only MDA clinic in the state, and one of only few in the region, to offer both: nusinersen (Spinraza), approved for children and adults, which is administered in several doses the first year and annually after that; and onasemnogene abeparvovec-xioi (Zolgensma), a single-dose treatment approved for use in children with SMA Type 1 under age 2.

Both are gene therapies designed to address genetic mutations in the SMN1 and/or SMN2 genes, which make the protein required to control muscle movement. Both are also extremely expensive, with the first 10 years of treatment with Spinraza estimated at $4 million and a single dose of Zolgensma costing $2.1 million, making it the most expensive drug ever marketed.[1]

The cost could be worth it, though, given the benefits of the drugs. “Clinical trials showed huge improvement,” said Brad Troxler, M.D., who MDA Care Center director. Indeed, after four years, infants treated with Spinraza before they turned 6 weeks were still achieving and maintaining motor milestones such as walking and sitting without assistance, things SMA babies would not normally be able to do.[2]

Participants in the Zolgensma trials were demonstrating similar results, with all children who received the drug still alive at 2 years and none requiring ventilation.[3]

Don’t call the treatments cures, however, says Troxler. “‘Cure’ is a hard word to define,” he said. While improved, patients still don’t have normal neuromuscular function after receiving the drug, with some muscle weakness remaining and an increased risk of scoliosis and other issues related to the disease. “But if we give it early enough, they are able to walk and talk and eat so it’s pretty close to a cure,” he said.

The earlier the drugs are administered, the greater the benefit. “Time is neurons,” said Shelley Coskery, MSN, CRNP-AC, MDA Care Center coordinator. However, Alabama is one of the few states that doesn’t screen newborns for SMA, which could delay treatment until symptoms appear. “We’re working on it,” Coskery said. “We need to start treating these patients before they develop symptoms and then, hopefully, we will see fewer and fewer affected with the disease.”

Becoming one of the first centers to offer SMA treatments, she said, “puts us at the forefront of the gene replacement movement.” Indeed, the center is also beginning clinical trials for genetic therapies for children with Duchenne, one of the most common neuromuscular diseases.

The ability to provide such effective treatments to children who otherwise would have died before age 2 “is very profound,” Troxler said. “You can see the difference it makes on individual families in a really powerful way. Conversations historically been about how ‘this is a terrible disease that will likely end in your child’s death.’” Now, Troxler said, the conversation has changed to, “‘Your child has a horrible disease, but we have some therapies that are going to change what this looks like.’ It’s completely different.”

“There is a lot of excitement throughout the SMA community,” Coskery said. “We are very grateful when the parents send emails of the child standing and achieving milestones we didn’t think they would.”


[1] Thomas K. his New Treatment Could Save the Lives of Babies. But It Costs $2.1 Million. The New York Times. May 24, 2019.

[2] Biogen Announces New Data Further Establishing SPINRAZA® (nusinersen) as a Foundation of Care in Spinal Muscular Atrophy for a Broad Range of Patients. Available at: http://investors.biogen.com/news-releases/news-release-details/biogen-announces-new-data-further-establishing-spinrazar

[3] New Data Shows Long-Term Benefits of Zolgensma in SMA Patients. Available at: https://www.biospace.com/article/in-wake-of-data-manipulation-scandal-avexis-releases-long-term-efficacy-of-zolgensma-at-conference/

Hematology and Oncology, Inside Pediatrics, Neurology & Neurosurgery

Big Changes Coming to Children’s of Alabama’s Neuro-Oncology Division

Children's Cancer Hospital_WEB

The Pediatric Neuro-Oncology Program at Children’s of Alabama will launch new initiatives this year, including forming a relationship with Children’s Cancer Hospital in Cairo, Egypt, pictured above.

Girish Dhall, M.D., can quickly tick off the attributes of Children’s of Alabama’s Pediatric Neuro-Oncology Program that lured him from Children’s Hospital Los Angeles to become division director for the Hematology, Oncology, and Blood and Marrow Transplantation Program as well head of the Neuro-Oncology program here. “It’s a very robust and academically active program in the country,” he said. “One of the strong points is that we have four neuro-oncologists, four pediatric neurosurgeons, two pediatric neuroradiologists and one pediatric neuropathologist. This is not available in most hospitals in the country.”

Indeed, the Pediatric Neuro-Oncology Program at Children’s of Alabama is one of the strongest in the country, treating between 50 and 70 newly diagnosed patients a year and participating in cutting-edge clinical trials for children with brain tumors.

In 2020, Dhall and his team will welcome their first neuro-oncology fellow. “So we will train the next generation of pediatric neuro-oncologists,” he said.

“There is such a need to have more people trained,” Dhall said. “Pediatric brain tumors are the most common cancer in children and we don’t have enough people trained to treat them.”

“Neuro-oncology is very specialized,” said pediatric neuro-oncologist Laura “Katie” Metrock, M.D., who will run the fellowship program.  “The general hematology/oncology fellowship is more broad. This opportunity provides a full year of exposure to all aspects of neuro-oncology that are not available in the general fellowship.”

Metrock, who completed her own neuro-oncology fellowship at Emory University in Atlanta before coming to Children’s of Alabama, noted how much she appreciated her year of training. “I’m very excited to help others in that phase of their career,” she said. “If they choose to stay here then they will be helping kids in our community and if they go to other centers it provides more opportunity for collaboration.”

Metrock is also leading initiatives in neurofibromatosis (NF), which predisposes patients to nervous system tumors. “I took the position at Children’s of Alabama because I saw such a huge opportunity here,” she said. She is excited about working with the Neurofibromatosis Clinical Trials Consortium, which is based at the University of Alabama-Birmingham. The Consortium, directed by Bruce Korf, M.D., Ph.D., is a national leader in clinical and genetic studies on NF. “The ability to work directly in the front line of these trials coming through the Consortium was a huge opportunity,” Metrock said. “We have the opportunity to build something really special here for families and patients with NF.”

That includes a multidisciplinary clinic where children with NF-related cancers can obtain the variety of care they need from not only oncologists and hematologists, but geneticists, neurologists, endocrinologists and others. “We try to streamline their care and make sure they have access to other specialists, available therapies, and clinical trials,” Metrock said. That includes a partnership with the Pediatric Cancer Genetics Clinic. “We want to help the kids as they go through each phase and then ensure a smooth transition to the adult world,” Metrock said.

Among the other initiatives Dhall has begun is a global outreach in neuro-oncology. An oncologist from Vietnam recently trained in Alabama for two months and Dhall is now formalizing a relationship with the Children’s Cancer Hospital in Cairo, Egypt, which treats about 60 percent of the country’s entire pediatric cancer population. “We see about 150 pediatric cancer patients a year,” he said. “They see 4,000 a year. So the impact that we could have in helping train their doctors here is huge.”

Inside Pediatrics, Neonatology

Debriefing after Resuscitation: A Quality Improvement Initiative

Resuscitation_WEB

In October 2018, the Children’s of Alabama Neonatal Intensive Care Unit embarked on a quality improvement project, Debriefing Following Resuscitation/Code Events in the NICU, to identify opportunities to improve the resuscitation process, including staff satisfaction. It is one of several quality initiatives led by the Children’s Hospitals Neonatal Consortium.

The Neonatal Intensive Care Unit (NICU) can be an intimidating and stressful place to work.  One of the most stressful events in the NICU is a neonatal code or resuscitation, which may require intubation, chest compressions and special medications, all delivered under the pressure of knowing that seconds count. This requires that the team of doctors, nurses, respiratory therapists, pharmacists and other practitioners work together like a well-oiled machine.

Resuscitation codes are, by definition, rare events, said Children’s of Alabama neonatologist Hannah Hightower, M.D. Weeks may go by without any and then they might have several in one month. But they are definitely disruptive and stressful.

In October 2018, the Children’s of Alabama NICU embarked on a quality improvement project, Debriefing Following Resuscitation/Code Events in the NICU, to identify opportunities to improve the resuscitation process, including staff satisfaction. It is one of several quality initiatives led by the Children’s Hospitals Neonatal Consortium (CHNC), a group of more than 30 children’s hospitals around the country dedicated to using performance improvement methods to improve the delivery and quality of care in Level IV NICUs, which care for high acuity and medically complicated neonates.

The premise is simple. As soon as possible after the code, everyone gathers for a few minutes to discuss what went well, any equipment or medication problems, communication quality, and, of course, highlighting what could go better next time. They also complete a short form documenting the discussion. In just three months, the team at Children’s exceeded its goal of holding post-resuscitation debriefings after 80 percent of codes.

Such approaches can lead to improved resuscitation quality and reduced mortality, research finds. [1]

“The goal is to help everyone involved in the process improve skills, cope with the stress, and ultimately and most importantly, improve the process and patient outcomes by identifying potential latent safety threats,” Hightower said. “We want everyone on the team to feel free to express any concerns as well as provide support. Even the caregivers need a chance to decompress.”  “Not only does it provide a venue for raising issues related to caring for the patient, she said, “but it also lets us show appreciation for the things that went well.”

“It wasn’t a surprise to hear that one of the biggest issues is communication in a stressful period,” Hightower said. “We can always improve communication, whether that means discussing who is leading the code or controlling the volume so everyone can hear and understand what’s going on.” Discussing communication issues shortly after the code is important, she said, “because it’s at the front of your mind. By doing this immediately, you remember things you may not later and can articulate issues that might not be apparent in a week or two.”

Since implementing the initiative, the team has begun a proposal to further improve communication by emphasizing who is leading the code. Future projects include providing each member a way to give real time feedback not just to the code event, but also to the quality and effectiveness of the debrief. “We want to quickly identify systemic matters that can be improved for the next event. This is to develop a culture of freely expressing ideas and working through issues together as a team,” Hightower said.

The team is still collecting data on the primary outcome of latent safety events, a key component of any quality improvement initiative. Secondary outcomes include quality of the debriefs and composition of the responding code team.

“I credit our success to our strong nursing leadership and the willingness of the staff to be actively involved in quality improvement and do the extra work required to accomplish that goal,” Hightower said. “They have to step away from the patient and cover for each other during the debrief and even though it may take just a few minutes, to ask a nurse to step away from the patient is a big task.”

Although the team is still collecting data on the impact on staff satisfaction, she said, “anecdotally we have heard from nurses and other staff who feel they had a chance to say what they needed during the code or might need in the future. That’s gotten positive feedback.”

“It’s important to highlight the goal of this project is improved patient care, patient outcomes and staff satisfaction,” Hightower said. It’s also important that Children’s of Alabama is a part of a national collaborative with other major children’s hospitals, she said, and has been one of the most successful programs in the CHNC in terms of demonstrated outcomes. Other performance improvement initiatives with the CHNC include improving pain management and reducing nephrotoxic injury.

Resuscitation_CHART

In just three months after embarking on its quality improvement project, the NICU team at Children’s of Alabama exceeded its goal of holding post-resuscitation debriefings after 80 percent of codes.


[1] Wolfe H, Zebuhr C, Topjian AA, et al. Interdisciplinary ICU Cardiac Arrest Debriefing Improves Survival Outcomes Crit Care Med. 2014 Jul; 42(7): 1688–1695.

 

Inside Pediatrics, Nephrology

Pediatric Extracorporeal Photopheresis Offers New Option for Transplant Patients at Children’s of Alabama

Photopheresis_WEB

Children’s of Alabama nurses Daryl Ingram and Suzanne Gurosky next to the hospital’s photopheresis machine. After months of planning and training, Children’s of Alabama’s first photopheresis treatment was successfully provided on April 12, 2017. Previously, Children’s of Alabama patients were being transported to and from the University of Alabama at Birmingham (UAB) for treatment.

Children’s of Alabama’s Acute Renal Therapy team is now able to offer extracorporeal photopheresis (ECP) for heart transplant patients experiencing chronic rejection and bone marrow transplant patients who develop graft-versus-host-disease (GVHD). It is the only program in the state to provide the service to pediatric patients.

The U.S. Food and Drug Administration first approved ECP in 1988 to treat patients with a certain form of cutaneous T-cell lymphoma. Since then, ECP has demonstrated efficacy in GVHD, solid organ transplant rejection and rheumatoid arthritis, among others.

During the three-hour procedure, the patient’s leukocytes are separated from the peripheral blood, combined with a photoreactive drug and then exposed to ultraviolet irradiation, resulting in massive apoptosis. The cells are then reinfused into the patient.

It’s not quite clear how the process works, although theories suggest that when antigen-presenting cells clear the apoptotic cells, they differentiate into a more tolerogenic phenotype, resulting in decreased stimulation or depletion of effector T cells. Another theory is that it results in greater production of anti-inflammatory cytokines (interleukin 10) and reduced production of pro-inflammatory cytokines (especially interleukin 12 and TNFα), or that it triggers the generation of several T-regulatory cells.[1]

“Basically”, said Sahar Fathallah-Shaykh, M.D., medical director the Pediatric Dialysis Unit at Children’s of Alabama, “the leukocytes are now less reactive to the foreign tissue, reducing organ rejection and GVHD. However, she said, while studies find good rates of success in reversing organ rejection and GVHD, it’s not a cure. “It is used in conjunction with other immunosuppressive medications when other things haven’t worked. We add this and hopefully it works.”

Previously, Children’s of Alabama patients had to be transported to and from the University of Alabama at Birmingham (UAB) for this treatment. “It wasn’t an ideal setup,” said David Askenazi, M.D., who directs the Pediatric and Infant Center for Acute Nephrology at Children’s of Alabama. “There were different medical record systems, which wasn’t optimal for timely patient care of pediatric patients in an adult hospital.” So when the cardiology and bone marrow transplant team needed to bring the therapy to Children’s, Askenazi and his team, which already had experience with extra-corporeal therapies, stepped forward to run it.

“Bringing the program to Children’s was challenging,” Fathallah-Shaykh said. “The medical staff and physicians required extensive training, particularly in using the single lumen port needed for vascular access, which is unique to this procedure. But it was worth it.”

“Even though we don’t have many patients who require ECP,” she said, “the message is that we’re here, we’re available and we can help improve the care of our patients in a pediatric-friendly environment with pediatric nursing care.”


[1] Klassen J. The role of photopheresis in the treatment of graft-versus-host disease. Curr Oncol. 2010 Apr; 17(2): 55–58.

 

 

Hematology and Oncology, Inside Pediatrics

Children’s of Alabama Ramps Up Pediatric Oncology Research Program

HemOncFaculty_WEB

The faculty of the Pediatric Hematology, Oncology, and Blood and Marrow Transplantation program at Children’s of Alabama and the University of Alabama at Birmingham (UAB). The program is currently working to offer more potentially life-saving clinical trials to patients.

It’s only been a year since Girish Dhall, M.D., moved from Los Angeles, where he was an associate professor of pediatrics and director of the Neuro-Oncology Program at Children’s Hospital Los Angeles, to Birmingham to become division director for the Pediatric Hematology, Oncology, and Blood and Marrow Transplantation program at Children’s of Alabama and the University of Alabama at Birmingham (UAB). Yet he’s already made significant progress on one of his key goals: offering more potentially life-saving clinical trials to patients.

“We’re trying to increase our research portfolio through multiple mechanisms,” he said. Children’s already belongs to the largest pediatric cancer research organization in the world, the Children’s Oncology Group (COG), an international consortium of more than 200 children’s hospitals, universities, and cancer centers. Children’s of Alabama and UAB participate in the COG Phase I Consortium, the Neurofibromatosis Consortium and the Next Consortium, all of which conduct cutting-edge clinical trials for pediatric patients with nervous system tumors.

While COG is a major force in pediatric oncology, the number of trials it offers is limited. With about 150 new cancer patients a year seen at Children’s of Alabama, Dhall said, more opportunities are needed. “Even though we’ve come from a survival rate of zero 50 or 60 years ago to nearly 70 percent, 30 percent of patients still relapse,” he said.

Thus, Children’s of Alabama and UAB joined the Sunshine Project, which is a part of the National Pediatric Cancer Foundation. It emphasizes basic and translational research in the areas of bone and soft tissue sarcoma and brain tumor immunology, Dhall said.

Children’s of Alabama and UAB are also joining the Pacific Pediatric Neuro-Oncology Consortium,  an international research group with study sites in the U.S., Canada, Europe and Australia. It focuses on translating the latest findings in brain tumor biology into better treatments. “Their mission is to conduct high-risk, high-reward trials that are scientifically sound and cutting edge,” Dhall said. Membership will provide access to multiple brain tumor trials for Children’s of Alabama patients.

To manage the expected growth in clinical trials, Dhall is also reorganizing the department’s clinical trial infrastructure to improve efficiency and recruiting additional staff to prepare for the anticipated increase. He also wants to add other scientists who can build on the department’s portfolio not just in brain tumors, but also in sickle cell disease and leukemia. “That’s my hope for the next year,” he said.

He predicts that the number of clinical trials, today at about 10, will double within the next two years.

“Patients who relapse after front-line therapy have a very poor prognosis with poor survival,” Dhall said. “So, for us to be able to offer treatment options here means they don’t have to travel to other sites like Atlanta or Memphis, which is a huge disruption for patients at the end of life.”

“As a physician,” he said, “this gives me hope and it keeps me going.”