Learn about Children’s of Alabama and the innovative programs, research and advances in pediatric health care being made at one of the No. 1 hospitals for children in the Southeast during the Pediatric Academic Societies (PAS) Meeting in Washington, D.C., April 27 to May 1.
Children’s of Alabama and the University of Alabama at Birmingham (UAB) are proud sponsors of the 2023 PAS Meeting and will have a team in attendance. You can visit us at Booth #536 during the conference, learn from the numerous posters and sessions presented by our faculty and fellows, and keep up with PAS sessions and events through the Children’s of Alabama sponsored app. We will also be hosting a Children’s and UAB Alumni and Friends Reception Saturday, April 29, at the Renaissance Washington, D.C. Downtown. For more information, contact Heather Watts at hwatts@uabmc.edu.
Since 1911, Children’s of Alabama has provided specialized medical care for ill and injured children, offering inpatient, outpatient and primary care throughout central Alabama. Children’s serves patients from every county in Alabama and nearly every state. Children’s is a private, not-for-profit medical center that serves as the teaching hospital for UAB pediatric medicine and surgical divisions.
Children’s of Alabama has launched a new podcast called the Children’s of Alabama PedsCast. It’s focused on research, innovative programs and advances in pediatric health care happening at the hospital and making a significant impact on the lives of patients and families not only in Alabama, but throughout the Southeast. PedsCast, which debuted in September 2022, is a pediatric subspecialist peer-to-peer podcast that features physicians, surgeons, clinical specialists and other experts in the field of pediatrics.
Click here to listen to PedsCast and learn about topics like the Food is Medicine program, led by Children’s nephrologist Daniel Feig, M.D., Ph.D., M.P.H. You can also hear from neonatologist Colm Travers, M.D., about the Golden Week program and how it helps some of the tiniest preterm babies during their first week of life.
PedsCast complements the Inside Pediatrics podcast, which originally launched in November 2017 and now focuses on providing medical information and advice for parents.
Dr. Carmen Tong and the Children’s of Alabama urology team are preparing to start using the new Da Vinci surgical robot.
When Stacy Tanaka, M.D., arrived at Children’s of Alabama as the chief of pediatric urology, she resolved to bring in more technology. “I don’t want families of patients who need our services to go elsewhere because they think we can’t provide it,” she said at the time. That was in January 2022. By the end of her first year, one big piece of the puzzle was in place.
The Da Vinci surgical robot arrived in December 2022, and according to Carmen Tong, D.O., director of pediatric robotic surgery, staff should be ready to use it within the next several months. “I’m so excited to offer this service for our children,” she said.
The surgical robot provides an alternative to laparoscopic surgery, in which instruments are inserted through two or three small incisions. Laparoscopic surgery is minimally invasive, but the technique is not ideal. “The instruments don’t articulate at the wrist, so they don’t mimic actual hands in the body,” Tong said. This makes certain maneuvers, such as internal suturing, quite challenging. “It’s as though you’re using chopsticks,” she said. There is also a steep learning curve.
The robot, however, “completely changed the landscape of minimally invasive surgery,” according to Tong. It provides a three-dimensional view with improved depth perception. In addition, the instruments enable much more refined movements—mimicking hands and fingers—and are gentler, which is particularly important when operating on babies, who have very delicate tissue. Overall, robotic surgery is less invasive, less disfiguring and results in quicker recovery than the traditional open technique. One small study also found it resulted in shorter surgeries and less suturing than using a laparoscopic approach for the same procedure.[i]
One major advantage is the three-dimensional, magnified view of the surgical field through the console, which isn’t available with the tiny cameras used in laparoscopic procedures. “It’s fabulous,” Tong said. “You’re able to see exactly what you’re picking up and what you’re cutting and stopping the bleeding on. From a safety standpoint, it’s a superior product.” One study found that robotic-assisted surgery could complement the motor skills of the surgeon’s nondominant hand, eliminating the innate difference in dexterity between hands and conveying ambidexterity.[ii]
Having the Da Vinci robot also means Children’s no longer has to rely on access to the surgical robot at the University of Alabama at Birmingham (UAB), which is an adult hospital.
[i] Silay MS, Danacioglu O, Ozel K, Karaman MI, Caskurlu T. Laparoscopy versus robotic-assisted pyeloplasty in children: preliminary results of a pilot prospective randomized controlled trial. World J Urol. 2020;38(8):1841-1848. doi:10.1007/s00345-019-02910-8
Dr. David Joseph is a pediatric urologist at Children’s of Alabama.
Spina bifida, a condition in which the neural tube doesn’t completely close, is one of the most common congenital malformations, affecting approximately one out of every 2,700 births. While neurosurgeons provide immediate care, it isn’t long before urologists and nephrologists get involved. That’s because damage to the spinal cord and nerves may keep brain signals from reaching the bladder. If that happens, urine can back up into the kidneys, possibly causing kidney damage. “Yet nearly all newborns with spina bifida show normal kidney function at birth,” Children’s of Alabama pediatric urologist David Joseph, M.D., said. “But over time, at least half will deteriorate to some degree.”
Which begs the question: How do you manage these children? A 10-year, nine-center initiative at Children’s of Alabama has been trying to answer that question. Called Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida (UMPIRE), the initiative is designed to provide an evidence-based protocol for testing and monitoring kids with spina bifida to identify early kidney injury. The Centers for Disease Control and Prevention (CDC) funds the study, which is now following more than 500 children with the most severe form of spinal bifida, myelomeningocele, in which a sac of fluid containing part of the spinal cord and nerves protrudes through an opening in the baby’s back.
Unlike most clinical trials, where the outcomes are evaluated at the end, the UMPIRE investigators review the data every quarter and tweak the protocol accordingly. “Obviously, this is not as clean as a randomized control trial,” Joseph said. “But it’s an effective way to manage a small population without a control group.”
This approach has led to some important revelations. For example, the team learned that bringing newborns in for imaging every three months for the first year as they’d been doing had no benefit at the nine-month visit. They also recognized that prophylactic antibiotics to prevent infection weren’t needed in newborns. Children’s chief of pediatric urology Stacy Tanaka, M.D., discovered that each center assessed urodynamics (lower urinary tract function) differently, which was a serious problem given the reliance on those tests to classify a patient’s level of damage and determine treatment.
Finding participants for the study hasn’t been a problem, Joseph said. “I don’t think we’ve had a family in the past seven years that has turned down the opportunity to be in the study,”—something he attributes to Betsy Hopson, MSHA, coordinator of the Children’s of Alabama Comprehensive Spina Bifida Program. The goal is to follow the children for at least 10 years or for as long as the CDC continues to fund the study.
“The urologic community looks to the UMPIRE program for the protocol in anticipation that it will help direct future management,” Joseph said.
An initiative led by Dr. Ammar Saadoon Alishlash is helping children with acute chest syndrome.
Acute chest syndrome (ACS) is a respiratory disease that starts suddenly, progresses rapidly and is the leading cause of death in children with sickle cell disease in the U.S. and other countries. However, in the last three years, since Children’s of Alabama instituted a standardized ACS protocol, there have been no ACS-related deaths among the hospital’s patients included in the protocol.
Children’s admits as many as 100 children with ACS every year, and the new protocol has improved outcomes among these patients, decreasing the average number of inpatient days from seven to four (a 42% drop) and reducing ICU admissions and mortality.
“We did not expect such significant results,” pediatric pulmonologist Ammar Saadoon Alishlash, M.D., the leader of the initiative, said. When the initiative began, it was up to each child’s physician whether to follow the protocol or standard procedure because it wasn’t clear if the protocol would actually improve outcomes. “But now we’re pushing to have all patients diagnosed with acute chest syndrome be put on the protocol,” he said.
The protocol is based on the latest evidence on the management of ACS. It includes order sets for tests and medications that are embedded in the electronic medical record, which makes it possible for the patient to receive appropriate care in the emergency room rather than waiting until they’re admitted. It also provides three order sets depending on where the child is in the hospital: in the emergency department, the hematology floor or the ICU. “Each has a specific set of orders designed for that specific population to improve outcomes wherever they are in the hospital,” Alishlash said. The standardization also reduces variation in how physicians treat the patients, which is one reason for the improved outcomes, he said. The protocol involves initiating therapy early in the emergency department before the condition progresses. The main interventions include oxygen supplementation and respiratory support.
To further improve ACS outcomes, Alishlash, who leads the pediatric pulmonary sickle cell disease program at Children’s and the University of Alabama at Birmingham, is performing clinical and laboratory research on the condition. He received a National Institutes of Health grant to study the effects of environmental exposures on its development and to test novel therapies. He has also identified risk factors for ACS, including low oxygen levels during sleep and an association between where the child lives and the condition. “To prevent death in these small children is a great achievement,” he said. “Hopefully it will dramatically improve outcomes in our sickle cell patient community.”
Dr. Michael Lopez received a nearly $1 million grant to study a new pathway in Duchenne muscular dystrophy.
What happens when you knock out a ubiquitous protein in muscle that appears to be involved in numerous neuromuscular diseases, including Duchenne muscular dystrophy (DMD)? That’s the question Children’s of Alabama pediatric neurologist Michael Lopez, M.D., Ph.D., and his mentors, University of Alabama at Birmingham (UAB) professor Peter King, M.D., and assistant professor Matthew Alexander, Ph.D., are trying to answer.
Lopez recently received a Career Development Award worth nearly $1 million from the National Institute of Neurologic Disorders and Stroke to better understand a novel pathway involved in the development and progression of DMD.
The disease, which primarily affects males, is caused by a mutation in the gene that encodes for the dystrophin protein, which is critical for musculoskeletal health. Without this protein, muscles degrade over time, resulting in a severe paralysis that affects breathing and eventually causes the heart to fail. Patients typically die in their early 20s or 30s.
There is no satisfactory treatment for DMD. A multidisciplinary approach involving neurology, cardiology, pulmonary care and rehabilitation—among other specialties—helps patients manage the disease. Immune-dampening corticosteroids are the primary medical therapy.
Lopez and his team identified a new pathway involved in the sustained inflammation that underlies the disease. While chronic inflammation is driven, in part, by elevated levels of the cytokine transforming growth factor β (TGFβ1), clinical studies using drugs to inhibit TGFβ1 have been, by and large, unsuccessful. Lopez thinks that’s because the TGF signaling is more complicated, so any attempt to reduce levels must account for downstream signaling via transcription factors, called Smads, that receive instructions from TGFβ.
While it’s been known for some time that the Smad2 and Smad3 factors are important players in the TGFβ pathway, Lopez’s research identified another Smad called Smad8 that is not only turned on in a cellular model of DMD but is 48 times higher than other Smad factors. His findings were published in the International Journal of Molecular Science in July. “It appears to be a previously unrecognized pathway that could cause larger dysregulation of gene expression within the muscle,” he said.
When the researchers silenced Smad8 in cultured muscle cells, they found the cells differentiated into muscle fibers more successfully. “That’s a key experiment because it shows that too much of Smad8 was likely doing the opposite: preventing the muscle cells from differentiating into myofibers,” Lopez said.
The grant provides the funds to breed transgenic mouse lines in which the gene that encodes for Smad8 is deleted in cells destined to become muscle cells. “That way, we can answer the question, ‘Is it necessary for the normal function of muscle, and does it make DMD less severe in the mouse?’” Lopez said. “The premise is that we can intervene on this pathway and reverse these impairments.”
Surgeons perform a laser interstitial thermal therapy (LITT) procedure at Children’s of Alabama.
A new procedure called laser interstitial thermal therapy (LITT) allows Children’s of Alabama surgeons to take a minimally invasive approach to brain surgery and target tissue for ablation with greater precision.
Usually, patients with drug-resistant epilepsy who experience intractable seizures undergo resective surgery, in which a surgeon removes part of the brain. The procedure is very invasive, however, entailing a craniotomy, or removing part of the skull and cutting through the dura, which covers the brain. Some areas of the brain are difficult to navigate, and removing certain sections, such as the eloquent cortex, can lead to a loss of important functions, such as sensory processing or speech. Resective surgery also requires several days in the hospital and carries a risk of infection and bleeding.
“The small LITT device enables us to get into a deep region of the brain easily and safely,” pediatric neurologist Kathryn Lalor, M.D., said. “We can find the seizure onset with the electrode and then target the same area with LITT.”
The robotic system inserts a 2-to-3-millimeter probe (about the size of the tip on a new crayon) through a hole drilled into the skull. MRI guidance precisely locates the target area responsible for seizures. Once the probe is in place, a burst of laser energy destroys the tissue.
The device was initially FDA approved for temporal and medial structures in the brain, where much of adult epilepsy surgery occurs. Now, Children’s and other pediatric centers are demonstrating its effectiveness at treating epilepsy in other areas of the brain. “There’s a lot of research on how to make the energy delivery even more specific, so no unintended areas are affected,” Lalor said.
Using the device also reduces brain swelling thanks to its less invasive nature. “So, the recovery time is much quicker, and many of these patients go home the next day,” she said. In fact, studies find few complications and a good safety record.
In 2022, the team completed six surgeries using the LITT system.
Dr. Scott Turner is leading a pediatric migraine study at Children’s of Alabama.
The University of Alabama at Birmingham’s pediatric neurology group at Children’s of Alabama is launching its first externally funded study on migraines this year, marking the start of what they hope will become a robust research program in the area. Such research is needed given that an estimated 17% of children have frequent or severe headaches according to their parents. [i],[ii] The Children’s headache clinic team knows these numbers well—they see hundreds of children with headaches each year.
The five-year study, funded by the Patient-Centered Outcomes Research Institute (PCORI), is a comparative effectiveness trial designed to determine which works better at preventing pediatric migraines: medication (amitriptyline) plus cognitive behavioral therapy (CBT) or CBT alone. Current guidelines recommend using the two together to prevent migraines, but there is limited data on whether CBT is just as effective on its own.
“The big question is, do they really need amitriptyline?” nurse practitioner Scott Turner, DNP, the principal investigator for the Children’s of Alabama site, said. “Or would CBT alone actually be effective?” If it is, he said, patients might not need medication, which always carries a risk of side effects.
CBT teaches kids how their body and brain experience pain and how to use relaxation skills to reduce stress and pain. Therapists also work with patients to help them reduce negative thought and feeling patterns, such as always thinking the worst is going to happen or that a migraine will ruin an important event. Parents learn how to reinforce their child’s active coping efforts.
Children’s is one of 15 sites participating in the study. Its primary outcome is reducing the number of headache days and migraine-related disability from baseline to 28 weeks. Secondary outcomes include changes in headache severity and effects on the patient’s physical functioning and quality of life. Participants will receive CBT via telehealth, an approach that worked well during the pandemic and provides greater availability. The goal is to recruit about 400 children nationally, and Children’s hopes to enroll approximately 25 patients in the study beginning this spring.
Although he’s in charge of the study at Children’s, Turner initially doubted that CBT alone could be better than CBT with medication. “I would have thought that pill-taking was essential,” he said. But after researching the topic and learning more about CBT, he’s unsure. “I guess we’ll find out in about five years.”
[i] Nieswand V, Richter M, Gossrau G. Epidemiology of Headache in Children and Adolescents-Another Type of Pandemia. Curr Pain Headache Rep. 2020 Aug 25;24(10):62. doi: 10.1007/s11916-020-00892-6. PMID: 32840694; PMCID: PMC7447651.
[ii] Lateef TM, Merikangas KR, He J, Kalaydjian A, Khoromi S, Knight E, Nelson KB. Headache in a national sample of American children: prevalence and comorbidity. J Child Neurol. 2009 May;24(5):536-43. doi: 10.1177/0883073808327831. PMID: 19406755; PMCID: PMC2794247.
Dr. Kathryn B. Lalor is a pediatric neurologist at Children’s of Alabama.
A new procedure that can reduce the number and severity of epileptic seizures in children is now available at Children’s of Alabama. The NeuroPace RNS®, or responsive neurosurgical stimulation, is a small device about the size of a matchbox. When placed inside the skull with two wires attached to the brain surface and/or inside the brain, it monitors and responds to brain signals, often short-circuiting a seizure before it begins. It’s been approved for use in adults since 2013, but with recent studies on its safety and effectiveness in children, more centers like Children’s are now offering it “off label” to patients whose seizures don’t respond to medication and/or other surgical interventions.
“It’s an adjunctive therapy, meaning we don’t do it as an initial treatment or thinking someone will necessarily be cured, although that is always our goal,” pediatric neurologist Kathryn B. Lalor, M.D., said. In a multicenter study of 17 patients under age 18, the average number of seizures fell 54.4% over the 1.7-year follow-up. Most patients also experienced less intense, shorter or less frequent seizures. One patient became seizure-free, although four showed no improvement.[1]
The device wouldn’t be a first step in managing seizures, Lalor said, because it’s surgical. “We would only undertake it if we know the seizures can’t be controlled with medications alone,” she said. It also has advantages over medications, including fewer, if any, long-term side effects. One major benefit of the device is that it seamlessly uploads data on its activity to a database clinicians can access, enabling them to track and measure seizures objectively.
“Right now, we know about seizures we witness,” Lalor said. “But there are silent seizures or ones that happen during sleep or when no one is around.” Better data enables doctors to ensure they’re treating all the seizures because even silent seizures can have an effect. With this data, she said, the team can remotely adjust the amount of stimulation the device sends and/or change a child’s medication.
While the device is still not FDA-approved for children, Lalor said more insurance companies are covering it, and a growing number of hospitals offer it with successful outcomes. There is also an ongoing multi-center trial—including the University of Alabama at Birmingham—evaluating its use in adolescents ages 12 to 17.
“We’re excited to be able to offer this,” Lalor said. The team hopes to implant the first device early this year.
[1] Nagahama Y, et al. Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study. Neurosurgery. 2020;39(6):997-1004.
Dr. Michael E. Seifert is the medical director of the Pediatric Kidney Transplant Program at Children’s of Alabama.
A new protocol at Children’s of Alabama is giving sensitized children who need a new kidney a brighter glimmer of hope for successful donor match and transplant.
Children who need a kidney transplant typically wait about a year or two for an organ. But if they’ve been exposed to external blood products, been pregnant or had a previous organ transplant, they could find themselves waiting up to five times longer. That’s because they’ve become sensitized to certain proteins that are foreign to their immune system, which results in high antibody levels that react to foreign tissues. “That makes finding a compatible transplant for them really, really problematic,” pediatric nephrologist Michael E. Seifert, M.D., said. Plus, those antibodies significantly increase the risk of an immediate rejection or graft failure.
Historically, finding a compatible kidney donor for sensitized patients has been challenging, but thanks to a process called desensitization, that’s changing for some. It involves using a combination of immunosuppressive therapies to try to reduce the immune reaction to potential donor organs. Although it’s been used in adults for years, pediatric centers like Children’s have only recently introduced their own protocols. “With these immunomodulatory therapies, we try to turn down the volume on their sensitization,” Seifert said. “You can’t get rid of it altogether. Once a patient is sensitized, they’re always sensitized to some extent.”
The desensitization protocol is a combination of plasmapheresis—a kind of dialysis for blood that removes some of the problematic antibodies and immune proteins—and IV and oral immunosuppressants to prevent the antibodies from returning. Together, Seifert said, “this creates a more potent and widespread ratcheting-down of the immune response that allows some transplants to be done safely.”
The process requires close collaboration between clinicians and the immunology, or HLA, laboratory to choose the right cocktail of immunosuppressants and the right time for transplant. While it’s still challenging to find compatible organs, Seifert says the therapies can help shorten the time on the waitlist for some patients and give them access to more donors.
The team has used the protocol on several children so far, one of whom was able to receive a transplant. “So far, the patients are doing really, really well on it,” Seifert said. “And it’s been a success. But it’s a more challenging transplant because they are still much more likely to reject this kidney than a straightforward kidney transplant. We balance that risk against the risks of remaining on the kidney transplant waitlist for several years, waiting for a compatible donor.”
The children also need more attention post-transplant to keep their immune system at bay without triggering complications like infections, and they’ll have to maintain that throughout their lives, Seifert said. They will also always have a higher risk of rejection and premature graft loss. Yet if the transplant fails, subsequent transplants become more challenging, given greater sensitization.
“It’s a Catch-22,” Seifert said, “in that we achieve our goal, which is getting them a transplant, but it’s a lot more work for us to keep that transplant going.”
