Inside Pediatrics

New hope for neonates with severe congenital kidney disease

_{ECMO in use at Children’s of Alabama (file photo)}

Almost a decade ago, Nephrology specialists at Children’s of Alabama embarked on a journey to improve outcomes in neonates with severe congenital kidney disease by adapting the Aquadex machine, a small extracorporeal circuit used for adults with heart failure. Traditionally, extracorporeal membrane oxygenation (ECMO) was deemed unsuitable for this population due to perceived nonviability. In 2016, at the family’s request, a baby with severe congenital kidney failure and severe respiratory failure was placed on ECMO to be given a chance at life. The baby also required kidney support therapy (KST) to survive. After receiving a kidney transplant at age 2, the child now goes to school, plays sports, sings and dances.

Since 2016, of the 31 neonates with congenital kidney failure who were admitted to the Children’s neonatal intensive care unit (NICU), five required ECMO support and KST in the first two weeks of life. In February 2024, Kara Short, MSN, CRNP, CPNP-PC, David Askenazi, M.D., MSPH, and others published a case report in Pediatrics, highlighting the complex treatment of the five babies and the journey to NICU discharge for the four survivors. This study challenges the previous norms and conventions that these babies had no chance at life.

Congenital kidney failure poses unique challenges to neonates, affecting not only renal homeostasis but also respiratory integrity. Diagnoses among the five patients in the study included posterior urethral valves, bilateral renal dysplasia and autosomal recessive polycystic kidney disease. Despite gestational age ranging from 35.6 to 37.1 weeks and birth weight from 2,740 grams to 3,140 grams, all five patients received KST by postnatal day seven. Additionally, they were all placed on ECMO within the first nine postnatal days due to severe respiratory distress after being unresponsive to conventional interventions.

Four of the five patients survived and are thriving today. Pulmonary hypertension resolved in each survivor, with three requiring no oxygen support and one needing only nocturnal oxygen. Three survivors underwent successful kidney transplants, while one awaits transplant evaluation. This challenges the traditional notion of reflexively assigning nonviability to neonates with congenital kidney failure and severe pulmonary complications.

This research highlights the significance of ECMO and kidney support therapy in mitigating the adverse effects of pulmonary edema, uremia and electrolyte complications. The use of a filter through the ECMO circuit—to perform continuous venovenous hemodialysis (CVVHD), continuous venovenous hemofiltration (CVVH) with the Aquadex machine, peritoneal dialysis and intermittent hemodialysis—showcases the synergism and need for different approaches to manage these complex cases.

Managing congenital kidney failure requires a multidisciplinary approach involving neonatology, nephrology, surgery and multiple ancillary divisions. “As healthcare providers, we all bring something to the table,” Askenazi said. “The families need clear, concise information so they can understand their options when making treatment decisions. Our job is to develop programs, systems and plans to help those kids have the best chance at life.”

The families of the neonates faced challenging decisions, including the choice of full medical support or palliative care. Despite the complexity and potential extended NICU stay, all five families opted for full medical support. Clear communication, counseling and informed decision-making were instrumental when families made medical decisions about their baby’s care.

The successful outcomes of neonates with congenital kidney failure undergoing ECMO challenge previous assumptions of nonviability. Meticulous ECMO, respiratory, nutritional and kidney support therapies are essential to favorable long-term results. Further investigation is needed to define the optimal strategies to improve outcomes in severe congenital kidney disease cases. “We want to share this information with other programs to let them know that these kids have a chance at life; what we learned in this very small cohort is that these lungs can develop and grow if given a chance,” Short said.

“When thinking about the future, we’re asking ourselves: How can we get the very best technology to care for these babies? How can we help other programs improve so they can better care for their kids? How do we ensure that families are counseled with all viable options in an honest and comprehensive way?” Askenazi said. “We will continue to make progress. We have recently received a grant from the National Institutes of Health (NIH) to partner with industry to make a better device for neonates. We recognize that we must continue to educate our colleagues across the U.S. and the world about what we have learned from these miracle babies.”

February 5, 2024 by childrensal

Orthopedics

Improving practices for elbow fracture treatment

_{Children’s of Alabama orthopedic surgeons hope to streamline the process and reduce costs of elbow fracture treatment.}

Elbow fractures are among the most common childhood injuries, accounting for about 10% of all childhood fractures. But according to a study led by Children’s of Alabama orthopedic surgeon Kevin Williams, M.D., the process for treating them isn’t as efficient or cost-effective as it can be.

Recently, Williams and his team evaluated a year’s worth—170 total—of supracondylar humerus fractures, a type of displaced break that occurs just above the elbow joint at the end of the humerus bone and needs to be put back in place and sometimes stabilized, often operatively. They found that surgeons at Children’s treated one of these fractures operatively every other day, but only 30–40% of patients were first seen at Children’s. The rest were transported from other areas of the state, with some coming from as far as Mississippi and Georgia. This means more time had elapsed before surgery, which is potentially problematic because prolonged displacement can increase swelling or compress nerves and blood vessels. This, in turn, increases the risk of compartment syndrome, a painful and debilitating condition that occurs when pressure within the muscles builds to dangerous levels, decreasing blood flow to nerve and muscle cells.

On average, transfers among cases in the study required almost three hours and came from about 70 miles away.

The study also assessed transportation methods, finding that children arrived faster when transported in private vehicles than ambulances. Patients often arrived unprepared for the immediate surgery required, and often, additional X-ray views were required to determine treatment.

Given the findings, Williams and his team are now investigating ways to streamline the transfer process and ensure patients arrive from other institutions ready for surgery.

They are also examining standard practices for non-displaced breaks, which can generally be managed with immobilization and usually don’t require surgery. Such patients often undergo repeated X-rays, which cost about $700 and expose the child to radiation. Williams’ findings indicate that obtaining repeated X-rays for such stable cases is unnecessary and too costly considering that the results don’t change the treatment modality.

Williams hopes to collaborate with other institutions to identify and develop best practices for managing elbow fractures. “Collaborative research allows updating approaches to continually provide the best, most up-to-date care for every child,” he said.

In the meantime, he advises prompt specialist referral for elbow fractures with rapid swelling, noticeable deformities, and impaired mobility. “It’s important to make sure that these children are seen as quickly as possible so we can give the care necessary,” he said.

Elbow fractures typically occur during play or sports when the child reaches out with their hands to block their fall. Proper and timely treatment is crucial to avoid long-term disabilities and complications.

“It’s very important for us to treat patients with displaced elbows operatively if the fracture is fairly displaced or angulated to make sure that the elbow heals and functions properly in the future,” Williams said.

“In this location, the bone doesn’t grow as much as other bones, such as those near the shoulder or wrist,” Williams said. “So, it’s imperative that we have these bones put back into place exactly where they were, or they could grow aberrantly with some type of angulation, causing some dysfunction in the future and potentially even resulting in nerve or muscle damage.”

January 30, 2024 by childrensal

Neurology & Neurosurgery

Deep brain stimulation for progressive dystonia

_{In 2023, Children’s of Alabama performed deep brain stimulation on progressive dystonia patients for the first time.}

Progressive dystonia disorders, characterized by changes in movement patterns, can profoundly impact a child’s quality of life. In adults, such disorders are routinely treated with a procedure called deep brain stimulation (DBS). However, this intervention is less commonly used in pediatric populations.

In 2023, Curtis Rozzelle, M.D., and Emily Gantz, M.D., performed Children’s of Alabama’s first DBS procedures for progressive dystonia patients. This innovative therapy has shown promising results in several pediatric patients with limited treatment options.

_{Curtis Rozzelle, M.D.}

“We’re excited that this innovative procedure is now transferring over to our pediatric patients,” Rozzelle, a pediatric neurosurgeon at Children’s, said. “Kids with progressive dystonia seem to do particularly well, while those with other types of movement disorders may have mixed results.”

Studies suggest that pediatric patients with progressive dystonia respond well to deep brain stimulation, especially after failing conventional medications. The decision to apply DBS in pediatric cases stems from the specific needs of young patients and advancements in the field.

“Until Dr. Gantz arrived at the University of Alabama at Birmingham, we didn’t have a movement disorder neurologist here who also had training and experience with deep brain stimulation,” Rozzelle said. “When she arrived, Dr. Gantz opened the door for us to be able to perform the technical aspects of the surgical procedure. Now, we’ve done several.”

Not every child is an ideal candidate for DBS. The decision to initiate DBS is patient-specific, based on the severity of symptoms and the inadequacy of other treatments. A careful evaluation of each patient’s unique situation, including factors such as genetic mutations and the progression of the disease, must be completed before offering DBS surgery.

Each deep brain stimulation procedure at Children’s uses stereotactic surgical techniques and the ClearPoint targeting system. This system, employed in an MRI scanner, ensures safe, precise electrode placement in the globus pallidus interna (GPI), a key target for treating progressive dystonia.

_{Emily Gantz, M.D.}

“When we implant the electrode into a specific region of the brain, we can either edit the input throughout the stimulation, or we can take it completely away,” Gantz said. “Think of it as a series of relay circuits in the brain. If someone has dystonia, one of those relay circuits isn’t working properly. By putting in the stimulator and applying an electrical current intermittently, we can suppress the abnormal brain activity.

“The stimulator stays in for life, so the procedure doesn’t need to be repeated,” she continued. “Occasionally, we’ll have to change the device’s battery, but they’re rechargeable and designed to last for up to 20 years.”

After the initial procedure, patients return to see Gantz to have the device programmed. “I set the programming on their stimulator so they can make slight adjustments at home. It can take a little while for the device to be effective; we usually leave it alone for a few months and then reevaluate,” Gantz said. “We have guidelines for which settings will most likely help, and we start there. We’re looking to ensure we don’t get side effects, such as visual disturbances or muscle pulling, more than anything.”

The pediatric patients who have begun DBS for progressive dystonia at Children’s are responding well to the new treatment. “I’m really excited about DBS and its future as a treatment in pediatric neurology, specifically movement disorders,” Gantz said. “It may eventually come into play in other treatment areas, and I’m glad the door is open to us here. I think there will be many more patients who will benefit from it.”

January 30, 2024 by childrensal

Behavioral Health

PIRC paves the way to better mental health

_{Stefanie Blakely, Liam Blakely and Psychiatric Intake Response Center (PIRC) therapist Ashley Loftis}

Stefanie Blakely was at a work event one night in October 2022, when she received a text message that would leave almost any parent in shock. It was from her 12-year-old son, Liam. He was considering suicide.

“I just felt like the world stopped completely,” Stefanie said.

Scared and nervous, Stefanie felt she needed to get to Liam immediately. But he was on the other side of town, and she worried she might not be able to get to him quickly enough to keep him safe. She left the event and drove to pick him up, calling and texting with him along the way. When she arrived, Liam shared the emotions that led to his text. He was still upset.

“I just was really lost as a parent trying to figure out what the best resource was for my son at that point,” Stefanie said.

Stefanie works at Children’s of Alabama and was familiar with the hospital’s Psychiatric Intake Response Center, or PIRC. Liam’s therapist also had mentioned it. While driving down the road wondering how to help Liam, Stefanie remembered it. She pulled into a parking lot, looked up the number and called.

_{Cindy Jones, MA, LPC-S, NCC}

The PIRC is a phone response center for adults seeking mental health resources for their children or adolescents. Callers can have free, confidential conversations with licensed mental health clinicians who assess a child or teen’s mental, emotional and behavioral needs and recommend the best treatment options, including the contact information of multiple mental health professionals in their community.

“For our PIRC therapists, it’s been a very rewarding experience for them to be able to talk to folks who need that help and who are looking to do the right thing for their child. They are getting an opportunity to be there in that moment,” PIRC director Cindy Jones said. “And answering callers’ questions, we do notice a lot of times that if we are there for them, that it decreases the anxiety and the stress level and the frustration that a lot of parents or caregivers or whomever have while trying to find those right resources.”

When Stefanie called, she “got the most reassuring voice on the other end of the line,” she said. Ashley Loftis, the therapist she spoke with, advised her to take Liam to the Children’s Emergency Department. “I think that may have saved my life that night,” Liam said.

The call led to a positive turn in what had been a long process for Liam. Stefanie says he started struggling with depression around 3^rd grade and was diagnosed that year with attention deficit hyperactivity disorder (ADHD). School closures resulting from the COVID-19 pandemic led to more challenges. “The isolation of being stuck at home was very difficult for him,” Stefanie said. Even when schools reopened, Liam was still struggling and met with school counselors. His pediatrician recommended increasing his ADHD medications, but by early 2022, it was obvious to Stefanie that more resources were needed. He started seeing a licensed therapist, and in the fall of that year, his pediatrician put him on a low dose of Zoloft. But he was still dealing with depression and having trouble sleeping.

Then came the night of the text message. Initially, it seemed like a low point. “I felt that feeling when you can feel the color just draining from your face into your body,” Stefanie said. Ultimately, however, it became a turning point, leading to changes in Liam’s mental health services.

“They gave us the guidance that we needed,” he said. “And I think that may be what started my journey to better mental health.”

One of the next steps in that journey was the Children’s Partial Hospitalization Program, or PHP—a day treatment program that helps patients who, at the time, are not candidates for an inpatient stay but need more intense treatment than the typical outpatient structure provides. There, Liam worked with a therapist who was able to identify his depression, anxiety, ADHD and obsessive-compulsive disorder (OCD) as symptoms of a larger issue. She suggested having him evaluated for autism spectrum disorder (ASD), with which he was diagnosed a few months later. “[The ASD diagnosis] has been huge for us in navigating his mental health as well as his school experience,” Stefanie said. Now, Liam visits the Children’s outpatient clinic every six months, and his doctor has a full picture of who he really is.

But the process of understanding Liam and getting him the help he needs began at the PIRC.

Stefanie says she’s incredibly thankful for it and for the calming therapist on the other end of the line. “To have someone be the definitive voice of reason to say, ‘This is what you need to do,’ in a moment when you feel just completely lost—not knowing what’s going on or what your next steps are supposed to be—is so nice,” she said. “And I was so grateful in that moment.”

For more information on the PIRC, click here. If you need help for your child, you can call the PIRC at 205-638-PIRC (7472).

January 30, 2024 by childrensal

Behavioral Health

Bridging the mental health gap for children in Alabama

_{The PATHS program at Children’s of Alabama is helping connect patients with mental health providers more quickly.}

The United States is experiencing a crisis regarding children’s mental health, with many emergency rooms overwhelmed with urgent mental health visits.¹ Adding to the crisis, said Children’s of Alabama child psychiatrist Vinita Yalamanchili, M.D., is a severe shortage of pediatric psychiatrists and other mental health providers, particularly in rural areas.

“The mental health needs of children have increased exponentially,” she said. “There’s just no way we can match those needs.”

Pediatric Access to Telemental Health Services (PATHS) at Children’s is designed to address both issues. The program is dedicated to increasing primary care providers’ ability to diagnose, treat and manage mild-to-moderate behavioral health conditions in children and adolescents.

_{Vinita Yalamanchili, M.D.}

“It can take three to six months to see a therapist or psychiatrist,” Yalamanchili said. But waiting that long for treatment means kids in crisis are at risk of self-harm. With PATHS, they can get expert care from their primary care provider, often within 24 hours.

Primary care practices enroll with the program and receive access to the PATHS team, which includes child/adolescent psychiatrists and psychologists, psychiatric nurse practitioners, licensed clinical social workers and licensed professional counselors. In return, they agree to start behavioral health screenings for well-child visits and report results to PATHS; participate in one-hour, bi-weekly educational sessions on pediatric and adolescent mental health issues; and maintain ongoing responsibility for their patients’ behavioral health care and treatment.

Providers call PATHS when they have a patient who needs additional assistance. After an initial consult with a social worker, they are directed to the most appropriate team member to help. Yalamanchili, for instance, is usually the point person for medications. “I will tell the provider exactly how to prescribe the medicine and give them different options,” she said. For children who don’t need medication, the provider may talk to an early development specialist or a psychologist for information about topics like sleep training or behavioral management.

“You’re providing a consult for the provider to assist them in helping this child,” Yalamanchili said.

If the child needs more intensive care, they can interact directly with one of the PATHS specialists from their primary care office via telehealth. “This allows a patient not to have to come to Birmingham to see us,” she said. “It’s a really nice bridge until a local psychiatrist can see them.”

Initially founded to help rural practitioners, PATHS now works with providers throughout the state, even those just a few miles away. “They have the same waiting time of three to six months for psychiatric care,” Yalamanchili said. PATHS can continually extend its reach, she said, because as providers gain more education and confidence, they need fewer consults, freeing space for more practices.

“Because we also provide education, I think a pediatrician may not call me for a while because they’ll say, ‘Well, you’ve taught me enough that now I feel comfortable doing this on my own,’ ” she said.

The PATHS team also provides information about mental health specialists in the practice’s area.

“It’s actually one of my favorite jobs, because I am providing care very quickly to children,” Yalamanchili said. “And the pediatricians are just so grateful for these services.”

Sorter M, Stark LJ, Glauser T, McClure J, Pestian J, Junger K, Cheng TL. Addressing the Pediatric Mental Health Crisis: Moving from a Reactive to a Proactive System of Care. J Pediatr. 2023 May 13:113479. ↩︎

January 30, 2024 by childrensal

Nephrology

New Leadership on Dialysis Unit

_{Kaci Caradine and Dr. Daniel Feig took on new leadership roles on the Children’s of Alabama Pediatric Dialysis Unit in the fall of 2023.}

As more children requiring kidney dialysis survive and thrive—able to leave the hospital and return for treatment on an outpatient basis—the Pediatric Dialysis Unit at Children’s of Alabama has needed to adapt and grow. New leadership is poised to tackle this shift with aplomb, planning to increase staffing, expand education for team members and boost current programs for patients and families.

As of fall 2023, the unit is headed by medical director Daniel Feig, M.D., Ph.D., MPH, medical director of pediatric nephrology at Children’s, along with nursing director Kaci Caradine, BSN, RN, CNML. The pair replace the outstanding former medical director Sahar Fathallah, M.D., who is pursuing other professional opportunities at Children’s, and former nursing director Suzanne White, RN, who retired.

Within the last several years, the dialysis unit’s patient load doubled. It now includes about 20 patients who undergo outpatient hemodialysis treatments three times weekly, along with another 15 who receive home-based, nightly peritoneal dialysis and visit the unit about once a month. Most commonly, pediatric dialysis patients are affected by congenital abnormalities of the kidneys or urinary tract that lead to irreversible kidney failure, Feig said. Others require dialysis due to problems such as sepsis, solid organ transplantation, autoimmune diseases and other chronic issues.

“As we continue to make great improvements in the care we deliver, more kids are able to leave the hospital and lead full lives,” said Caradine, previously the director of nursing for Children’s Cardiovascular ICU.

Feig agreed, noting that referrals to the Children’s dialysis unit have also increased, both from the Southeast and around the nation. “We’ve gotten better at treating kidney failure in the Neonatal ICU and the very youngest patients, so kids who didn’t use to survive are now growing up with kidney failure,” said Feig, who’s also a professor of pediatrics and director of the Division of Pediatric Nephrology at the University of Alabama at Birmingham (UAB). “Now, the average age in the dialysis population is dropping from young teenager to about 5 to 7 years old.”

To keep pace, Feig and Caradine intend to quickly add to the dialysis team, which currently consists of 17 nurses, three nurse practitioners, nine attending physicians, and other roles that include a social worker, a dietitian and a counselor.

But many new clinicians to the unit don’t have experience in dialysis, making it crucial to “develop education and career development programs that get new staff up to speed,” Feig said. “We’re pulling together a didactic program involving the physicians and nurse practitioners who care for these patients, so they have a greater understanding of kidney disease and the challenges these kids face.”

“We want to develop a comprehensive educational program and onboarding curriculum for our new nurses,” Caradine agreed, “as well as ensure our current nurses are able to grow their knowledge base to continue to provide state-of-the-art care for our patients.”

Additional priorities include enhancing the Food as Medicine program, which provides packages of ingredients to patients’ families to assist them in preparing dialysis-safe meals. “This program is associated with huge improvements in patients’ quality of life and lab testing, and they’re much more able to stick to a prescription diet,” Feig said. “Expanding the program to a larger portion of the unit is a goal that will allow us to help all of our families.”

January 29, 2024 by childrensal

Neurology & Neurosurgery

A new procedure for epilepsy patients in Vietnam

_{Children’s of Alabama director of neurophysiology Trei King with a Vietnamese EEG team during a trip to Vietnam in September 2023. (Submitted photo)}

With the waning of the COVID-19 pandemic, a team of neurosurgeons from Children’s of Alabama, Johns Hopkins All Children’s Hospital and Nationwide Children’s Hospital in Columbus, Ohio, were finally able to fly the 9,000 miles back to Vietnam in 2023 to continue training surgeons on surgical techniques to manage drug-resistant epilepsy.

Children’s of Alabama’s relationship with Vietnamese neurosurgeons began in 2013 with an initial visit to a team in Ho Chi Minh City. Until the pandemic hit, the team, including pediatric neurosurgeon Brandon Rocque, M.D., pediatric epilepsy surgery director Pongkiat Kankirawatana, M.D., and director of neurophysiology Trei King, BA, R.EEG.T, CNIM, visited annually to provide hands-on training at hospitals in Hanoi and Ho Chi Minh City.

Their efforts are desperately needed in a country with just two adult and two pediatric neurosurgery training programs for its 95 million people and only six pediatric neurosurgeons serving a population of more than 50 million in the northern part of the country.

“Vietnam did a very good job of managing COVID, with an extremely low per capita death rate,” Rocque said. Nonetheless, there were significant disruptions to medical care and training during lockdowns.

On their return trip to Vietnam in September 2023, the team assisted surgeons in Ho Chi Minh City with epilepsy resection surgeries. Since the Children’s team left, the local surgeons have completed at least two of these procedures on their own, albeit with some long-distance help from the Children’s surgeons. “They called us in the middle of the night, and we helped them troubleshoot the equipment a bit for the epilepsy monitoring,” Rocque said.

On the same trip, at the National Children’s Hospital in Hanoi, the team performed the country’s first subdural grid electrode implantation, a procedure designed to pinpoint where seizures are occurring. “Everything went really well,” Rocque said. “We monitored the patients for a couple of days and were able to clearly localize where their seizures were.” Then, they removed the electrodes and performed the resection.

The procedure had never been performed in Vietnam because of concerns about infection from the temporary electrodes and the need to keep patients heavily sedated. However, those concerns were overcome when the hospital adopted international standards for the procedure.

The grid implantation, performed in two pediatric patients, received national media coverage, triggering requests from families throughout the country. “It opens up the possibility of many more patients getting treated,” Rocque said.

The team also visited the National Cancer Hospital in Hanoi to assist with an established program using selective dorsal rhizotomy to reduce spasticity in the legs from cerebral palsy. They helped evaluate patients, assisted with surgery and participated in a symposium on the procedure attended by more than 50 physicians throughout Vietnam.

The team also assisted the Vietnamese neurosurgeons in performing extraoperative video-electrocorticogram monitoring.

January 29, 2024 by childrensal

Endocrinology

Going ‘beyond the scale’ in prediabetes treatment

_{A Children’s of Alabama clinic offers a family-centered approach to prevent prediabetes from progressing to diabetes. (Stock photo)}

A lag in care for children with obesity and its complications can spell the difference between prediabetes and a full-blown case of diabetes. Recognizing this, Children’s of Alabama pediatric nurse practitioner Grant Adams, CRNP—who has always had a “big heart for children struggling with obesity”—spearheaded a new clinic at Children’s to fill the gap.

The result is the Prediabetes and Metabolic Syndrome Clinic, which was established in late 2022 and runs half-days every Tuesday at the Children’s Diabetes and Endocrine Clinic. The clinic is meant to prevent delays in care for children referred by their pediatricians for prediabetes, weight management and related issues.

These young people face the high risk that their prediabetes will progress into diabetes, a disease which affects more than 350,000 children and adolescents under age 20 in the United States, according to the Centers for Disease Control and Prevention (CDC). Nearly 20% of children and adolescents nationwide cope with obesity, predisposing them to diabetes as well as other health conditions.

Children’s pediatric endocrinologist Christy Foster, M.D., assisted Adams in establishing the clinic, which also includes physicians, a registered dietitian and a social worker. The team aims to move “beyond the scale” with a family-centered approach that emphasizes healthy eating habits and movement as well as medication management.

“My vision was to instill habits that would be lifelong,” Adams said. “We want to reinforce that just because there’s a family history of diabetes, it’s certainly not inevitable.”

To that end, clinic visits—which take place every three to six months—deeply involve parents and other caregivers. While staff members closely monitor patients’ well-being and lab work, the resulting positive changes often have ripple effects on the entire family.

“Rather than doing more prescriptive-style medicine where everyone is assigned the same interventions, we work with families to see what can be reasonably done for and with them,” said endocrinologist Jessica Schmitt, M.D., an assistant professor in the Division of Pediatric Endocrinology and Diabetes at Children’s and the University of Alabama at Birmingham (UAB).

“At every visit, we talk about how food is fuel,” Adams added. “Regardless of a child’s age, it’s not their responsibility to buy and cook the food, especially if they’re not teenagers. They rely on a family approach—and families buy in.”

Even so, results are mixed. Some children and teens who visit the clinic improve their diets and lifestyles dramatically, with associated improvements in their weight, blood sugar levels, and problems such as high cholesterol.

“This is a lifelong commitment, not a diet,” Adams said. “It isn’t a sprint, it’s a marathon.

“If we can affect this generation, my vision is that their kids will be affected positively,” he added. “Obesity is a pandemic, and we’ve got to stop it somewhere. I’ve decided it needs to start with kids. This is a generational problem, and we can make a positive impact.”

January 29, 2024 by childrensal

Endocrinology

Hypothalamic obesity – a potential breakthrough

_{Setmelanotide provides hope for patients with hypothalamic obesity.}

Acquired hypothalamic obesity has long presented a complex challenge in healthcare, leaving pediatric patients struggling to lose weight. An innovative study involving a medication called setmelanotide aims to address this problem. Hussein Abdul-Latif, M.D., shed light on this groundbreaking research, offering insights into its origin, mechanism and potential impact.

Often arising from injuries or conditions affecting the hypothalamus, such as craniopharyngioma, acquired hypothalamic obesity makes it very difficult for pediatric patients to lose weight. There is also some evidence that slower metabolic rates and potential hormone deficiencies contribute to the problem in this specific patient population, along with other factors not fully understood yet.

Setmelanotide targets melanocortin receptors, which are crucial in regulating the body’s satiety signals. Abdul-Latif noted the medication’s impact on correcting the disrupted signals that lead to continuous hunger and reduced metabolism—two key factors contributing to this form of obesity.

“Our study is an extension of studies looking at the various genetic components to acquired hypothalamic obesity,” Abdul-Latif said. “We knew this medication was effective in treating obesity related to certain genetic conditions, so the next natural step was to consider whether it could be used for hypothalamic obesity resulting from injury to the hypothalamus.”

The ongoing phase three trial involves multiple sites, including Children’s of Alabama, enrolling patients up to 30 years old. So far, Children’s has recruited five patients to test the medication.

This trial utilizes a double-blinded method, where some participants receive the medication while others receive a placebo. Throughout the study period, researchers monitor each patient’s weight, satiety and skin pigmentation changes over a designated period. To date, only minor adverse events have been noted, including darkening of the skin and injection site issues.

Abdul-Latif also stressed the significance of this research in offering hope to those struggling with acquired hypothalamic obesity. He highlighted that this condition, previously perceived as challenging to treat effectively, now has a potential breakthrough. The medication provides promise for a segment of the population in need of more personalized solutions, hinting at a positive outlook for the future of treating this condition.

The clinical trial should end in April 2025. “At the end of the study, we give the medication to everybody regardless of their study cohort. That’s a nice incentive for prospective participants who may be desperate for something to help them lose weight,” Abdul-Latif said.

While the medication shows promise, Abdul-Latif emphasized the importance of exercise and hormone supplementation in conjunction with the treatment. The goal is to not only aid weight loss but also improve overall health and optimize the medication’s efficacy.

This groundbreaking research signifies a critical step forward in addressing acquired hypothalamic obesity. For participating patients, setmelanotide offers a newfound sense of hope. The ongoing clinical trial and subsequent FDA approval could signal a transformative breakthrough, marking a significant milestone in health care. As the study progresses, continued enrollment, diligent monitoring, and analysis of results will pave the way for a deeper understanding of setmelanotide’s efficacy and its potential to revolutionize the treatment of acquired hypothalamic obesity.

January 29, 2024 by childrensal

Endocrinology

Exploring GABA and GAD for Type 1 Diabetes

_{A study led by Gail J. Mick, M.D., shows promising results for treating new-onset cases of type 1 diabetes with GABA and GAD.}

Could an over-the-counter supplement help save insulin production in new-onset type 1 diabetes? That’s the question pediatric endocrinologists Gail J. Mick, M.D., Kenneth McCormick, M.D. (now retired) and colleagues at Children’s of Alabama set out to explore. The answer, according to their recently published article in the journal Nature Communications, is, quite possibly.

The study explored the potential of the amino acid gamma-aminobutyric acid (GABA), found in health food stores, and glutamic acid decarboxylase (GAD), an enzyme that acts on glutamate to form GABA, to preserve pancreatic islet function.

GABA is an important neurotransmitter in the brain. However, it is also critical to insulin production, with GABA receptors found within the islet beta cells responsible for insulin production. Meanwhile, GAD converts abundant circulating glutamate from dietary protein and intestinal microbiota into GABA.

Animal studies showed their potential to stimulate insulin secretion, inhibit glucagon overproduction, dampen inflammation and promote beta cell regeneration. Still, getting a clinical trial approved in a pediatric population took years.

“Nobody does first-line studies in children,” Mick said. “For safety reasons, studies are typically conducted in adults, but in type 1 diabetes, adults differ from children. In children, the autoimmune destruction of insulin secretion is faster.

“It took a lot of luck, hope and a dream we were going to cure diabetes with something safe and oral” to get FDA approval for the trial, she said.

The study randomized 97 children (average age of 11) within five weeks of their diagnosis to oral GABA with or without a GAD-alum injection. However, the researchers were constrained to low doses of the compounds, given the FDA’s concern about potential side effects.

Although the study didn’t meet its primary goal of preserving beta cell insulin production, the GABA/GAD combination significantly reduced glucagon levels, improving blood sugar levels. The study also found lower levels of the inflammatory cytokine expression implicated in the pathogenesis of type 1 diabetes. There were no adverse effects.

“Not only did we see reduced glucagon, but there were also beneficial immunologic effects,” Mick said. “We’re delighted by that.” The immunology results were recently published in the journal Biomedicines.

The positive outcomes show enough promise that further studies with higher GABA doses are warranted, Mick said, perhaps in combination with other agents, such as GLP-1 receptor agonists, which also have beta-cell regeneration effects.

“It’s fascinating,” Mick said. “Just fascinating.”

January 29, 2024 by childrensal

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