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
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
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
Neonatology

Link Between Infant Mortality and Insurance Type

A study shows that the the infant mortality rate is higher for pregnant people insured by Medicaid compared to private insurance.

A new study published in JAMA Network Open suggests that the type of health insurance pregnant people have may impact infant mortality rates. The research, led by Children’s of Alabama neonatologist Colm P. Travers, M.D., found that pregnant people with private health insurance had lower rates of infant deaths compared to those insured by Medicaid.

“The type of health insurance you have has been associated with adverse outcomes in adults and pediatric populations and differences in access to care, including prenatal care,” Travers said. “But few studies showed a difference in infant outcomes, particularly infant mortality rates, when comparing private health insurance to Medicaid public health insurance.”

The study analyzed data on more than 13 million births that occurred in the U.S. from 2017 to 2020. Overall, 46% of the pregnant people in the study had Medicaid insurance, while 54% had private insurance.

The infant mortality rate—defined as the number of deaths in the first year of life per 1,000 live births—was 2.75 deaths per 1,000 live births for those with private insurance compared to 5.30 deaths per 1,000 live births for those covered by Medicaid.

Those with private insurance also had a 43% lower risk of postneonatal mortality (from 28 days to one year after birth); a 10% lower risk of a low-birthweight infant; a 20% lower risk of vaginal breech delivery; and an 8% lower risk of preterm birth. They were 24% more likely to have received first-trimester prenatal care than those with Medicaid.

Travers said the difference may result from the onerous application process for Medicaid, which delays access to early prenatal care. Previous research shows such delays are associated with worse infant health outcomes.[1],[2]

To address this issue, Travers suggested exploring policies around presumed eligibility for pregnant Medicaid beneficiaries. “The idea there would be that once you’re pregnant, you would automatically have access to prenatal care appointments while waiting on Medicaid approval,” he said.

Travers also suggested more help for Medicaid beneficiaries with navigating the healthcare system and scheduling essential prenatal appointments. “Community health workers or healthcare navigators could have a role,” he said. Peer coaches, known as doulas, could also provide valuable emotional and informational support throughout pregnancy and childbirth.

“From a holistic perspective, infants should have good health outcomes, irrespective of their parents’ socioeconomic status,” he said. “Babies shouldn’t die because of the kind of health insurance their mother has.”

[1] Swartz JJ, Hainmueller J, Lawrence D, Rodriguez MI. Expanding prenatal care to unauthorized immigrant women and the effects on infant health. Obstet Gynecol. 2017;130(5):938-945.

[2] 22. Taylor YJ, Liu TL, Howell EA. Insurance differences in preventive care use and adverse birth outcomes among pregnant women in a Medicaid nonexpansion state: a retrospective cohort study. JWomens Health (Larchmt). 2020;29(1):29-37.

January 29, 2024 by
Neonatology

The Benefits of Early Breast Milk Fortification

A study led by Ariel Salas, M.D., suggests that early breast milk fortification may boost growth in extremely preterm infants.

A new study led by Children’s of Alabama neonatologist Ariel A. Salas, M.D., suggests that feeding extremely premature infants—those born at 28 weeks of gestation or less—with breast milk fortified with human-derived nutrients shortly after birth could help boost growth and, possibly, cognitive and neurological development.

The first two weeks of life are critical for the growth and development of these neonates. While older infants are fed bovine-fortified breast milk soon after birth, there has long been a reluctance to feed it to these fragile neonates, Salas said.

“Starting fortification early has always been a challenge for clinicians because we always get worried about introducing bovine-derived nutrients too early in infants’ diet,” given the risk of necrotizing enterocolitis, he said. “So, there was a lot of pushback about doing this study.” Using a human-derived product, however, provided reassurance, and the study was approved.

The study randomized 150 extremely preterm infants with a mean birth weight of 795±250 grams and a median gestational age of 26 weeks to receive either fortified breast milk starting on day two after birth or unfortified breast milk. After two weeks, all babies transitioned to standard breast milk with bovine fortification. Eleven infants died during the observation period. The outcome was assessed in 105.

Those receiving the human-derived, fortified breast milk early on gained weight faster from birth to 36 weeks and had lower head circumference-for-age declines than the control group. Head circumference correlates with brain size, which is vital for cognitive and motor development.

Although there was no overall change in fat-free mass, Salas attributes that to the fact that the team could not measure fat mass in the sickest babies, given the invasive method used for measurement.

“The ones that would benefit the most from this early intervention were not being scanned for that outcome,” he said. However, they still showed benefits in terms of body length and head circumference. His team is now testing a non-invasive urine analysis technique to measure body fat.

The study also found no difference in outcomes in babies fed donor milk versus milk from their own mothers, but Salas hypothesizes that less fortification might be needed in maternal milk, which is already higher in protein than donor milk.

Salas said that few feeding interventions have been shown to improve head growth in preemies.
“We might be one of the few studies that show that effect,” he said. His team plans to follow the babies to see if the head circumference growth correlates with cognitive and neurological outcomes at two years of age.

“If the positive effects on length and head circumference translate into potential benefits for neurodevelopment at two years of age, early human milk fortification could be justified” despite its higher cost, he said.

The results were so significant that “we decided to change our practice,” Salas said. Now, all extremely preterm infants at Children’s receive human-derived, protein-fortified donor milk for the first two weeks of life.

“I’ve been doing clinical trials for almost eight years and always wondered how impactful they will be in common practice. And this one, I think, will be very impactful,” Salas said.

January 29, 2024 by
Gastroenterology

Cavender to lead new polyposis clinic

A new polyposis clinic, led by pediatric gastroenterologist Cary Cavender, M.D., is aimed at enhancing pediatric gastrointestinal care.

As the medical landscape evolves, so does the need for specialized care, particularly in areas that impact vulnerable populations. Successfully managing gastrointestinal issues in children can be extremely challenging, but a new clinic at Children’s of Alabama and the University of Alabama at Birmingham (UAB) will soon provide a hub of specialized care.

The Children’s of Alabama Polyposis Clinic was conceived to fill a crucial gap in pediatric gastroenterology. Recognizing the need to provide focused expertise and coordinated care for patients with polyposis syndromes “was the major impetus for establishing a dedicated clinic,” pediatric gastroenterologist Cary Cavender, M.D., said.

Scheduled to open in early 2024, the clinic will initially operate on a quarterly basis. To best serve patients, many of whom are at increased risk for cancer, the clinic will integrate with members of the oncology team specializing in cancer predisposition. Among their other duties, oncology team members will coordinate genetic counseling for high-risk patients at the Oncology Cancer Predisposition Clinic, ensuring families receive comprehensive support.

The new polyposis clinic will also offer advanced diagnostic and treatment procedures, including advanced endoscopy and colonoscopy techniques like pill cam endoscopy, as well as medication management. Cavender anticipates seeing approximately 15 to 20 patients at first each year, with potential growth as awareness increases. “Our patients need routine monitoring and early and more frequent colonoscopies to ensure they stay as healthy as possible. Since many of these diseases have genetic components, many families with these types of GI issues are already tuned in and aware of the need for consistent screening,” said Cavender, who’s also a professor of pediatrics at UAB. “We’ll make those services available to everyone in one convenient location.”

Polyposis syndromes, particularly familial adenomatous polyposis (FAP), present unique challenges. Cavender notes the varied penetrance of the FAP gene within families, and emphasizes the importance of early screening. The clinic’s services will extend beyond diagnostics to include treatments such as sulindac, a medication inhibiting polyp growth, administered orally for patient convenience.

The polyposis clinic stands out as a unique endeavor—one of the first of its kind in the Southeast. Cavender believes it will serve as a vital resource, offering top-tier care for children with polyposis syndromes. With a focus on early detection and a multidisciplinary approach, the clinic aims to provide families with a path forward, instilling confidence in managing these complex conditions. “Early detection makes all the difference for kids with these conditions. Our clinic will enable us to offer the most advanced procedures and genetic testing to identify problems early. Our focus means we’re on the cutting edge of delivering care,” Cavender said.

Cavender’s vision for the clinic extends beyond medical interventions to fostering awareness among health care providers and ensuring that every child in need finds a dedicated and expert team ready to guide them toward a healthier future. “Some of our health system doctors might not even know there are pediatric GI specialists that can help take care of this type of thing,” Cavender said. “Providing a path forward through the clinic will help patients and families navigate these complex GI syndromes successfully.”

January 26, 2024 by
Gastroenterology

Improving Inflammatory Bowel Disease Care

Children’s of Alabama and the Univ. of Alabama at Birmingham are embarking on five-year study with the Crohn’s and Colitis Foundation.

In an effort to confront the challenges faced by patients with inflammatory bowel disease (IBD), the Crohn’s and Colitis Foundation recently received a transformative grant from the Centers for Disease Control and Prevention (CDC). This comprehensive five-year project marks a pivotal collaboration with Children’s of Alabama and the University of Alabama at Birmingham (UAB), targeting the identification and resolution of barriers hindering the diagnosis and care of individuals affected by IBD.

Traci Jester, M.D., associate professor of Pediatric Gastroenterology, Hepatology and Nutrition at UAB, is a project co-investigator. The project holds promise in transforming the approach to IBD management. The grant encompasses a three-part strategy; the first phase involves patient recruitment at both the Pediatric Inflammatory Bowel Disease Clinic at Children’s and the UAB Gastroenterology Inflammatory Bowel Disease Clinic.

The study aims to comprehensively address barriers to timely diagnosis and care through data collection initiatives. The initial phase involves survey-based assessments covering a variety of factors such as psychological resilience, socio-economic status and healthcare access. Then, patient-centric focus groups comprised of a cohort of patients from the initial phase of the study will delve deeper into the challenges faced and identify potential solutions.

As the study unfolds over its five-year span, the final phase will focus on developing and testing strategic interventions. These interventions aim to bridge the gaps in disease awareness among the public and specific demographics while also focusing on educating primary care providers to ensure timely referrals to specialists.

The choice of UAB as the collaboration site for this groundbreaking study stems from its robust research infrastructure, diverse patient population and track record of successfully investigating health disparities across various medical fields. This partnership builds on previous collaborations, signifying a shared commitment to improving patient care and advancing IBD research.

IBD encompasses chronic inflammatory conditions affecting various sections of the gastrointestinal tract. Both Crohn’s disease and ulcerative colitis, two well-known inflammatory bowel conditions, affect large numbers of children throughout the country. Jester highlighted that while Crohn’s disease can impact any part of the gastrointestinal tract, ulcerative colitis typically involves inflammation in the colon.

“Both adults and children can be diagnosed with inflammatory bowel disease, but the incidence in diagnosis is actually rising in the pediatric population,” Jester said. “We’re seeing younger and younger patients being diagnosed—roughly 25% of all patients with inflammatory bowel disease are identified before the age of 18.”

One of the primary barriers to prompt diagnosis and treatment revolves around a lack of awareness among both patients and health care providers regarding the prevalence and symptoms of IBD. Jester explained how this can lead to delayed referrals and inadequate support for patients, compounded by socioeconomic factors like transportation issues and limited resources.

Jester expressed enthusiasm for this pivotal project and its potential to enhance care for all patients affected by IBD. The collaboration between UAB, Children’s and the Crohn’s and Colitis Foundation reflects a concerted effort to create tangible improvements in disease management and patient outcomes.

“We’re very excited about this project here at UAB and partnering with such a national organization as the Crohn’s and Colitis Foundation,” Jester said. “We’re very much looking forward to improving care for all of our patients.”

January 26, 2024 by
Hematology and Oncology

New researcher brings focus on DIPG treatment

Rintaro Hashizume, M.D., Ph.D., is researching intranasal delivery for DIPG medication.

In 2023, the University of Alabama at Birmingham (UAB) Department of Pediatrics welcomed Rintaro Hashizume, M.D., Ph.D., a scientist specializing in pediatric neuro-oncology. Hashizume, an associate professor of hematology and oncology, brings a commitment to pediatric brain tumor research, focusing specifically on the daunting challenge presented by diffuse intrinsic pontine glioma (DIPG).1

DIPG is an aggressive brain tumor that primarily affects children and has a grim prognosis, with most patients succumbing to the disease within 12 months. What makes DIPG particularly challenging is its location in a vital area of the brain that controls breathing and heartbeat, rendering surgery impractical.

Traditional chemotherapy faces significant hurdles in treating DIPG, primarily due to the blood-brain barrier and the lack of genomic alterations in pediatric brain tumors. However, in 2012, genome-wide sequencing identified a specific mutation in DIPG, providing a crucial target. Hashizume’s lab has been developing therapies that specifically target this mutation, particularly through epigenetic targeting therapy.

One groundbreaking aspect of Hashizume’s research is intranasal delivery for drug administration. This method bypasses the blood-brain barrier, offering a non-invasive and convenient alternative method of drug delivery to the brain tumor. Hashizume’s team is exploring liposome-encapsulated drugs delivered intranasally, aiming to enhance the effectiveness of radiation therapy for the treatment of DIPG.

Intranasal delivery enables the liposome-encapsulated drug to enter the brain through specific neural pathways that bypass the blood-brain barrier. The liposome carrier protects the therapeutic drug as it passes through nasal membranes; when it gets into the brain, the liposome opens to disperse the drug. “Using this method, the drug can be delivered quickly to target areas,” Hashizume said.

While emphasizing the importance of mechanistic research, Hashizume acknowledges the urgency of translating discoveries into clinical applications. He envisions intranasal delivery becoming a feasible option for clinical trials, stressing the need for a swift transition from preclinical studies to clinical trials, especially considering the critical nature of pediatric brain tumors.

“I think we’ll need a combination treatment approach using radiation, since that’s a current standard therapy in DIPG that can help provide transient relief from the disease,” Hashizume said. “Clinical trials are needed to discover how we can enhance the radiation’s effect in combination with the intranasally delivered drug.”

Hashizume’s dedication to pediatric brain tumors spans more than 15 years. Originally a physician-scientist in Japan, he transitioned to the University of California San Francisco (UCSF) with a focus on adult brain tumors. However, a pivotal moment led him to shift his research focus exclusively to pediatric neuro-oncology. The catalyst for this change was his long-standing connection with Girish Dhall, M.D., director of the Division of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation at Children’s of Alabama, who played a crucial role in recruiting him to the hospital.

With the support of organizations like the Pediatric Brain Tumor Consortium, Hashizume aims to accelerate the translation of research into clinical practice. As research progresses, the potential for new, effective treatments for these devastating tumors becomes increasingly tangible.

  1. This research was supported by a grant from Prayers From Maria Children’s Glioma Cancer Foundation. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the Prayers from Maria Children’s Glioma Cancer Foundation. ↩︎
January 25, 2024 by
Hematology and Oncology

Thrombosis Program Growing Rapidly

Illustration of a blood clot (Stock image)

With increased rates of blood clots in children—especially those who are hospitalized—the need for a dedicated pediatric thrombosis program at Children’s of Alabama came to fruition five years ago. Since then, the program has made its mark by creating institutional guidelines for venous thromboembolism (VTE) management, developing educational materials for patients and families, and participating in prestigious clinical trials.

“We’ve grown tremendously—it didn’t take long to get the word out,” said Children’s pediatric hematologist Hope Pritchett Wilson, M.D., who is also an assistant professor in the Division of Hematology & Oncology at the University of Alabama at Birmingham (UAB). “Most of it is through word of mouth alone.”

Hope Wilson, M.D.

This past year proved record-breaking for the program, exceeding the yearly average of 50 to 60 new thrombosis diagnoses in young patients. What accounts for its growth? Wilson explained that advances in critical care for the sickest children, which often involves placing a central venous catheter, makes clotting more likely. VTE awareness has also grown, enabling clinicians here and elsewhere to better pinpoint affected children.

But managing these children’s care is often a long-term prospect. Girls, for example, may be unable to use estrogen-based medications for menstrual problems or birth control, while student-athletes on blood thinners may need to refrain from contact sports due to an increased bleeding risk. A small subset of young patients will need lifelong anticoagulation therapies.

At Children’s dedicated thrombosis clinic, held every Thursday, clinicians are now receiving referrals from all across the city and state. A multidisciplinary staff that includes specialists in hematology and pharmacy as well as a nurse practitioner, nurse coordinator and research nurse means the team can “all bring different expertise and lived experiences to think of a child holistically,” Wilson said. “One of the more recent collaborations we’ve established, with interventional radiologists, offers a direct path to patients who may need further intervention and may benefit from various procedures.”

The team’s mounting expertise has empowered them to develop institutional guidelines for VTE management tailored to patients here and create more effective educational materials for patients and families. The clinic has also participated in prestigious clinical trials—including a pivotal international multi-center study comparing outcomes with six weeks versus three months of VTE treatment in children—that have proven practice-changing.

“As we see results, we can implement them directly,” Wilson said. “Our names are in the conversation now regarding different trials because we provide quality care, have high patient volume and successfully enroll children into clinical trials.”

Moving forward, Wilson said the program may begin other forms of outreach in an attempt to pinpoint all children who might benefit from its expertise and efforts. Staff members are planning to survey families whose children are seen in the clinic about gaps or barriers to ensure more equitable care.

“Now that we’ve established ourselves, let’s go back and do some advertising because there are likely some children we’re missing,” she said. “We want to service local and statewide communities as best we can. If more blood clots are happening nationally, there are probably more happening locally, and we want to be positioned to help these children.”

January 25, 2024 by
Cardiology

Heart team discovers new lung injury biomarker

Ahmed Asfari, M.D., with a patient in the Pediatric & Congenital Heart Center of Alabama at Children’s of Alabama.

Nearly all children who undergo cardiac surgery suffer lung injury afterward, and its treatment can determine whether the injury is short-lived or will follow a child for a lifetime. That’s why the discovery at Children’s of Alabama of a new biomarker to predict which patients are at higher risk of this complication—steering the use of respiratory support—is being heralded as a groundbreaking development that may reap benefits for children far and wide.

Using samples from a Children’s biorepository, heart specialists revealed that blood levels of a protein called proteoglycan 4, commonly known as lubricin, significantly differ between children undergoing long- and short-term mechanical ventilation after cardiac surgery. Until now, physicians haven’t been able to predict which patients stood at higher risk of lung injury in this care setting.

It’s the first time the finding has been reported in the United States, said Ahmed Asfari, M.D., a cardiac intensivist at the Pediatric & Congenital Heart Center of Alabama at Children’s.

“There’s been nothing like this in regards to acute lung injury, especially for our patient population with congenital heart surgery,” said Asfari, who’s also an assistant professor in the Department of Pediatrics and Division of Cardiology at the University of Alabama at Birmingham (UAB). “When we tested the blood of patients with very long mechanical ventilation duration and compared them to patients with short duration, we found the level of this marker goes down, especially within two days of surgery.”

The discovery wouldn’t have been possible without the Children’s biorepository (left), which houses samples dating back over a decade. All patients under age 8 admitted for heart surgery had blood collected at several points in care, including before and after heart and lung bypass treatment, contributing to this research. The findings were validated at the Dr. Tannin Schmidt Lab at the University of Connecticut and published in Translational Pediatrics.

Asfari said the breakthrough likely will change the landscape for children’s care in the future. “Having the ability to have a serum biomarker that we can use to grade the level of acute lung injury will be extremely helpful,” he said.

The next stage of research will also expand insight into how widely the biomarker may be used. Blood testing now includes larger numbers of patients, along with those in different age groups and with varying cardiac physiology and anatomy, as well as those undergoing other types of surgery, and those both on and off bypass.

“The next step of our research will be doing it prospectively, looking at the patients, healthy children, and also patients with acute lung injury with different physiology—not just heart disease—and over a longer period,” Asfari said.

If the results hold, he predicts the new biomarker might one day become a gold-standard test to predict patients’ odds of suffering acute lung injury.

“It has very good potential to be used at bedside,” Asfari said. “This kind of study and research is very important to adjust the care we’ll provide for each individual patient and shines a light on the role of customized medicine for the future.”

January 25, 2024 by