Association of pancreatic fat on imaging with pediatric metabolic co-morbidities.

BACKGROUND: The relationship between pancreatic fat on imaging and metabolic co-morbidities has not been established in pediatrics. We sought to investigate the relationship between pancreatic fat measured by MRI and endocrine/exocrine dysfunctions along with the metabolic co-morbidities in a cohort of children. OBJECTIVE: To investigate relationships between pancreatic fat quantified by MRI and endocrine and exocrine conditions and metabolic co-morbidities in a cohort of children. MATERIALS AND METHODS: This was a retrospective review of pediatric patients (n = 187) who had a clinically indicated MRI examination between May 2018 and February 2020. After 51 patients without useable imaging data were excluded, the remaining 136 subjects comprised the study sample. Laboratory studies were assessed if collected within 6 months of MRI and patient charts were reviewed for demographic and clinical information. MRI proton density fat fraction (PDFF) sequence had been acquired according to manufacturer's specified parameters at a slice thickness of 3 mm. Two blinded radiologists independently collected PDFF data. RESULTS: The median age at MRI was 12.1 (IQR: 9.0-14.8) years and the majority of patients were Caucasian (79%), followed by African American and Hispanic at 12% and 11% respectively. There was a higher median pancreas fat fraction in patients with exocrine conditions (chronic pancreatitis or exocrine insufficiency) compared to those without (3.5% vs 2.2%, p = 0.03). There was also a higher median fat fraction in the head of pancreas in patients with endocrine insufficient conditions (insulin resistance, pre-diabetes, type 1 and type 2 diabetes) compared to those without endocrine insufficiency when excluding patients with active acute pancreatitis (3.5% vs 2.0%, p = 0.04). Patients with BMI > 85% had higher mean fat fraction compared to patients with BMI ≤ 85% (head: 3.8 vs 2.4%, p = 0.01; body: 3.8 vs 2.5%, p = 0.005; tail: 3.7 vs 2.7%, p = 0.049; overall pancreas fat fraction: 3.8 vs 2.6%, p = 0.002). CONCLUSION: Pancreas fat is elevated in patients with BMI > 85% and in those with exocrine and endocrine insufficiencies.

Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVE: Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS: This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement (<0.5 units/kg/day), or high insulin requirement (≥0.5 units/kg/day). RESULTS: At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 41 (20%) had high insulin requirement. Insulin-independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; P = 0.03). Patients with insulin independence had a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (P = 0.03). Higher peak C-peptide measured by stimulated mixed-meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at 1 year (P = 0.006 and 0.03, respectively). CONCLUSIONS: We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.

Bone Health Outcomes at 1 Year after Hematopoietic Stem Cell Transplantation in a Heterogeneous Pediatric Population.

Impaired bone mineral density (BMD) is a known complication of hematopoietic stem cell transplantation (HSCT) in adults and may lead to increased fracture risk. Less is known in children about the risks for impaired BMD and fragility (low trauma) fractures after HSCT. In this study, we evaluated the incidence of fragility fractures in a large diverse pediatric HSCT recipient population and identified risk factors for both fracture and impaired BMD. We reviewed the records of 237 patients age ≤21 years at the time of transplantation who underwent HSCT at our institution between January 2015 and March 2018. The primary endpoint was the incidence of fragility fractures, and the secondary endpoint was assessment of BMD on dual-energy X-ray absorptiometry (DXA). DXA studies were available for analysis in 79 of 206 patients who were alive at 1 year after HSCT, and the median height-for-age adjusted z-score for spine BMD was 0.15. Among the 237 patients in this study, 25 (10.5%) had evidence of at least 1 fragility fracture on imaging. In the patients with at least 1 fragility fracture, 18 (72%) sustained spine fractures. The median time to fracture was 5.9 months after HSCT. Mortality at 1 year was proportionally higher, although not statistically significantly so (P = .11) in patients who had at least 1 fragility fracture (24%; 6 of 25) compared with patients without a fragility fracture (12%; 25 of 212). Vitamin D status at 1 year post-HSCT was sufficient (>20 ng/mL) in 94% of the patients assessed (160 of 171). There was no difference in the incidence of fracture between vitamin D-sufficient patients and vitamin D-insufficient patients (P = 1.0). The incidence of fracture was significantly higher in patients with graft-versus-host disease (GVHD) compared with those without GVHD (15% vs 6%; P = .02). There was no significant difference in fracture occurrence between patients who received reduced-intensity conditioning and those who received myeloablative conditioning. The cumulative glucocorticoid dose was significantly associated with fracture in patients exposed to glucocorticoids for >3 months (P = .03). The incidence of fragility fractures, especially vertebral compression fractures, after pediatric HSCT is striking. Furthermore, there may have been additional, asymptomatic patients in our cohort with undetected, occult fractures. The high incidence of fragility fractures seen in this study advocates for establishing bone health screening protocols with attention to spinal imaging in pediatric patients undergoing HSCT.

Age at and indication for diagnosis of Turner syndrome in the pediatric population.

Early diagnosis of Turner syndrome (TS) enables timely intervention and may improve outcomes, but many are still diagnosed late. The objectives of our study were to describe the age and clinical features leading to diagnosis of TS in a large referral center. We hypothesize that newer testing modalities, such as noninvasive prenatal testing (NIPT), may lead to a decline in the age of diagnosis. Medical records of TS patients followed at The Cincinnati Center for Pediatric and Adult TS Care between 1997 and 2016 were reviewed for age at diagnosis, karyotype, and clinical indication(s). Patients (<18 years) were included (n = 239). Thirty-seven percent of patients were diagnosed prenatally or neonatally (≤1 month). The median age of diagnosis was 1.5 (IQR 0.0-10.0) years. If not made during those periods, the median age was 9.3 (IQR 3.2-12.5) years. The most common indications for diagnosis were before birth, unspecified prenatal testing (57%); in neonates/infants, lymphedema (21%); in childhood, short stature (72%); and in adolescence, short stature (45%) followed by pubertal delay with short stature (22%). The age of TS diagnosis in our cohort is young. However, when the diagnosis is not made before 1 year, the median age of diagnosis has not changed in recent years. The age at diagnosis could decrease with prenatal testing, although our study may not have assessed a long enough period of increased use of NIPT. Together with an increase in provider clinical awareness, this may result in more age-appropriate screening of comorbidities and earlier therapeutic intervention.