bluuebunny/crossref_metadata_2025_split huggingface dataset:
LBODP085 Effects Of Elexacaftor-tezacaftor-ivacaftor On Glucose Tolerance And Other Metabolic Parameters In Children With Cystic Fibrosis
Authors: Choudhari Pooja , Ham Melissa Rebecca 
Published: November 2022

Abstract
Cystic fibrosis related diabetes (CFRD) occurs in up to 20% of teenagers and has detrimental effects on lung function and nutritional status. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have had positive and mixed effects on glucose tolerance in children. Our study aimed to investigate the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on glucose tolerance, as well as on anthropometric measures and lipids, in children. We hypothesized that glucose tolerance and BMI would improve. We completed a retrospective study of children at a Pediatric Cystic Fibrosis (CF) Center who were started on ETI after December 2019. Our inclusion criteria were children 12 years and older who were on ETI for at least one year. We did not include children on long-term corticosteroids, with type 1, type 2, or other secondary diabetes, or who were post-transplant. Blood glucose at 2 hours after an oral glucose tolerance test (2-hour BG), Hemoglobin A1c (HgbA1c), lipids, and weight and BMI z-scores were assessed after at least one year on ETI. For patients with CFRD, only HgbA1c was performed for monitoring glycemic control. These measures were compared to corresponding measures in control groups of children older than or at 12 years old, heterozygous or homozygous for F508d, who were seen at the CF Center 4 years prior, and therefore were not receiving ETI. Patients with normal and impaired glucose tolerance (NGT/IGT) were compared to controls with similar glucose tolerance and separated by age. Patients with CFRD were compared to controls with CFRD only. Average length of time on ETI was 18.7 months. CFRD was diagnosed in 8.6% of patients and impaired glucose tolerance in 13.8% of patients. Previous CFTR modulators were used in 31.6% of patients. Average 2-hour BG increased by 3.2 mg/dl (n=44, p=0.6) and average HgbA1c decreased by 0. 05% (n=53, p=0.18) after the use of ETI. Weight z-score increased by 0. 07 (n=54, p=0.38) and BMI z-score increased by 0.13 (n=58, p=0.31). Total cholesterol increased significantly by 17.6 mg/dl (n=56, p&lt;0. 0001), but in contrast, triglycerides only increased by 4.75 mg/dl (p=0.46). Change in average 2-hour BG for children in the NGT/IGT control group (total n=30) were similar to children receiving ETI: 12-13 years: 3.6 versus 3.2 mg/dl, 13-14 years: -9. 0 versus -3.5 mg/dl, and 14-18 years: 18.5 versus 8.6 mg/dl (all p&gt;0. 05). In children with CFRD, the control (n=7) and ETI (n=5) groups had similar changes in HgbA1c (-0.56% versus -0.5%, p=0.94). In a retrospective analysis of children, 2-hour BG and HgbA1c changed minimally after at least one year on ETI and did not differ significantly when compared to controls. Minimal changes were also seen for BMI, weight, and triglycerides after use of ETI. However, total cholesterol increased significantly with the use of ETI.
Presentation: No date and time listed
ODP373 A Tale of Two Syndromes: Coexistence of Russell-Silver and Klinefelter Syndrome
Authors: Pillai Chanthu 
Published: November 2022

Abstract

Background/Aims
Klinefelter syndrome is a common condition characterized by an extra X chromosome, tall stature, gynecomastia, and hypogonadism. Russell-Silver syndrome is a rare disorder characterized by intrauterine growth restriction, poor growth after birth, and triangular facies. The coexistence of Russell-Silver and Klinefelter syndrome has so far not been reported in the literature. This study aimed to characterize the phenotype of such an individual.

Methods
Clinical and endocrinal investigations were performed and followed by pathogenic variant screening of candidate genes.

Results
An 8-year-old boy was evaluated for short stature. He was a former 27-week preemie who had postnatal growth failure. His mean parental height was5'6" (66 inches). His growth chart showed that he was below the 0. 01% percentile in both height and weight for age. He had behavioral issues. On physical exam, he had high riding prepubertal testes and proportional limbs. He was evaluated by both genetics and endocrine. His bone age was delayed by 4 years. He passed his growth hormone stimulation test. He had a nondiagnostic bone survey. His chromosomal microarray showed an XXY karyotype. Further testing was collected because it did not explain his short stature. He was found to have maternal uniparental disomy of 7q32.2. He was started on growth hormone and his most recent growth velocity was 4 cm a year. He continues to be below the 0. 01% percentile in both height and weight for age Conclusion: This is the first report on a patient with the coexistence of Russell-Silver and Klinefelter syndrome. It shows that the short stature and postnatal growth of Russell-Silver syndrome is the prevailing phenotype in this rare combination.
Presentation: No date and time listed
ODP376 Accuracy of Doppler Assessment of the Uterine Arteries for the Diagnosis of Pubertal Onset in Girls: A Scoping Review
Authors: Cheuiche Amanda , de Paula Leila , Lucena Iara , Moro Candice , Silveiro Sandra 
Published: November 2022

Abstract

Introduction
The uterine artery pulsatility index (PI) assessed by Doppler ultrasonography (US) reflects the blood flow impedance in the vessel distal to the sampling point and tends to decrease with the onset of puberty, being suggested as a parameter to define pubertal development.

Objective
To evaluate the accuracy of the uterine artery PI for the diagnosis of puberty in girls.

Methods
A PRISMA-ScR-compliant scoping review was performed in the MEDLINE and Embase databases with "puberty" and "Doppler ultrasonography" as search terms. Studies that included girls aged 0-18 years who underwent pelvic US with Doppler of the uterine arteries and calculation of the PI were considered eligible.

Results
Ten studies comprising 1385 girls aged 1.2-18 years were included. The selected studies were published between 1996 and 2021 and included participants from five countries (Italy, Brazil, Iran, Belgium and Denmark). Six studies included girls who were referred for evaluation of pubertal disorders, mainly thelarche or early-onset pubarche, while four studies selected only healthy girls. Nine studies found a significant difference in Doppler and PI according to pubertal stage, with PI cutoff points ranging from 2.5 to 4.6 for the diagnosis of onset of puberty, with a sensitivity of 77-94%, specificity of 85-100% and accuracy of 79-98%.

Conclusion
Doppler assessment of the uterine arteries with PI calculation is a useful noninvasive tool in the diagnosis of onset of secondary sexual characteristics in girls.
Presentation: No date and time listed
ODP392 Persistence with daily growth hormone treatment among pediatric patients with growth hormone deficiency in the UK
Authors: Loftus Jane , Wogen Jen , Oliveri David , Benjumea Darrin , Jhingran Priti , Chen Yong , Alvir Jose , Sanz Elena Rivero , Kowalik Jack Charles 
Published: November 2022

Abstract

Background
Suboptimal adherence to, and persistence with, daily somatropin therapy to treat children with growth hormone deficiency (GHD) has been documented previously, and has also been shown to have negative effects on the growth response.

Objectives
To describe discontinuation of, and persistence to, daily somatropin treatment among pediatric patients with GHD in the UK.

Methods
This was a retrospective cohort study of pediatric patients (≥3 and &lt;16 years) with &gt;1 medication prescription for daily injectable somatropin from 1 st July 2000 to 31 st December 2020 in the IQVIA Medical Research DATA (IMRD) database. Patients were required to have &gt;1 diagnostic code for GHD during the 6 months preceding and including the first somatropin prescription date ("index date"), and to be continuously enrolled in the database &gt;6 months preceding and &gt;3 months following index date. Patients with &gt;1 somatropin prescription during the 6 months prior to index date, or with diagnoses for other causes of short stature were excluded. Patients were followed for up to 48 months post-index. Early persistence was defined as the proportion of patients prescribed ≥1 somatropin refill subsequent to the initial prescription. Discontinuation was defined as the first date at which a medication gap (defined as either &gt;60 days or &gt;90 days between prescriptions) for somatropin occurred. Persistence (non-discontinuation) over time was evaluated using Kaplan-Meier methods to assess time to first discontinuation event. The relationship of patient characteristics with time to medication discontinuation was evaluated using Cox proportional hazards models.

Results
Among pediatric patients included in this study (n=117), the majority (n=84, 71.8%) had 48 months of available follow-up; 56.4% were male and mean (median) age was 8.6 (8. 0) years. About 98% of patients exhibited early persistence. Persistence over the follow-up period decreased with follow-up duration. Using a 60-day gap definition, persistence at 12, 24, 36, and 48 months was estimated among 48.3%, 35.4%, 26.7%, 16.5% of patients; using a more conservative 90-day definition, an estimated 72.4%, 58.6%, 52.8%, and 43.3% were persistent at the same time periods. No significant patient predictors of time to discontinuation were identified.

Conclusions
Despite high early persistence with somatropin, a sizable proportion of patients were increasingly non-persistent over time. In this UK-based study more than 1 in 4 patients were non-persistent at 12 months and more than 1 in 2 were non-persistent at 48 months. These results suggest that strategies to support improved medication-taking behavior among pediatric patients with GHD in the UK are warranted.
Presentation: No date and time listed
ODP395 Relationship of serum total insulin-like growth factor-binding protein-3 with triglyceride to high-density lipoprotein cholesterol ratio and glucose tolerance in Korean children and adolescents
Authors: Choi Iee H , Kim Minsun , Kim Sun-Young 
Published: November 2022

Abstract

Objectives
We investigated the relationships between serum IGF-I/ IGFBP-3 levels and degrees of triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio in Korean children and adolescents who underwentoral glucose tolerance test.

Methods
children and adolescents without known diabetes were checked an oral glucose tolerance test and collected the clinical and laboratory data. Serum IGF-I and total IGFBP-3 levels, TG/HDL ratio, total cholesterol, low-density lipoprotein cholesterol (LDL),AST, ALT, C-peptide levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, and glycated hemoglobin (HbA1c) levels were measured.

Results
Serum TG/HDL ratio and IGF-I/ total IGFBP-3 levels were significantly higher in individuals with type 2 diabetes (DM) than in those with normal glucose tolerance (NGT) (P&lt;0. 05). TG/HDL ratio was not related with age and IGF-I levels and it was correlated with serum IGFBP-3 levels, HbA1c, C-peptide, HOMA-IR, and body mass index. However, these relationships were altered in patients with insulin resistance state, especially in those with DM. In the DM group, TG/HDL ratio and total IGFBP-3 levels were positively correlated stronger than no-DM groups. In addition,TG/HDL ratio and total IGFBP-3 levels were positively correlated with total cholesterol and LDL levels but not with age.

Conclusions
TG/HDL ratio, the marker of small dense LDL particles, is related with IGFBP-3, especially in patients with type 2 diabetes. The IGF-I-IGFBP-3 axis, especially IGFBP-3, may play roles in the pathogenesis and metabolic control of lipid metabolism.
Presentation: No date and time listed
ODP619 Trends in Obesity in Gender Diverse Adolescents in Northern Nevada
Authors: Miah Faria , Brereton Caroline , Kelley Erin , Eckert Kathryn 
Published: November 2022

Abstract
Obesity in the pediatric population is increasing with 19.3% of adolescents having a body mass index (BMI) at or above 95th percentile. Childhood obesity impacts physical and psychological health, increasing the risk of developing various diseases. Studies show that prevalence of gender diverse (GD) adolescents is increasing and is estimated to be 7 per 1000 in the US. GD adolescents are at increased risk for cardiovascular disease and mental health disorders. GD adolescents who are diagnosed with obesity are at an increased risk for poor health outcomes. There is a lack of research regarding the prevalence of obesity and the impact of hormone therapy in GD adolescents. A retrospective chart review was conducted at Renown Regional Medical Center in Reno, NV. A total of 119 adolescents, aged 8-21, diagnosed with gender dysphoria prior to June 2021, were enrolled using ICD-10 codes. Patient demographics including age, sex assigned at birth, gender identity, BMI, and use of puberty blockers or hormone therapy were retrieved. Patients were categorized into two groups - no treatment and treatment with puberty blockers and/or testosterone. Average change in BMI was calculated. Fisher exact tests were conducted using SAS version 9.4. Nineteen of the 119 GD patients enrolled were classified as obese using age and sex appropriate BMI charts (15.9%). Thirteen participants were assigned female at birth (AFAB) and six were assigned male at birth (AMAB). Of these participants, 12 had no medical interventions and 7 were treated with puberty blockers and/or without testosterone. No participants received estrogen therapy. The average change in BMI was +1.84 (no treatment group) and + 3.70 (treatment group). The average change in BMI for AFAB participants was +2.24 and +3.16 for AMAB participants. Association of obesity with treatment compared to no treatment was not found to be statistically significant (p=0.4125). The prevalence of obesity in this population was similar to the prevalence of obesity in non-GD adolescents regionally. In Nevada, obesity in adolescents age 10-17 increased from 12.9% to 16% from 2018-2021. We expected to observe a higher prevalence of obesity in the adolescent GD population compared to the non-GD pediatric population. Additionally, we expected to see a greater increase in BMI in the group of GD patients receiving treatment. Although the results were not statistically significant, patients undergoing treatments did experience a greater average increase in BMI compared to those who had no medical intervention. The lack of statistical significance is likely due to having a small sample size. Further research is needed to observe obesity trends in adolescent GD populations, as well as the effects of hormone therapy on BMI.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
OR05-6 Designing a Gender Affirming Hospital: Patient Perspectives on Gender Inclusive Care
Authors: Fisher Erin , Gist Lauren , Inwards-Breland David , Marinkovic Maja , Marino-Kibbee Bixby , Patel Aarti , Rhee Kay , Richardson Tay , Yeh Debra 
Published: November 2022

Abstract

Background
Studies have shown transgender and non-binary individuals encounter discrimination and harassment in medical settings leading to delays in seeking care and worse physical and mental health outcomes. Organizations, including the American Academy of Pediatrics, published recommendations for medical centers to foster respectful and inclusive care through systems, environmental, and educational changes. However, it is unclear whether health systems are making these changes and what the impact may be for transgender and non-binary youth.

Objective
To explore perspectives of transgender and non-binary patients regarding the current state of gender inclusive care at our medical center and identify areas for improvement.

Design/Methods
A qualitative study was conducted at a large academic center. Participants aged 13-21 years were recruited from the Center for Gender Affirming Care to participate in a semi-structured interview and demographics survey regarding their experiences across various clinical settings within the medical center. Interviews were audio-recorded and transcribed verbatim. Survey results were analyzed using descriptive statistics. Two independent coders reviewed the transcripts, developed a preliminary coding scheme, and reached consensus on any coding discrepancies. ATLAS.ti® was used for thematic analysis.

Results
Thirty participants completed an interview and survey. Mean age of participants was 17 years, with 30% identifying as female/trans female, 47% male/trans male, and 23% identifying as nonbinary or gender fluid. Several key themes emerged. Overall participants are satisfied with their care and attributed improvements to societal progress and systems/environmental changes. Parent advocacy and diversity among staff promoted positive and affirming experiences. However, participants identified personnel, systems, and environmental areas needing improvement including: 1) Provider training on use of pronouns, gender affirming terminology, and exam techniques, 2) Reliable and accurate display of chosen name and pronouns in the electronic medical record (EMR) and patient labels, and standardized check-in processes to prevent misnaming/misgendering, 3) Desire for more LGBTQ-inclusive décor and resources.

Conclusions
While national recommendations were published more than 5 years ago, it is clear from our participants that not all recommendations have been implemented consistently across all clinical settings. Eliciting feedback from patients may provide tangible ways to improve care for this population.
Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.
OR18-5 A Prospective Clinical Trial of Vosoritide in Selected Genetic Causes of Short Stature
Authors: Boucher Kimberly , Dham Niti , Kanakatti Shankar Roopa , McCarthy Tara , Merchant Nadia , Zhang Anqing , Dauber Andrew 
Published: November 2022

Abstract

Objectives
Vosoritide is a C-type natriuretic peptide analog which binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation via its inhibition of the ERK1/2-MAPK pathway. It was recently approved for increasing linear growth in children with achondroplasia. Our study aims to assess the safety and efficacy of vosoritide in children with genetic mutations in 6 categories: hypochondroplasia, Rasopathies (including Noonan syndrome), aggrecan deficiency, carriers of heterozygous NPR2 mutations, CNP deficiency, and SHOX deficiency.

Methods
This is a prospective, Phase II study with a goal N of 35 subjects. All subjects must have a documented genetic mutation in one of the 6 categories, be prepubertal between the ages of 3 and 11 for boys and 3 and 10 for girls, and have a height &lt; -2.25 SD. Subjects are followed for a 6-month observation period to establish a baseline annualized growth velocity (AGV) and then receive daily subcutaneous vosoritide (15 mcg/kg/day) for 12 months. The primary outcomes are rate of AEs and change in AGV from baseline. Pharmacokinetic studies and pharmacodynamic studies, using cGMP production as a pharmacodynamic marker, are completed at Day 1 and Months 6 and 12.

Results
To date, 27 subjects have enrolled in the trial (20 hypochondroplasia, 3 Noonan, 2 NPR2, 2 Aggrecan). Median baseline height is -3.1 SD (IQR -3.6, -2.6). 14 subjects have initiated on vosoritide, and 10 completed 6 months of therapy. Median increase in AGV was 3.9 cm/yr (IQR 2.2, 4.6). The two subjects with NPR2 mutations had increased AGVs of 4.4 and 9.2 cm/yr. The two subjects with Noonan syndrome had an increase in AGV of 7.5 and 3.3 cm/yr. One subject with Noonan syndrome, a 4-year-old male, had previously been treated with growth hormone (GH) for 2 years. His AGV was 6.7 cm/yr while on GH, 4.1 cm/yr during the 6-month observation period, and 11.6 cm/year during the first 6 months of vosoritide treatment. There were no serious adverse events related to vosoritide treatment. One subject had a brief episode of syncope with her first injection which self-resolved, and she continued on therapy with no further incidents. PK parameters were similar to previously published parameters for vosoritide in children with achondroplasia. In preliminary data, vosoritide Cmax and AUC correlated strongly with peak increase in cGMP (r=0.70, p=0.01;r=0.84, p&lt;0.01, respectively) but not with increase in AGV (r=0.35, p=0.32).

Conclusions
This is the first clinical trial of vosoritide for children with genetic short stature who do not have achondroplasia. Vosoritide treatment may work as a precision therapy to improve growth in multiple genetic conditions which interact with the ERK1/2-MAPK pathway.
Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.
PMON313 Hyperinsulinemic Hypoglycemia and Growth Hormone Deficiency Secondary to 20p11 Deletion
Authors: Wee Erica , Dileepan Kavitha , Tsai S L , Paprocki Emily 
Published: November 2022

Abstract

Introduction
Hyperinsulinism (HI) and growth hormone deficiency (GHD) are known causes of hypoglycemia but not commonly found together. We present a 4-month-old boy with hypoglycemia found to have both HI and GHD with subsequent genetic diagnosis of 20p11 deletion. This deletion has been associated with panhypopituitarism. This case represents a few to report HI as a manifestation of this deletion. Treatment with both recombinant human growth hormone (rhGH) and Diazoxide led to blood glucose (BG) normalization.

Clinical Case
A 4-month-old, full-term, large for gestational age (96th percentile), born to a nondiabetic mother presented with hypoglycemic seizures. He had transient hypoglycemia at birth, normal newborn screen, and exclusively breastfeeding with normal growth and development. He had a negative 60-hour video EEG. Further work-up was significant for serum glucose of 54 mg/dL despite blood draw being 20 minutes after a breastfeed, prompting endocrinology evaluation. Physical exam showed no dysmorphism and normal genitalia. He had a serum glucose of 39 mg/dL while asymptomatic. Critical sample revealed detectable insulin (3.2 mcIU/mL), low beta hydroxybutyrate (145.6 mcmol/L) and low growth hormone (GH) (4.2 ng/dL). He had normal cortisol, lactic acid and ammonia. A glucagon challenge showed an increase in BG of 26 mg/dL (35--&gt;61 mg/dL). He had a GH stimulation test with arginine (peak GH 3.8 ng/dL) and glucagon (peak GH 6.6 ng/dL). He had mildly elevated liver enzymes that resolved on repeat testing. Plasma amino acid, plasma acylcarnitine profile, urine organic acids, and brain MRI were normal. He was initially started on rhGH with continued hypoglycemia, hence, Diazoxide, and chlorothiazide were added. His BG was monitored until dextrose infusion was successfully weaned, while maintaining normoglycemia. Genetic testing with next-generation sequencing revealed 20p11.22-p11.21 deletion. He was discharged on Diazoxide (12 mg/kg/day), chlorothiazide, and rhGH (0.27 mg/kg/week).

Conclusion
It is important to determine the cause of hypoglycemia so specific treatment can be provided. HI is a common cause of hypoglycemia in infants due to abnormal insulin secretion in the pancreatic beta cells. GHD can also cause hypoglycemia and be associated with other pituitary hormone deficiencies. Evaluation of our patient's hypoglycemia revealed HI, GHD and 20p11 deletion. This deletion has been associated with hypoglycemia due to GHD and few reports with HI. This patient will need to be regularly screened for other pituitary hormone abnormalities. Other features of 20p11 deletion include cognitive delay, craniofacial dysmorphisms, gastrointestinal and genitourinary anomalies. While hypoglycemia is often the result of a single cause, this case shows that there are pathological conditions that can present with both GHD and HI, so the differential diagnosis for hypoglycemia should remain broad.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.