bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-586 Gut Hormones Response to 24-H High Carbohydrate Overfeeding Is a Determinant of Metabolic Adaptation to Carbohydrate Intake in Healthy Individuals
Authors: Vinales Karyne Lima , Holltein Tim , Begaye Brittany , Walter Mary , Krakoff Jonathan , Piaggi Paolo 
Published: May 2020

Abstract
Background: We previously demonstrated that short-term (24h) changes in carbohydrate (CARBOX) or fat oxidation rates in response to overfeeding diets with different macronutrient content are highly correlated within an individual, suggesting the existence of human metabolic phenotypes (carbohydrate vs. fat oxidizers). Gut hormones have a role in feeding and substrate oxidation, thus we investigated if the changes in gut hormones concentration during overfeeding diets or fasting explain the degree of metabolic flexibility in healthy humans.Methods: While residing in our clinical research unit, 67 healthy, weight-stable volunteers (37±10y, BMI: 26±4 kg/m2, body fat: 28±10%; mean±SD, 54 men) with normal glucose regulation had 24-h EE measurements in a whole-room indirect calorimeter during energy balance (EB, diet: 50% carbohydrate, 20% protein), three overfeeding diets, and fasting in a crossover design. The overfeeding diets (200% of weight-maintaining energy requirements) included diets with 20%-protein [50%-carbohydrate (SOF), 75%-carbohydrate (CNP), and 60%-fat (FNP)]. Metabolic flexibility was determined by the difference between respiratory quotient (RQ) during overfeeding/fasting from EB conditions. Plasma GLP-1, PYY, PP, and total ghrelin concentrations were measured by ELISA after an overnight fast the morning of and after each diet. Results: PYY increased after all overfeeding diets (3.4±13.1, 7.0±16.2, and 7.6±14.4 pg/mL; all p&lt;0.05, SOF, CNP and FNP respectively) and decreased with fasting (-11.6±14.2 pg/mL; p&lt;0.001). GLP-1 increased after fasting (2.7±5.8 pg/mL; p&lt;0.001) and FNP (1.3±4.5 pg/mL; p=0.02) and decreased with CNP (-0.9±6.3 pg/mL; p=0.04). PP only increased after fasting (92.8±133.4 pg/mL; p&lt;0.001), while ghrelin decreased with SOF (-31.3±108 pg/mL; p=0.02) and CNP (-43.1±120 pg/dL; p=0.005) but not with FNP (p=0.51). After adjustment for body composition and other known EE determinants, no hormonal changes were associated with the change in 24-h EE in any diet (all p&gt;0.05); however, during CNP greater decreases in GLP1, PYY, and Ghrelin were associated with less increase in 24-h RQ (all r&gt;0.25; all p&lt;0.05) while greater decrease in PP was associated with larger increase in 24-h RQ (r=-0.31, p=0.01). Specifically, greater increase in CARBOX during CNP was positively associated with the changes in GLP-1 (r=0.30; p=0.02) and Ghrelin (r=0.32, p=0.01). In a linear model, only the change in GLP-1, PP, and Ghrelin concentrations during CNP were independent predictors of the change in RQ [β=0.003; -0.0001; and 0.000006 per 1 pg/mL increase each, p=0.008; 0.02 and 0.02 respectively], after accounting for age and sex. Conclusion: In a carbohydrate rich environment, individuals with normal glucose regulation who maintain GLP-1 and ghrelin levels are better adapted to metabolize this type of diet.
SUN-345 Use of Anti-FGF23 Monoclonal Antibody in the Treatment of Children and Adolescents with X-Linked Hypophosphatemic Rickets
Authors: Cassinelli Hamilton Raul , Brenzoni Luciana , Alconcher Laura , Forclaz Veronica , D′Amato Silvia , Rozenfeld Paula , Bergada Ignacio 
Published: May 2020

Abstract
Background: X-linked hypophosphataemia is the most common heritable form of rickets in children, disorder caused by mutations in PHEX, leading to elevated secretion of FGF23, renal phosphate wasting with consequent hypophosphataemia, diminish synthesis of 1,25(OH)2 vitamin D, rickets/osteomalacia, and disproportionate short stature. Conventional treatment with oral phosphate supplementation and active vitamin D heals rickets, prevents progressive growth failure, but in a substantial proportion of patients treatment is unsuccessful and/or associated with adverse effects. Since 2018, burosumab, a human monoclonal antibody against FGF23, was approved for the treatment of X-linked hypophosphataemia.Aim: We report a pilot experience on the efficacy and safety of treatment with burosumab in children and adolescents with X-linked hypophosphataemia (XLH). Methods and patients: Eight XLH patients (5 males) (5 pre pubertal and 3 Tanner IV) with an age range from 2.9 to 16.2 years, were recruited, 6/8 had family history of XLH, the remaining two were confirmed with molecular study. All discontinue conventional therapy at least 7 days before treatment with Burosumab which was administered every 2 weeks SC for 6 months, at a starting dose of 0.8 mg/kg/dose. Growth velocity, Thacher Rickets Severity Score, fasting serum calcium (mg/dl), phosphorus (P)(mg/dl), alkaline phosphatase (ALP)(IU/L), PTH (pg/dl), 25OH Vitamin D (ng/ml) and tubular phosphate reabsorption (TPR) (X±SD) were evaluated at basal, 3, and 6 months of treatment. Results: All patients had normal 25OH2 Vitamin D: 35.3±8.6 ng/ml at the start of therapy and had significantly improvement of serum P: basal 2.2±0.51, 3 months: 3.24±0.43 and at 6 months 3.01±0.38 mg/dl (p&lt;0.005). The mean serum ALP level decreased from 686.9±410.8 to 535.8±302.4 and 402.5±106.7 IU/L (p&lt;0.05) respectively. TPR normalized during treatment: 67.3±9, 86±3.1, and 86.9±6.1 %(p&lt;0.001). The severity of rickets, as well, showed a significant improvement: 4.0±2.0, 2.3±1.2, and 1.0±0.8 (p&lt;0.005), respectively. The non-pubertal children increased their growth velocity from 3.7±1.2 cm/yr to 7.0±1.4, and 7.9±2.0 cm/yr (p&lt;0.05) respectively. Serum calcium and PTH levels did not show any significantly variation. Mild adverse events such as local reactions and headaches were observed. Conclusions: 1) Treatment with burosumab restores phosphate metabolism, 2) Growth and the Thacher Rickets Severity Score improved during treatment, 3) all patients showed a good safety profile with only minor adverse events. This is the first report of children with XLH treated with burosumab in Latin-America.
SAT-145 Cholesterol Uptake as a Critical Vulnerability in Triple Negative Breast Cancer
Authors: O’Neill Kathleen 
Published: May 2020

Abstract
Triple Negative Breast Cancer (TNBC) is an aggressive subtype of cancer with poor prognosis due to high metastatic potential and lack of targeted therapies. Normal epithelial cells express the microRNA-200c (miR-200c), a potent suppressor of epithelial-to-mesenchymal transition (EMT). However, miR-200c is silenced or lost in TNBC, allowing a de-differentiated, non-epithelial phenotype and aberrant expression of genes conferring invasive and chemoresistant characteristics. Recent literature has demonstrated that EMT promotes altered tumor cell metabolism, creating novel vulnerabilities that can be exploited therapeutically. In addition to driving global metabolic changes, miR-200c-induced reversal of EMT alters key cholesterol metabolism genes that support the uptake of dietary cholesterol from the bloodstream. Intracellular cholesterol homeostasis is critical for cell survival and is carefully regulated, but how these homeostatic mechanisms adapt during tumor progression is poorly understood. Based on preliminary data, I hypothesize that TNBCs depend on exogenous cholesterol uptake and availability to maintain cell viability and an invasive phenotype. This work aims to identify novel cholesterol-related targets in breast cancer and delineate mechanisms regulating cholesterol homeostasis in normal and cancer physiology.Restoration of miR-200c in TNBC leads to alteration of the cholesterol uptake components low- and very-low-density-lipoprotein receptors LDLR and VLDLR, through direct and indirect mechanisms previously unexplored in cancer. miR-200c further inhibits Niemann-Pick Type C (NPC1), a lysosomal protein necessary for utilization of exogenous cholesterol. Interestingly, expression of NPC1 in TNBC correlates with a unique inability of cells to proliferate in the absence of exogenous LDL supply, suggesting defects in de novo cholesterol biosynthesis. Further, NPC1 inhibition leads to cell death in TNBC but not more epithelial-like breast cancers. Whether this cell death is due to disruption in critical cholesterol supply or due to defective lysosome dysfunction is currently being investigated. Overall, this work suggests a role of NPC1 in cancer cell metastasis that has not been previously explored, and identifies cholesterol uptake as a targetable dependency in TNBC.
SAT-079 Is There an Association Between the Detection Method for Pediatric Thyroid Nodules and the Risk of Malignancy?
Authors: Eng Liane , Chen Jarreau Spencer Sim , Lam Leslie S 
Published: May 2020

Abstract
Background
Thyroid nodules are less common in children compared to adults, but have a higher likelihood of malignancy. There are few studies, particularly in the pediatric population, examining the association between how and by whom the nodule is detected and the risk of malignancy. Several adult studies have suggested a high rate of malignancy in incidentally discovered thyroid nodules (1,2). However, this was not similarly seen in pediatric thyroid nodules according to one study (3). As fine needle aspiration (FNA) in pediatric patients may be more labor intensive and diagnostic excision is the recommendation for nodules with indeterminate or potentially malignant cytology, if the detection method can be a predictive measure of malignancy, it may enhance the evaluation of pediatric thyroid nodules.
Objective
The aim of this study is to determine if there is an association between how and by whom a thyroid nodule is detected and the risk of malignancy in the pediatric population.
Study Design and Methodology
We retrospectively reviewed the medical records of pediatric patients (≤21 years of age) who had a thyroid nodule with definitive cytologic or pathologic diagnosis from January 2010 to June 2019. Patients were categorized into 3 groups based on how and by whom the nodule was detected: (1) patient or parent, (2) provider, or (3) imaging obtained for non-thyroid indications (incidental). Characteristics that were evaluated included rate of malignancy, size of the nodule, location of the nodule, and size of the cancer (if present).
Results
A total of 78 patients with concerning thyroid nodules were analyzed. Within the study, the cancer rate was 27% (21/78), which is comparable to the reported malignancy rate of pediatric thyroid nodules in the literature (22-26%) (4), suggesting that our sample population may be representative of the general pediatric thyroid nodule population. In our study, though the absolute numbers were small, there was a higher rate of malignancy in the incidental group (3/5, 60%) compared to the patient/parent (9/34, 26%) and provider (9/39, 23%) groups. The average size of the thyroid nodule was similar in all 3 groups. The strength of this study was the inclusion of only patients with definitive diagnosis of the thyroid nodule and the possibility of the findings being applicable to the general pediatric population.
Conclusions
In our sample study, incidentally discovered pediatric thyroid nodules had a higher rate of malignancy as compared to those discovered by patients/parents or providers.
References
1.
Kang HW, et al. Thyroid 2004; 14(1):29-33.
2.
Liebeskind A, et al. J Ultrasound Med 2005; 24(5):629-634.
3.
Gupta A, et al. J Pediatr 2014; 164(3):658-660.
4.
Francis GL, et al. Thyroid 2015; 25(7):716-758.
SAT-141 Glycoprotein NMB (GPNMB) Is Pro-Tumorigenic in TSC2-Null Cancer Cells and Is a Potential Drug Target and Biomarker for Lymphangioleiomyomatosis (LAM)
Authors: Gibbons Erin , Taya Manisha , Seger Christina , Hammes Stephen R 
Published: May 2020

Abstract
Lymphangioleiomyomatosis (LAM) is an estrogen-sensitive lung disease found almost exclusively in women that is characterized by hyperproliferation of smooth muscle cells forming small tumors, or LAM lesions throughout the lungs of patients. Growth of these tumors leads to progressive loss of pulmonary function, and sometimes subsequent lung transplantation. LAM tumor cells contain mutations in either the TSC1 or TSC2 genes, leading to activation of the mTORC1 pathway. In fact, mTOR inhibitors such as sirolimus are commonly used to treat LAM; however, these drugs are not always effective and have significant side effects, suggesting the need for new therapeutic targets. Interestingly, another important feature of LAM cells is that they express melanocytic markers that are normally found in melanocytes or melanoma cells. From RNASeq analysis of a mouse model for LAM that we designed, we discovered significant upregulation of the melanocytic marker Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB), a type I transmembrane protein. GPNMB was not only highly expressed in our mouse model (a uterine specific TSC2-null mouse), it was also expressed in TSC2-null cell lines, and human LAM patient lung samples. In our hands, knocking down GPNMB expression by siRNA directed against GPNMB mRNA decreased migration and proliferation in TSC2-null cells. Additionally, we found that GPNMB’s large ectodomain is shed by TSC2-null cells and can be detected in the blood of human patients with LAM. Finally, MMP 2 and 9 can be secreted as a result of ectodomain shedding and its interaction with integrins. Accordingly, we did indeed see a decrease in MMP 2/9 expression in TSC2-null cells with reduced GPNMB expression from treatment with siRNA directed against GPNMB mRNA. Overall, our results demonstrate the potential importance of GPNMB in LAM tumor progression, and suggest that GPNMB may be a possible LAM biomarker and target for its treatment.
SAT-649 Comparison of the Accuracy and Concordance of 3 CGM Devices vs SMBG During Aerobic Exercise
Authors: Henske Joseph A , Thostenson Jeff D 
Published: May 2020

Abstract
Introduction: Real-time continuous glucose monitoring (rt-CGM) and flash glucose monitoring (FGM) devices have become important tools for managing type 1 diabetes. These devices are approved for management decisions in steady-state conditions, however there is a decline in accuracy during aerobic exercise with respect to MARD and lag time.1 It is possible that newer technologies may be superior to previous devices.
Question: With the newest rtCGM, FGM, and long-term CGM devices, do we continue to see an increase in MARD during continuous aerobic exercise? Is there a difference between glucose readings of the 3 devices when worn simultaneously during exercise?
Design: A single subject with T1DM, experienced in glucose management during exercise, wore 3 devices simultaneously - the DEXCOM G6 (San Diego, CA; rt-CGM1, worn on the abdomen), the Eversense (Germantown, DM; long-term CGM or rt-CGM2, implanted in the left arm), and the Abbott Freestyle Libre 14-day (Chicago, IL; FGM, worn on the right arm). The rt-CGM2 was calibrated using a blood glucose meter (Ascensia Contour Next) which was also used for comparator SMBG. Glucose was recorded 10 minutes before and after exercise and every 10 minutes during a 60 minute run at moderate intensity. 6 exercise sessions were averaged for data analysis. Subject wore an insulin pump and reduced the basal rate by 50% 90 minutes prior to exercise and resumed the basal immediately post-exercise. Carbohydrates were not used within 3 hours prior to exercise but could be consumed during exercise if needed to avoid hypoglycemia.
Results: Glucose value during 60 minutes of exercise dropped from mean of 167 to 114 mg/dL with SMBG, 174 to 115 mg/dL with rt-CGM, 175 to 115 with rt-CGM2, and 150 to 106 mg/dL with FGM. Average measured glucose was 140.0, 145.8, 145.6, and 129.3 mg/dL for SMBG, rt-CGM1, rt-CGM2, and FGM respectively. P-value &lt;0.05 for FGM. MARD (calculated compared to SMBG) for 10 minutes pre-exercise, during exercise, and post-exercise for rt-CGM1 was 5.1%, 11.7%, and 8.6% respectively. For rt-CGM2 MARD was 7.7%, 11.4%, and 10.0% respectively. For FGM, MARD was 12.7%, 5.3%, and 21.3% respectively. Overall MARD was 9.8% for rt-CGM1, 10% for rt-CGM2, and 8.0% for FGM.
Conclusions: Blood glucose values dropped with aerobic exercise with observed lag between CGM and SMBG. Rt-CGM1 and Rt-CGM2 showed increased MARD vs SMBG during exercise. Interestingly, lower MARD was seen for FGM during aerobic exercise likely due to bias towards lower glucose levels at baseline as reported by FGM. There was no significant difference seen during exercise between rt-CGM1 and rt-CGM2 despite the differing location of the sensors (transdermal vs subcutaneous) and method of glucose analysis (glucose oxidase vs fluorescence).
References: (1) Zaharieva et al. Diabetes Technol Ther 2019; 21: 313-321.
SAT-429 Systemic Safety Analysis of Mycophenolate in Graves’ Orbitopathy
Authors: Lee Alan C H , Diana Tanja , Frommer Lara , Kahaly George Jean 
Published: May 2020

Abstract
Context
The dual antiproliferative mechanism of mycophenolate appears to be beneficial in Graves’ orbitopathy (GO).
Methods
The safety data, which is of utmost importance in immunomodulation, from the two major randomized mycophenolate trials [“Chinese trial” (1) and “European Group on Graves’ Orbitopathy (EUGOGO) trial” (2)] and the original database of the EUGOGO trial were systematically analyzed. Treatment efficacy stratified by individual visual parameters of clinical disease activity and severity were also compared.
Results
A total of 129 adverse events (AE) involving 50 patients (29.4%) were noted among all mycophenolate-treated patients. Mycophenolate sodium plus intravenous glucocorticoid (MPS+GC) group of the EUGOGO trial recorded significantly more AE (55.4% versus 4.6% of patients affected) and serious adverse events (SAE) (12.5% versus 0%) than mycophenolate mofetil (MMF) group of the Chinese trial. The excess of AE may partly be contributed by GC use. None of those SAE was side effect (SE). Most SE in MPS+GC group (79%) were mild. Gastrointestinal disorders, infection and liver dysfunction affected 8.8%, 7.1% and 1.2% of all mycophenolate-treated patients (versus 5.4%, 5.4% and 1.2% of all patients on GC monotherapy, respectively). When compared to GC monotherapy, MPS+GC did not significantly increase the overall SE rate (25.3% versus 19.7%) nor did risks of infection or liver dysfunction, but it result in more mild gastrointestinal disorders (SE rate in EUGOGO trial 10.8% versus 4.9%). No cytopenia, serious infection, severe hepatotoxicity or treatment related mortality was reported among mycophenolate-treated patients. The much higher AE rates of mycophenolate trials in other autoimmune diseases or transplantations suggested that major mycophenolate toxicities were mostly dose- and duration-dependent. Regarding efficacy, mycophenolate achieved better overall response than GC monotherapy. Approximately 70% (versus 90% in MMF group) and 30% (versus 60–70% in MMF group) of patients in MPS+GC group achieved endpoints in most individual visual parameters of activity and severity, respectively. MPS+GC group of the EUGOGO trial performed better than MMF group in terms of improvement of pain and eye movement.
Conclusions
The risk-benefit ratio of 6-month courses of low dose mycophenolate treatment in active moderate-to-severe GO, either as monotherapy or as combination with GC, is highly favorable given its reassuring safety profile with low rate of mild to moderate SE and promising efficacy.
References:
(1) Ye et al., Clin Endocrinol (Oxf). 2017;86(2):247–55
(2) Kahaly et al. Lancet D&E. 2018;6(4):287–98
MON-321 AgRP and Food Cravings Decrease with Treatment of Cushing’s Disease
Authors: Haseltine Katherine N , Robins Hannah , Cohen Vanessa , Baratz Hannah , An Anjile , Kleiner Sandra , Geer Eliza Brevoort 
Published: May 2020

Abstract
Cushing’s disease (CD) is characterized by chronic exposure to excess glucocorticoids due to an ACTH-producing tumor. Obesity is a prominent feature of CD, although the mechanisms of weight gain have not been completely elucidated. In some patients, obesity persists despite appropriate medical or surgical treatment of CD and normalization of cortisol levels (1). Few studies have followed patients prospectively to understand the effect of CD remission and cortisol normalization on appetite and body weight. Previous studies have not shown a correlation between appetite or food cravings and circulating total peptide YY (PYY), ghrelin, or leptin concentrations, leading to interest in other hormones which may regulate appetite in CD (2). One of these is the neuropeptide Agouti-related protein (AgRP). AgRP is known to promote appetite and decrease energy expenditure by acting as a melanocortin antagonist at the level of the hypothalamus. Plasma AgRP may be elevated in patients with active CD and decreases with normalization of cortisol levels (3). We sought to determine if AgRP may play a role in regulating appetite or food cravings in CD. Plasma AgRP was measured before and prospectively after treatment in 19 patients with CD. Patients completed surveys on appetite and food cravings at these same time points. As expected, AgRP significantly decreased following treatment for CD, with mean AgRP before treatment 128.72 pg/mL (SD 55.41) and mean AgRP after treatment 75.23 pg/mL (SD 23.46). Using a paired t-test, the mean difference of 53.5 pg/mL was significant (p=0.0006). In addition, there were significant decreases in BMI, weight, and waist circumference with CD treatment. We found that plasma AgRP concentrations did not correlate with an 8-question visual analogue scale (VAS) used to assess hunger and satiety. However, treatment of CD significantly reduced Trait Food Craving Questionnaire scores in parallel with circulating AgRP levels using a one-way analysis of variance (p=0.004). Our data suggest that AgRP may play a role in food craving, rather than appetite, in patients with CD. Further research may clarify the relationship between AgRP and food cravings in CD patients before and after treatment. References:
1. Geer et al. Endocrinol Metab Clin North Am. 2014; 43: 75-102.
Geer et al. Pituitary. 2016; 19: 117-126.Page-Wilson et al, J Clin Endocrinol Metab. 2019; 104 (3): 961-969.