bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-LB116 FGF-21 Is A Reliable Marker Of Insulin Resistance Before The Occurrence Of Glucose Intolerance
Authors: sawah ahmed , Seyoum Berhane , Msallaty Zaher 
Published: May 2020

Abstract
Background and aims: Fibroblast growth factor (FGF)-21 is a polypeptide that results in metabolic rearrangement mostly related to glucose and lipid metabolism. Serum FGF-21 level is elevated in obesity and in type 2 diabetes. The goal of this study is to evaluate the relationship between FGF-21 and peripheral insulin resistance in a wide range of baseline BMI and glucose metabolism status. Materials and methods: seventy one participants reported to the clinical research center in a fasting state twice. BMI and fat mass were calculated. Glucose metabolism was determined by fasting glucose, hemoglobin A1c and OGTT. Serum lipids panel was measured. Peripheral insulin resistance was determined using the hyperinsulinemic euglycemic clamp study. FGF-21 level was measured using enzyme-linked immunosorbent assay before and after clamp study. Study was approved by university institutional review board. Results: Of 71 participants, 48 were obese and 23 were lean. Normal glucose metabolism was documented in 43 individuals. Serum FGF-21 was significantly elevated in insulin resistant compared to insulin sensitive subgroups (0.28 ng/ml ± 0.136 vs. 0.14 ng/ml ± 0.112. p &lt; 0.001). Despite the fact that FGF-21 is elevated in all obese population, the level was significantly higher in the insulin resistant obese subgroup compared to the insulin sensitive obese one (0.30 ng/ml ± 0.167 vs. 0.17 ng/ml ± 0.126. P =0.003). Furthermore, significantly higher FGF-21 level was also found in lean insulin resistant compared to lean insulin sensitive subgroups (0.18 ng/ml ± 0.106 vs. 0.09 ng/ml ± 0.061, p = 0.04]. Adjustment to preexisting impaired glucose tolerance did not affect the correlation between FGF-21 level and insulin resistance which remained statically significant in the seemingly healthy obese and lean subgroups. Conclusion: Serum FGF-21 level strongly correlates to peripheral insulin resistance in both obese and lean population. Nonetheless, FGF-21 level rises way before glucose metabolism abnormality can be detected. Our study suggests a cutoff level for each subgroup which may enable clinicians to risk-stratify patients and allow for early intervention.
SAT-LB63 A Case of PTHrP-Negative Hypercalcemia of Malignancy
Authors: Murati Jonila , Cannavo Ariana , Lee Sun , Pearce Elizabeth N 
Published: May 2020

Abstract
Case Presentation:
A 55-year-old male who had recently arrived from Haiti presented to the Emergency Department with chief complaint of a progressively enlarging neck mass. He first noticed the mass in 2000. From 2000-2017, he underwent resection of the mass three times in Haiti, with recurrence after each surgery. On presentation, he reported unintentional 10 kg weight loss over several months and night sweats. Endocrine was consulted for evaluation of hypercalcemia. On examination and imaging, 8.7 x 14.0 x 14.0 cm fungating tumor on the nape of his neck extending to the occipital area and cervical lymphadenopathy were noted. Labs were notable for WBC of 21.7 K/uL, hemoglobin of 6.0 g/dL, calcium of 12.0 mg/dL, albumin of 3.1 g/dL, free calcium of 6.4 mg/dL, corrected calcium of 12.6 mg/dL, phosphorus of 2.6 mg/dL, and intact PTH of &lt; 4 pg/mL. The PTH-related peptide (PTHrP) level was found to be normal at 19 pg/mL (reference range 14–27 pg/mL). SPEP was normal. Neck mass and cervical lymph nodes were biopsied. Histopathological examination of neck mass showed an ulcerated, moderately-differentiated squamous cell carcinoma with multifocal areas of necrosis. There was no evidence of malignancy in the cervical lymph nodes. CT scan showed 3 mm lung nodules, thought to be granulomas, and no clear evidence of metastatic disease. Hypercalcemia was treated with IV hydration and one dose of bisphosphonate and patient underwent resection of neck mass. Immediately after surgery, his calcium level precipitously decreased and has remained normal in the months since surgery.
Discussion: Hypercalcemia of malignancy is a common finding affecting up to 44.1% of patients with malignancy (1,2). The major mechanism, accounting for approximately 80% of malignancy-related hypercalcemia, is mediated via PTHrP, which can cause hypercalcemia by increasing bone resorption and renal tubule calcium reabsorption (2). Squamous cell carcinoma (SCC), especially of the lungs, breast, or GI tract, is more frequently associated with hypercalcemia. There are also several case reports of primary cutaneous SCC associated with hypercalcemia. In these cases, tumors were large and hypercalcemia was thought to be due to elevated PTHrP (3,4,5). The skin has been shown to express PTHrP and PTHrP receptors (10). PTHrP has also been detected in 100% of cutaneous SCCs even in the absence of hypercalcemia. (6,7). Furthermore, PTHrP mRNA has been localized in 100% of squamous tumors with hypercalcemia and PTHrP peptide were detected in 91% of cases in a study of 11 patients (9). The patient presented in this case did not have an elevated level of PTHrP. However, resolution of hypercalcemia with resection of the mass supports a diagnosis of hypercalcemia of malignancy. This case illustrates that hypercalcemia due to primary cutaneous SCC typically, but not always, results in an elevated serum PTHrP level.
OR28-03 Drug Repurposing Identifies Inhibitors of the Proteostasis Network to Augment Radioiodine Uptake in Combinatorial Approaches Targeting Thyroid Cancer
Authors: Read Martin L , Brookes Katie , Fletcher Alice , Thornton Caitlin E M , Alshahrani Mohammed , Khan Rashida , Nieto Hannah R , Adcock Holly V , Webster Jamie R M , Cox Liam , Alderwick Luke J , Boelaert Kristien , Smith Vicki E , McCabe Christopher J 
Published: May 2020

Abstract
New combinatorial drug strategies are urgently needed to improve radioiodine (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. Drug repurposing offers the promise of identifying already approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. However, a lack of thyroid cell-based assays amenable to high-throughput screening has limited progress. We utilised the mutated yellow fluorescent protein (YFP) as a surrogate biosensor of intracellular iodide and screened the Prestwick Chemical Library (1200 drugs; 95% approved) for quenching of YFP fluorescence. This allowed us to identify putative candidate drugs which increased iodide uptake &gt;2 SD above mean. Categorisation of these revealed a high proportion of drugs that modulate the proteostasis network (19/48; ~40%), including key processes in protein homeostasis such as endoplasmic reticulum-associated protein degradation (ERAD) and autophagy. Secondary screening validated the activity of proteostasis modulators in enhancing iodide uptake after ranking 73 leading compounds based on their pharmacologic (AUC, EMAX and EC50) and specificity of response (NIS+ve vs NIS-ve YFP-thyroid cells) at ten different drug doses (0.1 to 50 μM). Of importance, several repurposed drugs (e.g. ebastine, Prestwick N, Prestwick C and clotrimazole) in combination with the HDAC inhibitor vorinostat induced a robust enhancement in RAI uptake in thyroid cancer cells (TPC-1 and 8505C NIS+ve cells, up to 11-fold vs DMSO, P&lt;0.001), which was significantly greater than using vorinostat alone (up to 3-fold, P&lt;0.01). For clotrimazole, we designed 7 new chemical derivatives, 3 of which showed enhanced aqueous solubility and retained the ability to significantly enhance RAI uptake. TaqMan RT-PCR revealed that, in contrast to vorinostat, our repurposed drugs failed to alter NIS mRNA expression, highlighting post-transcriptional mechanisms. Critically, 11 repurposed drugs induced significant gains in RAI uptake in human primary thyroid cells (up to 4.1-fold; P&lt;0.05), the most physiological setting for NIS function. In conclusion, we performed high-throughput screening and identified proteostasis modulators, as well as other repurposed drugs, that markedly enhance radioiodine uptake. Further clinical investigation of these drugs might offer new combinatorial approaches, especially with existing therapies, to improve the treatment of thyroid cancer.
SUN-LB112 Efficacy & Safety After Switchover to Remogliflozin in Indian T2DM Patients - a Real World Study
Authors: Bhattacharyya Supratik , Katare Sagar 
Published: May 2020

Abstract
INTRODUCTON: Remogliflozin is new SGLT2i recently approved in India, but more economical than the previously available SGLT2i. It is prudent to evaluate its effectiveness & tolerability in comparison to other SGLT2i in real world setting. METHODS: In this observational retrospective study, medical data from EMR of tertiary care hospital in Kolkata was retrieved. The records of adult Type 2 diabetes mellitus (T2DM) patients who were on a dual therapy of Metformin plus SGLT2i (Canagliflozin, Dapagliflozin or Empagliflozin) for at least 6 months with adequate glycaemic control (HbA1c to target based on age & duration of diabetes) & subsequently switched over to Remogliflozin 100 mg twice daily because of economic reasons were screened. The day of switchover was considered as index day (Day 1) The patient records whose data was unavailable, metformin dose was altered during period of next 6 months, who had evidence of active UTI on index day, were receiving injectable anti-diabetic drugs or had recorded eGFR &lt;45 mL/min were excluded. The effectiveness was assessed in terms of maintenance of HbA1c, FBS, PPBS, body weight after 3 & 6 months of treatment. The safety was assessed by adverse events recorded in medical records in terms of abnormal symptoms, signs or laboratory reported values during the observation period of 6 months & compared to equivalent period of 6 months before index day. The data was collected & analysed using appropriate statistical techniques. RESULTS: After screening, medical records of 50 adult T2DM patients (54% male) were found to be eligible. The mean baseline characteristics on Index day in terms of Age, HbA1c levels, FBS, PPBS, weight & BMI was 51.3±12.5 years, 6.8±0.4%, 108.7±8.1 mg/dL, 144.5±21.3 mg/dL, 65.5±5.7 kg & 25.8±2.8 kg/m2 respectively. After treatment period of 6-months with Remogliflozin-based regimen, the mean HbA1c, FBS, PPBS, -Body weight & BMI was 6.7±0.8%, 110.3±10.5 mg/dL, 138.5±12.7 mg/dL, 66.3±6.5 kg & 25.9±3.2 kg/m2 Mean change from baseline in HbA1c levels, FBS, PPBS, weight & BMI were-0.1±0.19%, -1.6±7.2 mg, -6.0±8.3 mg, +0.8±0.2kg, & +0.1±0.0.7 kg/m2 respectively. These change from baseline of all above parameters were not found to be statistically significant (P&gt;0.05) No events of hypoglycaemia, disturbance in electrolytes or any unusual adverse events were reported. Combined incidence of UTI & genital Mycotic infection was similar during 6 month observation period as compared to 6 months prior to index day. (8% vs 6%) CONCLUSION: In real world clinical practice, replacement of ongoing SGLT2i with Remogliflozin was observed to provide consistent glycaemic control without any tolerability issues. Hence, novel SGLT2i Remogliflozin can be considered as equivalent alternative for SGLT2i based regimen in management of Indian T2DM patients
SUN-LB66 Oral Risedronate Treatment in Children With Osteogenesis Imperfecta
Authors: Nguyen Antoine T , Pitukcheewanont Pisit , Ryabets-Lienhard Anna 
Published: May 2020

Abstract
Introduction: To date, there are no approved pharmaceutical therapies for children with OI. Intravenous bisphosphonates have been used for years to treat children with OI with variable efficacy and tolerability. However, a few studies have evaluated the effects and tolerability of oral risedronate in children with OI (1)(2). In this study, we aimed to present our experience with oral risedronate treatment in children with OI. Methods: A retrospective chart review of patients with OI and history of multiple fragility fractures, who were treated with oral risedronate and followed in our bone clinic between the years of 2013 and 2019. Primary outcomes included changes in fracture rate, urinary N-terminal telopeptide (uNTX), height z-scores, and lumbar and femur BMD z-scores. Safety and tolerability of risedronate were reviewed. Wilcoxon matched-pairs sign-ranks test was used to assess the medians (IQR) between pre- and post-treatment with p value of &lt; 0.05 set as statistically significant.Results: A total of 17 patients ages 5—19 ys were reviewed (11 males, 65% type I OI, 12% type III, 18% type XI, and 5% unknown). At the time of the review, 69% were on weekly, 19% on daily, and 12% on monthly risedronate treatment. Mean duration of therapy was 2.7 y ± 2.3 y, ranging 0.5 to 8 ys. The bone resorption marker, uNTX, decreased &gt; 30% from baseline in 93% of subjects within the first year of treatment, and was statistically lower by the end of treatment period [245 (159, 393) to 170 (39, 261), p=0.02]. Height z-score did not change with treatment, -0.80 (-1.20, 0.10) pre- and -0.85 (-1.60, -0.40) post-treatment, p = 0.2 in patients with Type I OI. There was a clinically significant reduction in the rate of fractures from baseline 0.6 per y (0.4, 0.8) to 0.24 (0, 0.5) by the end of the treatment period, though it did not reach statistical significance. Within a year of treatment, 80% of children were fracture free with improvement in bone pain and mobility. BMD pre- and on treatment for lumbar and femur were -2.5 (-3.43, -1.94) and -2.36 (-3.25, -1.35), and -2.05 (-2.95, 0.3) and -1.18 (-1.73, 2.13), respectively. However, there was no statistical significance. There was one case of reflux without erosive esophagitis, which resolved with reflux treatment. Overall, risedronate was well tolerated with no cases of clinically significant acute phase reaction, hypocalcemia, erosive esophagitis, or osteonecrosis of the jaw.Conclusion: Based on our experience, oral risedronate effectively decreased bone resorption, showed a trend towards decrease in fracture rate with improvement in symptoms, and was well tolerated in children with OI. More data are needed to systematically evaluate its long-term effects on growth, bone mineral density, fracture frequency, and quality of life in children with different types of OI. Reference: (1) Rauch et al., J Bone Miner Res. 2009; 24: 1282-1289 (2) Bishop et al., Lancet. 2013;382(9902):1424-32.
SUN-LB129 Thyroglobulin Stimulates the Secretion of Thyroxine From Thyroid Epithelial Cells in Suspension Culture via Nuclear Factor-κB Signaling Pathway
Authors: Tanaka Mei , Yamada Yukiko , Hayashi Moyuru , Emoto Naoya , Shimonaka Motoyuki 
Published: May 2020

Abstract
The nuclear factor (NF)-κB signaling pathway controls a variety of biological functions such as cell growth and differentiation as well as immune and inflammatory responses. Two distinct pathways of NF-κB activation are known. NF-κB signaling via non-canonical pathway plays an important role in maintaining normal thyroid function, namely, thyroid cells survival and expression of thyroid-specific proteins, such as NIS, TPO and thyroglobulin (Tg). The primary function of thyroid cells is the production of thyroid hormones, which are cleaved out by various processing enzymes from the modified tyrosine residues of the Tg molecule. Although Tg is currently recognized as no more than a scaffold protein for thyroid hormone synthesis, our group has shown that Tg stimulates the proliferation of rat thyroid follicular FRTL-5 cells via PI3K pathway. The signaling pathways underlying various functions of thyroid cells have been extensively investigated but some discrepancies still exist, depending on the experimental model systems and the types of cells used. Recently, our group discovered that Tg may directly regulate the synthesis of thyroid hormones in thyroid cells. In this study, we performed suspension culture of porcine thyroid cells and aimed to elucidate the mechanism of the effect of Tg on thyroid cells. Porcine thyroid epithelial cells were prepared from thyroid gland by enzymatic digestion and cultured in monolayer or in suspension culture. Various concentrations of Tg were added to the medium and cultured for several days. Then, the conditioned medium was collected and the amount of thyroid hormone was measured by reversed phase chromatography; the cells were harvested and mRNA levels of hormone-processing enzymes, cathepsin B, K, L and dipeptidyl peptidase I, II (DPP I, II), were measured by quantitative PCR. The amount and activation of cell signaling molecules were also evaluated by western blotting. Tg stimulated the secretion of thyroid hormone, thyroxine, from porcine thyroid cells in suspension culture, however, no stimulation by Tg was observed in monolayer culture. The expression of mRNAs of cathepsin B, K and L were reduced and that of DPP II was increased by the treatment of Tg in suspension culture. Tg increased the amount of NF-κB p52 and Rel B dose dependently. On the other hand, TSH had little effects on the amount of these proteins. Tg and TSH both activated PDK1 and MAPK p44/42 but not Akt. These results suggest that Tg regulates thyroid hormone synthesis in totally different way from TSH by altering the expression levels of hormone-processing enzymes in thyroid cells. This stimulatory effect might be mediated by NF-κB signaling pathway, whereas the proliferative effect of Tg under these conditions might be exerted via MAPK signaling pathway. The detailed mechanisms of these effects of Tg on thyroid cells are under investigation.
MON-LB47 An International Simulated Use Study (PRESTO) to Evaluate Nurse Preferences Between the Lanreotide Autogel New Syringe and Octreotide Long-Acting Release Syringe
Authors: Adelman Daphne T , Truong-Thanh Xuan-Mai , Feuilly Marion , Houchard Aude , Cella David 
Published: May 2020

Abstract
Background: A new lanreotide autogel/depot (LAN) syringe was developed based on feedback from a human factors study to improve user experience.
Methods: PRESTO was a multinational, simulated-use study in nurses with ≥2 years’ experience injecting LAN or octreotide long-acting release (OCT LAR) in patients with acromegaly and/or neuroendocrine tumors, which aimed to assess injector preference between the LAN new syringe and the current OCT LAR syringe. Participating nurses were invited to test both the LAN new syringe (120 mg) and the current OCT LAR syringe (20 mg or 30 mg), using injection pads. The sponsor was not involved in these sessions. In an anonymous web-based questionnaire, nurses reported overall preference (‘strong’ or ‘slight’; primary endpoint), and rated and ranked the importance of nine attributes for each syringe (1 [not at all] to 5 [very much]).
Results: In total, 90 nurses attended injection sessions and completed valid questionnaires. Overall, 97.8% of nurses expressed a preference (85.6% ‘strong’, 12.2% ‘slight’) for LAN new syringe (p&lt;0.0001 vs current OCT LAR). Attribute performance ratings were consistently higher for LAN new syringe vs current OCT LAR, with the greatest differences in ‘fast administration’ and ‘confidence the syringe will not be clogged’ (mean [standard deviation]: 2.6 [1.2] and 2.3 [1.5], respectively; p&lt;0.0001). The attribute ranked most important was ‘confidence the syringe will not be clogged’ (24.4%) and least important was ‘convenience of syringe format, including packaging, from preparation to injection’ (34.4%).
Conclusions: The PRESTO study showed that nurses preferred the user experience of the LAN new syringe over the current OCT LAR syringe across all attributes tested.
MON-LB016 Tyrosine Kinase Inhibitor Induced Hypothyroidism in Pediatric and Young Adult Population: An Institutional Review
Authors: Arora Shruthi , Chuang Janet 
Published: May 2020

Abstract
Tyrosine Kinase Inhibitor Induced Hypothyroidism in Pediatric and Young Adult Population: An institutional reviewBackground:Tyrosine kinase inhibitors (TKIs) are a class of molecular targeted therapies approved for the treatment of several hematological and solid tumors in pediatric population. Thyroid dysfunction, most commonly primary hypothyroidism, is a well described adverse effect in adults. There is no available data in the pediatric population regarding the risk of thyroid dysfunction with the use of TKIs.Objective:To document the incidence of hypothyroidism in the pediatric and young adult patients on TKI therapy.Methods:A retrospective chart review including patients’ ≤ 21 years of age who had been treated with at least 1 of 10 predetermined TKIs for malignancy was performed. Demographics, TKI use and duration, thyroid hormone labs, and history of head/neck radiation were collected. We excluded patients with pre-existing thyroid disease prior to start of TKI therapy. Thyroid dysfunction was defined as TSH &gt;5mcIU/mL during TKI therapy. Results:A total of 152 patients who were treated with TKIs for malignancy were identified. The mean age was 12.4 years (SD 6.5). About 20% of patients had therapy with multiple TKI drugs. A total of 24 patients were noted to have TSH elevation &gt;5mcIU/ml of which 19 had a TSH &gt;10 mcIU/mL or low free T4. Fourteen patients were started on levothyroxine. Average duration of TKI therapy prior to development of thyroid dysfunction was 6.7 months but over half developed hypothyroidism within 3 months of initiation of TKI therapy. Cabozantinib and pazopanib were responsible for 70% of TKI associated cases of thyroid dysfunction.Conclusion:This is the first report of incidence of primary hypothyroidism in pediatric and young adult patients treated with TKIs. Thyroid dysfunction can develop in the first few months of therapy and often is clinically significant. Early recognition and treatment of this complication will be important for patient care especially as use of these class of drugs increase.