bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-664 Are Hospitals Doing Enough in Caring for Patients with Diabetes?Results of a Landmark Survey: Current State of Inpatient Diabetes Care and Glycemic Management
Authors: Rhinehart Andrew S , Mabrey Melanie , Garrett Valerie 
Published: May 2020

Abstract
BACKGROUND
On average, 1 of every 3 hospitalized patients — the majority with diabetes — requires insulin to control blood glucose during their stay. Although widely prescribed and absolutely necessary, insulin is inherently dangerous: 50% of all medication errors involve insulin, including 1/3 of all fatal medication errors. Results of a nationwide survey indicate that prioritization of glycemic control is lacking, which hinders high reliability and increases risk of morbidity and mortality.
METHODS
Healthcare professionals who serve in roles involving diabetes care and glycemic management were invited to participate in an online survey. To qualify, an initial question that read: “Where do you work?” had to be answered “hospital or health system with focus on inpatients” (those who answered “physician’s office or clinic with focus on outpatients” were disqualified). There were a total of 619 respondents from 408 U.S. hospitals.
KEY RESULTS
• The consensus among respondents is that fear of hypoglycemia has a strong influence on the prescribing of insulin (i.e., causes non-prescribing or lack of intensification following hyperglycemia). On a scale of 1 to 5, with 1 being ‘very little if any influence’ and 5 being ‘considerable influence,’ the average weighted score was 3.45.
• About 70% of respondents are of the opinion glycemic control is ‘extremely important’ or ‘very important’ to nurses and physicians, whereas about 48% believe this to be true of senior clinical executives and 25% believe this to be true of non-clinical senior executives.
• Only 24% of respondents maintain their hospital uses primarily basal bolus for subcutaneous insulin therapy. Close to 34% maintain their hospital uses primarily sliding scale and 42% maintain their hospital uses sliding scale and basal bolus equally as often. The top three barriers to full adoption of basal bolus insulin are: (1) inadequate prescriber knowledge about basal-bolus-correction regimens, (2) beliefs that sliding scale is acceptable practice and not harmful, and (3) difficulties coordinating glucose monitoring, insulin administration and meal delivery.
• Slightly more than 2/3 of respondents work at a hospital that routinely tracks and reports the rate of hypoglycemia (on a monthly or quarterly basis). Of those, 54% use a threshold of 60 and/or 70 mg/dL exclusively, which encompasses all episodes of hypoglycemia without accounting for severity; only 24% use thresholds of 60 and/or 70 mg/dL as well as thresholds of 40, 50 and/or 54 mg/dL, allowing episodes of greater severity to be isolated for analysis and quality improvement.
CONCLUSION
Results of the survey indicate better care, specifically better glycemic control, is needed for hospitalized patients with diabetes. With the shift from volume to value and a stronger focus on quality and safety, this data should be catalyst for making glycemic control a strategic imperative.
MON-070 Cross-Reactivity of Human Insulin and Insulin Analogues in Human Insulin Immunoassay Complicates Case of Medical Child Abuse
Authors: Walch Abby , Long Roger 
Published: May 2020

Abstract
Background: Measurement of insulin levels with human insulin immunoassays is important in the investigation of hypoglycemia; however, cross-reactivity with insulin analogues complicates clinical assessment.
Clinical Case: A 2-month-old male presented with hypoglycemia. Initial tests were consistent with hyperinsulinemic hypoglycemia: low serum glucose (29 mg/dL, n 70 to 99), elevated insulin (90.1 mU/L, n 3.0 to 19.0), suppressed beta-hydroxybutyrate (0.16 mmol/L, n 0.02 to 0.27), and suppressed free fatty acids (0.27 mmol/L, n 0.50 to 1.60). C-peptide level resulted undetectable (&lt;0.1 ng/mL, n 0.8 to 3.5) raising suspicion for exogenous insulin administration. History revealed an older brother with type 1 diabetes mellitus treated with insulins glargine and lispro. Only one caregiver was present in the hospital, who denied knowledge of exogenous insulin administration. Hypoglycemia persisted despite placement of a continuous 1:1 sitter, high-dose intravenous glucose (glucose infusion rate up to 21.6 mg/kg/min), and treatment with diazoxide. A repeat insulin measurement with the Roche Diagnostics assay specific for human insulin was performed on a critical sample and resulted elevated (13.9 uIU/L, n 2.6 to 24.9), suggestive of endogenous insulin. However, an extensive study of commercial human insulin immunoassays by Heurtault et al., including the Roche Diagnostics assay, has demonstrated cross-reactivity with insulin analogues and their metabolites [1]. Given persistent concern for exogenous insulin administration, the patient’s caregiver was asked to leave the bedside for an extended period of time which resulted in normoglycemia. Diazoxide and dextrose-containing IV fluids were discontinued. Patient maintained normoglycemia for the remainder of the admission and was discharged in the care of child protective services.
Conclusions: Cross-reactivity exists in human insulin immunoassays with insulin analogues and their metabolites complicating the determination of endogenous versus exogenous insulin as the cause of hyperinsulinemic hypoglycemia. It is important to know the cross-reactivity of the assay used if a diagnosis of surreptitious insulin administration is suspected. Separation of patient and possible perpetrators and involvement of child protective services is essential in suspected cases of exogenous insulin administration. Evaluation in cases where self-injection of insulin is suspected may be more difficult to decipher, and inclusion of c-peptide measurement at the time of hypoglycemia is critical.
Reference: [1] Heurtault B, Reix N, Meyer N, et al. Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification. Clin Chem Lab Med. 2014; 52:355-362.
SUN-603 Electronic Cigarette Exposure Induces Pro-Inflammatory Changes in Adipose Tissue in Apolipoprotein E (APOE) Knockout Mice
Authors: Espinoza-Derout Jorge , Shao Xuesi M , Molina-Mancio Jocelyn , Hasan Kamrul M , Mtume Norma , Sinha-Hikim Amiya P , Friedman Theodore C 
Published: May 2020

Abstract
Electronic nicotine delivery systems or electronic cigarettes (e-cigarettes) are becoming exceptionally popular in the world as an alternative to conventional nicotine cigarettes, both in smokers and people who have never smoked. Nicotine can induce lipolysis in adipose tissue, leading to increased serum free fatty acids (FFA). Increased levels of FFA are one of the key elements in inducing a pro-inflammatory response and lead to ectopic lipid accumulation, lipotoxicity, mitochondrial dysfunction and metabolic disease. Our laboratory has shown that chronic e-cigarette exposure induces cardiac dysfunction, atherosclerosis and hepatic steatosis in the ApoE knockout (KO) model associated with increased levels of serum FFA. In this study, we investigated the role of adipose tissue in the metabolic changes associated with e-cigarette exposure. ApoE KO mice were exposed to saline, e-cigarette without nicotine [e-cigarette (0%)] and e-cigarette with 2.4% nicotine [e-cigarette (2.4%)] aerosol for 12 weeks. Western blot analyses from adipose tissue showed that mice treated with e-cigarette (2.4%) had decrease levels of SIRT1 when compared to mice treated with saline or e-cigarette (0%). Transcriptomic analysis of the differentially expressed genes shows a differential transcriptional response to e-cigarette (2.4%) in adipose tissue in comparison with e-cigarette (0%) or saline. The RNA-seq examination using ingenuity pathway analysis (IPA) software, revealed dysregulation of fibrosis, agranulocyte and granulocyte adhesion and diapedesis pathways in e-cigarette (2.4%) -exposed adipose tissue. Overall, we found an inflammatory phenotype associated with decreased levels of SIRT1 in adipose tissue of mice treated with e-cigarette (2.4%). Understanding the consequences of e-cigarette use on metabolic disease is directly relevant to the development of policies related to e-cigarette use.
SUN-751 RORγ Is a Master Regulator of Tumor Lipid Metabolism
Authors: Chen Hong-Wu 
Published: May 2020

Abstract
Lipid and cholesterol metabolism reprogramming is strongly linked to tumorigenesis and therapeutic resistance. Our recent genetic disruptions via CRISPR KO and gene silencing and pharmacological inhibition clearly demonstrated that nuclear receptor RORγ plays a crucial role in control of lipid and cholesterol biosynthesis gene programs specifically in certain types and subtypes of cancer cells and tumors. Indeed, its antagonists display potent tumor inhibitions in patient-derived xenografts (PDX) and in immune-intact tumor models. Interestingly, RORγ inhibition resulted in decreased cholesterol synthesis rate specifically in tumors without significant impact to the host animal cholesterol homeostasis. Our ChIP-seq demonstrated that in a subtype of breast cancer RORγ cistrome is largely overlapping with that of SREBP2, a well-established master regulator of lipid and cholesterol biosynthesis. Our further analyses found that RORγ functions dominantly over that of SREBP2 via its association with SREBP2 and facilitation of its genome-wide recruitment and histone H3K27 acetylation. Inhibition of RORγ completely negates the negative feedback activation of the cholesterol program induced by cholesterol-lowering drug statins and mediated by SREBP2. Treatment of animals with the antagonists in combination with statins showed a highly synergistic anti-tumor effects. Together, our study uncovers RORγ as a novel master regulator of lipid and cholesterol metabolism operating selectively in subtypes of cancer.
SAT-493 A Case of Profound Hypothyroidism Secondary to Immune Check Point Inhibitors
Authors: Tun Yin Nwe , Rodriguez Giovanna , Bahtiyar Gul 
Published: May 2020

Abstract
Background: The discovery of immune check-point inhibitors (ICI) revolutionized cancer treatment. CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies have been approved in recent years. However, the advantageous clinical outcomes can also be associated with potentially severe immune related adverse effects (irAEs) such as hypophysitis, thyroiditis, type 1 diabetes mellitus, and adrenal insufficiency [1]. We report to highlight the importance of awareness of irAEs and collaboration of endocrinology and oncology specialties in managing oncology patients with ICI in an underserved community hospital in Brooklyn, NY.
Clinical case: 62 years old woman with unremarkable thyroid history presented with chronic mid-chest pain and dysphagia in 2016 found to have a mass in middle third of esophagus. Biopsies revealed invasive squamous cell carcinoma (T3N0). She underwent radiotherapy and esophagectomy.
On 1/2018, surveillance imaging detected a new tracheobronchial angle lymph node, which was confirmed as hypermetabolic and likely malignant by PET scan. Patient received additional 5 cycles of radiotherapy followed with 5 cycles of chemotherapy with Oxaliplatin and Capecitabine. Since post-chemotherapy PET scan showed local recurrence, patient was started on PD1 inhibitor, Pembrolizumab 200 mg Q3 week. After 3 doses patient developed cold intolerance, weight gain and low mood. Her TSH was 173 uIU/ml (0.27-0.42), FT4 &lt;0.1 ng/dL (0.9-1.8) and referred to endocrine clinic. Repeat TSH was 190 uIU/ml, FT4 0.2 ng/dL, TPOAbs 619 IU/ml (&lt;35) and TSI&lt;0.1 IU/L (&lt;0.55). Adrenal insufficiency was ruled out and started on levothyroxine 50 mcg in the morning, increased to 75 mcg. After 2 months of levothyroxine use, TSH was 11.8 uIU/ml and FT4 1.3. Pembrolizumab therapy is restarted shortly after.
Conclusion: National Comprehensive Cancer Network guideline for management of immunotherapy related toxicities recommends routine monitoring of TSH and FT4 at baseline and every 4-6 weeks during immunotherapy, follow up every 12 weeks and TPO antibodies if TSH is high. This patient’s clinical symptoms of hypothyroidism might be confused by nonspecific symptoms of underlying malignancy. Combination radiotherapy and immunotherapy place this patient at higher risk of developing hypothyroidism. This case showed the successful collaboration of endocrinology and oncology team in giving vulnerable patient an optimized care with good clinical outcome.
References:
(1). Ferrari SM, et al. Autoimmune Endocrine Dysfunctions Associated with Cancer Immunotherapies. Int J Mol Sci. 2019;20(10):2560. Published 2019 May 24.
(2). John A. Thompson, et al. Management of ImmunotherapyRelated. Toxicities, Version 1.2019J Natl Compr Canc Netw 2019;17(3):255–289
SUN-125 Phase Ib Study of Dual Therapy with an Aromatase Inhibitor Exemestane and Carboplatin-Based Therapy for Postmenopausal Women with Advanced Non-Small Cell Lung Cancer
Authors: Young Patricia A , Marquez-Garban Diana C , Goodglick Lee , Noor Zorawar S , Moatamed Neda , Elashoff David , Grogan Tristan , Romero Tahmineh , Sasano Hironobu , Saito Ryoko , Rausch Rebecca , Hamilton Nalo , Dubinett Steven M , Garon Edward , Pietras Richard J 
Published: May 2020

Abstract
Objectives: Estrogen receptors (ER-alpha, ER-beta) and aromatase (key enzyme for estrogen synthesis) are expressed in most human non-small cell lung cancers (NSCLCs). High intratumoral estrogens and elevated aromatase in NSCLC are reported to predict poor clinical outcome. In vitro, estrogen stimulates NSCLC gene expression and, tumor progression and diminishes tumor cell apoptosis. Furthermore, preclinical NSCLC models demonstrate that aromatase inhibitors (AIs) prevent these processes, and that cisplatin with AIs elicits dramatic growth inhibition. Additionally, depletion of autocrine/paracrine estrogen production hypersensitizes cells to DNA-damaging effects of platinum therapy, providing a rationale for this trial. This open-label, phase 1b, single-center study evaluated safety and tolerability of AI exemestane combined with carboplatin and pemetrexed in postmenopausal women with stage IV non-squamous, NSCLC.
Materials/Methods: Exclusion criteria included untreated CNS metastasis, major surgery in prior 4-weeks to therapy, prior/concurrent investigational or standard therapy (except TKI and/or immunotherapy in prior 4-weeks). Trial patients received escalating doses of exemestane (starting 1-week before chemotherapy) at 25 mg PO daily (Cohort 1) or 50 mg PO daily (Cohort 2) with carboplatin (AUC 6 mg x min/mL) and pemetrexed (500 mg/m2) IV q3 weeks for 4 cycles. Thereafter, patients could continue therapy with exemestane and/or pemetrexed.
Result: Ten patients consented for study and 2 patients screen-failed. Three patients completed therapy in Cohort 1, and five patients were treated in Cohort 2. The median number of cycles was 15 (range 1-54). The MTD was exemestane 50 mg PO daily with combination chemotherapy. Intention to treat analysis showed an overall response rate (ORR) of 62.5% [5 of 8 patients with partial remission (PR)] and clinical benefit rate was 87.5% (7 of 8 patients with stable disease or PR). ORR was significantly associated with tumor aromatase expression (p=0.02). There was no correlation between ORR and ER-alpha or progesterone receptor by IHC. Circulating estrogen levels decreased with exemestane, and quality of life measures did not significantly change. No patients left the study for adverse events.
Conclusion: CCombination chemotherapy with exemestane in postmenopausal women with Stage IV non-squamous, NSCLC is safe and well-tolerated. Biomarker studies show that ORR correlates significantly with tumor aromatase expression. These findings support future clinical trials to confirm antitumor efficacy with this combination therapy.
OR23-05 Human Absorption, Metabolism, Excretion, and Absolute Oral Bioavailability of 14C-CRN00808, an Orally Bioavailable, Nonpeptide, Selective, Somatostatin Receptor 2 (sST2) Biased Agonist for the Treatment of Acromegaly
Authors: Madan Ajay , Luo Rosa , Cook Stephen Ferrara , Struthers Scott , van Marle Sjoerd , Krasner Alan 
Published: May 2020

Abstract
Injected depot formulations of somatostatin peptide analogs are routinely used to treat acromegaly and neuroendocrine tumors (NETs). CRN00808, a small molecule nonpeptide selective somatostatin receptor 2 (sst2) agonist, is being evaluated for efficacy and safety in patients with acromegaly. The current Phase 1 study was conducted in two Parts: In Part A, the absorption, metabolism, excretion, and mass balance of a single oral dose of 20 mg [14C]-CRN00808 (3.0 MBq) oral solution was characterized in six healthy male subjects. Plasma, blood, urine, and feces were collected for up to 432 hours, and were analyzed for total radioactivity and CRN00808 concentrations (plasma only). Metabolite profiling was conducted on the plasma, urine, and feces samples. In Part B, the absolute bioavailability of CRN00808 was determined by administering a single oral dose of 20 mg CRN00808 compared with a single micro-tracer intravenous (IV) bolus injection of 50 µg [14C]-CRN00808 (0.0185 MBq) in five healthy male subjects. The IV dose was administered approximately 90 minutes after the oral dose. Plasma samples were collected for up to 144 hours and were analyzed for total radioactivity and CRN00808 concentrations (plasma only).
Key data from Part A and Part B will be presented. Available data from Part A of the study show that &gt;90% of radioactivity was recovered within 7 days of dosing. The primary route of excretion was the feces (&gt;90%) with minimal excretion in the urine (&lt;10%). Absorption of total [14C]-CRN00808-derived radioactivity in plasma was rapid (median Tmax=1 hour), and the mean Cmax, AUC0-∞, and t1/2 were determined to be 194 ng-equivalents/mL, 3340 ng-equivalents.hr/mL, and 31 hours, respectively. The pharmacokinetic parameters of unchanged CRN00808 in plasma were similar, suggesting that majority of the circulating drug-derived radioactivity is accounted for by unchanged CRN00808 and there are no abundant circulating metabolites. Treatment emergent adverse events associated with CRN00808 were generally mild and transient, and consistent with those reported with other somatostatin agonists. In conclusion, results from this clinical trial in healthy volunteers confirm that CRN00808 has excellent drug-like properties for chronic once-daily oral treatment of patients with acromegaly.
MON-154 Inhaled Corticosteroids and Adrenal Insufficiency: A Meta-Analysis and Systematic Review
Authors: Pare Aurelie , Tsoukas Michael 
Published: May 2020

Abstract
Inhaled corticosteroids have been associated with adrenal insufficiency in adult and pediatric populations¹,². When inhaled corticosteroids are absorbed orally, they can have a systemic effect. Corticosteroid type, particle size, delivery method, liver metabolism via CYP 3A4, protein binding, and half-life all impact the magnitude of the systemic effect of inhaled corticosteroids³. We conducted a systematic review and meta-analysis in order to establish the prevalence of adrenal insufficiency among adult patients taking inhaled corticosteroids. We searched the PubMed, Embase and Cochrane databases for “adrenal insufficiency” AND “inhaled corticosteroids”, yielding 318 search results. We also hand-searched the references of relevant articles. In total, 30 studies were included in our meta-analysis. Amongst these, 15 studies were RCTs and 13 studies were cross-sectional studies. All of these studies used ACTH stimulation testing to diagnose adrenal insufficiency. Risk of bias assessment was completed for all studies using the Cochrane risk of bias assessment tool. Patients with asthma were the population examined in 90% of the included studies. Prevalence of adrenal insufficiency demonstrated by ACTH stimulation testing varied from under 5% to up to 55% among different studies. We recommend that further studies carefully examine and report the clinical impact of abnormal ACTH stimulation testing results, the concomitant use of oral corticosteroids, and the impact of the inhaled corticosteroid delivery method, the corticosteroid type, the corticosteroid dosage, and the duration of therapy.
References:
1. Lapi F, Kezouh A, Suissa S, Ernst P. The use of inhaled corticosteroids and the risk of adrenal insufficiency. Eur Respir J. 2013;42(1)-79-86.
2. Goldbloom EB, Mokashi A, Cummings EA, et al. Symptomatic adrenal suppression among children in Canada. Arch Dis Child. 2017;102(4)-338-339.
3. Ahmet A, Kim H, Spier S. Adrenal suppression- A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy. Allergy Asthma Clin Immunol. 2011;7-13.
SUN-096 Incidentally Found Severe Hypercalcemia in a Pediatric Patient, Diagnostic Challenge
Authors: Burdea Liliana , Salazar Natalia , Minutti Carla , Mantis Stelios 
Published: May 2020

Abstract
Introduction: Idiopathic infantile hypercalcemia is an intriguing feature of Williams syndrome (WS), occurring in ~15% of diagnoses and is typically not clinically severe. Symptomatic hypercalcemia usually resolves during childhood, but lifelong abnormalities of calcium(Ca) and vitamin D metabolism may persist. The cause of the abnormality in Ca metabolism is still unknown. Hypercalciuria generally accompanies hypercalcemia, but isolated hypercalciuria, especially after infancy, can also occur. Nephrocalcinosis is relatively rare, found in less than 10% of patients undergoing renal ultrasonography. We report a 13-month-old female infant with a history of peripheral pulmonary stenosis and constipation, who presented with severe hypercalcemia that led to a new diagnosis of WS. Case presentation: A 13-month-old girl with a history of peripheral pulmonary stenosis, global developmental delay, and constipation presented to the neurology clinic for evaluation of gross motor delay. She was found to have upper body part hypotonia, decreased reflexes, and on laboratory evaluation, severe hypercalcemia with Ca level of 15.0 mg/dL (8.7 - 10.7). The patient was admitted for management of severe hypercalcemia. Physical exam was also remarkable for subtle features of WS: a happy baby, very social, with prominent eyes, full cheeks, flat nasal bridge, round nasal tip, full lips, and a wide smile. Repeated Ca level on admission was 15.9 mg/dL, with normal albumin level of 4.6 g/dL (2.9-5.5), elevated ionized calcium (iCal) of 1.99 mmol/L (0.95 - 1.32), and intact parathyroid hormone (PTH) of &lt;4.0 pg/mL (8.0 - 85.0). Further evaluation revealed a normal 25 hydroxy-vitamin D:41 ng/mL (30-80) and low 1,25-dihydroxy vitamin D:10pg/mL (31-87). Further evaluation revealed elevated urine calcium to creatinine ratio of 0.7 (normal for age &lt;0.56) and renal ultrasound remarkable for medullary nephrocalcinosis. The patient had a complete blood count within normal limits and a PTH related protein of 26 pg/mL (14-27), ruling out malignancy. Hypercalcemia responded well to intravenous fluids and diuretics, the patient being discharged home after two days on furosemide and potassium supplements with close electrolytes monitoring. The patient required calcium reducing therapy for four months to maintain Ca levels within 9-12 range. The medication was decreased gradually based on calcium and ical levels. The patient is currently doing well, with a normal calcium level, and has being off medication for the past three months. Conclusion: This is a rare case of severe hypercalcemia, which led to the diagnosis of WS. Although idiopathic infantile hypercalcemia occurs in 15% of patients with WS, usually the presentation is mild, and the patients do not require medical interventions. Our patient presented with severe hypercalcemia and subtle physical features of WS that led to genetic testing and final diagnosis.