bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-397 The Osteosee System Measurements, Based on Parametric Electrical Impedance Tomography, Correlate with Dual X-Ray Absorptiometry Results for the Diagnosis of Osteoporosis
Authors: Rouach Vanessa , Pushevsky Yuliana , Mayboroda Alla , Osherov Alina , Guindy Michal 
Published: May 2020

Abstract
Introduction: Dual X-Ray Absorptiometry (DXA) is the gold standard for the diagnosis of osteoporosis, but it has its pitfalls. The OsteoSee @Clinic is a novel portable and user-friendly system, which uses parametric Electrical Impedance Tomography (pEIT), being developed to allow screening and diagnosis of osteoporosis at the primary care clinic
Aim: To test the new system and compare its results to those of the DXA system.
Methods and Subjects: This prospective study was conducted between 01/01/2019 and 01/06/2019. Subjects who presented for a routine DXA scan (lumbar spine and proximal femur with Lunar Prodigy GE healthcare system) were enrolled. After signing an informed consent form, they were scanned with the OsteoSee @Clinic system (OsteoSee Ltd., Israel) using 5 electrodes placed around the left distal forearm and around the pelvis.
Results: OsteoSee @Clinic data were compared to DXA total hip bone mineral density (BMD). Correlations were examined between pEIT-index of the pelvis versus DXA total hip BMD. Sensitivity and specificity were calculated according to the diagnosis obtained by DXA based on the total hip T-score. An analysis based on 182 subjects (35 healthy, 115 osteopenia, 32 osteoporosis) scanned on the wrist showed an R-value of 0.795 (p-value &lt; 0.001) representing the correlation between the pEIT-wrist index and DXA results. From the ROC plot, we obtained a sensitivity of 84% and specificity of 71% to diagnose osteoporotic vs osteopenic & normal subjects, and a sensitivity of 82% and specificity of 86% for identifying osteopenic & osteoporotic vs normal subjects. An analysis of 98 subjects (17 healthy, 66 osteopenic, 15 osteoporosis) scanned on the pelvis showed an R-value of 0.740 (p-value &lt; 0.001), representing the correlation between the pEIT-pelvis index and DXA BMD. From the ROC plot, we obtained a sensitivity of 80% and specificity of 81% to diagnose osteoporotic vs osteopenic & normal subjects, and a sensitivity of 70% and specificity of 76% for identifying osteopenic & osteoporotic Vs normal subjects.
Conclusions: The OsteoSee @Clinic system results correlate well with DXA measurements, especially when taking into account clinical interpolations. Sensitivity and specificity values indicate that the OsteoSee @Clinic system can provide screening and diagnosis of osteoporosis. With the DXA system being costly to operate and inaccessible to many patients, the OsteoSee @Clinic system may address the unmet need for diagnosing and treating osteoporosis, and offer an alternative for a broader screening of the population at risk of fractures.
Disclosure: The study was funded by OsteoSee Ltd., Israel
OR27-02 An Exploration of Novel Clinical Benchmarks for Assessing the Practice of Gonadectomy in Conditions Affecting Sex Development - on Behalf of the I-DSD Consortium
Authors: Lucas-Herald Angela K , Bryce Jillian , Cools Martine , Ahmed S Faisal 
Published: May 2020

Abstract
Introduction: Although the practice of gonadectomy in the field of differences/disorders of sex development (DSD) has undergone intense scrutiny, objective knowledge regarding current practice of gonadectomy is lacking in conditions affecting sex development. Methods: The International DSD Registry (www.I-DSD.org) was examined for clinical information reported by the DSD specialist centre on age at presentation, year of birth, diagnosis, karyotype, sex of rearing and age at gonadectomy in all cases over the age of 16 years at the time of search and who had a disorder of androgen action or synthesis, gonadal dysgenesis or a non-specific DSD.Results: Of the 3,618 cases available in the registry, 757 (21%) met the inclusion criteria and data regarding gonadectomy status were available in 668 (88%) from 44 participating centres. Of these, 248 (37%) with a median age of 24 years (range 17, 75) were registered as male and 420 (63%) with a median age of 26 years (16, 86) were registered as female. Gonadectomy was reported from 36 centres in 351 of these 668 cases (53%) of whom 302 (86%) had a 46 XY karyotype. Females were more likely to undergo gonadectomy (n=311, p&lt;0.0001) and the most common diagnoses were complete androgen insensitivity syndrome (n=161, 24%) and partial gonadal dysgenesis (n=94, 14%). Of the 351 cases, the primary indication for gonadectomy was reported in 268 (76%) cases and included mitigation of tumourigenesis risk in 172 (64%), conformity to sex assignment in 74 (28%) and another indication in 22 (8%). Gonadectomy was bilateral in 295 (84%), unilateral in 16 (5%) and unknown in 40 (11%). The median ratio for age at first presentation to age at gonadectomy in those who presented before the age of 5 years and those who presented after the age of 10 years was 0.1 (range) and 0.9 (range), respectively (p&lt;0.0001). Of the 351 cases, 17 (5%) had undergone a gonadectomy before their first presentation to the specialist centre and these cases were distributed across 9 of the 36 centres. Conclusions: Not only does the rate of gonadectomy vary according to underlying diagnosis and sex of rearing, it also seems that there is a variable discrepancy between the age at presentation and age at gonadectomy. The use of this objective marker to identify trends in practice may improve our understanding of the causes of variation.
SAT-744 Spiral Steroid Lactones Are Synthesized by Condensation of a Steroid Precursor with Coenzyme a Derivatives
Authors: Chasalow Fred I 
Published: May 2020

Abstract
Background: Szent-Gyorgyi proposed that digoxin wasn’t really drug but was a substitute for an endogenous cardiotonic steroid (ECS). Endogenous ouabain and marinobufagenin have been proposed as ECS.
Hypothesis: Ionotropin, our first candidate for the ECS, is unique among steroids because it is the phosphocholine ester of a steroid with 23 carbon atoms. Logically, either there must be a novel mechanism for adding carbon atoms to a pregnenolone-like precursor or a novel mechanism for side-chain cleavage from a cholesterol-like precursor.
Experimental design: Serum samples were extracted with acetonitrile, filtered and analyzed by MS-N on an LTQ-XL ion trap mass spectrometer. The instrument permits multiple rounds of fragmentation and identification of the parent ion and each fragment ion. This process permitted recognition of ions that were phosphocholine esters and of the mass of the steroid fragments. The chemical formula of each steroid fragment was determined by trial and error analysis. Although not every mass ion has a unique chemical formula, in fact, each of the steroid ions had a unique formula. Possible isomers were resolved by consideration of knowledge of steroid biosynthetic pathways.
Major results: In brief, human serum samples had steroid fragment ions consistent with 23 (354 Da) and 25 (398 Da) carbon atoms. This provides an additional constraint as the synthetic mechanism must account for both products. These mass ions were consistent with condensation of either acetyl-CoA or acetoacetyl-CoA with the phosphocholine ester of pregna-5,7-diene-3β,17α-diol-20-one. After condensation, the steroid adduct would be dehydrated and cyclized to form the corresponding spiral steroid phosphocholine ester. This pathway is similar to the mechanism of addition of 2 carbon fragments to a long chain fatty acid. This is the first explanation for the biosynthesis of endogenous mammalian ECS. Spiral lactones would be expected to cross react with many antibodies specific for digoxin, ouabain or marinobufagenin. Either one of the spiral lactones would satisfy Szent-Gyorgyi’s suggestion as the endogenous digoxin-like material.
Conclusions: In summary, we have isolated 2 spiral steroid lactones from mammals and identified the mechanism of their biosynthesis. We propose, as the spiral steroids share structural features with the spironolactone class of potassium sparing diuretics, that they also share functions. Nicholls proposed that a candidate for ECS should not be accepted without [a] isolation, [b] precursors, and [c] a biosynthetic path. As there has been no satisfaction of these requirements for ouabain or marinobufagenin, their existence as ECS in mammals needs to be reconsidered.
SUN-610 Acquired Generalized Lipodystrophy: A Rare Side Effect of PD1-Inhibitor Therapy
Authors: Shah Amy , Rodriguez Juan Pablo Perdomo 
Published: May 2020

Abstract
Background:Program cell death-1 (PD1) inhibitors, such as nivolumab and pembrolizumab, have shown efficacy as adjuvant treatment for cancers, including melanoma, and their frequency of use is increasing. A potential, but rare, side effect of PD1-inhibitors is acquired generalized lipodystrophy (AGL), an immune-related adverse event characterized by loss of subcutaneous adipose tissue (SAT) and insulin resistance-associated complications. AGL can result in irreversible endocrinopathies, including diabetes. Clinical Case: A 60-year-old overweight female (BMI 29.2), with no related metabolic complications or medical history of autoimmune disorders, was treated with nivolumab (240mg IV q2 weeks) for 1 year for metastatic melanoma on her right arm (staged T4bN2a) that underwent wide local resection. She completed therapy with no complications or lab abnormalities.One-month post-treatment, she noticed rapid weight loss and facial atrophy. Within 3 months, she had a 58% weight loss withsignificant loss of SAT; insulin resistance and diabetes(impaired fasting glucose 201; A1c 9.2%);hepatic steatosis diagnosed by liver biopsy; hypertriglyceridemia (5,309 mg/dL,); and undetectable leptin levels. She also developed prominent forearm muscles and leg veins. GAD antibody was negative. The loss of SAT and rapid weight loss, physical exam findings, onset of diabetes, steatosis and hypertriglyceridemia—all closely following therapy with nivolumab—led to a diagnosis of nivolumab-associated AGL. In addition to treatment for hypertriglyceridemia, the patient was placed on multiple oral and parenteral antihyperglycemic medications, including metformin, SGLT2i, GLP-1, and DPP4, but all were discontinued due to side effects. Ultimately, her A1c increased to 12.4% and she was placed on basal/bolus therapy. Discussion: AGL is associated with an increased risk of lymphoma. Metreleptin, a recombinant analogue of human leptin, is approved for treatment of metabolic complications of AGL. Some instances of lymphoma in AGL have occurred while the patient was receiving metreleptin, but data is inconclusive as to whether development of lymphoma is a side effect of metreleptin.(Brown RJ, Chan JL, Jaffe ES, et al, 2016) We believe treatment with metreleptin would have benefited our patient, but she declined due to potential side effects, including lymphoma. Nine months after nivolomuab therapy, her melanoma is in remission but she still has lipodystrophic characteristics with insulin resistant diabetes. She is being treated with pioglitazone and multiple daily insulin injections but has not achieved euglycemia despite a total daily insulin dose of 2 u/kg. Of note, injecting insulin and use of a continuous glucose monitor have been a challenge given the lack of SAT. Although AGL resulting from PD1-inhibitor therapy is rare, it is a condition for which this patient will need life-long treatment.
SAT-391 Safety and Efficacy of Conventional Therapy with Calcium and Activated Vitamin D in Patients with Chronic Post-Operative Hypoparathyroidism: Results of a Cross-Sectional Case-Control Study
Authors: Mazoni Laura , Apicella Matteo , Matrone Antonio , Saponaro Federica , Biagioni Isabella , Cosci Bianca , Cetani Filomena , Marcocci Claudio 
Published: May 2020

Abstract
Introduction: Conventional therapy of chronic post-operative hypoparathyroidism (PO-HypoPT) with calcium and activated vitamin D is suboptimal and associated with several complications, including impairment of the quality of life. Aim of this study was to compare clinical, biochemical and instrumental parameters in 120 patients who underwent total thyroidectomy for differentiated thyroid cancer, 60 with PO-HypoPT (Group A) treated with conventional therapy and 60 without (Group B), matched for age and sex, followed a tertiary referral center. Matherials and methods: An “ad hoc” CRF was used to collect epidemiological, clinical (symptoms, treatment) and biochemical data (total and ionized calcium, albumin, phosphate, magnesium, calcium/phosphate product, creatinine, 25-OH vitamin D, PTH, TSH, eGFR, 24-h urinary calcium and creatinine), and renal ultrasound. Results: The median duration of PO-HypoPT was 7 years (IQR 4-13). All patients of group A were treated with calcitriol (median 0.5 μg/daily; IQR 0.5-1.0), and 33/60 (55%) were also given calcium carbonate supplementation (median 1000 mg/daily; IQR 500-1000). Hypocalcemia related symptoms were more frequent in group A (27/60 - 45%) than in group B (1/60 - 1.7%) (p&lt;0.01). Total and ionized serum calcium [median 8.9 (IQR 8.5-9.1) vs 9.3 (IQR 9.0-9.5) mg/dl; median 1.16 (IQR 1.1-1.2) vs 1.23 (IQR 1.21-1.27) mmol/L] (p&lt;0.01), magnesium [median 1.9 (IQR 1.8-2.0) vs 2 (IQR 1.9-2.1) mg/dl - p&lt;0.01] and PTH [median 10 (IQR 8-13) vs 29 (IQR 22-35) pg/ml - p&lt;0.01] were significantly lower in Group A vs Group B. Conversely, serum phosphate [median 3.7 (IQR 3.4-4.1) vs 3.3 (IQR 3.0-3.6) mg/dl - p&lt;0.01], calcium-phosphate product [median 33 (IQR 30-36) vs 30 (IQR 27-34) - p=0.012] and 25-OH vitamin D [median 34.1 (IQR 29.2-41.3) vs 26.7 (IQR 18.1-33.4) - p&lt;0.01) were significantly higher in Group A vs Group B. Twenty-four hour urinary calcium was higher in group A [median 248 mg (IQR 166-363)] than in group B [median 165 mg (IQR 94-229)] (p&lt;0.01). The rate of nephrolithiasis was significantly higher in group A (21/60 pts - 35%) than in group B (7/60 pts - 11.7%) (p&lt;0.01). Moreover, there was a significant correlation of neprholithiasis with 24h urinary calcium but not with total and ionized serum calcium. Conclusions: This cross-sectional case-control study confirms that treatment of chronic PO-HypoPT with conventional therapy is suboptimal, even in a tertiary referral center, and associated with an increased risk of nephrolithiasis. Following the recent publication of treatment guidelines, the question of whether a better quality of care, including the use of rhPTH, will improve the biochemical control and decrease the rate of hypercalciuria and the risk of nephrolithiasis remains to be established.
SUN-070 European Registries for Rare Endocrine Conditions (EuRRECa): Results from the Platform for E-reporting of Rare Endocrine Conditions (e-REC)
Authors: Ali Salma R , Bryce Jillian , Cools Martine , Danne Thomas , Dattani Mehul T , Dekkers Olaf M , Hiort Olaf , Linglart Agnes , Netchine Irene , Nordenstrom Anna , Patocs Attila , Pereira Alberto M , Persani Luca , Reisch Nicole , Smyth Arlene , Sumnik Zdenek , Taruscio Domenica , Visser W Edward , Ahmed S Faisal 
Published: May 2020

Abstract
Background EuRRECa (European Registries for Rare Endocrine Conditions) is a group of web-based projects that work closely with the European Reference Network (ERN) for Rare Endocrine Conditions (endo-ern.eu) and helps the ERN with inventorying its clinical activity. To understand the number of new encounters of rare conditions within this network, it has launched an e-reporting programme for rare endocrine conditions (e-REC) that are covered within this network. Methods 46 endocrine centres within 18 countries volunteered to participate in e-REC from July 2018 to June 2019. An electronic reporting ‘card’ developed through REDcap was issued monthly to enquire whether clinicians had encountered a new case of any condition within the 8 Endo-ERN main thematic groups (MTGs). Results On a monthly basis over 1 year, a median of 14 (range 11, 21) paediatric centres and 13 (11, 25) adult centres actively reported cases. A median of 53 (22, 80) paediatric cases and 96 (42, 250) adult cases were reported monthly. Amongst paediatric cases, conditions within the Sex Development and Maturation (SDM) theme were most commonly reported comprising 38% of all reported conditions, with XY, DSD being the most commonly reported condition (24% of cases). Amongst adults, Pituitary and Thyroid conditions were most commonly reported, 34% and 26% of all conditions, respectively. Amongst conditions within the Pituitary group, pituitary adenoma was the most commonly reported condition (74% of cases) and non-metastatic thyroid carcinoma was the most commonly reported condition (95% of cases) amongst the Thyroid group. In children, the median number of cases reported per centre was 21 (9, 32) for conditions affecting SDM. In adults, a median of 37 (6, 75) Pituitary and 22 (5, 80) Thyroid cases were reported per centre. Conclusion e-REC is a simple, yet effective, platform that can be used to capture information on new encounters with patients with several rare conditions and can be adapted to serve the needs of other discrete networks that are interested in understanding the occurrence of rare conditions.
MON-367 Unusual Presentation of Hypercalcemia Preceding the Diagnosis of Methotrexate-Induced Pneumocystis Jirovecii Pneumonia from Treatment of Necrotizing Myopathy
Authors: Nguyen Minhthao , Mohiuddin Afshan 
Published: May 2020

Abstract
Background: Pneumocystis Jirovecii infection is a common opportunistic infection often seen severely immunocompromised individuals, such as those with HIV/AIDs. This is an unusual case where the patient displayed persistent hypercalcemia, with an eventual diagnosis of PCP likely due to immunosuppression from methotrexate (MTX) therapy.
Case: A 79 year old male was brought to the hospital for acute change in mental status and hypercalcemia (13.4mg/dl). The patient was acutely encephalopathic, oriented to self only; his baseline was a high level executive at a company. An extensive neurologic workup including CT, MRI, EEG, spinal fluid examination was negative with a persistent hypercalcemia. Additional workup showed no increase in bone turnover, suppressed PTH, non-elevated pPTHrP. He was found to have diffuse mild PET avidity of bilateral lungs on PET scan, with bronchoscopy for evaluation of potential granulomatous disease. PCR of the BAL fluid obtained during bronchoscopy was positive, and the patient was ultimately treated with an extended course of Atovaquone for Pneumocystis Jirovecii pneumonia (PCP). The patient was felt to have an immunosuppressed state secondary to being treated for a necrotizing myopathy with methotrexate. The patient’s mentation slowly but substantially improved with a combination of a prednisone taper and Atovaquone, with discontinuation of the MTX. The patient’s hypercalcemia improved with treatment of PCP.
Conclusion: Although a cause of hypercalcemia secondary to primary hyperparathyroidism causing necrotizing myopathy is known in the literature, it is unusual to see the opposite, where few case reports have documented hypercalcemia due to immunosuppression from low-dose methotrexate treatment for necrotizing myopathy resulting in pulmonary pneumocystis and hypercalcemia. Additionally, MTX induced immunodeficiency is often associated with severe immunosuppression or lymphoproliferative disorders - however the patient had an extensive work up with negative results for malignancy
MON-630 Elevating the Patient Voice in Type 1 Diabetes Clinical Trials: A Comparison of In-Depth Exit Interviews and Diabetes-Specific Questionnaires
Authors: Ervin Claire , Joish Vijay N , Castro Colleen , DiBenedetti Dana , Evans Emily , Carroll Amy , Lapuerta Pablo 
Published: May 2020

Abstract
Healthcare decisions are more effective when the patient voice is included in clinical research, and the Food and Drug Administration encourages the patient’s voice in drug development and regulatory decision-making. Clinical trials should not only demonstrate the effect of a drug on clinical outcomes but should also demonstrate that these outcomes are important or meaningful to patients. Several qualitative and quantitative methods are available to collect patient experience data (e.g., traditional patient-reported outcome [PRO] measures, interviews with clinical trial participants). We aimed to understand if in-depth exit interviews were more effective assessments of the patient experience in recent type 1 diabetes (T1D) clinical trials than existing diabetes-specific PROs. In-depth qualitative interviews were conducted with 41 adults with T1D who had completed or withdrew from a phase 3 study of sotagliflozin, a dual inhibitor of SGLT1 and SGLT2. A targeted literature review was conducted to identify diabetes-specific PROs used in randomized controlled clinical trials of novel T1D medications reported over the past 5 years. Included trials had to investigate a pharmaceutical intervention for adults with T1D and report a diabetes-specific PRO. The concepts assessed in the PRO measures were mapped against those elicited during the 41 exit interviews. A total of 336 publications were identified in the literature search of which 26 were eligible for analysis. Eight diabetes-specific PROs were identified and reviewed from which 54 concepts related to the patient experience were identified. The patient exit interviews included 42/54 (78%) of the patient experience-related concepts identified across all 8 PROs from the literature review. Of the 8 PRO instruments, the Diabetes Quality of Life Measure (DQOL) covered the most concepts (18/54, 33%), followed closely by the Audit of the Diabetes-Dependent Quality of Life (ADDQoL; 16/54, 30%). Some of the most prominent concepts from both approaches were related to impact on life and family; fear of complications; and impact on physical activity, lifestyle and social perceptions. There were several concepts identified in the exit interviews that were not covered in any of the 8 PRO instruments (related to keeping blood sugars within a desired range, ability to manage changes in insulin use). Overall, the exit interviews appeared to provide a more comprehensive picture of patient experience domains. Although existing diabetes PRO measures cover a range of concepts and may adequately assess changes in certain outcomes, data from patient exit interviews provide more comprehensive insights into the patient experience. Exit interview data may provide a more detailed understanding of the disease burden and impact of treatment on improvements in well-being, daily functioning, and treatment satisfaction.