bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-643 Diabetes’ Cost to Us Taxpayers: Thirty-Day Readmission and Resource Utilization Among Diabetics Patients Admitted with ST-Elevation Myocardial Infarction: A Propensity Score Match Analysis
Authors: Nasserifar Shabnam , Ho Kam Sing 
Published: May 2020

Abstract
PURPOSE: To determine the relationship between diabetes and thirty-days readmission, mortality, morbidity, and health care resource utilization in patients who were admitted with ST-Elevation Myocardial Infarction (STEMI) in the United States. METHOD: A retrospective study was conducted using the AHRQ-HCUP Nationwide Readmission Database for the year 2014. Adults (≥ 18 years) with a primary diagnosis of STEMI (1), along with a secondary diagnosis of diabetes were identified using ICD-9 codes as described in the literature (2). The primary outcome was the rate of all-cause readmission within 30 days of discharge. Secondary outcomes were reasons for readmission, readmission mortality rate, morbidity, and resource use (length of stay and total hospitalization costs and charges). Propensity score (PS) using the 1:1 nearest neighbor matching without replacement was utilized to adjust for confounders (3). Independent risk factors for readmission were identified using a Cox proportional hazards model (4). RESULTS: In total, 116,124 hospital admissions among adults with a primary diagnosis of STEMI were identified, of which 18.05% were diabetics. 1:1 PS matching was performed based on demographic (age, gender, hospital status, etc.) and clinical characteristics (Charlson comorbidity score. The 30-day rate of readmission among diabetics and non-diabetics with STEMI were 9.31% vs. 6.18% (p &lt;0.001). The most common readmission for both groups was recurrent myocardial infarction. During the index admission for STEMI, the length of stay (LOS) among diabetics and non-diabetics patients were not statistically different (4.74 vs 4.58 days, p=0.12). However, the total hospital cost for the diabetic patients was statistically different ($27,027 vs $24,807, p &lt;0.001). Most importantly, diabetics patients’ in-hospital mortality rate during their index admission was significant higher (10.20% vs 5.92%, p &lt;0.001). Amongst those readmitted, the LOS, total hospital cost, or in-hospital mortality among diabetics were not statistically different when compared to their counterparts during their readmission. Diabetes (HR 1.60, CI 1.27-2.02, p &lt;0.001) was an independent predictor associated with higher risks of readmission. Other independent predictors associated with increased 30-day readmission include acute exacerbation of CHF, acute exacerbation of COPD, acute kidney injury, secondary diagnosis of pneumonia, history of COPD, history of ischemic stroke, history of atrial fibrillation & atrial flutter, history of chronic kidney disease, history of iron deficiency, and use of mechanical ventilator. CONCLUSION: In this study, diabetics patients admitted with STEMI have a higher 30 days of readmission rate, total hospital cost, and in-hospital mortality (p &lt;0.001) than their non-diabetic counterparts.
MON-197 Developing a Research Database About Primary Aldosteronism: Rationale and Baseline Characteristics
Authors: Wang Wen , Ren Yan 
Published: May 2020

Abstract
Introduction There were limited evidence supporting the management of PA, primarily due to lack of high quality of data. Developing a research database through integrate both retrospective and prospective collected data regarding clinical care and outcomes of patients with PA may provide valuable evidence on management of PA. Methods The establishment of PA research database involved two steps. Firstly, patients with confirmation of PA between 1 Jan 2009 to 31 Aug 2019 were identified and data were extracted from EMR. Secondly, patients who have positive confirmatory testing for PA and agree to participant a prospective cohort will be enrolled. Data regarding clinical care and long-term outcomes will be prospectively collected based on the case report forms since 1 Sep 2019. We evaluated the quality of research database through assessment of quality of key variables. Results Totally, 904 patients diagnosed as PA in WCH were identified, of which 507 patients had positive confirmatory testing for PA were finally included into the retrospective database. Among included patients, the mean age was 49.2 years old, and the mean BMI was 24.72 kg/m2. There were 37 (7.3%) patients diagnosed as chronic kidney disease (CKD), 13 (2.6%) as coronary artery disease (CAD), 95 (18.7%) as diabetes mellitus (DM) and 77 (15.2%) as obstructive sleep apnea-hypopnea syndrome (OSA). The mean systolic blood pressure (SBP) was 155.8 mmHg, and the mean diastolic blood pressure (DBP) was 96.2 mmHg. Among included patients, the lowest serum potassium during admission was 2.96 mmol/L, and the mean serum aldosterone was 26.4 ng/dL. Validation of data extracting and linking showed the accuracy were 100%. Evaluation of missing data showed that the completeness of BMI (95.9%), SBP (1%) and DBP (1%) were high. Conclusion Through retrospective and prospective cohort of PA, a research database about PA with high quality and comprehensive data will be established. We anticipate that the research database will provide a high level of feasibility for management of PA in China.
SAT-555 Can Histology Predict the Presence of KCNJ5 Somatic Mutation in Aldosterone-Producing Adenomas?
Authors: Yamazaki Yuto , Gao Xin , Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Morimoto Ryo , Gomez-Sanchez Celso E , Nakamura Yasuhiro , Satoh Fumitoshi , Sasano Hironobu 
Published: May 2020

Abstract
Aldosterone-producing adenoma (APA) is well known to harbor marked intratumoral heterogeneity in terms of morphology and CYP11B2 (aldosterone synthase) localization. In histology, APA is generally characterized by two distinct cell subtypes, namely “clear cells” and “compact cells”. Clear tumor cells harbor abundant lipid droplets in their cytoplasms and compact tumor cells generally featuring small round shape have abundant intracytoplasmic organelles including mitochondria.
Relatively close correlation between these histological characteristics (morphology and CYP11B2 immunohistochemistry) and genotypes of aldosterone-driver gene somatic mutation has been reported. Among them, KCNJ5-mutated APAs have been reported to harbor clear cell predominant features, while APAs with other rare somatic mutations including ATP1A1, ATP2B3 and CACNA1D harbor heterogenous or relatively compact cell predominant morphometry. However, these previous evaluation were based on eyeball analysis with relatively low reproducibility. Therefore, we developed the more quantitative methods using digital image software in order to analyze the widespread area, which can reflect intratumoral heterogeneity, with high reproducibility to analyze the further detailed correlation between histopathological characteristics and genotype in APA. We explored the utility of immunohistochemistry including CYP11B2 and KCNJ5. We further attempted to propose histopathological scoring system to predict the presence of KCNJ5 somatic mutation in APAs.
Results of our present study revealed that KCNJ5 was predominantly immunolocalized in zona glomerulosa among adrenal cortex (vs. ZF, P=0.0002, vs. ZR, P=0.0002), furthermore, predominantly in APCCs than in non-APCCs (P=0.0019). Among the tumors, KCNJ5 immunoreactivity was significantly higher in KCNJ5-wild type APAs than in mutated ones (P=0.0037). KCNJ5-mutated APAs had significantly lower nuclear / cytoplasm ratio and abundant clear cell components than those with wild type, harboring large tumor size. In conclusion, we firstly proposed a novel histopathological predicting scoring system for the presence of KCNJ5 somatic mutation, including the following histopathological findings; N/C ratio, clear cell (%), tumor size, CYP11B2 immunoreactivity and KCNJ5 immunoreactivity. It is true that no single histological factors above could precisely predict the presence of KCNJ5 somatic mutation but this newly developed combined histopathological predicting scoring system could provide relatively high accuracy to predict KCNJ5 somatic mutation in APAs (AUC=96%, sensitivity:100%, specificity:90%, 4 points or more). However, further prospective validation by large number of cases is required for clarification.
SAT-133 Breast Tumor Kinase (Brk/PTK6) Mediates Triple Negative Breast Cancer Cell Migration and Taxol Resistance via SH2 Domain-Dependent Activation of RhoA and AhR
Authors: Dwyer Amy Renee , Kerkvliet Carlos J Perez , Krutilina Raisa , Playa Hilaire , Park Deanna , Thomas Warner , Smeester Branden , Seagroves Tiffany Nicole , Lange Carol A 
Published: May 2020

Abstract
Triple negative breast cancer (TNBC) patients have higher recurrence rates and a worse prognosis relative to patients diagnosed with other breast cancer subtypes. Protein tyrosine kinase 6 (PTK6; also called Brk), a soluble tyrosine kinase, is overexpressed in 86% of breast cancer patients, however its precise function in the context of TNBC is poorly defined. PTK6 expression is elevated in TNBC models in response to both cellular and endocrine stress, coordinated transcriptionally by the Hypoxia-Inducible Factors (HIFs) and glucocorticoid receptor (GR). We showed previously that PTK6 expression, but not its intrinsic kinase activity, is required for breast cancer cell motility. To further delineate the mechanisms of PTK6 signaling, we created kinase-intact domain structure mutants of PTK6 via in frame deletions of the N-terminal SH3 or SH2 domains. MDA-MB-231 cells expressing a PTK6 variant lacking the SH2 domain (SH2-del PTK6) were less responsive to growth factor-stimulated cell motility relative to wild type or kinase dead (KM) controls. To identify signal transduction pathways activated in TNBC cells harboring PTK6 domain mutants, we used a reverse phase protein array (RPPA), which revealed that the SH2 domain of PTK6 mediates TNBC cell motility via activation of the RhoA and/or AhR signaling pathways. Moreover, in TNBC cells, including a taxane-refractory TNBC model, addition of AhR or Rho inhibitors to paclitaxel (Taxol) enhanced cytotoxicity. Together, these studies reveal that the SH2-domain of PTK6 is an effector of advanced cancer phenotypes in GR+ TNBC cells and identify RhoA and AhR as novel therapeutic targets in PTK6+ tumors.
SAT-431 Insulin Resistance, Lipid Profile and High-Sensitivity C-Reactive Protein in Patients with Autoimmune Thyroiditis
Authors: Neves Celestino , Neves João Sérgio , Pereira Miguel , Oliveira Ana , Medina José Luís , Delgado Luís , Carvalho Davide 
Published: May 2020

Abstract
Introduction: Thyroid function and autoimmunity has been associated with cardiovascular events in patients with autoimmune thyroiditis. Objectives: To evaluate the association between thyroid function, antithyroid antibodies levels, insulin resistance and markers of cardiovascular risk in patients with autoimmune thyroiditis. Methods: We evaluated 228 patients with autoimmune thyroiditis, 93.9 % female, with a mean age of 47.06 ± 15.35 years. We analyzed thyroid function, anti-thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO), HOMA-IR, HOMA-B, QUICKI, HISI (Hepatic Insulin Sensitivity Index), WBISI (Whole-Body Insulin Sensitivity Index), the levels of lipid profile, high-sensitivity C-reactive protein (hs-CRP), homocysteine, folic acid, and vitamin B12. We defined 3 groups based on TSH levels: TSH between 0.35-2.49 µUI/ml, (n = 166), TSH between 2.50-4.94 µUI/ml, (n = 43) and TSH over 4.95 µUI/ml, (n = 19), and normal levels of free T4 and free T3. A 75-g OGTT was performed in the morning and blood samples were obtained every 30 min for 120 min for measurements of plasma glucose, insulin, and C-peptide. For the statistical analysis we used the Mann-Whitney test and Spearman correlations. Results are expressed as means ± SD or percentages. A two-tailed p&lt;0.05 was considered statistically significant. Results: There were no significant differences regarding median age or median BMI between groups. We did not find any significant differences comparing group with TSH 0.35-2.49 and group with TSH 2.50-4.94, in all parameters evaluated. Group with TSH 2.50-4.94 had higher indexes of QUICKI (0.69 ± 0.39 vs 0.48 ± 0.13; p = 0.02) and HISI (79.83 ± 63.72 vs 41.73 ± 29.02; p = 0.01) than group with TSH over 4.95. The group with TSH over 4.95 demonstrated a higher index of HOMA-IR than group with TSH 2.50-4.94 (3.77 ± 2.93 vs 1.95 ± 1.24; p = 0.01). In the TSH 0.35-2.49 group we found significant correlations between TSH and HOMA-IR (r= 0.18; p = 0.01), total cholesterol and anti-TPO (r =0.23; p = 0.002), anti-Tg and HDL-cholesterol (r= -0.17; p=0.002), anti-Tg and triglycerides (r=0.34; p &lt; 0.001), and anti-Tg and LDL-cholesterol (r=0.16; p=0.03). In the TSH 2.50-4.94 group we observed positive correlation between Apo A1 and HOMA-B (r=0.58; p&lt;0.001), HOMA-IR and LDL-cholesterol (r=0.34; p=0.02) and WBISI and HDL-cholesterol (r=0.34; p=0.02). In the TSH over 4.95 group we observed a correlation between TSH and triglycerides (r=0.70; p&lt;0.001) and between anti-Tg and hs-CRP (r=0.64; p=0.004). Conclusions: The association among TSH, lipid profile, insulin resistance, hs-CRP and antithyroid antibodies in patients with autoimmune thyroiditis may contribute to an increased cardiovascular risk, not only in patients with subclinical hypothyroidism but also in those classified as euthyroid.
SAT-595 Early Weight Gain Impact onto the Arcuate Leptin Receptor Expressing Neurons Activity During Development
Authors: Zampieri Thais T , Bohlen Tabata M , Donato j Jose , Frazao Renata 
Published: May 2020

Abstract
The arcuate nucleus (ARH) is considered the main mediator of the effects of leptin on energy homeostasis, as well, part of the hypothalamic circuitry through which the sex steroids mediate the ovulatory cycle and therefore reproduction. While it is known that aging influences synaptic plasticity of ARH neurons, the effects of increased weight gain early in life onto in the activity of ARH neurons are still poorly understood. In order to demonstrate whether prepubertal adiposity gain is able to modulate the synaptic transmission in leptin receptor (LepR)-expressing cells of the ARH, we employed a postnatal over-nutrition model by raising mice in small litters (SL), while control mice were maintained in regular litters (6-8 pups per litter). The spontaneous currents of LepR-expressing neurons in the ARH were measured by whole-cell patch-clamp recordings in hypothalamic slices obtained from prepubertal, pubertal and adult female LepR-reporter mice. As expected, mice raised in SL exhibited increased body weight compared to control mice at prepubertal and pubertal stage (prepubertal, t(59) = 6.9, P &lt; 0.001; pubertal, t(59) = 5.3, P &lt; 0.001), despite no difference at adult age (t(59) = 1.5, P = 0.4). By evaluating ARH neuronal activity we observed an increased average of excitatory and inhibitory currents frequency during development, in both control females (sEPSC: F(2, 46)= 17.76, P&lt; 0.0001, sIPSC: F(2, 21)= 4.064, P= 0.0322) and in mice raised in SL (sEPSC: F(2, 49)= 27.76, P&lt; 0.0001, sIPSC: F(2, 19)= 6.714, P= 0.0062). However, SL and control mice exhibited similar sEPSC amplitudes at all stages of development. A significant interaction between litter size and excitatory transmission frequency onto LepR-expressing cells were noted at the pubertal and adult stages (F(2, 95)= 3.164, P= 0.046), despite no changes in the amplitudes of these signals (interaction: F(2, 95) = 0.1516, P= 0.8596; age: F(2, 95) = 0.9961, P= 0.3731; litter size: F(1, 95) = 0.076, P= 0.7832). By evaluating the inhibitory transmission to ARH LepR-expressing neurons, no significant interaction between litter size and inhibitory transmission frequency were observed (F(2, 40) = 0.09271, P= 0.9117). However, the average sIPSC amplitude were significantly reduced in the ARH cells recorded from mice raised in SL, when compared to the control group (F(2, 42) = 22.86, P&lt; 0.0001), despite no identifiable interaction between litter size and inhibitory transmission (F(2, 42) = 0.6619, P= 0.5212). Taken together our results suggest that early weight gain influences the excitatory transmission pattern in LepR-expressing neurons by increasing presynaptic excitatory inputs and suppressing postsynaptically transmission to ARH neurons.
SUN-198 Metastatic Progression of Adrenocortical Carcinoma: Phenotypic Transformation to ACTH-Independent Cushing’s Syndrome
Authors: Ocampo Javier , Luzuriaga Maria Gracia , Ayala Alejandro Raul 
Published: May 2020

Abstract
Background: Adrenocortical carcinoma (ACC) is a rare malignancy. Around 60% of adrenal carcinomas are functioning tumors and may present with distinctive phenotypes (1). Very rarely, as the disease progresses, changes in secretory patterns may be observed.
Clinical Case: A 39-year-old female presented to the hospital with a 1-month history of abdominal pain associated with hirsutism, weight gain, acne, and amenorrhea. Computed tomography of the abdomen showed a 7 cm left adrenal mass with areas of necrosis as well as presumptive metastatic disease involving the liver and lungs. Biopsy of the adrenal mass confirmed the diagnosis of adrenocortical carcinoma. Initial laboratories were compatible with hyperandrogenemia (increased 24-hour urine 17-ketosteroid level of 106.3 mg/24 hr (n 6.0-15.0) and mildly elevated testosterone of 65 ng/dL (n&lt;45)). Aldosterone, renin, and metanephrines levels were normal. The patient underwent adrenalectomy after 1 month and was placed on hydrocortisone replacement. Follow-up biochemical testing showed a decrease in 17-ketosteroids level to 24.7 mg/24hr. DHEAS and testosterone were persistently elevated. Following discontinuation of hydrocortisone, her 24-hour urine cortisol was normal at 18 ug/24hr, (n 6-24) and ACTH was suppressed at 1.8 pg/mL (n 7-63). She was started on mitotane therapy shortly after.
Three months after initiation of treatment, she was admitted for a pulmonary embolism. At that time, she had clear signs of hypercortisolism, such as weight gain, hyperglycemia, easy bruising as well as purple striae. Progressive metastatic disease with enlarged lung and liver masses was observed in imaging. On this occasion, her morning cortisol was elevated at 35 ug/dL and ACTH was suppressed at 1 pg/mL. Th hyperandrogenemia was more evident this time with DHEAS of 778 ug/dl. Steroid supplementation was discontinued, and ketoconazole was started. An elevated 24-hour urinary cortisol (2085 ug/24hr) confirmed the diagnosis of Cushing Syndrome. Given the progression of disease while on mitotane, the patient was started on chemotherapy with etoposide, doxorubicin, and cisplatin.
Conclusion: This case represents an unusual example of the phenotypic transformation of adrenal cancer resulting in new-onset ACTH-independent Cushing’s syndrome while the patient was on treatment. Awareness of such changes in secretory pattern are important to guide therapy and minimize morbidity associated with hypercortisolism.
Reference: (1) Puglisi S, Perotti P, Pia A, Reimondo G, Terzolo M. Adrenocortical Carcinoma with Hypercortisolism. Endocrinol Metab Clin North Am. 2018 Jun;47(2):395-407.
SAT-059 Congenital Craniopharyngioma: A Rare and Challenging Disease
Authors: Lopes Fernanda Sousa Cardoso , Oliveira Renata Santarem , Braz Délia Oliveira , Pacheco Nayla Samia Silva , de Castro Luiz Claudio Goncalves 
Published: May 2020

Abstract
Introduction: Congenital central nervous system tumors are seldomly seen, with just few reported cases of neonatal craniopharyngioma (NCP). Albeit being a benign tumor arising from epithelial vestiges along the adenohypophysis migration, NCP may have an aggressive behavior due to its location.Case Report: We report a two-month-old female infant referred to the Pediatric ward due to recurrent sepsis episodes, uncontrollable crying, large fontanelle and signs of adrenal insufficiency. Laboratory evaluation showed low serum cortisol 0.11 μg/dL(REF: 6.2-19.4 μg/dL), ACTH 6.66 pg/mL(REF: 7.2-63.3pg/mL) and Na 133 mEq/L(REF: 136-145mEq/L), normal Free T4 1.01 ng/dL(REF: 0.93-1.7 ng/dL) and a slightly elevated prolactin 59.43 ng/mL(REF: 4.79-23.3ng/mL). A transfontanelar ultrasound demonstrated a cystic and calcified sellar/suprasellar tumor. Encephalus Magnetic Resonance Imaging described a 36x42x33 mm multicystic sellar/suprasellar mass extending to the middle line and occupying all sellar space, leading to a deformed and compressed third ventricle, and displacing the mesencephalus, the cerebral pedunculus and the optic chiasm. Imaging evaluation suggested a craniopharyngioma. She started hydrocortisone therapy due to hypercortisolism and was submitted to transsphenoidal surgery, but just a partial resection of the tumor was possible. She needed levothyroxine and desmopressin replacement after surgery. On the 10th post-operative day she died due to infectious complications. The histological analysis of the tumor diagnosed an adamantinomatous-type grade I craniopharyngioma.Comments: Central nervous system tumors developing in the first 60 days of life are considered congenital. Besides being a rare condition, NCP are challenging and life-threatening. Although for some groups the complete resection of the tumor is considered the gold standard approach to those patients, sometimes it cannot be performed due to limitations intrinsic to the tumor biology and due to the patient’s age, worsening the prognosis of the infant. Multihormonal deficits and shortened survival of this patient were consequences of the tumor characteristics, delayed diagnosis of craniopharyngioma and the poor results during and after the surgical intervention.