bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-069 Advantages of Next Generation Sequencing (NGS) in Hypophosphatemic Disorders Diagnosis. First Case of SLC9A3R1 Gene Pathogenic Variant Detected in a Pediatric Patient
Authors: Ramirez, Biochemist Pablo , Palma Isabel Di , Viterbo Gisela , Perez-Garrido, Biochemist Natalia Isabel , Pujana, Biochemist Matias , Juanes Matias , Belgorosky Alicia , Marino Roxana Marcela 
Published: May 2020

Abstract
Background: Hereditary hypophosphatemic rickets (HHR) is a group of inherited disorders characterized by hypophosphatemia due to renal-phosphate wasting and impairment of vitamin D metabolism, rickets and disproportioned short stature. Different genetic defects are known to cause HHR, but similar clinical and biochemical features were reported. Dominant-X-linked HR (XLHR) is the most frequent form, with an incidence of 1 in 20.000, although dominant and recessive autosomal forms are also described. XLHR is caused by inactivating mutations in the PHEX gene (located at Xp22.1), encoding a endopeptidase which regulates the phosphaturic secretion. Affected individuals present with a broad phenotypic spectrum, ranging from isolated hypophosphatemia up to severe symptoms of rickets. Therefore NGS studies represent an useful tool for molecular diagnosis characterization Aim: to develop a reliable NGS diagnostic tool for HHR and related disorders.
Patients and Methods: we develop a NGS panel including 13 genes related with HHR or other hypophosphatemic disorders, using Illumina TruSeq Custom Amplicon technology.
We analyzed 12 patients which have been sent to our laboratory for molecular genetic testing under suspicion of HHR based on clinical phenotype and laboratory studies but with no proven mutation in PHEX gene by Sanger sequencing or MLPA analysis or other hypophosphatemic disorder.
Results: A previously reported pathogenic variant (p.Arg153Gln) was found in SLC9A3R1 gene encoding NHERF1cotransporter, which interact with phosphate and sodium renal transporter NaPi2a in a 13 months old girl. There are only 5 reported cases with alterations in this gene and all of them were adult patients with nephrolithiasis. The patient was referred to our hospital due to hypercalcemia. She had poor weight gain and laboratory findings showed high serum calcium (16,6 mg/dl), mild serum phosphate (3.9 mg/dl), very low parathyroid hormone (PTH) (&lt; 3 ng/ml), normal 25OHvit D (40 ng/ml) levels, and elevated urinary calcium/ creatinine rate (2), and low phosphate tubular reabsorption (85%). Ultrasound showed nephrolithiasis. Since she had hypophosphatemia and renal phosphate wasting with symptomatic severe PTH independent hypercalcemia probably secondary to excessive calcitriol production with hypercalciuria, a molecular alteration of CYP24A1 or SLC34A1genes was suspected.
Conclusion: NGS allowed to report for the first time the identification of a mutation in the SLC9A3R1 gene in a pediatric patient. An early diagnosis might improve long term outcome starting the right therapy to avoid progression of nephrolithiasis and nephrocalcinosis and chronic renal failure.
MON-526 Comparison of ACR-TIRADS to American Thyroid Association Guidelines: Can We Choose Wisely Without Missing Malignancy?
Authors: Halperin Ilana Jaye , Qiang Judy 
Published: May 2020

Abstract
Thyroid ultrasound has been widely used to determine which nodules need further work up. The goal of this study was to apply the new ACR-TIRADs criteria to a retrospective data set and compare the outcomes to the ATA scoring system. Methods: In a retrospective study, ultrasonographic images of the all nodules biopsied in 2015 were reviewed by radiologists, blinded to fine needle aspiration (FNA) biopsy result, using a checklist to report the image. The checklist was prepared based on 2015 ATA guideline. The ultrasonographic characteristics of thyroid nodules were compared with the result of biopsy to determine positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity of checklist in predicting malignancy. These results were published previously. The same data was then reviewed using the ACR-TiRADS tool to assess the number of US and FNA that would been avoided and the number of non-benign cytologies that would have been avoided had these criteria guided care in 2015. Results: 419 thyroid nodules were reviewed 7.1% were malignant, 10.3% were FLUS and 78.3% were benign. Sensitivity of the ACR-TIRADs and ATA respectively was to detect non-benign nodules was 70% and 97% Specificity was 29% and 11%. Positive predictive value was 18% and 9% whereas Negative predictive value was 81% and 98%. 28% of the FNAs done in 2015 could have been avoiding if applying the TIRADs criteria, however 15 non-benign and 8 malignant cases would have been missed.Conclusion: The TIRADs approach adds value to the system by reducing many unnecessary biopsies but clinicians need to use their own judgement as some non-benign cases will be missed.
SUN-585 Associations Between UCP1(rs1800592),UCP2(rs6593366) and UCP3(rs1800849) with Fasting Glucose, Body Mass Index, and Energy Expenditure
Authors: Figueroa-Vega Nicté , Perez-Luque Elva L , Malacara Juan M 
Published: May 2020

Abstract
Background: The uncoupling proteins (UCPs) belong to the mitochondrial inner membrane anion carrier superfamily and play an important role in energy homeostasis. UCP-1 is expressed mostly in brown adipose tissue (BAT) and act in the thermogenesis and regulation of energy expenditure. UCP-2 has a role in the metabolism of fatty acids direct and indirectly path insulin secretion. UCP-3 is specific of skeletal muscle and BAT and may affects the adaptive and translocation of fatty acids. Genetic polymorphisms in these proteins have been associated with obesity, as rs1800592 (-3826 A/G) in UCP-1 gene. The rs659366 (-866GA) UCP-2 has being associated with high expression of its RNAm, decrease of obesity risk, and increase of energy expenditure. The rs1800849 (-55CT) UCP-3 has been associated with low risk of type 2 Diabetes Mellitus, but its association with body mass index is controversial. Objective: To analyze the association of the polymorphisms rs1800592 UCP-1, rs659366 UCP-2, and rs1800849 UCP-3 with BMI and resting energy expenditure (REE). Material and Methods: We included 120 subjects with BMI&gt;30kg/m2 and 100 subjects with BMI between18.5 -24.9 kg/m2, aged 20 to 50 years. Anthropometric data were recorded and the REE was measure for indirect calorimetric. Fasting glucose and lipid profile were assessed. Leptin, insulin and acylated-ghrelin were quantified by ELISA. Genomic DNA was extracted using comercial kit. Genotyping for three polymorphisms was performed by allelic discrimination using Taqman probes. Results: All the three polymorphisms of UCPs showed distribution in accordance with Hardy-Weinberg equilibrium. The weight, BMI, glucose, triglycerides, leptin, insulin, HOMA-IR, and REE levels were signitifcantly higher in obese subjects. There was a strong correlation between REE with BMI (r=0.42, p&lt;0.00001) and with insulin levels (r=0.229, p=0.001) in all group. No differences in genotypic and allelic frequencies of rs1800592 UCP-1, rs659366 UCP-2 and rs180084 UCP-3 polymorphisms between obese and lean subjects. No differences among the genotypes rs1800592 UCP-1 and rs1800849 UCP-3 with metabolic variables. In rs659366 UCP-2 polymorhism, the REE and glucose concentrations were lower in carriers of rs659366AA genotype (F=3.11, p=0.046; F=2.97, p=0.053, respectively) in whole group. In obese subjects with rs659366AA UCP-2 genotype, the REE was significantly low (F=4.15, P=0.017). Conclusion. In this work the obese subjects with rs659366AA genotype had low REE. We found low glucose concentrations in the carries of rs659366 AA genotype.
SAT-LB128 A Case of Metformin Associated Lactic Acidosis and the Importance of Medication Reconciliation in End-Stage Renal Disease
Authors: Tsai Karen , Ning Weihuang Vivian , Barnett Braden , Lin Eugene 
Published: May 2020

Abstract
Background: Metformin is commonly used in the treatment of diabetes mellitus due to its low cost, ease of administration and titration, and favorable side effect profile as it does not cause weight gain and rarely causes overt hypoglycemia. An important yet rare side effect of metformin use is metformin associated lactic acidosis (MALA) which can be seen in patients with significant renal impairment and is associated with high mortality.
Clinical Case: We present a 54-year-old man with hypertension, type 2 diabetes mellitus, and recently diagnosed end-stage renal disease (ESRD) on hemodialysis who presented with shortness of breath and syncope and found to have an elevated lactate to 40.5 mmol/L (reference range: 0.5-2 mmol/L). Notably, the patient was admitted at an outside hospital two and a half weeks prior for a new diagnosis of ESRD and initiated on hemodialysis three times a week. At the time of discharge from his prior hospitalization, he was instructed to continue his diabetes medications: metformin 1g twice a day, glipizide 10 mg twice a day, and pioglitazone 30 mg daily. The patient was admitted to the intensive care unit and found to have MALA. Nephrology was consulted and the patient clinically improved with hemodialysis. Within six hours of presentation, the patient’s clinical course rapidly improved with complete resolution of lactic acidosis and hemodynamic instability within 48 hours.
Conclusion: Although metformin is the most commonly used drug in diabetes mellitus, the side effect of metformin associated lactic acidosis is rarely seen in the inpatient setting. Patients with ESRD are at high risk for complications resulting from poor medication management. However, because metformin is primarily renally cleared, it should be discontinued in those with significant renal impairment. With increased awareness and understanding of MALA, providers can prevent MALA by appropriately stopping or dose reducing metformin in patients with chronic kidney disease. Educating patients on their medications—including their uses, side effects, and drug-drug and drug-food interactions—could help reduce the aforementioned medication-related problems. Clinicians should have a high suspicion of metformin associated lactic acidosis in any patient presenting with multi-organ failure due to its variable clinical presentation. If MALA is suspected, providers should consult nephrology so that patients can be started on hemodialysis.
SAT-LB69 Severe Disabling Musculoskeletal Pain as a Side Effect of Bisphosphonates: A Case Report and Review of Literature
Authors: Bawal Dionise Ysabelle Vellon , Gomez Maria Honolina Sero 
Published: May 2020

Abstract
We report a case of a 57-year-old woman who developed severe musculoskeletal pain after taking one dose of Alendronate 70mg for treatment of osteoporosis. The pain was so debilitating that the patient was unable to sit up, stand, or move without assistance, and any kind of movement aggravated the pain.
Key words: bisphosphonate, severe muscle pain, case report, osteoporosis
Methods
A detailed case report is presented. A review of the current literature on the side effects of bisphosphonates was made for reference.
Results
Development of severe, disabling musculoskeletal pain was noted after taking one dose of Alendronate 70 mg tablet. The pain was severe enough to hinder the patient from sitting or standing up, and any form of movement seemed to worsen the pain. Discontinuation of the drug, pain relievers and complete bed rest afforded slight relief of symptoms. Complete resolution of pain only occurred after 72 hours. Review of literature showed that muscle pain with intake of bisphosphonates occurred in a few patients, and were mostly found in case reports or case series. Other commonly associated side effects with bisphosphonate therapy were also briefly discussed.
Conclusion
The case presented emphasizes that bisphosphonate therapy, although frequently used uneventfullyn, may still produce adverse effects in a few patients. A handful may present with severe debilitating muscle pain as seen in our patient. Literature review showed that another subset of patients may react differently and present with cardiac or ocular symptoms. What must be taken from this paper is the importance of patient education regarding these possible adverse events that although infrequent, may still happen. These unpleasant adverse effects may greatly affect compliance and ultimately have a bigger impact in the fight against osteoporosis.
SUN-LB65 Circulating Micrornas Linked to Bone Metabolism Are Affected by Sequential Anti Osteoporotic Treatment in Postmenopausal Osteoporosis
Authors: Yavropoulou Maria , Makras Polyzois , Anastasilakis Athanasios , Papatheodorou Athanasios , Rauner Martina , Hofbauer Lorenz C , Tsourdi Elena 
Published: May 2020

Abstract
Depending on osteoporosis severity a long-term treatment, often in the form of a sequential regimen, may be required. The expression of microRNAs (miRs) related to bone metabolism in the serum is potentially affected by anti-osteoporotic treatment. Here, we investigated the effect of sequential treatments on microRNA expression profile in the serum.
Methods: This is an observational, open label, non-randomized clinical trial that included 37 postmenopausal women with osteoporosis who were treated with denosumab (Dmab) for 1 year. Patients had been previously treated for 2 years with either teriparatide (n=20), or zolendronate (n=6), or were treatment-naïve (n=11). We evaluated changes in the relative serum expression of selected miRs linked to bone metabolism at 3 and 12 months of Dmab treatment at each group separately.
Results: In the group of patients who were previously treated with teriparatide, the relative expressions of miR-21a-5p, miR-29a, and miR-2861 were significantly decreased at both 3 months (fold change 0.13, p&lt;0.001 for miR-21a-5p; fold change 0.68, p=0.044 for miR-29a; fold change 0.16, p&lt;.0001 for miR-2861), and 12 months (fold change 0.09, p&lt;0.001 for miR-21a-5p; fold change 0.65, p=0.044 for miR-29a; fold change 0.19, p&lt;0.001 for miR-2861) of Dmab treatment. The relative expression of miR-23a-3p was also significantly decreased (fold change 0.65, p&lt;0.001) at 12 months of Dmab treatment. The relative expression of miRs was not changed among patients previously treated with zolendronate. No change was also observed during Dmab treatment in previously treatment-naïve osteoporotic women.
Conclusions: The expression of circulatings miRs linked to bone metabolism during Dmab treatment is depended on previous treatment status. Patients previously on teriparatide treatment present alterations of the relative expression of miRs related to the expression of key osteoblastic genes such as RUNX-2 (miR-23), collagen type 1 (miR-29a) and HDAC5 gene (miR-2861) during subsequent treatment with Dmab Our data suggest that teriparatide may influence the subsequent anti-resorptive effect of Dmab on bone metabolism at post-transcriptional level.
SUN-LB83 Outpatient Radiofrequency Ablation Is a Safe and Effective Treatment Option for Benign Thyroid Nodules in North America
Authors: Aljammal Jules , Ahmad Shahzad , Hussain Iram 
Published: May 2020

Abstract
Background: Radiofrequency ablation (RFA) of thyroid nodules is a non-mainstream treatment option for benign thyroid nodules. Studies in Asia and Europe (1) have demonstrated RFA to be an effective outpatient alternative to surgery, however, these results have not been reproduced in North America. Hypothesis: RFA of symptomatic benign thyroid nodules can reduce morbidity associated with thyroidectomies, without sacrificing favorable clinical outcomes. Methodology: A retrospective review of 11 patients (all female and Caucasian) with 13 thyroid nodules treated with RFA in our practice was conducted (Nov 2018 - Oct 2019). The 9 nontoxic nodules were biopsied twice, and 4 toxic adenomas were biopsied once; all had benign cytopathology results prior to RFA. RFA was done under local anesthesia/conscious sedation, with follow-up telephone call after 2 days to assess complications (pain, voice change, hematoma/swelling, skin burns). Nodule volume in mL (length x depth x width in cm x 0.525), cosmetic score (2), and thyroid function tests (TSH and free T4) were recorded pre-procedure, and 6 - 10 weeks post procedure. The volume reduction rate (VRR) was calculated as follows: [(baseline volume - final volume)/baseline volume] x 100 (%). Results: The mean age of the patients was 45 years; 7 were euthyroid (not on thyroid hormone replacement), and 4 had hyperthyroidism. The mean volume of treated thyroid nodules decreased from 12.3 cc to 5.6 cc, with a mean VRR of ~ 54%. Thyroid nodules with volumes less than 10 cc (smaller) had a VRR of ~ 75%, whereas nodules with volumes more than 10 cc (larger) had a VRR of ~ 50%. The VRR between smaller and larger nodules (p-value: 0.11), and toxic adenomas and nontoxic thyroid nodules (p-value: 0.26), was not significantly different. 3 out of 4 patients with toxic adenomas normalized their TSH levels; 1 patient normalized free T4 levels, but TSH remained suppressed. None of the patients developed hypothyroidism. The cosmetic scores (indicating visible or palpable mass) improved by 50%. All patients had complete resolution of compressive symptoms. Minimal discomfort only reported at time of procedure. No complications were reported at the 2-day, or the 6-10-week follow-up. Conclusions: Outpatient RFA is a safe and effective treatment for benign thyroid nodules and toxic adenomas. There were no complications in our study, however, this may be limited by the small sample size and relatively short follow-up duration. Advantages of RFA include avoiding lifelong thyroid hormone replacement and complications of surgery and/or general anesthesia. We propose that RFA be considered as a first-line therapy for the treatment of benign thyroid nodules for these reasons. References: (1) Feldkamp, et al. Exp Clin Endocrinol Diabetes. 2020 Jan 7. doi: 10.1055/a-1075-2025. (2) Dobnig, et al. Thyroid. 2018 Apr;28(4):472-480. doi: 10.1089/thy.2017.0547.
SUN-LB1 Atypical Presentation Of Myocardial Infarction In A Young Patient With Polycystic Ovarian Syndrome
Authors: Mandal Shobha , Pradhan Ravi Ranjan , Avetisova Mariam , Kowalczewski Barbara Lidia Mols 
Published: May 2020

Abstract
Background: Polycystic ovarian syndrome (PCOS) is a very common and complex endocrine problem in women of childbearing age, with a prevalence of 4 to 12% globally. Myocardial infarction (MI) is the leading cause of death in women worldwide. PCOS increases the risk of MI because of chronic inflammation, endothelial dysfunction, impaired pulse wave velocity and its association with metabolic syndrome, and hormonal imbalance.
Clinical Case: A 36-year-old female with a history of PCOS, hirsutism, severe acne on spironolactone, presented to ER with a chief complaint of lower back pain for 10 days that started after lifting a 60-pounds printer. The pain was attributed to musculoskeletal type, one dose of ketorolac intramuscularly was given and she was discharged on cyclobenzaprine. The next morning, she presented with worsening back pain and new-onset vomiting. Physical exam was normal except for BMI 34.6kg/m2; vitals were stable. Lab work showed elevated troponin of 1.43 which rose to 10.6 ng/ml (normal 0.00-0.034), cholesterol 125 mg/dL (less than 200), HDL 33 mg/dL (normal 40-59), LDL 164 mg/dL (normal 100-129). Electrocardiogram showed sinus tachycardia with Q wave changes in leads III and V1 to V3. Echocardiogram showed hypokinesia of left ventricular wall in the mid to apical anterior septum. Computed tomography (CT) scan of the thoracic spine was negative for abscess or fracture. CT of abdomen and pelvis as well as CT angiography chest were negative. Urine drug screening was also negative.
As her presentation was attributed to MI, patient was started on heparin drip, aspirin, atorvastatin, and metoprolol. She underwent cardiac catheterization that showed 99% ostial left anterior descending artery stenosis; a drug-eluting stent was successfully placed. After intervention her back pain resolved. She was discharged on dual antiplatelet therapy (aspirin and Prasugrel) along with atorvastatin, metoprolol and nitroglycerin.
Conclusion: This case suggests an association of PCOS with MI. A meta-analysis has shown a two-fold increase in risk of coronary artery disease in patients with PCOS (1). Future studies are need to examine opportunities for cardiovascular disease risk reduction in PCOS patients.
Reference:1. de Groot PCM, Dekkers OM, Romijn JA, Dieben SWM, Helmerhorst FM. PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Human Reproduction Update 2011. 17 495-500.
SAT-LB91 Asparaginase Induced Severe Hypertriglyceridemia Requiring Multiple Plasmapheresis Sessions
Authors: Aftab Hassaan , Kantorovich Vitaly 
Published: May 2020

Abstract
Background: Asparaginase (ASP) is an essential component of chemotherapy for acute T-cell lymphoblastic lymphoma (T-ALL). Hypertriglyceridemia (HTG) is a known side effect of ASP therapy in children and adults (incidence up to 67 and 12.5%, respectively). The mechanism of HTG is multifactorial and involves lipoprotein lipase (LPL) suppression. Acute pancreatitis can occur in 13% of patients. There are no treatment guidelines currently available for ASP-induced HTG.
Clinical Case: A 33 year old male with history of prediabetes, HTG and T-ALL being treated with CALGB 10403 chemotherapy protocol (vincristine, methotrexate, cytarabine and pegylated-ASP) presented to the ED with acute onset abdominal pain radiating to the back with associated nausea. He denied alcohol use. Home medications included fenofibrate, metformin and atorvastatin. His TG level prior to initiating chemotherapy was 454 mg/dL (ref range &lt; 150) with an HbA1C of 6.5%. Upon presentation; TG level was 11,650 mg/dL, lipase was 563 U/L (13-60) with CT abdomen findings suggestive of mild pancreatitis. He was treated in the ICU with insulin drip at 0.05 - 0.1 unit/kg/hr with repeat TG level 6,490 mg/dL after 48 hours. He eventually required 5 serial plasmapheresis sessions over a 10 day hospital course in order to achieve a goal TG level under 500 mg/dL.
Conclusion: ASP is part of standard multiagent chemotherapy for patients with ALL however poses the risk of developing severe HTG. This side effect may be explained by multiple mechanisms including increased synthesis of very low-density lipoprotein (VLDL), decreased LPL activity as a result of an increase in the apoCIII/apoCII ratio, and increase in serum chylomicrons. Studies have shown patients who had extreme HTG had a higher frequency of ApoE3/4 phenotype, suggesting that screening for ApoE polymorphism may identify patients at high risk for developing this. HTG secondary to ASP is often asymptomatic, with severe elevations in TG levels observed around 10 days after the 3rd administration of ASP and resolving 2-3 weeks after drug discontinuation. There are no treatment guidelines for ASP-associated HTG as there is no single typical clinical course. Management for severe HTG includes insulin infusion and plasmapheresis. Insulin rapidly activates LPL leading to mean TG reduction of 50% within the first 24 hours as compared to 66% reduction after single plasmapheresis therapy. However, there is paucity of data regarding the appropriate insulin dose and whether there is a linear dose-response in TG level reduction. Further studies are required to develop standard treatment guidelines for ASP-induced HTG which may help alleviate serious complications such as acute pancreatitis.
Reference: Tozuka et al “Characterization of hypertriglyceridemia induced by L-asparaginase therapy for acute lymphoblastic leukemia and malignant lymphoma.” Annals of Clinical & Laboratory Science 1997