bluuebunny/crossref_metadata_2025_split huggingface dataset:
7524 Cholesterol ester storage disease
Authors: Ebrahimi N , Lara R Cardenas , Tariq S 
Published: October 2024

Abstract
Disclosure: N. Ebrahimi: None. R. Cardenas Lara: None. S. Tariq: None.
Introduction: Cholesterol ester storage disease (CESD) is a lysosomal disease that has deficiency of lysosomal acid lipase (LIPA or LAL). This is a rare autosomal recessive disorder of cholesterol metabolism first described by Fredrickson in 1963. As of 1989, approximately 50 cases of CESD had been reported. There's a good chance that more CESD individuals were misdiagnosed for other illnesses.A deficiency in the LIPA enzyme leads to access storage of macrolipids and specific complex carbohydrates called macropolysaccharides in the cells of various tissues. Clinical manifestations include hepatic steatosis, hepatomegaly, and fibrosis, resulting in micronodular cirrhosis of the liver. Patients are often not properly diagnosed with CESD until they are adults. Case presentation:51 years old female presented to my clinic for uncontrolled complicated type 2 diabetes. After reviewing her medical history, she noted, she and her sister have a rare condition called CESD. She was not aware of any treatment available and currently on atorvastatin 80 mg daily, evolocumab 140 mg every 14 days, and ezetimibe 10 mg daily.She follows up with hepatologist and cardiologist for annual imaging and monitoring the progression of her condition. She gets FibroScan annually. Her last scan indicated fibrosis score of 4/ FIB-4 index 1.58, meaning intermediate risk of advanced fibrosis.Lab: AST 46, ALT 52, total cholesterol 137, LDL 59, HDL 57, TG 119Recent abdominal CT showed fatty liver disease with mild hepatomegaly.Physical exam: slightly enlarged liver noted.After reviewing all labs and imaging, I started her on sebelipase alfa 1mg/kg/dose IV every 14 days, and will follow up every 6 months. Discussion: CESD is an autosomal recessive disorder that is inherited affecting male and female sexes equally.Abnormally reduced activity of acid lipase, a lysosomal enzyme that hydrolyzes triglycerides and cholesterol esters, is the hallmark of this condition. About half of the patients have hepatic fibrosis at the time of diagnosis. Hepatic cirrhosis and liver failure, along with portal hypertension and resulting esophageal varices often occur in advanced stages.When distinguishing clinical signs, such hepatomegaly, CESD dx may be suspected. A comprehensive exam, full patient history, and specialized testing that identify low LIPA enzyme activity in specific body cells and tissues can all be used to confirm a diagnosis. Most common gene variant, E8SJM, if negative sequencing of LIPA gene is done.Baseline evaluation of lipid biomarkers, echocardiogram, stress test, liver function tests, liver biopsy, kidney function biomarkers, complete blood count, coagulation tests, and sebelipase antibody testing. Genetic counseling is recommended for close family members.In 2015 FDA approved a new medication which is an enzyme replacement therapy called sebelipase alfa. It is administered by IV infusion every 2 wks.
Presentation: 6/3/2024
8532 Circulating Neprilysin in Pregnancy
Authors: Kulovic-Sissawo Azra , Weiss Elisa , Jantscher-Krenn Evelyn , Hiden Ursula 
Published: October 2024

Abstract
Disclosure: A. Kulovic-Sissawo: None. E. Weiss: None. E. Jantscher-Krenn: None. U. Hiden: None.
Background: In the complex nature of pregnancy, the female organism undergoes pivotal vascular and metabolic changes orchestrated by a tightly regulated interplay of bioactive regulatory molecules. The neutral endopeptidase, neprilysin, exists both in a membrane-bound and a soluble form (sNEP), of with the latter present in the circulatory system. Neprilysin degrades an exciting range of bioactive peptides involved in glycemic control (insulin B chain, GLP-1) and vascular tone regulation (angiotensin I and II, bradykinin, ANP, BNP), and both of them are altered in pregnancy. Objective: Due to the substrate-specificity of neprilysin and its multifaceted role we hypothesize that neprilysin may be involved in metabolic and vascular adaptions during pregnancy. However, the link between sNEP and maternal metabolism in pregnancy has not yet been investigated. Methodology: Serum sNEP concentration (n=102), longitudinally collected from metabolically healthy women (trial number NTC05496712), was measured at three visits throughout gestation (gestational age: 12.5±0.7; 20±0.8; 33±1.6 weeks) and post-partum (2±1.2 days after delivery) using commercially available sandwich ELISA. In addition, sNEP levels in pregnancy were compared to a cohort of non-pregnant women within reproductive age (n=50). Clinical and anthropometric measurements were determined and the association of sNEP and metabolic characteristics elucidated. Results: Circulating sNEP levels were non-normally distributed (median ± IQR: 2334±232624 pg/ml, n=82, gestational age 12.5±0.7 weeks) and showed high biological variability, with individual levels remaining constant over gestation. After delivery, however, sNEP concentration decreased (median± IQR: 1968±171060 pg/ml n=82, p=0.0001). sNEP showed a positive correlation with systolic blood pressure (Spearman, n=56, r=0.321, p=0.02) at early stages of pregnancy and non-fasting GLP-1 (Spearman, n=98, r=0.309, p=0.002) throughout gestation, but not with blood glucose, insulin resistance or BMI. In the non-pregnant state sNEP concentration (median±IQR: 4322±392152 pg/ml, n=38) positively correlated with body fat percentage (Pearson, n=38, r=0.405, p=0.01), fasting glucose (Pearson, n=43, r=0.301, p=0.05) and body mass index (Spearman, n=38, r=0.369, p=0.02) but did not correlate with systolic blood pressure (Pearson, n=36, r=-0.120, p=0.48). Conclusion: For the first time, the link between sNEP, metabolism and blood pressure during uncomplicated pregnancy was investigated. The decrease in post-partum circulating sNEP as compared to levels throughout pregnancy suggests a particular way of sNEP regulation and release during gestation. Our data indicate that in both, pregnant and non-pregnant state, sNEP may be involved in metabolic and cardiovascular regulation, with circulating sNEP levels showing massive individual differences.
Presentation: 6/3/2024
8571 Co existence of aldosterone excess in adrenal myelolipomas
Authors: Mishra I , Baliarsinha A 
Published: October 2024

Abstract
Disclosure: I. Mishra: None. A. Baliarsinha: None.
Co existence of aldosterone excess in adrenal myelolipomas Abstract: Adrenal myelolipomas are benign, lipomatous tumours, most of which present as adrenal incidentalomas.Co existence of cortisol excess states and aldosterone producing carcinomas is reported with adrenal myelolipomas,however isolated aldosterone excess without imaging features of adrenal malignancy is rare.We describe 3 cases presenting for evaluation of hyperaldosteronism but with imaging features consistent with myelolipomas. Case 1;58 year female presented with hypertension and spontaneous hypokalemia.On evaluation BMI was 25.3kg/m2,Gr 2 hypertensive retinopathy with systemic examination within normal limits.Biochemical evaluation revealed; Pl.Aldo(ng/dl)32.5; PRA(ng/ml/hr)0.54; ARR 60.5; SIT Pl.Aldo(ng/ml)27.8; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 16×13mm lesion baseline HU &lt; - 20 ?adrenal myelolipoma; Mx Left adrenalectomy H/P Adrenocortical hyperplasia;post op-resolution of hypokalemia with persistence of hypertension controlled with decreased number of drugs. Case 2;38 year male presented with resistant hypertension ,cerebro vascular accident,right hemiparesis and diuretic induced hypokalemia.On evaluation BMI was 31 kg/m2,Gr 1 hypertensive retinopathy with right hemiparesis.Biochemical evaluation revealed; Pl.Aldo(ng/dl)12.3; PRA(ng/ml/hr) 0.82; ARR 15; SIT Pl.Aldo(ng/ml)7.79; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 28×30mmlesion baseline HU &lt; -20? adrenal myelolipoma; Mx Left adrenalectomy H/P adrenal myelolipoma;post op-resolution of hypokalemia ,recovery of weakness and normalization of hypertension without drugs. Case 3;49 year male presented with hypertension ,incidental detection of adrenal lesion on ultrasound for pain abdomen and normokalemia.On evaluation BMI was 27 kg/m2,no significant findings on general examination with systemic examination within normal limits. Biochemical evaluation revealed; Pl.Aldo(ng/dl)12.2; PRA(ng/ml/hr) 0.58; ARR 20.2; SIT Pl.Aldo(ng/ml)11; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 22x 26 mm lesion baseline HU &lt; -20? adrenal myelolipoma; Mx drug therapy for hypertension due to refusal for surgical therapy with monitoring of blood pressure. In surgically treated adrenal myelolipomas, adrenal hormone excess is reported in 5-6% of cases, with autonomous cortisol secretion being most common .Even on the background of CT findings consistent with myelolipomas, patients fulfilling the screening and confirmatory criterias of primary hyperaldosteronism must be subjected to apt therapeutic modality.The presence of aldosterone clusters with excessive aldosterone synthase activity in these lesions could be reason for occurrence of primary hyperaldosteronism in myelolipomas.
Presentation: 6/3/2024
7496 Differences in seasonality's influence on individual lipid parameters: A time series analysis
Authors: Edo N , Sawa T , Terakawa A , Uchino T , Yamazaki H , Uno K , Uno K , Morita K , Ishikawa T , Teramoto T , Tsukamoto K 
Published: October 2024

Abstract
Disclosure: N. Edo: None. T. Sawa: None. A. Terakawa: None. T. Uchino: None. H. Yamazaki: None. K. Uno: None. K. Uno: None. K. Morita: None. T. Ishikawa: None. T. Teramoto: None. K. Tsukamoto: None.
Introduction: Many studies have reported seasonal changes in serum lipid levels. However, how much the seasonality affects the individual lipid parameters is still undetermined. Therefore, this study aimed to evaluate the differences in seasonality's influence on lipid parameters. Participants and Methods: We retrospectively collected data on TC, HDL-C, LDL-C, and TG levels measured between March 2016 and February 2021. All participants were over 18 years old and were included in this study regardless of underlying disease or treatment status. Next, we made two datasets: one with simultaneous TC, HDL-C, and TG measurements (Group A, n = 137,964) and the other with simultaneous HDL-C, LDL-C, and TG measurements (Group B, n = 119,614). Non-HDL-C and LDL-C (Friedewald: F) levels were calculated in Group A. Using the monthly median levels, we made monthly time series data for each sex. Upon adjusting for the monthly mean age, the data were decomposed into seasonal component (St), trend component, and remainder component (Rt), using seasonal and Trend decomposition using Loess method, which was performed by the "forecast::stl()" function of R software. Finally, the degree of seasonality's influence was evaluated by calculating the following parameters using the dispersions of each component: St/(St + Rt). Results: In Group A, the parameters calculated were as follows: TC; 0.78, HDL-C; 0.79, non HDL-C; 0.49, LDL-C (F); 0.63, and TG; 0.35 for male individuals, and TC; 0.76, HDL-C; 0.81, non HDL-C; 0.37, LDL-C (F); 0.51, and TG; 0.44 for female individuals. In Group B, these were as follows: HDL-C; 0.81, LDL-C; 0.28, and TG; 0.32 for male individuals, and HDL-C; 0.84, LDL-C; 0.28, and TG; 0.33 for female individuals. Discussion: Our results suggest that the effects of seasonality were more evident in TC and HDL-C levels and that they were more subtle in non-HDL-C, measured LDL-C, and TG levels. Therefore, considering in which season they are measured would be preferable when evaluating the HDL-C level. On the contrary, non-HDL-C and directly measured LDL-C levels might be able to be assessed, regardless of the season.
Presentation: 6/3/2024
5109 Evaluation of an educational intervention to primary care providers to increase screening for primary aldosteronism
Authors: Figueiredo Maria Gabriela de Faria , Wagoner Jill , Young William F , Fishbein Lauren Michelle , McDermott Michael T 
Published: October 2024

Abstract
Disclosure: M.D. Figueiredo: None. J. Wagoner: None. W.F. Young: None. L.M. Fishbein: None. M.T. McDermott: None.
Introduction: Primary aldosteronism (PA) accounts for at least 5% of hypertension cases and up to 20% of resistant hypertension. Underdiagnosis leads to delayed treatment and increases cardiovascular morbidity and mortality. Our objective was to assess the impact of an educational series for primary care providers (PCPs) on increasing screening rates for PA. Methods: Educational intervention consisted of a 5-day, 2-minute email series for 111 PCPs on PA screening, confirmation, and treatment (trained group). Following the training, EMR data were extracted for patients with PAC (plasma aldosterone concentration) or PRA (plasma renin activity), new hypertension diagnosis code, or a new MRA prescription within 1 year pre- or post-intervention and data pre- and post- intervention were compared. A proper screen included sending both PAC and PRA simultaneously. IRB approval was obtained. Results: In the pre-intervention year, 57 patients were properly screened for PA by the 111 PCPs. Post-intervention, 151 patients were screened for PA showing a 2.65-fold increase in screening with the educational intervention. Using a paired T-test across quartiles pre- and post-intervention, this increase was statistically significant (P=0.0148). We further demonstrated a sustained effect throughout the 12 months post-intervention per quartile (Q+1 n=29, Q+2 n=45, Q+3 n=33, Q+4 n=42). Of the total cohort screened (both pre- and post-intervention), 28% had a positive screen for PA (defined liberally as PAC &gt;5 ng/dL with PRA &lt;1 ng/mL/h). Discussion: The educational intervention drove an increase in PCP screening for PA in the year post-intervention and this increase was sustained across all quartiles of the year. Of the screened cohort (pre- and post-intervention), 28% screened positive for PA, and those patients were more frequently referred to specialists post-intervention. Our study has some limitations, including the relatively small sample size of PCPs educated and patients screened, and the 2020 start to the COVID-19 pandemic impact during the post-intervention period. Conclusion: Our findings advocate for continued education to reinforce PA screening criteria using an easy, not time consuming and effective educational tool. Continuous education is crucial to reinforce next steps in confirmation and treatment.
Presentation: 6/3/2024
6478 Loss of TSPO Inhibits Autophagy and Exacerbates Steatosis via Fatty Acid Uptake
Authors: Li Yuchang , Chen Liting , Sottas Chantal , Patel Nrupa D , Raul Mahima C , Garza Samuel , Papadopoulos Vassilios 
Published: October 2024

Abstract
Disclosure: Y. Li: None. L. Chen: None. C. Sottas: None. N.D. Patel: None. M.C. Raul: None. S. Garza: None. V. Papadopoulos: None.
Nonalcoholic fatty liver disease (NAFLD) is a chronic clinicopathological condition characterized by substantial lipid accumulation in hepatocytes, posing an increased risk of liver injury. Previous research suggested that the depletion of translocator protein (TSPO, 18kDa), a ubiquitously distributed high-affinity cholesterol- and drug-binding protein located in the outer mitochondrial membrane, triggers simple steatosis (SS) in hepatocytes. However, the precise role of TSPO in SS remains elusive. In this study, we investigated the impact of Tspo deletion in rats fed with an 8-week high-fat-fructose-cholesterol (GAN) diet. Feeding TSPO knockout (KO) rats with the GAN diet led to the development of insulin and glucose resistance, accompanied by elevated plasma cholesterol and hepatic triacylglycerol levels. Fatty acid synthase, responsible for de novo lipogenesis, was upregulated in the livers of these rats. Furthermore, livers from GAN diet-fed TSPO KO rats showed increased CD36 expression, a fatty acid translocase facilitating the transport of long-chain free fatty acids into cells. In vitro experiments on Huh7 cells with stably overexpressed CD36 (CD36_OE) demonstrated impaired mitochondrial membrane potential and mitochondrial function, manifested by reduced oxygen consumption rate and ATP production. Acetyl-CoA (AcCoA), a precursor for fatty acid synthesis, exhibited significant upregulation in CD36_OE compared to control in Huh7, regardless of fatty acid treatment. This pattern of elevated AcCoA was consistent with observations in the livers of TSPO KO rats fed with GAN diet. The elevated AcCoA stimulated the acetylation of the regulatory-associated protein of mTOR (Raptor), activating mTORC1 and hindering autophagy. These results were corroborated by immunoprecipitation studies conducted on liver samples from both wild-type (WT) and TSPO KO rats fed with GAN diet. Additionally, the inhibition of autophagy in response to TSPO loss in livers from rats fed with GAN diet was mediated by unc-51-like autophagy-activating kinase 1 (ULK1) phosphorylation. In summary, our study underscores that TSPO deficiency intensifies the progression of NAFLD by amplifying CD36-mediated free fatty acid uptake, compromising mitochondrial function, increasing AcCoA levels, and impairing autophagy during the initial stages of steatosis (SS).
Presentation: 6/2/2024
6490 Microalbuminuria and Steatotic Liver Disease in Patients with Type 2 Diabetes: A Retrospective Cross-Sectional Study in Mexico City
Authors: Martinez-Sanchez Froylan , Diaz-Jarquin Alejandra , Feria-Agudelo Sandra Milena , Corredor-Nassar Maria Juliana , Martinez-Perez Carolina , Soto-Montes Zeltzin , Vargas-Abonce Valerie Paola , Paz-Zarza Victor Manuel , Gonzalez-Alvarez Gibran , Tenorio-Aguirre Erika Karina , Cordova-Gallardo Jacqueline , Mendez-Sanchez Nahum 
Published: October 2024

Abstract
Disclosure: F. Martinez-Sanchez: None. A. Diaz-Jarquin: None. S. Feria-Agudelo: None. M. Corredor-Nassar: None. C. Martinez-Perez: None. Z. Soto-Montes: None. V. Vargas-Abonce: None. V. Paz-Zarza: None. G. Gonzalez-Alvarez: None. E. Tenorio-Aguirre: None. J. Cordova-Gallardo: None. N. Mendez-Sanchez: None.
Introduction: Microalbuminuria (MAU) is an independent cardiovascular risk factor in patients with type 2 diabetes. Albuminuria has been associated with increased hepatic steatosis in various population studies, with conflicting results. Although the definition of Metabolic dysfunction associated steatotic liver disease (MASLD) has been modified in recent years, the relationship between MASLD and albuminuria in patients with type 2 diabetes has not been fully yielded. Objective: To evaluate the association between MAU and hepatic steatosis in patients with type 2 diabetes. Materials and Methods: Retrospective cross-sectional observational study of 1115 patients with type 2 diabetes. The data were collected from the internal medicine outpatient clinic from 2018 to 2023. Clinical and biochemical data were also collected. Patients with ICD-10 codes for alcoholism and alcoholic hepatitis were excluded. MAU was determined by 24-hour urine collection. Hepatic steatosis was defined by a Fatty Liver Index (FLI) &gt; 60. Binary logistic regression analysis was used to determine the independent association between MAU and hepatic steatosis. Results: The mean age of the patients was 59.6 ± 14.1 years, 68.2% were women, the mean body mass index (BMI) was 28.6 ± 6.2 kg/m2, and had a mean waist circumference of 88 ± 16.6 cm. The median duration of diabetes before the first medical consultation at our institution was 7 (3-14) years. The median FLI was 61 (35 - 83), and median MAU was 9.44 (2.14 – 49.95) mg/24h; 71.7%, 20.1%, and 8.2% had MAU in &lt;30, 30-300, and &gt;300 mg/24h, respectively. Multivariate analysis showed that having 30-300 and &gt;300 mg/24h of MAU had an Odds Ratio of 4.317 (2.485 – 7.500) and 5.480 (2.306 - 13.023) for hepatic steatosis. Conclusion: Microalbuminuria was associated with increased odds for hepatic steatosis in patients with type 2 diabetes, independently of age, sex, hemoglobin A1c, duration of diabetes, glucose-lowering drugs (metformin, insulin, SGLT-2i, GLP-1, DPP-4i, thiazolidinediones, and sulfonylureas), fibrates, statins, total cholesterol, and serum creatinine. The results cannot determine whether MAU is a risk factor for hepatic steatosis or vice versa. Prospective cohort studies are required to determine if there is a risk between both entities.
Presentation: 6/2/2024
7807 Significance of Assessing QTc Interval in Chronic Hypoparathyroidism and its Clinical and Biochemical Correlates
Authors: Namjoshi P V , Saha S , Sharma V , Narang R , Mani K , Goswami R 
Published: October 2024

Abstract
Disclosure: P.V. Namjoshi: None. S. Saha: None. V. Sharma: None. R. Narang: None. K. Mani: None. R. Goswami: None.
Background: Patients with chronic hypoparathyroidism (cHypoPT) and hypocalcemia are at risk of QTc prolongation and life-threatening arrhythmias. Information on clinical and biochemical correlates of QTc in cHypoPT is limited. Design: Observational study in cHypoPT cohort, tertiary-care-center.Materials and methods: Eighty-eight nonsurgical cHypoPT patients (age 44.1±15.4 years, 45 males) were assessed for QTc interval and its possible correlates including arrhythmic symptoms (palpitations/giddiness/syncope), and serum total calcium, phosphorus, 25(OH)D, and iPTH. Results: The mean QTc was 428±34 ms and showed a significant inverse correlation with serum total calcium measured on the same day (r=-0.43, p&lt;0.001). 13.6% of cHypoPT had prolonged QTc. The mean serum total calcium (7.05±1.94 vs. 8.49±1.01 mg/dL, p=0.02) was significantly lower in patients with prolonged QTc. Patients with arrhythmic symptoms had significantly higher mean QTc (p=0.02) and tended to have lower average serum total calcium during follow-up (p=0.06). Multivariable regression showed female gender, higher current age, BMI, and low serum calcium as the significant independent determinants of QTc. For every mg/dL decrease in serum total calcium, QTc increased by 13 ms. Receiver operating characteristic (ROC) analysis revealed serum total calcium at cut-off 8.27 mg/dL discriminated prolonged QTc with area-under-curve being 0.72 [95% CI: 0.51, 0.93]. Conclusion: cHypoPT patients have an increased risk of QTc prolongation which was associated with arrhythmic symptoms, female sex, higher age, BMI, and low serum total calcium. ROC analysis indicated maintaining serum total calcium level of at least 8.27 mg/dL to minimize the risk of prolonged QTc. The study indicates the need for close monitoring of arrhythmic symptoms as well as ECG in cHypoPT patients.
Presentation: 6/1/2024