bluuebunny/crossref_metadata_2025_split huggingface dataset:
9173 The Use Of The Frax Tool And Its Adjustments In Women Living With Diabetes: A Cohort Study In Primary Care In Brazil
Authors: de Oliveira Fernando M , MC Leal Rafaela , Vasconcellos Comim Fabio , Orlandin Premaor Melissa 
Published: October 2024

Abstract
Disclosure: F.M. de Oliveira: None. R.M. Leal: None. F.V. Comim: None. M.O. Premaor: None.
In recent decades, an increased risk of fractures in people living with diabetes has been described. This risk appears to be independent of bone mineral density (BMD). Therefore, screening instruments for fracture risk have been proposed in this population. The FRAX® algorithm is one of them. However, the initially described FRAX® algorithm has some limitations in PVDM. Some studies suggest that minor modifications to this instrument can improve its performance. These modifications appear to work well in other countries, such as Canada. However, we do not know whether these adjustments work in the Brazilian population. The objective of our study was to evaluate the calibration and accuracy of the FRAX® algorithm with and without adjustments for women living with DM (MLDM). Methods: To this end, a cohort study was carried out that included women receiving primary care in the city of Santa Maria, Rio Grande do Sul. The risk for major and hip fractures was calculated using the FRAX® tool. The FRAX® risk was calculated:
1. Without adjustments (unadjusted FRAX®)
2. Increasing the entered age by ten years in individuals with DM (FRAX® 10 years)
3. Inserting the diagnosis of DM as rheumatoid arthritis (FRAX® AR)
Of the 1,301 women eligible to participate in the study, 1,057 were enrolled, and 854 completed the 5-year follow-up. There were no differences between the area under the ROC curve of the unadjusted calculated FRAX® score and the FRAX® 10-year or FRAX® AR for major and hip fractures. The accuracy for major fracture was 0.948 (unadjusted FRAX®), 0.947 (FRAX® 10 years) and 0.946 (FRAX® AR). Furthermore, for hip fractures, the accuracies were 0.989 (unadjusted FRAX®), 0.988 (FRAX® 10 years) and 0.988 (FRAX® AR). On the other hand, both the FRAX® 10 years and the FRAX® AR were better calibrated, presenting a lower Chi-square. The calibration for major and hip fractures was, respectively, 15.4 (FRAX® unadjusted), 14.4 (FRAX® 10 years) and 14.4 (FRAX® AR), and 0.87 (unadjusted FRAX®), 0.32 (FRAX® 10 years) and 0.69 (FRAX® AR). In conclusion, the FRAX algorithm showed good accuracy in WLDM followed in primary care. The FRAX® 10-year and FRAX® AR settings were better calibrated in this population. These data suggest that using the FRAX® tool with adjustments could help identify the risk of fractures in WLDM in primary care in Brazil.
Presentation: 6/3/2024
6785 Thrombocytopenia: A new adverse effect of Romosozumab
Authors: Dejhansathit Siroj , Akabogu Nwamaka , Stanley Brian , marium fnu , Bazuaye Efosa M , Sophia Krusniak Lara , Zubair Khan Uzma 
Published: October 2024

Abstract
Disclosure: S. Dejhansathit: None. N. Akabogu: None. B. Stanley: None. F. marium: None. E.M. Bazuaye: None. L.S. Krusniak: None. U.Z. Khan: None.
Introduction: Romosozumab, a monoclonal anti-sclerostin antibody, is a new anabolic agent approved by the US FDA in 2019 for treatment of osteoporosis. Osteocytes produce sclerostin which inhibits bone formation. Consequently, suppressing sclerostin enhances osteoblast function leading to improved bone mass and reduction in fractures. Romosozumab therapy has demonstrated efficacy in lowering vertebral and nonvertebral fractures. Despite its effectiveness, cardiovascular events are the main concern and it is contraindicated in individuals with prior history or increased risk of myocardial infarction or stroke. This case marks the first incidence of immune thrombocytopenia (ITP) associated with Romosozumab use. Case Description: A 72-year-old Caucasian woman with a past medical history of chronic kidney disease, GERD, seizure disorder, and asthma was referred to Endocrinology clinic for osteoporosis management. Osteoporosis was diagnosed in 2019 on DXA scan showing T-scores at lumbar spine (LS), femoral neck, and total hip as -3.1, -3.1, and -3.0, respectively. She was treated with Zoledronic acid injections. Workup at this visit showed elevated parathyroid level, while calcium, vitamin D, magnesium, phosphorus levels were within the normal range. Repeat DXA in February 2023 revealed a 4.8% decreased in BMD at LS. Due to severity of osteoporosis, treatment with Romosozumab monthly was initiated. After receiving the third dose of Romosozumab, she experienced epistaxis and easy bruising of her skin. Labs revealed severe thrombocytopenia (platelet count of 12,000/microL). Peripheral blood smear showed no platelet clumping or megakaryocytes. HIV and HCV testing returned negative, prompting a referral to hematology. A presumptive diagnosis of ITP was made. Treatment with prednisone was initiated. A careful history and review of medications was conducted for identification of secondary causes of thrombocytopenia. Romosozumab was the only medication added recently, leading to a suspicion that it might be the causative factor for thrombocytopenia. Consequently, Romosozumab was discontinued. Subsequent complete blood count revealed a return of the normal platelet count. Conclusion: Given the novelty of Romosozumab, limited data exist on its safety profile. This case marks the first reported incidence of thrombocytopenia associated with Romosozumab use underscoring the importance of identifying drugs as a secondary cause of thrombocytopenia. This case emphasizes the need for ongoing pharmacovigilance and monitoring when using novel therapeutic agents like Romosozumab.
Presentation: 6/3/2024
7949 Unraveling a Unique Presentation of Paget’s Disease of Bone
Authors: Puri Sadhana , Bovee Laura , Narla Radhika 
Published: October 2024

Abstract
Disclosure: S. Puri: None. L. Bovee: None. R. Narla: None.
Background: Paget's Disease of Bone (PDB) is a disorder characterized by rapid bone destruction and repair, which results in distortion of bone architecture. PDB occurs most commonly in adults over 55 and of European descent. PDB presents with both lytic and sclerotic lesions, predominantly in the axial skeleton. Serum alkaline phosphatase (ALP) levels and bone turnover markers (BTMs) are typically elevated in PDB. Clinical Case: A 53-year-old African-American woman with a history of breast cancer, PTSD, depression, and obesity (BMI 37) presented with worsening back pain over the past six months. Her pain would start at the center of her back and radiate to her left lower extremity. She endorsed rapid weight loss and night sweats and had lumbar bony tenderness on exam, prompting a spinal MRI. Spinal MRI was significant for diffuse sclerosis of the L3 vertebral body only. The radiology report provided a broad differential for this finding, including metastases, lymphoma, infection, PDB, and hemangioma. Due to progression of the patient’s back pain and concern for possible malignancy, a whole-body SPECT was completed which showed isolated tracer uptake into the L3 vertebral body extending into the pedicles and spinous process. Similar findings were noted on bone scans dating back to 2001. Per the radiology report, the presence of sclerosis with minimal expansion is most suggestive of PDB. Endocrinology was consulted for guidance on treatment and surveillance imaging for this patient. The endocrinology team discussed the case with radiology, who confirmed that the patient’s imaging findings had classic features of PDB. Bone specific ALP (B-ALP) and procollagen type 1 amino-terminal propeptide (P1NP) as bone turnover markers (BTMs) were within normal limits. A DEXA scan is pending to evaluate for concurrent osteoporosis. Clinical Lessons: PDB was favored as the most likely diagnosis primarily due to the sclerotic appearance of the patient’s vertebral lesion on imaging, radicular symptoms, and exam finding of bony point tenderness. Other diagnoses, such as metastatic disease, were considered and were thought to be unlikely given that the vertebral lesion is monostotic and stable. This case highlights the necessity of carefully evaluating radiographic findings and clinical history in the diagnosis of PDB. In this case, the patient was from a demographic group unlikely to have PDB and, unexpectedly, did not have elevated BTMs. It is important to consider PDB on the differential diagnosis in cases such as this because PDB can present in myriad ways and in a variety of patient populations.
Presentation: 6/2/2024
6928 Vitamin D excess in a patient with hypoparathyroidism after parathyroidectomy
Authors: Zavgorodneva Z , Barsegian A , Zhang F 
Published: October 2024

Abstract
Disclosure: Z. Zavgorodneva: None. A. Barsegian: None. F. Zhang: None.
Introduction. We describe a case of a patient with mild persistent hypoparathyroidism after parathyroidectomy with autotransplantation, which was indicated for ESRD-related secondary hyperparathyroidism. The patient presented with nonspecific complaints and was found to have a high Vitamin D level after long-term moderate-dose Vitamin D supplementation. Case report. A 71-year-old male with a past medical history of end-stage renal disease (ESRD) undergoing hemodialysis for the past 18 years, as well as a history of parathyroidectomy with autoimplantation of parathyroid glands in the forearm in 2010 due to severe secondary hyperparathyroidism, presented to the hospital complaining of generalized weakness and lower extremity cramps that had been ongoing for a few weeks. Further investigations did not reveal evidence of infectious processes. A review of medications indicated the absence of statins among his outpatient medications. No focal neurological deficits or objective signs of muscle weakness were identified. Laboratory findings showed no significant metabolic derangements or haematological abnormalities. Inflammatory markers and creatine phosphokinase were within normal ranges. As part of the workup for generalized subjective weakness and ESRD, Vitamin D levels were checked, revealing a result of of120 ng/mL. The patient reported taking over-the-counter 2000 IU of Vitamin D twice daily for the past six years despite having a normal level of Vitamin D checked five years prior to admission. Calcium supplements were initiated in the postoperative period and continue to be administered at a dose of 600 mg daily. Analysis of the PTH-calcium axis demonstrated persistent mild hypoparathyroidism with hypocalcemia since the time of the surgery. However, there was an observed tendency for calcium levels to improve, especially in the last six years. Vitamin D supplement was discontinued, and the patient was subsequently discharged home with the continuation of physical therapy. Discussion. Explaining the origin of the high level of Vitamin D in this patient poses a challenge. There is limited data in the literature regarding the long-term effects of vitamin D use when the initial Vitamin D levels are normal. Additionally, there are numerous abstracts suggesting significantly higher doses of Vitamin D received for up to 6 years without any evident biochemical or clinical consequences. Moreover, the typical consequences of Vitamin D toxicity, such as hypercalcemia, can not be present in patients who underwent parathyroidectomy. Therefore, it is possible to consider that the severe generalized subjective weakness may be a sign of Vitamin D toxicity itself.
Presentation: 6/1/2024
8702 Age-Sex Differences in Global Burden of Ischemic Heart Disease Attributable to High LDL in the Last 3 Decades:Global, Regional, National Variations, Age Dynamics, and Implications for Global Health
Authors: Adedara V , Maddineni K , Dekhne A , Chinthapalli M , Potluri G , Parisapogu A , Markandu K , Desai H 
Published: October 2024

Abstract
Disclosure: V. Adedara: None. K. Maddineni: None. A. Dekhne: None. M. Chinthapalli: None. G. Potluri: None. A. Parisapogu: None. K. Markandu: None. H. Desai: None.
Background: Ischemic Heart Disease (IHD) stands as the foremost cause of mortality globally, contributing to 9.6 million deaths. Elevated levels of low-density lipoprotein cholesterol (LDL-C) consistently feature among the risk factors associated with IHD. Methods: Employing the Global Burden of Disease framework, we computed mortality and DALYs linked to IHD attributable to LDL-C, stratified by age-sex, year, and covering 204 countries and territories during the period from 1990 to 2019. Non-fatal health outcomes were estimated using DISMOD MR 2.1, Bayesian meta-regression tool for epidemiological modelling. Results were expressed in absolute counts and age-standardized rates (ASR) per 100,000 person-years. Results: The total number of deaths attributed to IHD due to elevated LDL-C increased from 2.5 million (95% Uncertainty Interval: 2-3.1 million) in 1990 to 3.7 million (95% UI: 2.8-4.8 million) in 2019. Concurrently, DALYs increased from 60.4 million (95% UI: 50.4-70.7 million) in 1990 to 84.9 million (95% UI: 69.5-101.3 million) in 2019. In terms of ASR, the annual percentage change (APC) in death rates decreased by 36%, and DALY rates decreased by 32% from 1990 to 2019. Regionally, East Asia exhibited the highest increase in APC in death counts by 191%, followed by Commonwealth Low-Income countries at 164%, and Oceania at 160% during the same period. Conversely, the Commonwealth High-Income region experienced the highest decrease at 41%. Males displayed higher APC in death (48% vs. 44%) and DALYs (42% vs. 38%) compared to females over the last three decades. In terms of ASR, males observed a higher decrease compared to females. In 2019, the age group 80-84 years had the highest number of deaths at 534,079 (264,177-813,898), while DALYs were most pronounced in the 55-59 year age group, reaching 10.6 million (8.9-12.3 million). Conclusion: IHD remains a significant global health challenge, with high LDL-C levels being a crucial modifiable risk factor. Age-sex disparities in the burden of IHD are evident, driven by variations in LDL-C metabolism, hormonal changes, and lifestyle factors. Recognizing and addressing these disparities is essential for developing effective prevention and treatment strategies tailored to different populations and age groups.
Presentation: 6/2/2024
8294 Association between gene mutations and DNA methylation of CYP11B2 in aldosterone-producing adenoma
Authors: Kometani Mitsuhiro , Mizoguchi Ren , Demura Masashi , Aiga Ko , Konishi Seigo , Aono Daisuke , Karashima Shigehiro , Takeda Yoshiyu , Yoneda Takashi 
Published: October 2024

Abstract
Disclosure: M. Kometani: None. R. Mizoguchi: None. M. Demura: None. K. Aiga: None. S. Konishi: None. D. Aono: None. S. Karashima: None. Y. Takeda: None. T. Yoneda: None.
Context: Primary aldosteronism (PA) causes hypertension and cardiovascular complications. Recently, in aldosterone producing adenomas (APA), various genetic mutations have been identified. In addition, epigenetic mechanisms, such as DNA methylation, are also involved in excessive aldosterone production. Several studies have shown that aldosterone synthase (CYP11B2) is hypomethylated in APA. On the other hand, the relationship between specific genetic variants identified in APA and DNA methylation has not been fully clarified. Objective: To investigate the relationship between specific genetic mutations in APA and DNA methylation of CYP11B2. Methods: We analyzed 48 patients (female 23 cases) diagnosed with APA and treated between 2001 and 2022. First, Gene mutation analysis using next-generation sequencing was performed. KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CACNA1H, which are known mutations in PA, and PRKACA, PRKA1A, GNAS, CTNNB1, and ARMC5, which are known mutations in Cushing’s syndrome, were evaluated. Next, DNA methylation analysis of the CYP11B2 promoter using pyrosequencing were performed using APA. We targeted three CpG regions near the transcription start site of CYP11B2. Results: The respective mean values for all patients were: age 52 years, systolic blood pressure 138 mmHg, diastolic blood pressure 87 mmHg, ARR 1,326, serum potassium level 3.4 mEq/L, and tumor diameter 15 mm. Genetic mutation analysis revealed KCNJ5 gene mutations in 33 of the 48 patients. Among the other cases, mutations in the CTNNB1 gene were found in three cases, mutations in the ATP1A1 gene in two cases, mutations in the CACNA1D gene in one case, and PRKACA gene mutations in one case. The remaining seven patients had no mutations in any of the analyzed genes. When DNA methylation of the promoter region of CYP11B2 was analyzed in APAs with and without mutations in KCNJ5, we found that in all three CpG regions, DNA methylation rate was significantly reduced in APAs with mutations in KCNJ5 gene (CpG1 22% vs. 30%, CpG2 42% vs. 73%, CpG3 47% vs. 75%, respectively). Conclusions: The most common genetic mutation in APA was the KCNJ5 mutation; APA with the KCNJ5 mutation had significantly lower methylation rates than CYP11B2. This suggests that genetic mutations in APA affect DNA methylation and result in hormone overproduction.
Presentation: 6/3/2024
8418 Association of GLP-1 Receptor Agonists and SGLT-2 Inhibitors with Major Adverse Cardiovascular Events and Serious Liver Events among Patients with Type 2 Diabetes and MASLD
Authors: Kutz Alexander , Wexler Deborah J , Liu Jun , Paik Julie M , Patorno Elisabetta 
Published: October 2024

Abstract
Disclosure: A. Kutz: None. D.J. Wexler: None. J. Liu: None. J.M. Paik: None. E. Patorno: None.
Introduction and study question Little is known about the cardiovascular (CV) and hepatic effectiveness of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium–glucose cotransporter 2 inhibitors (SGLT-2i) in people with type 2 diabetes (T2D) and known metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical practice. We assessed the comparative CV and hepatic effectiveness and the safety of GLP-1 RA and SGLT-2i in people with T2D and prevalent MASLD. Methodology Using pooled data from Medicare fee-for-service (2013–2020) and a large U.S. health insurance database (2013-June 2022), we conducted two propensity-score fine stratification weighted cohort studies including adults with T2D and a diagnosis of MASLD who initiated GLP-1RA, SGLT-2i, or dipeptidyl peptidase 4 inhibitors (DPP-4i, reference). Using Cox proportional hazards models, we assessed the primary CV effectiveness composite outcome of acute myocardial infarction, ischemic stroke, hospitalization for heart failure, or all-cause mortality. The primary hepatic effectiveness outcome was a composite of serious liver events (hospitalization for ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, bleeding esophageal varices, hepatic encephalopathy, or liver transplantation). The safety outcome was a composite of severe adverse events (lower limb amputation, non-vertebral fracture, emergency admission for hypoglycemia, or hospitalization for acute kidney injury, diabetic ketoacidosis [DKA], severe genital or urinary tract infection, acute pancreatitis, or biliary event). Major results Compared with DPP-4i (n=17,084 initiators), the hazard ratio (HR) for the primary CV outcome associated with GLP-1 RA (n=13,666 initiators) was 0.67 (95% CI, 0.56 to 0.81), corresponding to an incidence rate difference (IRD) per 1,000 person-years of -21.6 (95% CI, -26.7 to -16.6). The HR for the primary hepatic outcome was 0.47 (95% CI, 0.25 to 0.90), the IRD -2.1 (95% CI -3.4 to -0.9). Similar CV benefits were observed for SGLT-2i (n=11,108) vs DPP-4i (n=16,979), with a HR for the primary CV outcome of 0.82 (95% CI 0.70–0.96) and an IRD of -11.0 (95% CI -16.2 to -5.8). For the primary hepatic outcome, the HR was 0.81 (95% CI 0.45 to 1.44) and the IRD -1.1 (95% CI -2.4 to 0.3). Severe adverse events were not more frequent with GLP-1RA or SGLT-2i compared with DPP-4i. Interpretation and conclusion Among people with T2D and MASLD, the use of GLP-1 RA or SGLT-2i was associated with fewer CV events, vs DPP-4i, while GLP-1 RA also reduced serious liver events. Compared with DPP-4i, GLP-1RA or SGLT-2i were not associated with higher safety adverse event rates.
Presentation: 6/2/2024
7246 Cardiac Paraganglioma: A Rare Entity
Authors: Javed Laraib , Jonea Lim 
Published: October 2024

Abstract
Disclosure: L. Javed: None. L. Jonea: None.
Cardiac paragangliomas are an exceptionally uncommon subset of neuroendocrine neoplasms. We present a case of a patient presenting with this condition. 70-year-old woman with pertinent past medical history of chronic veinous insufficiency complicated by recurrent abscesses of her right leg since venaseal procedure. The patient had positive IgG lambda on immunofixation that raised concerns for MGUS. Therefore, a F-18 FDG PET-CT scan was performed for further evaluation. PET-CT revealed a hypermetabolic mass in the upper inner right thigh and the right atrium (SUV 17.6) raising concern for septic thrombi. She was admitted in the hospital for initiation of antibiotic therapy. Transesophageal echocardiogram (TEE) revealed a 4.5 cm x 4.0 cm mass in the right atrioventricular (AV) groove region, extending over the root of the main pulmonary artery. Following discharge, despite completing six weeks of IV antibiotic therapy a CT scan on a subsequent clinic visit revealed the same mass as seen on TEE. CT imaging raised suspicion of neuroendocrine tumor. This led to referral to the endocrinology department. Laboratory results showed elevated normetanephrine and dopamine levels increasing likelihood of paraganglioma. Lab Results: 24 hr urine normetaneprhine :7197(N ≤ 376 mcg), 24 hr urinary dopamine :879 (N ≤400 mcg), 24 urinary metanephrine: 84 (N ≤96 mcg) & 24 hr urinary epinephrine &lt;3 (N ≤20 mcg). Her home systolic blood pressure readings varied between 120’s & 170’s. She was initiated on Prazosin 1 mg daily in addition to the existing antihypertensive medications of nebivilol, amlodipine & furosemide. Few months later, this patient successfully underwent cardiac mass resection. Histologic findings of the resected mass were consistent with paraganglioma. Post-surgery, anti-hypertensive medications were discontinued, and blood pressure normalized to systolic readings in the 90s to 120s and diastolic readings in the 60s to 80s. Repeat biochemical tests indicated a normalization of normetanephrine & dopamine levels, validating the success of the resection. This case features an extremely rare entity cardiac paraganglioma that had an atypical clinical manifestation of being asymptomatic. Timely diagnosis and appropriate management are crucial for patient outcomes. Surgical intervention, although fundamental, bears significant risks, necessitating meticulous preoperative management to mitigate potential complications. The medical approach focuses on averting perioperative complications such as hypertensive crisis, cardiac arrhythmias and myocardial infarction. This is achieved by administering alpha and beta adrenoceptor blockers for a minimum of two weeks before the scheduled surgery. Regular follow up is also essential due to the unpredictable malignant potential of these tumors.
Presentation: 6/3/2024