bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSAT227 Clinically Suspected Calcium Malabsorption and Secondary Hyperparathyroidism Due to Chronic Proton Pump Inhibitor Use in a Child
Authors: Asaad Neveen , Murthy Deepa Badrinath , Baby Merilyn , Shah Bina 
Published: November 2022

Abstract

Background
Proton Pump Inhibitors (PPI) are commonly in clinical practice as agents to treat multiple acid-related gastrointestinal disorders. Studies have shown that long-term PPI-based therapy may be associated with decreased bone mineral density that could be related to hypochlorhydria-associated malabsorption of calcium and gastrin-induced parathyroid hyperplasia.

Clinical Case
We report the case of a 6-year-old female born premature at 25 weeks, with global developmental delay, chronic lung disease, G-tube and tracheostomy dependent that was admitted for tracheal reconstruction surgery. She was on a PPI (lansoprazole) since the age of 4 years. She was found to have mild hypocalcemia 8.5 mg/dL (Ref 8.8-10.4 mg/dL), mild hypomagnesemia 1.5 mg/dL (Ref 1.6-2.6 mg/dL), and hyperparathyroidism 117 pg/dL (Ref 14-72 pg/dL). Her vitamin D 25 hydroxy level was 28 ng/dL (Ref&lt;19 ng/dL) and vitamin D 1,25 dihydroxy 44.8 pg/dL (Ref 19.9-79.3 pg/dL). In addition, her bone x-ray showed evidence of demineralization, with nofracture. PTH (308.6, 429.4, 253.1pg/mL) continue to rise over the next 2 months despite normal Ca/vitamin D level. We suspected the etiology of hypocalcemia and hyperPTH was related to chronic PPI use. This was also associated with markedly elevated, hypergastrinemia of 574 pg/dL (Ref &lt;100 pg/dL), PTHrp was not detectable. Due to high risk of aspiration, her pulmonologist noted that her PPI needed to be continued at the time. She was fed via G-tube and took Pediasure 1.4 L daily which contained elemental calcium of 32 mg/kg/day. Her vitamin D intake was 1000 units daily. However, we suspected that she had calcium malabosoprtion in light of hypochlorhydria and hypergastrinemia, both leading to hyperPTH.
Subsequently, she was started on oral calcium citrate 1200mg daily as the absorption of calcium citrate is non PH dependent. One month later, her PPI was discontinued as well. She responded well to therapy and calcium normalized to 9.7 mg/dl (Ref 8.8-10.4 mg/dl) after 3 months, Gastrin 85 pg/dL (Ref&lt;100 pg/dL) and PTH 90.1 pg/dL (Ref 14-72 pg/dL).

Conclusion
Bone health status of patients on long-term PPI treatment should be addressed with particular attention to calcium/vitamin D intake. The possible mechanisms of hyperPTH and bone demineralization induced by PPIs include calcium malabsorption. In addition, hypochlohydria induced hypergastrinemia can also exacerbate hyperPTH by causing parathyroid hyperplasia. Bone health and mineral status of patients on long-term PPIs should be regularly monitored.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF18 | PSAT143 Brain Determinants of Dynamic Bone Remodeling in Females
Authors: Babey Muriel , Krause William , Zhang Xiao , Argiris Jennay , Nikkanen Joni , Herber Candice , Scheller Erica , Ingraham Holly 
Published: November 2022

Abstract
Central estrogen signaling in the medial basal hypothalamus (MBH) coordinates energy expenditure, food intake, and reproduction, as well as skeletal homeostasis. Prior work from our lab found that estrogen signaling via Estrogen Receptor alpha (ERa) in the arcuate (ARC) nucleus normally restrains bone formation in female mice only. We asked if the high bone mass in the Esr1Nkx2-1Cre mouse model, which ablates ERa in the MBH, is maintained or deteriorates with chronic overnutrition, as this is known to increase bone frailty in humans. To carry out this study, Esr1Nkx2-1Cre mutant female mice were fed HFD (Research Diets, D12492, 60% fat) or chow (SCD, 5058; LabDiet, 4% fat) for 17 weeks beginning at 10 weeks of age and housed at 22C. Although neither cohort gained significant weight on HFD nor exhibited marked changes in other metabolic parameters (%fat, GTT, ITT, etc.), this dietary challenge reversed and normalized the high bone mass in mutant females. Specifically, the ratio of BV/TV in the distal femur decreased dramatically from 36% to 6%, as measured by 3D-microcomputed tomography (micro-CT); cortical bone also decreased similarly. For comparison, control females fed HFD showed a non-significant decrease in bone mass (4.9% to 3.9% BV/TV). Unexpectedly, the large drop in bone mass in Ers1Nkx2-1Cre females fed HFD was uncoupled from an increase in bone marrow adipose tissue (BMAT). In contrast, control cohorts showed a marked 9-fold increase in BMAT following HFD. Thus, the high bone mass in mutant Ers1Nkx2-1Cre females, which persists in aged and estrogen-depleted females, quickly disintegrates with a dietary challenge. Recent RNA-Seq data from microdissected ARC tissue reveals several secreted factors that are dramatically elevated in mutant females but drop 10-20-fold after HFD. Current studies are underway to ask if these candidate factors from the ARC impact bone mass or the osteogenic capacity of skeletal stem cells. Our findings are in stark contrast to the notion that dietary excess reduces bone health by increasing bone fat at the expense of osteogenesis. Instead, based on our model, we posit that dietary excess directly determines dynamic bone remodeling by acting on the brain.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:30 p.m. - 12:35 p.m.
RF30 | PSAT138 Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient with Hypophosphatasia
Authors: Khanjee Naveed , Maalouf Naim 
Published: November 2022

Abstract

Background
Hypophosphatasia (HPP) is a rare inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with concomitant HPP are limited due to concerns for a greater likelihood of atypical femoral fractures (AFF) with anti-resorptive agents such as bisphosphonates and denosumab. We present a patient with HPP and OP who was treated with the anti-sclerostin antibody romosozumab-aqqg (Romo).

Clinical Case
An 81-year-old female was referred for management of OP. Fracture history included a hip fracture around age 40, and bilateral metatarsal fractures around age 65. Her initial DXA scan at age 57 showed osteoporosis at the lumbar spine (LS, T-score: -2.8) and femoral neck (FN, T-score -3.2). Sequential osteoporosis treatment over the subsequent 20 years included several years of oral bisphosphonates, hormone replacement therapy, teriparatide for one year followed by two years of alendronate, and one denosumab injection. Despite almost 20 years of pharmacologic osteoporosis treatment, her bone mineral density (BMD) worsened. HPP was suspected on the basis of low serum alkaline phosphatase (AP) levels ranging from 25-37 U/L (ref: 35-104 U/L). The diagnosis was substantiated by an elevated plasma vitamin B6 level of 305 mcg/L (ref: 5-50 mcg/L) and confirmed by genetic testing showing a diagnostic missense mutation c.571G&gt;A in exon 6 in the ALPL gene. After diagnosing HPP, her osteoporosis was treated with an additional year of teriparatide followed by raloxifene, which she tolerated poorly.
Following two years of expectant management, during which time her BMD worsened despite calcium and vitamin D supplementation to T-scores of –4.4 at the LS, she was started on Romo. After 11 monthly injections, a follow up DXA scan showed improvements of 21%, and 10% at the LS and total hip, respectively. These changes were substantially greater than what she experienced with her first year of teriparatide therapy (+4% and +8%, respectively). Blood AP remained low on Romo (37 IU/L and 29 IU/L at 9 and 12 months post-Romo initiation). She tolerated Romo and well and experienced no fractures during treatment.

Discussion
Management of osteoporosis in patients with HPP is challenging, as bisphosphonates and denosumab are generally avoided due to concern for an increased risk of AFF. Case reports of patients with HPP have suggested good BMD response to teriparatide. To our knowledge, this is the first report of a patient with HPP and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum AP, but improved BMD significantly more than in response to teriparatide. In conclusion, Romo is a potential treatment option for OP in patients with HPP for whom limited alternatives exist. Optimal osteoporosis treatment following a 1-year course of Romo remains to be determined.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:05 p.m. - 1:11 p.m.
LBODP024 Successful Adrenal Vein Sampling Using Dexamethasone Premedication In Patients With Iodine Contrast Media Allergy
Authors: Younes Nada , Therasse Eric , Bourdeau Isabelle , Lacroix André 
Published: November 2022

Abstract

Background
Preparation of patients with iodine contrast media (ICM) allergy who require adrenal vein sampling (AVS) to establish source of aldosterone excess in confirmed primary aldosteronism (PA) is controversial. Usual premedication with high dose prednisone can interfere with cortisol determinations, possibly altering the aldosterone-to-cortisol ratios for the identification of lateralized aldosterone excess.

Objective
Evaluate the efficacy and safety of premedication with high dose dexamethasone to perform AVS in patients with ICM.

Methods
177 consecutive patients with confirmed PA who underwent bilateral simultaneous basal and post ACTH bolus AVS at our center between January 2010 and December 2020 were retrospectively analyzed for reported ICM allergy. A total of 7 patients (4%) with history of allergic reactions to ICM were premedicated with three doses of 7.5 mg dexamethasone rather than the usual 50 mg of prednisone.

Results
No breakthrough allergic reactions were reported in the 7 patients. The mean age at the time of AVS procedure was 55.1 ± 16.8 years. Patients had been hypertensive for a mean of 6.7 ± 5.9 years. The mean systolic blood pressure on the day of the procedure was 137.4 ± 4.2 mmHg and the mean diastolic blood pressure 77.1 ± 12.9 mmHg. Most patients had at least 2 anti-hypertensive medications in their drug regimen prior to AVS procedure, none being mineralocorticoid receptor antagonists. Dexamethasone suppression effect on AVS: All basal peripheral cortisol levels were suppressed, &lt; 50 nmol/L, confirming lack of meaningful cortisol co-secretion. The basal and post-ACTH selectivity index were respectively &gt;2 and &gt; 5 bilaterally in all patients, confirming adequate cannulation of both adrenal veins. Basal peripheral plasma aldosterone concentration (PAC) was also reduced by dexamethasone administration by an average of 66 ± 30% in comparison with PAC measured before AVS. Despite basal suppression, PAC increased following ACTH bolus injection with an average rise of 698.8 ± 644.5% from baseline. AVS results: Four patients had lateralized (A/C ratio &gt; 2 basally and &gt;4 post ACTH), while three had bilateral source according to AVS results. Follow up data for a mean of 58 ± 41.4 months was available for 6 patients. In the three patients who underwent unilateraladrenalectomy for lateralized source, basal and post-ACTH lateralization ratios were concordant. All 3 patients had contralateral suppression, confirmed adrenocortical adenoma at histopathology and clinical (n=3) (normal blood pressure without medication) and/or biochemical cure (n=2) (direct renin concentration &gt; 10 ng/dL) at follow up.

Conclusion
AVS using dexamethasone premedication is safe and accurate for diagnosing source of aldosterone excess in patients with PA and ICM allergy.
Presentation: No date and time listed
ODP136 A Rare Case of Necrotizing Myopathy after Statin Use
Authors: Liu Zhao , Oktaei Hooman 
Published: November 2022

Abstract

Introduction
Statin associated necrotizing autoimmune myopathy is an extremely rare side effects of stain use. The incidence is approximately 2-3/100,000 Patients treated with statins. It usually associated with significant proximal muscle weakness, strikingly elevated creatine kinase (CK) levels and persistent symptoms despitestatin discontinuation. Here, we present a case with necrotizing myopathy after statin use as a reminder to clinicians for appropriately suspicious of this phenomenon while on treatment of statins. Clinical case: A 35 year old male with a past medical history of Autism, Type 2 Diabetes Mellitus, Hyperlipidemia, and Hypertension was brought to emergency room for right leg pain. Family states he had difficulty walking for a few weeks and had a fall from couch a week ago. Initial Vitals showed HR at 134 bpm, temp 35.9, BP 157/85 mmHg, RR 19 breaths/min. Labs showed Creatinine. 3.29 mg/dL, CO2 24 mmol/L, Na 141 mmol/L, K 4.2 mmol/L, Ca 9.5 mg/dL, glucose 265 mg/dL, AST/ALT 914/919 units/L, CK&gt;14,000 units/L, WBC 9.2 thou/mcL, Hb 12.6 g/dL, TSH 9.42 mcIU/mL, Free T3 1.41 pg/mL, Free T4 0.95 mcg/dL. Urinalysis showed large blood with RBC of 1. Myoglobin&gt;8750 mcg/L. Neuro motor exam showed strength 4/5 in bilateral lower extremities. His home medications including atorvastatin 20 mg nightly for 2 years, metformin and olmesartan, which all had been held. He was treated for rhabdomyolysis with aggressive hydration and Creatinine was improving. However, CK continued trending up to 42,915 units/L on day 5 with unreleased symptoms of lower extremity weakness. Neurology was consulted. Differential diagnosis of myopathy were suspected. His CK was continue to trend up to 45,585 units/L on day 10. Decision was made to have muscle biopsy with pathology showed: necrotizing myopathy without any clear evidence of inflammation. Although some autoimmune necrotizing myopathy may not show inflammation like those seen with HMG-CR antibodies or signal recognition antigen antibodies. Autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR Ab) was above 550. Following the biopsy, he received IV Solu-medrol 1g daily×4 doses, and then PO Prednisone 80 mg daily and then tapered down to 40 mg daily. He was also promptly started on IVIG 400 mg/kg/day for 5 days and methotrexate 7.5 mg weekly. His CK started to improve, down to 5815 units/L three weeks later. No significant improvement of strength.

Conclusion
Our case demonstrates that the appropriate diagnosis of statin induced necrotizing autoimmune myopathy with muscle biopsy and HMGCR Ab. We also wanted to alert future clinicians to have an early suspicious of such rare side effect and initiate treatment as early as possible which may bring the maximum benefit for patients.
Presentation: No date and time listed
ODP137 Achilles Tendon Size and Characteristics for Diagnosis of Familial Hypercholesterolemia Among Thai Patients
Authors: Warachit Parksook Wasita , Gomutput Patrawon , Muanpetch Suwanna , Ganokgroj Poranee , Kerr Stephen , Numkarunarunrote Numphung , Khovidhunkit Weerapan 
Published: November 2022

Abstract

Background
The presence of tendon xanthomas, defined as thickening or nodularities of tendons, is subjective and remains largely undetected in patients with familial hypercholesterolemia (FH) in clinical practice. This study aimed to determine Achilles tendon thickness cutoff values associated with the highest diagnostic accuracy for identifying FH among Thai patients.

Methods
63 subjects with possible, probable or definite FH according to the Dutch Lipid Clinic Network criteria, 58 subjects with hypercholesterolemia not compatible with FH and 55 normolipidemia subjects were recruited. Achilles tendon thickness was measured on each side separately at the point of maximum thickness using Lange skinfold calipers, Slim Guide skinfold calipers, plain radiograph of lateral ankles and ultrasonography. Ultrasonographic characteristics of the tendons were also recorded. The diagnostic performance of the maximum Achilles tendon thickness (maximum value of either left or right Achilles tendon of each person) obtained by each method was determined by Receiver-Operating Characteristic curves and optimal cut-points determined by Youden's index. Spearman rank-order correlation coefficient assessed factors associated with Achilles tendon thickness.

Results
Of all subjects, the mean age was 47 (±13) years, and 45% were male. The study groups were comparable in baseline characteristics except for a higher LDL cholesterol burden, a longer duration of lipid lowering therapy and a higher percentage of subjects receiving high intensity statins and ezetimibe in the FH group. Both types of skinfold calipers demonstrated 61% accuracy for diagnosing FH. An anteroposterior (AP) diameter on plain radiographs ≥7.7 mm had an 80% accuracy with 75% sensitivity and 82% specificity, whereas ultrasonographic thickness ≥6.4 mm. showed a 76% accuracy with 46% sensitivity and 93% specificity. Tendon border irregularities, diffuse hypoechogenicity and calcification were reported in a higher percentage of patients with FH, compared with the other 2 groups. Factors showing a significant correlation with Achilles tendon thickness in the FH group were years since FH diagnosis, a higher Dutch Lipid Clinic Network score and a higher body mass index (BMI). In the overall cohort, factors showing a significant correlation were higher LDL cholesterol burden and higher BMI.

Conclusion
Achilles tendon thickness measured by calipers showed low accuracy for FH diagnosis. An AP diameter on plain radiographs demonstrated highest sensitivity, whereas ultrasonographic thickness and area of Achilles tendon showed high specificity. Tendon irregularities, diffuse hypoechogenicity and calcification might serve as supportive findings.
Presentation: No date and time listed
ODP141 Complement Activation and Homeostasis Works Primarily Through the Alternative Pathway in Polycystic Ovary Syndrome
Authors: Atkin Stephen , Butler Prof Alexandra , Sathyapalan Thozhukat 
Published: November 2022

Abstract

Introduction
It has been shown that complement factors are increased in polycystic ovary syndrome (PCOS) and that these may be affected by obesity and insulin resistance. Hypothetically, this may increase cardiometabolic risk but, paradoxically, increased clotting is not a feature of PCOS. To investigate this, proteomic analysis of the complement system was undertaken, including inhibitory proteins.

Methods
Plasma was collected from 244 women (147 with PCOS and all 3 diagnostic features and 97 controls). Somalogic proteomic analysis was undertaken for the following complement system proteins: C1q, C1r, C2, C3, C3a, iC3b, C3b, C3d, C3adesArg, C4, C4a, C4b, C5, C5a, C5b-6 complex, C8, properdin, Factor B, Factor D, Factor H, Factor I, Mannose-binding protein C (MBL), Mannan-binding lectin serine protease 1 (MASP3), Complement decay-accelerating factor (DAF) and Complement factor H-related protein 5 (CFHR5).

Results
The alternative pathway of the complement system was primarily activated in PCOS, with increased C3 (p&lt;0. 05), properdin and Factor B (p&lt;0. 01). In addition, inhibition of this pathway was also seen in PCOS, with increase in CFHR5, Factor H and Factor I (p&lt;0. 01). There were also increases in the downstream complement factors of iC3b and C3d, associated with an enhanced B cell response, and C5a, associated with inflammatory cytokine release (p&lt;0. 01).

Conclusion
This is the most comprehensive evaluation of the complement system in PCOS to date and reveals upregulation of the alternative complement system that appears to be offset by the concurrent upregulation of its inhibitors. However, any additional dysregulation of the system, such as occurs with COVID19 infection, may give rise to an increased risk for clotting in women with PCOS.
Presentation: No date and time listed
ODP155 Successful Treatment of PEG-Asparaginase Related Hypertriglyceridemia with Omega-3 Acid Ethyl Esters
Authors: Radovanovic Natasa , Crawford Andrew 
Published: November 2022

Abstract

Introduction
Young adults diagnosed with acute lymphoblastic leukemia (ALL) have been increasingly treated with a pediatric-inspired regimen including asparaginase, to improve both quality and quantity of survival. Peg-asparaginase (PEG-ASP) is a long-acting formulation of L-asparaginase (L-ASP), an enzyme that selectively kills leukemic cells by depleting plasma asparagine. Treatment with PEG-ASP provides multiple benefits including increased complete remission rates and overall survival, however, numerous toxicities can occur including fatigue, nausea, vomiting, hypersensitivity, thrombosis, pancreatitis, hepatotoxicity, and, less commonly, hypertriglyceridemia (HTG). Several treatment approaches have been reported for patients with PEG-ASP induced HTG but strong evidence supporting any specific option is lacking. Clinical case: A 24-year-old woman presented with sacral joint septic arthritis that led to the discovery of underlying B-cell acute lymphoblastic leukemia (B-ALL). Soon after diagnosis the CALGB 10403 protocol, which contains PEG-ASP, was initiated. Sixteen days after the initial PEG-ASP dose of 3,750 units it was noted her plasma serum was lipemic with TG of 669 mg/dL, which peaked the next day to 1,314 mg/dL while the patient remained asymptomatic and without signs or symptoms of pancreatitis. She was started on a brief course of insulin drip (lasting 6 hours) and a low-fat diet. Four days later fish oil (omega-3 acid ethyl esters) 2 gm twice daily was added, and two days later micronized fenofibrate 67 mg as well. She was tolerating this regimen for three days when fenofibrate had to be discontinued due to elevated liver enzymes while fish oil was continued. Triglycerides continued to successfully trend down over the course of two weeks, and after reaching a level of 111 mg/dL she was re-challenged with another dose of PEG-ASP 3,750 units. After the second dose of PEG-ASP, her TGs became elevated again but peaked at 542 mg/dL. She received a third dose of PEG-ASP 3,750 units two months later when TG remained below 200 mg/dL. A month later she received a fourth/final dose of PEG-ASP 3,750 units which led to transient elevation of TGs peaking at 437 mg/dL but returning to levels below 200 mg/dl within two months. Throughout the course of her treatment with PEG-ASP, she continued to take fish oil.

Conclusion
Multiple studies showed that the benefit to toxicity ratio of asparaginase in young adults with ALL is favorable. Our conclusion is that in patients who develop HTG, fish oil can be utilized as a treatment and continued as long as they are receiving PEG-ASP, especially in patients unable to tolerate fenofibrate. We would like to bring attention to this case with the current positive outcome given the fact there is currently limited evidence on the safety of re-challenging patients with PEG-ASP after experiencing HTG.
Presentation: No date and time listed