bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence patterns in naïve and prevalent use of infliximab and its biosimilar
Authors: Alanaeme Chibuike J. , Sarvesh Sujith , Li Cynthia Y. , Bernatsky Sasha , Curtis Jeffrey R. , Yun Huifeng
Published: November 2022

Introduction

Although short-term clinical trials have demonstrated that switching from infliximab (INF) bio-originator to its biosimilar is safe with no significant loss of efficacy, there are limited real-world data comparing their patterns of use and adherence.

Methods

Using 2015–2018 IBM Marketscan data, we established 4 cohorts of patients with at least one administration or pharmacy claim for INF bio-originator or biosimilar in 2017, including INF naïve biosimilar users, INF prevalent biosimilar users, INF naïve bio-originator users, and INF prevalent bio-originator users, defined according to their prior use of INF from 2015 to their first INF administration in 2017. The proportion of days covered (PDC) was calculated for patients with at least 6, 12, or 18 months of follow-up time. Factors associated with optimal adherence (PDC > 80%) were evaluated using log-binomial models.

Results

We identified 96 INF naïve biosimilar users, 223 INF prevalent biosimilar users, 2,149 INF naïve bio-originator users, and 10,970 INF prevalent bio-originator users. At the end of 18 months of follow-up, 64% of INF prevalent bio-originators, 48% of INF naïve biosimilars, 41% of INF naïve bio-originators, and 36% of INF prevalent biosimilars had optimal adherence. Depression, previous hospitalization, and greater use of prior biologics were negatively associated with adherence, whereas IBD diagnoses (referent to RA) and age 55–64 (referent to < 35) were positively associated with high adherence.

Conclusion

INF prevalent users had higher adherence in our analyses than INF naïve users. However, further studies with larger sample size are needed to evaluate INF biosimilar users’ adherence.
NDFuzz: a non-intrusive coverage-guided fuzzing framework for virtualized network devices
Authors: Zhang Yu , Zhong Nanyu , You Wei , Zou Yanyan , Jian Kunpeng , Xu Jiahuan , Sun Jian , Liu Baoxu , Huo Wei
Published: November 2022

Network function virtualization provides programmable in-network middlewares by leveraging virtualization technologies and commodity hardware and has gained popularity among all mainstream network device manufacturers. Yet it is challenging to apply coverage-guided fuzzing, one of the state-of-the-art vulnerability discovery approaches, to those virtualized network devices, due to inevitable integrity protection adopted by those devices. In this paper, we propose a coverage-guided fuzzing framework NDFuzz for virtualized network devices with a novel integrity protection bypassing method, which is able to distinguish processes of virtualized network devices from hypervisors with a carefully designed non-intrusive page global directory inference technique. We implement NDFuzz atop of two black-box fuzzers and evaluate NDFuzz with three representative network protocols, SNMP , DHCP and NTP , on nine popular virtualized network devices. NDFuzz obtains an average 36% coverage improvement in comparison with its black-box counterparts. NDFuzz discovers 2 0-Day vulnerabilities and 1 1-Day vulnerability with coverage guidance while the black-box fuzzer can find only one of them. All discovered vulnerabilities are confirmed by corresponding vendors.
Impact of diastolic dysfunction in patients with preserved ejection fraction undergoing permanent cardiac pacemaker placement
Authors: Jeong Hyung Ki , Kim Hyeon Wook , Kim Sung Soo , Kim Hyun Kuk , Ki Young Jae , Choi Dong Hyun , Park Keun Ho , Lee Ki Hong , Yoon Namsik , Park Hyung Wook , Cho Jeong Gwan
Published: November 2022

Background

Chronic right-ventricular (RV) pacing can exacerbate heart failure in patients with a low ejection fraction (EF). There is little information on the effects of diastolic dysfunction (DD) in patients with preserved EF undergoing permanent pacemaker (PPM) placement. We aimed to investigate the clinical outcomes in these patients.

Methods

This multicenter, retrospective analysis of PPM use in Chonnam, South Korea, included all patients with preserved EF undergoing transvenous PPM implantation for atrioventricular blockage from 2017 to 2019. Patients were divided into two groups according to DD, which were assessed by including mitral flow velocities (E′ velocity, E/E′ ratio), peak velocity of the tricuspid regurgitant, and left atrial maximum volume index. Composite outcomes were defined as (1) cardiovascular death, and (2) hospitalization by heart failure during the follow-up period.

Results

One hundred sixty-seven patients (66 men; overall mean age, 75.3 ± 11.9 years) were divided into two groups: 125 normal versus 42 DD. Compared with normal subjects, the DD group included older patients (mean age, 79.1 ± 9.9 vs. 74.0 ± 12.3; p = 0.016), and had longer paced QTc interval (pQTc, 168.5 ± 20.1 vs. 159.1 ± 16.3 ms; p < 0.001). Fifteen patients were hospitalized and two died. In a Cox proportional regression analysis, DD (hazard ratio [HR], 7.343; 95% confidence interval [CI], 2.035–26.494; p = 0.002) and pQRSd (HR, 1.046; 95% CI, 1.004–1.091; p = 0.033) were independent predictors of composite outcomes.

Conclusion

In patients with DD, RV pacing raised the risk of pacing-induced heart failure despite preserved left-ventricular function. Thus, patients with DD should be monitored intensively.
Improvement of the shelf life of grey mullet (Mugil cephalus) fish steaks using edible coatings containing chitosan, nanochitosan, and clove oil during refrigerated storage
Authors: Aref Samar , Habiba Ramadan , Morsy Noha , Abdel-Daim Mohamed , Zayet Fatma
Published: November 2022

The effects of edible coatings made of chitosan, or chitosan nanoparticles, and their combinations with clove oil on the physical, chemical, microbiological, and sensory properties of grey mullet (Mugil cephalus) steaks during refrigerated storage (4 °C) for 24 days were evaluated. The data indicated that metrics for all of these characteristics were improved significantly (P ≤ 0.05) in coated fish steak samples compared to the control sample. The coated steaks texture values were higher than those of control sample through storage time with nanochitosan coating containing clove oil having best value 2.51 kg/cm2among tested samples at the end of storage period. However, pH values of coated samples were lower, a good indicator, than corresponding one of the control (6.46) with nanochitosan coatings with or without clove oil showed low mean values (6.11–6.13). Similar trend regarding chemical indices, i.e. total volatile basic-nitrogen, trimethylamine, peroxide, and thiobarbituric acid reactive substances values for samples coated with nanochitosan with or without clove oil giving better lower values than control or other treatments. Also, the coating delayed microbial (aerobic plate count, psychrotrophic bacteria, yeasts and molds, and total coliform bacteria) growth during the refrigeration storage period, and coated samples produced better results compared to the control sample. Sensory evaluations showed that the treatment enhanced the scores of fish steak samples compared to the control. The results showed that a nanochitosan coating with clove oil was the best treatment prolonged the shelf life of mullet steaks and efficiently maintained the quality attributes to an acceptable level during refrigerated storage for 24 days. Thus, these findings can be bases for producer to provide consumers with fresh fish steaks with good shelf life at refrigerated temperature for up to 24 days.

Graphical Abstract
The use of neutrophil CD64 and monocyte HLA-DR sepsis index in the diagnosis of neonatal sepsis
Authors: Alanwary Sherif , Bakir Rana , El Hawary Rabab , Hashim Mohamed
Published: November 2022

Background

Neonatal septicemia remains one of the main causes of neonatal morbidity and mortality. However, there are challenges hindering the early diagnosis.

Results

nCD64 percent and MFI were not of statistical significance between the confirmed sepsis, clinical sepsis, and control groups (p = 0.453 and 0.149, respectively); meanwhile, the mHLA-DR percent and MFI were both of statistical significance (p = 0.001, 0.0001, respectively) with lower values in the proven sepsis group. Calculating the sepsis index, its value was 74.1% ± 45 SD in the control, 105.5% ± 73 SD probable sepsis group, and 180.6% ± 143 SD in the proven sepsis group; this was of a high statistical significance (p = 0.0001).

Conclusion

HLA-DR expression on monocytes and nCD64/mHLA-DR sepsis index are reliable indices for the early diagnosis of neonatal sepsis. The sepsis index could be feasibly analyzed by automated flow cytometry even in developing countries. In the future, these markers should be widely assessed as their results are rapid, reliable, and of low cost.
Scalar optical hopfions
Authors: Wan Chenhao , Shen Yijie , Chong Andy , Zhan Qiwen
Published: November 2022

Hopfions are three-dimensional (3D) topological states discovered in field theory, magnetics, and hydrodynamics that resemble particle-like objects in physical space. Hopfions inherit the topological features of the Hopf fibration, a homotopic mapping from unit sphere in 4D space to unit sphere in 3D space. Here we design and demonstrate dynamic scalar optical hopfions in the shape of a toroidal vortex and expressed as an approximate solution to Maxwell’s equations. Equiphase lines correspond to disjoint and interlinked loops forming complete ring tori in 3D space. The Hopf invariant, product of two winding numbers, is determined by the topological charge of the poloidal spatiotemporal vortices and toroidal spatial vortices in toroidal coordinates. Optical hopfions provide a photonic testbed for studying topological states and may be utilized as high-dimensional information carriers.
Direct comparison of echocardiography speckle tracking and cardiac magnetic resonance feature tracking for quantification of right ventricular strain: a prospective intermodality study in functional mitral regurgitation
Authors: Johannesen Justin , Fukuda Rena , Zhang David T. , Tak Katherine , Meier Rachel , Agoglia Hannah , Horn Evelyn , Devereux Richard B. , Weinsaft Jonathan W. , Kim Jiwon
Published: November 2022

Background

Functional mitral regurgitation (FMR) is a known risk factor for right ventricular dysfunction (RVDYS). RV global longitudinal strain (GLS) is an emerging index of RV function; however, the magnitude of agreement between RV GLS by echocardiography (echo) and cardiac magnetic resonance (CMR) and the relative utility of each modality for both the diagnosis of RVDYS and prognostication of all-cause mortality and heart failure hospitalization remain unknown.

Results

32% of patients had RVDYS (EF < 50%) on CMR, among whom there was more advanced NYHA class and lower LV and RV ejection fraction (all p < 0.05). RV GLS was impaired in patients with RVDYS whether quantified via STE or FT-CMR, with strong correlation between modalities (r = 0.81). Both STE and FT-CMR derived GLS yielded excellent detection of RVDYS (AUC 0.94 for both), paralleling similar performance for free wall strain by both modalities (FT-CMR AUC 0.94, STE AUC 0.92) with lower accuracy demonstrated by STE derived septal strain (STE AUC 0.78 and FT-CMR AUC 0.92). RV S’ and TAPSE showed lower diagnostic accuracy (RV S’ AUC 0.77 and TAPSE AUC 0.81). During median follow up of 51 months (IQR 42, 60 months), all-cause mortality or HF hospitalization occurred in 25% (n = 25). Both STE and FT-CMR derived RV GLS stratified risk for adverse prognosis (STE p = 0.007, FT-CMR p = 0.005) whereas conventional RV indices, TAPSE and RV S’, did not (TAPSE p = 0.30, S’ p = 0.69).

Conclusion

RV GLS is a robust marker of RVDYS irrespective of modality which provides incremental diagnostic value and improves risk stratification for event free survival beyond conventional RV indices.
Addressing Racism in Human Genetics and Genomics Education
Authors: Gouvea Julia Svoboda
Published: November 2022

This installment of Current Insights reviews recent work addressing racism in human genetics and genomics education.
ODP082 Bone mass and body composition analysis in transgender women: a 1 year follow up.
Authors: Oliveira Otavio D , dos Santos Livia Marcela , de Oliveira Otãvio Lima , Orozco Bruno Marcos Mazoca , Haddad João Magliari , de Amori Alessandra Toledo , de Macedo Luciana Pereira
Published: November 2022

Introduction

Sex steroid hormones play a key role in bone health, however medical therapies for gender dysphoria lead to hormonal changes.

Purpose

Understanding the changes in bone mass and body composition is extremely important, because this treatment will be carried out over a long period of time.

Methods

In a prospective study, we included 19 trans women (male-to-female trans persons) before and after 1 year of therapy with estrogen and cyproterone acetate. Bone densitometry model Hologic-Discovery performed at baseline and after 6, 12 months of therapy. All participants signed the TCLE, project approved by CEP-CAAE: 36823220.6. 0000. 0062.

Results

Analysis of 19 transgender women with a mean age of 25 years +/- 10 years. LS-BMD (lumbar spine) at initial time (0m) 1,070±0,155g/cm2 and after 6 months (6m) 0,995±0,092g/cm2 and 12 months (12m) after 1,020±0,096 g/cm2, p=0,04; FN-BMD (Femur Neck) 0m= 1. 047±0.205g/cm2; 6m= 0.917±0.127g/cm2 and 12m= 0.909±0.120 g/cm2; p=0. 01. TH-BMD (Total Hip) 0m= 1.100±0.162 g/cm2; and 6m= 1. 021±0. 099g/cm2; 12m= 1. 015±0.119g/cm2; p=0. 02. About body composition: the percentage of body fat: 0m= 30.2±8. 0%, 6m= 31.3±7.9%; 12m= 33.2±10.2%; p=0.10; android/gynecoid ratio: 1. 00±0.26, 6m= 0.95±0.22; 12m= 1. 00±0.39; p=0,76, VAT mass (cm3) 411.8±252.1, 6m= 357.6±145.3, 12m= 395.5±167.7 p= 0,67 and Lean/Height2 (kg/m2) 0m= 17. 03±2.98, 6m= 15.94±1.8, 12m= 16.74±2.10; p=0.46 and Appen. Lean/Height2 (kg/m2) 7.89±1.67, 6m= 7.42±1.10 and 12m= 7.52±1. 01; p=0.90 Conclusion: In 1 year of hormone therapy with estrogen and cyproterone acetate, we found decrease in bone mass in the analyzed sites and no change in body fat and lean mass.

Presentation: No date and time listed
ODP091 Giant Parathyroid Adenoma Presenting with Pseudoclubbing - A Case Report
Authors: Deb Prasun , Devarasetty Madhu , Vulpala Alekya , Nalla Smitha
Published: November 2022

Giant parathyroid adenoma is a rare type of parathyroid adenoma defined as weighing >3.5 grams. Although it presents with primary hyperparathyroidism,the clinical and laboratory findings are more profound. Bone changes are common in long standing hyperparathyroidism but presentation with clubbing is rare. Here,we report a case of 60 year male with history of finger deformities and swelling in neck,who on evaluation had hypercalcemia with high PTH levels. He underwent parathyroidectomy for the gaint parathyroid adenoma but had eventful postoperative period with prolonged hypocalcemia. This emphasizes the importance of timely management of hyperparathyroidism to prevent untoward consequences.

Presentation: No date and time listed
ODP098 Hyperparathyroidism Caused by Two Large Water Clear Cell Adenomas
Authors: Ali Rafal , Miller Eli , Al-Sudani Hussein , Kuo Lindsay
Published: November 2022

Background

In ambulatory settings, primary hyperparathyroidism is the most prevalent cause of hypercalcemia. Approximately 85% of primary hyperparathyroidism cases are caused by a solitary parathyroid adenoma; other causes include diffuse parathyroid hyperplasia, multiple parathyroid adenomas, and parathyroid cancer. Chief cell adenomas are the most prevalent; adenomas can also consist of oxyphil cell adenomas, lipoadenomas, or mixed cell adenomas. Water clear cell adenoma (WCCA) is a rare tumor formed of large clear cells with foamy pink cytoplasm. Fewer than 30 cases have been recorded in the literature.

Case

A 52-year-old male with polyuria and polydipsia, diagnosed with hypercalcemia was referred to an endocrinologist. His calcium was 10.9 mg/dl, corresponding parathyroid hormone (PTH) 74 pg/ml, 24-hour urine calcium 818 mg/24hr, vitamin D 25–hydroxy 24.2 ng/ml. He was referred to an endocrine surgeon. A 4-dimensional CT scan revealed soft tissue masses posterior to the thyroid and in the tracheoesophageal groove, consistent with potential parathyroid masses. In the operating room, baseline intraoperative PTH (ioPTH) was 371 pg/ml. A large left superior gland was removed from its normal position, and the ioPTH dropped to 104 pg/ml at 10 minutes post-resection, followed by a rise to 525 pg/ml. A large descended (ectopic) right superior gland was then identified and resected, and the ioPTH decreased to 72, 44, and 57 pg/ml at 10, 15 and 20 minutes post-resection. The remaining parathyroid glands were not identified due to adipose tissue in the neck and likely gland suppression in the setting of high PTH. The pathology report of the two excised glands (left superior 3.2×1.7×0.5cm and 3.703g, right superior 3.4×1.3×0.4cm and 1.86g) demonstrated water clear cell tissue. Post-operatively, patient's polyuria and polydipsia resolved. Labs collected 3 months after surgery demonstrated normalization of the calcium and PTH. The patient was advised to continue follow up every six months.

Conclusion

Water clear cell parathyroid adenomas are extremely rare. Water clear-cell lesions are considered indolent because excised adenomas are markedly larger than conventional adenomas and grow to a considerable size before becoming biochemically active and diagnosed. Clinical presentation of water clear cell parathyroid lesion is like other causes of primary hyperparathyroidism. The only way to diagnose is via histopathological examination. In rare cases, clear cell renal carcinoma can metastasize to the parathyroid gland causing a similar presentation. Additionally, the rate of hypercalcemia recurrence is higher in WCCA as compared to chief cell adenoma. Therefore, closer follow up of these patients is recommended. Reporting additional cases will aid in our understanding of this uncommon entity, elucidating possible causes/associations, natural history, typical appearances, and post-treatment prognosis.

Presentation: No date and time listed
ODP099 Hyperparathyroidism Causing life Threatening Hypercalcaemia in Pregnancy
Authors: Lee Jessica , Casey Edel , Otigbah Miss Chineze , Tompsett Miss Kathryn , Pittathankal Mr Antony , Sirkova Dr Aneliya , Stojanovic Dr Nemanja
Published: November 2022

31 year old woman (G2P0) 14 weeks pregnant was admitted for investigation of acute renal failure. Her creatinine was 171umol/L (normal: 45-84umol/L). Prior to her admission, patient was under investigation for a small for gestational age (SGA) baby, and had amniocentesis for suspected triplody. However, the result was normal. On admission, the patient gave a history of severe nausea and vomiting that started at 6 weeks gestation. There was also a history of constipation, lethargy and weakness. Admission blood tests showed a severe primary hyperparathyroidisim with corrected calcium level of 4.1mmol/L (normal: 2.2-2.6mmol/L), PTH=36.9 (1.6-6.9pmol/L), and thyrotoxicosis (TSH<0. 01, FT4=32.2 (12-22pmol/L). Her 24hour Urinary calcium was raised at 19.1mmol (normal: 2.5-7.5mmol/24hours) and 25 OH Vitamin D3 was 64nmol/L (Vitamin D >50 considered replete). On examination, there was a palpable nodule in the region of the left thyroid lobe. The patient was treated with 6 hourly IV fluids and carbimazole 20mg OD. Ultrasound of the neck showed a heterogenous vascularised lesion along the inferior aspect of the left thyroid lobe, 21×22×26mm in size. The lesion was thought to be a large atypical parathyroid adenoma (APA), although a parathyroid carcinoma could not be ruled out on ultrasound. Meanwhile, the patient remained hypercalcaemic with corrected calcium of 3.2mmol/L, despite aggressive IV fluids and cinacalcet 60mg BD. Her renal function improved, creatinine=110umol/L. The patient was also noted to be hypertensive, with BP ranging between 150/80 to 160/110mmHg. She was still having GI symptoms, namely retching and vomiting. In light of biochemical and clinical findings, parathyroidectomy was done in the second trimester of pregnancy. The surgery was uneventful. Cinacalcet was stopped and Ad Calcium was normal within 48hours of surgery. Ad cal=2.58, PTH low at 0.7. Patient was discharged after parathyroidectomy. The histology report was in keeping with atypical parathyroid adenoma (APA). Ultimately, our patient had a spontaneous vertex delivery of a male infant at 35+2. The baby was SGA and spent time in SCBU with fits and hypocalcaemia (Ad Cal=1.8). Baby was seen by neonatologist post discharge, and has normal development at the time of writing.

Presentation: No date and time listed
ODP102 Indicators for the effects of calcimimetics on hypercalcemia in the elderly patients with primary hyperparathyroidism.
Authors: Yamamoto Koichro , Nakano Yasuhiro , Tokumasu Kazuki , Honda Hiroyuki , Hasegawa Kou , Obika Mikako , Hanayama Yoshihisa , Otsuka Fumio
Published: November 2022

Primary hyperparathyroidism (PHPT) is the most common disorder causing hypercalcemia, in which parathyroid hormone (PTH) is excessively secreted from a parathyroid tumor. PHPT occurs mainly in elderly women, and patient with PHPT present symptoms including nephrolithiasis, bone fracture, and cognitive impairment or can be asymptomatic. Excessive secretion of PTH leads to elevated serum levels of alkaline phosphatase as well as calcium and decreased serum inorganic phosphate level. Parathyroid surgery is the only established treatment, and the treatment reduces elevated serum levels of calcium and PTH, increases bone mineral density, reduces the occurrence of bone fractures, and decreases the risk of renal stones. However, some PHPT patients, especially elderly patients, refuse to undergo surgical therapy for various reasons including perceived risk. Calcimimetic treatment, including cinacalcet and evocalcet administration, has also been reported to be effective for reducing serum calcium level in patients with PHPT. However, the relationship between the efficacy of calcimimetic treatment for PHPT and patient characteristics related to the effectiveness of calcimimetics remains to be elucidated. To investigate the relevance of clinical parameters to the effectiveness of calcimimetics for PHPT, we retrospectively analyzed patients with PHPT who received calcimimetic treatment in our department. We included nine patients including 8 females (88.9%) and one male (11.1%) in the study. The median age of the patients was 81 years (interquartile range (IQR): 61-86 years). Laboratory tests before calcimimetic treatment revealed that median level of serum corrected calcium (cCa) was high (11.1 (IQR: 10.5-12.7) mg/dL), serum inorganic phosphate was low (2.3 (2.3-2.4) mg/dL), and plasma intact PTH was high (251. 0 (198.3-498.5) pg/mL). The fractional excretion of calcium was higher than 1% (1.3% (1.12-1.48%)), %tubular reabsorption of phosphate was low (79.9% (77.1-83.9%)), nephrogenous cyclic adenosine monophosphate (cAMP) was high (3.4 (2.4-4. 0) nmoL/dL GF), and urinary cAMP was normal (4.3 (4. 0-5.3) μmoL/day). Median reduction rate of serum cCa level due to calcimimetic treatment was 5.8% (0-13.4%) at the first follow-up (median treatment duration: 22 (20-29) days). Notably, reduction rate of serum cCa level had significant correlations with age (R=0.95), dual energy X-ray absorptiometry % young adult mean (DEXA %YAM) in the femoral neck (R=-0.92), and urinary cAMP level (R=-0.85). Thus, the present study suggested that elevated serum cCa levels may be reduced by treatment with calcimimetics more effectively in PHPT patients of relatively advanced age, patients with low DEXA %YAM, and patients with low urinary cAMP.

Presentation: No date and time listed
PSAT157 Efficacy of Bisphosphanate Treatment in Pediatric Patients with Osteoporosis Due to Immobilization
Authors: Lee Myeongseob
Published: November 2022

Introduction

Osteoporosis is medical condition commonly associated with immobilization in children, which can lead to a vicious cycle of disability, worsening osteoporosis, and recurrent fractures. Currently, bisphosphonates are widely used as a standard therapy in children with osteoporosis, but there are limited data on efficacy according to its dosage and duration. We aimed to evaluate efficacy of bisphosphonate treatment according to the dosage and duration in pediatric patients with osteoporosis due to immobilization.METHOD: We reviewed medical records of pediatric patients who were diagnosed with osteoporosis due to immobilization rated as Gross Motor Function Classification System (GMFCS) grade V, and who received bisphosphonate therapy with regular check-up for at least 1 year. The dosage and duration of the treatment, biochemical laboratory measurements, data of bone densitometry, and the occurrence of side effects were collected.

Results

Subjects were 21 children. The average duration of bisphosphonate treatment was 2.0 ± 0.9 years, and mean cumulative dose per body weight of bisphosphonate was 7.7 ± 2.5 (mg/kg/year). After the treatment, mean lumbar spine bone mineral contents (BMC) significantly increased from 14.20 ± 8.58 (g) to 19.38 ± 9.89 (g) (p<0.05), lumbar spine bone mineral density (BMD) significantly increased from 0.40 ± 0.14 (g/cm2) to 0.49 ± 0.14 (g/cm2) (p<0.05), and height-adjusted lumbar spine BMD Z-score also showed improvement from -2.66 ± 1.66 to -1.66 ± 1.38 with statistical significance (p<0.05). The cumulative dose and the duration of treatment were not related to its efficacy, but increasing average dose per body weight in each cycle (mg/kg/cycle) showed significant effects on increasing change in height-adjusted lumbar spine BMD z-score (β = 1.065, p <0.05).

Discussion

BMC, BMD, and height-adjusted BMD z-score significantly increased after bisphosphonate treatment in pediatric patient with osteoporosis due to immobilization. Independent of cumulative dosage and duration, the efficacy of bisphosphonate treatment increased significantly as average dose per body weight in each cycle increased. Further studies with sufficient number of subjects and long term follow-up observation are needed.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT185 Pseudohypoparathyroidism Type 1B: A Medication Compliance Challenge
Authors: Barreiro Sacco Susana , Echegoyen Francisco Barrera , Lagari-Libhaber Violet
Published: November 2022

Introduction

Pseudohypoparathyroidism (PHP) encompasses five metabolic disorders characterized by target organ PTH resistance. The focus of this paper is PHP Type 1B (PHP1B), a disease that typically presents in children with symptomatic hypocalcemia. Only 15-20% of cases are genetic, making our case of Familial PHP1B even rarer.

Case Presentation

A 23-year-old African-American female with hypothyroidism and PHP1B diagnosed in 2005 presented to the emergency department with symptomatic hypocalcemia. As a child, she was evaluated for progressive femur, tibia, radius, and ulna bowing in the setting of short stature without phenotypic features of Albright's Hereditary Osteodystrophy. Her biochemical profile was consistent with pseudohypoparathyroidism and imaging showed costochondral junction enlargement. Genetic testing revealed STX mutation confirming PHP1B diagnosis. Extensive studies of her family revealed several affected members, including one of her two children.Patient has history of multiple hospitalizations for symptomatic hypocalcemia. During this admission, her laboratories demonstrated: calcium 4.4 mg/dL (8.6-10.3 mg/dL), phosphorus 7.3 mg/dL (2.5-4.5 mg/dL), PTH 574 pg/mL (16-65 pg/mL), 1,25-dihyroxyvitamin D < 8 ng/mL (18-78 ng/mL), and 25-hydroxyvitamin D 7.6 ng/mL (30-100 ng/mL).She has an extensive history of non-compliance with medications and endocrinology appointments. During the last visit, she complained of ostealgia, particularly in long bones. While discussing the importance of maintaining adequate calcium levels, the patient expressed feeling overwhelmed by her regimen (calcitriol 1 mcg QAM and 0.5 mcg QHS, calcium carbonate 1,200 mg TID). After a lengthy conversation regarding the need for long-term medical therapy, she became increasingly distraught.

Conclusion

When normocalcemia is achieved with high doses of calcium and calcitriol, patients with PHP1B have an average life expectancy. Given that patients are typically diagnosed in childhood, taking several medications multiple times a day can be challenging and lead to poor compliance. When this occurs, PHP1B becomes a life-altering disease with a significant decrease in quality of life.In 2018 Wierenga et al. reported that being emotionally overwhelmed by chronic disease prevents a patient from appropriately caring for themselves. Their research shows that older males with higher levels of education have better emotional regulation than young females with low educational levels. Providing patients at high risk of psychological stress with a multidisciplinary team including cognitive-behavioral therapists can improve their quality of life and compliance while decreasing the healthcare costs associated with poorly controlled chronic diseases.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT197 Treatment of Paget's Disease of the Skull With Denosumab: A Case Report
Authors: Torfah Maisoon , Shams Elham , Correia Marcelo
Published: November 2022

Background

Paget's disease of bone (PDB) is a common skeletal disorder characterized by increased osteoclastic activity and bone resorption followed by increased osteoblastic bone formation leading to an abnormality in modeling and remodeling of bone. Bisphosphonates are the most common treatments for PDB, with zoledronic acid being the most effective medication, but treatment would be difficult if bisphosphonates are contraindicated.

Clinical case: We report a case of PDB of the skull in a 75-year-old woman presenting with a persistent headache that was successfully treated with denosumab. The patient had been complaining of severe headaches since December 2020. Her skull x-ray and laboratory results [calcium 8.2 mg/dL (range: 8.5-10.5 mg/dL), albumin 4 g/dL (range: 3.4- 4.8 g/dL), alkaline phosphatase 132 U/L (range: 35-104 U/L)] were consistent with PDB. Brain MRI and bone scintigraphy also showed skull changes consistent with PDB. Importantly, a DXA scan from July 2020 showed osteopenia, and her primary care provider treated it with denosumab in the first week of December 2020. At the time of PDB diagnosis in January 2021, zoledronic acid could not be administered because of mild hypocalcemia that was corrected with calcium carbonate. However, the headaches resolved, alkaline phosphatase normalized, and zoledronic acid was put on hold. Up until January 2022, she remains asymptomatic and alkaline phosphatase remains normal.

Conclusion

This case illustrates the successful management of PDB of the skull with denosumab, a human monoclonal antibody against RANKL. To the best of our knowledge, there have not been reported cases of full recovery of PBD with denosumab. Although PBD pathophysiology remains poorly understood, this case suggests that increased RANKL activity might mediate PBD directly or indirectly. Thereby, denosumab might be an effective treatment for some cases of PDB.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT205 A Case of Persistent Primary Hyperparathyroidism Secondary to an Occult Supernumerary Parathyroid Adenoma
Authors: Cruz Maria Nikki , Ong-Ramos Celeste
Published: November 2022

Background

Persistent primary hyperparathyroidism accounts for the vast majority of patients who require reexploration. With the advancements in preoperative localization, surgical outcomes have improved over time. However, in patients with failed reoperative parathyroid exploration, an occult supernumerary parathyroid adenoma should be considered.

Clinical Case

A 60 year-old female diagnosed with primary hyperparathyroidism presented with recurrent nephrolithiasis, osteoporosis and declining eGFR. Initial laboratory evaluation showed elevated serum calcium (1.54 mmol/L, normal 1.09-1.30) and intact PTH (146 pg/mL, normal 18.50-88.0). 99mTc-sestamibi scintigraphy showed a sestamibi-avid focus in the inferior aspect of the right lobe hence, she underwent radionuclide-guided focused right parathyroidectomy. Post-operatively, her intact PTH level was still elevated (171.2 pg/mL). Histopathologic examination showed a normocellular parathyroid gland and a multifocal papillary thyroid carcinoma. The failed 1st surgery was attributed to the false positive scintigraphy from the papillary thyroid carcinoma. She then underwent total thyroidectomy with central neck dissection and 3½ parathyroidectomy with intraoperative parathyroid hormone assay. However, serial PTH monitoring after exploration and parathyroidectomy failed to decrease the PTH level by 50%. Histopathologic examination showed normocellular parathyroid glands. The bilateral carotid sheath, retropharyngeal region and superior mediastinum were explored but no ectopic parathyroid tissues were seen. Post-operatively, calcium and PTH were still elevated (1.48 mmol/L and 200.5 pg/mL, respectively). FDG PET CT imaging failed to show any ectopic parathyroid gland or adenoma. No further surgical intervention was done and she was medically managed with Cinacalcet 30 mg twice daily. 15 months after her parathyroid gland exploration, calcium and PTH were still elevated (1.46 mmol/L and 156.80 pg/mL, respectively). F18 Choline PET CT imaging was done showing a small hypoenhancing persistently FCH-positive focus in the left thyroid bed and sliver of enhancing tissue relating to a parathyroid adenoma.

Conclusion

This case highlights the diagnostic and therapeutic challenges in a patient with persistent primary hyperparathyroidism after a failed 2nd surgery. Occult parathyroid adenomas can cause significant symptoms regardless of its size and its imperceptible nature on imaging. The role of medical management is emphasized in this case when surgical management was not possible. Furthermore, re-evaluation for growth of the possible occult parathyroid adenoma should be done, which in this case took 15 months until its detection.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
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

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<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 <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<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

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

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>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

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, < 50 nmol/L, confirming lack of meaningful cortisol co-secretion. The basal and post-ACTH selectivity index were respectively >2 and > 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 > 2 basally and >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 > 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