Low Serum Vitamin E Level Associated with Low Hand Grip Strength in Community-Dwelling Adults: Korean National Health and Nutrition Examination Survey (KNHANES VII) 2016-2018

This study assessed the association between serum vitamin E levels and hand grip strength (HGS) in community-dwelling adults data of 1011 men aged 50 years and older and 1144 postmenopausal women were analyzed. Low HGS was defined as HGS below the sex-stratified median value. Proportion of low HGS was the greatest in the lowest quintile of serum vitamin E level (17.81 mg/L, 43.6%; p 0.05). Individuals with the lowest quintile vitamin E level had elevated odds of low HGS independent of covariates, findings which merit further validation.ope

Application of the Trabecular Bone Score in Clinical Practice

The trabecular bone score (TBS) was introduced as an indirect index of trabecular microarchitecture, complementary to bone mineral density (BMD), and is derived using the same dual energy X-ray absorptiometry images. Recently, it has been approved for clinical use in Korea. Therefore, we conducted a comprehensive review to optimize the use of TBS in clinical practice. The TBS is an independent predictor of osteoporotic fractures in postmenopausal women and men aged >50 years. The TBS is potentially useful in monitoring the skeletal effects of anabolic agents but not of antiresorptive agents. In postmenopausal women with type 2 diabetes mellitus, the TBS assesses osteoporotic fracture risk not captured by BMD. However, high body mass index and soft tissue thickness can cause underestimation of the TBS; however, this limitation has been improved in recent versions of the TBS software. However, a high precision error and low reproducibility limit the use of TBS. This review may provide information on the application of the TBS in clinical practice based on reliable evidence.ope

Elevated gamma-glutamyl transpeptidase level is associated with an increased risk of hip fracture in postmenopausal women

The aim of this study was to evaluate the association between gamma-glutamyl transferase (GGT) levels and the risk of hip fracture among middle-aged women by using the Korean National Health Insurance Service claims database from 2002 to 2015. After exclusion of those with any chronic liver disease, heavy alcohol consumption, any missing values required for our analysis, or GGT levels less than 1 or greater than 99 percentile, we classified subjects into three groups according to baseline GGT levels. A total of 127,141 women aged 50 years or older were included for analysis (GGT range: 8-106 U/L). During an average 12.1 years of follow-up, 2758 patients sustained hip fractures (2.17%). Compared with the group in the lowest tertile, the group in the highest tertile had the highest cumulative incidence of hip fracture. One log-unit increase in GGT was associated with a 17% increased risk of hip fracture. Subgroup analysis by BMI (≥ 25 vs. < 25 kg/m2), presence of diabetes, levels of other liver enzymes, and alcohol consumption level did not show significant effect modification. In summary, elevated baseline GGT level was associated with an increased risk of hip fracture in postmenopausal women, independent of alcohol consumption and chronic liver disease.ope

Qualitative focus group interview study of communication between patients, dentists and physicians for efficient osteonecrosis of the jaw practices

Objectives: To investigate problems and the current status of existing methods of communication between patients, dentists and physicians for the prevention and treatment of medication-related osteonecrosis of the jaw (MRONJ). Design: A focus group interview study with a descriptive design using qualitative content analysis of transcripts. Setting: Secondary care in Korea. Participants: 3 patient groups and 4 health professional groups in a total of 32 participants including patients with osteoporosis or bone metastasis, dentists and physicians. Results: This study revealed that patients lacked medical knowledge of osteoporosis drugs, whereas dentists and physicians lacked each other's expertise. All patients reported undergoing dental treatments during the osteoporosis drug treatment, but dentists and physicians had different MRONJ experiences depending on their work setting in primary or secondary care. Patients expressed dissatisfaction with the current system of communication with health professionals via letter as they found this to be a slow process. Dentists and physicians reported the need for effective communication because they felt defensive when sending and receiving medical consults. Conclusions: Despite the low incidence of MRONJ among patients with osteoporosis, it is difficult to treat; thus, it is necessary to inform dentists, physicians and patients about the importance of MRONJ prevention. To this end, close communication among all involved stakeholders about osteoporosis drugs is required.ope

Retropharyngeal Ectopic Parathyroid Adenoma Localized by 18F-Fluorocholine Positron Emission Tomography/Computed Tomography: A Case Report

Ectopic parathyroid adenomas of the retropharyngeal space are relatively rare. Herein, we report a case of primary hyperparathyroidism (PHPT) secondary to a retropharyngeal parathyroid adenoma. A 22-year-old woman presented with elevated serum calcium and parathyroid hormone (PTH) levels, revealed during a medical check-up. The patient had a history of ureteral stones and a confirmed low bone mass. Neck 99mTechnetium-sestamibi singlephoton emission computed tomography (CT) and ultrasonography did not reveal any suspicious lesions. There was no evidence of hereditary PHPT based on the results of targeted gene sequencing. Surgical exploration was unsuccessful, and the PHPT persisted after the first surgery. Approximately a year after the failed operation, 18F-fluorocholine (FCH) positron emission tomography/CT (PET-CT) became available, and when performed, it revealed increased uptake in the retropharyngeal space of the right side of the neck. The results of parathyroid venous sampling were concordant with a >2-fold elevation of PTH level in the veins on the right side of the neck compared to the peripheral veins. The 1.8 cm-diameter mass was successfully removed resulting in an 87% reduction in intraoperative PTH level (198.0-26.5 pg/mL). Subsequently, normalizations of calcium and PTH levels were achieved. In summary, ectopic parathyroid adenomas, including retropharyngeal lesions, should also be suspected when investigating an elusive case of PHPT. 18F-FCH PET-CT can be a useful complementary modality for detecting culprit lesions.ope

Machine Learning Applications in Endocrinology and Metabolism Research: An Overview

Machine learning (ML) applications have received extensive attention in endocrinology research during the last decade. This review summarizes the basic concepts of ML and certain research topics in endocrinology and metabolism where ML principles have been actively deployed. Relevant studies are discussed to provide an overview of the methodology, main findings, and limitations of ML, with the goal of stimulating insights into future research directions. Clear, testable study hypotheses stem from unmet clinical needs, and the management of data quality (beyond a focus on quantity alone), open collaboration between clinical experts and ML engineers, the development of interpretable high-performance ML models beyond the black-box nature of some algorithms, and a creative environment are the core prerequisites for the foreseeable changes expected to be brought about by ML and artificial intelligence in the field of endocrinology and metabolism, with actual improvements in clinical practice beyond hype. Of note, endocrinologists will continue to play a central role in these developments as domain experts who can properly generate, refine, analyze, and interpret data with a combination of clinical expertise and scientific rigor.ope

Contrast-free (Zero-contrast) TAVR for Severe Aortic Stenosis in Patient with Chronic Kidney Disease

Transcatheter aortic valve replacement (TAVR) or transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) is a minimally invasive interventional procedure that repairs a valve without removing the old, damaged valve. Instead, a replacement valve is wedged into the location of the native aortic valve. During TAVR, contrast is used for conventional aortic root angiography, positioning of the TAVR valve device, and assessing the peripheral vasculature. Therefore, contrast-induced acute kidney injury (AKI) is a major concern when performing TAVR and is associated with increased mortality in patients with impaired renal function. Although the exact mechanism of post-TAVR AKI is unknown and appears multifactorial, contrast medium has been reported as a major contributing factor. We report a case of zero-contrast TAVR for severe AS in a patient with chronic kidney disease (CKD). The procedure was successfully performed with only fluoroscopic and transesophageal echocardiography (TEE) guidance.ope

Elevated urinary N-Acetyl-β-D-glucosaminidase is associated with high glycoalbumin-To-hemoglobin A1c ratio in type 1 diabetes patients with early diabetic kidney disease

Urinary N-acetyl-β-D-glucosaminidase (uNAG) predicted the progression of diabetic kidney disease (DKD) prior to development of albuminuria in diabetes patients. We sought whether uNAG level is associated with glycoalbumin-to-hemoglobin A1c ratio (G/A ratio), a marker of postprandial hyperglycemia and glycemic excursion, independent of albuminuria and kidney function. The association between uNAG excretion and G/A ratio was assessed in 204 consecutive subjects with type 1 diabetes (T1D) (mean age 43.9 years; 49.0% men). uNAG excretion level increased along with older age, hyperglycemia, and degree of albuminuria, but was not correlated with body mass index or estimated glomerular filtration rate (eGFR). Elevated uNAG showed robust association with higher G/A ratio (adjusted β = 0.103, P = 0.020) after adjustment for age, sex, body mass index, duration of diabetes, uACR, angiotensin blockers use, fasting plasma glucose, and hemoglobin level. uNAG showed better discriminatory performance for individuals with high G/A ratio than albuminuria (AUC 0.613 vs. 0.518, P = 0.038). Measurement of uNAG improved AUC for high G/A ratio from 0.699 to 0.748 (P = 0.043) when added to conventional risk factors (cutoff 5.24 U/g creatinine; sensitivity 62.5% and specificity 58.0%). In conclusion, Elevated uNAG was found to be associated with high G/A ratio in patients with T1D with early stage DKD, independent of age and albuminuria.ope

Effects of Altered Calcium Metabolism on Cardiac Parameters in Primary Aldosteronism

BACKGROUND: Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA. METHODS: Forty-two patients (mean age 48.8±10.9 years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins. RESULTS: The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was 8.9±0.3 mg/dL (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ρ=-0.424, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (β=-0.366, P=0.068 and β=-0.252, P=0.070, respectively). CONCLUSION: Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.ope

Germline Mutations Related to Primary Hyperparathyroidism Identified by Next-Generation Sequencing

Primary hyperparathyroidism (PHPT) is characterized by overproduction of parathyroid hormone and subsequent hypercalcemia. Approximately 10% of PHPT cases are hereditary, and several genes, such as MEN1, RET, CASR, and CDC73, are responsible for the familial forms of PHPT. However, other genetic mutations involved in the etiology of PHPT are largely unknown. In this study, we identified genetic variants that might be responsible for PHPT, including familial PHPT, benign sporadic PHPT, and sporadic parathyroid cancer, using next-generation sequencing (NGS). A total of 107 patients with PHPT who underwent NGS from 2017 to 2021 at Severance Hospital were enrolled. We reviewed the pathogenic variants, likely pathogenic variants, and variants of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Of the 107 patients (mean age: 47.6 ± 16.1 years, women 73.8%), 12 patients were diagnosed with familial PHPT, 13 with parathyroid cancer, and 82 with benign sporadic PHPT. Using NGS, we identified three pathogenic variants in two genes (CDC73 and MEN1), 10 likely pathogenic variants in six genes (CASR, CDC73, LRP5, MEN1, SDHA, and VHL), and 39 non-synonymous VUS variants that could be related to parathyroid disease. Interestingly, we identified one GCM2 variant (c.1162A>G [p.Lys388Glu]) and five APC variants that were previously reported in familial isolated hyperparathyroidism, benign sporadic PHPT, and parathyroid cancer. We also analyzed the characteristics of subjects with positive genetic test results (pathogenic or likely pathogenic variants), and 76.9% of them had at least one of the following features: 1) age < 40 years, 2) family history of PHPT, 3) multiglandular PHPT, or 4) recurrent PHPT. In this study, we analyzed the NGS data of patients with PHPT and observed variants that could possibly be related to PHPT pathogenesis. NGS screening for selected patients with PHPT might help in the diagnosis and management of the disease.ope