Differential Impact of Subcutaneous and Visceral Fat on Bone Changes after Gastrectomy.

Background: Osteoporosis and fragility fractures are crucial musculoskeletal complications in long-term survivors of gastric cancer. However, the relationship between changes in body composition after gastrectomy and bone loss has not been investigated. Therefore, this study aimed to explore whether computed tomography (CT)-derived body composition parameters are associated with bone loss after gastrectomy in patients with gastric cancer. Methods: We retrospectively reviewed medical records and abdomen CT scans of patients who underwent gastrectomy at Yonsei University Severance Hospital between 2009 and 2018. Patients with non-metastatic gastric adenocarcinoma and preoperative and postoperative non-contrast CT scans were analyzed. Section area of skeletal muscle (SMA), visceral fat (VFA), and subcutaneous fat (SFA) were assessed using semi-automatic segmentation software. Changes in trabecular bone attenuation of L1 mid-vertebra level (L1 Hounsfield units [HU]) were measured. Results: Fifty-seven patients (mean age, 65.5±10.6; 70.2% males) were analyzed, and the median duration was 31 months. Fortyseven patients (82.5%) lost weight after gastrectomy. Baseline SMA and VFA did not differ between the bone loss and preserved groups; however, baseline SFA was significantly higher in the bone preserved group than in the bone loss group (P=0.020). In a multivariable linear regression model adjusted for confounding factors, one standard deviation higher VFA at baseline was associated with greater annualized L1 HU loss (%) (P=0.034). However, higher preoperative SFA was associated with protection against bone loss after gastrectomy (P=0.025). Conclusion: Higher preoperative SFA exhibited a protective effect against bone loss after gastrectomy in patients with non-metastatic gastric cancer, whereas VFA exhibited a negative effect.

Secular trends in the incidence and treatment patterns of primary hyperparathyroidism in Korea: a nationwide cohort study.

Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults are relatively limited in Asian countries. This study aims to provide an overview of the secular trends in incidence, clinical characteristics, and treatment patterns of PHPT in South Korea. We used Korea's National Health Insurance Claim database (2005-2020) to identify newly diagnosed PHPT cases. Individuals with age below 19, fewer than 2 E21.0 diagnoses, fewer than 2 PTH measurements, secondary hyperparathyroidism, undergoing dialysis or kidney transplantation within a year of diagnosis, parathyroidectomy (PTX) within a year prior to the diagnosis code, and diagnosis of multiple endocrine neoplasm or parathyroid carcinoma were excluded from the analysis. A total of 6837 patients with PHPT (PTX, n = 2989; non-surgery, n = 3848) were compared with 1:10 age- and sex-matched controls (n = 68 370). The mean age of patients with PHPT was 56.0 years, with 77.4% being women. The annual incidence of PHPT increased from 0.23/100 000 persons in 2005 to 1.75 in 2020, with higher rate in women than in men. Compared with 2005-2010 (n = 675), the number of newly diagnosed PHPT cases increased up to 3.1-fold (n = 2119) in 2011-2015 and 6.0-fold (n = 4043) in 2016-2020 periods. Among all patients with PHPT, 43.7% of patients underwent PTX, with decrement of proportion of bilateral surgery among PTX group across time (11.9% in 2005-2010 to 8.9% in 2016-2020, P for trend .033). Among all patients with PHPT, non-surgery group increased from 41.6% in 2005-2010 to 58.0% in 2016-2020 (P for trend <.001). Patients with PHPT had higher odds of osteoporosis (odds ratio [OR] 7.03), renal stones (OR 10.55), chronic kidney diseases (OR 7.42), and cardiovascular, metabolic, and neurological conditions after adjustment for comorbidity index. In summary, the incidence of PHPT increased from 2005 to 2020 with predominance of non-surgical treatment, which calls for research focus on improving non-surgical management.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

BACKGROUND: The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. METHODS: In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. RESULTS: The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] µg/ng, P < 0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m2 and those without sarcopenia. CONCLUSIONS: A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m2 and sarcopenia.

Metabolic phenotyping with computed tomography deep learning for metabolic syndrome, osteoporosis and sarcopenia predicts mortality in adults.

BACKGROUND: Computed tomography (CT) body compositions reflect age-related metabolic derangements. We aimed to develop a multi-outcome deep learning model using CT multi-level body composition parameters to detect metabolic syndrome (MS), osteoporosis and sarcopenia by identifying metabolic clusters simultaneously. We also investigated the prognostic value of metabolic phenotyping by CT model for long-term mortality. METHODS: The derivation set (n = 516; 75% train set, 25% internal test set) was constructed using age- and sex-stratified random sampling from two community-based cohorts. Data from participants in the individual health assessment programme (n = 380) were used as the external test set 1. Semi-automatic quantification of body compositions at multiple levels of abdominal CT scans was performed to train a multi-layer perceptron (MLP)-based multi-label classification model. External test set 2 to test the prognostic value of the model output for mortality was built using data from individuals who underwent abdominal CT in a tertiary-level institution (n = 10 141). RESULTS: The mean ages of the derivation and external sets were 62.8 and 59.7 years, respectively, without difference in sex distribution (women 50%) or body mass index (BMI; 23.9 kg/m2). Skeletal muscle density (SMD) and bone density (BD) showed a more linear decrement across age than skeletal muscle area. Alternatively, an increase in visceral fat area (VFA) was observed in both men and women. Hierarchical clustering based on multi-level CT body composition parameters revealed three distinctive phenotype clusters: normal, MS and osteosarcopenia clusters. The L3 CT-parameter-based model, with or without clinical variables (age, sex and BMI), outperformed clinical model predictions of all outcomes (area under the receiver operating characteristic curve: MS, 0.76 vs. 0.55; osteoporosis, 0.90 vs. 0.79; sarcopenia, 0.85 vs. 0.81 in external test set 1; P < 0.05 for all). VFA contributed the most to the MS predictions, whereas SMD, BD and subcutaneous fat area were features of high importance for detecting osteoporosis and sarcopenia. In external test set 2 (mean age 63.5 years, women 79%; median follow-up 4.9 years), a total of 907 individuals (8.9%) died during follow-up. Among model-predicted metabolic phenotypes, sarcopenia alone (adjusted hazard ratio [aHR] 1.55), MS + sarcopenia (aHR 1.65), osteoporosis + sarcopenia (aHR 1.83) and all three combined (aHR 1.87) remained robust predictors of mortality after adjustment for age, sex and comorbidities. CONCLUSIONS: A CT body composition-based MLP model detected MS, osteoporosis and sarcopenia simultaneously in community-dwelling and hospitalized adults. Metabolic phenotypes predicted by the CT MLP model were associated with long-term mortality, independent of covariates.

Association of secondhand smoke with fracture risk in community-dwelling nonsmoking adults in Korea.

Although the detrimental effects of active smoking on bone health have been widely recognized, the impact of secondhand smoke exposure on fracture risk in non-smokers remains less understood. A total of 4843 nonsmokers aged 40-69 yr, who participated in the Korean Genome and Epidemiology Study from 2001 to 2018, were analyzed. The participants were categorized into two groups based on their exposure status to secondhand smoke: currently exposed and unexposed. The exposure group was subsequently divided into two subgroups based on the median weekly exposure time (high vs low). The incidence of new fractures was determined using self-reported questionnaires. The identified fractures were categorized according to the fracture site: overall, vertebral, hip, non-vertebral, and non-vertebral non-hip fractures. The mean age of the participants was 52.4 yr (84.1% women). Exposure to secondhand smoke was associated with an increased risk of fracture (adjusted hazard ratio [aHR]: 1.27, P = 0.028) after adjusting for multiple covariates including age, sex, BMI, household income, bone density of mid-shaft tibia, C-reactive protein, alcohol consumption, and fracture history. Secondhand smoke remained as a significant risk factor for fracture, independent of the major osteoporotic fracture probabilities estimated using a fracture risk assessment tool (aHR: 1.24, P = 0.038). The high exposure group had higher risk of fracture than that of the unexposed group (aHR: 1.33, P = 0.025), whereas the fracture risk did not differ significantly between low exposure and unexposed groups (aHR: 1.18, P = 0.253), suggesting a potential dose-response relationship. Secondhand smoke showed robust association with increased risk of non-vertebral (aHR: 1.37, P = 0.008) or non-vertebral non-hip fractures (aHR: 1.36, P = 0.013), while its association with vertebral fracture was attenuated (aHR: 1.03, P = 0.908). Secondhand smoke was associated with an elevated risk of fracture in nonsmokers, independent of clinical risk factors.

The assessment of halitosis with a new screening tool in medication-related osteonecrosis of the jaw.

OBJECTIVES: This study aimed to identify the levels of halitosis in patients with Medication-related osteonecrosis of the jaw (MRONJ) and osteoporosis and to suggest a new MRONJ screening method using halitosis measurement. MATERIALS AND METHODS: From October 2019 to April 2023, participants aged 19 years or older without periodontal disease were selected. Seventy-five participants, 25 in each group, were divided into an MRONJ group, an osteoporosis group without MRONJ, and a control group without osteoporosis and not taking osteoporosis drugs or antibiotics. Each participant underwent halitosis assessment twice using an exhaled breath analyzer to measure halitosis twice by blowing a straw for 1 min. Measured concentrations of hydrogen, hydrogen sulfide, and methyl mercaptan were compared between groups. RESULTS: Data from 22 patients in the MRONJ group, 25 in the osteoporosis group, and 25 in the control group were analyzed. The concentrations of hydrogen sulfide and methyl mercaptan were significantly higher in the MRONJ group than in the other groups, but the concentrations of hydrogen did not differ between the groups. When comparing the concentrations of hydrogen sulfide and methyl mercaptan in osteoporosis patients and solid cancer patients in the MRONJ group, there was a significant difference in hydrogen sulfide concentration, but there was no significant difference in methyl mercaptan. CONCLUSIONS: Quantifying the level of halitosis can be used to screen for MRONJ in patients taking bisphosphonates, such as patients with osteoporosis, prostate cancer, and breast cancer. CLINICAL RELEVANCE: MRONJ is accompanied by bad breath, and the concentrations of hydrogen sulfide and methyl mercaptan are associated with MRONJ.

Elevated morbidity and mortality in patients with chronic idiopathic hypophosphatemia: a nationwide cohort study.

Background: Chronic idiopathic hypophosphatemia (CIH) induced by X-linked hypophosphatemic rickets or tumor-induced osteomalacia is a rare inherited or acquired disorder. However, due to its rarity, little is known about the epidemiology and natural course of CIH. Therefore, we aimed to identify the prevalence and long-term health outcomes of CIH patients. Methods: Using the Korean Health Insurance Review and Assessment claims database, we evaluated the incidence of hypophosphatemia initially diagnosed from 2003 to 2018. After excluding secondary conditions that could change serum phosphorus levels, we identified 154 patients (76 men and 78 women) with non-secondary and non-renal hypophosphatemia. These hypophosphatemic patients were compared at a ratio of 1:10 with age-, sex-, and index-year-matched controls (n = 1,540). Results: In the distribution of age at diagnosis, a large peak was observed in patients aged 1-4 years and small peaks were observed in ages from 40-70 years. The age-standardized incidence rate showed non-statistically significant trend from 0.24 per 1,000,000 persons in 2003 to 0.30 in 2018. Hypophosphatemic patients had a higher risk of any complication (adjusted hazard ratio [aHR], 2.17; 95% confidence interval [CI], 1.67-2.69) including cardiovascular outcomes, chronic kidney disease, hyperparathyroidism, osteoporotic fractures, periodontitis, and depression. Hypophosphatemic patients also had higher risks of mortality and hospitalization than the controls (aHR, 3.26; 95% CI, 1.83-5.81; and aHR, 2.49; 95% CI, 1.97-3.16, respectively). Conclusion: This first nationwide study of CIH in South Korea found a bimodal age distribution and no sex differences among patients. Hypophosphatemic patients had higher risks of complications, mortality, and hospitalization compared to age- and sex-matched controls.

Romosozumab is associated with greater trabecular bone score improvement compared to denosumab in postmenopausal osteoporosis.

In this study, romosozumab demonstrated significantly greater improvement in trabecular bone score compared to denosumab therapy in postmenopausal women previously treated with antiresorptive agents. Notably, in patients previously treated with anti-resorptive agents, treatment with romosozumab resulted in similar increases in trabecular bone score compared to that of drug-naïve patients. PURPOSE: Romosozumab significantly increases bone mineral density (BMD) and rapidly reduces fracture risk. Whether romosozumab can improve the spinal trabecular bone score (TBS) as a bone quality indicator merits further investigation. METHODS: Data for postmenopausal women starting romosozumab or denosumab treatment at Severance Hospital, Korea, were analyzed. Romosozumab and denosumab groups were 1:1 matched using propensity scores, considering relevant covariates. Good responders were defined as those with TBS improvement of 5.8% or greater. RESULTS: Overall, 174 patients (romosozumab, n = 87; denosumab, n = 87) were analyzed. Matched groups did not differ in age (64 years), weight, height, previous fracture (38%), lumbar spine or femoral neck BMD (T-score, -3.4 and -2.6, respectively), or prior bisphosphonate or selective estrogen receptor modulator (SERM) exposure (50%). The romosozumab group exhibited a greater increase in lumbar spine BMD (15.2% vs. 6.9%, p < 0.001) and TBS (3.7% vs. 1.7%, p = 0.013) than the denosumab group. In patients transitioning from bisphosphonate or SERM, romosozumab users showed greater improvement in TBS compared to denosumab users (3.9% versus 0.8%, P = 0.006); the drug-naive group showed no significant difference (3.6% versus 2.7%, P = 0.472). The romosozumab group had a higher proportion of good responders than the denosumab group (33.3% vs. 18.4%, p = 0.024). Romosozumab therapy for 12 months resulted in 3.8-fold higher odds of a good response in TBS than denosumab after covariate adjustment (adjusted odds ratio 3.85, p = 0.002). CONCLUSION: Romosozumab could improve bone mass and bone quality, measured by TBS, in postmenopausal osteoporosis, particularly as a subsequent regimen in patients previously taking anti-resorptive agents.

Cortical and Trabecular Bone Deficit in Middle-Aged Men Living with HIV.

A significant increase in the risk of hip fracture was observed in middle-aged men living with human immunodeficiency virus (MLWH), almost a decade earlier than those without infection. Data regarding cortical and trabecular bone deficit of hip, an important determinant of bone strength, in MLWH are limited. Quantitative CT was performed in consecutive MLWH aged ≥30 years between November 2017 and October 2018 at Severance Hospital, Seoul, Korea. Volumetric bone mineral density (vBMD) and cortical bone mapping parameters of hip (cortical thickness [CTh], cortical bone vBMD [CBMD], cortical mass surface density [CMSD], endocortical trabecular density [ECTD]) were compared to age-matched and body mass index (BMI)-matched controls (1:2) using a community-based healthy adults cohort. Among 83 MLWH and 166 controls (mean age: 47.2 years; BMI: 23.6 kg/m2 ), MLWH had lower total hip vBMD (280 ± 41 versus 296 ± 41 mg/cm3 ), CMSD (155 versus 160 mg/cm2 ), and ECTD (158 versus 175 mg/cm3 ) than controls that remained robust after adjustment for covariates (adjusted ß: total hip vBMD, -18.8; CMSD, -7.3; ECTD, -18.0; p < 0.05 for all). Cortical bone mapping revealed localized deficit of CTh, CBMD, and CMSD in the anterolateral trochanteric region and femoral neck in MLWH compared to controls, with a more extensive ECTD deficit. In MLWH, lower CD4 T-cell count (/100 cells/mm3 decrement) and protease inhibitor (PI)-based regimen (versus non-PI regimen) at the time of antiretroviral treatment initiation were associated with lower total hip vBMD (adjusted ß -7.5 for lower CD4 count; -28.3 for PI-based regimen) and CMSD (adjusted ß -2.6 for lower CD4 count; -12.7 for PI-based regimen; p < 0.05 for all) after adjustment for covariates including age, BMI, smoking, alcohol use, hepatitis C virus co-infection, tenofovir exposure, and CT scanner types. MLWH had lower hip bone density with cortical and trabecular bone deficit compared to community-dwelling controls. © 2023 American Society for Bone and Mineral Research (ASBMR).

Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma.

Genomic and transcriptomic profiling has enhanced the diagnostic and treatment options for many cancers. However, the molecular characteristics of parathyroid cancer remain largely unexplored, thereby limiting the development of new therapeutic interventions. Herein, we conducted genomic and transcriptomic sequencing of 50 parathyroid tissues (12 carcinomas, 28 adenomas, and 10 normal tissues) to investigate the intrinsic and comparative molecular features of parathyroid carcinoma. We confirmed multiple two-hit mutation patterns in cell division cycle 73 (CDC73) that converged to biallelic inactivation, calling into question the presence of a second hit in other genes. In addition, allele-specific repression of CDC73 in copies with germline-truncating variants suggested selective pressure prior to tumorigenesis. Transcriptomic analysis identified upregulation of the expression of E2F targets, KRAS and TNF-alpha signaling, and epithelial-mesenchymal transition pathways in carcinomas compared to adenomas and normal tissues. A molecular classification model based on carcinoma-specific genes clearly separated carcinomas from adenomas and normal tissues, the clinical utility of which was demonstrated in two patients with uncertain malignant potential. A deeper analysis of gene expression and functional prediction suggested that Wilms tumor 1 (WT1) is a potential biomarker for CDC73-mutant parathyroid carcinoma, which was further validated through immunohistochemistry. Overall, our study revealed the genomic and transcriptomic profiles of parathyroid carcinoma and may help direct future precision diagnostic and therapeutic improvements.

In-depth proteomic signature of parathyroid carcinoma.

OBJECTIVE: Diagnosing parathyroid carcinoma (PC) is complicated and controversial that early diagnosis and intervention are often difficult. Therefore, we aimed to elucidate the protein signatures of PC through quantitative proteomic analyses to aid in the early and accurate diagnosis of PC. DESIGN: We conducted a retrospective cohort study. METHODS: We performed liquid chromatography with tandem mass spectrometry using formalin-fixed paraffin-embedded samples. For the analyses, 23 PC and 15 parathyroid adenoma (PA) tissues were collected from 6 tertiary hospitals in South Korea. RESULTS: The mean age of the patients was 52 years, and 63% were women. Proteomic expression profiling revealed 304 differentially expressed proteins (DEPs) with a cut-off of P < .05 and fold change >1.5. Among DEPs, we identified a set of 5 proteins that can discriminate PC from PA: carbonic anhydrase 4 (CA4), alpha/beta hydrolase domain-containing protein 14B (ABHD14B), laminin subunit beta-2 (LAMB2), CD44 antigen (CD44), and alpha-1-acid glycoprotein 1 (ORM1) that exhibited the highest area under the curve of 0.991 in neural network model. The nuclear percentage of CA4 and LAMB2 in immunohistochemistry was significantly lower in PC tissue than in the PA (CA4: 2.77 ± 1.96%, 26.2 ± 3.45%, P < .001; LAMB2: 6.86 ± 3.46%, 38.54 ± 4.13%, P < .001). The most enriched canonical pathways in PC included glycoprotein-6 signaling and mammalian target of rapamycin (mTOR). CONCLUSIONS: We identified key proteins differentially expressed between PC and PA using proteomic analyses of parathyroid neoplasms. These findings may help to diagnose PC accurately and elucidate potential therapeutic targets.

Chest X-ray-based opportunistic screening of sarcopenia using deep learning.

BACKGROUND: Early detection and management of sarcopenia is of clinical importance. We aimed to develop a chest X-ray-based deep learning model to predict presence of sarcopenia. METHODS: Data of participants who visited osteoporosis clinic at Severance Hospital, Seoul, South Korea, between January 2020 and June 2021 were used as derivation cohort as split to train, validation and test set (65:15:20). A community-based older adults cohort (KURE) was used as external test set. Sarcopenia was defined based on Asian Working Group 2019 guideline. A deep learning model was trained to predict appendicular lean mass (ALM), handgrip strength (HGS) and chair rise test performance from chest X-ray images; then the machine learning model (SARC-CXR score) was built using the age, sex, body mass index and chest X-ray predicted muscle parameters along with estimation uncertainty values. RESULTS: Mean age of the derivation cohort (n = 926; women n = 700, 76%; sarcopenia n = 141, 15%) and the external test (n = 149; women n = 95, 64%; sarcopenia n = 18, 12%) cohort was 61.4 and 71.6 years, respectively. In the internal test set (a hold-out set, n = 189, from the derivation cohort) and the external test set (n = 149), the concordance correlation coefficient for ALM prediction was 0.80 and 0.76, with an average difference of 0.18 ± 2.71 and 0.21 ± 2.28, respectively. Gradient-weight class activation mapping for deep neural network models to predict ALM and HGS commonly showed highly weight pixel values at bilateral lung fields and part of the cardiac contour. SARC-CXR score showed good discriminatory performance for sarcopenia in both internal test set [area under the receiver-operating characteristics curve (AUROC) 0.813, area under the precision-recall curve (AUPRC) 0.380, sensitivity 0.844, specificity 0.739, F1-score 0.540] and external test set (AUROC 0.780, AUPRC 0.440, sensitivity 0.611, specificity 0.855, F1-score 0.458). Among SARC-CXR model features, predicted low ALM from chest X-ray was the most important predictor of sarcopenia based on SHapley Additive exPlanations values. Higher estimation uncertainty of HGS contributed to elevate the predicted risk of sarcopenia. In internal test set, SARC-CXR score showed better discriminatory performance than SARC-F score (AUROC 0.813 vs. 0.691, P = 0.029). CONCLUSIONS: Chest X-ray-based deep leaning model improved detection of sarcopenia, which merits further investigation.

Increased risk of incident diabetes after therapy with immune checkpoint inhibitor compared with conventional chemotherapy: A longitudinal trajectory analysis using a tertiary care hospital database.

AIMS/HYPOTHESIS: Immune checkpoint inhibitor (ICI) has been emerged as a promising cancer treatment. However, ICI use induces immune-related adverse events, including diabetes mellitus. We compared the risk of new-onset diabetes between patients receiving an ICI and those receiving conventional chemotherapy (CC). METHODS: Using a tertiary care hospital database, we included cancer patients without a previous history of diabetes who were treated with either CC or an ICI. One-to-five nearest neighbor propensity matching was applied, and the risk of diabetes was estimated using a Cox proportional hazards model. Latent class growth modeling was performed with a trajectory approach to determine distinct clusters that followed similar glucose trajectory patterns over time. RESULTS: Among 1326 subjects, 1105 received CC, and 221 received an ICI. The risk of new-onset diabetes was significantly higher in the ICI group than the CC group (adjusted hazard ratio 2.454, 95 % confidence interval 1.528-3.940; p < 0.001). The ICI group had a higher proportion of subjects in the trajectory cluster with an increasing glucose pattern than the CC group (10.4 % and 7.4 %, respectively). Within the ICI group, the subjects with an increasing glucose pattern were predominantly male and associated with enhanced lymphocytosis after ICI administration. CONCLUSIONS: ICI therapy is associated with an increased risk of incident diabetes compared with CC. The glucose levels of patients treated with an ICI, especially males and those with prominent lymphocytosis after ICI treatment, need to be monitored regularly to detect ICI-associated diabetes as early as possible.

Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism.

Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi-single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient's clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

Prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea.

Approximately 29% of Korean adults have hypertension; however, the prevalence of primary aldosteronism among the hypertensive population is largely unknown. The aim of our study was to evaluate the prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea. We retrospectively analyzed 1173 patients with newly diagnosed or preexisting hypertension who were referred to our tertiary-care hospital between January 2013 and December 2018. Patients were screened for primary aldosteronism with the aldosterone-renin ratio and underwent a saline infusion test for diagnostic confirmation. Adrenal computed tomography and adrenal venous sampling were performed for subtype classification for primary aldosteronism. Among the 1173 patients (mean age, 51.8 years; women, 53.2%), 360 (30.7%) had positive screening-test results, of whom 71 (6.1%) were finally diagnosed with primary aldosteronism. Conclusive subtype differentiation was made in 55 patients, of whom 15 (27%) had an aldosterone-producing adenoma, 4 (7%) had unilateral adrenal hyperplasia, and 36 (66%) had bilateral adrenal hyperplasia. Patients with primary aldosteronism had a higher ambulatory blood pressure, left ventricular mass index, and urinary albumin-to-creatinine ratio than those without. Moreover, the primary aldosteronism group had a higher prevalence of left ventricular hypertrophy and albuminuria than the non-primary aldosteronism group. Primary aldosteronism may be more common (6.1%) among Korean patients with hypertension than generally recognized. Primary aldosteronism was associated with a higher degree and prevalence of target organ damage and a higher blood pressure level. Wide application of screening tests for primary aldosteronism may be beneficial in detecting this potentially curable cause of hypertension.

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.

Parathyroid venous sampling for the preoperative localisation of parathyroid adenoma in patients with primary hyperparathyroidism.

Preoperative localisation studies are essential for parathyroidectomy in patients with primary hyperparathyroidism. If the location of abnormal parathyroid glands cannot be identified through non-invasive studies, parathyroid venous sampling (PVS) may be employed. In this study, we evaluated the utility of preoperative PVS in parathyroid surgery. Patients with primary hyperparathyroidism who underwent preoperative PVS at Severance Hospital between January 2015 and June 2020 were identified. Patients for whom the results of non-invasive imaging studies were inconsistent or negative underwent PVS. The results of PVS were compared with operative findings and pathologic results. For 14 patients, the results of preoperative ultrasonography and 99mTc-sestamibi single-photon emission computed tomography (SPECT) were negative; for 20 patients, either the result of only one test was positive, or the results of the two tests were inconsistent. With respect to the lateralisation of diseased adenoma, the results of PVS and pathological examination were inconsistent only for one patient in either group (total: 2/34 patients). This study showed that PVS could be used effectively for preoperative localisation in patients with primary hyperparathyroidism in whom the location of diseased parathyroid glands cannot be determined through non-invasive image studies.

Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism.

BACKGROUND: Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. METHODS: A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). RESULTS: NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. CONCLUSION: We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

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.

Diagnostic Utility of Somatostatin Receptor 2A Immunohistochemistry for Tumor-induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder caused by excessive fibroblast growth factor 23 (FGF23) secretion. FGF23 immunohistochemistry (IHC) is proposed as a useful adjunctive marker to confirm TIO diagnosis. However, it often stains focally, limiting its diagnostic utility. OBJECTIVE: This work aimed to compare the diagnostic performance between somatostatin receptor 2A (SSTR2A) and FGF23 IHC for TIO. METHODS: We retrospectively reviewed TIO-diagnosed patients in Severance Hospital between July 2006 and May 2020. Histologic evaluation was performed using histoscore (H score) (expression area proportion score [0-2] × intensity score [1-3], [total, 0-6]). FGF23 and SSTR2A IHC were performed using unstained slides from 18 localized TIO patients and 9 and 15 non-TIO controls with bone and soft-tissue tumors, respectively. SSTR2A positivity was defined as cytoplasmic, membranous, or Golgi staining in more than 1% of tumor cells, and negativity as nonspecific nuclear staining. FGF23 positivity was defined as cytoplasmic expression in more than 1% of the tumor area and negativity as nonspecific nuclear staining. RESULTS: Suspicious lesions were successfully detected in 14 of 15 patients who underwent 68Ga-DOTATOC scans. Diffuse cytoplasmic SSTR2A expression was identified in all TIO patients and focal weak nuclear staining in 12 of 15 controls. FGF23 cytoplasmic expression was identified in 11 of 18 TIO patients and diffuse nuclear staining in 9 of 9 controls. The H score was higher in SSTR2A than in FGF23 IHC (median [interquartile range]: 6 [6-6] vs 1 [0-2], P < .001). CONCLUSION: SSTR2A IHC with H-score quantification might be a more sensitive, adjunctive diagnostic tool than FGF23 IHC for TIO diagnosis.