Association of sodium-glucose cotransporter 2 inhibitor use with risk of osteoporotic fracture among older women: A nationwide, population-based cohort study.

INTRODUCTION: We investigated the relationship between sodium-glucose cotransporter-2 inhibitor (SGLT2i) and fracture in elderly women diagnosed with type 2 diabetes mellitus (T2DM) and newly prescribed antidiabetic medications (ADMs). MATERIAL AND METHODS: We used the population-based cohort study data from the National Health Insurance Service of Korea (2013-2020). Women ≥65 years old with T2DM, who were newly prescribed ADMs other than glucagon-like peptide-1 receptor agonists and thiazolidinedione, and who had comprehensive health check-up data were included. RESULTS: A total of 1,333 SGLT2i users were matched in a 1:2 ratio with 2,626 non-SGLT2i users. After propensity score matching, mean age, body mass index, number of ADMs, and other covariates were well-balanced between SGLT2i users and non-SGLT2i users. During the follow-up period, a higher incidence of vertebral fractures in SGLT2i users than in non-SGLT2i users (incidence rate 19.2 vs. 13.8 per 1,000 person-years; hazard ratio 1.40, 95 % confidence interval 1.00-1.96, p = 0.049). No significant difference was noted in other types of fracture. CONCLUSION: SGLT2i use showed an increased risk of vertebral fracture than non-SGLT2i use in elderly women. Although further validation is required, SGLT2i should be cautiously prescribed in older women due to the potential association with fracture risk.

Bone Loss after Solid Organ Transplantation: A Review of Organ-Specific Considerations.

This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

GNUV201, a novel human/mouse cross-reactive and low pH-selective anti-PD-1 monoclonal antibody for cancer immunotherapy.

BACKGROUND: Several PD-1 antibodies approved as anti-cancer therapies work by blocking the interaction of PD-1 with its ligand PD-L1, thus restoring anti-cancer T cell activities. These PD-1 antibodies lack inter-species cross-reactivity, necessitating surrogate antibodies for preclinical studies, which may limit the predictability and translatability of the studies. RESULTS: To overcome this limitation, we have developed an inter-species cross-reactive PD-1 antibody, GNUV201, by utilizing an enhanced diversity mouse platform (SHINE MOUSE™). GNUV201 equally binds to human PD-1 and mouse PD-1, equally inhibits the binding of human PD-1/PD-L1 and mouse PD-1/PD-L1, and effectively suppresses tumor growth in syngeneic mouse models. The epitope of GNUV201 mapped to the "FG loop" of hPD-1, distinct from those of Keytruda® ("C'D loop") and Opdivo® (N-term). Notably, the structural feature where the protruding epitope loop fits into GNUV201's binding pocket supports the enhanced binding affinity due to slower dissociation (8.7 times slower than Keytruda®). Furthermore, GNUV201 shows a stronger binding affinity at pH 6.0 (5.6 times strong than at pH 7.4), which mimics the hypoxic and acidic tumor microenvironment (TME). This phenomenon is not observed with marketed antibodies (Keytruda®, Opdivo®), implying that GNUV201 achieves more selective binding to and better occupancy on PD-1 in the TME. CONCLUSIONS: In summary, GNUV201 exhibited enhanced affinity for PD-1 with slow dissociation and preferential binding in TME-mimicking low pH. Human/monkey/mouse inter-species cross-reactivity of GNUV201 could enable more predictable and translatable efficacy and toxicity preclinical studies. These results suggest that GNUV201 could be an ideal antibody candidate for anti-cancer drug development.

Cancer Risk in Graves Disease with Radioactive 131I Treatment: A Nationwide Cohort Study.

Radioactive 131I (RAI) therapy has potential effects for the treatment of Graves disease (GD). However, whether RAI therapy for GD increases cancer risk remains controversial in medicine and public health. We aimed to investigate whether the risk of cancer increases in patients with GD receiving RAI therapy compared with those who did not. Methods: We used the Korean National Health Insurance Service's National Health Information Database from 2004 to 2020 and defined GD as prescribing antithyroid drugs, RAI, or thyroidectomy as a treatment for GD (International Classification of Diseases, 10th revision, E05 group). We investigated the hazard ratios (HRs) of overall and site-specific cancers associated with RAI in patients with GD. Subsequent cancer was defined as a primary malignancy treated at least 1 y after RAI therapy. Results: In total, 10,737 patients with GD who received RAI therapy (7,193 women, 67.0%; mean age, 43.7 ± 13.4 y) were matched to 53,003 patients with GD who had never received RAI treatment (35,471 women, 66.9%; mean age, 43.8 ± 13.2 y) in a 1:4-5 ratio by age, sex, and health checkup data. The median follow-up duration was 8.7 y (interquartile range, 5.2-12.1 y), and the median cumulative RAI dose was 555 MBq (interquartile range, 370-630 MBq) in the RAI therapy group. During 2004-2020, the overall subsequent cancer rates were 5.66 and 5.84 per 1,000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted HR of 0.97 (95% CI, 0.88-1.06); this remained at 0.96 (95% CI, 0.83-1.10) after adjustment for multiple clinical confounding factors. For cancer subtypes, the risk of leukemia was significantly increased, with an HR of 2.39 (95% CI, 1.17-4.91). However, a loss of statistical significance was observed after adjusting for confounding factors, which may be attributed to the limited number of absolute events. Moreover, cancer-specific mortality was not different between the RAI and the non-RAI groups, with an adjusted HR of 0.99 (95% CI, 0.66-1.47). Conclusion: This study identified that the overall cancer risk in patients with GD who received RAI therapy compared with those who did not was not significant in Korea. Further long-term studies are needed to determine the risks and advantages of RAI therapy in patients with GD.

Associations Between Physical Activity and the Risk of Hip Fracture Depending on Glycemic Status: A Nationwide Cohort Study.

CONTEXT: Although physical activity (PA) is recognized to reduce fracture risk, whether its benefits differ according to glycemic status remains unknown. OBJECTIVE: We investigated the effect of PA on incident hip fracture (HF) according to glycemic status. METHODS: We studied 3 723 097 patients older than 50 without type 1 diabetes mellitus (DM) or past fractures. HF risks were calculated using Cox proportional hazard regression. Participants were categorized by glycemic status into 5 groups: normal glucose tolerance, impaired fasting glucose, new-onset type 2 DM, type 2 DM less than 5 years, and type 2 DM of 5 years or greater. PA was evaluated using the Korean adaptation of the International Physical Activity Questionnaire Short Form. RESULTS: The highest HF risk were associated with the lowest PA level (<500 metabolic equivalent task [MET]-min/wk). While similar risks emerged across MET 500 to 1000, 1000 to 1500, and greater than 1500 categories, the relationship showed variations in different glycemic status groups. Exceptions were particularly noted in women with normoglycemia. However, a consistent inverse pattern, with few exceptions, was observed both in men and women with type 2 DM of 5 years or greater. Furthermore, the benefit of PA in the prevention of HFs was most evident in participants with type 2 DM of 5 years or greater. Compared to the reference group (lowest physical activity level <500 MET-min/wk within type 2 DM ≥5 years), the adjusted hazard ratios were 0.74 (0.62-0.88) in men and 0.74 (0.62-0.89) in women, suggesting a significant reduction in risk. CONCLUSION: Higher PA levels are associated with a lower risk of HF. This protective effect of PA on fracture risk is greatest in patients with DM, particularly in those with DM of 5 years or greater.

2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism.

Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.

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.

Risk of dementia in primary aldosteronism compared with essential hypertension: a nationwide cohort study.

BACKGROUND: Although hypertension is a critical risk factor for dementia, the association between primary aldosteronism (PA) and dementia has been scarcely reported. We aimed to investigate whether the risk of dementia in patients with PA was elevated compared with patients with essential hypertension (EH). METHODS: From the National Health Insurance Claim database in Korea (2003-2017), 3,687 patients with PA (adrenalectomy [ADX], n = 1,339, mineralocorticoid receptor antagonist [MRA] n = 2,348) with no prior dementia were age- and sex-matched at a 1:4 ratio to patients with EH (n = 14,741). The primary outcomes were all-cause dementia events, including Alzheimer's disease, vascular dementia, or other dementia combined with a prescription of one or more medications for dementia (donepezil, galantamine, memantine, or rivastigmine). Multivariable Cox regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals for the outcome incidence rates between patients with PA and their EH matches. RESULTS: During a median follow-up of 5.2 years, there were 156 cases of all-cause dementia (4.2%), 140 cases of Alzheimer's disease (3.8%), and 65 cases of vascular dementia (1.8%). Compared with EH, the risk of all-cause dementia was increased in treated PA (unadjusted hazard ratio [HR] 1.26; p < 0.011). Among PA, MRA group had higher risks of all-cause dementia, especially vascular dementia, adjusted for age, sex, income, comorbidities, and concurrent medication (adjusted HR 1.31; p = 0.027 and adjusted HR 1.62; p = 0.020, respectively) compared to EH. ADX group seemed to have a lower dementia risk than the EH group, but there was no statistical significance after full adjustment. This trend became more prominent when the dementia risks were evaluated from the time of hypertension diagnosis rather than treatment initiation for PA. CONCLUSION: The findings of this cohort study suggest that PA, especially the MRA group, is associated with an increased risk of dementia. Monitoring cognitive function in PA patients even after treatment initiation might be warranted to prevent dementia.

Weight-adjusted waist as an integrated index for fat, muscle and bone health in adults.

BACKGROUND: Unhealthy body composition, including high fat mass, low muscle mass and low bone mass, is a critical health issue in adults. The weight-adjusted waist index (WWI) estimates fat and muscle mass and may have implications for bone health. We examined its association with body composition outcomes in a large Korean adult cohort. METHODS: This study used data from the Korean National Health and Nutrition Examination Survey (2008-2011). WWI was calculated as waist circumference (cm) divided by the square root of body weight (kg). Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD), appendicular lean mass (ALM) and total body fat percentage. Unhealthy body composition was defined as combined presence of high fat mass, low bone mass and low muscle mass. RESULTS: A total of 5983 individuals (3034 men [50.7%] and 2949 women [49.3%]; mean age: 63.5 ± 8.7 years) were included. WWI was positively correlated with total body fat percentage (r = 0.478, P < 0.001) and inversely with ALM/weight (r = -0.485, P < 0.001) and BMD at the lumbar spine (r = -0.187, P < 0.001), femoral neck (r = -0.269, P < 0.001) and total hip (r = -0.255, P < 0.001). Higher WWI quartiles correlated with lower BMD, T-scores and ALM/weight, along with increased total body fat, evident in both genders and more pronounced in women, even after adjusting for confounders. This trend remained statistically significant across WWI quartiles for all analyses (P < 0.001). Higher WWI quartiles were also significantly associated with higher odds of unhealthy body composition, with adjusted odds ratio in the highest WWI group of 18.08 (95% CI, 4.32-75.61) in men and 6.36 (95% CI, 3.65-11.07) in women. The optimal cutoff values of WWI for unhealthy body composition were 10.4 cm/√kg in men and 10.5 cm/√kg in women. CONCLUSIONS: In community-dwelling adults, high WWI values are associated with unfavourable body composition outcomes, indicating high fat mass, low muscle mass and low bone mass. WWI can potentially serve as an integrated index of body composition, underscoring the need for further research to validate its use in clinical settings.

Effect of a Wearable Device-Based Physical Activity Intervention in North Korean Refugees: Pilot Randomized Controlled Trial.

BACKGROUND: Effective health interventions for North Korean refugees vulnerable to metabolic disorders are currently unelucidated. OBJECTIVE: This study aimed to evaluate the effects of digital health interventions in North Korean refugees using a wearable activity tracker (Fitbit device). METHODS: We conducted a prospective, randomized, open-label study on North Korean refugees aged 19-59 years between June 2020 and October 2021 with a 12-week follow-up period. The participants were randomly assigned to either an intervention group or a control group in a 1:1 ratio. The intervention group received individualized health counseling based on Fitbit data every 4 weeks, whereas the control group wore the Fitbit device but did not receive individualized counseling. The primary and secondary outcomes were the change in the mean daily step count and changes in the metabolic parameters, respectively. RESULTS: The trial was completed by 52 North Korean refugees, of whom 27 and 25 were in the intervention and control groups, respectively. The mean age was 43 (SD 10) years, and 41 (78.8%) participants were women. Most participants (44/52, 95.7%) had a low socioeconomic status. After the intervention, the daily step count in the intervention group increased, whereas that in the control group decreased. However, there were no significant differences between the 2 groups (+83 and -521 steps in the intervention and control groups, respectively; P=.500). The effects of the intervention were more prominent in the participants with a lower-than-average daily step count at baseline (<11,667 steps/day). After the 12-week study period, 85.7% (12/14) and 46.7% (7/15) of the participants in the intervention and control groups, respectively, had an increased daily step count (P=.05). The intervention prevented the worsening of the metabolic parameters, including BMI, waist circumference, fasting blood glucose level, and glycated hemoglobin level, during the study period. CONCLUSIONS: The wearable device-based physical activity intervention did not significantly increase the average daily step count in the North Korean refugees in this study. However, the intervention was effective among the North Korean refugees with a lower-than-average daily step count; therefore, a large-scale, long-term study of this intervention type in an underserved population is warranted. TRIAL REGISTRATION: Clinical Research Information Service KCT0007999; https://cris.nih.go.kr/cris/search/detailSearch.do/23622.

All-cause and cause-specific mortality risks associated with calcium supplementation with or without vitamin D: A nationwide population-based study.

BACKGROUND: Current evidence regarding the mortality outcomes associated with calcium supplementation with or without low-dose vitamin D is conflicting. OBJECTIVES: To investigate the effects of calcium supplementation with or without vitamin D on all-cause and cause-specific mortalities in a large-scale cohort. METHODS: This study used data from the Korean National Health Insurance System database and National Death Registry. A total of 27,846 participants aged >55 years who had taken calcium supplements with or without vitamin D for at least 90 days (calcium supplementation only [CaO], n = 6256; calcium supplementation in combination with vitamin D [CaD], n = 21,590) were matched in a 1:1 ratio to those who did not take calcium or vitamin D supplements (control group) using propensity scores. RESULTS: No difference in all-cause mortality risk was found between the CaO and control groups: (adjusted hazard ratio [HR] = 1.00; 95% confidence interval [CI]: 0.92-1.10). However, all-cause mortality was lower in the CaD group (HR = 0.85; 95% CI: 0.80-0.89) compared with that in the control group. Mortality risk associated with cardiovascular disease (CVD) was decreased in the CaD group when the daily vitamin D dose received was less than 1000 IU (HR = 0.72; 95% CI: 0.64-0.81). Subgroup analysis showed significant effect of vitamin D with calcium in individuals who were female, aged ≥65 years or had previous history of cancer or CVD. CONCLUSION: In combination with calcium, vitamin D supplementation provides better outcomes for all-cause mortality, particularly CVD-associated mortality, in a duration-dependent manner.

Linear association between radioactive iodine dose and second primary malignancy risk in thyroid cancer.

BACKGROUND: We aimed to investigate whether the risk of second primary malignancy (SPM) in patients with thyroid cancer (TC) receiving radioactive iodine (RAI) therapy rises in a cumulative, dose-dependent manner compared with those not undergoing RAI. METHODS: Using the Korean National Health Insurance Service National Health Information Database (2002-2019), we investigated hazard ratios of SPM associated with RAI in TC. SPM was defined as a second primary malignancy diagnosed at least 1 year after TC diagnosis. RESULTS: Of 217 777 patients with TC (177 385 women and 40 392 men; mean [SD] age, 47.2 [11.6] years), 100 448 (46.1%) received RAI therapy. The median (IQR) follow-up duration was 7.7 (5.5-10.3) years, and the median (IQR) cumulative RAI dose was 3.7 (1.9-5.6) GBq. From 2004 to 2019, SPM incidence rates were 7.30 and 6.56 per 1000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted hazard ratio of 1.09 (95% confidence interval = 1.05 to 1.13); this rate remained at 1.08 (95% confidence interval = 1.04 to 1.13) after adjustment for multiple clinical confounding factors. Notably, SPM risk increased significantly, from 3.7 GBq with full adjustments, and a strong linear association between cumulative RAI dose and SPM was observed in the restricted cubic spline analysis. Regarding cancer subtypes, myeloid leukemia and salivary gland, trachea, lung and bronchus, uterus, and prostate cancers were the most significantly elevated risks in patients who underwent RAI therapy. CONCLUSIONS: This study identified that SPM risk increased linearly in a dose-dependent manner in patients with TC undergoing RAI therapy compared with those not undergoing RAI therapy.

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.

Biomarkers for Locally Advanced Hepatocellular Carcinoma Patients Treated with Liver-Directed Combined Radiotherapy.

Introduction: In the era of biomarker-driven cancer therapy, robust biomarkers for hepatocellular carcinoma (HCC) have not been well-defined. In this hypothesis-generating study, we investigated biomarkers that can be incorporated to predict treatment outcomes in patients with locally advanced HCC who are administered liver-directed combined radiotherapy (LDCRT). Methods: Ninety-nine patients with HCC who were treated with conventional fractionation LDCRT between July 2016 and October 2018 were enrolled in this prospective single-arm study. Clinical outcomes and possible serum biomarkers, including soluble programmed cell death ligand-1 (sPD-L1), interleukin (IL)-10, IL-6, cell-free DNA (cfDNA), inter-alpha inhibitor H4, and interferon-gamma, were analyzed. The primary endpoint was disease progression, and additional endpoints were local failure-free rate, intrahepatic failure-free rate, and lung metastasis-free rate. Results: The median follow-up period was 18.7 months. The 1-year progression-free rate was 38.2%. Increasing baseline sPD-L1 per pg/mL, previous treatment history, protein induced by vitamin K absence-II >1,629 mAU/mL, and multiple tumors were the adverse factors for progression based on multivariate analysis. Survival tree analysis revealed three prognostic groups for progression, in which patients with multiple lesions and baseline sPD-L1 ≥41.07 pg/mL showed the worst outcomes. For dynamic changes in biomarker levels, sPD-L1 fold change and cfDNA fold-change values were unfavorable factors for progression. Conclusion: Baseline sPD-L1, sPD-L1 fold change, and cfDNA fold-change values showed the highest potential as biomarkers for predicting post-treatment progression after LDCRT in HCC patients. By incorporating clinical factors, these biomarkers may be useful for devising a biomarker-driven treatment paradigm in locally advanced HCC.

Identification of Healthy and Unhealthy Lifestyles by a Wearable Activity Tracker in Type 2 Diabetes: A Machine Learning-Based Analysis.

Lifestyle is a critical aspect of diabetes management. We aimed to define a healthy lifestyle using objectively measured parameters obtained from a wearable activity tracker (Fitbit) in patients with type 2 diabetes. This prospective observational study included 24 patients (mean age, 46.8 years) with type 2 diabetes. Expectation-maximization clustering analysis produced two groups: A (n=9) and B (n=15). Group A had a higher daily step count, lower resting heart rate, longer sleep duration, and lower mean time differences in going to sleep and waking up than group B. A Shapley additive explanation summary analysis indicated that sleep-related factors were key elements for clustering. The mean hemoglobin A1c level was 0.3 percentage points lower at the end of follow-up in group A than in group B. Factors related to regular sleep patterns could be possible determinants of lifestyle clustering in patients with type 2 diabetes.

Optimization of GFAG crystal surface treatment for SiPM based TOF PET detector.

Coincidence timing resolution (CTR) is an important parameter in clinical positron emission tomography (PET) scanners to increase the signal-to-noise ratio of PET images by using time-of-flight (TOF) information. Lutetium (Lu) based scintillators are often used for TOF-PET systems. However, the self-radiation of Lu-based scintillators may influence the image quality for ultra-low activity PET imaging. Recently, a gadolinium fine aluminum gallate (Ce:GFAG) scintillation crystal that features a fast decay time (∼55 ns) and no self-radiation was developed. The present study aimed at optimizing the GFAG crystal surface treatment to enhance both CTR and energy resolution (ER). The TOF-PET detector consisted of a GFAG crystal (3.0 × 3.0 × 20 mm3) and a SiPM with an effective area of 3.0 × 3.0 mm2. The timing and energy signals were extracted using a high-frequency SiPM readout circuit and then were digitized using a CAMAC DAQ system. The CTR and ER were evaluated with nine different crystal surface treatments such as partial saw-cut and chemical polishing and the 1-side saw-cut was the best choice among the treatments. The respective CTR and ER of 202 ± 2 ps and 9.5 ± 0.1% were obtained with the 1-side saw-cut; the other 5-side mechanically polished GFAG crystals had respective values which were 18 ps (9.0%) and 1.3% better than those of the all-side mechanically polished GFAG crystal. The chemically polished GFAG crystals also offered enhanced CTR and ER of about 17 ps (8.2%) and 2.1%, respectively, over the mechanically polished GFAG crystals.

Raloxifene Use After Denosumab Discontinuation Partially Attenuates Bone Loss in the Lumbar Spine in Postmenopausal Osteoporosis.

Discontinuation of denosumab (DMab) is associated with decline in bone density. Whether raloxifene can be effective to attenuate bone loss after DMab discontinuation in certain conditions when other antiresorptives cannot be used remains unclear. Data on postmenopausal women with osteoporosis who discontinued DMab treatment after short-term use (1-to-4 doses) at Severance Hospital, Seoul, Korea, between 2017 and 2021 were reviewed. Changes in bone mineral density (BMD) at 12 months after DMab discontinuation was compared between sequential raloxifene users (DR) and those without any sequential antiresorptive (DD) after 1:1 propensity score matching. In matched cohort (66 patients; DR n = 33 vs. DD n = 33), mean age (69.3 ± 8.2 years) and T-score (lumbar spine - 2.2 ± 0.7; total hip - 1.6 ± 0.6) did not differ between two groups at the time of DMab discontinuation. Sequential treatment to raloxifene in DR group attenuated the bone loss in lumbar spine after DMab discontinuation compared to DD group (DR vs. DD; - 2.8% vs. - 5.8%, p = 0.013). The effect of raloxifene on lumbar spine BMD changes remained robust (adjusted ß + 2.92 vs. DD, p = 0.009) after adjustment for covariates. BMD loss at femoral neck (- 1.70% vs. - 2.77%, p = 0.673) and total hip (- 1.42% vs. - 1.44%, p = 0.992) did not differ between two groups. Compared to BMD at DMab initiation, DR partially retained BMD gain by DMab treatment in lumbar spine (+ 3.7%, p = 0.003) and femoral neck (+ 2.8%, p = 0.010), whereas DD did not. Raloxifene use after DMab treatment attenuated lumbar spine BMD loss in postmenopausal women with short exposures (< 2 years) to DMab.

Structural insight into a molecular mechanism of methenyltetrahydrofolate cyclohydrolase from Methylobacterium extorquens AM1.

Bioconversion of the C1 compounds into value-added products is one of the CO2-reducing strategies. In particular, because CO2 can be easily converted into formate, the efficient and direct bioconversion of CO2 through formate assimilation is attracting attention. The tetrahydrofolate (THF) cycle is the highly efficient reconstructed formate assimilation pathway, and 5,10-methenyltetrahydrofolate cyclohydrolase (FchA) is an essential enzyme involved in the THF cycle. In this study, a kinetic analysis of FchA from Methylobacterium extorquens AM1 (MeFchA) was performed and revealed that the enzyme has much higher cyclization than hydrolyzation activity, making it an optimal enzyme for formate assimilation. The crystal structure of MeFchA in the apo- and the THF-complexed forms was also determined, revealing that the substrate-binding site of the enzyme has three differently charged regions to stabilize the three differently charged moieties of the formyl-THF substrate. The residues involved in the substrate binding were also verified through site-directed mutagenesis. This study provides a biochemical and structural basis for the molecular mechanism underlying formate assimilation.

Cardiovascular risks associated with calcium supplementation in patients with osteoporosis: a nationwide cohort study.

AIMS: This study aimed to evaluate the real effects of calcium supplementation on cardiovascular outcomes within a population-based cohort. METHODS AND RESULTS: From a nationwide health screening database in South Korea, a total of 11 297 patients with osteoporosis who had taken calcium supplementation with or without vitamin D for at least 90 days [total calcium group; calcium supplementation only (CaO), n = 567; calcium supplementation in combination with vitamin D (CaD), n = 10 730] were matched at a 1:1 ratio to patients who had not taken calcium supplements (control group) by using propensity scores. The overall mean age was 59.9 ± 8.8 years and the percentage of women was 87.9% in our study population. Over a median follow-up of 54 months, the incidence rate of composite cardiovascular diseases (CVDs) per 1000 person-years was not different between the groups: 9.73 in the total calcium group and 8.97 in the control group [adjusted hazard ratio (HR): 1.12; 95% confidence interval (CI): 0.99-1.28; P = 0.08]. However, calcium supplementation without vitamin D was associated with an increased risk of composite CVD (HR: 1.54; 95% CI: 1.17-2.04; P < 0.01), especially non-fatal myocardial infarction (HR: 1.89; 95% CI: 1.23-2.91; P < 0.01), compared with no calcium supplementation. CONCLUSION: Our population-based study supported that taking calcium supplementation combined with vitamin D did not appear to be harmful to cardiovascular health, but reminded that calcium supplementation without vitamin D should be used carefully even in populations with low dietary calcium intake.

Statin Therapy and the Risk of Osteoporotic Fractures in Patients with Metabolic Syndrome: a Nested Case-Control Study.

OBJECTIVE: We aimed to investigate the association between statin use and the risk of major osteoporotic fractures in patients with metabolic syndrome (MetS). METHODS: A nested case-control study was performed in patients with MetS (≥50 years) who had no history of osteoporotic fracture using the Korean National Health Insurance Service-Health Screening Cohort. This study included 17,041 patients diagnosed with new-onset osteoporotic fractures and controls matched in a 1:1 ratio by age, sex, body mass index, cohort entry date, and follow-up duration. Conditional logistic regression analysis was used to evaluate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: During a 4-year follow-up period, the risk of major osteoporotic fractures was significantly reduced by 9% (OR, 0.91; 95% CI, 0.85-0.97) in statin users compared with that in non-users. Among subtypes of major osteoporotic fracture, a risk reduction with statin therapy was significant for vertebral fracture (OR, 0.86; 95% CI, 0.79-0.94) but not for non-vertebral fracture (OR, 0.97; 95% CI, 0.88-1.06). Longer duration (OR, 0.97; 95% CI, 0.96-0.99, per 1-year increase) and higher cumulative dose (OR, 0.97; 95% CI, 0.95-0.99, per 365 defined daily doses) of statins were negatively associated with the risk of major osteoporotic fracture. CONCLUSION: This study supports the hypothesis that statin therapy has a beneficial effect on major osteoporotic fractures, especially vertebral fractures, in patients with MetS.