Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Background: Identifying risk factors for postpartum type 2 diabetes in women with gestational diabetes mellitus (GDM) is crucial for effective interventions. We examined whether changes in insulin sensitivity after delivery affects the risk of type 2 diabetes in women with GDM. Methods: This prospective cohort study included 347 women with GDM or gestational impaired glucose tolerance, who attended the follow-up visits at 2 months postpartum and annually thereafter. Changes in insulin sensitivity were calculated using the Matsuda index at GDM diagnosis and at 2 months postpartum (ΔMatsuda index). After excluding women with pregestational diabetes or those followed up only once, we analyzed the risk of postpartum type 2 diabetes based on the ΔMatsuda index tertiles. Results: The incidence of type 2 diabetes at the two-month postpartum visit decreased with increasing ΔMatsuda index tertiles (16.4%, 9.5%, and 1.8%, P=0.001). During a 4.1-year follow-up, 26 out of 230 women who attended more than two follow-up visits (11.3%) developed type 2 diabetes. Compared to the lowest tertile, subjects in the highest ΔMatsuda index tertile showed a significantly reduced risk of type 2 diabetes (hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.93; P=0.036) after adjusting for confounders. Conclusion Improvement in insulin sensitivity after delivery is associated with a reduced risk of postpartum type 2 diabetes in women with GDM. Postpartum changes in insulin sensitivity could be a useful prediction for future type 2 diabetes development in women with GDM.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort. Methods: Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD. Results: Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs. Conclusion The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Objectives: . Cultural familiarity and safety must be considered when assessing olfactory ability. The YSK olfactory function (YOF) test is a new olfactory function test using culturally familiar odorants to Koreans. Methods: . The YOF test comprises three subtests for threshold (T), discrimination (D), and identification (I). The identification test included eight universal and four Korean culture-friendly odorants, which were selected considering eight major functional groups. Data were obtained from 1,127 subjects over 19 years old. Subjects were classified as having normosmia (n=542), hyposmia (n=472), and anosmia (n=113) by self-reported olfactory function. The YOF test and the Korean version of the Sniffin’ stick test (KVSS-II) were performed on the same day in random order. Diagnostic cutoffs for anosmia and hyposmia were calculated using the Youden index (J). Results: . The mean values for each T/D/I subtest and the total TDI score were as follows: normosmia (T, 4.6±2.3; D, 8.6±2.1; I, 11.1±1.7; TDI score, 24.2±4.5); hyposmia (T, 3.3±2.2; D, 7.1±2.5; I, 9.2±3.1; TDI score, 19.5±6.4); and anosmia (T, 1.7±1.2; D, 5.1±2.5; I, 5.0±3.2; TDI score, 11.8±5.6). The correlation coefficients between the YOF test and KVSS-II were 0.57, 0.65, 0.80, and 0.86 for T, D, I, and the TDI score, respectively (P<0.001). The diagnostic cutoffs were a TDI score ≤14.5 (J=0.67) for anosmia and 14.5(TDI score ≤21.0 (J=0.38) for hyposmia. The diagnostic efficacy of the YOF test (area under the curve [AUC], 0.88) was equivalent to that of the KVSS-II (AUC, 0.88; P=0.843; DeLong method). Conclusion . The YOF test is a new olfactory test using safe and Korean culture-friendly odorants. It showed equivalent validity with the conventional olfactory function test. Furthermore, the YOF test provides information on the major functional groups of odorants, potentially enabling a more comprehensive interpretation for patients with olfactory disorders.

BACKGROUND AND OBJECTIVES: Hypertension is becoming one of the most common health conditions in children and adolescents due to increasing childhood obesity. We aimed to provide the auscultatory blood pressure (BP) normative reference values for Korean non-overweight children and adolescents. METHODS: BP measurements in children and adolescents aged 10 to 18 years were performed in the Korean National Health and Nutrition Examination Survey (KNHANES) from 1998 to 2016. BP was measured using a mercury sphygmomanometer. Sex-, age- and height-specific systolic BP (SBP) and diastolic BP (DBP) percentiles were calculated in the non-overweight children (n=10,442). We used the General Additive Model for Location Scale and Shape method to calculate BP percentiles. RESULTS: The 50th, 90th, 95th, and 99th percentiles of SBP and DBP tables and graphs of non-overweight children and adolescents aged 10 to 18 years were presented by age and height percentiles. We found that the SBP and DBP at the 95th percentile were well correlated with height. The BP tables presented by height contained BP values from 124 cm to 190 cm for boys and from 120 cm to 178 cm for girls. Boys had higher SBP and DBP. CONCLUSIONS: We provided the sex-, age- and height-specific auscultatory BP values using the KNHANES big data. These may be useful in diagnosis and treatment of hypertension in Korean children and adolescents.
Adolescent ; Auscultation ; Blood Pressure ; Child ; Diagnosis ; Female ; Humans ; Hypertension ; Korea ; Methods ; Nutrition Surveys ; Pediatric Obesity ; Reference Values ; Sphygmomanometers