Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research.

Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1-10%), salicylic acid (0.2-2%), and lactobionic acid (1.2-12%) were used as representative substances for α-hydroxyacid (AHA), ß-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50-80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.

Urinary iodine concentration and thyroid hormones: Korea National Health and Nutrition Examination Survey 2013-2015.

PURPOSE: An epidemiologic study that evaluated population's iodine nutrition status and its relationship with thyroid hormones is lacking in iodine-sufficient area. This nationwide study aimed to evaluate the iodine nutrition status in Korea and relationship between urine iodine concentration (UIC) and thyroid hormones. METHODS: A total of 8318 subjects of the Korea National Health and Nutrition Examination Survey VI (2013-2015) with UIC and thyroid hormone evaluation were included. Median UIC level and estimated 24-h iodine intake were calculated. The prevalence of iodine deficiency or excess was obtained using estimated average requirement or above the tolerable upper intake level cut-point method by estimated iodine intake. We analyzed UIC with regard to age, sex, social economic status, and geographic characteristics. RESULTS: The median UIC in general population and estimated iodine intake in adult population were 293.9 µg/L (above requirement according to World Health Organization classification) and 249.3µg/day, respectively. The prevalence of iodine deficiency and excess was 14.0 and 13.4%. The median UIC was higher among SAC [511 (299.9-948.5)] and lower among seventies [251.2 (98.9-761.6)] compared to other age groups. The median UIC increased with household income level (p for trend < 0.001). The subjects living in rural and inland region had lowest UIC among the enrolled subjects. The subgroups with higher median UIC were associated with higher mean TSH levels. CONCLUSIONS: This first nationwide study in Korea demonstrated that the median of UIC and estimated iodine intake lie at nearly 300 µg/L and 250 µg/day, respectively, which shows an overall excellent iodine nutrition.

Non-immune-related hypothyroidism and its relationship with excess iodine.

PURPOSE: In iodine-sufficient areas, autoimmune hypothyroidism has been regarded as the major subtype of hypothyroidism. Non-immune-related hypothyroidism has received little attention because it is considered to be rare. The aim of this study was to evaluate the prevalence of non-immune-related hypothyroidism in Korea and to identify its associating factors. METHODS: A total of 6434 participants in the Korea National Health and Nutrition Examination Survey VI (2013-2015) without known thyroid disease who were examined for thyroid stimulating hormone, free thyroxine, TPO Ab, and urine iodine concentration (UIC) were enrolled. The weighted proportions, demographic variables, and severity of immune-related and non-immune-related hypothyroidism were compared. To assess the effect of iodine on hypothyroidism in TPO Ab positive or negative populations, the weighted prevalence of hypothyroidism was assessed in each population according to UIC or estimated iodine intake subgroups. RESULTS: The prevalence of undetected hypothyroidism in Korea was 3.8% (n = 233). Of these 233 cases, 171 (71.8%) were non-immune-related. In the TPO Ab negative population, the prevalence of hypothyroidism was increased significantly in the subgroup with UIC between 250 and 749 µg/L (HR 2.12 [1.17, 3.83]) and ≥ 750 µg/L (HR 3.42 [1.93, 6.04]) or the subgroups with estimated iodine intake ≥ 750 µg/day (HR 2.81 [1.64, 4.80]). CONCLUSIONS: This nationwide study demonstrated that most cases of hypothyroidism in iodine-sufficient areas are non-immune-related and are associated with excess iodine above a certain level. More attention to this unrecognized but widespread potential health risk is needed.

Lysates of a Probiotic, Lactobacillus rhamnosus, Can Improve Skin Barrier Function in a Reconstructed Human Epidermis Model.

The main function of the skin is to protect the body from the external environment. The barrier function of the skin is mainly provided by the stratum corneum, which consists of corneocytes bound with the corneodesmosomes and lamellar lipids. Skin barrier proteins like loricrin and filaggrin also contribute to the skin barrier function. In various skin diseases, skin barrier dysfunction is a common symptom, and skin irritants like detergents or surfactants could also perturb skin barrier function. Many efforts have been made to develop strategies to improve skin barrier function. Here, we investigated whether the microfluidized lysates of Lactobacillus rhamnosus (LR), one of the most widely used probiotic species for various health benefits, may improve the skin barrier function in a reconstructed human epidermis, Keraskin™. Application of LR lysate on Keraskin™ increased the expression of tight junction proteins; claudin 1 and occludin as determined by immunofluorescence analysis, and skin barrier proteins; loricrin and filaggrin as determined by immunohistochemistry and immunofluorescence analysis and qPCR. Also, the cytotoxicity of a skin irritant, sodium lauryl sulfate (SLS), was alleviated by the pretreatment of LR lysate. The skin barrier protective effects of LR lysate could be further demonstrated by the attenuation of SLS-enhanced dye-penetration. LR lysate also attenuated the destruction of desmosomes after SLS treatment. Collectively, we demonstrated that LR lysate has protective effects on the skin barrier, which could expand the utility of probiotics to skin-moisturization ingredients.

Delayed TSH recovery after dose adjustment during TSH-suppressive levothyroxine therapy of thyroid cancer.

BACKGROUND: Delayed thyroid-stimulating hormone (TSH) recovery during treatment of Graves' disease is caused by long-term excessive thyroid hormone, which results in downregulation of pituitary thyrotrophs. However, it is unknown whether delayed TSH recovery exists after levothyroxine (LT4) dose reduction in patients with differentiated thyroid cancer (DTC) after long-term TSH suppression. METHODS: We retrospectively reviewed 97 DTC patients with LT4 dose reduction after long-term TSH suppression. TSH levels at baseline (point 1), 6 months (point 2) and 12-18 months (point 3) after LT4 dose reduction were compared. A delayed TSH recovery group whose TSH levels changed to upper target TSH category (2015 revised ATA guidelines) from point 2 to point 3 was identified, and risk factors were analysed. RESULTS: The median TSH level at point 3 was significantly higher than that of point 2 (0.17 vs 0.09 mIU/L; P<.001). The delayed TSH recovery group (44.3%) showed increased body weight (60.84 vs 62.73 kg; P=.01), while normal response group did not. Greater reduction (%) in the LT4 dose per weight [HR 1.10, 95% CI (1.00-1.22), P=.04] and higher BMI before thyroid surgery [1.19, 1.03-1.38, P=.01] predicted the occurrence of delayed TSH recovery, while higher dose of LT4 per weight after reduction showed preventive effect [HR 0.01, 95% CI (0.00-0.54); P=.02]. CONCLUSIONS: Delayed TSH recovery was common during LT4 dose reduction after long-term TSH suppression for DTC management. Six months may not be enough for TSH recovery and to evaluate thyroid hormone status by serum TSH.

CT and microbiologic follow-up in primary multidrug-resistant pulmonary tuberculosis.

BACKGROUND: Little attention has been paid to the initial and follow-up computed tomography (CT) features in primary multi-drug resistant tuberculosis (pMDR-TB) setting. PURPOSE: To describe serial CT findings and clinical course of pMDR-TB with antibiotic treatment. MATERIAL AND METHODS: For the last 10 years, 340 MDR-TB patients were managed in a tertiary referral hospital. Among them, we included 44 (27 men, 17 women; mean age, 40 years; age range, 20-81 years) pMDR-TB patients; 37 treated with chemotherapy only and seven treated with medical therapy plus surgery. CT findings were evaluated regarding tree-in-bud sign, acinar nodule, peribronchial, segmental or lobar consolidation and cavity, and their extent. Sputum negative conversion rates and serial CT scores were assessed. To compare changes in disease extent between initial and follow-up CT studies, paired t-test was performed. RESULTS: Two most frequent patterns of lung abnormality were tree-in-bud sign (37 of 44, 84.1%) and acinar nodule (41 of 44, 93.2%). Among 37 patients treated with chemotherapy only, 36 showed negative sputum conversion within 3 months after second-line drug commencement, maintained for >12 months. The other seven undergoing surgery during medical treatment showed excellent outcome with negative conversion achieved within one month after surgery and maintained for >12 months. CT scores showed significant decrease on serial CT studies (P < 0.001) in all. CONCLUSION: In pMDR-TB, two most frequent abnormal CT patterns are tree-in-bud sign and acinar nodule. In 98% of patients, negative sputum conversion is achieved, and CT score also shows decrease in extent after TB chemotherapy.

Use of online clinical videos for clinical skills training for medical students: benefits and challenges.

BACKGROUND: Multimedia learning has been shown effective in clinical skills training. Yet, use of technology presents both opportunities and challenges to learners. The present study investigated student use and perceptions of online clinical videos for learning clinical skills and in preparing for OSCE (Objective Structured Clinical Examination). This study aims to inform us how to make more effective us of these resources. METHODS: A mixed-methods study was conducted for this study. A 30-items questionnaire was administered to investigate student use and perceptions of OSCE videos. Year 3 and 4 students from 34 Korean medical schools who had access to OSCE videos participated in the online survey. Additionally, a semi-structured interview of a group of Year 3 medical students was conducted for an in-depth understanding of student experience with OSCE videos. RESULTS: 411 students from 31 medical schools returned the questionnaires; a majority of them found OSCE videos effective for their learning of clinical skills and in preparing for OSCE. The number of OSCE videos that the students viewed was moderately associated with their self-efficacy and preparedness for OSCE (p < 0.05). One-thirds of those surveyed accessed the video clips using mobile devices; they agreed more with the statement that it was convenient to access the video clips than their peers who accessed the videos using computers (p < 0.05). Still, students reported lack of integration into the curriculum and lack of interaction as barriers to more effective use of OSCE videos. CONCLUSIONS: The present study confirms the overall positive impact of OSCE videos on student learning of clinical skills. Having faculty integrate these learning resources into their teaching, integrating interactive tools into this e-learning environment to foster interactions, and using mobile devices for convenient access are recommended to help students make more effective use of these resources.

Associations between body mass index and clinico-pathological characteristics of papillary thyroid cancer.

OBJECTIVE: Epidemiological studies have demonstrated that excess weight increases the risk of thyroid cancer. However, the associations between excess weight and prognostic factors for thyroid cancer are uncertain. We evaluated the relationships between body mass index (BMI) and clinico-pathological features and outcomes of papillary thyroid cancer (PTC). PATIENTS AND METHODS: Retrospective analysis of 2057 patients with PTC was performed. Patients were grouped according to BMI (underweight, normal weight, overweight and obesity)-based World Health Organization standardized categories. Logistic regression models were used to assess the relationships between BMI and clinico-pathological features of PTC. A Cox proportional hazards model was used to examine the association between BMI and disease recurrence. RESULTS: A 5-kg/m(2) increase in BMI was associated with PTC tumours larger than 1 cm [odds ratio (OR) 1.31, P < 0.001], with microscopic extrathyroidal invasion (OR 1.23, P = 0.006), and with advanced tumour-node-metastasis (TNM) stage (OR, 1.30, P = 0.003), which is independent of confounding variables such as gender, age, serum TSH, total cholesterol and fasting glucose level. The multivariate-adjusted OR [95% confidence intervals (CI)] in the overweight (25.0-29.9 kg/m(2)) and obese (BMI ≥ 30) groups for tumours larger than 1 cm were 1.41 (1.10-1.81) and 2.17 (1.23-3.82), respectively, compared to the normal weight group (BMI 18.5-24.9). The multivariate-adjusted OR (95% CI) for microscopic extrathyroidal extension in the obesity group was 1.88 (1.06-3.32), and the OR for advanced TNM stage in the overweight group was 1.35 (1.02-1.79) compared to the normal weight group. During follow-up (median, 84 month; range, 1-185), 43 patients (2.1%) experienced recurrence. There were no significant differences in recurrence of PTCs among BMI groups. CONCLUSIONS: Higher BMI was strongly associated with larger tumour size, extrathyroidal invasion and advanced TNM stage of PTCs. However, there was no difference in recurrence rate among BMI groups. This study suggests that excess weight is associated with aggressive features of PTCs. Further studies with long-term follow-up are needed to confirm this finding.

Multifocality, but not bilaterality, is a predictor of disease recurrence/persistence of papillary thyroid carcinoma.

BACKGROUND: Although papillary thyroid carcinoma (PTC) often presents as multifocal or bilateral tumors, but whether multifocality or bilaterality is associated with disease recurrence/persistence is controversial. We evaluated the association between multifocality and bilaterality of PTC and disease recurrence/persistence. We also analyzed the location and number of tumors in multifocal PTC. METHODS: We reviewed the medical records of 2,095 patients who underwent total thyroidectomy for PTC. Tumors were classified as solitary or multifocal PTC according to the number of tumors present. Multifocal PTCs were subdivided into multifocal-unilateral and multifocal-bilateral PTC based on the tumor location. Solitary tumor or multifocal tumors located in one lobe were classified as unilateral PTC, and tumors in both lobes were classified as bilateral PTC. We analyzed the clinicopathologic features and clinical outcomes in each classification. Logistic regression models were used to assess the relation between multifocality or bilaterality and disease recurrence/persistence. RESULTS: Extrathyroidal invasion, cervical lymph node metastasis, and advanced TNM stage were significantly more frequent in multifocal PTC than in solitary PTC. Extrathyroidal invasion, cervical lymph node metastasis, advanced TNM stage, and distant metastasis were significantly more frequent in bilateral PTC than in unilateral PTC. The clinicopathologic parameters did not differ significantly between patients with multifocal-unilateral and multifocal-bilateral PTC. Multifocality was found to be an independent predictor of disease recurrence/persistence [odds ratio (OR) 1.45, 95 % confidence interval (CI) 1.01-2.10, p = 0.04]. However, there was no association between bilaterality and disease recurrence/persistence (OR 0.98, 95 % CI 0.64-1.48, p = 0.92). In multifocal PTC, the number of tumors (OR 1.75, 95 % CI 1.04-2.97, p = 0.04), but not the location of tumors (OR 0.56, 95 % CI 0.31-1.02, p = 0.06), was significantly associated with disease recurrence/persistence. CONCLUSIONS: Although multifocal and bilateral PTC had aggressive pathologic features, only multifocality was associated with an increased risk of disease recurrence/persistence. This suggests that the number of tumor foci, but not their location, is a significant predictor of clinical outcomes.

ERK phosphorylation is not increased in papillary thyroid carcinomas with BRAF(V600E) mutation compared to that of corresponding normal thyroid tissues.

BACKGROUND: An association between a BRAF(V600E) mutation and upregulation of mitogen-activated protein kinase (MAPK) pathways in human papillary thyroid carcinoma (PTC) tissues has not been demonstrated well outside of in vitro studies. The aims of this study were to evaluate the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) in human PTCs with BRAF(V600E) mutations compared to that of corresponding normal thyroid tissue and to determine the expressions of Raf kinase inhibitor protein (RKIP) and MAPK phosphatase 3 (MKP-3), possible regulators of ERK1/2 activation. METHODS: We analyzed the presence of BRAF(V600E) mutation and the expressions of BRAF, total ERK, p-ERK, RKIP, and MKP-3 in 33 PTCs and corresponding normal thyroid gland tissues using western blot analysis. RESULTS: BRAF(V600E) mutation was found in 28 (84.8%) of 33 PTCs, 96.4% (27/28) of which showed decreased p-ERK activity, while 75% (21/28) showed increased MKP-3 expression. There were significant differences in p-ERK and MKP-3 expressions between BRAF(V600E) (+) PTCs and normal thyroid glands (p < 0.001). There were no differences in expressions of BRAF, total ERK, and RKIP between PTCs and normal thyroid tissue, irrespective of the presence of BRAF(V600E) mutation. CONCLUSIONS: In human BRAF(V600E) (+) PTCs, ERK phosphorylation is decreased compared to normal thyroid glands and the observed decrease in ERK1/2 MAPK phosphorylation in BRAF(V600E) (+) PTCs may be associated with increased MKP-3 activity.

Evaluation of medical school faculty members' educational performance in Korea in 2022 through analysis of the promotion regulations: a mixed methods study.

PURPOSE: To ensure faculty members' active participation in education in response to growing demand, medical schools should clearly describe educational activities in their promotion regulations. This study analyzed the status of how medical education activities are evaluated in promotion regulations in 2022, in Korea. METHODS: Data were collected from promotion regulations retrieved by searching the websites of 22 medical schools/universities in August 2022. To categorize educational activities and evaluation methods, the Association of American Medical Colleges framework for educational activities was utilized. Correlations between medical schools' characteristics and the evaluation of medical educational activities were analyzed. RESULTS: We defined 6 categories, including teaching, development of education products, education administration and service, scholarship in education, student affairs, and others, and 20 activities with 57 sub-activities. The average number of included activities was highest in the development of education products category and lowest in the scholarship in education category. The weight adjustment factors of medical educational activities were the characteristics of the target subjects and faculty members, the number of involved faculty members, and the difficulty of activities. Private medical schools tended to have more educational activities in the regulations than public medical schools. The greater the number of faculty members, the greater the number of educational activities in the education administration and service categories. CONCLUSION: Medical schools included various medical education activities and their evaluation methods in promotion regulations in Korea. This study provides basic data for improving the rewarding system for efforts of medical faculty members in education.

Time trend in tumour size and characteristics of anaplastic thyroid carcinoma.

OBJECTIVE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies. Nevertheless, there have been reports that some patients experience long-term survival and those in whom ATCs of small size are often detected. We evaluated the time trend of characteristics of ATC such as size and association with coexistent differentiated thyroid carcinoma (DTC). We also found the characteristics of patients showing long-term survival. DESIGN AND PATIENTS: This is a retrospective observational cohort study from the two major tertiary referral hospitals in Seoul, Korea. Ninety-five patients who had been diagnosed with ATC from 1995 to 2010 were included. We classified them into three groups according to the time of initial diagnosis: group 1 (1995-1999), group 2 (2000-2004) and group 3 (2005-2010). RESULTS: The mean tumour size decreased significantly according to groups; 6·2, 5·5 and 4·0 cm in group 1, 2 and 3, respectively (P = 0·02). The frequency of cases with coexistent DTC increased; 10·3%, 35·1% and 48·3% in group 1, 2 and 3, respectively (P = 0·02). Fifteen of 95 patients survived more than 24 months, and among them, 13 are still alive who underwent curative surgery. Among 15 long-term survivors, nine patients with ATC arising from DTC had ATC tumour portion less than 1 cm. Another five patients with ATC without coexistent DTC had relatively small-sized tumours (1·0-4·0 cm). CONCLUSION: The tumour size of ATC decreased, and cases with coexistent DTC increased over the last two decades. We found that patients with ATC showing long-term survival are those who had atypical presentations such as anaplastic transformation in early stage of DTC or small size of tumours without coexistent DTC.

Different diagnostic cut-off values of urinary fractionated metanephrines according to sex for the diagnosis of pheochromocytoma in Korean subjects.

The diagnosis of pheochromocytoma depends on the documentation of catecholamine overproduction. The use of urinary fractionated metanephrines has recently become common for the diagnosis of pheochromocytoma. In order to avoid false positive and false negative results, optimal cut-off levels are necessary; however, there have been few published reports on whether different cut-off levels are needed to diagnose pheochromocytoma according to sex. We reviewed the medical records of 815 subjects (including 103 pheochromocytoma patients) whose of 24-h urinary fractionated metanephrine was measured using high-performance liquid chromatography methods and adrenal imaging at Samsung Medical Center. Receiver operating characteristic (ROC) curves were used to determine cut-off values according to sex. The upper limit values of fractionated metanephrine in healthy volunteers and the control group were significantly higher in male subjects compared with females. When we applied cut-off values according to sex, the diagnostic efficacies (defining a positive test as either metanephrine or normetanephrine levels above the cut-off value) were a sensitivity of 96% in male subjects and 98.1% in female subjects and a specificity of 88.6% in male subjects and 94.1% in female subjects. However, when we applied cut-off values without considering sex, the specificity decreased from 88.6% to 77.8% in male subjects. In this study, urinary fractionated metanephrines had a high level of sensitivity and specificity for the diagnosis of pheochromocytoma. However, diagnostic cut-off values were higher in male subjects than in female subjects. Therefore, different cut-off values may be needed according to sex to diagnose pheochromocytoma in Koreans.

Bone Mineral Density Screening Interval and Transition to Osteoporosis in Asian Women.

BACKGRUOUND: Bone mineral density (BMD) testing is indicated for women aged 65 years, but screening strategies for osteoporosis are controversial. Currently, there is no study focusing on the BMD testing interval in Asian populations. The current study aimed to evaluate the estimated time interval for screening osteoporosis. METHODS: We conducted a study of 6,385 subjects aged 50 years and older who underwent dual-energy X-ray absorptiometry screening more than twice at Samsung Medical Center as participants in a routine health checkup. Subjects were divided based on baseline T-score into mild osteopenia (T-score, <-1.0 to >-1.5), moderate osteopenia (T-score, ≤-1.5 to >-2.0), and severe osteopenia (T-score, ≤-2.0 to >-2.5). Information about personal medical and social history was collected by a structured questionnaire. RESULTS: The adjusted estimated BMD testing interval for 10% of the subjects to develop osteoporosis was 13.2 years in mild osteopenia, 5.0 years in moderate osteopenia, and 1.5 years in severe osteopenia. CONCLUSION: Our study provides extended information about BMD screening intervals in Asian female population. Baseline T-score was important for predicting BMD screening interval, and repeat BMD testing within 5 years might not be necessary in mild osteopenia subjects.

Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients.

BACKGRUOUND: Telomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients. METHODS: We prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma. RESULTS: Of 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; P<0.001), larger primary tumor size (OR, 2.02; P<0.001), and aggressive histological type (OR, 7.78 in follicular thyroid carcinoma; OR, 10.33 in poorly differentiated thyroid carcinoma; OR, 45.92 in anaplastic thyroid carcinoma; P<0.001). Advanced T stage, advanced N stage, and distant metastasis at diagnosis were highly prevalent in mutated thyroid cancers. However, initial distant metastasis was not present in patients with TERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences. CONCLUSION: This study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

Daily urine iodine excretion while consuming a low-iodine diet in preparation for radioactive iodine therapy in a high iodine intake area.

OBJECTIVE: Recommended durations of low-iodine diet (LID) in preparation for radioactive iodine therapy (RAIT) vary among major guidelines and are important for patients in areas where iodine intake is high. The aim of this study was to investigate daily changes in urine iodine excretion after starting a LID. DESIGN: The daily iodine/creatinine (I/Cr) ratios and simple iodine concentration (simple I) of morning spot urine from 19 patients with differentiated thyroid carcinoma were measured for 2 weeks from the start of LID for RAIT preparation. We set the cut-off of I/Cr and simple I for poor LID preparation at >66·2 µg/gCr and >150 µg/l, respectively. The day when daily I/Cr or simple I became equal to or below the cut-off both by 95% CI and 90th percentile was defined as the end-point for the appropriate duration of LID for RAIT. RESULTS: On day 6 of LID, the I/Cr ratio decreased below the cut-off (≤66·2 µg/gCr) both by 95% CI (0-60·8) and by 90th percentile (51·9). Simple I reached the cut-off (≤150 µg/l) on day 3 by both parameters (95%CI: 2·3-90·5; 90th percentile: 126·5). The morning spot-urine I/Cr and simple I on day 7 and day 14 were significantly lower than on day 0 (P < 0·05). CONCLUSIONS: One week of a strict LID is enough to decrease the level of urine iodine excretion in preparation for RAIT even in high iodine intake areas. These results provide essential data for future outcome studies regarding LID preparation for RAIT.

Identification of HLA-DRB1 alleles associated with Graves' disease in Koreans by sequence-based typing.

The human leukocyte antigen (HLA) region, particularly class II genes, plays a primary role in the susceptibility to development of GD. We investigated the allelic polymorphism of HLA class II DRB1 genes to examine its association with GD in Koreans. We performed the high resolution polymerase chain reaction-sequence based typing (PCR-SBT) of HLA-DRB1 in 133 patients with GD and 200 healthy controls. Compared to healthy controls, the patients with GD had increased frequencies of DRB1*030101 (4.9% vs.1.8%, p = 0.034), DRB1*080201 (5.3% vs. 2.3%, p = 0.050) and DRB1*140301 (3.4% vs. 1.0%, p = 0.043). In contrast, the frequencies of DRB1*070101 (3.0% vs. 7.3%, p = 0.024) and DRB1*130201 (4.1% vs. 9.0%, p = 0.010) were decreased in the patients with GD. However, the corrected p values were not significant in above all alleles. Patients with DRB1*040301 were significantly older than controls (45 years vs. 35 years, p = 0.017). DRB1*040301, DRB1*150201, DRB1*120101 and DRB1*120201 were associated with male predominance, strong familial associations, thyroid ophthalmopathy and radioactive iodine therapy, respectively. In conclusion, there were no significant HLA-DRB1 alleles associated with GD in Koreans, although some alleles were correlated with the clinical characteristics.

Transient left ventricular systolic dysfunction with thrombus and subsequent cardioembolic stroke in short-term overt hypothyroidism.

A 57-year-old woman was referred for cardiomegaly on a chest X-ray taken during thyroxine withdrawal for radioiodine therapy after total thyroidectomy. Baseline transthoracic echocardiography showed left ventricular (LV) wall motion abnormalities and an LV apical mural thrombus. Coronary angiography revealed normal epicardial coronary arteries. Despite anticoagulation treatment, the patient developed abrupt aphasia, agraphia and acalculia. The distal branch of the inferior segmental branch on the left middle cerebral artery was not well visualized on magnetic resonance angiography. Three days later, the patient had made a near full neurological recovery. After 4 weeks of anticoagulation therapy, the apical mural thrombus and wall motion abnormalities resolved. This is the first reported case in the medical literature of transient LV systolic dysfunction with thrombus and subsequent cardioembolic stroke in a patient with short-term overt hypothyroidism.

Anti-proliferative effect and action mechanism of dexamethasone in human medullary thyroid cancer cell line.

INTRODUCTION: Dexamethasone is known to inhibit the cell proliferation of certain transformed cell lines. In this study, the effect and action mechanism of dexamethasone were examined in the human medullary thyroid cancer cell line, TT cells. METHODS: TT cells were treated with or without dexamethasone. 5-Bromo-2'-deoxyuridine uptake assay was used to evaluate cell proliferation. Cell cycle and its regulatory proteins were assessed by flow cytometry and western blot analysis, respectively. Apoptosis was analyzed by Hoechst staining and Annexin V assay. RESULTS: Dexamethasone significantly reduced TT cell proliferation by 60% (p < 0.01). A substantial portion of cells was arrested at the G1 phase. The expression levels of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK2 were decreased. In addition, the phosphorylation of retinoblastoma protein, which is a critical checkpoint protein in the transition of G1 to S phase, was decreased. On the other hand, the expression level of p27(Kip1), which is a cyclin/CDK inhibitor, was enhanced. Hoechst staining showed many fragmented nuclei in the dexamethasone-treated cells. The proportion of early apoptotic cells was also increased in the Annexin V assay. CONCLUSION: Dexamethasone inhibited the proliferation of TT cells through cell cycle arrest at the G1 phase and increased apoptosis.

Trends in Childhood Thyroid Cancer incidence in Korea and Its Potential Risk Factors.

Background: Although the incidence of thyroid cancer had been increasing until a few years ago, a decrease has been observed in the last years, probably due to the reduction of the screening tests in Korea. Childhood thyroid cancer has been increasing in the past with the same trend as in adults, but there have been few reports on recent trends. We analyzed the trends of thyroid cancer in Korean children and related factors. Methods: From national statistics and cancer register database, the data of age-specific incidence rate in Korean childhood thyroid cancer from 1999 to 2017 was obtained, and levels of seaweed intake, the number of computed tomography (CT) and neck ultrasonography (US), obesity prevalence rate, and smoking and alcohol consumption rates in children were analyzed. Results: The age-specific incidence of thyroid cancer in Korean children has increased in both genders between 1999 and 2017 (2.0 in 1999 vs. 7.2 in 2017, per population of 100,000), especially in the age group of 14-18 years (1.5 in 1999 vs. 5.5 in 2017, per population of 100,000). During the same period, levels of seaweed intake, number of CT scans and neck US, and prevalence of obesity in children increased significantly, while childhood smoking and alcohol consumption rates decreased. Conclusion: Unlike the adult thyroid cancer in Korea, childhood thyroid cancer continues to increase, and the cause might be accompanied by actual increases due to the environmental factors such as excessive iodine intake, exposure to medical radiation, and increased obesity prevalence as well as the screening effect.