The effect of statin treatment on glucose homeostasis in prediabetic individuals: A prospective, randomized, controlled trial.

BACKGROUND: This study aimed to evaluate the effects of rosuvastatin and pravastatin on glucose homeostasis and other biomarkers in individuals at high risk of developing diabetes. METHODS: This prospective, randomized, open-labeled, and controlled trial included prediabetic individuals with impaired fasting glucose and impaired glucose tolerance. The participants were randomized into three groups: rosuvastatin (10 mg), pravastatin (40 mg), or control. Biomarkers of diabetes and glucose and insulin responses to oral glucose tolerance tests were assessed at baseline and after six months of treatment. The primary outcomes were comparisons of glucose homeostasis and biomarkers of diabetes among groups at baseline and after six months of treatment. RESULTS: A total of 141 subjects with IFG were screened and 41 participants were recruited. Twenty-two subjects were randomized to either the rosuvastatin or pravastatin group and 19 subjects were assigned to the control group. After six months of treatment, all groups had similar cholesterol and triglyceride levels. Likewise, HbA1c levels, glucose, and insulin excursions during oral glucose tolerance test, were similar among the three groups. However, compared to the other groups, the rosuvastatin group had higher HOMA-IR (insulin resistance) and a lower Matsuda index (insulin sensitivity). CONCLUSION: Among prediabetic individuals with IFG, rosuvastatin treatment was associated with increased insulin resistance and decreased insulin sensitivity compared to pravastatin and control groups. Further research is needed to elucidate the underlying mechanisms and clinical implications of these findings.This trial was registered with the statins on glucose homeostasis in subjects with impaired fasting glucose and ClinicalTrials.gov, NCT01816997.

Determination of the Elemental Iodine in Human Breast Milk by Inductively Coupled Plasma mass Spectrometry.

Adequate iodine status in lactating women is defined by a maternal median urinary iodine concentration (UIC) ≧ 100 µg/L. However, the above-mentioned criterion does not account for the secretion of iodine into breast milk and could not truly reflect the amount of iodine delivered to the infants. Measuring breast milk median iodine concentration (BMIC) is crucial, but the method to measure BMIC has not been developed and validated in Taiwan. We adopted the ammonia dilution method without prior sample digestion to measure BMIC by inductively coupled plasma mass spectrometry (ICP-MS). Samples and iodate calibrators were prepared into an aqueous solution containing Triton X-100, 0.5% ammonia solution, and tellurium (128Te) as the internal standard. Precision, accuracy, serial dilution, and recovery tests were performed for method validation. The range of intra-assay and inter-assay coefficient of variation for the four human breast milk samples with different iodine concentrations were 3.2-4.7% and 2.3-5.5%, respectively. The standard NIST 1549 milk powder was prepared into three different concentrations of 50 µg/L, 100 µg/L, and 200 µg/L to assess the accuracy; the bias was < 5%. A recovery of 95-105% was achieved for four human breast milk samples spiked with sodium iodide solution. The serial dilution test confirmed linearity up to 0.998. The limit for detection and quantification was 0.78 µg/L and 2.34 µg/L, respectively. The results of the current study confirmed that this ICP-MS method is accurate and reliable in measuring BMIC.

Iodine Concentration in the Breast Milk and Urine as Biomarkers of Iodine Nutritional Status of Lactating Women and Breastfed Infants in Taiwan.

Breast milk iodine concentration (BMIC) can be different when median urinary iodine concentration (UIC) is similar. The BMIC, UIC/creatinine (Cr), estimated 24-h urinary iodine excretion (24-h UIE) of lactating women in Taiwan is unknown. This study enrolled lactating women from Taipei Veterans General Hospital (August 2021-February 2023). Each participant provided a random spot urine sample, two breast milk samples, a blood sample, and completed a food frequency questionnaire on the same day. Iodine measurement was performed by inductively coupled plasma mass spectrometry. The median UIC of the enrolled 71 women was 91.1 µg/L, indicating insufficient iodine status; however, the median BMIC was 166.6 µg/L and this suggested that the amount of iodine delivered through breast milk was adequate for the breastfed infants. BMIC was correlated with UIC/Cr and 24-h UIE (both rs = 0.49) but not with UIC (rs = 0.18) or thyroid stimulating hormone (rs = 0.07). Women who did not consume dairy products (adjusted odds ratio: 24.41, 95% confidence interval: 1.26-471.2) and multivitamins (adjusted odds ratio: 8.26, 95% confidence interval: 1.76-38.79) were at increased odds for having lower BMIC. The results suggest that measuring maternal UIC alone may not be sufficient, as BMIC, UIC/Cr, and 24-h UIE are all important biomarkers. Ingestion of dairy products and multivitamins were independently associated with BMIC.

Clinical characteristics of neutropenic patients under antithyroid drug: Twelve-year experience in a medical center.

BACKGROUND: Thionamide-induced agranulocytosis (TiA) is a rare adverse event with a reported incidence of approximately 0.1% to 1.75%. Prompt recognition of TiA is critical to reduce the mortality rate. However, the differential diagnosis between cases of TiA and non-TiA neutropenia can be challenging due to the potential simultaneous involvement of other causes of neutropenia, such as concomitant chemotherapy, liver dysfunction, or infection. The aim of the present study was to investigate the possible factors associated with the development of TiA. METHODS: This was a retrospective cohort study of patients treated with antithyroid drugs (ATDs) in Taipei Veterans General Hospital, Taipei, Taiwan, from 2006 to 2018. Patients who developed a neutropenic event during treatment with ATDs were identified from their medical records. The diagnosis of TiA was based on the following: (1) development of neutropenia during treatment or within 7 days after previous exposure to the same ATDs; (2) complete resolution of neutropenia within 1 month after discontinuation of the culprit drug with an absolute neutrophil count (ANC) >1500/µL; and (3) exclusion of other causes of neutropenia. The incidence and risk factors of TiA were analyzed and compared with those of non-TiA neutropenia. RESULTS: Among 6644 patients treated with ATDs, 66 (mean age: 53 ± 15 years; 16.2% men) developed a neutropenic event and 20 were diagnosed with TiA (incidence: 0.3%). In the univariate analysis, compared with non-TiA neutropenia, TiA was associated with a lower Charlson Comorbidity Index, shorter treatment duration, lower cumulative ATD dosage, higher ATD dosage, higher ANC, and higher levels of free T4 at the time of the neutropenic event. In the multivariate logistic regression analysis, after adjusting for age, gender and the time to neutropenia, the cumulative ATD dose to neutropenia and ATD dosage at the time of the neutropenic event, Charlson Comorbidity Index, free T4 levels (odds ratio [OR], 4.44; 95% CI, 1.48-13.25), and ANC (OR, 1.00; 95% CI, 1.00-1.01) remained independently associated with TiA. CONCLUSION: Patients with TiA were more likely to have higher levels of free T4 and ANC at the time of the neutropenic event vs those with non-TiA neutropenia.

A Shift in Molecular Drivers of Papillary Thyroid Carcinoma Following the 2017 World Health Organization Classification: Characterization of 554 Consecutive Tumors With Emphasis on BRAF-Negative Cases.

Most studies for comprehensive molecular profiling of papillary thyroid carcinoma (PTC) have been performed before the 2017 World Health Organization (WHO) classification, in which the diagnostic criteria of follicular variants of PTC have been modified and noninvasive follicular thyroid neoplasm with papillary-like nuclear features has been introduced. This study aims to investigate the shift in the incidence of BRAF V600E mutations in PTCs following the 2017 WHO classification and to further characterize the histologic subtypes and molecular drivers in BRAF-negative cases. The study cohort consisted of 554 consecutive PTCs larger than 0.5 cm between January 2019 and May 2022. Immunohistochemistry for BRAF VE1 was performed for all cases. Compared with a historical cohort of 509 PTCs from November 2013 to April 2018, the incidence of BRAF V600E mutations was significantly higher in the study cohort (86.8% vs 78.8%, P = .0006). Targeted RNA-based next-generation sequencing using a FusionPlex Pan Solid Tumor v2 panel (ArcherDX) was performed for BRAF-negative PTCs from the study cohort. Eight cribriform-morular thyroid carcinomas and 3 cases with suboptimal RNA quality were excluded from next-generation sequencing. A total of 62 BRAF-negative PTCs were successfully sequenced, including 19 classic follicular predominant PTCs, 16 classic PTCs, 14 infiltrative follicular PTCs, 7 encapsulated follicular PTCs, 3 diffuse sclerosing PTCs, 1 tall cell PTC, 1 solid PTC, and 1 diffuse follicular PTC. Among them, RET fusions were identified in 25 cases, NTRK3 fusions in 13 cases, BRAF fusions in 5 cases including a novel TNS1::BRAF fusion, NRAS Q61R mutations in 3 cases, KRAS Q61K mutations in 2 cases, NTRK1 fusions in 2 cases, an ALK fusion in 1 case, an FGFR1 fusion in 1 case, and an HRAS Q61R mutation in 1 case. No genetic variants, from our commercially employed assay, were detected in the remaining 9 cases. In summary, the incidence of BRAF V600E mutations in PTCs significantly increased from 78.8% to 86.8% in our post-2017 WHO classification cohort. RAS mutations accounted for only 1.1% of the cases. Driver gene fusions were identified in 8.5% of PTCs and were clinically relevant given the emerging targeted kinase inhibitor therapy. Of the 1.6% of cases for which no driver alteration was detected, the specificity of drivers tested and tumor classification require further investigation.

Measurements of elemental iodine in soy sauces in Taiwan using a modified microplate method.

Background: Soy sauce is widely used in a variety of Asian dishes to enhance flavor. Soybean and most soybean products, including soy sauces, are listed as prohibited foods in a low iodine diet. However, the iodine content in soy sauces is largely unknown. The aim of this study was to determine the iodine content in domestic soy sauces in Taiwan. Methods: Twenty-five different kinds of soy sauces were diluted with distilled water and with a dilution factor of fifty or above. Iodine concentrations of the diluted samples were measured colourimetrically based on the Sandell-Kolthoff reaction by a modified microplate method. All the measurements were repeated twelve times on three different days for determination of mean and standard deviation (SD), and coefficients of variance (CV). Serial dilution and recovery tests were also performed for validation. The results were confirmed by an inductively coupled plasma mass spectrometry (ICP-MS) method. Results: Among the twenty-five surveyed soy sauces, most of them (n=22) were iodine-free (<16 ug/L, and thus un-detectable). The iodine concentrations (mean ± SD) of the three iodine-containing soy sauces were 2.7 ± 0.1, 5.1 ± 0.2, and 10.8 ± 0.6 mg/L, respectively. The inter-assay, intra-assay and total CVs were all <5.3% for the modified microplate method. The results obtained by ICP-MS were consistent with those of the modified microplate method. The recovery rates in the serial dilution test and recovery test ranged from 94.7% to 118.6%. Two of the three iodine-containing soy sauces were supplemented with kelp extract, while the other one without kelp extract had the highest amount of salt among the three iodine-containing soy sauces. Therefore, we postulate that iodized salt instead of kelp extract is the source of higher iodine content in that sauce. Conclusion: The results suggest that most soy sauces are iodine-free and may be allowed during low iodine diets.

2022 Taiwan clinical multicenter expert consensus and recommendations for thyroid radiofrequency ablation.

Radiofrequency ablation (RFA) is a minimally invasive management strategy that has been widely applied for benign and recurrent malignant thyroid lesions as an alternative to surgery in Taiwan. Members of academic societies for specialists in interventional radiology, endocrinology, and endocrine surgery collaborated to develop the first consensus regarding thyroid RFA in Taiwan. The modified Delphi method was used to reach a consensus. Based on a comprehensive review of recent and valuable literature and expert opinions, the recommendations included indications, pre-procedural evaluations, procedural techniques, post-procedural monitoring, efficacy, and safety, providing a comprehensive review of the application of RFA. The consensus effectively consolidates advice regarding thyroid RFA in clinical practice for local experts.

Analytical validation of an inductively coupled plasma mass spectrometry method for urinary iodine concentration measurements in Taiwan.

BACKGROUND: Urinary iodine concentration (UIC) measured by Sandell-Kolthoff spectrophotometric method has been used in the Nutrition and Health Surveys in Taiwan but this method is time consuming and produces toxic waste from arsenic trioxide. The aim of this study was to develop and validate an inductively coupled plasma mass spectrometry (ICP-MS) system to determine UIC in Taiwan. METHODS: Samples and iodine calibrators were diluted 100-fold into an aqueous solution containing Triton X-100, 0.5% ammonia solution, and tellurium (128Te) as an internal standard. Digestion prior to analysis was not necessary. Precision, accuracy, serial dilution, and recovery tests were performed. A total of 1243 urine samples covering a wide range of iodine concentrations were measured by both Sandell-Kolthoff method and ICP-MS. Passing-Bablok regression and Bland-Altman plots were used to compare values across methods. RESULTS: The limit for detection and quantification by ICP-MS was 0.95 µg/L and 2.85 µg/L, respectively. The intra-assay and inter-assay coefficients were <10%, with a recovery range of 95%-105%. The results obtained by ICP-MS and the Sandell-Kolthoff method were highly correlated (Pearson's correlation: r = 0.996, 95% confidence interval [CI]: 0.9950-0.9961, p < 0.001). For UIC between 20 and 1000 µg/L, the y-intercept for the Passing-Bablok regression was -1.9 (95% CI: -2.5599 to -1.3500) and the slope was 1.01 (95% CI: 1.0000-1.0206). CONCLUSION: This validated ICP-MS system can be used for measuring UIC.

Mean HbA1c and HbA1c variability are associated with differing diabetes-related complications in patients with type 2 diabetes mellitus.

AIMS: To study the different effects of mean HbA1c and HbA1c variability on diabetes-related complications in patients with type 2 diabetes mellitus. METHODS: 1869 patients with type 2 diabetes were followed-up for a median of 9.5 years in a Diabetes Shared Care Program. Mean HbA1c (HbA1c-mean) and standard deviation of HbA1c (HbA1c-SD) were calculated during the first 5 years. The clinical outcomes included nephropathy (urine albumin-to-creatinine ratio [UACR] > 300 mg/g and doubling of serum creatinine), retinopathy (any and advanced), and mortality (due to all-causes, and cardiovascular disease [CVD]). RESULTS: HbA1c-mean was independently associated with UACR > 300 mg/g (Hazard ratio [HR] 1.308 [95% confidence interval {CI}, 1.194-1.433]), any retinopathy (HR 1.274 [1.171-1.385]), and advanced retinopathy (HR 1.237 [1.014-1.509]). HbA1c-SD was independently associated with UACR > 300 mg/g (HR 1.478 [1.189-1.837]), doubling of serum creatinine (HR 2.133 [1.470-3.095]), all-cause mortality (HR 1.880 [1.561-2.266]), and CVD mortality (HR 1.431 [1.069-1.915]). Receiver operating characteristic (ROC) curves showed HbA1c-mean was more associated with any retinopathy, whereas HbA1c-SD was more associated with doubling of serum creatinine, all-cause and CVD mortality. CONCLUSION: Both HbA1c-mean and HbA1c-SD predicted most diabetes-related complications in patients with type 2 diabetes. However, HbA1c-mean was more effective at predicting retinopathy, while HbA1c-SD was more effective at predicting deterioration of renal function and increased mortality.

A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes.

CONTEXT: There is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic ß-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of ß-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment. OBJECTIVE: This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone. METHODS: Participants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment. RESULTS: A total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (-0.36, P = 0.0373) and 450 mg/day (-0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-ß score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial. CONCLUSION: Addition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.

Factors related to overweight and obese populations maintaining metabolic health.

Background: For people who are overweight or obese, maintaining a metabolically healthy status can decrease the risks of developing cardiovascular diseases and Type 2 diabetes. Despite this, only a limited amount of research has discussed the metabolically healthy overweight and obesity (MHOO) population in Asia and the factors associated with them maintaining their metabolic health. Methods: This study enrolled 195 MHOO participants from communities in northern Taiwan during 2009-2010 (baseline). Of the 195 participants, 89 completed the follow-up assessment after a median follow-up time of nine years. Body type was determined by body mass index (BMI, kg/m2). We defined overweight as a BMI ≥ 24 kg/m2 and <27 kg/m2 and defined obese as a BMI ≥ 27 kg/m2. Metabolic health was defined as the absence of cardiometabolic diseases and the presence of ≤1 of the cardiometabolic risk factors, namely hypertension, hyperglycemia, hypertriglyceridemia, and low serum high-density lipoprotein cholesterol. Metabolic health, BMI, and other covariates were evaluated at both baseline and follow-up. Generalized estimating equations (GEE) models were used to analyze the factors associated with maintenance of metabolic health during the follow-up period. Results: At baseline, the mean age of the study participants was 47.4 (SD 5.3) years and 46 (51.7%) of the participants were women. There were 51 (57.3%) individuals who maintained their metabolic health status at the time of the nine-year follow-up. The detrimental factors pertaining to metabolic health included older age, longer duration until follow-up, BMI ≥ 27 kg/m2, and increase in waist circumference. No significant relationships were observed between sociodemographic factors and lifestyle factors, such as sex, level of education, cigarette smoking, alcohol consumption, and physical activity, and sustained metabolic health among MHOO individuals. Conclusions: To maintain metabolic health and prevent negative changes in health status, control of bodyweight and waist circumference should remain a priority for MHOO individuals even when there are no metabolic disorders present.

Soluble tumor necrosis factor receptor 2 is associated with progressive diabetic kidney disease in patients with type 2 diabetes mellitus.

BACKGROUND: Chronic low-grade inflammation is considered one of the major mechanisms for the progression of diabetic kidney disease. We investigated the prognostic value of circulating soluble tumor necrosis factor receptor 2 (sTNFR2) for early nephropathy in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 364 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 were followed up for a median of 4 years. Renal outcomes were defined as a composite of either or both a >30% decline in the eGFR and/or albuminuria stage progression determined with consecutive tests. RESULTS: Seventy-three patients developed renal composite events. Serum concentrations of sTNFR2 were strongly associated with the risk of renal function decline and progressive changes in albuminuria. Through a receiver operating characteristic curve analysis, a serum sTNFR2 level of 1.608 ng/mL was adopted as the discriminator value for predicting renal outcomes (area under the curve 0.63, 95% confidence interval 0.57-0.70, p < 0.001), yielding a sensitivity of 75.3% and a specificity of 51.2%. The association of sTNFR2 levels ≥1.608 ng/mL to renal outcomes was significant after adjusting for relevant variables (hazard ratio 2.27, 95% confidence interval 1.23-4.20, p = 0.009) and remained consistent across subgroups stratified by age, sex, systolic blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system blockers. CONCLUSIONS: Higher circulating levels of sTNFR2 are independently associated with an eGFR decline and progressive albuminuria in patients with type 2 diabetes.

The role of growth hormone and IGF-1 in retinopathy: a prospective study of retinopathy in patients with acromegaly and impaired fasting glucose.

AIMS: To investigate the effects of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis on the incidence and progression of retinopathy. METHODS: We enrolled 91 patients with acromegaly and 123 subjects with impaired fasting glucose (IFG) between 2008 and 2016 to examine the incidence and prevalence of retinopathy. Patients attended follow-ups in our clinics and underwent examinations according to the national guidelines for diabetes management. Both cohorts attended follow-ups until June 2019. RESULTS: Both groups had similar HbA1c, cholesterol, and blood pressure levels. However, patients with acromegaly had higher GH (8.05 ± 16.18 vs. 0.78 ± 1.25 ng/mL) and IGF-1 (547.0 ± 342.1 vs. 146.7 ± 51.4 ng/mL) levels than in subjects with IFG. During the follow-up period, 8 patients (8.8%) with acromegaly and 12 patients (9.8%) with IFG developed some degree of retinopathy. Three patients with acromegaly and two with IFG progressed to proliferative retinopathy. Patients with acromegaly had the same incidence of non-proliferative retinopathy (odds ratio [OR] 0.830; 95% CI 0.318-2.164) and a non-statistically significantly higher incidence of proliferative retinopathy (OR 2.461; 95% CI 0.404-14.988). CONCLUSION: The data reveals that GH and IGF-1 might play a crucial role in the development of proliferative retinopathy and influence its progression. Therefore, we suggest screening patients with acromegaly should be similar to diabetes patients.

Do Metabolically Healthy People with Obesity Have a Lower Health-Related Quality of Life? A Prospective Cohort Study in Taiwan.

The association between metabolically healthy obesity (MHO) and health-related quality of life (HRQOL) has not been thoroughly evaluated. This study enrolled 906 adult participants aged 35-55 years between 2009 and 2010 in Northern Taiwan; 427 participants were followed up after eight years. Normal weight, overweight, and obesity were evaluated via body mass index. Metabolic health was defined as the absence of cardiometabolic diseases and having ≤1 metabolic risk factor. HRQOL was evaluated using the 36-Item Short Form Health Survey (SF-36), Taiwan version. Generalized linear mixed-effects models were used to analyze the repeated, measured data with adjustment for important covariates. Compared with metabolically healthy normal weight individuals, participants with metabolically unhealthy normal weight and obesity had a significantly poorer physical component summary score (ß (95% CI) = -2.17 (-3.38--0.97) and -2.29 (-3.70--0.87), respectively). There were no significant differences in physical and mental component summary scores among participants with metabolically healthy normal weight, overweight, and obesity. This study showed that metabolically healthy individuals with obesity and normal weight had similar HRQOL in physical and mental component summary scores. Maintaining metabolic health is an ongoing goal for people with obesity.

Changes in metabolic syndrome affect the health-related quality of life of community-dwelling adults.

Metabolic syndrome (MetS) is associated with cardiovascular diseases, type 2 diabetes, chronic renal diseases, and all-cause mortality. Furthermore, MetS is associated with poor health-related quality of life (HRQOL). However, the impact of dynamic changes in MetS on changes in the HRQOL was not previously explored. This was an eight-year, prospective cohort study in which 906 middle-aged adults from Shipai, Taipei in northern Taiwan were enrolled during 2009-2010 (baseline). Of those sampled, 427 participants completed the follow-up investigation after 8 years. The HRQOL was measured using the Short Form Health Survey (SF-36). Other variables including age, sex, marital status, level of education, smoking, alcohol consumption, baseline body mass index, and changes in physical activity were adjusted. Compared with adults who never experienced MetS, adults with persistent MetS had a negative change in mental HRQOL (ß - 4.20, 95% CI - 7.54 to - 0.86, p = 0.01). The negative changes of persistent MetS on the HRQOL were in the domains of vitality and mental health (ß - 4.42, 95% CI - 8.10 to - 0.73 and ß - 3.47, 95% CI - 6.90 to - 0.04, respectively). Women and overweight adults were vulnerable to the detrimental effects of persistent MetS. For better HRQOL, more resources should be devoted to reversing MetS in public health.

Increased regulated on activation, normal T-cell expressed and secreted levels and cysteine-cysteine chemokine receptor 5 upregulation in omental adipose tissue and peripheral blood mononuclear cells are associated with testosterone level and insulin resistance in polycystic ovary syndrome.

OBJECTIVE: To study the relationship between circulating chemokine cysteine-cysteine motif ligand (CCL) 5 levels and cysteine-cysteine chemokine receptor type 5 (CCR5) expression in peripheral blood mononuclear cells (PBMCs) and adipose tissue with hyperandrogenism and insulin resistance in patients with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): Fifteen women with PCOS and 15 controls matched for body mass index and age were enrolled in this study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Plasma levels of CCL3, CCL4, and CCL5 were determined using enzyme-linked immunosorbent assay kits, and omental adipose tissue and PBMCs were analyzed using real-time polymerase chain reaction to determine the expression level of CCR5 in participants. RESULT(S): Levels of CCL5 were significantly higher in women with PCOS. Expression of CCR5 in adipose tissue and PBMCs was significantly higher in women with PCOS compared with that in women in the control group. Cysteine-cysteine chemokine receptor type 5 expression also was upregulated in THP-1 cells after chronic exposure to testosterone. Levels of CCL5 had a significant positive correlation with testosterone levels in women with PCOS. Moreover, CCR5 showed a positive correlation with fasting glucose levels, homeostasis model insulin resistance index, and C-reactive protein. CONCLUSION(S): Increased levels of CCL5 and overexpression of CCR5 in PBMCs and adipose tissue are associated with hyperandrogenism and insulin resistance in women with PCOS. Additionally, CCR5 and CCL5 may be used as biomarkers in the pathogenesis of PCOS.

Iodine nutritional status of lactating women in northern Taiwan in 2019.

BACKGROUND: Pregnant and lactating women are vulnerable to iodine deficiency. This study was conducted to evaluate the iodine nutritional status of lactating women in northern Taiwan. METHODS: Women recruited from Taipei Veterans General Hospital (TVGH) in 2019 provided a spot urine sample and completed a Food Frequency Questionnaire. The urinary iodine concentration (UIC) was measured by inductively coupled plasma mass spectrometry. RESULTS: The overall median UIC in 198 women was 120.4 µg/L, indicating a sufficient iodine status. Univariate analysis revealed a lower median UIC in women of younger age (p = 0.004), who were not taking multivitamins (p = 0.004), not on a postpartum nourishment diet (p = 0.04), and whose infant received more breast milk (p = 0.004). The median UIC was <100 µg/L in the group aged 20 to 29 years (UIC: 74.4 µg/L) and in women whose infants' diet was composed of >50% breast milk (UIC: 86.1 µg/L). A postpartum nourishment diet was followed by 73.7% (n = 146) of the women. Nevertheless, a significant decrease in the intake frequency of iodine-containing foods, including seaweeds (p < 0.001), seafood (p < 0.001), dairy products (p = 0.009), and multivitamins (p < 0.001) was observed compared with the intake noted in a previous survey of pregnant women in TVGH. Following multivariate analysis, only younger age (20-29 vs ≥30 years; odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.49-7.65), no use of multivitamin (OR: 1.89; 95% CI: 1.03-3.48), and infant diet composition (>50% breast milk vs <50% breast milk; OR: 2.93; 95% CI: 1.37-6.25) were independently associated with UIC < 100 µg/L. CONCLUSION: The results suggest that the iodine status in lactating women in northern Taiwan is adequate. However, iodine deficiency may continue to be present in certain subgroups, such as women of younger age and those who do not take multivitamins.

Serum uric acid and blood pressure among adolescents: data from the Nutrition and Health Survey in Taiwan (NAHSIT) 2010-2011.

PURPOSE: Elevated serum uric acid (UA) is frequently observed in adults with high blood pressure (BP); however, data from adolescents are limited. We examined the association between serum UA and BP in a nationally representative sample of Taiwan adolescents. MATERIAL AND METHODS: Some 1384 participants, aged 14-19 years, from the Nutrition and Health Survey in Taiwan 2010-2011 were included for the study. Elevated BP was defined as systolic or diastolic BP ≥120/80 mmHg. The analyses examined the relationship between serum UA and BP using linear regression and odds ratios of having an elevated BP using logistic regression. RESULTS: In this study population, the mean age was 16.0 years, mean serum UA was 5.8 mg/dL, 22.5% were obese (body mass index ≥24 kg/m2) and 9.8% had an elevated BP. Compared to girls, boys are more likely to be obese and to have higher serum UA and BP. After full adjustments, systolic BP, diastolic BP and mean arterial pressure increased 0.45, 0.48 and 0.47 mmHg, respectively, for each 1-mg/dL increase in UA (p = 0.07, 0.03 and 0.02, respectively). The odds of having an elevated BP were 3.4 times higher in subjects of the upper tertile of serum UA than those of the lower tertile (p = 0.02). CONCLUSION: Adolescents with factors as male, obesity, and UA ≥5.5 mg/dL were prone to have an elevated BP, regardless of age and family history of hypertension. The present study found that serum UA levels are significantly correlated to BP in Taiwanese adolescents.

Growth hormone control and cardiovascular function in patients with acromegaly.

BACKGROUND: Acromegaly is associated with cardiovascular alterations. Up to 50% acromegalic patients suffered from treatment failure after multiple modalities. We investigated correlation between cardiovascular function and control of growth hormone (GH) in acromegalic patients following transsphenoidal adenomectomy (TSA). METHODS: We recruited acromegalic patients who had undergone TSA between 2006 and 2014 in this cross-sectional study. Patients were assigned to group 1, controlled acromegaly (GH <1.0 ng/mL and normalized insulin-like growth factor-1 [IGF-1]); group 2, partially controlled acromegaly (either GH >1.0 ng/mL or non-normalized IGF-1); or group 3, uncontrolled acromegaly (GH >1.0 ng/mL and non-normalized IGF-1). Echocardiography evaluated the left ventricular mass index, left ventricular ejection fraction, and the early transmitral filling velocity (E)-to-late transmitral filling velocity (A) and the E-to-the early diastolic mitral annular velocity (E') ratios. Carotid tonometry evaluated the intima-media thickness of the carotid artery, carotid-femoral pulse wave velocity, augmentation index, aortic characteristic impedance (Zc), and pulse pressure amplification. RESULTS: Thirty-three patients participated in this study. Fourteen of the 33 patients were males (42%). Mean age at diagnosis was 50.33 years (SD 18.45). Compared to patients in group 1, patients in group 3 had younger age and shorter years after operation, without statistical significance. Cumulative GH levels were progressively higher from group 1 to group 3, without statistical significance. The groups did not differ with respect to cardiovascular structure and function evaluated by echocardiography and carotid tonometry. Only Zc value had a difference that was of borderline significance (group 1: 109.13 ± 32.99; group 2: 129.30 ± 32.27; group 3: 159.56 ± 77.4 dynes × s/cm5; ANOVA p = 0.088; p = 0.086 for group 1 vs group 3). CONCLUSION: In the patients with acromegaly who had undergone TSA, cardiac structure and vascular stiffness did not differ among the groups with different levels of GH control.

Detection of NTRK1/3 Rearrangements in Papillary Thyroid Carcinoma Using Immunohistochemistry, Fluorescent In Situ Hybridization, and Next-Generation Sequencing.

NTRK1/3 rearrangements have been reported in 2.3-3.4% of papillary thyroid carcinoma (PTC) and are regarded as potential therapeutic targets. Recently, the application of immunohistochemistry (IHC) to detect NTRK rearrangements has been widely discussed. The current study aimed to characterize the clinicopathological features of PTC with NTRK1/3 fusions, to examine the utility of pan-TRK IHC, and to compare IHC with fluorescent in situ hybridization (FISH) and next-generation sequencing (NGS). In a cohort of 525 consecutive PTC cases, 60 BRAFV600E-negative cases underwent complete analyses of FISH, and 12 (2.3%) cases with NTRK1/3 break-apart were found. A novel ERC1-NTRK3 fusion was identified by NGS in one case. Pathological features of non-infiltrative tumor border, clear cell change, and reduced nuclear elongation and irregularity were significantly more common in NTRK1/3-rearranged PTC when compared with 48 BRAFV600E-negative non-NTRK1/3 PTC cases. In whole tissue sections, pan-TRK IHC was positive in 3/7 (42.9%) cases with an ETV6-NTRK3 rearrangement including 2 cases with low percentage of stained tumor cells, 2/3 (66.7%) with non-ETV6 NTRK3 rearrangements, and 2/2 (100%) with NTRK1 rearrangements. All FISH-negative cases were negative for pan-TRK in tissue microarray sections. As a result, pan-TRK IHC showed a sensitivity of 58.3% and specificity of 100% for NTRK1/3 rearrangements in BRAFV600E-negative PTC. In conclusion, NTRK1/3-rearranged PTC shared some unique morphologic features. Pan-TRK IHC showed high specificity and moderate sensitivity for NTRK1/3-rearranged PTC and should be interpreted with caution due to staining heterogeneity. Based on the above findings, we propose an algorithm integrating morphology, IHC, and molecular testing to detect NTRK1/3 rearrangements in PTC.