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.

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.

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.

Soluble Tumor Necrosis Factor Receptor Type 1 Levels Exhibit A Stronger Association With Renal Outcomes Than Traditional Risk Factors in Chinese Subjects With Type 2 Diabetes Mellitus.

OBJECTIVE: Associations between albuminuria and renal outcomes are inconsistent in patients with type 2 diabetes (T2D). Soluble tumor necrosis factor receptor type 1 (sTNFR1) is involved in declined kidney function and poor renal outcomes but this has not been confirmed among Chinese T2D patients. This study aimed to examine the association of sTNFR1 and renal outcomes in a cohort of these patients. METHODS: Two hundred and eighty-three Chinese T2D patients were enrolled in a prospective observational study which excluded individuals with estimated glomerular filtration rates (eGFR) <30 mL/min/1.73m2. Composite renal outcomes included either or both a >30% decline in eGFR and worsening albuminuria from consecutive tests of blood/urine during a 3.5-year follow-up. RESULTS: Higher sTNFR1 levels were associated with impaired renal outcomes. sTNFR1 levels of ≥979 pg/mL yielded the most sensitivity and specific predictions of renal outcomes according to the receiver operating curve (area under the curve 0.68, P<.001; sensitivity 78.3%, specificity 48.9%). Renal events occurred more frequently in subjects with sTNFR1 ≥979 pg/mL than in others (sTNFR1 <979 pg/mL; 29% versus 10%; P<.001 by log-rank test). The association between sTNFR1 ≥979 pg/mL and renal outcomes remained significant after adjustment for relevant covariates (adjusted hazard ratio 2.43, 95% confidence interval 1.18 to 5.02; P = .01) and consistent across subgroups stratified by age, sex, blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system inhibitors. CONCLUSION: Increased sTNFR1 levels were associated with renal outcomes in Chinese T2D subjects, making sTNFR1 a potential biomarker in diabetic kidney disease.

Changes in cardiovascular risk factors in patients with acromegaly after trans-sphenoidal adenomectomy.

The surgical treatment of acromegaly reduces mortality, however its impact on cardiovascular risk factors is unclear. This study was carried out to determine the changes in cardiovascular risk factors in patients with acromegaly who received trans-sphenoidal surgery. We recruited 127 patients with acromegaly who received trans-sphenoidal adenomectomy between August 2003 and May 2014 and follow-up for 12 months. Fasting GH and IGF-1 levels were evaluated every 3 months, and cardiovascular risk factors were assessed before and 12 months after surgery. The main outcomes were changes in cardiovascular risk factors after surgery. One year after trans-sphenoidal adenomectomy, 68 patients (53.5%) had a fasting GH level <2.0 ng/mL, IGF-1 was normalized in 74 patients (58.3%), and both fasting GH and IGF-1 were under control in 51 patients (40.2%). Levels of glycated hemoglobin (HbA1c) (8.57 ± 3.19 vs. 6.66 ± 0.90%, p = 0.001) and triglycerides (130.6 ± 61.5 vs. 108.0 ± 47.5 mg/dL, p = 0.027) were significantly decreased and serum creatinine was significantly increased (0.665 ± 0.222 vs. 0.754 ± 0.223 mg/dL, p = 0.001) after trans-sphenoidal adenomectomy. However, there were no significant changes in body weight, systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol and cardiovascular risk score after trans-sphenoidal adenomectomy. In the patient with high cardiovascular risk before surgery, systolic blood pressure, total cholesterol, fasting glucose, triglycerides and high-density lipoprotein cholesterol improved after trans-sphenoidal adenomectomy. In this study, HbA1c and triglycerides were significantly decreased after trans-sphenoidal adenomectomy in the patients with acromegaly irrespective of endocrinological outcomes. The other traditional cardiovascular factors might be improved after trans-sphenoidal adenomectomy in the patients with a high cardiovascular risk.

UPSTROKE TIME PER CARDIAC CYCLE IS ASSOCIATED WITH CARDIOVASCULAR PROGNOSIS IN TYPE 2 DIABETES.

Objective: Upstroke time per cardiac cycle (UTCC) in the lower extremities has been found to be predictive of cardiovascular mortality in the general population. Therefore, the purpose of the study was to test the associations between increasing UTCC and outcomes in patients with type 2 diabetes. Methods: A total of 452 patients with type 2 diabetes (age, 67.5 ± 8.6 years; male, 54%) registered in a share-care program participated in the study at an outpatient clinic in Taipei Veterans General Hospital across a mean of 5.8 years. Primary outcomes were all-cause mortality hospitalization for coronary artery disease, stroke, revascularization, amputation, and diabetic foot syndrome. Secondary end-point outcome was all-cause mortality. Results: Increment of UTCC associations with primary and secondary outcomes were undertaken prior to baseline characteristic adjustments. A UTCC of 20.1% exhibited the greatest area under curve (AUC), sensitivity, and specificity balance to predict composite events in receiver operating curves (AUC, 0.63 [P = .001]; sensitivity, 67.7%; specificity, 54.9%). Sixty-four composite events and 17 deaths were identified from medical records. UTCC ≥20.1% was associated with the occurrence of composite events and an increased risk of mortality. For composite events, an adjusted hazard ratio (HR) of 2.45 and 95% confidence interval (CI) of 1.38 to 4.35 (P = .002) were calculated. For all-cause mortality, an adjusted HR of 1.91 and 95% CI of 0.33 to 10.99 (P = .467) were calculated. Conclusion: Increasing UTCC was associated with cardiovascular outcomes in patients with type 2 diabetes. Therefore, UTCC is advocated as a noninvasive screening tool for ambulatory patients with type 2 diabetes. Abbreviations: CAD = coronary artery disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; HR = hazard ratio; PAD = peripheral artery disease; UTCC = upstroke time per cardiac cycle.

Sex differences in relationships between metabolic syndrome components and factors associated with health-related quality of life in middle-aged adults living in the community: a cross-sectional study in Taiwan.

BACKGROUND: Metabolic syndrome (MetS) is a widespread condition with important effects on public health, in general. There is a lack of relevant research on possible sex differences in the relationship between MetS and health-related quality of life (HRQoL) and also the sex differences in factors associated with HRQoL. The aims of this study were to identify: 1) whether women exhibit greater negative impacts on physical domain HRQoL from MetS compared with men; 2) whether women exhibit greater mental domain impacts compared with men; and 3) whether factors associated with HRQoL scores are different for men and women. METHODS: This cross-sectional study was conducted in Taipei, Taiwan. Using random sampling, a total of 906 participants aged 35-55 years were recruited. MetS was defined according to the MetS criteria for the Taiwanese population, and HRQoL were assessed using physical component summary (PCS) and mental component summary (MCS) scores of the Short Form Health Survey (SF-36), Taiwan version. Demographics, physical activity, medical history, and blood tests as covariates were recorded and checked. The associations were assessed by multiple linear regression. RESULTS: After adjusting for covariates, women but not men with more components of MetS had significantly lower PCS scores (ß = - 0.542, p = 0.036). The number of components of MetS was not a significant factor in MCS score differences between the sexes. Furthermore, there were sex differences regarding age, education level, physical activity, and smoking status in association with PCS scores. For MCS scores, sex differences were found in education level, marital status, and habits of smoking and alcohol consumption. CONCLUSIONS: There were sex differences in the relationships between metabolic syndrome components and factors associated with HRQoL among middle-aged adults living in the community in Taiwan. Further research should be conducted to investigate mechanisms of these sex differences.

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 6 months of treatment. The primary outcomes were comparisons of glucose homeostasis and biomarkers of diabetes among groups at baseline and after 6 months of treatment. RESULTS: A total of 141 subjects with impaired fasting glucose (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 6 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 homeostasis model assessment for insulin resistance (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.

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.

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.

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.

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.

Interaction between glycaemic control and serum insulin-like growth factor 1 on the risk of retinopathy in type 2 diabetes.

BACKGROUND: There is strong experimental evidence that insulin-like growth factor 1 (IGF-1) plays a role in the development of diabetic retinopathy. We carried out this study to determine the association between serum IGF-1 levels and retinopathy in patients with type 2 diabetes and whether this association is modified by the severity of hyperglycaemia. MATERIALS AND METHODS: A total of 480 consenting patients with type 2 diabetes were enrolled between 1 August 2001 and 31 December 2002. All participants provided a medical history and underwent a physical examination, biochemical assessment and eye fundi examination. These patients were followed up in our clinics according to our national guidelines until 31 December 2009. RESULTS: Compared with the middle tertile, increased levels of IGF-1 did not increase the risk of mild-to-moderate retinopathy (RR, 1·11; 95% CI, 0·63-1·95) and severe retinopathy (RR, 1·84; 95% CI, 0·79-8·57) at baseline. In the longitudinal analysis, increased levels of IGF-1 showed a nonsignificantly increased hazard ratio (HR) for the progression of retinopathy (HR, 1·61; 95% CI, 0·52-4·96) and severe retinopathy (HR, 1·63; 95% CI, 0·65-4·09). However, in patients with relatively good glycaemic control, there was a significantly increased risk of the progression of retinopathy (HR, 2·21; 95% CI, 1·01-5·91) and a cumulative incidence of severe retinopathy (HR, 4·82; 95% CI, 1·10-18·25) in individuals with the highest serum IGF-1 levels. CONCLUSIONS: Our data suggested serum IGF-1 was a contributing factor in severe diabetic retinopathy and this effect may be masked by poor glycaemic control.

Pre-existing diabetes mellitus in patients with multiple myeloma.

OBJECTIVES: Type 2 diabetes mellitus is present in approximately 10% of patients at diagnosis of multiple myeloma (MM) and is associated with increased risks of adverse events caused by novel antimyeloma agents. However, the impact of type 2 diabetes on the survival of patients with MM has not been studied. METHODS: We enrolled newly diagnosed patients with MM in Taipei Veterans General Hospital between 1999 and 2007 and identified those with pre-existing diabetes. The impact of pre-existing diabetes on patients with MM was evaluated by comparing clinical features, treatments and adverse reactions related to glycaemic control and overall survival (OS) of patients with and without pre-existing diabetes. RESULTS: Of 310 patients with MM, 73% were men and 40 (12.9%) had pre-existing diabetes. Compared with their non-diabetic counterparts, MM patients with pre-existing diabetes had a significantly higher proportion of renal impairment [(RI), serum creatinine ≥ 2.0 mg/dL] and International Staging System stage III at diagnosis, and a significantly lower proportion of bisphosphonate use and a lower rate of RI reversal (P = 0.087). During the course of the disease, hyperglycaemia and hypoglycaemia of any grade were noted in 23 (67.6%) and 6 (17.6%) of these patients, respectively. Antidiabetic therapy was changed in 10 (29.4%) of 34 evaluable patients. MM patients with pre-existing diabetes had a significantly higher all-cause mortality risk (hazard ratio, 1.509; 95% confidence interval, 1.023-2.225, P = 0.037) compared with their non-diabetic counterparts. CONCLUSIONS: Our study demonstrated the impact of pre-existing diabetes on clinical features and OS in patients with MM.

Does atropine use increase intraocular pressure in myopic children?

PURPOSE: Because pupillary dilation caused by muscarinic antagonists is a predisposing factor for glaucoma, we examined the effects of long-term atropine treatment for myopia on intraocular pressure (IOP) and studied the risk factors of elevated IOP among myopic children. METHODS: A retrospective chart review was conducted in 621 myopic children (aged 6 to 15 years) whose spherical equivalent refractive error ranged from -1.00 to -6.00 D in each eye and who had received atropine therapy. For all children, we collected their complete ocular examination data and IOP measurements beginning in 2008. We then calculated the cumulative dose and the duration of atropine therapy in the 3 years before the date of recruitment to quantitatively assess the effects of atropine therapy on IOP. RESULTS: Four hundred eighty-nine children who received atropine therapy were classified as the "treatment" group, whereas 132 children who did not receive atropine therapy were classified as "reference" group. Statistical analyses did not find any relation between the dose or duration of atropine therapy and the risk of having elevated IOP. However, the age of the myopic children and the spherical equivalent values were positively associated with the risk of having elevated IOP irrespective of whether they had been treated with atropine or not. CONCLUSIONS: Topical atropine therapy for up to 3 years seemed to be safe in myopic children; neither the cumulative dose nor the duration of atropine therapy was statistically associated with the risk of having elevated IOP. However, the safety of longer atropine therapy still needs more study. Clinicians should be careful to monitor the changes in IOP among older myopic children or myopic children with more severe myopia.

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.

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.

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.