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Abstract We present an in‐depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low‐density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence‐based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

IntroductionThere is a lack of real-world evidence regarding the impact of concomitant metformin and renin-angiotensin system inhibitors (RASis) on sodium-glucose cotransporter-2 inhibitor (SGLT2i)-associated kidney outcomes. This study was aimed to investigate whether SGLT2i-associated kidney outcomes were modified by the concomitant use of metformin or RASis in patients with type 2 diabetes.MethodsSGLT2i users were identified from three electronic health record databases during May 2016 and December 2017 and categorized into those with and without concomitant use of metformin or RASis. Propensity score matching was performed to minimize baseline differences between groups. Study outcomes were mean estimated glomerular filtration rate (eGFR) change and time to 30%, 40%, and 50% eGFR reductions. A meta-analysis was performed to combine the estimates across databases.ResultsAfter matching, there were 6,625 and 3,260 SGLT2i users with and without metformin, and 6,654 and 2,746 SGLT2i users with and without RASis, respectively. The eGFR dip was similar in SGLT2i users with and without metformin therapy, but was greater in SGLT2i users with RASis compared to those without RASis. Neither metformin nor RASi use had a significant effect on SGLT2i-associated eGFR reductions, as evidenced by the hazard ratios (95% CIs) of 30% eGFR reductions for SGLT2is with versus without metformin/RASis, namely 1.02 (0.87–1.20)/1.09 (0.92–1.31). Such findings were also observed in the outcomes of 40% and 50% eGFR reductions.ConclusionUsing metformin or RASis did not modify SGLT2i-associated kidney outcomes in type 2 diabetes.

Purpose: Autoimmune polyendocrine syndrome (APS) is a rare immune-endocrinopathy characterized by the failure of at least two endocrine organs. Clinical characteristics have mainly been described in the Western population. This study comprehensively analyzed the demographic and clinical manifestations of APS II and APS III in Taiwan. Methods: Patients aged ≥20 years with a diagnosis of APS II or APS III in ten hospitals between 2001 and 2021 were enrolled. The clinical and serological characteristics of the patients were retrospectively reviewed. Results: Among the 187 enrolled patients (45 men and 142 women); only seven (3.7%) had APS II, while the others had APS III. Fifty-five patients developed hyperthyroidism and 44 patients developed hypothyroidism. Men were diagnosed with APS at a younger age than women (16.8 vs 27.8 years old, P = 0.007). Most patients were initially diagnosed with type 1 diabetes mellitus. There was a positive correlation between age at diagnosis and the likelihood of developing thyroid dysfunction. For every year older patients were diagnosed with APS III, the risk of developing hyperthyroidism increased by 3.6% (P = 0.002), and the risk of developing hypothyroidism increased by 3.7% (P = 0.035). Positive anti-parietal cell antibodies (APCA) were associated with a higher risk of anemia in patients with APS III (P < 0.001). Conclusion: This study provides the most comprehensive analysis of APS II and APS III in Asia. The percentage of patients with APS II was significantly lower than in the Western population. A second autoimmune endocrinopathy may develop several years after the first one. APCA examination is valuable when evaluating anemia in patients with APS.

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.

Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.

Abstract Stroke survivors suffer from various physical, emotional, and cognitive impairments. These changes are dynamic and depend on multiple factors, including underlying diseases, baseline brain function and pathology, the site of the stroke and the post‐stroke inflammation, neurogenesis as well as the subsequent remodeling of the neuro‐network. First we review the structural and pathological changes of the brain in stroke survivors with diabetes mellitus, which may lead to post‐stroke cognitive dysfunction. Second, we provide evidence of hyperglycemia, diabetes mellitus, hypoglycemia, and their relationship with post‐stroke cognitive impairment (PSCI) and post‐stroke dementia (PSD). In addition to conventional biomarkers, such as HbA1c, we also provide other novel tools to predict PSCI/PSD, such as glycemic variability, receptor for advanced glycation end products, and gut microbiota. Finally, we attempt to provide some modifying methods for glycemic control, focusing on the prevention of PSCI/PSD.

Abstract Background Reduced-port laparoscopic gastrectomy can potentially reduce postoperative pain and improve recovery time. However, the inherent difficulty caused by the narrow manipulation angle makes this operation difficult, especially during lymph node dissection. The intrinsic advantage of the da Vinci® robotic system might offset this difficulty, maintaining adequate surgical quality with risks of surgical complications equal to those by the conventional four-port robotic approach. The aim of this study was to compare the reduced-port robotic approach and the conventional four-port approach in terms of postoperative pain and short-term surgical outcomes. Methods All patients who underwent radical gastrectomy with D2 lymph node dissection using the da Vinci Xi robotic system, including reduced-port or conventional four-port approach, were analyzed retrospectively. The primary outcome was postoperative pain assessed using the numerical rating scale (NRS). The secondary outcomes were the number of harvested lymph nodes, operation time, length of hospital stay, and postoperative 30-day complications. Results Forty-eight patients were enrolled in the study, 10 cases in the reduced-port and 38 in the conventional four-port group. Postoperative NRS revealed no significant difference between the reduced-port and conventional four-port groups [postoperative day (POD) 1: 4.5 vs. 3, p = 0.047, POD 3: 4 vs. 3, p = 0.178]. After propensity score matching, there were no significant differences in the median number of harvested lymph nodes, operation time, and length of hospital stay between the groups. The postoperative 30-day complications were more frequent in the conventional four-port group, but there was no significant difference compared with the reduced-port group after propensity score matching. Conclusions Reduced-port robotic gastrectomy with D2 lymph node dissection might be comparable to the conventional four-port robotic operation in terms of postoperative pain, surgical quality, and short-term outcomes. However, further studies are required to confirm our results and clarify the advantages of the robotic reduced-port approach.

Abstract Background Iatrogenic hepatic artery pseudoaneurysm is a rare complication following laparoscopic cholecystectomy. Trans-arterial embolization (TAE) is an effective way to control bleeding after a ruptured aneurysm. But uncommonly, rebleeding may occur which will require a second embolization or even laparotomy. Case presentation We report a case of a 45-year-old woman who underwent robotic-assisted cholecystectomy after the diagnosis of type II Mirizzi syndrome. During the operation, the anterior branch of the right hepatic artery was damaged and Hem-o-lok clips were applied to control the bleeding. The postoperative course was smooth, and the patient was discharged 6 days after the procedure. However, one week after hospital discharge, she presented to the emergency department with right upper abdominal tenderness, melena, and jaundice. After examination, the computed tomography angiography (CTA) revealed a 3 cm pseudoaneurysm at the distal stump of the right hepatic artery anterior branch. TAE with gelfoam material was performed. Three days later, the patient had an acute onset of abdominal pain. A recurrent pseudoaneurysm was found at the same location. She underwent TAE again but this time with a steel coil. No further complication was noted, and she was discharged one week later. Conclusions Even with the assistance of modern technologies such as the robotic surgery system, one should still take extra caution while handling the vessels. Also, embolization of the pseudoaneurysm with steel coils may be suitable for preventing recurrence.

Abstract Background To assess the effect of sodium glucose cotransporter-2 inhibitors (SGLT-2is) for type 2 diabetes on kidney outcomes stratified by patient baseline estimated glomerular filtration rate (eGFR) levels (i.e., eGFR ≤ 60, 60 90 mL/min/1.73 m2). Methods Patients from three large healthcare delivery systems in Taiwan who had initiated SGLT-2is or other glucose-lowering drugs (oGLDs) between May 2016 and December 2017 were included. Main outcomes were the times to 30%, 40%, and 50% eGFR reduction after treatment initiation. One-to-one propensity score matching in the overall study cohort and in each eGFR subgroup between SGLT-2i and oGLD users was applied to ensure between-group comparability in baseline characteristics. Results There were 13,666 matched pairs of SGLT-2is and oGLD users in the overall cohort. While a sustained eGFR decline was revealed in oGLD-treated patients (mean values [standard errors] from 85.61 [0.43] to 82.49 [0.44] mL/min/1.73 m2 during the 12 months after treatment initiation), the mean eGFR values of SGLT-2i users decreased in the first 3 months (85.68 [0.37] to 79.71 [0.41] mL/min/1.73 m2) but then improved and sustained until the end of follow-up. There were 2300, 5705, and 5509 matched SGLT-2i and oGLD users in the eGFR ≤ 60, 60 90 subgroups, respectively. Using SGLT-2is versus oGLDs was significantly associated with slower eGFR declines; hazard ratios (HRs) were 0.51 (95% CI 0.37–0.69), 0.51 (0.37–0.70), and 0.47 (0.31–0.71) for 40% eGFR reduction in the eGFR ≤ 60, 60 90 subgroups, respectively. The renoprotective effect of SGLT-2is versus oGLDs was confirmed in the outcomes of 30% and 50% eGFR reduction across the three eGFR subgroups. Conclusions This study supports the renoprotective benefit of real-world SGLT-2i use irrespective of patient baseline kidney function.

IntroductionWe investigated health service utilization, including hospitalizations and emergency department visits, for women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan.MethodsData from the Health and Welfare Data Science Center were used to conduct this nationwide population-based study. We identified pregnant women and the date of childbirth according to Birth Certificate Applications from 2007 to 2018. The study population was divided into four groups: known DM, newly diagnosed DM, GDM, and no DM/GDM. To assess quality of healthcare during the gestation period, trends in 30-day readmission rate, number of emergency department visits/hospitalizations per 100 childbirths, and length of hospital stay from 2008 to 2017 were examined.ResultsA total of 1830511 childbirths and 990569 hospitalizations were identified for analyses. Between 2008 and 2017, women with hyperglycemia in pregnancy (known DM, newly diagnosed DM, and GDM) had a higher rate of hospitalization, a longer length of hospital stay, and higher rates of various maternal and fetal outcomes, compared with women with no DM/GDM. Nevertheless, the differences between women with GDM and those with no DM/GDM in the aforementioned outcome measures were modest. Women with GDM had a modest decrease in the 30-day readmission rate (p for trend 0.046) with no significant difference in the number of emergency department visits during the study period.DiscussionOur findings provide evidence of the quality of healthcare for women with GDM between 2008 and 2017 in Taiwan.

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly around the world. The severity of COVID-19 ranges from asymptomatic carriers to severe acute respiratory distress syndrome (ARDS). Accumulating evidence has shown that COVID-19 may be associated with multiple organ complications including cardiac injury, viral myositis and neurological deficits. Numerous laboratory biomarkers including lymphocytes, platelets, lactate dehydrogenase and creatine kinase (CK) have been associated with the prognostic outcomes of patients with COVID-19. However, dynamic correlations between levels of biomarkers and clinical course have not been studied.Herein, we report a 74-year-old female patient with severe COVID-19 which progressed to ARDS requiring intubation and mechanical ventilation. The laboratory findings showed lymphopenia, hypogammaglobulinemia, and elevated inflammatory biomarkers and CK. She received intensive therapy with hydroxychloroquine, lopinavir/ritonavir, and azithromycin with limited effects. Immunomodulatory treatments with high dose intravenous immunoglobulin and baricitinib were prescribed with satisfactory biochemical, radiographic and clinical recovery. We found an interesting correlation between serum CK elevation and inflammatory biomarkers, which reflected clinical improvement. This case demonstrates that inflammatory biomarkers, cytokines, and CK level correlated with disease severity and treatment response, and combined use of intravenous immunoglobulin and baricitinib is a potential treatment in patients with severe COVID-19.

Abstract Aims/Introduction We sought to determine if postmenopausal women who develop breast cancer are at increased risk of developing diabetes mellitus. Materials and Methods The Taiwan National Health Insurance Research Database was searched from 2001 to 2015 for women aged ≥55 years (postmenopausal) with a diagnosis of primary breast cancer. Participants were age‐matched with women without breast cancer in a 1:5 ratio. Cox proportional hazards analyses were used to examine associations between breast cancer, risk factors and the development of diabetes mellitus. Results A total of 4,607 women with primary breast cancer and 23,035 age‐matched controls without breast cancer were included (mean age 58.6 ± 9.1 years). Adjusting for age, income, urbanization, Charlson Comorbidity Index and medical conditions, the risk of diabetes mellitus for participants with breast cancer at 1, 5, 10 and 15 years was 1.70‐, 1.34‐, 1.27‐ and 1.24‐fold higher, respectively, than for participants without breast cancer (adjusted hazard ratio [aHR] 1.70, 95% confidence interval [CI] 1.40–2.05; aHR 1.34, 95% CI 1.17–1.54; aHR 1.27, 95% CI 1.13–1.44; aHR 1.24, 95% CI 1.11–1.40). The risk of diabetes mellitus at 1 year for breast cancer patients receiving hormone therapy was 1.22‐fold higher than in those not receiving hormone therapy (aHR 1.22, 95% CI 0.86–1.74), but without statistical significance. Conclusions Postmenopausal women with breast cancer are at increased risk of developing diabetes mellitus, independent of receiving hormone therapy, and should be closely monitored to establish an early diagnosis and therapeutic intervention for improving related outcomes.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations. Keywords: Atherosclerosis, Risk factors, Performance guide

Finding non-invasive and sensitive biomarkers for early screening of high-risk patients remains important in clinical practice. A higher concentration of urine exosomal thyroglobulin protein was found in late-stage patients with thyroid carcinoma compared to those with early stage in our previous study. This prospective study aims to find new prognostic biomarkers before surgery for decision-making with this platform. We enrolled patients newly diagnosed with papillary and follicular cancer from 2017 to 2018. Preoperative urine samples were collected and the exosomal proteins were analyzed. The association of the concentration of urine exosomal proteins with lymph node metastasis and MACIS score (metastasis, age, completeness of resection, invasion, and size) was analyzed with multiple logistic regression. In total, 21 patients were included, with a mean age of 51.29 ± 10.29 years and a majority of female patients (85.71%). The concentration of urine exosomal TIMP (tissue inhibitor of metalloproteinase) was significantly higher in patients with lymph node metastasis (p = 0.01). Multiple logistic regression analysis showed association of urine exosomal TIMP (adjusted odds ratio (aOR): 3.09, 95% confidence interval (CI): 0.99–9.6, p = 0.052), angiopoietin-1 (aOR: 2.24, 95% CI: 0.97–5.15, p = 0.058) with lymph node metastasis. However, no association was noted between MACIS score and various urine exosomal protein candidates. Preoperative urine exosomal data could suggest certain peptides having the potential as prognostic indicators for screening patients with high-risk before surgery. Further study with a large cohort and long follow-up is needed to identify the application of urine exosomal proteins on prognostic prediction.

Abstract Diabetes remains a global epidemic and a tremendous health challenge, especially in the Asian population. Dramatic increases in the prevalence of diabetes across different countries or areas in Asia have been reported in recent epidemiological studies. Although clinical guidelines have strengthened appropriate antihyperglycemic medications and lifestyle modifications for optimal diabetes management, inadequate glycemic control still occurs in many patients with an increased risk of developing microvascular and macrovascular complications. Insulin administration is the main therapy for diabetes in response to the inability to secrete insulin, and is recommended in current guidelines to treat patients with type 2 diabetes after failure of oral antidiabetic drugs. Clinical studies have shown that long‐acting insulin analogs improve basal glycemic control with reduced risk of hypoglycemia. In the present review, we discuss previous challenges with basal insulin therapy in Asia, the pharmacological development of insulin analogs to overcome the unmet medical needs and recent clinical studies of the new ultra‐long‐acting insulin analog, insulin glargine U300. Furthermore, relevant findings of current real‐world evidence are also included for the comparison of the efficacy and safety of different insulin formulations. Based on the accumulating evidence showing a low incidence of hypoglycemia and technical benefits of dose titration, treatment with glargine U300 can be a promising strategy for Asian diabetes patients to achieve glycemic targets with favorable safety.

Summary: Background/Objective: The atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category is one of six diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). In this study, we report the diagnostic distribution of thyroid fine needle aspiration (FNA) cytology and analyze the outcome of AUS/FLUS cases. Methods: A total of 29,937 thyroid FNA results, reported between April 2012 and December 2016, were retrieved from the database of a medical center. We reviewed the electronic medical records and analyzed the management of these patients. Results: Overall frequency of AUS/FLUS is 3.1% in our laboratory, which is at the lower limit of the recommended range. Of these, 891 reports of AUS/FLUS from 770 patients were identified. Out of the 770 patients, 367 had surgical intervention. In these 367 patients, final surgical pathology yielded 204 (55.6%) malignancies, 12 indeterminateness (3.3%), and 151 (41.1%) benignity. Among these surgical patients, 113 (30.8%) had received a repeat FNA of the thyroid before thyroid resection. The difference between the malignancy rates among patients who directly received surgery after the first AUS/FLUS diagnosis (132 of 254, 52.0%) and patients having a repeat FNA before surgery (72 of 113, 63.7%) was not statistically significant. Conclusion: Our results are in agreement with AUS/FLUS diagnoses in less than 7% of specimens, and confirm that it is appropriate to perform either a repeat thyroid FNA or thyroid lobectomy, with the clinical decision being subject to the standardized management protocols of the second edition of TBSRTC in the AUS/FLUS category. Keywords: Atypia, The Bethesda System, Thyroid FNA cytology

Background: Most patients with thyroid cancer typically receive thyroidectomy with ablative radioactive iodine therapy. Such patients were followed with thyroid ultrasonography and serial serum thyroglobulin evaluation. Exosomes are nanovesicles secreted into extracellular environments, including plasma, saliva, urine, and other body fluids of patients with cancer. We try to find the early prognostic and exosomal biological markers of urine.Methods: We analyzed urinary exosomal proteins, including thyroglobulin and galectin-3, to identify early prognostic biological markers in urine for patients receiving operation and radioactive iodine ablative therapy. We enrolled sixteen newly diagnosed patients with papillary thyroid carcinoma and follicular thyroid carcinoma. We collect all patient's urine samples before operation, immediately after operation, post-operatively at three and six months (4 collections per patient). The levels of pre-operative and post-ablative of U-Ex Tg and galectin-3 in patients with thyroid cancer were measured.Results: Trends in urinary thyroglobulin concentrations in patients with post-ablative thyroid cancer were detected in the first sixteen patients. Importantly, serum thyroglobulin was not detected in five patients after operation and radioactive I-131 ablation, while U-Ex Tg still showed an increasing trend, which implicating the probable recurrence of thyroid cancer. This is the first study to evaluate whether U-Ex Tg is a future biological marker as a substitute for serum thyroglobulin.Conclusion: Our study have developed a brand-new evaluation for tracking thyroid cancer. The most useful scenario in using a test that is potentially more sensitive than existing serological testing is to eliminate the suspicion of recurrence and remove subjects from long term follow up.Trial Registration:ClinicalTrials.gov: NCT02862470; 5, August 2016. https://clinicaltrials.gov/ct2/show/NCT02862470?term=NCT02862470&rank=1.ClinicalTrials.gov: NCT03488134; 3, August 2018. https://clinicaltrials.gov/ct2/show/NCT03488134?term=NCT03488134&draw=2&rank=1.

Background/purpose: The thyroid gland is an uncommon site for the presence of extramedullary hematopoiesis (EMH). We report the cases of four Taiwanese women with hematopoietic elements on the smears of thyroid fine needle aspiration (FNA) samples and compare the findings with those of previously reported cases. Methods: We retrieved the data of cases in which thyroid FNA performed between January 2000 and December 2016. The clinical manifestations, laboratory data, and image findings of cases with thyroid EMH were reported. A review of English literature was performed, and the reported cases were compared with our series. Results: During the study period, 63,361 specimens of thyroid FNAs were identified. Four specimens contained hematopoietic elements from four women. Ultrasound study revealed calcifications in three patients. A review of English literature yielded 18 reports of thyroid EMH involving 29 patients. Twenty-six patients were women, and three were men. Nodule calcifications were found in 13 patients. Four patients had primary myelofibrosis, and one had chronic anemia. None had a thyroid malignancy. Conclusion: Four patients were noted to have bone marrow elements on the smears among 63,361 thyroid FNA samples. These four Taiwanese women presented with nodular goiter and foci of hematopoietic elements by thyroid FNA without any chronic disease of hematopoietic tissue or any evidence of a thyroid malignancy. Keywords: Extramedullary hematopoiesis, Fine needle aspiration, Thyroid

Abstract This study examined associations of thyroid hormone levels and insulin resistance (IR) in non-diabetic individuals. Using a cross-sectional design, 2007–2008 data from the National Health and Nutrition Examination Survey (NHANES) were analyzed. NHANES participants ≥20 years of age with complete data of interest were included. The homeostatic model assessment (HOMA) was used to quantify IR, and treated as a continuous variable. Self-reported diabetes or a fasting glucose ≥7 mmol/L were used as criteria to exclude diabetic subjects. Race, liver function, obesity, hypertension, dyslipidemia, smoking, physical activity, vigorous recreational activity, 2-hour glucose, hemoglobin A1C (HbA1C), high-density lipoprotein, triglyceride, vitamin D and C-reactive protein were covariates significantly associated with HOMA-IR. A total of 1,560 non-diabetic subjects were included in the analysis. When adjusted for all factors significant in the univariate analysis (race, liver function, obesity, hypertension, dyslipidemia, smoking, physical activity, vigorous recreational activity, 2-hour glucose, HbA1C, high-density lipoprotein, triglyceride, vitamin D, and CRP) low total triiodothyronine (TT3) and low free T3 (FT3) were significantly associated with decreased HOMA-IR (adjusted coefficient = −0.486, 95% confidence interval [CI]: −0.936, −0.036; adjusted coefficient = −1.151, 95% CI: −1.952, −0.350, respectively). Insulin resistance is associated with low thyroid hormone levels in non-diabetic individuals.

Background/Purpose: Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. Results: When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR) should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS) or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. Conclusion: With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA. Index words: Primary aldosteronism, Guideline, TAIPAI, TSA

In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C 40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 without chronic dialysis (CKD stage 3–5), statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.

Background/purpose: Diabetes mellitus (DM) prevalence has been rapidly increasing in Taiwan and globally. Team care for DM has been provided through diabetes shared-care networks in Taiwan more than 20 years. Methods: The study analyzed the National Health Insurance (NHI) claims data from 2005 to 2014 to better understand diabetes care accountability and utilization in Taiwan. Results: The completion rate of annual check-ups for various metabolic measurements increased significantly, which indicates improvement in diabetes management quality. The average annual visits and drug cost for each patient increased enormously from 2005 to 2014. The annual number of outpatient department/inpatient department (OPD/IPD) patients with diabetes undergoing dialysis increased. The number of OPD visits in patients with diabetes was 1.9 times higher than that in all patients in general. IPD cost appeared to increase, whereas both drug cost and the average length of hospitalization per patient decreased. Endocrine and metabolic diseases were still the leading cause of OPD expenses. The leading cause of IPD expenses was respiratory diseases. An increasing trend was noted in the medical cost for patients with microvascular instead of macrovascular complications. OPD care for patients with diabetes was rather evenly distributed since 2009. Regarding IPD care, medical centers and regional hospitals each hospitalized 37% of the diabetic outpatients in 2014. Conclusion: Accountability of diabetes care in Taiwan improved significantly till 2014. The ongoing fight against DM and tracing, examining and learning from the overall outcomes in future decades is still required. Keywords: Accountability, Complication, Cost, Diabetes mellitus, Utilization

Background/Purpose: Patients with diabetes have a higher risk of developing chronic complications and cause a huge burden to the public health care system as well as on patients and their families. We studied these diabetic complications about kidney, eye and peripheral vascular diseases to understand their prevalence and distributions in a national survey. Methods: We analyzed diabetic complications using National-Health-Insurance claims filed from 2005 to 2014. We used this database to evaluate their developments of kidney, eye, and peripheral vascular diseases according to the International-Classification-of-Diseases, Ninth Revision using clinical modification diagnosis codes. Results: The prevalence of diabetic kidney disease (DKD) significantly increased from 10.49% to 17.92% from 2005 to 2014. The prevalence rate of diabetic foot significantly decreased from 1.34% to 1.05% from 2005 to 2014, and the rate of severe infection also significantly decreased from 50.69% to 45.85%. The amputation rate significantly decreased from 24.91% to 17.47% among all patients with diabetic foot. Conclusion: In this study, the trends in DKD and dialysis prevalence were similar to those of the 2012 report. The rate of increase in dialysis prevalence is lower in this study than in the 2012 report. The prevalence of diabetic foot, severe infection, and amputation in this report exhibited significantly decreasing trends. This improvement may be attributable to care from multidisciplinary teams. We should dedicate more resources to our prevention program of DKD and retinopathy to further improve outcomes in the future. Keywords: Diabetic foot, Diabetic kidney disease, Diabetic nephropathy, Diabetic retinopathy, End-stage kidney disease

Background. Diabetes mellitus (DM) has become a significant worldwide public health problem and economic burden because a great proportion of healthcare costs has been spent on the treatment of DM and its related complications. The aim of this study was to examine the costs and length of stay (LoS) of hospitalizations due to diabetes-related complications in Taiwan. Methods. This study is a retrospective claim database analysis using the Longitudinal Cohort of Diabetes Patients, with 2012 used as the base year. The hospitalization costs and LoS per admission were estimated for each complication of interest using data from the LHDB 2004 to 2012 cohorts. The presence of eight DM-related complications were identified using the ICD-9-CM codes and procedure codes. ANOVA was used to examine the relationships of diabetes duration with the LoS and costs of the complications. Results. A total of 27,473 DM patients who were hospitalized in 2012 due to one of the examined DM-related complications were identified. The most common complications that caused the hospitalizations were nonfatal stroke (34.7%) and nonfatal ischemic heart disease (IHD) (28.7%). Amputation was the complication with the longest hospital stay, with a mean±SD of 21.6±14.1 days, followed by nonfatal stroke (13.6±11.3), ulcer (12.7±11.8), and fatal IHD (12.2±13.6). The complications with the greatest hospitalization cost were fatal IHD (mean=TWD 306,209.8; median=TWD 221,417.0; 1TWD=0.034USD) and fatal myocardial infarction (mean=TWD 272,840.1; median=TWD 174,008). Conclusions. This study indicates that DM-related complications are associated with significant hospital LoS and costs. The study results could be useful for economic evaluations of diabetes treatments and the estimation of the overall economic impact of diabetes.

Radiofrequency ablation (RFA) is a minimally invasive technique, used with ultrasound or computed tomography guidance, which can produce tissue coagulation necrosis in various kinds of tumors in the human body. In the past 10 years, numerous studies about RFA in benign thyroid nodules have been published. Reviewing these studies, we noticed that the effectiveness of ablation was higher when it was performed with the “moving-shot technique” via an internally cooled electrode. A consensus statement published from the Korean Society of Radiology also suggested the moving-shot technique as a standard ablation procedure for benign thyroid nodule ablation in Korea. In Taiwan, most symptomatic benign nodules are currently treated with surgical removal. RFA for mass lesions is primarily performed for the treatment of metastatic hepatic tumors. In our case, we have attempted to introduce RFA for benign thyroid nodules in Taiwan. Because endocrinologists in Taiwan were not familiar with this technique, we adopted a stepwise approach in learning how to perform RFA. We conducted ex vivo animal ablation exercises to gain experience in setting the radiofrequency generator for the right ablation mode and appropriate power output. The thyroid nodule volume reduction rate after 1 year of follow up was approximately 50% in this case. The most important thing we learned from this trial is that we confirmed the safety of thyroid nodule ablation. To the best of our knowledge, this is the first reported study of RFA of a thyroid nodule in Taiwan.

Sesamin (SSM) is a water-insoluble compound that is easily eliminated by liver metabolism. To improve the solubility and bioavailability of SSM, this study developed and characterized a self-nanoemulsifying drug delivery system (SNEDDS) for the oral delivery of SSM and conducted pharmacokinetic assessments. Oil and surfactant materials suitable for SNEDDS preparation were selected on the basis of their saturation solubility at 37 ± 0.5 °C. The mixing ratios of excipients were determined on the basis of their dispersibility, transmittance (%), droplet sizes, and polydispersity index. An SNEDDS (F10) formulation comprising glyceryl trioctanoate, polyoxyethylene castor oil, and Tween 20 at a ratio of 10:10:80 (w/w/w) was the optimal formulation. This formulation maintained over 90% of its contents in different storage environments for 12 weeks. After the self-emulsification of SNEDDS, the SSM dispersed droplet size was 66.4 ± 31.4 nm, intestinal permeability increased by more than three-fold, relative bioavailability increased by approximately 12.9-fold, and absolute bioavailability increased from 0.3% to 4.4%. Accordingly, the developed SNEDDS formulation can preserve SSM’s solubility, permeability, and bioavailability. Therefore, this SNEDDS formulation has great potential for the oral administration of SSM, which can enhance its pharmacological application value.

Here we conducted a retrospective analysis of hospital-based trauma registry database for evaluating the impacts of comorbidities on the prognosis for traumatized patients using Index of Coexistent Comorbidity Disease (ICED) scores. We analyzed the data of patients with blunt trauma who visited emergency department between January 1, 2011, and December 31, 2015 in Chang-Gung Memorial Hospital, Keelung branch, a single level I trauma center in the Northern Taiwan. All consecutive patients with blunt trauma who admitted to the intensive care unit or ordinary ward after initial managements in the emergency department were included. We measured the hospital mortality of blunt traumatized patients using alive discharge as a competing risk. To investigate conditional independence of mortality and ICED scores given Injury Severity Score (ISS), we used log-linear models for modeling independence structures. Overall, we included 4997 patients (median age [IQR], 59 years old (44-75 years); 55.3% male). The mortality rate of blunt traumatized patients was higher in the higher ICED scores group compared to lower ICED scores group (4.7% vs 1.8%, p < 0.001). Meanwhile, the higher ICED scores group were associated with older age, higher ISS, and longer hospital stay than lower ICED scores group. Higher ICED group had higher probability of transition-to-death and lower probability of transition-to-discharge under the competing risk model. In the multivariable analysis of transition-specific Cox models, higher ICED group were associated with higher risk for hospital mortality compared to lower ICED group (HR 1.60; [95% CI 1.04-2.47]; p = 0.032). Also, higher ICED group were associated with lower probability of transition-to-discharge (HR 0.79; [95%CI 0.73-0.86]; p < 0.001). Additionally, higher ICED scores accounted for hospital mortality among patients with ISS < 25. In conclusion, our study suggested that severity of comorbidity was associated with higher hospital mortality among traumatized patients, particularly lower ISS.

An E1/226V variant Chikungunya virus (CHIKV) efficiently transmitted by Aedes albopictus to humans poses a significant threat to public health for those areas with the presence of Aedes albopictus, including Taiwan. Methods: We infected three imported CHIKV isolates including the E1/226V variant with Ae. albopictus and Aedes aegypti in the laboratory to understand the disease risk. Viral RNA was measured by real time reverse transcription polymerase chain reaction. Results: The viral susceptibility varied by virus strain and mosquito species and strain. The Asian virus strain started to replicate at 5–6 days post infection (dpi) with the maximum virus yield, ranging from 103.63 to 103.87 at 5–10 dpi in both species. The variant CHIKV Central/East/South African (CESA) virus genotype replicated earlier at 1 dpi with the maximum virus yield ranging from 105.63 to 106.52 at 3–6 dpi in Ae. albopictus females while the nonvariant virus strain replicated at 1–2 dpi with the maximum virus yield ranging from 105.51 to106.27 at 6–12 dpi. In Ae. aegypti, these viruses replicated at 1–2 dpi, with maximum yields at 4–5 dpi (range from 105.38 to 105.62). Conclusion: We concluded that the risk of CHIKV in Taiwan is high in all distribution areas of Ae. aegypti and Ae. albopictus for the CESA genotype and that the E1/226V variant virus strain presents an even higher risk.

Explaining the risks and benefits of recombinant tissue-plasminogen activator (rtPA) to eligible patients with acute ischemic stroke (AIS) within a few minutes is important but difficult. We examined whether a new thrombolysis program can decrease the door-to-needle (DTN) time when treating patients with AIS. Methods: A new rtPA thrombolysis program with video assistance was adapted for patients with AIS and their families. We retrospectively compared outcome quality before (2009–2011) and after (2012) the program began. Outcomes included DTN time, the percentage of rtPA thrombolysis within 3 hours of onset in all hospitalized patients with AIS who presented within 2 hours of onset (2hr%) and the percentage of rtPA thrombolysis in all hospitalized patients with AIS (AIS%). Results: We recruited patients with AIS who had undergone thrombolytic therapy before (n = 18) and after (n = 14) the initiation of the new program. DTN time decreased (93 ± 24 minutes to 57 ± 14 minutes, p

BACKGROUND: To identify the ranges of hemoglobin A(1c) (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) levels which are associated with the lowest all-cause mortality. METHODS: A retrospective cohort of 12,643 type 2 diabetic patients (aged ≥18 years) were generated from 2002 to 2010, in Far-Eastern Memorial Hospital, New Taipei city, Taiwan. Patients were identified to include any outpatient diabetes diagnosis (ICD-9: 250), and drug prescriptions that included any oral hypoglycemic agents or insulin prescribed during the 6 months following their first outpatient visit for diabetes. HbA1c, SBP, and LDL-C levels were assessed by the mean value of all available data, from index date to death or censor date. Deaths were ascertained by matching patient records with the Taiwan National Register of Deaths. RESULTS: Our results showed general U-shaped associations, where the lowest hazard ratios occurred at HbA1c 7.0-8.0%, SBP 130-140 mmHg, and LDL-C 100-130 mg/dL. The risk of mortality gradually increases if the patient's mean HbA1c, SBP, or LDL-C during the follow-up period was higher or lower than these ranges. In comparison to the whole population, the adjusted hazard ratio (95% CI) for patients with HbA1c 7.0-8.0%, SBP 130-140 mmHg, and LDL-C 100-130 mg/dL were 0.69 (0.62-0.77), 0.80 (0.72-0.90), and 0.68 (0.61-0.75), respectively. CONCLUSIONS: In our type 2 diabetic cohort, the patients with HbA1c 7.0-8.0%, SBP 130-140 mmHg, or LDL-C 100-130 mg/dL had the lowest all-cause mortality. Additional research is needed to confirm these associations and to further investigate their detailed mechanisms.

ObjectiveThe association between type 2 diabetes and low testosterone has been well recognized. However, testosterone levels in men with prediabetes have been rarely reported. We aimed to investigate whether prediabetes was associated with an increased risk of testosterone deficiency.MethodsThis study included 1,306 men whose sex hormones was measured during a medical examination. Serum total testosterone and sex hormone-binding globulin were measured; free and bioavailable testosterone concentrations were calculated by Vermeulen's formula. Prediabetes was defined by impaired fasting glucose (IFG), impaired postprandial glucose (IPG), or glycated hemoglobin (HbA1c) 5.7%-6.4%. Logistic regression was performed to obtain the odds ratios (OR) for subnormal total testosterone (ResultsNormoglycemia, prediabetes, and diabetes were diagnosed in 577 (44.2%), 543 (41.6%), and 186 (14.2%) men, respectively. Prediabetes was associated with an increased risk of subnormal total testosterone compared to normoglycemic individuals (age-adjusted OR=1.87; 95%CI=1.38-2.54). The risk remained significant in all multivariate analyses. After adjusting for MetS, the OR in prediabetic men equals that of diabetic patients (1.49 versus 1.50). IFG, IPG, and HbA1c 5.7%-6.4% were all associated with an increased risk of testosterone deficiency, with different levels of significance in multivariate analyses. However, neither prediabetes nor diabetes was associated with subnormal free testosterone in multivariate analyses.ConclusionsPrediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and MetS. After adjusting for MetS, the risk equals that of diabetes. Our data suggest that testosterone should be measured routinely in men with prediabetes.

BACKGROUND: Fatty infiltration of the pancreas has been shown to interfere with insulin secretion. Both insulin sensitivity and secretion are important in the pathogenesis of diabetes and prediabetes. However, the relationship between diabetes, prediabetes, and fatty pancreas remains unknown. We aim to investigate the relationships that fatty pancreas and nonalcoholic fatty liver disease (NAFLD) have with prediabetes and diabetes in a Chinese population. PATIENTS AND METHODS: This was a cross-sectional study. A total of 7,464 subjects were recruited. NAFLD and fatty pancreas were assessed by sonography. Clinico-metabolic parameters were compared among subjects with normoglycemia, prediabetes, and diabetes. Multinomial logistic regression was used to evaluate the relationship between fatty pancreas and NAFLD and diabetes or prediabetes with adjustment for cardiometabolic risk factors. RESULTS: With an increase in glycemia, a significantly greater proportion of subjects had NAFLD and fatty pancreas (test for trend p

Background: The Australian Foundation Residency Program prepares new-to-hospital and early career pharmacists for extended roles and advanced pharmacy practice. An understanding of the outcomes residents perceive they achieve through completion of a residency and what supports them in their achievements is limited. Aim: To explore pharmacists’ experiences during their residency and what they perceive as its outcomes and their achievements. Method: Focus groups and interviews were conducted and recorded with 12 early career or new-to-hospital pharmacists who recently completed a residency program in an Australian hospital. Recordings were transcribed and analysed using inductive thematic analysis. Ethical approval was granted by the University of Queensland Human Research Ethics Committee (Reference no: 2021/HE001225) and the study conforms to the Australian Statement on Ethical Conduct in Human Research. Informed consent was obtained from all participants via the distribution of project information sheets and completion of written consent forms. Results: Five distinct themes were generated from participants’ discussions of their experiences and achievements throughout their residency. The outcomes and achievements they described included gaining the confidence to take on new and challenging roles as well as advancing their career by developing a deeper understanding of their role and potential in the healthcare system. Skill development was accelerated by the structure and assessment requirements of the residency program and by support from mentors, which positively influenced their attitudes towards feedback and competency assessments. Participants reflected on the differences between postgraduate university-based learning and workplace-based learning and saw benefits in both. Conclusion: The residency was reported to offer a structured and supportive training pathway for pharmacists in the early stages of their hospital pharmacy career. Completion of residency facilitates pharmacists’ skill development and a deeper understanding of their roles. Dedicated and qualified mentorship and routine networking events between peers and past residents enhance these experiences and outcomes for residents. [ABSTRACT FROM AUTHOR]

Context: Recent studies suggest that the clinical characteristics and biological behavior of pituitary tumors (PITs) in patients with multiple endocrine neoplasia type 1 (MEN1) may not be as aggressive as previously reported. Increased imaging of the pituitary as recommended by screening guidelines identifies more tumors, potentially at an earlier stage. However, it is unknown if these tumors have different clinical characteristics in different MEN1 mutations. Objective: To assess characteristics of patients with MEN1 with and without PITs, and compare among different MEN1 mutations. Methods: Data of patients with MEN1 in a tertiary referral center from 2010 to 2023 were retrospectively analyzed. Results: Forty-two patients with MEN1 were included. Twenty-four patients had PITs, 3 of which were invasive and managed with transsphenoidal surgery. One PIT enlarged during follow-up. Patients with PITs had a higher median age at MEN1 diagnosis than those without PITs. MEN1 mutations were identified in 57.1% of patients, including 5 novel mutations. In patients with PITs, those with MEN1 mutations (mutation+/PIT+ group) had more additional MEN1-associated tumors than those without (mutation-/PIT+ group). The mutation+/PIT+ group had a higher incidence of adrenal tumors and a lower median age at initial manifestation of MEN1 than the mutation-/PIT+ group. The most common neuroendocrine neoplasm was nonfunctional in the mutation+/PIT+ group and insulin-secreting in the mutation-/PIT+ group. Conclusion: This is the first study comparing characteristics of patients with MEN1 with and without PITs harboring different mutations. Patients without MEN1 mutations tended to have less organ involvement and it might be reasonable for them to receive less intensive follow-up. [ABSTRACT FROM AUTHOR]