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BACKGROUND Many patients with papillary thyroid cancer (PTC) demonstrate satisfactory outcomes. However, 8%-28% of patients with PTC show tumor recurrence, which may affect prognosis. Therefore, identifying factors associated with tumor recurrence in patients with PTC may be helpful to refine therapeutic strategies. PATIENTS AND METHODS To identify factors associated with PTC recurrence, we retrospectively reviewed demographic features (sex and age), operation method, image character, serum thyroglobulin (Tg), accumulated radioactive iodine (I-131) therapeutic dose, I-131 uptake, and metastases at diagnosis in 829 patients with PTC. Patients were grouped into early (stage I and II; n = 698) and advanced (stage III and IV; n = 131) tumor-node-metastasis (TNM) stages. Recurrence rate, mortality rate, risk factors of recurrence, recurrent free survival and overall survival curve were compared between two groups. RESULTS Patients in the early stage demonstrated a lower recurrence rate (7.2%) than did those in the advanced stage (28.2%, p < 0.05). The mortality rate of patients with recurrence in the advanced stage was higher than that of those in the early stage (51.4% vs. 12.0%). The major impact factors on tumor recurrence in early TNM stage were distant metastasis and lymph node metastasis, while in advanced TNM stage were distant metastasis, male gender, total thyroidectomy with limited lymph node dissection, and a high serum Tg level. CONCLUSIONS Strategies to monitor tumor recurrence might be refined according to the TNM stages of PTC patients.

Background A proportion of lung cancers show sodium/iodide symporter (NIS) expression. Lung cancers with NIS expression may uptake radioiodine (RAI) and show RAI-avid lesions on RAI scan for differentiated thyroid cancer (DTC) surveillance. Aim To investigate the possibility of RAI uptake by lung cancer in a cohort with thyroid cancer. Methods RAI-avid lung cancers were analyzed using a prospectively maintained database of patients with thyroid cancer who were registered at a medical center between December 1, 1976 and May 28, 2018. NIS expression in lung cancer was assessed using immunohistochemical staining. Results Of the 5000 patients with thyroid cancer from the studied dataset, 4602 had DTC. During follow-up, 33 patients developed primary lung cancer. Of these patients, nine received an iodine-131 (131I) scan within 1 year before the diagnosis of lung cancer. One of these nine lung cancers was RAI-avid. NIS expression was evaluated, and three of the eight available lung cancers revealed NIS expression. The proportions of lung cancer cells with NIS expression were 60%, 15%, and 10%. The RAI-avid lung cancer had the highest level of expression (60%). The RAI-avid lung cancer had a spiculated border upon single-photon emission computed tomography/computed tomography, which led to an accurate diagnosis. Conclusion A proportion of lung cancer demonstrates NIS expression and is RAI-avid. Clinicians should be aware of this possibility in the interpretation of RAI scintigraphy.

The cardiovascular outcomes of insulin detemir in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS.A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke.The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively).Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke.ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus.

Background: Papillary thyroid carcinoma occasionally presents with concomitant hyperparathyroidism; however, the clinical significance has not been well established. This study aimed to evaluate the long-term cancer prognosis following a multimodality therapy. Methods: We conducted a case-control study using prospectively maintained data from a medical center thyroid cancer database between 1980 and 2013. The study cohort comprised patients with concomitant papillary thyroid carcinoma and hyperparathyroidism. Patients with papillary thyroid carcinoma only were matched using the propensity score method. Therapeutic outcomes, including the non-remission rate of papillary thyroid carcinoma and patient mortality, were compared. Results: We identified 27 study participants from 2537 patients with papillary thyroid carcinoma, with 10 patients having primary hyperparathyroidism and 17 having renal hyperparathyroidism. Eighty-five percent of the cohort was found to have tumor–node–metastasis stage I disease. During a mean follow-up of 7.7 years, we identified 3 disease non-remission and 4 mortality events. The non-remission risk did not increase (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.43–6.40; p = 0.47); however, the overall mortality risk significantly increased (HR, 4.43; 95% CI, 1.11–17.75; p = 0.04). All mortality events were not thyroid cancer related, including two identified cardiovascular diseases. Conclusions: Patients with papillary thyroid carcinoma who present with concomitant hyperparathyroidism are usually diagnosed at an early cancer stage with compatible therapeutic outcomes. However, hyperparathyroidism-related comorbidity may decrease long-term survival. Keywords: Papillary thyroid carcinoma, Hyperparathyroidism, Therapeutic outcomes

Differentiated thyroid cancer (DTC) from follicular epithelial cells is the most common form of thyroid cancer. Beyond the common papillary thyroid carcinoma (PTC), there are a number of rare but difficult-to-diagnose pathological classifications, such as follicular thyroid carcinoma (FTC). We employed deep convolutional neural networks (CNNs) to facilitate the clinical diagnosis of differentiated thyroid cancers. An image dataset with thyroid ultrasound images of 421 DTCs and 391 benign patients was collected. Three CNNs (InceptionV3, ResNet101, and VGG19) were retrained and tested after undergoing transfer learning to classify malignant and benign thyroid tumors. The enrolled cases were classified as PTC, FTC, follicular variant of PTC (FVPTC), Hürthle cell carcinoma (HCC), or benign. The accuracy of the CNNs was as follows: InceptionV3 (76.5%), ResNet101 (77.6%), and VGG19 (76.1%). The sensitivity was as follows: InceptionV3 (83.7%), ResNet101 (72.5%), and VGG19 (66.2%). The specificity was as follows: InceptionV3 (83.7%), ResNet101 (81.4%), and VGG19 (76.9%). The area under the curve was as follows: Incep-tionV3 (0.82), ResNet101 (0.83), and VGG19 (0.83). A comparison between performance of physicians and CNNs was assessed and showed significantly better outcomes in the latter. Our results demonstrate that retrained deep CNNs can enhance diagnostic accuracy in most DTCs, including follicular cancers.

Background/Purpose: The objectives of this study were to evaluate the associations between clinical parameters and quality of life (QOL) of patients with acromegaly in Taiwan and to identify the impacts of hormone control, regimens, or co-morbidities on acromegalic patients' daily life. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. Clinical data were recorded. The QOL of enrolled patients were assessed by using Acromegaly Quality of Life Questionnaire (AcroQoL). Results: This study enrolled 272 acromegalic subjects (117 males, 155 females). Remission, defined by normalization of IGF-1, had significant positive association with QOL scores in psychological/appearance (PSY/APP) dimension (β = 6.760, p = 0.023). Somatostatin analogues therapy had negative associations with total score and score in psychological (PSY) dimension (β = −4.720, p = 0.046 and β = −5.388, p = 0.035, respectively). Diabetes mellitus had negative associations with score in PSY dimension and psychological/personal relations (PSY/PER) dimensions (β = −5.839, p = 0.034 and β = −7.516, p = 0.013, respectively). Cerebral vascular accident (CVA) had significant negative associations with total score and scores in physical (PHY), PSY, and PSY/PER dimensions (β = −26.632, p = 0.013; β = −28.353, p = 0.024; β = −25.648, p = 0.026; and β = −34.586, p = 0.006, respectively). All these associations remained significant even after adjusted with sex and age. Conclusion: Our analysis suggested that not only hormone control but also therapeutic regimens and presence of co-morbidities might affect QOL of patients with acromegaly in some dimensions. Keywords: Taiwan acromegaly registry, Quality of life, Clinical parameters

Background/purpose: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. Results: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 μg/L, 2.4 ± 6.1 μg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 μg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. Conclusion: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly. Keywords: Acromegaly, Patient registry, Taiwan, Health outcome, Quality of life

This study verified the value of a computer-aided diagnosis (CAD) technique assisting in ultrasonography (US) diagnosis of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-avid thyroid incidentalomas on positron emission tomography. A total of 82 18FDG-avid thyroid incidentalomas from 74 non-thyroid cancer patients were retrospectively analyzed with respect to US and CAD parameters (anechoic area, hyper-echoic foci, hypo-echogenicity, heterogeneity, margin, taller-than-wide shape, eccentric area) and were compared with 38 other non-18FDG-avid nodules found in the same patient group. Fine-needle aspiration cytology or surgical intervention pathology was performed for diagnosis. No significant differences in nodule size or CAD parameters were found in 18FDG-avid nodules reported as benign, indeterminate or malignant. Significantly more taller-than-wide nodules were thyroid originating than metastatic (0.30 vs. 0.16, p

Background Primary aldosteronism (PA) is a common cause of secondary hypertension. Among the many leading causes of PA, the two most frequent are, bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenomas (APA). Since a solitary APA may be cured surgically, but BAH needs lifelong pharmacologic therapy, confirmation is mandatory before surgery. We herein sought to determine the diagnostic value of iodine-131 6-beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy to distinguish BAH from APA. Patients and methods Patients clinically suspected of PA from March 2000 to October 2016 were retrospectively analyzed. A total of 145 patients, including 74 postunilateral adrenalectomy and seven postradiofrequency ablation for adrenal mass, were reviewed. All patients received NP-59 adrenal scintigraphy prior to surgery. The accuracy of the NP-59 adrenal scintigraphy was confirmed by the pathologic findings and postoperative outcomes. Results Among 81 patients receiving interventional procedures for adrenal mass, adenoma was eventually diagnosed in 72 patients according to their pathologic results, with 60 unilaterally and seven bilaterally localized lesions by NP-59 scintigraphy; nevertheless, there were five negative findings initially. The sensitivity, specificity, and positive predictive value of NP-59 scintigraphy for APA detection were therefore 83.3, 44.4, and 92.3%, respectively. Moreover, single-photon emission computed tomography/computed tomography scan increased the sensitivity and specificity, but not the positive predictive value (85.0, 60.0, and 89.5%) of NP-59 scintigraphy in this study. Conclusion NP-59 adrenal scintigraphy is a useful imaging test to detect APA. Lateralization by this modality prior to surgical intervention may reduce the need for such invasive procedures as adrenal venous sampling.

Background This study compared event rates of diabetic ketoacidosis (DKA) and severe hypoglycemia, as well as glycemic control, among children, adolescents, and young adults with type 1 diabetes mellitus (T1DM) receiving basal-bolus or premixed insulin therapy. Methods A total of 825 individuals aged ≤ 20 years with T1DM, using either basal-bolus or premixed insulin regimens, were retrospectively recruited from 2001 to 2015. Rates of DKA after diagnosis, severe hypoglycemia, and the level of glycated hemoglobin A1c (HbA1c) improvement during the follow-up period were analyzed. Results Of the 825 patients, 226 receiving a premixed regimen were matched to the same number of patients receiving a basal-bolus regimen. In the matched cohort, DKA (10.62% vs. 5.31%; p = 0.037) and severe hypoglycemic episodes (25.22% vs. 10.62%; p

Albuminuria is a measurement and determinant factor for diabetic kidney disease (DKD). Angiotensin receptor blocker (ARB) is recommended for albuminuria in DKD with variable response. To find surrogate markers to predict the therapeutic effect of ARB, we carried out a prospective study to correlate plasma metabolites and the progression of renal function/albuminuria in DKD patients. A total of 56 type 2 diabetic patients with various stages of chronic kidney disease and albuminuria were recruited. ARB was prescribed once albuminuria was established. Urinary albumin-to-creatinine ratio (UACR) was determined before and six months after ARB treatment, with a &ge, 30% reduction of UACR considered an ARB responder. Plasma levels of 145 metabolites were measured before ARB treatment, only those associated with albuminuria were selected and compared between ARB responders and non-responders. Both lower tryptophan (Trp &le, 46.75 &mu, mol/L) levels and a higher kynurenine/tryptophan ratio (KTR &ge, 68.5 &times, 10&minus, 3) were significantly associated with macroalbuminuria (MAU), but only KTR (&ge, 54.7 &times, 3) predicts ARB responsiveness (sensitivity 90.0%, specificity 50%) in MAU. Together, these data suggest that the kynurenine/tryptophan ratio predicts angiotensin receptor blocker responsiveness in patients with diabetic kidney disease.

Objective Radioactive iodine (131I) has been used as a treatment for high-risk well-differentiated thyroid cancer after thyroidectomy. The aim of this study was to evaluate the long-term follow-up results after using high accumulated doses of 131I (>600 mCi) for the treatment of well-differentiated thyroid cancer. Patients and methods In this study, we retrospectively evaluated prospectively enrolled patients with well-differentiated thyroid cancer who were treated and followed up in Chang Gung Memorial Hospital in Linkou and Keelung, Taiwan. All the patients underwent thyroidectomy between 1979 and 2016. Results For our study, 228 patients with papillary and follicular thyroid carcinoma with distant metastases were enrolled. Of the 228 patients, 71 (31.1%) received 131I therapy with an accumulated dose of at least 600 mCi. Forty-four died because of disease-specific mortality (DSM) after a mean follow-up of 10.6±6.3 years. Compared with the patients in the DSM group, which included 27 survival cases, patients who were younger, and those with a multifocal tumor, more extensive thyroidectomy, and papillary thyroid carcinoma showed better prognosis. The DSM group included a higher percentage of patients who developed a secondary primary cancer after receiving a diagnosis of thyroid cancer than the survival group (18.2 vs. 3.7%). However, the difference did not reach statistical significance (P=0.075). Conclusion 131I provided an effective therapeutic modality for well-differentiated thyroid cancer patients with distant metastasis. After a mean of follow-up 10 years, more than 60% of cases resulted in DSM when high accumulated 131I doses were administered.

Published studies seldom tested the weight of different waist circumference (WC) cut-off values for the diagnosis of metabolic syndrome (MetS) in predicting clinical outcomes, including cardiovascular disease and diabetes.This is a Chinese population-based cross-sectional study screening subjects from a Health Examination Program since 1999 to 2015. The MetS identification and scores were determined either according to the Adult Treatment Panel III/American Heart Association/National Heart, Lung, and Blood Institute (ATP III/AHA/NHLBI)- or Asian-WC cut-off points. The developments of a higher brachial-ankle pulse wave velocity (baPWV), defined as ≥1400 cm/s, and diabetic-level hyperglycemia, defined as a high fasting glucose level ≥6.99 mmol/L or postprandial glucose level ≧11.10 mmol/L, were surveyed by comparing the areas under receiver operating characteristic curves (AUC-ROC) for both MetS scores.According to the ATP III/AHA/NHLBI- vs Asian-MetS criteria, 6633 vs 9133 (24.8% vs 34.2%, p 0.001) subjects were diagnosed as the MetS among 26,735 study subjects with a mean age of 55 ± 12 years. The stepwise increases in baPWV and prevalence of diabetic-level hyperglycemia were associated with both MetS scores after adjusting for age and sex. Both MetS scores yielded similar results for correlation with a higher baPWV (AUC-ROC = 0.685 for ATP III/AHA/HLBI- vs 0.680 for Asian-MetS, p = 0.271) and diabetic-level hyperglycemia (AUC-ROC = 0.791 for ATP III/AHA/HLBI- vs 0.784 for Asian-MetS, p = 0.546).In a stepwise manner, both ATP III/AHA/NHLBI- or Asian-MetS scores were strong risk factors for arterial stiffness and diabetes. Through a novel and holistic approach, the performance of the ATP III/AHA/NHLBI-MetS score for the risks of arterial stiffness and diabetes was comparable to the Asian-MetS score among a Chinese population.

Background The reported outcomes of the metabolic syndrome (MetS), containing atherosclerotic cardiovascular disease and diabetes, vary according to the definitions used. This study was designed to compare the performance of the Adult Treatment Panel III/American Heart Association/National Heart, Lung, and Blood Institute (ATP III/AHA/NHLBI) and International Diabetes Federation (IDF) criteria for the risks of atherosclerosis and diabetes. Methods We sifted subjects from a self-paid Health examination program from 1999 to 2015 in this cross-sectional population-based study. On the basis of the ATP III/AHA/NHLBI and IDF criteria, the MetS diagnosis and scores were concluded. A brachial-ankle pulse wave velocity (baPWV) more than or equal to 1400 cm/s indicated more severe arterial stiffness, and a high fasting glucose level more than or equal to 6.99 mmol/L or postprandial glucose level more than or equal to 11.10 mmol/L indicated diabetic-level hyperglycemia. Comparisons of the areas under receiver operating characteristic curves (AUC–ROC) for both MetS scores to correlate with a higher baPWV and diabetic-level hyperglycemia were evaluated. Results In the 26,735 enrolled subjects with an average age of 55 (± 12) years, 6633 and 7388 (24.8% vs. 27.6%, p

The efficacy of thyroxine suppressive therapy in reducing nodular growth and its effect to bone mineral density (BMD) in postmenopausal women is still debated. This study aimed to evaluate the therapeutic effect of thyroxine and its influence on BMD. Postmenopausal women with nodular or multinodular goiter during 2013-2015 at Chang Gung Memorial Hospital were enrolled and retrospectively traced back to the first date of visit or treatment. Ninety-four eligible patients were enrolled, of whom 45 were thyroxine-treated (LT-4 group) and 49 were treatment-naïve (control group). Data, including volume of nodules, were analyzed retrospectively. BMD was measured in each LT-4 group patient since the year of enrollment. Nodular volumes were reduced in both LT-4 (from 4.89 ± 4.46 to 4.10 ± 4.57 mL, p = 0.033) and control group (3.48 ± 4.36 to 3.09 ± 2.88 mL, p = 0.239) at initial 2-year follow-up. Nodular volume in LT-4 group increased insignificantly (from 4.89 ± 4.46 to 4.91 ± 5.40 mL, p = 0.711) at the end of 7-year follow-up. The best cut-off predictive nodular volume that may have responded to thyroxine is 2.6 mL (AUC, 0.740; sensitivity, 0.750; specificity, 0.733) during first 2 year. Lumbar spine, total hip and femoral neck BMD were not significantly changed during 2 year's thyroxine suppression therapy. In conclusion, thyroxine suppressive therapy in postmenopausal women had significant reduction in nodule volume at initial 2 years of treatment, especially in volume larger than 2.6 mL. Prolonged thyroxine treatment did not benefit nodular size reduction and may affect BMD minimally in postmenopausal women.

Background The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS. Methods An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and December 31, 2013 utilizing Taiwan National Health Insurance Research Database. A total of 1203 patients with T2DM after ACS or AIS were selected as the study cohort. Cardiovascular safety and efficacy of linagliptin were evaluated by comparing outcomes of 401 subjects receiving linagliptin after ACS or AIS to 802 matched control subjects not receiving any incretin-based therapy after ACS or AIS. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. Results The primary composite outcome after 15-month follow-up was 7% (28 patients) in the linagliptin group compared with 6.1% (49 patients) in the control group [hazard ratio (HR) 1.06; 95% confidence interval (CI) .66–1.68]. The linagliptin group also had similar risks of all-cause mortality, hospitalization for heart failure, percutaneous coronary intervention and coronary artery bypass grafting compared to the control group in terms of the secondary outcomes. Conclusions In T2DM patients after ACS or AIS, treatment with linagliptin was not associated with increased risks of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke.

Aims/Introduction Diabetic nephropathy is one of the leading causes of end-stage renal disease. Unfortunately, reliable surrogate markers for predicting the prognostic outcome of diabetic nephropathy are as yet absent. In order to find new markers in predicting the progression of diabetic nephropathy, we carried out a prospective study by investigating the correlation between serum metabolites and the annual change of estimated glomerular filtration rate (eGFR). Materials and Methods From September 2013 to September 2015, 52 diabetes patients at various stages of chronic kidney disease were enrolled. While serum levels of 175 metabolites were measured by AbsoluteIDQ™ p180 kit, only those with a significant difference in advancing chronic kidney disease stages were selected. After then, serial renal function change of these patients was followed up for 12 months, the outcome of renal function with each selected metabolite was compared according to the occurrence of a rapid decline (sustained annual decrement rate ≥5%) of eGFR. Results A total of 26 metabolites were found to be significantly associated with the severity of chronic kidney disease. Tryptophan (Trp) showed a significant association with the event of rapid decline in eGFR (P = 0.036). Serum concentration of Trp

Objective: The objective of this study was to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal function in different stages of chronic kidney disease (CKD). Design and Methods: We conducted a retrospective cohort study using longitudinal claims data from May 2016–December 2017 from the Chang Gung Research Database. Patients who used one of the three types of SGLT2 inhibitor available at Chang Gung Memorial Hospital, namely empagliflozin 10 mg/tab (Empa10), empagliflozin 25 mg/tab (Empa25), and dapagliflozin 10 mg/tab (Dapa), were included, with the same number of matched non-users. Analysis of variance was used for continuous variables and the chi-square test was applied for categorical variables. Differences in data between two groups were analyzed using an independent t-test, and the basic data before and after treatment were analyzed using generalized estimating equation (GEE). The association among renal function changes was analyzed using a Cox proportional hazards model, with the results presented as unadjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: Among the 7,624 SGLT2 inhibitor users, 1,696 patients used Empa10, 2,654 used Empa25, and 3,274 used Dapa. Compared with non-users, dapagliflozin had the lowest risk of estimated glomerular filtration rate (eGFR) decrease over 40% from baseline within 1 year (HR 0.36, 95% CI 0.25–0.51). By using the ICD-10-CM code N179, the acute kidney injury (AKI)-related hospitalization rate was lower in Empa10 and Dapa users than in non-users (HR 0.65, 95% CI 0.49–0.86). Conclusion: Lower risk of eGFR decrease over 40% and AKI-related hospitalization was found in all SGLT2 inhibitor users across the different CKD stages.

Introduction The aim of this study was to objectively analyze the correlation between dietary components and blood glucose variation by means of continuous glucose monitoring (CGM). Methods Patients with type 1 diabetes mellitus (T1DM) who received CGM to manage their blood glucose levels were enrolled into the study, and the components of their total caloric intake were analyzed. Glycemic variation parameters were calculated, and dietary components, including percentages of carbohydrate, protein and fat in the total dietary intake, were analyzed by a dietitian. The interaction between parameters of glycemic variability and dietary components was analyzed. Results Sixty-one patients with T1DM (33 females, 28 males) were enrolled. The mean age of the participants was 34.7 years, and the average duration of diabetes was 14 years. Glycated hemoglobin before CGM was 8.54%. Participants with a carbohydrate intake that accounted for < 50% of their total caloric intake had a longer DM duration and a higher protein and fat intake than did those with a carbohydrate intake that accounted for ≥ 50% of total caloric intake, but there was no between-group difference in total caloric intake per day. The group with a carbohydrate intake that accounted for < 50% of their total caloric intake also had lower nocturnal continuous overlapping net glycemic action (CONGA) 1, − 2 and − 4 values. The percentage of protein intake had a slightly negative correlation with mean amplitude of glycemic excursions (MAGE) (r = − 0.286, p

BACKGROUND Stiff-person syndrome (SPS) and its subtype, stiff limb syndrome (SLS), are rare neurological disorders characterized by progressive muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the central nervous system. SPS is an autoimmune disease triggered by anti-glutamic acid decarboxylase antibody (anti-GAD Ab). Clinically, anti-GAD Ab is associated with SPS, type 1 diabetes mellitus (T1DM), and other autoimmune diseases. AIM To investigate the link of autoimmune endocrine disorders with anti-GAD Ab in SPS subjects. METHODS This retrospective study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan. We collected the patients with SPS from January 2001 to June 2018. By reviewing 14 patients from medical records, we analyzed the clinical findings with coexisting autoimmune diseases, particularly diabetes mellitus and thyroid disease, which are associated with anti-GAD antibody titers or other immunological test results (anti-thyroid peroxidase and anti-nuclear antibodies). We also evaluated malignancies, major complications, and reported treatment to improve symptoms. Anti-GAD antibodies were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). The cut-off values of these tests are < 1 U/mL and < 5 U/mL, respectively. RESULTS The median age of all patients was 39.3 (range, 28.0-54.0) years with a median follow-up period of 6.0 (2.7-13.3) years. Five (35.7%) patients were female; twelve (85.7%) were diagnosed with classic SPS and two (14.3%) with SLS. The median age of onset of symptoms was 35.0 (26.0-56.0) years with a median follow-up duration of 9.0 (2.1-14.9) years in the classic SPS group; the SLS group had a median age of onset of 46.7 years and a shorter follow-up duration of 4.3 years. Among nine classic SPS patients who underwent the anti-GAD Ab test, three were anti-GAD Ab seropositive and each of these three patients also had T1DM, latent autoimmune diabetes in adults, and autoimmune thyroid disease, respectively. In contrast, other rare autoimmune diseases co-existed in six anti-GAD Ab seronegative SPS patients. None of the SLS patients had additional autoimmune diseases. CONCLUSION While typical clinical symptoms are crucial for the diagnosis of SPS, the presence of anti-GAD autoantibody may consolidate the diagnosis and predict the association with other autoimmune diseases.

Betel nut is the second largest economic food product in Taiwan. In Southeast Asia, the habit of chewing betel nut seems to be highly correlated with oral submucous fibrosis and oral squamous cell carcinoma. Oral submucous fibrosis is characterized by abnormal accumulation of oral submucous collagen fibers and limitation of mouth opening. Although the mechanism responsible for tissue damage is still unknown, prolonged irritation caused by betel nut and tobacco is considered to be a major factor contributing to the pathogenesis of oral submucous fibrosis. The effect of betel nut chewing on immune system remains unknown. Present study aims to investigate the change of plasma hormones including cortisol, testosterone, and inflammatory cytokine concentrations in male chewing betel nut compared with normal subjects. Heparinized blood was obtained from control group (normal young+mid-aged individuals), betel nut-chewing, and oral cancer male subjects. The study was approved by the Ethics Committee of the Chang-Gung Memorial Hospital. Written informed consent was granted by the patients. Plasma cortisol and testosterone concentrations were detected by commercial enzyme-linked immunosorbent assay (ELISA). The inflammatory cytokines, including interleukin-1β (IL-1β), IL-15, tumor necrosis factor-α (TNF-α), were analyzed by ELISA with commercial monoclonal capture antibodies and polyclonal detection antibodies. The median concentrations of plasma IL-1β, IL-15, and TNF-α were 3.14pg/ml, 3.14pg/ml, and 6.85pg/ml, respectively, in patients with oral cancer, compared with median plasma IL-1β, IL-15, and TNF-α concentration of 2.64pg/ml, 5.86pg/ml, and 5.38pg/ml, respectively, in patients with betel nut-chewing habit. In contrast, the median concentrations of plasma IL-1β, IL-15, and TNF-α in mid-aged males (aged 30-50) were 7.00pg/ml, 10.64pg/ml, and 31.73pg/ml, respectively, compared with median plasma concentration of IL-1β, IL-15, and TNF-α of 4.48pg/ml, 33.36pg/ml, and 97.77pg/ml in young males (aged 20-22), respectively. Also, significantly elevated plasma cortisol concentration was noted in betel nut-chewing (median 727.2ng/ml) and oral cancer patients (561.9ng/ml) compared to the mid-aged (176.8ng/ml) and young males (173.4ng/ml), respectively. In addition, lower plasma testosterone concentrations were found in betel nut-chewing subjects compared with young males (2.6±3.3ng/ml vs 6.2±2.9ng/ml). To summarize, the inflammatory cytokines and steroid hormones may reflect the degree of inflammation in betel nut-chewing males and the oral cancer subjects. The above findings suggest that betel nut-chewing or oral cancer inhibits plasma cytokines and regulates steroid hormones concentrations compared to mid-aged or young normal subjects. It is also indicated that betel nut-chewing causes decreased inflammatory cytokines as the same levels as in oral cancer subjects.

Background The effect of combined insulin and dipeptidyl peptidase-4 inhibitor (DPP4i) therapy on major adverse cardiovascular events (MACEs) in patients with diabetic foot is unclear. Methods We conducted this nationwide cohort study using longitudinal claims data obtained from the Taiwan National Health Insurance program and included 19,791 patients with diabetic foot from 2007 to 2014. Patients receiving DPP4i-based therapy and/or insulin-based therapy after a diagnosis of diabetic foot were categorized into combined, DPP4i- or insulin-based groups, respectively. The risk of MACEs including nonfatal myocardial infarction, nonfatal stroke, cardiac death, and heart failure was assessed using Cox proportional hazards analysis and propensity score matching. Results Among the 19,791 patients with diabetic foot (mean age, 58.8 years [SD, 12.5]; men, 51.2%), 6466 received DPP4i-based therapy, 1925 received insulin-based therapy, and 11,400 received combined DPP4i and insulin therapy. The DPP4i-based and insulin-based groups had a lower risk of MACEs (HR 0.53, 95% CI 0.50–0.57 DPP4i only; HR 0.89, 95% CI 0.81–0.97 insulin only) than the combined group. After propensity score matching, the incidence of all complications in the DPP4i-based group was still significantly lower than that in the combined group (HR 0.55, 95% CI 0.51–0.59 for MACEs; HR 0.32, 95% CI 0.24–0.42 for nonfatal myocardial infarction; HR 0.70, 95% CI 0.63–0.78 for nonfatal stroke; HR 0.22, 95% CI 0.13–0.38 for cardiac death; HR 0.22, 95% CI 0.19–0.25 for any death; HR 0.16, 95% CI 0.13–0.20 for amputation). In the diabetic foot patients with end-stage renal disease (ESRD), the benefit of a lower incidence of MACEs in the DPP4i-based group disappeared (HR 0.77, 95% CI 0.58–1.08). Conclusions This study demonstrated that the patients with diabetic foot receiving DPP4i-based therapy had a lower risk of MACEs than those receiving combined therapy with DPP4i and insulin, but that the effect disappeared in those with concurrent ESRD. Electronic supplementary material The online version of this article (10.1186/s13098-018-0378-6) contains supplementary material, which is available to authorized users.

Background Evidences support the benefits of moderate- to high-intensity statins for patients with acute myocardial infarction (AMI) except for those with type 2 diabetes mellitus (T2DM) on dialysis after AMI. This study was aimed to investigate the safety and efficacy of secondary prevention of cardiovascular diseases using moderate- to high-intensity statins in T2DM patients on dialysis after AMI. Methods A simulated prospective cohort study was conducted between January 1st, 2001 and December 31st, 2013 utilizing data from the Taiwan National Health Insurance Research Database. A total of 882 patients with T2DM on dialysis after AMI were selected as the study cohort. Cardiovascular efficacy and safety of moderate- to high-intensity statins were evaluated by comparing outcomes of 441 subjects receiving statins after AMI to 441 matched subjects not receiving statins after AMI. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. Results The Kaplan–Meier event rate for the primary composite outcomes at 8 years was 30.2% (133 patients) in the statin group compared with 25.2% (111 patients) in the non-statin group (hazard ratio [HR], .98; 95% confidence interval [CI] .76–1.27). Significantly lower risks of non-fatal ischemic stroke (HR, .58; 95% CI .35–.98) and all-cause mortality (HR, .70; 95% CI .59–.84) were found in the statin group. Conclusions In T2DM patients on dialysis after AMI, the use of moderate- to high-intensity statins has neutral effects on composite cardiovascular events but may reduce risks of non-fatal ischemic stroke and all-cause mortality. Electronic supplementary material The online version of this article (doi:10.1186/s13098-017-0272-7) contains supplementary material, which is available to authorized users.

Background: Subclinical hypothyroidism (SCH) is defined as elevation in serum thyroid-stimulating hormone (TSH) levels despite normal serum levels of free thyroxine. It remains controversial whether people with SCH have higher total cholesterol and low-density lipoprotein cholesterol levels compared to normal-thyroid subjects. The aim of this study was to assess the metabolic risk factors for SCH. Methods: Subjects were recruited from the health examination center of Chang Gung Memorial Hospital, Linkou, from January 1, 2010 to December 31, 2011. This was a cross-sectional review of medical records. The subjects were ethnic Taiwanese residents without known thyroid disease at baseline. Results: A total of 22,324 subjects received annual health examination at Chang Gung Memorial Hospital from 2010 to 2011. Among them, 15,943 subjects were included as the normal thyroid group (NG), and 203 subjects (101 men and 102 women) met the criteria for SCH. The prevalence of metabolic syndrome (MetS) in the NG was 26.2% in men and 18.7% in women, whereas that in the SCH group was 39.6% in men and 29.4% in women. Women in the SCH group showed significantly higher cholesterol, triglyceride, non-high density lipoprotein (HDL) and cholesterol/HDL levels than those in the NG (p

BackgroundIn Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes.MethodsForty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation.ResultsAt week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of β cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial.ConclusionsThis pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and β-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

The aims of this study were to investigate papillary and follicular thyroid carcinomas with bone metastasis in various clinical presentations and to determine the prognostic factors after multimodality treatment. A retrospective analysis was performed of 3,120 patients with papillary and follicular thyroid carcinoma. Of these patients, 131 (including 97 women, 71.8%) were diagnosed with bone metastasis and underwent follow-up at the Chang Gung Medical Center. Patients with bone metastasis were categorized into two groups. Group A was comprised of patients who were diagnosed with bone metastasis either before thyroidectomy or within 6 months of the initial thyroidectomy (90 patients, 68.7%). Group B was comprised of patients with bone metastasis who received a diagnosis 6 months post-thyroidectomy in the follow-up period (41 patients, 31.3%). After a mean follow-up period of 8.4 ± 7.0 years, there were 88 deaths (67.2%) attributed to thyroid cancer and 13 patients (9.9%) achieved disease-free status. A multivariate analysis showed that older age, early diagnosis, and brain metastasis were each associated with a poor prognosis. The difference in disease-specific mortality rates between groups A and B was significant (p < 0.0001). In conclusion, papillary and follicular thyroid cancers with bone metastasis have a high rate of mortality. Despite this high mortality, 9.9% patients still had an excellent response to treatment.

To investigate the correlation between gender and the clinical presentation of papillary thyroid cancer and the long-term followup results, 435 patients who underwent total or near-total thyroidectomy were enrolled in this study. Among these papillary thyroid cancer patients, 12.2% showed lymph node metastases and a higher incidence of male patients in the N1b group. There were 65 from 316 female (20.6%) and 49 from 120 male (40.8%) patients who had a postoperative disease progression. A total of 55 (12.6%) patients died of thyroid cancer. Male patients showed a higher thyroid cancer mortality than the females. Multiple regression analysis showed that male gender was an independent risk factor for cancer recurrence and mortality. Male patients with TNM stages II to IV of papillary thyroid cancer need to adopt aggressive surgical and postoperative131I therapy.

An increased risk of mortality in patients with uncontrolled acromegaly has been reported in several studies. We aimed to assess the impact of co-morbidities on the survival of patients with acromegaly after long-term treatment and follow-up.A retrospective analysis was performed for 285 patients with active acromegaly, who were admitted to the Chang Gung Memorial Hospital, Taiwan between 1978 and 2012. Of these patients, 106 (37.2%) were diagnosed with diabetes mellitus (DM). During the follow-up period, 21 cases of histological proved malignant in acromegalic patients, and DM with acromegaly had a higher incidence of malignancy (13.2% vs. 3.8%; p0.01). The 5-, 10-, and 20-year survival rates were 93.1%, 86.9%, and 84.7% for the DM group, respectively, and 96.5%, 96.5%, and 96.5% for the non-DM group, respectively. After a mean follow-up of 15.1 ± 0.6 years, age, DM, coronary heart disease, and malignancy were found to be significant factors of mortality. Control of growth hormone and IGF-1 levels also conferred a marginal survival benefit.DM and malignancy significantly influence the survival of patients with acromegaly; thus, these patients need close follow-up and appropriate therapy. (Endokrynol Pol 2016; 67 (5): 501-506).

Primary nonfunction (PNF) adversely impacts islet transplantation. In addition to determining whether sodium 4-phenylbutyrate (4-SPB), an anti-inflammatory agent, reduces PNF, this study investigates how 4-SPB affects PNF. Streptozotocin-induced diabetic C57BL/6 mice, that received 75 syngeneic islets underneath left subrenal space, were fed twice daily of either 4-SPB at 500 mg/kg body weight or isotonic saline (NaCl) from 2 days before through 7 days after transplantation. The graft was removed at days 3, 10 and 84 following transplantation. At 68 h following transplantation, serum levels of interleukin-1beta (IL-1beta) were 2.2+/-0.4 and 0.4+/-0.2 pmol/L (n=6, p0.005) for NaCl and 4-SPB groups, respectively. Graft genetic expression of IL-1beta was significantly suppressed in 4-SPB group (p0.01). At day 10, the blood glucose levels were 22.7+/-1.0 and 17.1+/-1.7 mmol/L (n=12, p0.05) and graft insulin contents (IC) were 35.0+/-8.3 and 107.6+/-29.7 pmol (n=12, p0.05) for NaCl and 4-SPB groups, respectively. Moreover, the 4-SPB group had a shorter temporary hyperglycemia (15+/-2, n=21 vs. 25+/-2 days, n=19, p=0.001) and a higher cumulative cure rate of diabetes (p0.001) than the NaCl group. In-vitro studies indicated that 4-SPB did not impact the islets function. These experimental results demonstrated that perioperative administration of 4-SPB decreased serum level and graft genetic expression of IL-1beta and attenuated PNF, which enhanced islet engraftment in a syngeneic transplantation mouse model.

Background To investigate the clinical features of thyroid cancer in aging patients and to present the results of treatment. From this we can provide bases for earlier diagnoses and better treatment of thyroid malignancies in older patients. Materials and methods In this study a retrospective analysis was performed with 204 thyroid cancer patients aged 60 years or older (132 women, with a mean age of 68.3 ± 6.6 years; 72 men, with a mean age of 67.0 ± 5.3 years). Results Of the 204 patients, 142 had well-differentiated thyroid carcinomas (96 papillary thyroid carcinomas, 43 follicular carcinomas, three Hurthle cell carcinomas) and three medullary carcinomas. Sixty-nine (33.8%) of the 204 patients died after treatment. Of these, three patients died of causes not related to thyroid cancer. For well-differentiated thyroid carcinomas, male gender, follicular carcinoma, and a larger tumour size indicated a poor prognosis. Of the 59 non-well-differentiated thyroid carcinomas, 39 were anaplastic thyroid carcinomas, nine metastatic cancers of the thyroid, seven lymphomas, and four squamous cell carcinomas. After treatment, 40 (67.8%) of the 59 patients died. In multivariant analysis of the differences in clinical parameters between aging and younger thyroid cancer patients, the current status, tumour size, follow-up period, sex, and stage at diagnosis were independent factors. From this data the delayed diagnosis of aging patients with thyroid cancer was of note when compared with younger patients. Conclusion Thyroid cancer in older patients is not a benign clinical disorder. Early diagnosis and urgent aggressive treatment are recommended courses of action for this type of cancer, especially for non-well-differentiated thyroid cancers.

BACKGROUND: Increased body mass index is related to the incidence of thyroid cancer. However, the presentation and therapeutic outcomes of different thyroid cancers and type 2 diabetes mellitus (DM) have not been studied. This study investigated the effect of type 2 DM on the clinical presentations and therapeutic outcome of well-differentiated thyroid cancer. METHODS AND FINDINGS: A retrospective analysis of adult thyroid cancer patients with or without type 2 DM admitted between January 2001 and December 2010 was performed at an institution. A total of 1,687 well-differentiated thyroid cancer patients with different histological patterns were enrolled. Among these subjects, 122 were type 2 DM patients. Patients with thyroid cancer and type 2 DM were significantly older than non-DM patients. After a mean follow-up period of 5.6±0.1 years, patients with thyroid cancer and type 2 DM showed a higher percentage of disease progression than non-DM patients (24.6% vs. 17.4%). In addition, disease-specific mortality was higher in the type 2 DM group (10.7% vs. 3.8%). Thyroid cancer patients with type 2 DM showed a higher percentage of secondary primary cancers than those without DM (10.7% vs. 4.9%). Thyroid cancer-specific survival rates in the type 2 DM and non-DM groups were 82.2% and 94.9% at 5 years, 72.9% and 91.4% at 10 years, and 36.5% and 61.3% at 20 years, respectively. Multivariate analysis showed that type 2 DM was independent of thyroid cancer-specific mortality. CONCLUSION: Patients with type 2 DM and well-differentiated thyroid cancer had an advanced tumor-node-metastasis stage at the time of diagnosis and an increased disease-specific mortality. Aggressive surgical procedures and close follow-up for well-differentiated thyroid cancer patients with type 2 DM are therefore necessary.

To understand the role of thyroid hormone in metastasis, we studied the expression of the anti-metastatic nm23 gene in eight human hepatocellular carcinoma (HCC) cell lines. These cells differentially expressed the anti-metastatic nm23 gene. A low level of nm23 proteins was found to have a high in vitro invasive activity which correlated closely with an overexpression of the thyroid hormone β1 nuclear receptor (h-TRβ1). Concurrent with the down-regulation of h-TRβ1, the invasive activity of HCC cells was suppressed by the thyroid hormone, 3,3′,5-triiodo- l -thyronine (T3). These results indicate that the invasive activity of HCC cells was regulated by T3, suggesting that T3 could be involved in modulating the functions of nm23.

The complementary role of hyperglycemia and suppression on islet beta cell regeneration was investigated in a syngeneic mouse model. gene silencing was performed by infecting islets of C57BL/6 with shRNA lentiviral particles. At 54 hours after viral infection, protein content in cultured targeting islets was 22% of that in freshly isolated islets. Six days after transplantation to diabetic mice, targeting islet graft had considerably more cells with Ki67-staining nuclei than nontargeting islets. The mice in the targeting-islet group had a significantly shorter duration of temporary hyperglycaemia than mice in the non-targeting-islet group. The long-termex vivobeneficial effect of silencing on graft function was also indicated by the significantly higher cumulative cure rate for diabetes in mice receiving 200 targeting islets than that in mice receiving 200 non-targeting islets. Our data suggest that hyperglycemia and persistent suppression have a synergistic effect on islet beta cell replication in adult mice.

Background and purpose: Recent studies have suggested increased prevalence of impulsive/compulsive behaviors (ICB) in patients with Parkinson’s disease (PD) as compared to general population in different ethnic groups. The spectrum of these behaviors includes dopamine dysregulation syndrome (DDS), punding, pathological gambling (PG), hypersexuality (HS), binge eating (BE), and compulsive shopping (CS). Methods: Two hundred and seventy-eight consecutive patients with idiopathic PD regularly followed-up at an outpatient clinic were interviewed and screened for the ICB between September 2008 and December 2008 using designated diagnostic criteria. All patients who screened positive for ICB or obsessive-compulsive disorder (OCD) were further confirmed by an experienced psychiatrist. Results: Of all the studied patients, 15 patients confirmed to have ICB (lifetime prevalence: 5.60%), 3 (1.12%) were diagnosed to have DDS, 1 (0.37%) punding, 4 (1.49%) PG, 8 (2.99%) HS, 1 (0.37%) BE, 0 (0%) CS. OCD was found in one patient (0.37%). Conclusions: The prevalence of ICB is lower in Taiwan as compared with the Caucasians, with similar risk factors. The possible reasons include differences in ethnicity, environmental, cultural, and social factors as well as the dosage and selection of dopaminergic medications.

Aim: Although percutaneous transluminal angioplasty (PTA) is an effective therapeutic procedure for critical limb ischemia, several clinical factors can influence the outcome of PTA for peripheral arterial disease (PAD). The aim of this study is to identify the outcome predictors of PTA in infected diabetic foot patients with PAD. Methods: Eighty-five diabetic patients with a total of 90 infected limbs treated by PTA participated in this study. Patients were initially admitted for infected foot ulcers and were later diagnosed with PAD. Even though all patients underwent successful PTA within 15 days of admission, limb salvage was successful in 66 cases while 24 underwent subsequent amputation. The clinical characteristics and laboratory variables of both groups before PTA were compared and analyzed. Results: Significantly higher level of C-reactive protein (CRP) was observed in the major amputation group before PTA. The cutoff value via receiver operating characteristic curve was 50 mg/L (81.8% specificity, 70.7% sensitivity). Multivariate logistic regression analysis revealed that CRP levels may serve as valuable marker in determining a successful outcome. Conclusion: Reduced CRP levels (

The goal of this study was to determine whether conservative surgical therapy had been adequate for low-risk patients with papillary thyroid cancer.1,931 patients were categorized as either low risk or high risk, using tumor-node-metastasis (TNM) staging from the sixth edition of International Union Against Cancer (UICC); TNM stage I was designated low risk during this retrospective review.After an average follow-up period of 8.7 years, 58 of 1,931 patients (3.0%) died from thyroid cancer. Ten-year survival rates of papillary thyroid carcinoma from sixth edition TNM stages I to IV are 99.7%, 95.6%, 90.7%, and 84.0%, respectively. Age, tumor size, (131)I therapeutic dose, and follow-up status were statistically significant when comparing high- and low-risk groups. Of the 1,432 patients in stage I, 338 underwent conservative surgical procedures. Among 338, 4 patients died of thyroid carcinomas (1.2%) and 15 (4.4%) had persistent or recurrent disease. In contrast, 2 of the 1,094 (0.2%) patients who received near-total thyroidectomy or limited lymph node dissection died from thyroid cancer, and 32 (2.9%) had persistent or recurrent disease.TNM stage I papillary thyroid carcinomas were with low cancer-specific mortality rate; otherwise, patients aged 45 years or younger should not be considered a homogeneous low-risk group. Initial extent of disease was an important predictor among these patients. In particular, local invasion with airway compression predicts outcomes.

Summary This study determined cancer survival rates and follow-up status at different pTNM stages to stratify risk groups in follicular thyroid carcinoma. Two hundred and fourteen follicular thyroid cancer patients (167 females, 47 males) who underwent surgery and followed-up treatment at a single medical center were enrolled in this retrospective study. Tumors were staged by UICC-TNM criteria (6th edition). Low risk for follicular thyroid cancer was defined as pT1N0M0. (Moderate-risk group) was defined as all other patients in pTNM stage I, and high risk as patients in stages II–IV. After mean follow-up of 9.6±0.3 years, 1.6% (2/120), 21.9% (7/32), 5.6% (1/18) and 52.3% (23/44) of patients in pTNM stages I–IV, respectively, died of thyroid cancer. Of 214 follicular thyroid cancer patients, 35 (16.4%), 85 (39.7%) and 94 (43.9%) were defined as low-, moderate- and high-risk groups at the time of surgery. None of the low-risk patients died, and all achieved disease-free status. In the moderate- and high-risk groups, 2.4% (2/85) and 27.7% (26/94) died of thyroid cancer. The moderate- and high-risk groups underwent near-total thyroidectomy and 131 I therapies, and 15 of 107 (14.9%) died of thyroid cancer while 18 (16.8%) had persistent disease at the end of the study period. Multiple regression analysis demonstrated that tumor size, radioactive iodide therapy and post-operative thyroglobulin level significantly differ between the mortality and survival groups. In conclusion, the low-risk follicular thyroid cancer group as defined by pTNM staging had excellent prognosis. Total thyroidectomy and post-operative radioactive iodide therapy are mandatory in moderate- and high-risk groups. Over one-fourth of the follicular thyroid cancer patients in the high-risk group died of thyroid cancer despite aggressive treatment.

Hypothesis Total thyroidectomy followed by radioactive iodine I 131 treatment is effective in papillary thyroid microcarcinoma (PTM) with lymph node or extrathyroid invasion. Design Retrospective study. Setting Chang Gung Medical Center, Linkou, Taiwan. Patients A total of 227 patients with PTM, categorized into high-risk (n = 12) and low-risk (n = 215) groups according to age, metastases, extent, and size criteria. Interventions Diagnosis and treatment of PTM. Main Outcome Measures Time and method of diagnosis, operative method, metastases, and survival. Results In 51 patients, PTM was identified on preoperative fine-needle aspiration cytology; in 75 patients, diagnosed in frozen sections during operation; and in 101 patients, diagnosed incidentally in the final histopathological examination. Among these 3 groups, 18% (9/51), 17% (13/75), and 78% (79/101), respectively, underwent subtotal thyroidectomy or lobectomy for tumors. Four cases (1.8%) displayed distant metastases at diagnosis. Only 0.9% of patients with PTM (2 of 227) died of thyroid cancer. One hundred eighty-nine cases of PTM were confined to the thyroid, 22 had lymph node metastases, and 16 showed extrathyroid extension, including soft-tissue invasion and distant metastases. Sex, operative methods, follow-up status, and mortality showed differences in these groups. Five of 227 patients remained in non–disease-free status at follow-up. Conclusions Approximately 10% of PTMs exhibited progressive clinical courses, while less than 1% resulted in mortality. Age, sex, and postoperative thyroglobulin level were the main prognostic factors in the high-risk group of patients with PTM. Conservative treatment of the incidental finding of PTM after suitable postoperative assessment is justified.

Thyroid nodule is common disorder in endocrine clinics. In Taiwan, thyroid ultrasonography with fine-needle aspiration cytology (FNAC) is the first-line examination procedure. Data in large series on the incidence of thyroid malignancy presenting with thyroid nodules are lacking in this area. To determine the incidence of malignancy in thyroid nodules and compare the results with other populations, this investigation retrospectively reviewed 21,748 subjects who were examined in one medical center from January 1986 to December 1999. All patients underwent thyroid ultrasonography studies using a real-time ultrasonographic machine and a 10-MHz transducer. Fine-needle aspirations were made in the suspected thyroid nodule and stained using the Romanowsky- based method developed by Liu. By the end of 2002, some 3629 patients (16.7%) had thyroid nodules after surgical treatment. This group comprised 3011 women with a mean age of 41.5 +/- 13.9 years, and 618 men with a mean age of 45.7 +/- 14.9 years. Of patients undergoing surgical treatment, 2761 (76.1%) patients were diagnosed with benign nodules, 858 (23.6%) with malignant nodules, and 10 (0.3%) with atypical adenoma (7 follicular and 3 Hurthle cells). The percentages of thyroid malignancy in each age group revealed two peaks in both genders, namely in patients aged 20 to 29 years and in elderly patients (aged over 65 years). The peak age for thyroid malignancy in both genders was 41 to 60 years (male) and 21 to 40 years (female). The highest ratio of malignancy occurred in the elderly group (37.2%) receiving surgical treatment. In young patients (below 19 years) the percentage of malignancy was no greater than for the whole age group (20.2% versus 25.6%). Anaplastic and metastatic cancers affecting the thyroid were the main subjects in the age group. The present results demonstrated a younger distribution for well-differentiated thyroid cancer, particularly papillary thyroid carcinoma, compared to previous studies. This outcome may have resulted from the routine application of ultrasonography with FNAC in assessing the thyroid nodules, possibly helping to achieve more timely detection. The incidence of thyroid malignancy in young patients was no higher than in adults. Early detection of thyroid malignancy may be the main reason for this phenomenon. Male subjects with thyroid nodules displayed a higher incidence of this malignancy than females. Aging subjects with thyroid nodules suffered a higher rate of malignancy and were poorly differentiated. In conclusion, this retrospective large-series study demonstrated that 3.9% (858/21,748 cases) of patients with thyroid nodules showed histopathologically proven malignancy. Thyroid cancer detected by ultrasonography with FNAC occurred an average of 10 years younger than in prior studies.