High left ventricular mass associated with increased risk of incident diabetes.

Evidence for the role of electrocardiography or echocardiography in determining left ventricular hypertrophy for the risk of diabetes is still controversial. We aimed to explore whether left ventricular mass, as measured by these methods, is associated with the risk of diabetes in a community population. We recruited 2696 participants aged 35 years or older without diabetes who had undergone screening with electrocardiography and echocardiography. Left ventricular mass index (LVMI) was calculated using a formula, and participants were divided into tertiles based on their LVMI tertiles. During a median follow-up period of median, 8.9 years, a total of 405 participants developed diabetes. The incidence and risk of diabetes significantly increased with higher LVMI tertiles. Multivariate Cox regression analysis demonstrated that individuals in the highest LVMI tertile had a greater likelihood of developing incident diabetes, with a hazard ratio of 1.40 (95% CI 1.06-1.91), even after adjusting related covariates. The highest risk of diabetes was observed in the presence of both the uppermost LVMI tertile and electrocardiographically determined left ventricular hypertrophy for the Chinese population. Left ventricular hypertrophy identified by either electrocardiography or echo may serve as a surrogate marker for identifying the risk of diabetes in clinical practice.

Comparison of two titration programmes for adding insulin detemir to oral antidiabetic drugs in patients with poorly controlled type 2 diabetes mellitus.

AIM: To explore the effect of active insulin titration versus usual titration on glycaemic control in patients with type 2 diabetes mellitus uncontrolled with oral antidiabetic drugs (OADs). METHODS: In a 24-week, prospective and randomized study, 172 patients with uncontrolled type 2 diabetes were randomly assigned to either active titration or usual titration. Efficacy and safety outcomes included changes in glycated haemoglobin (HbA1c) and fasting plasma glucose, percentage of individuals achieving HbA1c<53 mmol/mol, and hypoglycaemic events. RESULTS: At Week 24, change in HbA1c was -1.08% ± 1.60% in the active titration group and -0.95% ± 1.34% in the usual titration group (P = 0.569). The percentages of individuals achieving HbA1c<53 mmol/mol were 29.4% and 16.1% in the active and usual titration groups, respectively (P = 0.037). There was no significant difference in the incidence of hypoglycaemia between the two groups. Multivariate logistic regression indicated that, with active titration, baseline HbA1c levels and postprandial glucose excursion were significantly associated with achieving HbA1c<53 mmol/mol. CONCLUSION: Addition of basal insulin using active titration for 24 weeks provided a higher rate of HbA1c target achievement without significant hypoglycaemia compared to usual titration in individuals with uncontrolled type 2 diabetes.

Effects of SGLT2 inhibitors on stroke and its subtypes in patients with type 2 diabetes: a systematic review and meta-analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown impressive effects in reducing major vascular events in several randomized controlled trials (RCTs). The purpose of this study was to perform a meta-analysis to evaluate the effect of SGLT2 inhibitors on the risk of stroke and its subtypes. All data from prospective RCTs up to 20 October 2020 involving SGLT2 inhibitors that reported stroke events as the primary endpoint or safety in subjects with type 2 diabetes were subjected to meta-analysis. Five eligible RCTs (EMPA-REG, CANVAS, DECLARE-TIMI 58, CREDENCE and VERTIS CV) involving 46,969 participants were included. Pooled analysis of the RCTs showed no significant effect of SGLT2 inhibitors on total stroke [risk ratio (RR) = 0.95; 95% confidence interval (CI) 0.79-1.13, P = 0.585]. Subgroup analysis indicated that SGLT2 inhibitors had no significant effect against fatal stroke, non-fatal stroke, ischemic stroke or transient ischemic attack. When only hemorrhagic stroke was included, SGLT2 inhibitors were associated with a significant 50% reduction compared with placebo (RR = 0.49, 95% CI 0.30-0.82, P = 0.007). This meta-analysis shows that SGLT2 inhibitors have a neutral effect on the risk of stroke and its subtypes but a potential protective effect against hemorrhagic stroke.

Loss of Integrase Interactor 1 (INI1) Expression in a Subset of Differentiated Thyroid Cancer.

Alterations in the switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complex are enriched in advanced thyroid cancer. Integrase interactor 1 (INI1), encoded by the SMARCB1 gene on the long arm of chromosome 22, is one of the core subunits of the SWI/SNF complex. INI1 immunohistochemistry is frequently used for the diagnosis of malignant rhabdoid neoplasms. In the present study, we found normal and benign thyroid tissues generally had diffusely intense nuclear immunostaining. Loss of INI1 immunohistochemical expression was observed in 8% of papillary thyroid cancer and 30% of follicular thyroid cancer. Furthermore, loss of INI1 expression was associated with extrathyroidal extension (p < 0.001) and lymph node metastasis (p = 0.038). Analysis of The Cancer Genome Atlas database revealed that SMARCB1 underexpression was associated with the follicular variant subtype and aneuploidy in papillary thyroid cancer. We speculate that SMARCB1 is an important effector in addition to NF2 and CHEK2 inactivation among thyroid cancers with chromosome 22q loss.

Diabetic status and the relationship of blood glucose to mortality in adults with carbapenem-resistant Acinetobacter baumannii complex bacteremia.

BACKGROUND/PURPOSE: Diabetes is associated with increased mortality in Acinetobacter baumannii (AB) complex infection. This study investigated the risk factors and relationship of diabetic status and glycemic indices to mortality in patients with carbapenem-resistant (CR) AB complex bacteremia. METHODS: Relationship of glycemic indices to mortality were compared in adult diabetes (DM) and nondiabetes (non-DM) patients with CRAB complex bacteremia hospitalized from January 2010 to December 2015 in MacKay Memorial Hospital, Taiwan. RESULTS: Of 317 patients with CRAB complex bacteremia, 146 (46.06%) had diabetes. DM patients were elderly (mean age of 69.23 years) and the mortality rate was higher (64.38% vs. 52.05%, p = 0.036) than in non-DM patients. By multivariate analysis, septic shock was associated with increased mortality in DM patients. Hypoglycemia was associated with increased mortality in non-DM patients only (100% vs. 50.33%, p = 0.006). The lowest mortality was for the blood glucose range 70-100 mg/dL in non-DM patients (43.24%) and 100-140 mg/dL for DM patients (56.52%). Increased glycemic variability (coefficient of variation (CV) > 40% compared to < 20%) was associated with increased mortality in non-DM patients (86.36% vs. 47.12%, p = 0.003). CONCLUSION: Effects of dysglycemia on mortality due to CRAB complex bacteremia differ according to diabetic status. Mortality was higher in DM patients. In non-DM patients, hypoglycemia and increased CV were associated with increased mortality. The lowest mortality was for the blood glucose range 70-100 mg/dL in non-DM patients and 100-140 mg/dL for DM patients.

Is papillary thyroid microcarcinoma a biologically different disease? A propensity score-matched analysis.

BACKGROUND: Papillary thyroid microcarcinoma exhibits an indolent clinical course and could be a candidate for active surveillance in the appropriate setting. It remains unknown whether papillary microcarcinoma is biologically different from larger papillary carcinoma >1 cm. METHODS: We analyzed clinicopathological information and transcriptome data of papillary thyroid cancer samples from The Cancer Genome Atlas. Propensity-score matching was used to construct a matched cohort consisting of 29 microcarcinomas and 58 carcinomas. Principal component analysis and unsupervised hierarchical cluster analysis were carried out to investigate the similarity of gene expression profiles. RESULTS: After adjustment for differences in baseline clinicopathological and genetic factors, transcriptome could be grouped mainly on the basis of tumor class (BRAF-like vs RAS-like) and tumor size (microcarcinoma vs carcinoma). The gene set enrichment analysis showed that extracellular matrix-associated pathways were enriched in the MSigDB database. CONCLUSION: Papillary thyroid microcarcinomas display a distinct gene expression pattern different from the corresponding carcinomas. We hypothesize that tumor microenvironment may play a role in the microcarcinoma/carcinoma phenotypic divergence.

An Increased Neutrophil-to-Lymphocyte Ratio Predicts Incomplete Response to Therapy in Differentiated Thyroid Cancer.

Background: Previously we have shown that an elevated baseline neutrophil-to-lymphocyte ratio (NLR) was associated with a high risk of recurrence in patients with differentiated thyroid cancer. The clinical significance of the longitudinal changes in NLR following treatment remained unestablished. Methods: Adults patients with differentiated thyroid cancer were included in the study if the follow-up NLR data at 6 to 18 months after initial treatment were available. The response to treatment was categorized as excellent, indeterminate, biochemical incomplete, and structural incomplete as per guidelines of the American Thyroid Association. Results: Among 151 patients with thyroid cancer, a significant decrease in NLR following treatment was observed in those with stage I disease, those with low risk of recurrence, and those with an excellent response to therapy. Patients with a structural incomplete response had a significant increase in NLR at follow-up (p = 0.012). On multivariate analysis, incomplete response to therapy was associated with male sex (odds ratio [OR] = 3.35), tumor size (OR = 1.63), lymph node metastasis (OR = 4.80), distant metastasis (OR = 12.95), and increased NLR (OR = 13.68). Conclusions: An increase in systemic inflammation following treatment as measured by NLR is independently associated with an incomplete response to therapy in differentiated thyroid cancer.

Emergence of carbapenem-resistant Acinetobacter baumannii ST787 in clinical isolates from blood in a tertiary teaching hospital in Northern Taiwan.

BACKGROUND/PURPOSE: The purpose of this study is to investigate the predominant clones of carbapenem-resistant Acinetobacter baumannii (CRAB) in our hospital in Taiwan by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) technique. METHODS: We collected 108 non-duplicate A. baumannii clinical blood isolates from January 2012 to December 2013 in MacKay Memorial Hospital. PFGE and MLST were used for typing the A. baumannii isolates and for investigation of the predominant clones. Bacteria isolates were screened by polymerase chain reaction for the presence of the carbapenemase-encoding genes. RESULTS: All 108 isolates were classified as 33 pulsotypes by PFGE. The predominant clones were pulsotype 10 (12.04%) in 2012 and pulsotype 8 (16.67%) in 2013, respectively. The 31 predominant pulsotype isolates were typed by MLST, and ST787 (54.84%) and ST455 (45.16%) were identified. All isolates carried blaOXA-51-like genes, and blaOXA-23-like genes was founded in 101 isolates (93.52%). Other identified resistance genes included blaOXA-24-like and blaOXA-IMP. CONCLUSION: To the best of our knowledge, this study is the first to describe the microbiological characteristics of CRAB ST787, which carried high genetic resistance to carbapenem, but remained susceptible to colistin. CRAB ST787 was the predominant clone in our hospital in the study period.

Dipeptidyl Peptidase IV as a Prognostic Marker and Therapeutic Target in Papillary Thyroid Carcinoma.

Context: Dipeptidyl peptidase IV (DPP4) is overexpressed in thyroid cancer and certain malignancies. Furthermore, DPP4 has been identified as a discriminatory marker for thyroid cancer. However, it remains unclear whether DPP4 expression plays a prognostic role. Objective: The aim of this study was to investigate the expression and function of DPP4 in thyroid cancer and the mechanisms involved. Design: We determined the expression of DPP4 by immunohistochemistry in tissue microarrays of thyroid tumors. In vitro functional studies were performed after genetic and pharmacological inhibition of DPP4. Gene expression and pathway analyses were used to identify downstream targets. The therapeutic potential of DPP4 inhibition was evaluated in a mouse xenograft model. Results: High DPP4 expression was associated with extrathyroidal extension (P < 0.001), BRAF mutation (P < 0.001), and advanced tumor stage (P = 0.007) in papillary thyroid cancer. Patients in the high-DPP4 expression group were less likely to be classified as having no evidence of disease at final follow-up (P = 0.042). DPP4 silencing or treatment with DPP4 inhibitors significantly suppressed colony formation, cell migration, and invasion. Analysis of differentially expressed genes after DPP4 knockdown suggested that the transforming growth factor-ß signaling pathway is involved. In vivo experiments revealed that sitagliptin treatment reduced tumor growth and xenograft transforming growth factor-ß receptor I expression. Conclusions: Increased DPP4 expression is associated with cellular invasion and more aggressive disease in papillary thyroid cancer. Targeting DPP4 may be a therapeutic strategy for DPP4-expressing thyroid cancer.

CD74 expression and its therapeutic potential in thyroid carcinoma.

CD74, the invariant chain of major histocompatibility complex class II, is also a receptor for macrophage migration inhibitory factor (MIF). CD74 and MIF have been associated with tumor progression and metastasis in hematologic and solid tumors. In this study, we found that 60 and 65% of papillary thyroid cancers were positive for CD74 and MIF immunohistochemical staining respectively. Anaplastic thyroid cancer was negative for MIF, but mostly positive for CD74 expression. Normal thyroid tissue and follicular adenomas were negative for CD74 expression. CD74 expression in papillary thyroid cancer was associated with larger tumor size (P=0.043), extrathyroidal invasion (P=0.021), advanced TNM stage (P=0.006), and higher MACIS score (P=0.026). No clinicopathological parameter was associated with MIF expression. Treatment with anti-CD74 antibody in thyroid cancer cells inhibited cell growth, colony formation, cell migration and invasion, and vascular endothelial growth factor secretion. In contrast, treatment with recombinant MIF induced an increase in cell invasion. Anti-CD74 treatment reduced AKT phosphorylation and stimulated AMPK activation. Our findings suggest that CD74 overexpression in thyroid cancer is associated with advanced tumor stage and may serve as a therapeutic target.

Efficacy and safety of adding pioglitazone or sitagliptin to patients with type 2 diabetes insufficiently controlled with metformin and a sulfonylurea.

OBJECTIVE: To evaluate the efficacy and safety of add-on pioglitazone versus sitagliptin in patients with type 2 diabetes inadequately controlled on metformin and a sulfonylurea (SU). METHODS: This 24-week, randomized, open-label study compared pioglitazone (30 mg daily, n = 59) and sitagliptin (100 mg daily, n = 60) in patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0% to <11.0%) while receiving a stable dose of metformin (≥1,500 mg daily) and an SU (≥half-maximal dose). RESULTS: The mean changes in HbA1c from baseline was -0.94 ± 0.12% with pioglitazone and -0.71 ± 0.12% with sitagliptin, for a between-groups difference of -0.23 ± 0.16% (P = .16). The mean change in fasting plasma glucose (FPG) were -35.7 ± 4.0 mg/dL with pioglitazone and -22.8 ± 4.0 mg/dL with sitagliptin, for a between-groups difference of -12.9 ± 5.7 mg/dL (P = .02). Pioglitazone was associated with a significant decrease in high-sensitive C-reactive protein (hs-CRP), but sitagliptin did not. The mean weight gain was higher in the pioglitazone group, with a between-group difference of 1.6 kg (P<.01). Overall adverse events (AEs) were similar in both groups. However, the incidence of edema was higher with pioglitazone, and the incidence of gastrointestinal AEs was higher with sitagliptin. CONCLUSION: Pioglitazone and sitagliptin achieved similar improvements in overall glycemic control in patients with type 2 diabetes inadequately controlled with metformin and an SU. However there were some differences in terms of FPG, hs-CRP, lipids, body-weight change, and AEs.

Clinical and microbiological analysis of adult perianal abscess.

BACKGROUND: In Taiwan, Klebsiella pneumoniae is the predominant pathogen causing pyogenic liver abscess in patients with diabetes mellitus (DM). The purpose of our hospital-based study was to determine the predominant bacterial species causing perianal abscess in hospitalized patients with and without DM in Taiwan. METHODS: Data on patients admitted and then operated on for perianal abscess during the period of March 2001 to December 2008 were reviewed. Information extracted from medical records included clinical information and laboratory data as well as culture and antibiotic sensitivity results. RESULTS: A total of 183 patients underwent surgery for perianal abscess. The most common pathogen causing perianal abscess in non-DM patients was Escherichia coli (67.1%), and the most common pathogen isolated in DM patients was K pneumoniae (60%; p=0.009). Among the 25 patients with DM, incident DM was diagnosed in 24.0% (6 of 25). In addition, five patients had transient hyperglycemia. CONCLUSIONS: Escherichia coli was the predominant pathogen isolated from perianal abscesses in patients without DM. Klebsiella pneumoniae, however, was the predominant pathogen isolated in DM patients. In both DM and non-DM patients, more than 90% of K pneumoniae isolates showed in vitro sensitivity to first-generation cephalosporins.

Antimicrobial therapy and control of multidrug-resistant Pseudomonas aeruginosa bacteremia in a teaching hospital in Taiwan.

BACKGROUND AND PURPOSE: The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa is a challenging clinical problem. This study investigated the source of an outbreak of MDR P. aeruginosa infections and the role of combination therapy in its management. METHODS: MDR P. aeruginosa isolates were collected at the MacKay Memorial Hospital, Taipei, Taiwan, and antibiotic synergy was investigated based on antibiotic susceptibility tests using a combination of antibiotics. Isolates of patients with MDR P. aeruginosa bacteremia were selected for genetic analysis by pulsed-field gel electrophoresis. RESULTS: A combination of ceftazidime, amikacin, and sulbactam had significant synergistic effects against bloodstream MDR P. aeruginosa isolates and was more beneficial clinically compared with other antibiotic combinations. The major source of MDR P. aeruginosa infection was located and stringent infection control measures were enforced. CONCLUSION: The results of this study suggest that use of triple antimicrobial therapy (ceftazidime, amikacin, and sulbactam) can be a useful alternative treatment for MDR P. aeruginosa infection in certain circumstances.

Safety and effectiveness of rosiglitazone in type 2 diabetes patients with nonalcoholic Fatty liver disease.

BACKGROUND/PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging in severity from steatosis to cirrhosis. Type 2 diabetes mellitus is a cause of primary NAFLD. Thiazolidinediones have been shown to enhance insulin sensitivity, improve glycemic control in type 2 diabetes patients and to improve the histologic markers of nonalcoholic steatohepatitis. This study aims to determine the safety and effectiveness of rosiglitazone in inadequately controlled type 2 diabetes patients with NAFLD. METHODS: Taiwanese type 2 diabetes patients with inadequate control on insulin secretagogues and metformin, with no history of significant alcohol ingestion, with mildly elevated serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and a diagnosis of fatty liver determined by ultrasonography were enrolled. Patients were treated for 24 weeks with rosiglitazone, 4-8 mg daily. Primary endpoints were change in AST and ALT levels from baseline and reduction in A1C < 6.5%. RESULTS: Out of a total of 68 patients, 60 (88.2%) completed the study treatment without serious adverse events. Treatment in two (2.9%) patients was discontinued due to elevated AST or ALT levels to more than three times the upper limit of normal, and noncompliance or loss of follow-up in six (8.8%) patients. Of the 60 patients who completed the study treatment, mean fasting plasma glucose, A1C, fasting plasma insulin, mean ALT and homeostasis model assessment for insulin resistance were all significantly reduced. Normal AST and ALT levels were achieved and maintained for at least three consecutive measurements and through to the end of the study period in 20 (33.3%) patients. Weight increased by a mean of 2.6 +/- 2.4 kg (p < 0.001). CONCLUSION: Rosiglitazone was reasonably well tolerated in patients with inadequately controlled type 2 diabetes and NAFLD. One-third of patients showed improved liver function after treatment.