Ming-Lung Tsai

Sitagliptin and cardiovascular outcomes in diabetic patients with chronic kidney disease and acute myocardial infarction: A nationwide cohort study

BACKGROUND The cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in type 2 diabetic patients with chronic kidney disease (CKD) after acute myocardial infarction (AMI) are unclear. METHODS We analyzed data from the Taiwan National Health Insurance Research Database between March 1st, 2009 and December 31st, 2011. A total of 1025 AMI patients with diabetes with chronic kidney disease were selected as the study cohort. The study evaluated the cardiovascular safety and efficacy of sitagliptin by comparing 205 subjects (20%) who use sitagliptin to 820 matched subjects (80%) who do not. The primary outcomes included myocardial infarction, ischemic stroke or cardiovascular death. RESULTS Primary composite outcomes occurred in 54 patients in the sitagliptin group (26.3%) and in 164 patients in the comparison group (20.0%) (HR, 1.32; 95% CI, 0.97-1.79; P=0.079) during the mean follow-up of 1.02years (SD=0.71years). The sitagliptin group had similar risks of ischemic stroke, all-cause mortality or hospitalization for heart failure (HF) compared to the non-sitagliptin group (P=0.938, 0.523 and 0.795 respectively). However, sitagliptin use was associated with increased risks of recurrent myocardial infarction (HR, 1.73; 95% CI, 1.15-2.58; P=0.008) and percutaneous coronary revascularization (HR, 1.43; 95% CI, 1.04-1.95; P=0.026). CONCLUSIONS Among type 2 diabetic patients with CKD after AMI, the use of sitagliptin was not associated with an increased risk of cardiovascular death, ischemic stroke or hospitalization for HF but was associated with increased risks of recurrent MI and percutaneous coronary revascularization.

Thermal resistance and reliability of low-cost high-power LED packages under WHTOL test

The high-power Light Emitting Diode (LED) can be potentially used for general lighting to alleviate the global warming problem. However, the LED issues, associated with high cost, high junction temperature, low luminous efficiency, and low reliability, have to be resolved before becoming realized. Featuring low-junction-temperature and low-cost design, a novel high-power COP (Chip-on-Plate) LED package is proposed and its reliability under wet high temperature operation life (WHTOL) test is evaluated. The WHTOL test is with the condition of 85degC/85%RH and 350 mA (power=1.22 W) of forward current for 1008 hrs, specified in JESD22 Method A101-B. First of all, the thermal behaviors of the COP package are investigated by experimental measurement (with LED junction temperature tester and thermal couples), a thermal resistance circuit (TRC) method and a finite element method (FEM). The junction temperature (Tj) and surface temperature of the COP package are measured by the junction temperature tester and thermal couples, respectively. Furthermore, the reliability under WHTOL test is carried out. The results show that all COP packages with phosphorus in the silicone encapsulant failed after 309 hrs at WHTOL test, but all those without phosphorus passed for 1008 hrs. The failure sites are located at aluminum wire debonding to the chip and copper pad of the substrate. For the passing packages, their junction to air thermal resistances increase with the time of WHTOL by up to 12degC/W. This is due to the decrease of the thermal conductivity of the die attach, resulting from the moisture absorption. The natural and forced convections in the chamber for WHTOL test give the same the junction-to-aluminum substrate thermal resistance, but different chip junction temperatures with a 19degC difference, which might result in different reliability data. Therefore, the standard test of WHTOL should specify flow conditions in the test chamber.

Sitagliptin After Ischemic Stroke in Type 2 Diabetic Patients: A Nationwide Cohort Study.

AbstractThe cerebrovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) with ischemic stroke remains uncertain. The aim of this study was to assess the efficacy and safety of sitagliptin in patients with T2DM with recent ischemic stroke.We analyzed data from the Taiwan National Health Insurance Research Database between March 1, 2009, and December 31, 2011. Ischemic stroke patients were identified from individuals with T2DM. Patients who received sitagliptin were compared with those who did not to evaluate the cardiovascular safety and efficacy of sitagliptin. The primary outcome was a composite of ischemic stroke, myocardial infarction, or cardiovascular death.A total of 5145 type 2 diabetic patients with ischemic stroke met our inclusion criteria and were followed for up to 2.83 years (mean, 1.17 years). Overall, 1715 patients (33.3%) received sitagliptin and 3430 patients (66.7%) did not. The primary composite outcome occurred in 190 patients in the sitagliptin group (11.1%) and in 370 patients in the comparison group (10.8%) (hazard ratio [HR] = 1.02; 95% confidence interval [CI], 0.85–1.21). Patients treated with sitagliptin had a similar risk of ischemic stroke, hemorrhagic stroke, and all-cause mortality with an HR of 0.95 (95% CI, 0.78–1.16, P = 0.612), 1.07 (95% CI, 0.55–2.11, P = 0.834), and 1.00 (95% CI, 0.82–1.22, P = 0.989), respectively, compared with patients not treated with sitagliptin.Treatment with sitagliptin in type 2 diabetic patients with recent ischemic stroke was not associated with increased or decreased risks of adverse cerebrovascular outcomes.

An investigation into warpages, stresses and keep-out zone in 3D through-silicon-via DRAM packages

This paper aims to measure and simulate the warpages of 3D through-silicon via (TSV) die-stacked dynamic-random-access-memory (DRAM) packages during the manufacturing process. The related die stresses and keep-out zone (KOZ) for the stacked dies in the packages at room temperature are further calculated with the validated simulation model. The out-of-plane deformations (or warpages) of the packages from the full-field shadow moire are documented under temperature loading and found consistent with those from finite-element method (FEM). The results of the stresses and KOZs at the proximity of a single TSV for each die in the package at room temperature are presented. It is found that the sizes of KOZs in four-die stacked DRAM packages with and without epoxy molding compound (EMC) at room temperature are dominated by the horizontal pMOS transistors and more than double the size in wafer-level die. The sizes of KOZs at each die are similar in this four-die stacked DRAM package, even though the stresses at each die are apparently different.

Clinical outcomes of drug-eluting stents versus bare-metal stents in patients with cardiogenic shock complicating acute myocardial infarction

BACKGROUND To investigate the cardiovascular (CV) outcomes of drug-eluting stents (DESs) versus bare-metal stents (BMSs) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). METHODS Data from the Taiwan National Health Insurance Research Database was analyzed between January 1, 2007 and December 31, 2011. A total of 3051 AMI patients in CS were selected as the study cohort. Their clinical outcomes were evaluated by comparing 1017 subjects who used DESs to 2034 matched subjects who used BMSs. RESULTS The risk of the primary composite outcome (i.e., death, myocardial infarction, stroke, and coronary revascularization) was significantly lower in the DES group compared with the BMS group [56.1% vs. 66.2%, hazard ratio (HR), 0.74; 95% CI, 0.67-0.81] with a mean follow-up of 1.35years. The patients who received DESs had a lower risk of coronary revascularization (HR, 0.78; 95% CI, 0.67-0.91) and death (HR, 0.70; 95% CI, 0.62-0.79) than those who used BMSs. However, the risks of myocardial infarction (HR, 0.89; 95% CI, 0.66-1.18), ischemic stroke (HR, 1.02; 95% CI, 0.67-1.53) and major bleeding (HR, 0.80; 95% CI, 0.56-1.14) were similar between the two groups. CONCLUSIONS Among patients with CS complicating AMI, DES implantation significantly reduced the risk of percutaneous coronary revascularization and death compared to BMS implantation.

CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis.

Polymicrobial sepsis is a potentially fatal condition and a significant burden on health care systems. Acute lung injury is the most common complication of sepsis and results in high mortality. However, there has been no recent significant progress in the treatment of sepsis or acute lung injury induced by sepsis. Here we show that mice deficient in the circadian protein CLOCK had better survival than wild-type mice after induction of polymicrobial sepsis by cecal ligation and puncture. Inflammatory cytokine production was attenuated and bacterial clearance was improved in CLOCK-deficient mice. Moreover, acute lung injury after induction of sepsis was significantly decreased in CLOCK-deficient mice. Genome-wide profiling analysis showed that inhibin signaling was reduced in CLOCK-deficient mice. These data establish the importance of circadian CLOCK-inhibin signaling in sepsis, which may have potential therapeutic implications.

Prognostic Impact of 9-Month High-Sensitivity C-Reactive Protein Levels on Long-Term Clinical Outcomes and In-Stent Restenosis in Patients at 9 Months after Drug-Eluting Stent Implantation

Introduction The level of 9-month high-sensitivity C-reactive protein (hsCRP) in predicting cardiovascular outcomes is scanty in patients at 9 months after receiving drug-eluting stent (DES) implantations. This study aims to evaluate the relationship between 9-month follow-up hsCRP levels and long-term clinical outcomes in patients at 9 months after receiving DES. Methods A total of 1,763 patients who received 9-month follow-up angiography were enrolled and grouped according to hsCRP level 9 months after the DES implantation: group I (718 patients, hsCRP<1.0 mg/L), group II (639 patients, 1.0≦hsCRP≦3.0 mg/L), and group III (406 patients, hsCRP>3.0 mg/L). Results Group III patients had a lower cardiovascular event-free survival rate than group I or II patients during a follow-up of 64±45 months (64.5% vs. 71.6% vs. 72.8%, respectively, p = 0.012). Multivariate analysis showed that a follow-up hsCRP level <3.0 mg/L was an independent predictor of a major adverse cardiovascular event (cardiac death, reinfarction, target lesion revascularization, stenting in a new lesion, or coronary bypass surgery). Group III patients had a higher restenosis rate (11.3% vs. 5.8% vs. 6.6%, respectively, p = 0.002) and loss index (0.21±0.32 vs. 0.16±0.24 vs. 0.18±0.28, respectively, p = 0.001) than group I or II patients in 9-month follow-up angiography. Conclusions A high 9-month follow-up hsCRP level is an independent predictor of long-term clinical cardiovascular outcomes in patients at 9 months after DES implantation. It is also associated with a higher restenosis rate, larger late loss and loss index at 9 months after DES implantation.

Pericardiocentesis Adverse Event Risk Factors: A Nationwide Population-Based Cohort Study

Objectives: Echocardiography-guided pericardiocentesis has been the leading procedure for diagnosis and therapy of pericardial effusion. We aimed to identify risk factors for recurrence, complications, and mortality in pericardial effusion patients treated with pericardiocentesis. Methods: We identified and collected data from 8,101 patients receiving pericardiocentesis between 1997 and 2010 from the Taiwan National Health Insurance Research Database. A multivariate regression model was used to investigate risk factors for recurrence, complications, and death. Results: There were 8,565 admissions among 8,101 patients. The most common underlying condition was malignancy (41%), especially lung cancer (23%), tuberculosis (9.0%), and acute pericarditis (8.2%). Surgical drainage was required in 12.7% of cases. Recurrence was more likely in patients with malignancy (HR 2.20, p < 0.001), but complications were less likely (OR 0.52, p = 0.003). In-hospital death numbers and complication risks (OR 2.38, p < 0.001; OR 1.27, p = 0.01) were greater in the catheter-related cardiac procedure group than in the other groups. Conclusions: Malignant neoplasms and catheter-based cardiac procedures have become major risk factors for adverse events in patients receiving pericardiocentesis in Taiwan. Malignancy leads to an increase in recurrence and in-hospital mortality but is associated with a lower rate of acute complications. Cardiac catheterization procedures and surgery increase both complications and in-hospital mortality. i 2014 S. Karger AG, Basel

In-Hospital and 4-Year Clinical Outcomes Following Transcatheter Versus Surgical Closure for Secundum Atrial Septal Defect in Adults: A National Cohort Propensity Score Analysis.

AbstractAtrial septal defect (ASD) closure is major therapy for patients with secundum ASD. Although surgical closure (SC) and transcatheter closure (TC) are usually performed in such patients, data on the long-term outcomes comparing TC and SC in adults are limited.Data on the participants of this cohort study were retrieved from Taiwans National Health Insurance Research Database from 2004 to 2011. Secundum ASD patients > 18 years of age who underwent TC or SC were initially enrolled, and those with associated comorbidities were excluded. After propensity score matching, the clinical outcomes between the TC and SC groups were analyzed.There were 595 patients recruited in the TC group and 308 patients in the SC group. The SC group had a higher incidence of systemic thromboembolism (P < 0.001), ischemic stroke (P = 0.002), and all-cause mortality (P = 0.013) when compared with those of the TC group at the index hospitalization, and similar phenomena could also be seen in a around 4-year follow-up period after the procedures (systemic thromboembolism (P < 0.001, HR = 11.48, 95% CI: 3.29–40.05), ischemic stroke (P = 0.005, HR = 9.28, 95% CI: 1.94–44.39), and all-cause mortality (P = 0.035, HR = 2.28, 95% CI: 1.06–4.89). In addition, atrial fibrillation (P = 0.005) and atrial flutter (P = 0.049) more frequently developed in the SC group than in the TC group at the index hospitalization.The adult secundum ASD patients had lower incidence rates of systemic thromboembolism, ischemic stroke, and all-cause mortality after TC than those after SC in the 4-year follow-up after procedures. Transcatheter ASD closure should therefore be given priority

FTO modulates circadian rhythms and inhibits the CLOCK-BMAL1-induced transcription.

Variations in the human fat mass and obesity-associated gene, which encodes FTO, an 2-oxoglutarate-dependent nucleic acid demethylase, are associated with increased risk of obesity. These FTO variations were recently shown to affect IRX3 and the exact function of FTO is still controversial. Obesity is closely linked to circadian rhythm. To understand the role of FTO in circadian rhythm, we analyzed the circadian rhythm of FTO deficient mice. FTO deficient mice had robust circadian locomotor activity rhythms with prolonged periods. The light-induced phase shifts of circadian rhythms were also significantly affected in FTO deficient mice. Tissue explants of FTO deficient mice maintained robust peripheral rhythms with prolonged period. Overexpress of FTO represses the transcriptional activation by CLOCK and BMAL1. Core clock genes expression of mRNA and protein were also altered in FTO deficient mice. Furthermore, FTO co-immunoprecipitated with CRY1/2 in a circadian manner. These results indicate a fundamental link between the circadian rhythm and FTO and extend the function of FTO to the core clockwork machinery.