Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Fluorescent annexin A1 reveals dynamics of ceramide platforms in living cells

Upon its genesis during apoptosis, ceramide promotes gross reorganization of the plasma membrane structure involving clustering of signalling molecules and an amplification of vesicle formation, fusion and trafficking. The annexins are a family of proteins, which in the presence of Ca(2+), bind to membranes containing negatively charged phospholipids. Here, we show that ceramide increases affinity of annexin A1-membrane interaction. In the physiologically relevant range of Ca(2+) concentrations, this leads to an increase in the Ca(2+)sensitivity of annexin A1-membrane interaction. In fixed cells, using a ceramide-specific antibody, we establish a direct interaction of annexin A1 with areas of the plasma membrane enriched in ceramide (ceramide platforms). In living cells, the intracellular dynamics of annexin A1 match those of plasmalemmal ceramide. Among proteins of the annexin family, the interaction with ceramide platforms is restricted to annexin A1 and is conveyed by its unique N-terminal domain. We demonstrate that intracellular Ca(2+)overload occurring at the conditions of cellular stress induces ceramide production. Using fluorescently tagged annexin A1 as a reporter for ceramide platforms and annexin A6 as a non-selective membrane marker, we visualize ceramide platforms for the first time in living cells and provide evidence for a ceramide-driven segregation and internalization of membrane-associated proteins.

Recent environmental change and trace metal pollution in World Heritage Bathurst Harbour, southwest Tasmania, Australia

Bathurst Harbour in World Heritage southwest Tasmania, Australia, is one of the world’s most pristine estuarine systems. At present there is a lack of data on pollution impacts or long-term natural variability in the harbor. A ca. 350-year-old 210Pb-dated sediment core was analysed for trace metals to track pollution impacts from local and long-range sources. Lead and antimony increased from AD 1870 onwards, which likely reflects remote (i.e. mainland Australian and global) atmospheric pollution sources. Variability in the concentrations of copper and zinc closely followed the history of mining activities in western Tasmania, which began in the AD 1880s. Tin was generally low throughout the core, except for a large peak in AD 1989 ± 0.5 years, which may be a consequence of input from a local small-scale alluvial tin mine. Changes in diatom assemblages were also investigated. The diatom flora was composed mostly of planktonic freshwater and benthic brackish-marine species, consistent with stratified estuarine conditions. Since mining began, however, an overall decrease in the proportion of planktonic to benthic taxa occurred, with the exception of two distinct peaks in the twentieth century that coincided with periods of high rainfall. Despite the region’s remoteness, trace metal analyses revealed evidence of atmospheric pollution from Tasmanian and possibly longer-range mining activities. This, together with recent low rainfall, appears to have contributed to altering the diatom assemblages in one of the most pristine temperate estuaries in the world.

Comparison of Newer-Generation Drug-Eluting With Bare-Metal Stents in Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pooled Analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) Trials

OBJECTIVES This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. METHODS Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. RESULTS Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. CONCLUSIONS Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.

Nano-mechanical transduction of polymer micro-cantilevers to detect bio-molecular interactions

Using variothermal polymer micro-injection molding, disposable arrays of eight polymer micro-cantilevers each 500 μm long, 100 μm wide and 25 μm thick were fabricated. The present study took advantage of an easy flow grade polypropylene. After gold coating for optical read-out and asymmetrical sensitization, the arrays were introduced into the Cantisens(®) Research system to perform mechanical and functional testing. We demonstrate that polypropylene cantilevers can be used as biosensors for medical purposes in the same manner as the established silicon ones to detect single-stranded DNA sequences and metal ions in real-time. A differential signal of 7 nm was detected for the hybridization of 1 μM complementary DNA sequences. For 100 nM copper ions the differential signal was found to be (36 ± 5) nm. Nano-mechanical sensing of medically relevant, nanometer-size species is essential for fast and efficient diagnosis.

Biolimus-Eluting Stents With Biodegradable Polymer Versus Bare-Metal Stents in Acute Myocardial Infarction: Two-Year Clinical Results of the COMFORTABLE AMI Trial

BACKGROUND This study sought to determine whether the 1-year differences in major adverse cardiac event between a stent eluting biolimus from a biodegradable polymer and bare-metal stents (BMSs) in the COMFORTABLE trial (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) were sustained during long-term follow-up. METHODS AND RESULTS A total of 1061 patients were randomly assigned to biolimus-eluting stent (BES) and BMS at 11 centers, and follow-up rates at 2 years were 96.3%. A subgroup of 103 patients underwent angiography at 13 months. At 2 years, differences in the primary end point of cardiac death, target-vessel myocardial infarction, and target lesion revascularization continued to diverge in favor of BES-treated patients (5.8%) compared with BMS-treated patients (11.9%; hazard ratio=0.48; 95% confidence interval, 0.31-0.72; P<0.001) with a significant risk reduction during the second year of follow-up (hazard ratio 1-2 years=0.45; 95% confidence interval, 0.20-1.00; P=0.049). Differences in the primary end point were driven by a reduction in target lesion revascularization (3.1% versus 8.2%; P<0.001) and target-vessel reinfarction (1.3% versus 3.4%; P=0.023). The composite of death, any reinfarction and revascularization (14.5% versus 19.3%; P=0.03), and cardiac death or target-vessel myocardial infarction (4.2% versus 7.2%; P=0.036) were less frequent among BES-treated patients compared with BMS-treated patients. The 13-month angiographic in-stent percent diameter stenosis amounted to 12.0±7.2 in BES- and 39.6±25.2 in BMS-treated lesions (P<0.001). CONCLUSIONS Among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, BES continued to improve cardiovascular events compared with BMS beyond 1 year.

Drug-eluting stents vs. bare metal stents in patients with cardiogenic shock: a comparison by propensity score analysis.

BACKGROUND In patients with cardiogenic shock, data on the comparative safety and efficacy of drug-eluting stents (DESs) vs. bare metal stents (BMSs) are lacking. We sought to assess the performance of DESs compared with BMSs among patients with cardiogenic shock undergoing percutaneous coronary intervention (PCI). METHODS Out of 236 patients with acute coronary syndromes complicated by cardiogenic shock, 203 were included in the final analysis. The primary endpoint included death, and the secondary endpoint of major adverse cardiac and cerebrovascular events (MACCEs) included the composite of death, myocardial infarction, any repeat revascularization and stroke. Patients were followed for a minimum of 30 days and up to 4 years. As stent assignment was not random, we performed a propensity score analysis to minimize potential bias. RESULTS Among patients treated with DESs, there was a lower risk of the primary and secondary endpoints compared with BMSs at 30 days (29 vs. 56%, P < 0.001; 34 vs. 58%, P = 0.001, respectively) and during long-term follow-up [hazard ratio 0.43, 95% confidence interval (CI) 0.29-0.65, P < 0.001; hazard ratio 0.49, 95% CI 0.34-0.71, P < 0.001, respectively]. After propensity score adjustment, all-cause mortality was reduced among patients treated with DESs compared with BMSs both at 30 days [adjusted odds ratio (OR) 0.26, 95% CI 0.11-0.62; P = 0.002] and during long-term follow-up (adjusted hazard ratio 0.40, 95% CI 0.22-0.72; P = 0.002). The rate of MACCE was lower among patients treated with DESs compared with those treated with BMSs at 30 days (adjusted OR 0.42, 95% CI 0.19-0.95; P = 0.036). The difference in MACCEs between devices approached significance during long-term follow-up (adjusted hazard ratio 0.60, 95% CI 0.34-1.01; P = 0.052). CONCLUSION DESs appear to be associated with improved clinical outcomes, including a reduction in all-cause mortality compared with BMSs among patients undergoing PCI for cardiogenic shock, possibly because of a pacification of the infarct-related artery by anti-inflammatory drug. The results of this observational study require confirmation in an appropriately powered randomized trial.

Transition metal ligands as novel DNA-base substitutes

The base modified nucleoside dBP, carrying a non-hydrogen-bonding non-shape complementary base was incorporated into oligonucleotides (Brotschi, C.; Haberli, A.; Leumann C.J. Angew. Chem. Int. Ed. 2001, 40, 3012-3014). This base was designed to coordinate transition metal ions into well defined positions within a DNA double helix. Melting experiments revealed that the stability of a dBP:dBP base couple in a DNA duplex is similar to a dG:dC base pair even in the absence of transition metal ions. In the presence of transition metal ions, melting experiments revealed a decrease in duplex stability which is on a similar order for all metal ions (Mn2+, Cu2+, Zn2+, Ni2+) tested