TCT-819 Prediabetes and its Impact on 1-Year Clinical Outcome After Treatment with Newer-Generation Drug-eluting Stents in 2,986 All-Comer Patients

BACKGROUND Prediabetes (Pre-DM) is a risk factor state for developing diabetes mellitus (DM). Yet it is unclear whether detection of Pre-DM by routine assessment of glycated haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) among patients undergoing percutaneous coronary intervention (PCI) may help identify subjects with increased event risk. We assessed in all-comers who underwent PCI with contemporary drug-eluting stents (DES) the relation between glycaemia status and 1-year clinical outcome. METHODS HbA1c and FPG was determined in 2,362 non-DM participants in the multicenter, randomized, investigator-initiated TWENTE III trial, in order to identify Pre-DM (HbA1c 42-47mmol/mol; FPG 6.1- 6.9 mmol/L) and DM (HbA1c>=48mmol/mol; FPG >7 mmol/L). Another 624 patients had medically treated DM. The main clinical outcome parameter was a composite endpoint consisting of death, myocardial infarction, or revascularisation. RESULTS Glycaemic state was known in 2,986 trial participants: Pre- DM was present in 324 (11%), DM in 793 (27%), and normoglycaemia in 1,869 (63%) patients. Patients with Pre-DM and DM differed from normoglycemic patients in cardiovascular risk factors. The composite clinical endpoint in Pre-DM occurred in 11.1%, in DM in 10.5%, and in normoglycemic patients in 5.7% (

Bifurcation treatment with novel, highly flexible drug-eluting coronary stents in all-comers: 2-year outcome in patients of the DUTCH PEERS trial

Background: Percutaneous coronary intervention (PCI) in bifurcated lesions with second-generation drug-eluting stents (DES) was associated with increased myocardial infarction (MI) rates. Flexible stent designs that accommodate well to vessel tapering may be of benefit in challenging anatomies such as bifurcated target lesions, but so far data are scarce.Methods: We analyzed the 2-year follow-up data of the DUTCH PEERS (TWENTE II) trial, which randomized 1811 all-comer patients to PCI with newer generation resolute integrity zotarolimus-eluting (Medtronic) or promus element everolimus-eluting stents (Boston Scientific). In bifurcated lesions, provisional stenting was generally performed. Target vessel failure is a composite endpoint, consisting of cardiac death, target vessel MI, or target vessel revascularization.Results: Patients with at least one bifurcated lesion (n = 465, 25.7 %) versus patients with non-bifurcated target lesions only (n = 1346, 74.3 %) showed similar rates of clinical endpoints including target vessel failure (9.2 versus 7.9 %, p = 0.36) and definite stent thrombosis (0.4 versus 1.0 %, p = 0.38). Target vessel MI was more common in patients with bifurcated lesions (3.4 versus 1.6 %, p = 0.02); but after multivariate analysis with propensity score adjustment, bifurcation treatment was found not to be an independent predictor of target vessel MI (HR 1.40, 95 % CI 0.71–2.76; p = 0.34). Among patients with bifurcated lesions, DES type and side-branch size did not affect outcome, but periprocedural MI occurred more often after two-stent approaches (9.0 versus 2.1 %; p = 0.002).Conclusion: All-comer patients treated for bifurcated and non-bifurcated target lesions showed similar and low rates of clinical endpoints, suggesting that the DES used are efficacious and safe for treating bifurcated target lesions

TCT-588 2-Year Clinical Outcome of the Randomized, Multicenter DUTCH PEERS (TWENTE II) Trial, Comparing Cobalt-Chromium Zotarolimus-Eluting Resolute Integrity Stents and Platinum-Chromium Everolimus-Eluting Promus Element Stents in “All-Comer” Patients

Background: The multicenter, prospective, randomized, single-blinded, investigator-initiated DUTCH PEERS (TWENTE II) “All Comers” Trial demonstrated at 1-year follow-up the non-inferiority of third-generation Resolute Integrity zotarolimus-eluting stents (Medtronic Vascular, Santa Rosa, CA) versus Promus Element everolimus-eluting stents (Boston Scientific, Natick, MA), based on a similar incidence of the primary endpoint target vessel failure (TVF), a composite of cardiac death, target vessel revascularization (TVR), or myocardial infarction (MI). No other follow-up data beyond 12 months have been published from a randomized head-to-head comparison of both stents. Methods: In 4 study centers in the Netherlands, 1,811 patients were 1:1 randomly assigned to treatment with one of both stents. Patients with any clinical syndrome, any lesion type, and any number of lesions or vessels to be treated were included. Study monitoring and clinical event adjudication were performed by two independent Dutch contract research organizations (Diagram, Zwolle, and Cardialysis, Rotterdam, respectively). Results: DUTCH PEERS examines an all-comer patient population that included 59% of patients with acute coronary syndromes (20% of all patients presented with an acute STEMI) and 66% of patients with complex target lesions. We will compare for both stent groups the 2-year incidence of TVF (primary endpoint) and various secondary endpoints, including individual components of the primary endpoint, the incidence of stent thrombosis, and other composite endpoints, such as target lesion failure, major adverse cardiac events, and the patient-oriented composite endpoint. In addition, we will report the outcome of patients with longitudinal stent deformation after discontinuation of dual anti-platelet therapy. Conclusions: Clinical outcome of the DUTCH PEERS trial at 2-year follow-up will be presented

Final 5-Year Report of the Randomized BIO-RESORT Trial Comparing 3 Contemporary Drug-Eluting Stents in All-Comers

BACKGROUND: In a previous trial, higher 5‐year mortality was observed following treatment with biodegradable polymer Orsiro sirolimus‐eluting stents (SES). We assessed 5‐year safety and efficacy of all‐comers as well as patients with diabetes treated with SES or Synergy everolimus‐eluting stents (EES) versus durable polymer Resolute Integrity zotarolimus‐eluting stents (ZES). METHODS AND RESULTS: The randomized BIO‐RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug‐Eluting Stents in an All Comers Population) trial enrolled 3514 all‐comer patients at 4 Dutch cardiac centers. Patients aged ≥18 years who required percutaneous coronary intervention were eligible. Participants were stratified for diabetes and randomized to treatment with SES, EES, or ZES (1:1:1). The main end point was target vessel failure (cardiac mortality, target vessel myocardial infarction, or target vessel revascularization). Five‐year follow‐up was available in 3183 of 3514 (90.6%) patients. The main end point target vessel failure occurred in 142 of 1169 (12.7%) patients treated with SES, 130 of 1172 (11.6%) treated with EES, versus 157 of 1173 (14.1%) treated with ZES (hazard ratio [HR], 0.89 [95% CI, 0.71–1.12], P (log‐rank)=0.31; and HR, 0.82 [95% CI, 0.65–1.04], P (log‐rank)=0.10, respectively). Individual components of target vessel failure showed no significant between‐stent difference. Very late definite stent thrombosis rates were low and similar (SES, 1.1%; EES, 0.6%; ZES, 0.9%). In patients with diabetes, target vessel failure did not differ significantly between stent‐groups (SES, 19.8%; EES, 19.2%; versus ZES, 21.1% [P (log‐rank)=0.69 and P (log‐rank)=0.63]). CONCLUSIONS: Orsiro SES, Synergy EES, and Resolute Integrity ZES showed similar 5‐year outcomes of safety and efficacy, including mortality. A prespecified stent comparison in patients with diabetes also revealed no significant differences in 5‐year clinical outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01674803

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Essential Functions of the Histone Demethylase Lid

Drosophila Little imaginal discs (Lid) is a recently described member of the JmjC domain class of histone demethylases that specifically targets trimethylated histone H3 lysine 4 (H3K4me3). To understand its biological function, we have utilized a series of Lid deletions and point mutations to assess the role that each domain plays in histone demethylation, in animal viability, and in cell growth mediated by the transcription factor dMyc. Strikingly, we find that lid mutants are rescued to adulthood by either wildtype or enzymatically inactive Lid expressed under the control of its endogenous promoter, demonstrating that Lid's demethylase activity is not essential for development. In contrast, ubiquitous expression of UAS-Lid transgenes lacking its JmjN, C-terminal PHD domain, and C5HC2 zinc finger were unable to rescue lid homozygous mutants, indicating that these domains carry out Lid's essential developmental functions. Although Lid-dependent demethylase activity is not essential, dynamic removal of H3K4me3 may still be an important component of development, as we have observed a genetic interaction between lid and another H3K4me3 demethylase, dKDM2. We also show that Lid's essential C-terminal PHD finger binds specifically to di- and trimethylated H3K4 and that this activity is required for Lid to function in dMyc-induced cell growth. Taken together, our findings highlight the importance of Lid function in the regulated removal and recognition of H3K4me3 during development

Notch and MAML-1 Complexation Do Not Detectably Alter the DNA Binding Specificity of the Transcription Factor CSL

Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined.Here, we utilized protein-binding microarrays (PBMs) to compare the binding site preferences of isolated CSL with the preferred binding sites of CSL when bound to the CSL-binding domains of all four different human Notch receptors. Measurements were taken both in the absence and in the presence of Mastermind-like-1 (MAML1). Our data show no detectable difference in the DNA binding site preferences of CSL before and after loading of Notch and MAML1 proteins.These findings support the conclusion that accrual of Notch and MAML1 promote transcriptional activation without dramatically altering the preferred sites of DNA binding, and illustrate the potential of PBMs to analyze the binding site preferences of multiprotein-DNA complexes