Summary Background Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary ...lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial. Methods In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov , number NCT01331707. Findings Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned study treatment (six 1% in the zotarolimus-eluting stent group vs five 1% in the everolimus-eluting stent group; p=0·22). 12-month follow-up results were available for 1810 patients (one patient in the zotarolimus-eluting stent group withdrew consent). The primary endpoint was met by 55 (6%) of 905 patients in the zotarolimus-eluting stent group and 47 (5%) of 905 in the everolimus-eluting stent group. The zotarolimus-eluting stent was non-inferior to the everolimus-eluting stent (absolute risk difference 0·88%, 95% CI −1·24% to 3·01%; upper limit of one-sided 95% CI 2·69%; non-inferiority p=0·006). We noted no significant between-group differences in individual components of the primary endpoint. Definite stent thrombosis occurred in three (0·3%) patients in the zotarolimus-eluting stent group and six (0·7%) patients in the everolimus-eluting stent group (p=0·34). Longitudinal stent deformation was seen only in the everolimus-eluting stent group (nine 1·0% of 905 vs 0 of 906, p=0·002; nine of 1591 0·6% everolimus-eluting stents implanted became deformed), but was not associated with any adverse events. Interpretation Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions. Funding Boston Scientific, Medtronic.
The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents ...(ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts).
The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents. It is the first randomized trial ever to investigate the Resolute Integrity ZES and the first trial to compare both devices.
In total, 1,811 patients were 1:1 randomized to ZES versus EES. We performed a pre-specified assessment of the 5-year clinical outcomes in terms of safety and efficacy. The main endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Secondary endpoints included the individual components of TVF, and stent thrombosis. The study was independently monitored, and adverse clinical events were independently adjudicated.
Five-year clinical follow-up data was available in 1,798 (99.3%) patients. The ZES and EES groups showed favorable outcomes, with similar 5-year incidence of TVF (13.2% vs. 14.2%; p
= 0.62) and its individual components: cardiac death (4.5% vs. 4.9%; p
= 0.69), target vessel-related myocardial infarction (3.1% vs. 2.6%; p
= 0.47), and target vessel revascularization (7.6% vs. 8.6%; p
= 0.46). The 5-year incidence of definite or probable stent thrombosis was similar (1.5% vs. 1.3%; p
= 0.83).
At 5-year follow-up, the Resolute Integrity ZES and PROMUS Element EES showed similar and sustained results in terms of safety and efficacy for treating a broad population of all-comers.
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.
Abnormalities in regional cerebral blood flow (rCBF) have been reported to characterize depressive episodes; they are at least partly reversed by antidepressant treatment. Treatment-specific as well ...as response-related changes in rCBF have been reported. We explored the changes in rCBF induced by vagus nerve stimulation (VNS), a recently proposed antidepressant strategy, by application of single photon emission-computed tomography with
99mTc–hexamethyl-propylene amine oxime in otherwise treatment-refractory patients. Both region-of-interest (ROI) and statistical parametric mapping (SPM) analytic approaches were used. Decreases of rCBF in the amygdala, left hippocampus, left subgenual cingulate cortex, left and right ventral anterior cingulum, right thalamus and brain stem were observed; the only increase of rCBF was found by SPM analysis in the middle frontal gyrus. This pattern shares features with changes of rCBF previously associated with the administration of selective serotonin reuptake inhibitors. Similarities to other brain-stimulation strategies in antidepressant treatment were less pronounced.
We show successful transmission of 45.8 and 125 Gb/s coherent-detected polarization-multiplexed quadrature phase-shift keying (CP-QPSK) over both 2054 and 4108 km of 10 Gb/s ...nonreturn-to-zero-optimized field-deployed submarine cable. Moreover, we report successful transmission of 45.8 Gb/s coherent-detected polarization-multiplexed binary phase-shift keying (CP-BPSK) over 9420 km of legacy submarine fiber. We present single-channel transmission results, as well as wavelength-division multiplexed (WDM) transmission results with copropagating WDM channels placed on a 100 GHz and on a 50 GHz grid, where we optimized the transmission performance by sweeping the launch power and precompensation. For 45.8 Gb/s CP-QPSK, a margin with respect to the forward error correction (FEC) limit of 1.7 dBQ was obtained after transmitting over a 4108 km distance in a 50 GHz grid WDM configuration. Considering the transmission of 125 Gb/s CP-QPSK over the same distance and with the same channel configuration, a 1.1 dBQ margin was measured, showing the feasibility of a tenfold increase in transmission capacity over legacy submarine fiber. This significantly delays the costly alternative of deploying a new submarine cable. For the transmission of a 45.8 Gb/s CP-BPSK modulated signal on a 50 GHz WDM grid over a 9420 km distance, a margin of 1.2 dBQ with respect to the FEC limit is reported. This underlines the great robustness of CP-BPSK toward nonlinear fiber impairments and thereby the feasibility to cross transoceanic distances with this modulation format.
The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents ...(ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts).
The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents. It is the first randomized trial ever to investigate the Resolute Integrity ZES and the first trial to compare both devices.
In total, 1,811 patients were 1:1 randomized to ZES versus EES. We performed a pre-specified assessment of the 5-year clinical outcomes in terms of safety and efficacy. The main endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel–related myocardial infarction, or target vessel revascularization. Secondary endpoints included the individual components of TVF, and stent thrombosis. The study was independently monitored, and adverse clinical events were independently adjudicated.
Five-year clinical follow-up data was available in 1,798 (99.3%) patients. The ZES and EES groups showed favorable outcomes, with similar 5-year incidence of TVF (13.2% vs. 14.2%; plog-rank = 0.62) and its individual components: cardiac death (4.5% vs. 4.9%; plog-rank = 0.69), target vessel–related myocardial infarction (3.1% vs. 2.6%; plog-rank = 0.47), and target vessel revascularization (7.6% vs. 8.6%; plog-rank = 0.46). The 5-year incidence of definite or probable stent thrombosis was similar (1.5% vs. 1.3%; plog-rank = 0.83).
At 5-year follow-up, the Resolute Integrity ZES and PROMUS Element EES showed similar and sustained results in terms of safety and efficacy for treating a broad population of all-comers.
Display omitted
Methods To compare 2-year clinical outcome and patient-reported chest pain of patients with bifurcated vs. non-bifurcated lesions, we assessed data of the DUTCH PEERS randomized trial ...(clinicaltrials.govNCT01331707), in which 1,811 all-comers were treated with zotarolimus-eluting Resolute Integrity (Medtronic) or everolimus-eluting Promus Element (Boston Scientific) stents.
...the incidence of stent thrombosis, the composite endpoint target lesion failure, and the more patient-oriented composite clinical endpoints major adverse cardiac events and patient-oriented ...composite endpoint will be presented.
L-Arginine deficiency and supplementation in experimental acute renal failure and in human kidney transplant recipients.
The “L-arginine paradox” refers to situations where L-arginine (L-Arg) ...supplementation stimulates nitric oxide (NO) synthesis, despite saturating intracellular concentrations. This paradox is frequently observed in acute renal failure (ARF). First, the effects of L-Arg on renal function of rats with ARF were studied. Based on the promising results from these initial studies, the second part of our study searched for a form of ARF in humans that could be studied easily under conditions with little variance and yet was linked with endothelial dysfunction. Thus, we investigated the effects of L-Arg supplementation immediately after kidney transplantation in 54 patients.
In uranyl nitrate-induced ARF in rats the effects of L-Arg and L-NNA (inhibitor of nitric oxide synthase; NOS) on glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure (BP) and NOx (NO2-+NO3-) excretion were examined. Tissue L-Arg levels, NOS activities, immunodetection of NOS and superoxide dismutase (SOD), activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase, and nitrotyrosine immunoreactive protein (NT-IR) were determined and compared to sham operated animals. Secondly, in a randomized, double-blind study, the effects of L-Arg on GFR and RPF were investigated in 54 kidney transplant recipients, receiving IV L-Arg for three days. GFR and RPF were measured on days 1, 3, 5 and 10 by scintigraphy.
In experimental ARF, decreased RPF and GFR were associated with reduced tissue L-Arg levels, endothelial NOS-III expression, NO formation and NOx excretion. Reduction in GFR, RPF and NOx excretion were reversed upon administration of exogenous L-Arg. There also was a loss of Cu,Zn-SOD, a key enzyme against oxidative stress, and an elevation of NT-IR, an indicator of nitrosative stress and suggested marker for pathological actions of NO. However, NT-IR was not dependent on de novo NO synthesis and not related to the functional effects of L-Arg administration. In kidney transplant recipients receiving organs with a short cold ischemia time (CIT) and from young donors, that is, those with a higher likelihood of a functional endothelium, early administration of L-Arg improved renal function.
Both experimental and clinical data show that L-Arg deficiency and endothelial dysfunction are pathomechanistically relevant in ARF. The data suggest a therapeutic potential for the administration of L-Arg in ARF and kidney transplantation, at least in patients receiving kidneys with shorter CIT and from younger donors.
The objective of this study is to transport and deliver resveratrol to intracellular sites using apolipoprotein E3 (apoE3). Reconstituted high-density lipoprotein (rHDL) bearing resveratrol ...(rHDL/res) was prepared using phospholipids and the low-density lipoprotein receptor (LDLr)-binding domain of apoE3. Biophysical characterization revealed that resveratrol was partitioned into the phospholipid bilayer of discoidal rHDL/res particles (~19 nm diameter). Co-immunoprecipitation studies indicated that the LDLr-binding ability of apoE3 was retained. Cellular uptake of resveratrol to intracellular sites was evaluated in glioblastoma A-172 cells by direct fluorescence using chemically synthesized NBD-labeled resveratrol (res/NBD) embedded in rHDL/res. Competition and inhibition studies indicate that the uptake is by receptor mediated endocytosis via the LDLr, with co-localization of apoE3 and res/NBD in late endosomes/lysosomes. We propose that rHDL provides an ideal hydrophobic milieu to sequester resveratrol and that rHDL containing apoE3 serves as an effective "nanovehicle" to transport and deliver resveratrol to targeted intracellular sites.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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