Publications

No abstract is provided for this article.

Background We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions. Methods Between May 21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting countries to participate in this open-label, multicentre, randomised, superiority trial. Eligible patients were those aged 18 years or older undergoing elective, unplanned, or emergency procedures in native coronary arteries. Patients were randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation was stratified per centre with varying block sizes of four, six, or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at 3 years and was analysed by intention to treat. Patients and investigators were aware of treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00476957. Findings PROTECT randomised 8791 patients, of whom 8709 provided consent to participate and were eligible: 4357 were allocated to the E-ZES group and 4352 patients to the C-SES group. At 3 years, rates of definite or probable stent thrombosis did not differ between groups (1·4% for E-ZES [predicted: 1·5%] vs 1·8% [predicted: 2·5%] for C-SES; hazard ratio [HR] 0·81, 95% CI 0·58–1·14, p=0·22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge, 7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years. Interpretation No evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis. Funding Medtronic, Inc.

No abstract is provided for this article.

An experimental investigation into the structural performance of wire arc additively manufactured (WAAM) steel single-lap shear bolted connections is presented in this paper. The steel wire had a nominal yield stress of 420 MPa. Sixty specimens of different thicknesses, printing strategies and geometric features including end distances and plate widths were tested and analysed. The shear-out, net section tension fracture, localised tearing and curl-bearing failure modes were observed and discussed, while end-splitting was also evident. Digital image correlation (DIC) was used for detailed monitoring and visualisation of the surface strain fields that developed during testing, providing valuable insight into the developed failure mechanisms. The experimental results, which generally followed the anticipated trends, were used to assess the applicability of current design specifications developed for conventional steel bolted connections to WAAM steel bolted connections. It was found that both the cold-formed steel specifications (AISI S100 and AS/NZS 4600) and the structural steel specifications (AISC 360 and EN 1993-1) devised for conventionally manufactured steel elements, could yield considerable overestimations and underestimations of the test capacities, depending on the geometry. The overestimations are caused by shortcomings in the existing design provisions for out-of-plane failure modes, which are particularly prevalent among WAAM steel connections due to their material ductility and surface undulations, which promote curling. The underestimations relate primarily to the conservatism of the shear-out provisions. Further research is underway to underpin the development of improved design provisions.

No abstract is provided for this article.

To investigate whether the use of intravascular ultrasound virtual histology (IVUS-VH) leads to any improvements in stent deployment, when performed in patients considered to have had an optimal percutaneous coronary intervention (PCI) by quantitative coronary angiography (QCA).After optimal PCI result (residual stenosis by QCA<30%), IVUS-VH was performed in 100 patients by protocol, with the option to use the information left to the discretion of the operators. Patients were categorised as: Group1 (n=54), where the IVUS-VH findings were used to evaluate the need for further optimisation of the stent deployment; and Group2 (n=46), where the IVUS-VH was documentary such that the stenting results were considered optimal according to QCA. Optimal stent deployment on IVUS-VH was defined as: normal stent expansion, absence of stent malapposition, complete lesion coverage as indicated by a plaque burden (PB%) between 30-40% and necrotic core confluent to the lumen<10% or PB%<30% at the 5 mm proximal and distal to the stent. The first IVUS-VH in all patients demonstrated the achievement of optimal stent deployment, incomplete lesion coverage, stent under-expansion and stent-edge dissection in 60%, 31%, 20% and 8% of patients, respectively. There was no stent malapposition. In Group 1, 25 patients had optimal stent deployment and did not require further intervention, whilst in 29 patients further intervention was needed (additional stent, n=18; post-dilatation, n=29). Overall optimal stent deployment was finally achieved in 52/54 patients (96%) in Group 1 and 35/46 (76%) of Group 2, p<0.05.IVUS-VH may have a role in facilitating optimal stent implantation and complete lesion coverage.

Purpose To evaluate the atherosclerotic evolution in coronary bifurcations located proximally and distally to a bioresorbable scaffold. Methods Thirty bifurcations located &gt;5 mm beyond the scaffolded segment, being investigated with serial intravascular ultrasound virtual histology (IVUS-VH) examinations, at baseline and 2-years, in patients enrolled in the ABSORB cohort B1 study were included in this analysis. In each bifurcation, the frames portraying the proximal rim, in-bifurcation, and distal rim of the ostium of the side branch were analyzed. The geometric parameters and plaque types were evaluated at baseline and 2-years follow-up. Results There were no significant differences in the geometrical parameters such as lumen, vessel and plaque areas as well as in the composition of the atheroma between baseline and 2-years follow-up. When we separately examined the bifurcations located proximally and distally to the scaffolded segment, no changes were found at the distal bifurcations, while at the proximal bifurcations there was a statistical significant decrease in the plaque burden (36.67 ± 13.33% at baseline vs. 35.06 ± 13.20% at 2 years follow-up, p = 0.04). Ten necrotic core rich plaques were found at baseline, of which 2 regressed to either fibrotic plaque or to intimal thickening at 2 years follow-up. The other 8 did not change. Disease progression was noted in 3 plaques (1 adaptive intimal thickening, 1 fibrotic and 1 fibrocalcific plaque) that evolved to necrotic rich plaques. Conclusions Plaque regression was noted at the bifurcations located proximally to the bioresorbable scaffold but not at these located distally. Additional studies are required to confirm this finding and examine further the effect of drug elution on atherosclerotic evolution.

The expression of nuclear factor (NF)-κB is an indicator of cellular activation and of inflammatory mediator production. The aim of the present study was to characterise the expression and localisation of p65, the major subunit of NF-κB, in the bronchial mucosa of patients with chronic obstructive pulmonary disease (COPD), and to examine the relationship between p65 expression and disease status. Bronchial biopsies were obtained from 14 smokers with COPD, 17 smokers with normal lung function and 12 nonsmokers with normal lung function. The number of p65 positive (+) cells was quantified by immunohistochemistry and the expression of p65 in bronchial biopsies from the three groups was examined by Western blotting (WB). Smokers with normal lung function and patients with COPD had increased numbers of p65+ cells in the epithelium and increased p65 nuclear expression. In COPD patients the number of epithelial p65+ cells correlated with the degree of airflow limitation. WB analysis showed an increase in p65 in smokers with normal lung function and COPD patients (p&lt;0.05). Bronchial biopsies in smokers with normal lung function and chronic obstructive pulmonary disease patients show increased expression of p65 protein, predominantly in the bronchial epithelium. Disease severity is associated with an increased epithelial expression of nuclear factor-κB.

Recommended techniques for bifurcation stenting continue to be revised with specific attention to bioresorbable scaffolds (BRS). Optimal procedural success and long-term outcomes with BRS can perhaps be improved with careful attention to implantation techniques. Good vessel preparation is imperative for optimal expansion of the scaffold, and proper vessel sizing is necessary to ensure compliance with scaffold expansion limits and preservation of proper scaffold function. The European Bifurcation Club (EBC) recommends provisional stenting for the majority of bifurcation lesions: permanent metallic stents are sized according to the distal vessel diameter, with subsequent post-dilatation of the proximal vessel to ensure stent apposition in the proximal main vessel. Recent BRS-specific modifications to the EBC recommendation suggest that selecting the scaffold size based on the diameter of the proximal main vessel can mitigate the risk of overexpansion and potential strut fracture. Expansion of the BRS requires a thoughtful balance between the risk of malapposition associated with underdeployment and the risk of strut fracture due to overdeployment. Post-dilatation of scaffolds should be performed, always respecting the maximum expansion limit, to correct any potential scaffold malapposition and minimise flow disturbances. Finally, dual antiplatelet therapy plays an important role in BRS bifurcation treatment to avoid thromboembolic events.

Bronchial antigen challenge of sensitized atopic patients with asthma results in an early fall in FEV1, followed in a proportion of patients by a late (4 to 24 hours) fall. The late response is accompanied by an increase in bronchial reactivity, which is widely believed to reflect local influx and degranulation of inflammatory cells, particularly eosinophils, in association with elevated local secretion of cytokines. We hypothesized that the development of a late-phase bronchoconstrictor response and airway eosinophilia after allergen challenge of sensitized atopic patients with asthma is associated with elevated induced sputum concentrations of the eosinophil-active cytokines IL-5 and granulocyte-macrophage colony-stimulating factor and the proinflammatory cytokine tumor necrosis factor-alpha. We counted inflammatory leukocytes and measured cytokine concentrations in induced sputum at baseline and 24 hours after inhalational allergen challenge of 15 atopic patients with asthma who had previously demonstrated a late response. We observed significant increases in the numbers of eosinophils and the concentrations of their granule products, eosinophil cationic protein and eosinophil peroxidase. In contrast, the numbers of neutrophils and concentrations of two of their products, myeloperoxidase and human neutrophil lipocalin, did not significantly change. The numbers of sputum eosinophils correlated with the maximal late-phase fall in FEV1. Concentrations of IL-5 and tumor necrosis factor-alpha, but not granulocyte-macrophage colony-stimulating factor, were significantly elevated after allergen challenge. We conclude that the relatively noninvasive technique of induced sputum production can be used to monitor the effect of bronchial provocation on cytokine concentrations in asthma.

Objectives The aim of this study was to assess whether residual nonculprit (NC) lesions, defined as visual diameter stenosis ≥30% after successful percutaneous coronary intervention, affect the rate of future events in patients with acute coronary syndromes. Background In patients with acute coronary syndromes, approximately one-half of recurrent events after percutaneous coronary intervention arise from untreated lesions. Methods Patients enrolled in PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) were divided into 3 groups: those with no NC lesions, 1 NC lesion, or ≥2 NC lesions. Time to events for major adverse cardiac events was estimated up to 3 years. Results Among 697 patients, 13.3% had no NC lesions, 19.7% had 1 NC lesion, and 67.0% had ≥2 NC lesions. The median diameter stenoses of the NC lesions in the latter 2 groups were 36.7% (interquartile range: 31.0% to 43.4%) and 37.4% (interquartile range: 32.0% to 46.5%), respectively (p = 0.22). At least 1 thin-cap fibroatheroma was present in one-half the patients in each group. At 3 years, the incidence of major adverse cardiac events was 8.5%, 15.2%, and 24.3%, respectively (p = 0.0009). NC lesion–related events occurred in 0%, 5.0%, and 15.9% of patients, respectively (p < 0.0001). Of 105 NC lesion–related clinical events occurring during follow-up, 73 (69.5%) originated from angiographically evident baseline NC lesions (of which 36 had diameter stenosis >50%), while the other 32 arose from normal or near normal segments. Conclusions Residual NC lesions are common after percutaneous coronary intervention for acute coronary syndromes and portend a higher rate of recurrent ischemic events within 3 years, especially when angiographically more severe. Conversely, the absence of NC lesions by angiography is highly predictive of freedom from events not related to the originally treated culprit lesion(s).