Publications

Background: The ABSORB Cohort A trial results demonstrated the safety of the ABSORB bioresorbable vascular scaffold in 30 patients with single de novo native coronary artery lesions, with a low long-term MACE rate at 4 years of 3.4% and no scaffold thrombosis. Methods: The ABSORB Clinical Investigation enrolled 30 patients (Cohort A) in clinical sites in the European and Asia Pacific regions. The purpose of the ABSORB Clinical Investigation is to assess the safety and performance of the ABSORB Everolimus Eluting Vascular Scaffold (Abbott Vascular, Santa Clara, CA, USA) in the treatment of patients with a single de novo native coronary artery lesion. Key endpoints include ischemia driven major adverse cardiac events (ID-MACE) and its components out to 5 years with angiographic and IVUS endpoints at 6 months and 2 years and Multi-slice Spiral Computed Tomography (MSCT) imaging at 18 months. The ABSORB protocol was amended in the 4 sites who enrolled patients in Cohort A to add an optional additional MSCT im...

Heart Team (HT) and the SYNTAX Score II (SSII) have been integrated to the contemporary guidelines with the aim to provide a multidisciplinary decision-making process between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI).To prospectively assess the agreement between the HT decision and the SSII recommendation regarding the revascularization strategy in patients with 3-vessel coronary artery disease (CAD) of the SYNTAX II trial.The SSII predicts the 4-year mortality of an individual patient both after PCI and after CABG. Patients were treated by PCI when the SSII predicted a mortality risk favoring PCI or when risk predictions were equipoise between PCI and CABG. However, the HT could overrule the SSII and recommend either CABG or PCI.A total of 202 patients have been screened and 24 did not fulfill inclusion criteria. The median age was 67.0 (IQR 59.0-73.3), and 167 (82.7%) were male. The HT endorsed SSII treatment recommendation, for CABG or PCI, in 152 patients (85.4%). Three patients had preference for PCI, irrespective of the HT decision. The main reason for the HT to overrule the SSII and recommend CABG was the prospect of a more complete revascularization (21 of 25 patients). Patients recommended for CABG by the HT had significantly higher anatomical SYNTAX score (P = 0.03) and higher predicted mortality risk for PCI (P = 0.04) when compared with patients that were enrolled in the trial.The SYNTAX score II showed to be a suitable tool for guiding treatment decisions of patients with 3-vessel coronary artery disease being endorsed by the HT in the vast majority of the patients that have been enrolled in the SYNTAX II trial.

Background and aim Scaffold design and plaque characteristics influence implantation outcomes and local flow dynamics in treated coronary segments. Our aim is to assess the impact of strut embedment/protrusion of bioresorbable scaffold on local shear stress distribution in different atherosclerotic plaque types. Method Fifteen Absorb everolimus-eluting Bioresorbable Vascular Scaffolds were implanted in human epicardial coronary arteries. Optical coherence tomography (OCT) was performed post-scaffold implantation and strut embedment/protrusion were analyzed using a dedicated software. OCT data was fused with angiography to reconstruct three-dimensional coronary anatomy. Blood flow simulation was performed and wall shear stress (WSS) was estimated in each scaffolded surface and the relationship between strut embedment/protrusion and WSS was evaluated. Results There were 9083 struts analysed. Ninety-seven percent of the struts (n=8840) were well apposed and 243 (3%) were malapposed. At cross-section level (n=1289), strut embedment was significantly increased in fibroatheromatous plaques (76±48μm) and decreased in fibro-calcific plaques (35±52 μm). Compatible with strut embedment, WSS was significantly higher in lipid-rich fibroatheromatous plaques (1.50±0.81Pa), whereas significantly decreased in fibro-calcified plaques (1.05±0.91Pa). After categorization of WSS as low (<1.0 Pa) and normal/high WSS (≥1.0 Pa), the percent of low-WSS in the plaque subgroups were 30.1%, 31.1%, 25.4% and 36.2% for non-diseased vessel wall, fibrous plaque, fibro-atheromatous plaque and fibro-calcific plaque, respectively (p-overall<0.001). Table 1. Cross-section level Embedment/Protrusion and WSS according to the plaque type Plaque type Embedment depth (μm) Protrusion distance (μm) WSS (Pa) Non-atherosclerotic intimal thickening/normal vessel wall (n=2275) 47±34*Δ¥ 123±34¶Ξπ 1.44±0.9解 Fibrous (n=4191) 53±40*#& 118±38¶Ψ‡ 1.24±0.78αθ∞ Fibroatheromatous (n=2027) 76±48#ΦΔ 94.6±46Ω†Ψπ 1.50±0.81Σ§α Fibro-calcific (n=590) 35±52&Φ¥ 139±50‡†Ξ 1.05±0.91∞£Σ For embedment: *p=0.09, #p<0.001, &p<0.001, Φp<0.0001, Δp<0.0001, ¥p<0.0001. For protrusion: ¶p=0.74, Ξp<0.0001, πp<0.0001, Ψp<0.0001, ‡p<0.0001, †p<0.0001. For WSS: θp<0.001, §p=0.06, £p<0.0001, αp<0.0001, ∞p<0.0001, Ωp<0.0001. n=total strut number in each plaque type, p-values come from mixed-effects regression analysis. Conclusion The composition of the underlying plaque influences strut embedment which seems to have effect on WSS. The struts deeply embedded in lipid-rich fibroatheromas plaques resulted in higher WSS compared to the other plaque types.

The percutaneous treatment of coronary bifurcation stenoses is hampered by an increased rate of subsequent restenosis. The present study reports on the outcomes of a consecutive series of 58 patients with 65 de novo bifurcation stenoses treated with sirolimus-eluting stent implantation in both the main vessel and side branch. At 6 months, the incidence of major adverse cardiac events was 10.3% (1 death and 5 target lesion revascularizations) with no episodes of acute myocardial infarction or stent thrombosis.

We present high-resolution (0.4 arcsec) mid-infrared (mid-IR) polarimetric images and spectra of WL 16, a Herbig Ae star at a distance of 125 pc. WL 16 is surrounded by a protoplanetary disc of ∼ 900 au in diameter, making it one of the most extended Herbig Ae/Be discs as seen in the mid-IR. The star is behind, or embedded in, the ρ Ophiuchus molecular cloud, and obscured by 28 mag of extinction at optical wavelengths by the foreground cloud. Mid-IR polarization of WL 16 mainly arises from aligned elongated dust grains present along the line of sight, suggesting a uniform morphology of polarization vectors with an orientation of 33|$^\circ$|(east from north) and a polarization fraction of ∼ 2.0 per cent. This orientation is consistent with previous polarimetric surveys in the optical and near-IR bands to probe large-scale magnetic fields in the Ophiuchus star formation region, indicating that the observed mid-IR polarization towards WL 16 is produced by the dichroic absorption of magnetically aligned foreground dust grains by a uniform magnetic field. Using polarizations of WL 16 and Elias 29, a nearby polarization standard star, we constrain the polarization efficiency, p10.3/A10.3, for the dust grains in the ρ Ophiuchus molecular cloud to be ≃1.0 per cent mag−1. WL 16 has polycyclic aromatic hydrocarbon (PAH) emission features detected at 8.6, 11.2, 12.0, and 12.7 μm by our spectroscopic data, and we find an anticorrelation between the PAH surface brightness and the PAH ionization fraction between the north-west and south-west sides of the disc.

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) is characterised by oxidative stress and increased risk of lung carcinoma. Oxidative stress causes DNA damage which can be repaired by DNA-dependent protein kinase complex. <h3>Objectives</h3> To investigate DNA damage/repair balance and DNA-dependent protein kinase complex in COPD lung and in an animal model of smoking-induced lung damage and to evaluate the effects of oxidative stress on Ku expression and function in human bronchial epithelial cells. <h3>Methods</h3> Protein expression was quantified using immunohistochemistry and/or western blotting. DNA damage/repair was measured using colorimetric assays. <h3>Results</h3> 8-OH-dG, a marker of oxidant-induced DNA damage, was statistically significantly increased in the peripheral lung of smokers (with and without COPD) compared with non-smokers, while the number of apurinic/apyrimidinic (AP) sites (DNA damage and repair) was increased in smokers compared with non-smokers (p=0.0012) and patients with COPD (p&lt;0.0148). Nuclear expression of Ku86, but not of DNA-PKcs, phospho-DNA-PKcs, Ku70 or γ-H2AFX, was reduced in bronchiolar epithelial cells from patients with COPD compared with normal smokers and non-smokers (p&lt;0.039). Loss of Ku86 expression was also observed in a smoking mouse model (p&lt;0.012) and prevented by antioxidants. Oxidants reduced (p&lt;0.0112) Ku86 expression in human bronchial epithelial cells and Ku86 knock down modified AP sites in response to oxidative stress. <h3>Conclusions</h3> Ineffective DNA repair rather than strand breakage per se accounts for the reduced AP sites observed in COPD and this is correlated with a selective decrease of the expression of Ku86 in the bronchiolar epithelium. DNA damage/repair imbalance may contribute to increased risk of lung carcinoma in COPD.

Current generation of drug-eluting stents has significantly improved the outcomes of percutaneous coronary intervention by substantially reducing in-stent restenosis and stent thrombosis. However, a potential limitation of these stents is the permanent presence of a metallic foreign body within the artery, which may cause vascular inflammation, restenosis, thrombosis, and neoatherosclerosis. The permanent stents also indefinitely impair the physiological vasomotor function of the vessel and future potential of grafting the stented segment. Bioresorbable scaffolds (BRSs) have the potential to overcome these limitations as they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage and restoring pulsatility, cyclical strain, physiological shear stress, and mechanotransduction. While a number of BRSs are under development, two devices with substantial clinical data have already received a Conformité Européenne marking. This review article presents the current status of these devices and evaluates the challenges that need to be overcome before BRSs can become the workhorse device in coronary intervention.

Activation of several receptors, including mu-opioid, alpha 2-adrenergic, and neuropeptide Y receptors, inhibits excitatory nonadrenergic noncholinergic (NANC) neural responses in airways, which were mediated by the release of peptides from capsaicin-sensitive sensory nerves. This raises the possibility of a common inhibitory mechanism, which may be related to an increase in K+ conductance in sensory nerves. To examine this hypothesis, we have studied whether K(+)-channel blockers inhibit the effects of neuromodulators of sensory nerves in guinea pig bronchi by using selective K(+)-channel blockers. Charybdotoxin (ChTX; 10 nM), which blocks large conductance Ca(2+)-activated K(+)-channel function, completely blocked and reversed the inhibitory effects of a mu-opioid agonist, neuropeptide Y, and an alpha 2-adrenoceptor agonist on excitatory NANC responses. Neither inhibitors of ATP-sensitive K+ channels (BRL 31660 or glibenclamide, both at 10 microM) nor an inhibitor of small conductance Ca(2+)-activated K+ channels (apamin; 0.1 microM) were effective. This suggests that ChTX-sensitive K(+)-channel activation may be a common mechanism for the prejunctional modulation of sensory nerves in airways. This may have important implications for the control of neurogenic inflammation.