Publications

Our aim was to demonstrate the safety and efficacy of the Svelte sirolimus-eluting coronary stent-on-a-wire Integrated Delivery System (IDS) with bioresorbable drug coating compared to the Resolute Integrity zotarolimus-eluting stent with durable polymer in patients with de novo coronary artery lesions.Direct stenting, particularly in conjunction with transradial intervention (TRI), has been associated with reduced bleeding complications, procedure time, radiation exposure and contrast administration compared to conventional stenting with wiring and predilatation. The low-profile Svelte IDS is designed to facilitate TRI and direct stenting, reducing the number of procedural steps, time and cost associated with coronary stenting. DIRECT II was a prospective, multicentre trial which enrolled 159 patients to establish non-inferiority of the Svelte IDS versus Resolute Integrity using a 2:1 randomisation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at six months. Target vessel failure (TVF), as well as secondary clinical endpoints, will be assessed annually up to five years. At six months, in-stent LLL was 0.09±0.31 mm in the Svelte IDS group compared to 0.13±0.27 mm in the Resolute Integrity group (p<0.001 for non-inferiority). TVF at one year was similar across the Svelte IDS and Resolute Integrity groups (6.5% vs. 9.8%, respectively).DIRECT II demonstrated the non-inferiority of the Svelte IDS to Resolute Integrity with respect to in-stent LLL at six months. Clinical outcomes at one year were comparable between the two groups.

No abstract is provided for this article.

The aim of this study was to determine the accuracy of the intracoronary electrocardiogram (icECG) to detect ischaemia during bifurcation lesion percutaneous coronary intervention (PCI) with fractional flow reserve (FFR) as a reference.Patients with significant bifurcation lesions defined as FFR ≤0.80 were included. FFR and icECG were performed in the main vessel (MV) and side branch (SB) before and after provisional stenting. icECG was recorded with an uninsulated proximal wire end connected to a unipolar lead. The diagnostic accuracy of the icECG for the detection of ischaemia in the SB after MV stenting was determined with FFR as a reference. Overall, 37 patients were included. Seventeen bifurcations had an SB FFR ≤0.80 after MV stenting and 20 patients had an ST-segment elevation on the icECG. There was significant correlation between SB FFR and ST-segment elevation on the icECG (r=-0.533, p<0.001). The diagnostic accuracy of icECG ST-elevation to detect functionally significant SB stenosis revealed an AUC of 0.71 (95% CI: 0.64-0.80) with a sensitivity of 88% and specificity of 75% with a positive predictive value of 75% and negative predictive value of 88%. Neither SB FFR nor icECG correlated with SB percent diameter stenosis after MV stenting.Intracoronary ECG has a good ability to predict functionally significant stenosis at the SB after MV stenting during bifurcation PCI. This method provides a novel strategy to assess the significance of an SB lesion without the need of a pressure wire.

1. Several agonists modulate cholinergic neurotransmission in airways raising the possibility that there may be a common inhibitory mechanism, such as the activation of a common K+ channel in the nerve ending. To test this hypothesis, we examined whether blockers of K+ channels are able to depress the prejunctional inhibitory modulation of cholinergic contractile responses by various agonists in guinea-pig and human airways in vitro. 2. Electrical field stimulation (40 V, 0.5 ms) was applied to guinea-pig (0.5 Hz) or human (1 Hz) tracheal strips every 4 min to elicit cholinergic neural responses. The effects of the K+ channel blockers, charybdotoxin (ChTX, 10 nM), apamin (100 nM) and glibenclamide (1 microM), on the prejunctional inhibition of cholinergic contraction evoked by neuropeptide Y (NPY, 100 nM), an alpha 2-agonist, clonidine (10 nM), a mu-opioid agonist, [D-Ala2, NMePhe4, Gly-ol5]-enkephalin (DAMGO, 100 nM), and a KATP channel opener, lemakalim (300 nM) were tested in guinea-pigs. In human tissues, the effect of ChTX (10 nM) on the mu-opioid (DAMGO, 300 nM)-induced inhibition of cholinergic nerves was examined. 3. In guinea-pigs, ChTX (10 nM) significantly reversed the prejunctional inhibition of cholinergic contraction by NPY (84.2 +/- 16.2%), clonidine (71.9 +/- 22.4%), DAMGO (67.3 +/- 13.1%) and lemakalim (20.9 +/- 9.4%) (n = 5, P < 0.05, respectively), while apamin (100 nM) had no effect. Glibenclamide (10 microM) reduced only the lemakalim-induced inhibitory modulation. ChTX (10 nM) itself potentiated cholinergic contraction (24.6 +/- 9.4%, n = 5, P < 0.05) without affecting exogenously applied acetylcholine dose-response curves. Pretreatment with ChTX (10 nM) significantly reduced the inhibitory modulation of cholinergic nerves by NPY, clonidine and DAMGO, but not by lemakalim. 4. In human tissues, ChTX significantly reduced DAMGO-induced prejunctional inhibition of cholinergic contraction (13.6 +/- 8.5% with and 46.5 +/- 5.5% without ChTX, respectively; n = 5, P < 0.05). 5. These results may support a hypothesis that the activation of ChTX-sensitive K+ channels is involved in the inhibitory modulation of cholinergic neuro-transmission by agonists acting on presynaptic receptors in guinea-pig and human airways.

No abstract is provided for this article.

The cellular and molecular mechanisms governing bradykinin B1 and B2 receptor expression and function are poorly understood. We investigated the regulation of both B1 and B2 receptors in human embryonic lung fibroblasts (HEL 299) by the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta). TNF-alpha and IL-1beta both induced a rapid and transient increase in B1 and B2 receptor mRNA expression that was maximal by 2 h, accompanied by an increase in B1 and B2 receptor protein, as measured by radioligand binding assay with [(3)H]des-Arg(10)-kallidin, and [(3)H]bradykinin, respectively. The induced B1 receptors were functionally coupled, because the B1 agonist, des-Arg(10)-kallidin, induced an increase in arachidonic acid release in TNF-alpha-stimulated cells but not in control cells. The induction of B1 and the up-regulation of B2 receptors by TNF-alpha was partly mediated through activation of p38 mitogen-activated protein kinase and that of B2 receptor by protein kinase A. TNF-alpha and IL-1beta regulation of both B1 and B2 receptors was inhibited by dexamethasone. When compared with vehicle-treated cells, dexamethasone increased the rate of decline of both B1 and B2 receptor mRNAs. Nuclear run-on experiments demonstrate that the induction of B1 and the up-regulation of B2 receptors as well as the inhibitory effect of dexamethasone are entirely mediated through post-transcriptional mechanisms.

The implantation of a bioresorbable scaffolds (BRSs) is a new approach that provides transient vessel support with drug delivery capability, potentially without the limitations of permanent metallic implants [1]. The potential short- and long-term performance of this technology has been repeatedly investigated with optical coherence tomography (OCT) [2-7]. However, images acquired by OCT after implantation of BRSs are different from those with metallic stents due to the translucency of polymeric materials compared to the opacity of metallic compounds (Figure 5.3.1). Metallic struts appear on OCT as a reflective leading structure with abluminal shadowing, while polymeric struts appear as a “black box” area surrounded by bright reflecting frames without abluminal shadowing. As a consequence, in polymeric scaffolds the vessel wall behind the struts and the luminal area can easily be imaged and assessed, contributing to several advantages in quantitative analysis: (1) capability of measuring the lumen vessel wall interface at baseline; (2) accurate assessment of malapposed struts; (3) measurement of strut/strut core area; (4) precise measurements of flow area; and (5) measurement of neointimal area between and on top of the struts.

True 3D reconstruction of coronary arteries in patients based on intravascular ultrasound (IVUS) may be achieved by fusing angiographic and IVUS information (ANGUS). The clinical applicability of ANGUS was tested, and its accuracy was evaluated quantitatively. METHODS AND REUSLTS: In 16 patients who were investigated 6 months after stent implantation, a sheath-based catheter was used to acquire IVUS images during an R-wave-triggered, motorized stepped pullback. First, a single set of end-diastolic biplane angiographic images documented the 3D location of the catheter at the beginning of pullback. From this set, the 3D pullback trajectory was predicted. Second, contours of the lumen or stent obtained from IVUS were fused with the 3D trajectory. Third, the angular rotation of the reconstruction was optimized by quantitative matching of the silhouettes of the 3D reconstruction with the actual biplane images. Reconstructions were obtained in 12 patients. The number of pullback steps, which determines the pullback length, closely agreed with the reconstructed path length (r=0.99). Geometric measurements in silhouette images of the 3D reconstructions showed high correlation (0.84 to 0.97) with corresponding measurements in the actual biplane angiographic images.With ANGUS, 3D reconstructions of coronary arteries can be successfully and accurately obtained in the majority of patients.

This paper responds to the need for a theoretical model to describe the structural strength capacity of innovative hollow corrugated columns consisting of four cold-formed corrugated mild steel plates. Interest in these columns has been growing over a number of years, due to high ratio of axial load bearing capacity to weight. The paper utilises the Direct Strength Method (DSM) to calculate the axial strength of aforementioned columns while the results are compared with those obtained from experiments and finite element models. Existing formulations are extended to predict local failure of these columns over a vast range of slenderness with a good degree of accuracy. The results show the appropriateness of this method as an alternative for analytical capacity prediction of innovative corrugated columns.

Inferior outcomes with ACURATE neo, a self-expanding transcatheter heart valve (THV) for the treatment of severe aortic stenosis, were mainly driven by higher rates of moderate/severe paravalvular leak (PVL). To overcome this limitation, the next-generation ACURATE neo2 features a 60% larger external sealing skirt. Data on long-term performance are limited; however, clinical evidence suggests improved short-term performance which is comparable to contemporary THVs. This report reviews data on short-term clinical and echocardiographic outcomes of ACURATE neo2. A PubMed search yielded 13 studies, including 5 single arm and 8 nonrandomized comparative studies with other THVs which reported in-hospital or 30-day clinical and echocardiographic outcomes. In-hospital or 30-day all-cause mortality was ≤3.3%, which is comparable to other contemporary THVs. The rates of postprocedural ≧moderate PVL ranged 0.6%-4.7%. In multicenter propensity-matched analyses, neo2 significantly reduced the rate of ≧moderate PVL compared to neo (3.5% vs. 11.3%, p < 0.01), whereas rates were comparable to Evolut Pro/Pro+ (Neo2: 2.0% vs. Pro/Pro+: 3.1%, p = 0.28) and SAPIEN 3 Ultra (Neo2: 0.6% vs. Ultra: 1.1%, p = 0.72). The rate of permanent pacemaker implantation with neo2 was consistently low (3.3%-8.6%) except in one study, and in propensity-matched analyses were significantly lower than Evolut Pro/Pro+ (6.7% vs. 16.7%, p < 0.01), and comparable to SAPIEN 3 Ultra (8.1% vs. 10.3%, p = 0.29). In conclusion, ACURATE neo2 showed better short-term performance by considerably reducing PVL compared to its predecessor, with short-term clinical and echocardiographic outcomes comparable to contemporary THVs.

Abstract We reported previously that ESAT-6 from Mycobacterium tuberculosis directly inhibits human T cell IFN-γ production and proliferation in response to stimulation with anti-CD3 plus anti-CD28. To determine the mechanism of this effect, we treated T-cells with kinase inhibitors before stimulation in the presence of ESAT-6. Only the p38 MAPK inhibitor, SB203580, abrogated ESAT-6-mediated inhibition of IFN-γ production in a dose-dependent manner. In contrast, SB203580 did not reverse ESAT-6-mediated inhibition of IL-17 and IL-10 production, suggesting a specific effect of SB203580 on IFN-γ production. SB203580 did not act through inhibition of AKT, as an AKT inhibitor did not affect ESAT-6 inhibition of T cell IFN-γ production and proliferation, ruling out the possible off target effect of SB203580 through AKT. ESAT-6 did not expand FoxP3+ T regulatory cells, suggesting that Tregs do not play a role in ESAT-6 inhibition of T cell IFN-γ production. Incubation of T cells with ESAT-6 induced phosphorylation and increased functional p38 MAPK activity, but not activation of ERK or JNK. Silencing of p38α MAPK with siRNA rendered T-cells resistant to ESAT-6 inhibition of IFN-γ production. Taken together, our results demonstrated that ESAT-6 inhibits T cell IFN-γ production in a p38 MAPK-dependent manner.