Publications

In human airways synthetic human sequence calcitonin gene‐related peptide (hCGRP), a novel peptide produced by alternative processing of mRNA from the calcitonin gene, caused concentration‐dependent contraction of human bronchi (EC 50 4.9 × 10 −9 m ) and was significantly more potent than substance P or carbachol. The contractile response was unaffected by atropine (2 × 10 −6 m ), propranolol (10 −6 m ), indomethacin (10 −5 m ), tetrodotoxin (3 × 10 −6 m ), chlorpheniramine (10 −4 m ), cimetidine (10 −5 m ), or FPL55712 (10 −4 m ) suggesting a direct effect of CGRP on airways smooth muscle. CGRP was detected in human airways by radioimmunoassay with highest concentrations in cartilaginous airways. CGRP was localised by immunocytochemistry to both nerves and ganglia in human airways. CGRP, is a potent constrictor of human airways and may have important effects on airway function and be implicated in the pathogenesis of bronchial hyper‐responsiveness and asthma.

Background: Clinical implications of online 3-dimensional optical frequency domain imaging (3D-OFDI)-guided stenting for bifurcation lesions have not been investigated in the randomized controlled trials. The purpose of this study was to determine whether online 3D-OFDI-guided stenting is superior to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition at the bifurcation segment. Methods: The OPTIMUM trial (Online 3-Dimensional Optical Frequency Domain Imaging to Optimize Bifurcation Stenting Using UltiMaster Stent) was a randomized, multicenter clinical trial. Eligible patients had an angiographically significant stenosis in the bifurcation lesion treated with a provisional single stent strategy using the Ultimaster sirolimus eluting stent. Patients were randomly allocated to either online 3D-OFDI-guided or angiography-guided PCI. Patients randomized to 3D-OFDI guidance underwent online 3D-OFDI assessment after rewiring into the jailed side branch after stenting and proximal optimization technique, while in the angiography guidance arm, rewiring was performed using conventional fluoroscopic/angiographic guidance. The primary end point of this trial was the postprocedural average percentage of malapposed struts per lesion assessed by OFDI in the confluence zone of the main and side branches. Results: Between June 8, 2017 and September 26, 2018, 110 patients with 111 bifurcation lesions were randomized at 4 Japanese centers. Of these, 56 patients with 57 lesions were treated with 3D-OFDI-guided PCI, whereas 54 patients with 54 lesions were treated with angiography-guided PCI. In the 3D-OFDI guidance arm, the feasibility of online 3D-OFDI was 98.2%. The average percentage of incomplete stent apposition per lesion at bifurcation was lower in the 3D-OFDI guidance arm than that in the angiography guidance arm (19.5±15.8% versus 27.5±14.2%, P =0.008). The superiority of the 3D-OFDI guidance arm was also confirmed in the strut level analysis (odds ratio: 0.54 [95% CI, 0.36–0.81]; P =0.003). Conclusions: Online 3D-OFDI-guided bifurcation PCI was superior to angiography-guided bifurcation PCI in terms of acute incomplete stent apposition at bifurcation. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02972489.

Wire arc additive manufacturing (WAAM) is a metal 3D printing technique well recognised in the construction sector for its high efficiency, cost-effectiveness and flexibility in build scales. However, there remains a lack of fundamental data on the structural performance of WAAM elements, especially regarding their fatigue behaviour. A comprehensive experimental study into the fatigue behaviour of WAAM steel plates has therefore been undertaken and is reported herein. Following geometric and mechanical characterisation, a series of WAAM coupons was tested under uniaxial high-cycle fatigue loading. A total of 75 fatigue tests on both as-built and machined coupons, covering various stress ranges and stress ratios, have been conducted. The fatigue test results were analysed using constant life diagrams (CLDs) and S-N (stress-life) diagrams. The CLDs revealed that the fatigue strength of the as-built WAAM steel was relatively insensitive to the different stress ratios. The S-N diagrams showed that the surface undulations resulted in a reduction of about 35% in the fatigue endurance limit for the as-built WAAM material relative to the machined material, and a reduction of about 60% in fatigue life under the same load level. Preliminary S-N curves were also proposed for the WAAM steel.

Four decades have passed since the first trial suggesting the efficacy of aspirin in the secondary prevention of myocardial infarction. Further trials, collectively summarized by the Antithrombotic Trialists' Collaboration, solidified the historical role of aspirin in secondary prevention. Although the benefit of aspirin in the immediate phase after a myocardial infarction remains incontrovertible, a number of emerging lines of evidence, discussed in this narrative review, raise some uncertainty as to the primacy of aspirin for the lifelong management of all patients with chronic coronary syndrome (CCS). For example, data challenging the previously unquestioned role of aspirin in CCS have come from recent trials where aspirin was discontinued in specific clinical scenarios, including early discontinuation of the aspirin component of dual antiplatelet therapy after percutaneous coronary intervention and the withholding of aspirin among patients with both CCS and atrial fibrillation who require anticoagulation. Recent primary prevention trials have also failed to consistently demonstrate net benefit for aspirin in patients treated to optimal contemporary cardiovascular risk factor targets, indicating that the efficacy of aspirin for secondary prevention of CCS may similarly have changed with the addition of more modern secondary prevention therapies. The totality of recent evidence supports further study of the universal need for lifelong aspirin in secondary prevention for all adults with CCS, particularly in stable older patients who are at highest risk for aspirin-induced bleeding.

No abstract is provided for this article.

The current study aimed to assess the difference in lumen dimension measurements between optical coherence tomography (OCT) and quantitative coronary angiography (QCA) in the polymeric bioresorbable scaffold and metallic stent.In the randomised ABSORB Japan trial, 87 lesions in the Absorb arm and 44 lesions in the XIENCE arm were analysed. Post-procedural OCT-QCA lumen dimensions were assessed in matched proximal/distal non-stented/non-scaffolded reference (n=199), scaffolded (n=145) and stented (n=75) cross-sections at the two device edges using the Bland-Altman method. In the non-stented/non-scaffolded reference segments, QCA systematically underestimated lumen diameter (LD) compared with OCT (accuracy, -0.26 mm; precision, 0.47 mm; 95% limits of agreement as a mean bias±1.96 standard deviation, -1.18-0.66 mm). When compared to OCT, QCA of the Absorb led to a more severe underestimation of the LD (-0.30 mm; 0.39 mm; -1.06-0.46 mm) than with the XIENCE (-0.14 mm; 0.31 mm; -0.75-0.46 mm). QCA underestimated LD by 9.1%, 4.9%, and 9.8% in the reference, stented, and scaffolded segments, respectively. The protrusion distance of struts was larger in the Absorb arm than in the XIENCE arm (135±27 µm vs. 18±26 µm, p<0.001), and may have contributed to the observed differences.In-device QCA measurement was differently affected by the presence of a metallic or polymeric scaffold, a fact that had a significant impact on the QCA assessment of acute gain and post-procedural minimum LD.

With the advance of optical coherence tomography (OCT) technology, three-dimensional (3D) reconstruction based on the optical coherence tomography has become feasible. In bifurcation lesions, 3D OCT may guide positioning of the wire through the appropriate (distal) cells. The early studies suggested that such a guidance strategy could reduce the incidence of malapposition in bifurcation lesions. The pre-installed "real-time" 3D OCT on the console will promote the utilisation of 3D assessment in bifurcation treatment and possibly establish the clinical benefit of such guidance in the near future when investigated in a prospective study.

No abstract is provided for this article.

Objectives Using multislice computed tomography (MSCT), we sought to evaluate the geometry and apposition of the CoreValve ReValving System (CRS, Medtronic, Luxembourgh, Luxembourgh) in patients with aortic stenosis. Background There are no data on the durability of percutaneous aortic valve replacement. Geometric factors may affect durability. Methods Thirty patients had MSCT at a median 1.5 months (interquartile range [IQR] 0 to 7 months) after percutaneous aortic valve replacement. Axial dimensions and apposition of the CRS were evaluated at 4 levels: 1) the ventricular end; 2) the nadir; 3) central coaptation of the CRS leaflets; and 4) commissures. Orthogonal smallest and largest diameters and cross-sectional surface area were measured at each level. Results The CRS (26-mm: n = 14, 29-mm: n = 16) was implanted at 8.5 mm (IQR 5.2 to 11.0 mm) below the noncoronary sinus. None of the CRS frames reached nominal dimensions. The difference between measured and nominal cross-sectional surface area at the ventricular end was 1.6 cm2(IQR 0.9 to 2.6 cm2) and 0.5 cm2(IQR 0.2 to 0.7 cm2) at central coaptation. At the level of central coaptation the CRS was undersized relative to the native annulus by 24% (IQR 15% to 29%). The difference between the orthogonal smallest and largest diameters (degree of deformation) at the ventricular end was 4.4 mm (IQR 3.3 to 6.4 mm) and it decreased progressively toward the outflow. Incomplete apposition of the CRS frame was present in 62% of patients at the ventricular end and was ubiquitous at the central coaptation and higher. Conclusions Dual-source MSCT demonstrated incomplete and nonuniform expansion of the CRS frame, but the functionally important mid-segment was well expanded and almost symmetrical. Undersizing and incomplete apposition were seen in the majority of patients.

Opioids reduce the cholinergic responses to electrical field stimulation (EFS) in guinea pig and canine airways by a prejunctional effect. We determined whether a similar effect operates in human airways in vitro. [D-Ala2-NMePhe4-Gly-ol5]enkephalin (DAMGO) (10(-8)-10(-6) M), a selective mu-opioid receptor agonist, inhibited the response to EFS in a dose- and frequency-dependent manner. DAMGO (10(-6) M) produced 86% inhibition at 0.5 Hz and 38% inhibition at 4 Hz, but at 32 Hz there was no significant inhibition. Another selective mu-opioid receptor agonist H-Tyr-D-Arg-Gly-Phe(4-NO2)-Pro-NH2 diacetate (BW 443C) also inhibited responses to EFS, producing 57.7% inhibition at 4 Hz at a concentration of 10(-6) M. The inhibitory effect on EFS was blocked by the opioid receptor antagonist naloxone (10(-5) M), indicating that opioid receptors are involved. DAMGO (10(-6) M) had no effect on the contractile response to exogenous acetylcholine, indicating a prejunctional effect. We conclude that mu-opioid agonists inhibit cholinergic neurotransmission in human airways in vitro, and this could have therapeutic potential in the treatment of airway disease.

Short-term results of durable polymer everolimus-eluting stents have shown significant improvements in clinical and angiographic outcomes. This report presents the 1-year clinical and angiographic data from the SPIRIT FIRST Trial.This first-in-man single blind multi-centre randomized controlled trial assessed the safety and efficacy of everolimus and a durable polymer on a cobalt chromium stent in patients with de novo native coronary artery lesions. Of the 60 patients enrolled, a total of 56 patients (27 everolimus arm and 29 bare stent arm) were qualified to per-treatment analyses at 1 year. Quantitative angiographic and intravascular ultrasound (IVUS) analyses were performed. Angiographic late loss, IVUS neointimal volume obstruction and major adverse cardiac events (MACE) at 1 year were assessed as the study endpoints. At 1 year, the in-stent late loss and diameter stenosis of patients were 0.24 mm and 18% in the everolimus arm (n=20), as compared with 0.84 mm and 37% in the bare stent arm (n=25, p < 0.001). Significantly less neointimal hyperplasia was observed in the everolimus arm compared to the bare stent arm (neointimal volume, 13+/-9 mm3 vs. 37+/-17 mm3, p < 0.001; volume obstruction, 10+/-7% vs. 28+/-12%, p < 0.001). The overall MACE rate was 15.4% in the everolimus arm and 21.4% in the bare stent arm.The safety and efficacy of everolimus-eluting stent with a durable polymer observed at 6 months was sustained at 1 year.