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Intravascular ultrasound elastography is a method for measuring the local elastic properties using intravascular ultrasound (IVUS). The elastic properties of the different tissues within the atherosclerotic plaque are measured through the strain. Knowledge of these elastic properties is useful for guiding interventional procedures (balloon dilatation, ablation) and detection of the vulnerable plaque. In the last decade, several groups have applied elastography intravascularly with various levels of success. In this paper, the approaches of the different research groups will be discussed. The focus will be on our approach to the application of intravascular elastography.

Increased numbers of macrophages and neutrophils in the lung is a key feature of chronic obstructive pulmonary disease (COPD). The major neutrophil chemotactic agent in the airways of COPD patients is leukotriene (LT)B 4 and is released by macrophages. The present study examines the role and mechanism of Ca 2+ in platelet-activating factor (PAF)-stimulated LTB 4 release from human lung macrophages. Macrophages were isolated from lung tissue of subjects undergoing lung resection surgery and monocyte-derived macrophages (MDM) were obtained from nonsmokers, smokers without obstruction and COPD patients. Cells were stimulated with PAF and LTB 4 release and [Ca 2+ ] i was measured. Lung macrophages and MDM released LTB 4 following stimulation with PAF (mean effective concentration: 0.08±0.06 μM (n = 5) versus 0.17±0.12 μM (n = 17), respectively). Compared with MDM, lung macrophages released approximately eight-fold more LTB 4 . Neither smoking nor COPD altered MDM responses. PAF-stimulated LTB 4 release was abrogated by ethylene glycol tetraacetic acid suggesting a role for extracellular Ca 2+ . This was substantiated by using store-operated channel blockers econazole, SK&F96365 and Gd 3+ . However, econazole and SK&F96365 were more effective in MDM than lung macrophages. Neither LOE908 nor nifedipine could attenuate this response. These data suggest that platelet-activating factor-stimulated leukotriene B 4 release from human lung macrophages is mediated, in part, by Ca 2+ influx through receptor- but not voltage-operated Ca 2+ channels.

Non-ST-elevation acute coronary syndrome (NSTE-ACS) affects millions of patients. Although an invasive strategy can improve survival, the optimal treatment [i.e., percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] is not clear. We performed a meta-analysis of studies reporting outcomes between PCI and CABG in patients with NSTE-ACS. MEDLINE, EMBASE and Cochrane Library were assessed. The primary outcome was long-term mortality. Inverse variance method and random model were performed. We identified 13 observational studies (48,891 patients). No significant difference was found in the primary endpoint [CABG vs. PCI, incidence rate ratio (IRR) 0.93, 95% confidence interval (CI) 0.70; 1.23]. CABG was associated with lower long-term major adverse cardiovascular events (MACE) (IRR 0.64, 95% CI 0.54; 0.76) and lower long-term re-revascularization (IRR 0.37, 95% CI 0.30; 0.47). There was no significant difference in long-term myocardial infarction (CABG vs. PCI, IRR 0.96, 95% CI 0.50; 1.84) and peri-operative mortality (CABG vs. PCI, odds ratio 1.36, 95% CI 0.94; 1.95). For the treatment of NSTE-ACS, CABG and PCI are associated with similar rates of long-term mortality and myocardial infarction. CABG is associated with lower rates of long-term MACE and re-revascularization. Randomized comparisons in this setting are necessary.

<title>Abstract</title> <bold>Background: </bold>COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass-smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HIC), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting. <bold>Methods: </bold>LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years; (2) full-time resident of the study area; (3) daily biomass exposure, (4) post-bronchodilator FEV₁/FVC below the 5^th percentile of the Global Lung Initiative mixed ethnic reference population; (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily, low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George’s Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every six months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP) and theophylline levels at baseline, one month and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D.<bold>Trial Registration: </bold>NCT03984188 Registered June 12, 2019<bold>Trial acronym:</bold> Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD)

Chronic Obstructive Pulmonary Disease as an Inflammatory DiseaseChronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of the airways and lung parenchyma that is characterized by increased numbers of neutrophils, activated macrophages, and activated T-lymphocytes (Tc1 and Th1 cells) [1].The inflammation is amplified in COPD compared with smokers without COPD, and the molecular basis for this amplification is now better understood, providing novel targets for future therapies.Macrophages are markedly increased in COPD, and these cells play a key role in recruiting other inflammatory cells and in releasing mediators and proteases.Macrophages in the lungs are recruited from circulating monocytes by chemotactic factors such as CXCLI (GRO-a) and CCL2 (MCP1).The inflammatory changes in COPD are due to the release of multiple inflammatory mediators, including lipid mediators, cytokines, and chemokines [2].Many of these mediators are regulated by the proinflammatory transcription factor nuclear factor-κB (NF-κB), which is activated in epithelial cells and macrophages of COPD patients [2].Activated macrophages and neutrophils release elastolytic enzymes, particularly matrix metalloproteinase (MMP)-9, that contribute to the development of emphysema.In addition, cytotoxic Tc1 cells may induce the destruction of alveolar cells.Small airway narrowing and fibrosis appear to be the major mechanisms contributing to airflow limitation and air trapping, but the mechanisms of fibrosis are poorly understood.Th17 cells may play a role in orchestrating neutrophilic inflammation in COPD [3]. Corticosteroid ResistanceIn sharp contrast to asthma, the inflammation in COPD shows little response to corticosteroids.This steroid resistance may be explained by the reduced activity of a key nuclear enzyme, histone deacetylase 2 (HDAC2), which also accounts for the amplified inflammation in COPD [4].The reduction in HDAC2 is driven by increased oxidative stress through the activation of the enzyme phosphoinositide-3-kinase-δ (PI3Kδ), which is inhibited by low concentrations of theophylline [5].Clinical trials with low dose theophylline as a means of reversing corticosteroid-resistance in COPD are currently underway. Reduced Bacterial PhagocytosisAlveolar macrophages normally phagocytose inhaled microorganisms and keep the respiratory tract sterile, but in COPD, there is a defect in bacterial phagocytosis by macrophages that may result in chronic bacterial colonization [6].

Wire arc additive manufacturing (WAAM) is a metal 3D printing method that allows the cost-effective and efficient production of large-scale elements, and has thus gained great interest from architects and structural engineers. Integration of this novel technology into the construction industry, however, requires the development of a clear understanding of the mechanical behaviour of WAAM materials. To this end, a comprehensive experimental study into the mechanical properties and microstructure of WAAM plates made of normal- and high-strength steels has been undertaken and is reported herein. A total of 137 as-built and machined tensile coupons were tested, extracted in various directions relative to the print layer orientation from WAAM plates of two nominal thicknesses, built using different deposition strategies. Microstructural characterisation was also performed by means of optical microscopy and electron backscatter diffraction (EBSD). The EBSD analysis revealed a weak crystallographic texture, which explained the observed mechanical properties being almost isotropic. The geometric undulations of the as-built coupons resulted in some reduction in effective mechanical properties and a degree of anisotropy. Overall, the examined WAAM material exhibited consistent mechanical properties, a Young’s modulus comparable to conventionally-produced steels, marginally lower strength, reflecting the slower cooling conditions than is customary, and good ductility.

AIMS Patients with acute coronary syndrome (ACS) might represent a specific subgroup, in which bioresorbable scaffold implantation in percutaneous coronary intervention, might lead to better outcomes when compared to conventional treatment. ACS patients (STE-ACS patients in particular) are generally younger, and most often have lesions with softer plaques, a lower plaque burden and less extensive coronary artery disease. In this pre-specified subgroup analysis of the AIDA trial, we evaluated the clinical outcomes of Absorb BVS versus Xience EES treated patients presenting with or without ACS. Methods and results This analysis includes the 2-year outcomes of all 1845 patients randomized in the AIDA trial subdivided by clinical presentation, a pre-specified subgroup analysis. We compared patients presenting with ACS with those presenting without ACS (ACS versus no-ACS patients). Patients presenting with ACS were further sub-categorized according to the presence or absence of ST-segment elevation at presentation (STE-ACS versus NSTE-ACS patients). Baseline status by clinical presentation was known in all patients, and 842 (45.6%) patients presented with ACS, 456 (25.2%) with STE-ACS and 377 (20.4%) with NSTE-ACS.The rate of the 2-year primary endpoint of target vessel failure (TVF) was similar after treatment with Absorb BVS or Xience EES in ACS patients (10.2% versus 9.0% respectively; p=0.49) and in no-ACS patients (11.7% versus 10.7% respectively; p=0.67) Definite or probable device thrombosis occurred more frequently with Absorb BVS compared to Xience EES in ACS patients (4.3% versus 1.7% respectively, p=0.03) as well as in no-ACS patients (2.4% versus 0.2% respectively; p=0.002). There were no statistically significant interactions between clinical presentation and randomized device modality for TVF (p=0.80) and for the endpoint of definite or probable device thrombosis (p=0.17). Conclusions In ACS patients within AIDA, we found no difference in rates of target vessel failure between the Absorb BVS and Xience EES groups. Rates of definite or definite/probable device thrombosis were higher in the Absorb BVS group throughout all clinical presentations. No significant interaction between ACS and no-ACS patients and the occurrence of TVF Acknowledgement/Funding The AIDA trial was financially supported by an unrestricted research grant from Abbott Vascular.

No abstract is provided for this article.

Potassium (K+) channel activators, such as cromakalim, open ATP sensitive K+ channels and relax airway smooth muscle in vitro and inhibit induced bronchoconstriction in vivo in animals. The prolonged half life of cromakalim gives it potential as an oral bronchodilator. The effect of orally administered BRL 38227 (the active enantiomer of cromakalim), at doses of 0.125, 0.25, and 0.5 mg, on airway function and airway responsiveness to histamine and methacholine has been investigated in asthmatic patients.Seventeen patients with asthma were studied in three separate randomised double blind, placebo controlled studies. In the first study eight patients with moderately severe asthma were given 0.125, 0.25, and 0.5 mg of BRL 38227 or placebo, and responses to histamine were assessed before and five hours after treatment. In the second study responses to methacholine were measured before and five hours after 0.125 and 0.5 mg of BRL 38227 or placebo were given to nine patients with mild asthma. In the third study the effect of 0.5 mg of BRL 38227 or placebo was assessed in eight patients with mild asthma. Responses to histamine were measured before treatment and two and five hours after treatment. To provide a positive control study eight subjects who had taken part in studies 1 and 3 were also given oral salbutamol (8 mg) in a placebo controlled, double blind study. Responses to histamine were assessed before and two hours after treatment.BRL 38227 did not cause significant bronchodilatation or changes in airway responsiveness in any of the studies. Headache was reported in 19 of 25 of patients receiving (in some cases twice) 0.5 mg of BRL 38227. By contrast, oral salbutamol gave significant protection against histamine challenge (geometric mean 2.23 doubling dilutions).After a single oral dose of BRL 38227 no beneficial effect on airway function was detected, despite a high incidence of side effects, which indicates that the orally administered K+ channel activator BRL 38227 may not be useful in the management of asthma.

Although the safety profiles of coronary stents eluting sirolimus or paclitaxel do not seem to differ from those of bare metal stents in the short-to-medium term, concern has arisen about the potential for late stent thromboses related to delayed endothelialisation of the stent struts. We report four cases of angiographically-confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 days) or sirolimus-eluting (335 and 375 days) stents, and resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. If confirmed in systematic long-term follow-up studies, our findings have potentially serious clinical implications.