The measurement of exhaled NO has excited considerable interest, as it may provide a simple noninvasive means of measuring airways inflammation. There is now persuasive evidence that levels of NO are increased in association with airway inflammation and are decreased with anti-inflammatory treatment. Correlation of exhaled NO with more direct measurements of inflammation in the airways, such as induced sputum, bronchoalveolar lavage and bronchial biopsies, is needed. The great advantage of exhaled NO is that the measurement is completely noninvasive. It can, therefore, be performed repeatedly, and also in children and patients with severe airflow obstruction, where more invasive techniques are not possible. However, the measurement is not specific, and exhaled NO is increased in inflammation due to asthma, bronchiectasis, and respiratory tract infections. This means that absolute values are less important than serial measurements in individual patients. The value of this approach has been demonstrated in asthmatic patients, where the dose of inhaled steroid is changed, resulting in increased levels when the dose is reduced and lower levels when the dose is increased. Because exhaled NO is reduced by anti-inflammatory treatments, it may be of use in monitoring whether therapy is adequate. The technique may also have application in the monitoring of the anti-inflammatory effects of new antiasthma drugs, such as selective phosphodiesterase inhibitors, leukotriene antagonists and synthesis inhibitors, and immunomodulators. Because the measurement is precise and reasonably reproducible, it may facilitate the measurement of dose-response effects with anti-inflammatory treatments, which is difficult at present. The analysers for exhaled NO that are currently available are expensive, but in the future it is likely that technological advances will make it possible to miniaturize these analysers, so that they are portable and may even be used at home in conjunction with peak flow meters. -his may lead to their application in epidemiological research, which may be a useful screening measurement for community studies. Although we have discussed exhaled nitric oxide, other volatile substances may also be detected in exhaled air. Thus, ethane and pentane, which are volatile products of lipid peroxidation, and hydrogen peroxide, may be used to detect oxidant stress in the respiratory tract and may also be useful as markers of inflammation. There is little doubt that this is a rapidly expanding area of research.
Abstract Recent disruptive technological advances, including wire arc additive manufacturing (WAAM) and the concept of digital twins, have the potential to fundamentally transform the way in which we design, build and manage structures. WAAM is a method of metal 3D printing that is well suited to the price‐sensitive construction industry and has been used to manufacture the MX3D bridge – the world's first metal 3D printed bridge. The intricate geometry, undulating surface finish and particular material properties rendered the bridge outside the scope of any existing structural design standards; hence, physical testing and advanced numerical modelling were carried out for its safety assessment. The key features of the finite element model of the bridge, and its validation against in‐situ structural tests, are described herein. Subsequent numerical studies undertaken to verify the structural performance of the bridge under various loading scenarios are presented, while the basis for the development of the smart digital twin of the bridge is also introduced. The presented research provides insight into the use of advanced computational simulations for the verification and ongoing assessment of structures produced using new methods of manufacture.
Background Although randomized trials have established that coronary artery bypass grafting (CABG) is, on average, the most effective revascularization strategy compared with percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease (MVD), individual patients differ in many characteristics that can affect the benefits and harms of treatment. The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus) score was developed to predict different outcomes with CABG vs PCI on the basis of 8 patient characteristics and the smoking-treatment interaction. Objectives This study aimed to assess the ability of the 5-year major adverse cardiovascular event (MACE) model to predict treatment benefit of CABG vs PCI in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) trials. Methods This study identified 702 patients with diabetes and MVD to mirror the FREEDOM participants. Discrimination was assessed by C-index, and calibration was assessed by calibration plots in the PCI and CABG arms, respectively. The ability of the FREEDOM score to predict treatment benefit of CABG vs PCI was assessed. Results Overall, CABG was associated with a lower rate of 5-year MACE compared with PCI (12.4% vs 20.3%; log-rank P = 0.021) irrespective of a history of smoking (P interaction = 0.975). Both discrimination and calibration were helpful in the PCI arm (C-index: 0.69; slope: 0.96, intercept: −0.24), but moderate in the CABG arm (C-index: 0.61; slope: 0.61; intercept: −0.53). The FREEDOM score showed some heterogeneity of treatment benefit. Conclusions The FREEDOM score could identify some heterogeneity of treatment benefit of CABG vs PCI for 5-year MACE. Until further prospective validations are performed, these results should be taken into consideration when using the FREEDOM score in patients with diabetes and MVD. (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery [SYNTAX]; NCT00114972) (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease [BEST]; NCT00997828) (Future Revascularization Evaluation in Patients with Diabetes Mellitus [FREEDOM]; NCT00086450)
Objectives This paper reports the 3-year clinical outcomes of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) compared with the TAXUS (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stent (PES) in the randomized SPIRIT II (Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions) study. Background The Xience V EES is a new-generation drug-eluting stent (DES) that might offer advantages over the first-generation DES in terms of improved clinical outcomes and a better safety profile. Methods The SPIRIT II trial was a multicenter, prospective, randomized, single-blind, clinical trial, randomizing 300 patients with de novo coronary artery lesions in a ratio of 3:1 to either EES or PES. The primary end point was in-stent late loss at 180 days. Results At 3-year clinical follow-up cardiac death was numerically lower with EES than PES (0.5% vs. 4.3%, p = 0.056). The observed rate of myocardial infarction was 3.6% for EES and 7.2% for PES (p = 0.31). The rate of ischemia-driven target lesion revascularization was 4.6% and 10.1% for EES and PES, respectively (p = 0.14). Overall, there was a trend for lower major adverse cardiovascular events in the EES group compared with PES (7.2% vs. 15.9%, p = 0.053). The rate of stent thrombosis was low and comparable in both groups (EES 1.0% vs. PES 2.9%). Conclusions The present study reports the favorable 3-year clinical outcomes of the EES, which are consistent with the results from other studies of the EES with shorter follow-up.
The purpose of the Benestent II Pilot Phase was to explore the safety of reducing antithrombotic therapy in conjunction with implantation of heparin-coated stents. The study consists of three phases, where resumption of heparin therapy after stent implantation was progressively delayed in a stepped care approach. Material and Methods Palmaz-Schatz stents with heparin coating were implanted in 51 patients (88% male) with stable angina pectoris. Heparin treatment was withheld 6 hours following removal of the sheath introducer from the femoral artery. The mean age was 59 years, 10% had a previous myocardial infarction, diabetes was prevalent in 8%, hypertension in 24% and 59% were current or previous smokers. Target lesion was located in the left anterior descending artery in 51%, left circumflex in 8% and right coronary artery in 41%. TIMI flow I-II was present in 14% and TIMI III in 86%. The mean pre-procedural minimal lumen diameter (MLD) was 1.10mm and reference diameter 3.16 mm. Results Stent implantation was successful in all patients and following the procedure, mean MLD increased to 2.77mm and percent diameter stenosis was reduced from 65% to 19%. The maximum balloon size was 3.45±0.40mm. Post-stent dilatation was performed in 40 patients (80%). High pressure (>12 atm) was used in 22 of these cases (54%). Two patients needed a second stent; one for an occlusive distal dissection and one for a distal lesion. There were no major complications, i.e. death, myocardial infarction, urgent CABG, re-PTCA or cerebrovascular accident. Peripheral vascular complications required vascular surgery in 3 patients (5.9%) and blood transfusion in one (2%). Conclusions In this pilot study implantation of heparinized stents was associated with a 100% success rate, absence of serious complications and a moderate incidence of vascular complications. Further reduction of antithrombotic treatment may be feasible.
Several mediators produced by various inflammatory cells have now been implicated in asthma. They may contribute to the pathology of asthma by contracting airway smooth muscle, stimulating mucus secretion, and promoting bronchial oedema and chemotaxis of inflammatory cells. Because many mediators interact, antagonism of any single mediator is unlikely to have a major clinical effect.
