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Bioresorbable scaffolds (BRSs) may potentially overcome the many pitfalls related to drug eluting stents (DESs). Following CE mark approval, the rapid adoption of this novel treatment has led to its use in all comers with complex lesion morphology even without randomized comparison with the DESs. The only published randomized clinical study thus far is the ABSORB II. However, the current generation (ABBOTT Bioresorbable Vascular Scaffold, BVS™) still has a lot of limitations. The Mirage Microfiber Sirolimus Eluting Coronary Scaffold (MMSES™, Manli Cardiology™) is designed to address the concerns of BVSs, such as improved vessel wall conformability, reduced strut protrusion into lumen, fracture resistance allowing rapid deployment until rated burst pressure, excellent deliverability, faster degradation time, ability to store at ambient room temperature <25°C, and no restriction on size availability. In contrast to the BVSs, the MMSES struts are round and thinner with less protrusion into the lumen. This streamlined geometry results in lesser activation of coagulation cascade and better promotion of endothelialization. This feature is interesting, especially in view of recent reports of somewhat higher BVSs thrombosis as compared to DESs.
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Everolimus has been successfully tested in humans using both an erodable and a durable polymer in small previous studies.This single blind multi-centre non-inferiority randomised (3:1) controlled trial evaluated the safety and performance of the XIENCE V Everolimus Eluting Coronary Stent System (XIENCE V EECSS) versus the TAXUS Paclitaxel Eluting Coronary Stent System (TAXUS(R) PECSS) in the treatment of patients with a maximum of two de novo native coronary artery lesions located in two different epicardial vessels. Three hundred patients with evidence of myocardial ischaemia were allocated to stent implantation with an everolimus-eluting stent (n=223) or a paclitaxel-eluting stent (n=77). Suitable lesions had a diameter stenosis of <50-99%, a length of <28 mm, and a reference vessel diameter between 2.5 mm and 4.25 mm. The primary endpoint was in-stent late loss (LL) at 180 days. Percentage in-stent volume obstruction (%VO) was measured by intravascular ultrasound (IVUS) in a subset of 152 patients. Clinical secondary endpoints included ischaemia driven major adverse cardiac events (ID-MACE) at 180 days.At 6 months, the in-stent LL was 0.11+/-0.27 mm in the everolimus-eluting stent arm, as compared to 0.36+/-0.39 mm in the paclitaxel-eluting stent arm (p<0.0001). Percentage VO in the everolimus-eluting stent arm was 2.5+/-4.7% versus 7.4+/-7.0% in the paclitaxel-eluting stent arm (p<0.0001). Hierarchical MACE was 2.7% (6/222) in the everolimus-eluting stent arm vs. 6.5% (5/77) in the paclitaxel-eluting stent arm.This non-inferiority randomised trial not only met its primary endpoint, but also demonstrated the superiority of the everolimus-eluting stent over the paclitaxel-eluting stent in terms of in-stent late loss.
A computer-assisted technique has been developed to assess absolute coronary arterial dimensions from 35 mm cineangiograms. The boundaries of optically magnified and video-digitized coronary segments and the intracardiac catheter are defined by automated edge-detection techniques. Contour positions are corrected for pincushion distortion. The accuracy and precision of the edge detection procedure as assessed from cinefilms of contrast-filled acrylate (Perspex) models were -30 and 90 micrometers, respectively. The variability of the analysis procedure itself in terms of absolute arterial dimensions was less than 0.12 mm, and in terms of percentage arterial narrowing for coronary obstructions less than 2.74%. Short-, medium-, and long-term variability measurements were assessed from repeated coronary angiographic examinations performed 5 min, 1 hr, and 90 days apart, respectively. For all studies the mean differences in absolute diameters were less than 0.13 mm. The variability in obstruction diameter ranged from 0.22 mm for the best-controlled study (medium-term) to 0.36 mm for the least-controlled study (long-term); variability in reference diameter ranged from 0.15 to 0.66 mm, respectively. It is concluded that the biological variations are a source of major concern and that further attempts toward standardization of the angiographic procedure are seriously needed.
In many countries the majority of patients with asthma are now treated with inhaled β2-agonists as required and regular inhaled steroids. Compliance with asthma medication is poor, particularly for inhaled steroids, which do not give immediate relief of symptoms. An inhaler combining a β2-agonist and a steroid may improve compliance and give better control of asthma. We have studied the effect of a fixed combination dry powder inhaler (Turbuhaler®) containing terbutaline (250 µg) with budesonide (200 µg) compared with each drug given alone in a double-blind, crossover study in 74 patients with mild to moderate asthma. This was a multicenter study performed in general practice. After a 1-wk run-in period with placebo inhaler, each treatment was given twice daily for 4 wk in randomized order. Patients measured symptom scores and rescue inhaled β2-agonist use and recorded peak expiratory flow (PEF) twice daily. In nine patients recruited to a hospital center, airway responsiveness was measured by the concentration of methacholine required to produce a fall in FEV1 of 20% (PC20) at the end of each treatment period. Of 74 patients randomized, 68 completed all three treatment periods. Their mean age was 37 (18–60) yr and PEF 80 (43–116) % predicted. Combination treatment gave a significant improvement in morning and evening PEF budesonide or terbutaline treatment periods (p < 0.01), and a significant reduction in asthma symptom scores and rescue β2-agonist use (p < 0.05). There was a significant patient preference for the combination inhaler. Measurement of compliance by counting unused doses showed good compliance with no significant difference between treatments. In nine patients who underwent methacholine challenge, both combination and budesonide treatment significantly improved PC20 by almost two doubling dilutions compared with baseline, whereas there was no protection after treatment with terbutaline. The acute protection 1 h after inhalation was significantly greater (p < 0.05) after combination than after terbutaline inhalation. We suggest that a fixed combination inhaler containing a low dose β2-agonist and an inhaled steroid provides a small but significant improvement in the control of mild asthma and may simplify its long-term management.
There has been intense research into the role nitric oxide (NO) plays in physiological and pathological mechanisms and its clinical significance in respiratory medicine. Elevated levels of exhaled levels of exhaled NO in asthma and other inflammatory lung diseases lead to many studies examining NO as potential markers of airway inflammation, enabling repeated noninvasive and standardized monitoring of airway inflammation. In airway inflammation, NO is not merely a marker but may have anti-inflammatory and pro-inflammatory effects. Significant correlation has been found between exhaled NO and skin test scores in steroid naive asthmatic patients, allowing to discriminate patients with and without airway responsiveness. Exhaled NO is significantly elevated in acute asthma, or steroid-resistant severe asthma, or when the maintenance dose of inhaled steroids is reduced, and quickly reduced down to the levels in patients with stable asthma after steroid treatment. Exhaled NO has been successfully used to monitor anti-inflammatory treatment with inhaled corticosteroids in asthma. Exhaled NO is extremely sensitive and rapid marker of the dose-dependent effect of steroid treatment, or asthma deterioration, which is increased to any changes in lung function, provocative concentration causing a 20% fall in forced expiratory volume, sputum eosinophilia or asthma symptoms. Exhaled NO is not increased in stable chronic obstructive pulmonary disease (COPD), but patients with unstable COPD, or bronchiectasis have high NO levels. Exhaled and nasal NO are diagnostically low in cystic fibrosis and primary pulmonary dyskinesia. Analysis of exhaled air, including nitric oxide, is feasible and could provide a noninvasive method for use in monitoring and management of lung diseases.