Publications

Rationale: The SYGMA (Symbicort Given as Needed in Mild Asthma) studies evaluated the efficacy and safety of as-needed budesonide (BUD)-formoterol (FORM) in patients whose asthma was uncontrolled on as-needed inhaled short-acting bronchodilators (subgroup 1) or controlled on inhaled corticosteroids (ICS) or leukotriene receptor antagonists (subgroup 2). Objectives: To assess the influence of prestudy treatment in a post hoc analysis of the SYGMA studies. Methods: In the SYGMA 1 (NCT022149199) and SYGMA 2 (NCT02224157) 52-week, double-blind, randomized, parallel-group studies, 6,735 patients with mild asthma were randomized to as-needed BUD-FORM, low-dose BUD + as-needed terbutaline (BUD maintenance), or as-needed terbutaline (SYGMA 1 only). Exacerbation rates and changes in symptom control and lung function were compared among treatments for both subgroups. Results: In a pooled analysis of SYGMA 1 and 2, the annual severe exacerbation rate in subgroup 1 was significantly lower with as-needed BUD-FORM (0.08 [95% confidence interval (CI), 0.06-0.10]) than with BUD maintenance (0.10 [95% CI, 0.09-0.13]) (rate ratio [RR], 0.74 [95% CI, 0.56-0.98]; P = 0.03), and similar results were shown in subgroup 2 with BUD-FORM (0.12 [95% CI, 0.10-0.14]) and BUD maintenance (0.10 [95% CI, 0.09-0.13]) (RR, 1.10 [95% CI, 0.86-1.41]; P = 0.44). In SYGMA 1, the annual severe exacerbation rate in both subgroups was significantly lower with as-needed BUD-FORM than with as-needed terbutaline (subgroup 1: RR, 0.34 [95% CI, 0.20-0.58]; P < 0.001; subgroup 2: RR, 0.37 [95% CI, 0.25-0.54]; P < 0.001). The number needed to treat to prevent one severe exacerbation with as-needed BUD-FORM and BUD maintenance versus as-needed terbutaline were 20 and 34 in subgroup 1 and 13 and 12 in subgroup 2, respectively. Conclusions: These findings suggest that, for patients with mild asthma currently receiving short-acting β2-agonists alone, as-needed low-dose ICS-FORM should be preferred over maintenance ICS as initial controller treatment. For patients whose asthma is controlled on maintenance low-dose ICS, as-needed BUD-FORM is an alternative to maintenance ICS without the need for daily treatment, and both of these options are safer than switching to short-acting β2-agonist-only treatment.

Objective SYNTAX score II (SSII) is a long-term mortality prediction model to guide the decision making of the heart-team between coronary artery bypass grafting or percutaneous coronary intervention (PCI) in patients with left main or three-vessel coronary artery disease. This study aims to investigate the long-term predictive value of SSII for all-cause mortality in patients with one- or two-vessel disease undergoing PCI. Methods A total of 628 patients (76% men, mean age: 61±10 years) undergoing PCI due to stable angina pectoris (43%) or acute coronary syndrome (57%), included between January 2008 and June 2013, were eligible for the current study. SSII was calculated using the original SYNTAX score website (www.syntaxscore.com). Cox regression analysis was used to assess the association between continuous SSII and long-term all-cause mortality. The area under the receiver-operating characteristic curve was used to assess the performance of SSII. Results SSII ranged from 6.6 to 58.2 (median: 20.4, interquartile range: 16.1–26.8). In multivariable analysis, SSII proved to be an independent significant predictor for 4.5-year mortality (hazard ratio per point increase: 1.10; 95% confidence interval: 1.07–1.13; p<0.001). In terms of discrimination, SSII had a concordance index of 0.77. Conclusion In addition to its established value in patients with left main and three-vessel disease, SSII may also predict long-term mortality in PCI-treated patients with one- or two-vessel disease.

The decarbonisation of CaCO 3 was chemically performed upon reaction with NaOH solutions. The study highlighted convenient aspects for a further scale up since short residence times and low stirring rates led to high conversions.

The Continuous Strength Method provides excellent resistance predictions of stocky cross-sections under different loading conditions as it accounts for enhanced material properties, although the method is currently limited to crosssectional resistance. The axial stress in short columns potentially exceeds the yield strength as members are stable enough to allow partial yielding of non-slender cross-sections and the flexural buckling resistance prediction of these short columns is therefore usually underestimated, since equations currently codified in standards do not account for strain hardening effects. This paper presents the extension of the Continuous Strength Method to stainless steel Rectangular and Square Hollow Section columns, allowing strain hardening effects to be incorporated in the resistance prediction of members subjected to compression. The proposed approach is equivalent to the traditional approach for columns codified in different standards based on the Ayrton-Perry formulation but considers a different generalized imperfection parameter that depends on the cross-sectional slenderness and considered material, so strain hardening effects are directly introduced in the formulation. Results show that the proposed Continuous Strength Method approach provides improved predictions of the resistance of Rectangular and Square Hollow Section columns for all stainless steel grades. The reliability of the proposed approach has been demonstrated through the corresponding statistical analyses. Given the purely analytic nature of the proposed approach, it can be used for several materials, such as stainless steel, carbon steel and aluminium, and cross-section types for which the Continuous Strength Method has been defined. Finally, the better estimation of the flexural buckling behaviour of columns will have a direct impact on the accuracy of beam-column checks.

Objectives The aim of this study was to evaluate the use of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in “real-world” patients unsuitable for the alternative treatment. Background No data are available on the risk profile and outcomes of patients that can only undergo PCI or CABG. Methods In the SYNTAX (Synergy between PCI with TAXUS and Cardiac Surgery) trial, a multidisciplinary Heart Team reached a consensus on whether PCI and CABG could result in clinical equipoise; if so, the patient was randomized. If not, the patient was enrolled in a CABG-ineligible PCI registry or PCI-ineligible CABG registry. A proportion (60%) of patients in the CABG registry was randomly assigned to be followed up for 5 years. No statistical comparisons were performed between randomized and registry patients. Major adverse cardiac or cerebrovascular event (MACCE) rates are presented as observational only. Results A total of 3,075 patients were treated in the SYNTAX trial; 198 (6.4%) and 1,077 (35.0%) patients were included in PCI and CABG registries, respectively. The main reason for inclusion in the CABG registry was too complex coronary anatomy (70.9%), and the main reason for inclusion in the PCI registry was too high-risk for surgery (70.7%). Three-year MACCE was 38.0% after PCI and 16.4% after CABG. Stratification by SYNTAX score terciles demonstrated a step-wise increase of MACCE rates in both PCI and CABG registries. Conclusions The SYNTAX Heart Team concluded that PCI and CABG remained the only treatment options for 6.4% and 35.0% of patients, respectively. Inoperable patients with major comorbidities that underwent PCI had high MACCE rates. In patients not suitable for PCI, surgical results were excellent. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries, NCT00114972)

Fully bioresorbable Absorb poly-L-lactic-acid (PLLA) scaffolds (Abbott Vascular, Santa Clara, CA, USA) are a novel approach for the treatment of coronary narrowing. Due to the translucency of the material (PLLA), the optical coherence tomography (OCT) measurement methods used in the ABSORB trials were unique but not applicable for permanent metallic stents. When the Absorb scaffold and metallic stents are compared in the context of randomised trials, it is challenging to compare the two devices using the conventional methods. The primary purpose of this report is to explain the biases in conventional methodologies applied for metallic stents and for PLLA scaffolds at baseline and follow-up, and to propose a new standard methodology that enables us to compare two different devices using an almost identical and methodological language.A consensus amongst multiple core labs and expert researchers of OCT was reached on a new standard OCT measurement methodology that enables us to compare these two different devices. In brief, the proposed OCT methods are summarised as follows. 1) Both endoluminal and abluminal scaffold/stent contours should be traced. 2) Consistently, endoluminal and abluminal incomplete stent apposition areas should be measured. 3) The area occupied by scaffold/stent struts should be quantified directly or virtually. 4) The strut area should be systematically excluded from the flow area as well as the neointimal area. 5) Additional information on the degree of embedment could be reported using the interpolated lumen contour. Interobserver variability of the proposed method was excellent (intraclass correlation 0.89-100).A standardised OCT measurement methodology is proposed. This should be implemented in ongoing and future trials comparing the Absorb scaffolds and metallic stents.

A novel method for four-dimensional superficial wall strain and stress (4D-SWS) is derived from the arterial motion as pictured by invasive coronary angiography. Compared with the conventional finite element analysis of cardiovascular biomechanics using the estimated pulsatile pressure, the 4D-SWS approach can calculate the dynamic mechanical state of the superficial wall in vivo , which could be directly linked with plaque rupture or stent fracture. The validation of this approach using in silico models showed that the distribution and maximum values of superficial wall stress were similar to those calculated by conventional finite element analysis. The in vivo deformation was validated on 16 coronary arteries, from the comparison of centerlines predicted by the 4D-SWS approach against the actual centerlines reconstructed from angiograms at a randomly selected time-point, which demonstrated a good agreement of the centerline morphology between both approaches (scaling: 0.995 ± 0.018 and dissimilarity: 0.007 ± 0.014). The in silico vessel models with softer plaque and larger plaque burden presented more variation in mean lumen diameter and resulted in higher superficial wall stress. In more than half of the patients ( n = 16), the maximum superficial wall stress was found at the proximal lesion shoulder. Additionally, in three patients who later suffered from acute coronary syndrome, the culprit plaque rupture sites co-localized with the site of highest superficial wall stress on their baseline angiography. These representative cases suggest that angiography-based superficial wall dynamics have the potential to identify coronary segments at high-risk of plaque rupture and fracture sites of implanted stents. Ongoing studies are focusing on identifying weak spots in coronary bypass grafts, and on exploring the biomechanical mechanisms of coronary arterial remodeling and aneurysm formation. Future developments involve integration of fast computational techniques to allow online availability of superficial wall strain and stress in the catheterization laboratory.

<h3>Objective</h3> To compare vessel, lumen, and plaque volumes in atherosclerotic coronary lesions with inadequate compensatory enlargement versus lesions with adequate compensatory enlargement. <h3>Design</h3> 35 angiographically significant coronary lesions were examined by intravascular ultrasound (IVUS) during motorised transducer pullback. Segments 20 mm in length were analysed using a validated automated three dimensional analysis system. IVUS was used to classify lesions as having inadequate (group I) or adequate (group II) compensatory enlargement. <h3>Results</h3> There was no significant difference in quantitative angiographic measurements and the IVUS minimum lumen cross sectional area between groups I (n = 15) and II (n = 20). In group I, the vessel cross sectional area was 13.3 (3.0) mm² at the lesion site and 14.4 (3.6) mm² at the distal reference (p &lt; 0.01), whereas in group II it was 17.5 (5.6) mm² at the lesion site and 14.0 (6.0) mm² at the distal reference (p &lt; 0.001). Vessel and plaque cross sectional areas were significantly smaller in group I than in group II (13.3 (3.0)<i>v</i> 17.5 (5.6) mm², p &lt; 0.01; and 10.9 (2.8) <i>v </i>15.2 (4.9) mm², p &lt; 0.005). Similarly, vessel and plaque volume were smaller in group I (291.0 (61.0) <i>v</i> 353.7 (110.0) mm³, and 177.5 (48.4) <i>v</i> 228.0 (92.8) mm³, p &lt; 0.05 for both). Lumen areas and volumes were similar. <h3>Conclusions</h3> In lesions with inadequate compensatory enlargement, both vessel and plaque volume appear to be smaller than in lesions with adequate compensatory enlargement.

No abstract is provided for this article.