Publications

The ABSORB II trial is a prospective, randomized, active-controlled, single-blind, parallel two-arm, multicenter clinical trial. At that time, clinical evidence of the everolimus-eluting Absorb scaffold had been attained without the use of a comparator. There was a need to conduct a trial with the metallic comparator that was at that time the best-in-class drug-eluting stent. Angiography was documented prior to and after intracoronary administration of nitrate to assess vasomotion. Multiple matched angiographic views were used for the assessment of vasomotion and long-term luminal dimensions. For quantitative coronary angiography, preprocedural measurements did not differ between the two groups, whereas for quantitative intravascular ultrasound, both preprocedural vessel area and plaque area were larger in the metallic stent group than in the bioresorbable scaffold group. Rates of clinical device success and clinical procedural success were similar in the two treatment groups. The chapter tabulates the characteristics of patients and lesions at baseline.

To examine differences among participating countries in baseline characteristics, clinical practice, medication strategies and outcomes of patients randomized to coronary artery bypass grafting and percutaneous coronary intervention in the SYNTAX trial.In SYNTAX, centres in 18 different countries enrolled 1800 patients, of which 8 countries enrolled ≥80 patients, what was projected to be a large enough sample size to be included in the analysis. Baseline characteristics, practice patterns and clinical outcomes were compared between the USA (n = 245), the UK (n = 267), Italy (n = 197), France (n = 208), Germany (n = 179), Netherlands (n = 148), Belgium (n = 91) and Hungary (n = 83). The remaining patients from other participating countries were pooled together (n = 382).Five-year results demonstrated significantly different outcomes between countries. After adjustment, percutaneous coronary intervention patients in France had lower rates of major adverse cardiac and cerebrovascular events [hazard ratio (HR) = 0.60, 95% confidence interval (CI) 0.37-0.98], while the incidence of repeat revascularization was higher in Hungary (HR = 1.89, 95% CI 1.14-3.42). Coronary artery bypass grafting showed the lowest rate of repeat revascularization in the UK (HR = 0.32, 95% CI 0.12-0.85). There were numerous differences in the risk profile of patients between participating countries, as well as marked differences in surgical practice across countries in the use of blood cardioplegia (range 3.1-89.0%; P < 0.001), bilateral internal mammary artery usage (range 7.8-68.2%; P < 0.001) and off-pump procedures (range 3.9-44.4%; P < 0.001). Variation was also found for percutaneous coronary intervention in the number of implanted stents (range 4.0 ± 2.3 to 6.1 ± 2.6; P < 0.001) as well as for the entire stents length (range 69.0 ± 45.1 to 124.1 ± 60.9; P < 0.001). Remarkable differences were observed in the prescription of post-coronary artery bypass grafting medication in terms of acetylsalicylic acid (range 79.6-95.0%; P = 0.004), thienopyridine (6.8-31.1%; P < 0.001) and statins (41.3-89.1%; P < 0.001).Patient characteristics and clinical patterns are significantly different between countries, resulting in significantly different 5-year outcomes. This article presents specific data that can further improve outcomes in each country.NCT00114972.

Exhaled breath condensate analysis for noninvasive quantification of airway inflammation in asthma is a potentially useful research tool in children. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4, and Th1 cells, which secrete interferon (IFN)-γ, in asthma. We measured concentrations of IL-4 and IFN-γ in breath condensates of 37 children (11 normal, 12 steroid-naive, and 14 steroid-treated children with asthma). Exhaled IFN-γ was significantly lower in steroid-naive and steroid-treated children with asthma compared with normal control subjects (3.7 ± 0.2 versus 5.1 ± 0.4 pg/ml, p < 0.01 and 4.1 versus 5.1 pg/ml, p < 0.05). By contrast, mean exhaled IL-4 was elevated in asthma (53.7 ± 4.2 pg/ml) compared with normal children (35.7 ± 6.2 pg/ml, p < 0.05) and concentrations were lower with steroid treatment (37.5 ± 5.6 pg/ml, p < 0.05). Exhaled IL-4 was significantly lower in children with asthma on more than 600 μg inhaled steroid/day. The IL-4/IFN-γ ratio was significantly greater in children with asthma compared with control children and the children with asthma on inhaled steroid therapy. We have shown for the first time that IFN-γ and IL-4 can be assayed in exhaled breath condensate and shows an increased ratio of IL-4/IFN-γ, consistent with predominance of Th2 cells in airways of children with asthma. Exhaled breath condensate analysis may have a useful role in studying allergic inflammation in childhood asthma.

One of the major inducible cytokines secreted by mononuclear phagocytes is macrophage inflammatory protein 1 (MIP-1), which consists of two homologous polypeptides, MIP-1 alpha and MIP-1 beta. MIP-1 alpha possesses chemotactic and stimulatory activities for lymphocytes, eosinophils, and monocytes and may play a role in various pulmonary inflammatory conditions. We investigated the expression and release of MIP-1 alpha from human peripheral blood monocytes (PBM) and alveolar macrophages (AM) after stimulation with lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha, and interferon-gamma and the inhibitory effects of corticosteroids. LPS and IL-1 beta only enhanced MIP-1 alpha mRNA and protein in a dose- and time-dependent fashion. Dexamethasone (10(-9) to 10(-4) M) inhibited the basal and induced production and expression of MIP-1 alpha. In PBM, dexamethasone (10(-6) M) reduced LPS- and IL-1 beta-stimulated production of MIP-1 alpha protein by 50 and 63%, respectively, maximally at 24 h, whereas the inhibition of mRNA expression occurred maximally at 4 h. Similar trends were observed for AM. MIP-1 alpha mRNA decay was only slightly decreased in the presence of dexamethasone. Inhibition of LPS-induced MIP-1 alpha mRNA by dexamethasone was attenuated by the protein synthesis inhibitor cycloheximide, indicating the involvement of a protein intermediate. Corticosteroids are a potent inhibitor of IL-1 beta- and LPS-induced expression of MIP-1 alpha through mechanisms involving mainly inhibition of transcription and to a minor degree by reducing mRNA stability. Corticosteroids may be effective anti-inflammatory agents by preventing the expression of chemokines such as MIP-1 alpha.

Presently several new methods are being developed to recanalize obstructed arteries during catheterization. Intra-arterial high frequency ultrasonic imaging may be used as a guidance for these new techniques. Spark erosion is a new obstruction removal technology. Experiments have shown that this method can be applied in a selective way. An ultrasonic intra-arterial imaging system allows for the proper indication of the spark erosion catheter relative to the obstruction. The first in vitro results of this study illustrate that integration of catheter tip imaging and spark erosion is possible.

Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan–Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09–3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60–5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15–5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033). In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term.

&lt;i&gt;Background:&lt;/i&gt; Cigarette smoking is associated with decreased nitric oxide (NO) production and increased oxidative stress in the airways. Exhaled NO levels are not higher in asthmatic smokers than in healthy non-smokers, and the value of exhaled NO for diagnosing asthma in smokers has been questioned. &lt;i&gt;Objectives:&lt;/i&gt; To compare exhaled NO concentrations between healthy and steroid-naive and steroid-treated asthmatic smokers and non-smokers. To also assess the acute effect of cigarette smoking on exhaled NO and hydrogen peroxide (H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;) levels in asthmatic smokers. &lt;i&gt;Methods:&lt;/i&gt; Exhaled NO was measured by chemiluminescence and exhaled H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2 &lt;/sub&gt;spectrophotometrically. In 7 steroid-naive asthmatic smokers exhaled NO and H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2 &lt;/sub&gt;was measured both before and 15 min after smoking one cigarette. Data are given as median (range). &lt;i&gt;Results:&lt;/i&gt; Exhaled NO level was significantly higher in steroid-naive asthmatic smokers than in healthy smokers [7.7 (3.4–32.5) ppb vs. 3.2 (2.0–7.2) ppb, p &lt; 0.001]. Exhaled NO values were lower in smokers than in non-smokers both in healthy subjects and in steroid-naive asthmatic patients. Steroid-treated asthmatic smokers had a tendency for lower exhaled NO values [5.4 (1.7–12.0) ppb] compared to steroid-naive asthmatic smokers. Cigarette smoking caused an acute increase in exhaled H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2 &lt;/sub&gt;concentrations together with a decrease in exhaled NO concentration. &lt;i&gt;Conclusions:&lt;/i&gt; Our data suggest that an elevation in exhaled NO concentration is associated with asthma in smokers. This difference may be useful for diagnosing the disease in smokers, but its clinical value needs further evaluation. Acute increase in exhaled H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2 &lt;/sub&gt;concentrations suggests that smoking increases the oxidative stress in the asthmatic airways.

No abstract is provided for this article.