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Background: Interleukin (IL)‐10 is a pleiotropic cytokine with a broad spectrum of immunosuppressive and anti‐inflammatory effects. IL‐10 secretion from alveolar macrophages is defective in patients with asthma and lower concentrations of IL‐10 are found in bronchoalveolar lavage (BAL) from asthmatic patients than in normal control subjects. Reduced IL‐10 may result in exaggerated and more prolonged inflammatory responses in asthmatic airways. IL‐10 acting through the IL‐10 receptor (IL‐10R) stimulates the transcription factors STAT1 and STAT3. Methods: We investigated IL‐10 and IL‐10R expression in normal and asthmatic bronchial epithelium and BAL macrophages using reverse transcription‐polymerase chain reaction, immunohistochemistry and Western blotting. The functional effect of IL‐10 was examined using granulocyte–macrophage‐colony stimulating factor, enzyme‐linked immunosorbent assay and Western blotting for phosphorylated STAT1 and STAT3. Results: IL‐10 was not expressed in epithelial cells; furthermore these cells did not express the IL‐10R and had no functional response to exogenous IL‐10. Bronchial epithelial cells expressed variable levels of phosphorylated STAT1 and STAT3 with no change in expression between normal subjects and asthmatics. IL‐10 protein and IL‐10R expression was detected in alveolar macrophages from all subjects. Conclusion: Our study suggests that the bronchial epithelium is not a source of IL‐10 and cannot respond to exogenous IL‐10 because of a lack of IL‐10R expression.

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Despite successful primary percutaneous coronary intervention (PPCI), the incidence of heart failure (HF) following ST-elevation myocardial infarction (STEMI) remains high. We investigated using Trimethylamine N-oxide (TMAO), a gut microbiota-derived biomarker, to predict adverse functional left ventricular (LV) remodeling (FLVR) and/or diastolic dysfunction (DD), which are precursors of HF post-STEMI. This prospective, observational study enrolled 204 STEMI patients with multivessel coronary artery disease after PPCI. TMAO level was collected at the baseline and 3 months. An echocardiography was performed at the baseline and at 12 months. The primary endpoints were the number of patients developing Group 4 FLVR or ≥Grade II DD at 12 months. The median age was 65 [57.00, 76.00] and 39.7% were women. The primary endpoints occurred in 47 (23.0%) patients. Three months of TMAO can discriminate patients with/without ≥Grade II LV DD and FLVR Grade 4 with areas under the curve (AUC) of the ROC of 0.72 (95% CI: 0.63-0.81; p < 0.001) and 0.77 (95% CI: 0.63-0.91), respectively. Similar results were shown in the validation cohort of 31 patients. The addition of 3 months of TMAO to traditional risk factors significantly improved the AUCs from 0.675 to 0.736 for ≥Grade II DD and from 0.793 to 0.873 for FLVR Grade 4. In multivariable logistic regression, 3 months of TMAO was independently associated with ≥Grade II DD (OR: 1.29 (1.13-1.50), p < 0.001) and FLVR Grade 4 (OR: 1.28 (1.12-1.47), p < 0.001). Three months of TMAO is strongly associated with LV DD and adverse remodeling after STEMI and may help identifying such patients for early treatment.

The Svelte Stent Integrated Delivery System (IDS) is a novel fixed-wire thin-strut cobalt-chromium stent characterised by a very low entry profile. The aim of the present study is to evaluate the safety and the feasibility of the Svelte stent IDS implantation in humans.The present investigation is a prospective, multicentre non-randomised single-arm study. The primary endpoint was freedom from major adverse cardiac events (MACE) at 30 days post-procedure. Invasive follow-up was scheduled at six months post implantation. A total of 47 patients were enrolled and serial OCT imaging was performed in a subgroup of 18 patients. At the index procedure the lesion success rate was 97.9% (46 patients), the mean acute gain was 1.56 ± 0.43 mm with a mean minimum lumen diameter of 2.48 ± 0.43 mm. Post-implantation OCT imaging revealed a minimal mean prolapse area (0.10 ± 0.06 mm²), mean incomplete stent apposition area (0.12 ± 0.13 mm²) and mean intraluminal mass area (0.05 ± 0.03 mm²). Edge dissections were reported in eight cases (mean dissection width 0.17 ± 0.07 mm proximally and 0.25 ± 0.24 mm distally). At 30-day clinical follow-up, one case of myocardial infarction was reported. At six months, the angiographic mean in-stent late loss was 0.95 ± 0.76 mm. By OCT, a high percentage of struts was covered (97.6 ± 15.00 %) with a mean neointimal thickness of 0.31 ± 0.14 mm, all edge dissections were clinically silent and healed. Target lesion revascularisation (TLR) occurred in 11 patients (23.4%) and clinically driven TLR in three of these patients (6.4%). No cases of death or stent thrombosis were reported during the study.Implantation of the Svelte stent IDS was observed to be safe, feasible and associated with a low acute vascular injury and a high percentage of strut coverage at 6-month follow-up.

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<b>Introduction:</b> The SYGMA 1 &amp; 2 trials (NCT02149199; NCT02224157) showed as-needed budesonide/formoterol (BUD/FORM) was comparable to BUD maintenance in reducing exacerbation risk in mild asthma. <b>Aim:</b> To examine the efficacy of as-needed BUD/FORM and BUD maintenance for severe exacerbations using pooled data from SYGMA 1 &amp; 2. <b>Methods:</b> Mild asthma patients were randomised to placebo twice daily (bid) + as-needed BUD/FORM 200/6 µg (n=3366) or BUD 200 µg bid + as-needed terbutaline (BUD maintenance; n=3369). Treatment adherence, number and rate of severe exacerbations, time to first severe exacerbation and inhaled ICS load data were compared for these two treatments. <b>Results:</b> Mean maintenance adherence was 69.7% and 69.0% for as-needed BUD/FORM and BUD maintenance arms, respectively. As-needed BUD/FORM was comparable to BUD maintenance in number of severe exacerbations (294 vs 310), proportion of patients with severe exacerbations (7.4% vs 7.8%), as well as annual rate (0.096 vs 0.104; RR 0.93 [0.77, 1.11]; p=0.408) and time to first severe exacerbation (HR 0.94 [0.79, 1.12]; p=0.463) (figure). Total median daily ICS delivered dose was 78% lower with as-needed BUD/FORM (51.8 µg) compared with BUD maintenance (240.2 µg). <b>Conclusions:</b> In mild asthma, as-needed BUD/FORM provided comparable efficacy in reducing the risk of severe exacerbation to BUD maintenance with only 22% of the total median daily ICS dose.

This study was conducted to assess outcomes after percutaneous transluminal septal myocardial ablation (PTSMA) treatment in 131 patients (mean age 56 ± 16 years) with obstructive hypertrophic cardiomyopathy. In-hospital and follow-up complications as well as late PTSMA failure (defined as unsatisfactory clinical outcome and a significant residual outflow tract gradient, necessitating reintervention) were noted. Baseline clinical, echocardiographic, and PTSMA characteristics were examined as determinants of outcomes. Also, the effect of ethanol volume and the role of a learning curve were investigated. PTSMA was successful in 90% of the patients. In-hospital and follow-up cardiac events were noted in 20 patients, including cardiac death (in-hospital n = 4, follow-up n = 1), acute myocardial infarction due to ethanol leakage (n = 1), coronary dissection (n = 2), nonfatal cardiac tamponade (n = 1), and permanent pacemaker (n = 6) or cardiac defibrillator (in-hospital n = 4, follow-up n = 1) implantation. Late PTSMA failure was noted in 12 patients. All baseline characteristics were comparable between successful and failed PTSMA. Ethanol volume was related to peak creatinine kinase value (p <0.0001) but not to late PTSMA failure or greater need for pacemaker implantation. Late PTSMA failure occurred more frequently in PTSMA procedures performed in the early, less experienced time period (p <0.001). In conclusion, this study confirms that PTSMA, although effective, has a relatively high complication rate. Late PTSMA failure could not be predicted by baseline characteristics but could partially be explained by a learning-curve effect. This finding implies that PTSMA procedures should be restricted to experienced centers.

Patients with difficult asthma suffer chronic moderate to severe persistent asthma symptoms despite high doses of inhaled and oral corticosteroid therapy. These patients suffer a high level of treatment and disease related morbidity but little is known about the degree of airway inflammation in these patients.Fifty two patients were examined to assess levels of exhaled nitric oxide (NO) as a surrogate marker of inflammatory activity in this condition. From this group, 26 patients were defined with severe symptoms and current physiological evidence of reversible airway obstruction requiring high dose inhaled (> or = 2000 micrograms beclomethasone dipropionate (BDP) equivalent) or oral steroid therapy to maintain disease control.Exhaled NO levels were higher in subjects with difficult asthma (mean 13.9 ppb, 95% CI 9.3 to 18.5) than in normal controls (7.4 ppb, 95% CI 6.9 to 7.8; p < 0.002), but lower than levels in steroid naive mild asthmatics (36.9 ppb, 95% CI 34.6 to 39.3; p < 0.001). Prednisolone treated patients had higher exhaled NO levels than patients only requiring inhaled corticosteroids (17.5 ppb, 95% CI 11.1 to 24.0 versus 7.2 ppb, 95% CI 4.6 to 9.8; p = 0.016), suggesting greater disease severity in this group. Non-compliance with prednisolone treatment was observed in 20% of patients but this did not explain the difference between the treatment groups. Exhaled NO levels were closely correlated with symptom frequency (p = 0.03) and with rescue beta agonist use (p < 0.002), but they did not correlate with lung function.Exhaled NO may serve as a useful complement to lung function and symptomatology in the assessment of patients with chronic severe asthma, and in the control and rationalisation of steroid therapy in these patients.

Objectives This study sought to assess the extent and composition of atherosclerosis contributing to acute coronary syndrome events in women compared with men. Background Pathological studies suggest that plaque composition and burden may differ by sex. It is unclear whether sex impacts the extent, characteristics, and potential vulnerability of coronary plaques. Methods A total of 697 patients (24% women) with acute coronary syndromes were enrolled in the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Three-vessel multimodality intracoronary imaging (quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound [IVUS]) was performed after treatment of the culprit lesion(s). Events during a median 3.4-year follow-up were ascribed to recurrent culprit versus untreated nonculprit lesions. The authors performed a post hoc, sex-based subgroup analysis. Results Women were older and had more comorbid disease than men. By angiography, women had a similar number of angiographic culprit (p = 0.53) but fewer nonculprit (p = 0.05) lesions, and fewer vessels with nonculprit lesions (p = 0.048) compared with men even after multivariable adjustment (p = 0.002). By IVUS, women had fewer nonculprit lesions (p = 0.002), but similar plaque burden (PB) per lesion (55.6% vs. 55.3%; p = 0.35), and female sex was not predictive of severe (>70%) PB (p = 0.052). Plaque rupture was less common in women (6.6% vs. 16.3%; p = 0.002) even after adjusting for comorbidities (p = 0.004), as was the total necrotic core volume (p < 0.0001). The frequency of other plaque phenotypes was similar for men and women including pathological intimal thickening, thin-cap fibroatheromas (TCFA), and thick-cap fibroatheromas. Rates of major adverse cardiovascular events attributed to culprit and nonculprit lesions at 1-, 2-, and 3-year follow-up were not significantly different between men and women, although women were rehospitalized more frequently due to culprit lesion–related angina. For men, nonculprit lesion minimal lumen area ≤4.0 mm2, PB ≥70%, and TCFA predicted nonculprit MACE at 3 years, whereas for women, only TCFA and PB were predictive. Conclusions The PROSPECT study validates that despite having more comorbid risk factors than men, women have less extensive coronary artery disease by both angiographic and IVUS measures, and that lesions in women compared with men have less plaque rupture, less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA may also be a stronger marker of plaque vulnerability in women than men.

No abstract is provided for this article.

No abstract is provided for this article.