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Background/Introduction In patients with three-vessel coronary artery disease (CAD) and/or left main (LM) CAD, individual risk prediction plays a key role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Purpose The aim of this study was to assess whether these individualised revascularization decisions can be improved by applying machine learning (ML) algorithms and integrating clinical, biological, and anatomical factors. Methods The present study consisted of patients enrolled in the SYNTAX study, which is a randomized trial comparing PCI and CABG in patients with complex coronary artery disease. ML algorithms were used to develop a prognostic index for 5-year death, which was combined, in the second stage, with assigned treatment (PCI or CABG), and pre-specified effect-modifiers: disease type (3-vessel or LMCAD) and anatomical SYNTAX score. The model’s discriminative ability to predict the risk of 5-year death and treatment benefit between PCI and CABG was cross-validated in the SYNTAX trial (n=1800 patients) and externally validated in the CREDO-KYOTO registry (n=7362), and then compared to the original SYNTAX score II 2020 (SS2020). Results The gradient boosting ML model identified the top 10 prognostic factors at the time of decision making as: age, creatinine clearance, left ventricular ejection fraction, peripheral vascular disease, C-reactive protein, hemoglobin, HbA1c, glucose, systolic and diastolic pressure. The ML model performed best for predicting 5-year all-cause death with C-indexes of 0.78 (95% CI 0.75-0.81) in cross-validation and 0.77 (95% CI 0.76-0.79) in external validation. The ML model discriminated 5-year mortality better than the SS2020 in the external validation cohort (vs C-index 0.72 for SS2020, p <0.001) and identified heterogeneity in the treatment benefit of CABG versus PCI (Figure). Conclusions An ML-based approach for identifying individuals who benefit from CABG or PCI is feasible and effective. Implementation of this model in health care systems—trained to collect large numbers of parameters—may harmonize decision making.Figure

No abstract is provided for this article.

The Journal of the Pan African Thoracic Society (JPATS) is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Pulmonology (adult and pediatric), Critical Care, Sleep, Thoracic Surgery.

In many patients with mild asthma, the low frequency of symptoms and the episodic nature of exacerbations make adherence to regular maintenance treatment difficult. This often leads to over-reliance on short-acting β2-agonist (SABA) reliever medication and under-treatment of the underlying inflammation, with poor control of asthma symptoms and increased risk of exacerbations. The use of budesonide/formoterol 'as needed' in response to symptoms may represent an alternative treatment option for patients with mild asthma.The SYmbicort Given as needed in Mild Asthma (SYGMA) programme consists of two 52-week, double-blind, randomised, multicentre, parallel-group, phase 3 trials of patients aged 12 years and older with a clinical diagnosis of asthma for at least 6 months, who would qualify for treatment with regular inhaled corticosteroids (ICS). SYGMA1 aims to recruit 3750 patients who will be randomised to placebo twice daily (bid) plus as-needed budesonide/formoterol 160/4.5 μg, placebo bid plus as-needed terbutaline 0.4 mg, or budesonide 200 μg bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the superiority of as-needed budesonide/formoterol over as-needed terbutaline for asthma control, as measured by well-controlled asthma weeks; a secondary objective is to establish the noninferiority of as-needed budesonide/formoterol versus maintenance budesonide plus as-needed terbutaline using the same outcome measure. SYGMA2 aims to recruit 4114 patients who will be randomised to placebo bid plus as-needed budesonide/formoterol 160/4.5 μg, or budesonide 200 μg bid plus as-needed terbutaline 0.4 mg. The primary objective is to demonstrate the noninferiority of as-needed budesonide/formoterol over budesonide bid plus as-needed terbutaline as measured by the annualised severe exacerbation rate. In both studies, use of all blinded study inhalers will be recorded electronically using Turbuhaler® Usage Monitors.Given the known risks of mild asthma, and known poor adherence with regular inhaled corticosteroids, the results of the SYGMA programme will help to determine the efficacy and safety of as-needed budesonide/formoterol therapy in mild asthma. Patient recruitment is complete, and completion of the phase 3 studies is planned in 2017.ClinicalTrials.gov identifiers: NCT02149199 SYGMA1 and NCT02224157 SYGMA2. Registered on 16 May 2014 and 19 August 2014, respectively.

No abstract is provided for this article.

Background Renal impairment (RI) is associated with impaired prognosis in patients with coronary artery disease. Clinical and angiographic outcomes of patients undergoing percutaneous coronary intervention (PCI) with the use of drug-eluting stents (DES) in this patient population are not well established. Methods We pooled individual data for 5,011 patients from 3 trials with the exclusive and unrestricted use of DES (SIRTAX - N = 1,012, LEADERS - N = 1,707, RESOLUTE AC - N = 2,292). Angiographic follow-up was available for 1,544 lesions. Outcomes through 2 years were stratified according to glomerular filtration rate (normal renal function: GFR≥90 ml/min; mild RI: 90<GFR≥60 ml/min; moderate/severe RI GFR<60 ml/min). Results Patients with moderate/severe RI had an increased risk of cardiac death or myocardial infarction ([MI], OR 2.14, 95%CI 1.36–3.36), cardiac death (OR 2.21, 95%CI 1.10–4.46), and MI (OR 2.02, 95%CI 1.19–3.43) compared with patients with normal renal function at 2 years follow-up. There was no difference in cardiac death or MI between patients with mild RI compared to those with normal renal function (OR 1.10, 95%CI 0.75–1.61). The risk of target-lesion revascularization was similar for patients with moderate/severe RI (OR 1.17, 95%CI 0.70–1.95) and mild RI (OR 1.16, 95%CI 0.81–1.64) compared with patients with normal renal function. In-stent late loss and in-segment restenosis were not different for patients with moderate/severe RI, mild RI, and normal renal function. Conclusions Renal function does not affect clinical and angiographic effectiveness of DES. However, prognosis remains impaired among patients with moderate/severe RI.

Systemic and hemodynamic effects of nisoldipine, administered as a 4.5-μg/kg intravenous bolus over 3 minutes followed immediately by an infusion of 0.2 μg/kg/min over 30 minutes, were studied in 13 patients undergoing diagnostic catheterization for suspected coronary artery disease or follow-up catheterization after coronary angioplasty. Responses to the drug tended to be exaggerated in the first 8 minutes of the infusion, but thereafter produced a steady state, with heart rate increased by 14 ± 3% at 16 minutes and by 15 ± 3% at 24 minutes (p < 0.05), mean aortic pressure decreased 12 ± 2% and 13 ± 3% at the same times (p < 0.05) and coronary venous blood flow increased by 31 ± 5% and 34 ± 6% (p < 0.05). Myocardial oxygen consumption and the heart rate-systolic aortic pressure product were unchanged and cardiac output and stroke volume were significantly increased. Study during matched coronary sinus pacing produced similar trends. Nisoldipine is a potent coronary and peripheral vasodilator that maintains an increase in myocardial oxygen supply in excess of demand when given as an intravenous infusion.

In order to evaluate the role of calcium in the activation processes in eosinophils induced by platelet-activating factor (PAF), we investigated the changes in free cytoplasmatic Ca2+ concentration using fura-2. PAF causes a rapid and transitory rise of the intracellular free calcium ion concentration [( Ca2+]i) in purified guinea pig eosinophils of approx. 1000 nM above a basal level of 120.7 +/- 36.5 nM (n = 10). The effect was dose-related with a maximum rise at 1000 nM PAF and an EC50 of 17.4 nM and specifically inhibited by the PAF antagonist WEB 2086 with an IC50 of 95.5 nM. WEB 2086 did not affect either the leukotriene B4- or the fMet-Leu-Phe-induced elevation of [Ca2+]i. The response to PAF was dependent on external Ca2+ as it was significantly inhibited by EGTA (85.6 +/- 5.4%) and Ni2+ (95.8 +/- 2.1%) but not by the dihydropyridine antagonist nimodipine. We conclude that Ca2+ entry via receptor-operated Ca2+ channels may be involved in PAF-induced degranulation of eosinophils.