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Background Ticagrelor is a reversibly binding, direct-acting, oral, P 2 Y 12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction. Methods To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart. Discussion Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes. Trial registration EudraCT No. 2016–004746-28 . No.  NCT02701140 .  Trial status Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019. Trial sponsor Fondazione Policlinico Universitario A. Gemelli – Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.

Purpose To prospectively compare changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) in multivessel coronary artery disease (MVCAD) patients undergoing incomplete revascularization (IR) versus complete revascularization (CR) by coronary artery bypass grafting (CABG). Methods Seven male patients (age 68 ± 9 years) with MVCAD underwent myocardial perfusion PET/CT with [13N]ammonia before and at least 4 months after CABG. Segmental resting and stress MBF as well as MFR were measured. Resting and during stress left ventricle ejection fraction (LVEF) were also calculated. Results Three patients (43%) underwent CR and four (57%) IR. Among 119 myocardial segments, 101 (85%) were revascularized, and 18 (15%) were not. After CABG, stress MBF (mL/min/gr) and MFR are significantly increased in all myocardial segments, with a greater increase in the revascularized segments ( p  = 0.013). In both groups, LVEF significantly decreased during stress at baseline PET ( p  = 0.04), but not after CABG. Conclusion Stress MBF and MFR significantly improve after CABG in both revascularized and not directly revascularized myocardial segments. IR strategy may be considered in patients with high surgical risk for CR.

Background: Polycomb group (PcG) proteins are histone modifiers known to transcriptionally silence key tumour suppressor genes in multiple human cancers. The chromobox proteins (CBX2, 4, 6, 7, and 8) are critical components of PcG-mediated repression. Four of them have been associated with tumour biology, but the role of CBX2 in cancer remains largely uncharacterised. Methods: Addressing this issue, we conducted a comprehensive and unbiased genotranscriptomic meta-analysis of CBX2 in human cancers using the COSMIC and Oncomine databases. Results: We discovered changes in gene expression that are suggestive of a widespread oncogenic role for CBX2. Our genetic analysis of 8013 tumours spanning 29 tissue types revealed no inactivating chromosomal aberrations and only 40 point mutations at the CBX2 locus. In contrast, the overall rate of CBX2 amplification averaged 10% in all combined neoplasms but exceeded 30% in ovarian, breast, and lung tumours. In addition, transcriptomic analyses revealed a strong tendency for increased CBX2 mRNA levels in many cancers compared with normal tissues, independently of CDKN2A/B silencing. Furthermore, CBX2 upregulation and amplification significantly correlated with metastatic progression and lower overall survival in many cancer types, particularly those of the breast. Conclusions: Overall, we report that the molecular profile of CBX2 is suggestive of an oncogenic role. As CBX2 has never been studied in human neoplasms, our results provide the rationale to further investigate the function of CBX2 in the context of cancer cells.

BackgroundNon-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) are caused often by destabilization of non-flow limiting inflamed coronary artery plaques. 18F-fluorodeoxyglucose (FDG) uptake with positron emission tomography/computed tomography (PET/CT) reveals plaque inflammation, while intracoronary optical coherence tomography (OCT) reliably identifies morphological features of coronary instability, such as plaque rupture or erosion. We aimed to prospectively compare these two innovative biotechnologies in the characterization of coronary artery inflammation, which has never been attempted before.MethodsOCT and FDG PET/CT were performed in 18 patients with single vessel coronary artery disease, treated by percutaneous coronary intervention (PCI) with stent implantation, divided into 2 groups: NSTEMI/UA (n = 10) and stable angina (n = 8) patients.ResultsPlaque rupture/erosion recurred more frequently [100% vs 25%, p = 0.001] and FDG uptake was greater [TBR median 1.50 vs 0.87, p = 0.004] in NSTEMI/UA than stable angina patients. FDG uptake resulted greater in patients with than without plaque rupture/erosion [1.2 (0.86–1.96) vs 0.87 (0.66–1.07), p = 0.013]. Among NSTEMI/UA patients, no significant difference in FDG uptake was found between ruptured and eroded plaques. The highest FDG uptake values were found in ruptured plaques, belonging to patients with NSTEMI/UA. OCT and PET/CT agreed in 72% of patients [p = 0.018]: 100% of patients with plaque rupture/erosion and increased FDG uptake had NSTEMI/UA.ConclusionFor the first time, we demonstrated that the correspondence between increased FDG uptake with PET/CT and morphology of coronary plaque instability at OCT is high.

Objective:To date, no common risk stratification system is available to predict the risk of surgical or percutaneous myocardial revascularisation in patients with coronary artery disease (CAD). Thus, we sought to assess the European System for Cardiac Operative Risk Evaluation (EuroSCORE) validity to predict in-hospital mortality after percutaneous coronary intervention (PCI).Design, setting and participants:EuroSCORE was prospectively and systematically assessed in 1173 consecutive patients undergoing PCI in a high-volume single centre between April 2005 and October 2006.Main outcome measure:The receiver-operating characteristics (ROC) curve was used to describe performance and accuracy of the EuroSCORE risk model for the prediction of in-hospital mortality after PCI.Results:The EuroSCORE model demonstrated an overall relation between EuroSCORE rank and the incidence of in-hospital mortality, showing consistency in predicting patient risk across many subgroups and levels of global risk. At multivariable logistic regression analysis the EuroSCORE value was an independent in-hospital mortality predictor (p = 0.002) together with left main disease (p = 0.005), procedural urgency (p = 0.001), ACC/AHA C type lesion (p = 0.02) and PCI failure (p = 0.01). The area under the ROC curve for the EuroSCORE system was 0.91 (95% CI 0.86 to 0.97), indicating a good ability of the model to discriminate patients at risk of dying during the index hospitalisation.Conclusion:The EuroSCORE risk model, already extensively validated for the prediction of early mortality following open-heart surgery, can also be efficiently utilised in the setting of PCI. The introduction of the EuroSCORE assessment in patients with documented CAD may help to improve the revascularisation strategy decision-making process.

Letter to the Editor

Background: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. Methods: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. Results: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas ( P <0.01). Gene amplification correlates with mRNA overexpression ( P <0.01), suggesting a functional role of this aberration. Conclusion: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours.

The catalytic activity of Ni–Rh on the synthesized BEA zeolite in carbon dioxide reforming of methane has been investigated. Catalysts were prepared using the incipient wetness impregnation method, with a total content of metals up to 5 wt%. Catalysts were characterized through XRD, TPR, N2 adsorption, SEM, AAS, TG/DSC analyses. The prepared Ni–Rh zeolites were tested for their catalytic activity at 700 °C, at atmospheric pressure, and at CH4/CO2 ratio of 1. Catalytic results showed that bimetallic based zeolites exhibit high activity (CH4 and CO2 conversion equal to 73 and 78, respectively) but monometallic Rh catalysts were the only one stable against coke formation.

Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.Optical coherence tomography (OCT) has been widely adopted in research on coronary atherosclerosis and adopted clinically to optimize percutaneous coronary intervention. In this Review, Jang and colleagues summarize this rapidly progressing field, with the aim of standardizing the use of OCT in coronary atherosclerosis.