470 Percutaneous arterial closure devices and ultrasound-guided trans-femoral puncture observational investigation: insights from the PETRONIO registry

Abstract Aims To evaluate the safety of a single and combined use of ultrasound-guided femoral puncture (U) and percutaneous arterial closure devices (P) in femoral artery procedures (FAP) compared to fluoroscopic guidance (F) and manual compression (M) in a large radial-focused interventional centre. U and P, taken individually, have improved safety in femoral arterial access procedures compared to traditional techniques. Methods and results All FAP performed between July 2017 and December 2018 in our centre were divided into three phases: (i) control period with F and M mainly performed; (ii) phase out period where U and P were introduced; and (iii) intervention period where a 6-month expertise on the novel techniques was acquired. The overall population was further stratified into subgroups: F/M, U/M, F/P, and U/P. The primary study endpoint was in-hospital access site bleeding events (BE) according to the BARC criteria. The secondary endpoint was vascular site complications (VASC). 418 procedures (14%) out of 3025 were performed via FA access during the study period. The overall access-site in-hospital BE were 97 (23%). Decreasing rates of BE (phase 1: n = 46, 29%; phase 2: n = 38, 22% e phase 3: n = 13, 15%; P = 0.027) and VASC were observed during the three periods. BE occurred significantly more often in F/M group (F/M: n = 48; 32%; U/M: n = 12, 16%; F/P: n = 18, 21%; U/P: n = 19, 17%; P = 0.008). F/M subgroup was an independent predictor of BE both in multivariable analysis and propensity score matching analysis. Conclusions The introduction of ultrasound-guided femoral puncture and percutaneous arterial closure devices has reduced access site bleeding with a progressive improvement after the first 6 months learning period

Smoker's paradox in ST-elevation myocardial infarction: Role of inflammation and platelets.

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Sensitivity to Entrectinib Associated with a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer

In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib

Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes

Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration. PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p 15), the β coefficient of smoke on PRI was â\u88\u928.51 [â\u88\u9211.90 to â\u88\u925.11, p < 0.001] at baseline and â\u88\u923.41 [â\u88\u926.30 to â\u88\u920.51, p = 0.02] after 1 month. Hemoglobin was higher in smokers (13.8 ± 1.5 g/dL) than non-smokers (13.1 ± 1.7 g/dL, p < 0.001), but was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60) and at 1 month (Rho = 0.01, p = 0.80). Our analysis confirms that clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels

Favorable effect of glycoprotein IIbIIIa inhibitors among STEMI patients treated with primary PCI and incomplete ST resolution

Incomplete ST resolution after primary percutaneous coronary interventions (pPCI) in STEMI patients is a well known prognostic marker, associated with the occurrence of microvascular obstruction and increased mortality. The effects of the use of glycoprotein IIbIIIa inhibitors (GPIs) in this peculiar subset of high- risk patients is still unknown. The aim of the present study was to assess whether the GPIs administration would result in improved outcome in ST elevation myocardial infarction (STEMI) patients with incomplete ST resolution (ISTR). All consecutive STEMI patients who underwent pPCI at our hospital between 2005 and 2014 were enrolled (n = 2001). ST resolution was defined as incomplete with a < 70% resolution of initial ST shift. Mortality analyses were performed by Kaplan-Meier curves, multivariable analysis through Cox regressions and propensity matching score. The incidence of ISTR was 29% (n = 592). Among ISTR patients, GPIs use was an independent predictor of better prognosis (HR 0.39, 95% CI 0.16-0.96, p < 0.04). Propensity matched analysis confirmed that the use of GPIs was associated with a lower 30-day (6.1% vs 13.4%, p = 0.02) and 1-year (8.4% vs 15.1%, p = 0.045) mortality. STEMI patients treated with pPCI and presenting ISTR show a poor outcome. The use of GPIs in these patients is associated with improved survival at 30 days and at 1 year; the causes for these favorable effects remain speculative and could be related to the development and evolution of microvascular obstruction

Protocol of a multicenter international randomized controlled manikin study on different protocols of cardiopulmonary resuscitation for laypeople (MANI-CPR)

Introduction Out-of-hospital cardiac arrest is one of the leading causes of death in industrialised countries. Survival depends on prompt identification of cardiac arrest and on the quality and timing of cardiopulmonary resuscitation (CPR) and defibrillation. For laypeople, there has been a growing interest on hands-only CPR, meaning continuous chest compression without interruption to perform ventilations. It has been demonstrated that intentional interruptions in hands-only CPR can increase its quality. The aim of this randomised trial is to compare three CPR protocols performed with different intentional interruptions with hands-only CPR. Methods and analysis This is a prospective randomised trial performed in eight training centres. Laypeople who passed a basic life support course will be randomised to one of the four CPR protocols in an 8 min simulated cardiac arrest scenario on a manikin: (1) 30 compressions and 2 s pause; (2) 50 compressions and 5 s pause; (3) 100 compressions and 10 s pause; (4) hands-only. The calculated sample size is 552 people. The primary outcome is the percentage of chest compression performed with correct depth evaluated by a computerised feedback system (Laerdal QCPR). Ethics and dissemination . Due to the nature of the study, we obtained a waiver from the Ethics Committee (IRCCS Policlinico San Matteo, Pavia, Italy). All participants will sign an informed consent form before randomisation. The results of this study will be published in peer-reviewed journal. The data collected will also be made available in a public data repository. trial registration number NCT02632500