Ceresoli G.L.,Cliniche Humanitas Gavazzeni |
Zucali P.A.,Humanitas Cancer Center |
Mencoboni M.,Ospedale Villa Scassi |
Botta M.,Ospedale S. Spirito |
And 14 more authors.
British Journal of Cancer | Year: 2013
Background: The aim of this open label phase II study (NCT00407459) was to assess the activity of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab combined with pemetrexed and carboplatin in patients with previously untreated, unresectable malignant pleural mesothelioma (MPM). Methods: Eligible patients received pemetrexed 500 mg m-2, carboplatin area under the plasma concentration-time curve (AUC) 5 mg ml-1 per minute and bevacizumab 15 mg kg-1, administered intravenously every 21 days for six cycles, followed by maintenance bevacizumab. The primary end point of the study was progression-free survival (PFS). A 50% improvement in median PFS in comparison with standard pemetrexed/platinum combinations (from 6 to 9 months) was postulated.Results: Seventy-six patients were evaluable for analysis. A partial response was achieved in 26 cases (34.2%, 95% CI 23.7-46.0%). Forty-four (57.9%, 95% CI 46.0-69.1%) had stable disease. Median PFS and overall survival were 6.9 and 15.3 months, respectively. Haematological and non-haematological toxicities were generally mild; however, some severe adverse events were reported, including grade 3-4 fatigue in 8% and bowel perforation in 4% of patients. Three toxic deaths occurred. Conclusion: The primary end point of the trial was not reached. However, due to the limitation of a non-randomised phase II design, further data are needed before drawing any definite conclusion on the role of bevacizumab in MPM. © 2013 Cancer Research UK. All rights reserved.
Brignole M.,Arrhythmologic Center |
Botto G.L.,Ospedale S. Anna |
Mont L.,Hospital Clinic I Provincial |
Oddone D.,Arrhythmologic Center |
And 11 more authors.
Heart | Year: 2012
Objective: To evaluate the 2-year clinical improvement after 'Ablate and Pace' therapy and to identify the variables able to influence the efficacy of this therapy in patients with permanent atrial fibrillation (AF). Design: Prospective multicentre observational study. Setting: Cardiology departments of 19 general hospitals in Italy, Spain and Greece. Patients: 171 patients with drug-refractory severely symptomatic permanent AF considered for AV junction ablation. Interventions: Patients underwent AV junction ablation, received a right ventricular (RV) pacing or echo-guided cardiac resynchronisation (CRT) pacing and were followed-up to 24 months. Main outcome measures: Non-responders to Ablate and Pace therapy were defined those patients who, during the follow-up period had clinical failure (defined as death or hospitalisation due to heart failure, or worsening heart failure) or showed no improvement in their clinical condition. Results: Responders were 63% of RV-paced patients and 83% of CRT-paced patients. Another 27% showed no clinical improvement (7%) or worsened (20%) (nonresponders group). On multivariable Cox regression analysis, CRT mode and echo-optimised CRT were the only independent protective factors against nonresponse (HR=0.24, 95% CI 0.10-0.58, p=0.001 and HR=0.22, 95% CI 0.07-0.77, p=0.018 respectively). On comparing freedom from non-response, a trend in favour of echo-optimised CRT versus simultaneous biventricular pacing (p=0.077) was seen. Conclusions In patients affected by severely symptomatic permanent AF, Ablate and Pace therapy yielded a clinical benefit in 63% of RV-paced patients and 83% of CRT-paced patients. CRT pacing and echooptimised CRT were the only independent predictor of clinical benefit.
PubMed | Ospedale Villa Scassi, Ospedale G. Bosco, Ospedale S. Croce e Carle, Casa Di Cura S. Maria and 6 more.
Type: Journal Article | Journal: European heart journal | Year: 2015
Through contemporary literature, the optimal strategy to manage coronary chronic total occlusions (CTOs) remains under debate.The aim of the Italian Registry of Chronic Total Occlusions (IRCTO) was to provide data on prevalence, characteristics, and outcome of CTO patients according to the management strategy.The IRCTO is a prospective real world multicentre registry enrolling patients showing at least one CTO. Clinical and angiographic data were collected independently from the therapeutic strategy [optimal medical therapy (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]; a comparative 1-year clinical follow-up was performed.A total of 1777 patients were enrolled for an overall CTO prevalence of 13.3%. The adopted therapeutic strategies were as follows: MT in 826 patients (46.5%), PCI in 776 patients (43.7%), and CABG in the remaining 175 patients (9.8%). At 1-year follow-up, patients undergoing PCI showed lower rate of major adverse cardiac and cerebrovascular events (MACCE) (2.6% vs. 8.2% and vs. 6.9%; P < 0.001 and P < 0.01) and cardiac death (1.4% vs. 4.7% and vs. 6.3%; P < 0.001 and P < 0.001) in comparison with those treated with MT and CABG, respectively. After propensity score-matching analysis, patients treated with PCI showed lower incidence of cardiac death (1.5 vs. 4.4%; P < 0.001), acute myocardial infarction (1.1 vs. 2.9%; P = 0.03), and re-hospitalization (2.3 vs. 4.4% P = 0.04) in comparison with those managed by MT.Our data showed how CTO PCI might significantly improve the survival and decrease MACCE occurrence at 1 year follow-up in comparison with MT and/or CABG.
PubMed | Centro Of Riferimento Oncologico Of Basilicata, Italian National Cancer Institute, Ospedale Villa Scassi, Mario Negri Institute for Pharmacological Research and 8 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017
LBA8005 Background: Second-line therapy for advanced NSCLC patients (pts) after progression on platinum-based regimens typically employs CT or E. Improved PFS in E-treated pts is associated with EGFR sensitizing mutations. However, a test for optimizing treatment in pts with wild-type or unknown EGFR mutation status or squamous histology is of clinical value. VeriStrat (VS) is a serum protein test that assigns good (VSG) or poor (VSP) classification and has demonstrated prognostic and predictive utility. PROSE is a multicenter prospective randomized biomarker validation trial, designed to evaluate the ability of VS to predict survival in second-line NSCLC pts treated with E or CT. It is the first completed prospective randomized biomarker validation trial following the MARVEL design (Freidlin et al. JNCI. 2010).285 pts, stratified by ECOG-PS, smoking, and blinded pretreatment VS classification, were randomized 1:1 to receive E or CT at standard doses. Primary endpoint was overall survival (OS) and the primary hypothesis was significant interaction between VS status and treatment. Sample size was calculated based on an estimated 65%/35% VSG:VSP ratio and hazard ratio (HR) for interaction of 2.35, with a 2-sided =0.05 and 90% power.285 pts were randomized and 263 (129 CT, 134 E) included in the per protocol primary analysis. 68% of pts in CT arm and 72% in E arm were classified as VSG. Analysis was performed at 226 events. The trial reached its primary objective of significant interaction between treatment and VeriStrat classification with an interaction p value of 0.037. Pts in the VSP group performed worse on E compared to CT (HR: 1.72, 95% CI: 1.08-2.74); there was no significant difference in OS between treatments in the VSG group (HR: 1.09, 95% CI:0.79-1.50). 194/198 pts with histologic diagnosis had tissue available for EGFR and KRAS mutations.The results suggest that VS status is predictive of differential OS benefit for E versus CT in second line setting, complementing the result from a retrospective analysis of NCIC BR.21 where the prognostic behavior of VS was established (Carbone et al. JTO. 2012).NCT00989690.
PubMed | Ospedale Villa Scassi, Ospedale Niguarda Ca Granda, Ospedale Generale Regionale, Arrhythmologic Center and 6 more.
Type: Journal Article | Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology | Year: 2016
The aim of this study was to determine the long-term effects and determinants of success of cardiac pacing in patients affected by reflex syncope enrolled in the Syncope Unit Project 2 (SUP 2) study. Initial results have validated the effectiveness of a standardized guideline-based algorithm which can be used in clinical practice in order to select suitable candidates for cardiac pacing.In this prospective, multicentre, observational study, patients aged >40 years, affected by severe unpredictable recurrent reflex syncope, underwent carotid sinus massage (CSM), followed by tilt testing (TT) if CSM was negative, followed by implantation of an implantable loop recorder (ILR) if TT was negative. Those who had an asystolic response to one of these tests received a dual-chamber pacemaker. Of 281 patients who met the inclusion criteria, 137 (49%) received a pacemaker and were followed up for a mean of 26 11 months: syncope recurred in 25 (18%) of them. At 3 years, the actuarial syncope recurrence rate was 20% [95% confidence interval (CI) 12-30] and was significantly lower than in 142 patients who did not receive a pacemaker and were observed by means of an ILR [43% (95% CI 29-57), P = 0.01]. The 3-year recurrence rate was not different among 78 CSM+, 38 TT+, and 21 ILR+ patients, whereas it was lower in 20 patients with negative TT [5% (95% CI 0-15)] than in 61 patients with positive TT [24% (95% CI 10-38)].The benefit of cardiac pacing is maintained at 3 years, irrespective of the index diagnostic test, and is maximum in patients with negative TT.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01509534.
Valgimigli M.,Erasmus University Rotterdam |
Calabro P.,The Second University of Naples |
Cortese B.,Ospedale FatebeneFratelli |
Frigoli E.,Cardiostudy |
And 12 more authors.
Journal of Cardiovascular Translational Research | Year: 2014
Early invasive management and the use of combined antithrombotic therapies have decreased the risk of recurrent ischaemia in patients with acute coronary syndrome (ACS) but have also increased the bleeding risk. Transradial intervention (TRI) and bivalirudin infusion compared to transfemoral intervention (TFI) or unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decrease bleeding complications in patients with ACS. To what extent, a bleeding preventive strategy incorporating at least one of these two treatment options translates into improved outcomes is a matter of debate. The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX study is a large-scale, multicenter, prospective, open-label trial, conducted at approximately 100 sites in Europe aiming to primarily assess whether TRI and bivalirudin infusion, as compared to TFI and UFH plus provisional GPI, decrease the 30-day incidence of death, myocardial infarction or stroke across the whole spectrum of ACS patients. © 2014 Springer Science+Business Media New York.
Gaggioli G.,Ospedale Villa Scassi |
Laffi M.,Ospedale Villa Scassi |
Montemanni M.,Medicina Del Lavoro |
Mocini A.,Ospedale Villa Scassi |
And 2 more authors.
Europace | Year: 2014
Aims Little is known regarding the overall prevalence of syncope in a population of workers and the risk of occurrence during working time. Methods and Results A total of 452 consecutive workers (mean age: 46 ± 9 years) were invited to answer an anonymous questionnaire. They had been employed for 22 ± 10 years for a total of 9765 years worked. In the cohort, 160 subjects (35%) reported a total of 465 episodes of syncope during their lives; 64 (14%) suffered a syncopal episode after the start of employment, but only 26 (5.7%) reported syncope at work, 7 (1.5%) having had 2 episodes, and 1 (0.2%) 3 episodes (total: 36 episodes). The risk of syncope during work was 4.6 times higher for those who had a prior history of syncope [18 of 138 (13%)] than for those who did not [8 of 314 (3%), P = 0.001]. The occurrence of syncope during work for the patients with a history of syncope was one syncopal episode in every 99 years worked and for those who had already had an episode during work, one episode in every 16 years worked. Only one patient experienced minor trauma as a consequence of syncope during work and three were referred to the emergency department. All patients continued their employment without any problems. Conclusion The prevalence of syncope during work is low and its impact is benign. The probability of syncope during work is higher for subjects with a history of syncope. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved. The Author 2013.
Crimi G.,Ospedale Villa Scassi |
Passerone G.,University of Genoa |
Rubartelli P.,Ospedale Villa Scassi
Catheterization and Cardiovascular Interventions | Year: 2011
Transcatheter aortic valve implantation (TAVI) is a highly effective procedure for selected patients who are at high risk for aortic valve replacement; however, the incidence of severe complications is still relevant. Coronary occlusion during TAVI is a life-threatening complication that requires immediate diagnosis and treatment. We report the case of an 87-years-old woman affected by severe aortic stenosis, symptomatic for refractory heart failure, who underwent urgent balloon aortic valvuloplasty and subsequent elective transapical aortic valve implantation. Valve deployment was complicated by cardiac arrest and hemodynamic collapse, and left main coronary artery occlusion was recognized and successfully recovered by balloon angioplasty and stent implantation. Patient is alive and well 6 months after procedure. © 2011 Wiley-Liss, Inc.
Zucali P.A.,Instituto Clinico Humanitas |
Giovannetti E.,VU University Amsterdam |
Destro A.,Instituto Clinico Humanitas IRCCS |
Mencoboni M.,Ospedale Villa Scassi |
And 13 more authors.
Clinical Cancer Research | Year: 2011
Purpose: The pemetrexed/platinum agent combination represents the standard of care in first-line treatment for malignant pleural mesothelioma (MPM). However, there are no established indicators of responsiveness that can be used to optimize the treatment. This retrospective study aimed to assess the role of excision repair cross-complementing group-1 (ERCC1) and thymidylate synthase (TS) in tumors, and correlate expression levels and polymorphisms of these key determinants of drug activity with the outcome of MPM patients treated with carboplatin/pemetrexed in first-line setting. Experimental design: Analysis of TS and ERCC1 polymorphisms, mRNA and protein expression was done by PCR and immunohistochemistry [with the H-score (histologic score)] in tumor specimens from 126 MPM patients, including 99 carboplatin-/pemetrexed-treated patients. Results: A significant correlation between low TS protein expression and disease control (DC) to carboplatin/pemetrexed therapy (P = 0.027), longer progression-free survival (PFS;P = 0.017), and longer overall survival (OS; P = 0.022) was found when patients were categorized according to median H-score. However, patients with the higher tertile of TS mRNA expression correlated with higher risk of developing progressive disease (P = 0.022), shorter PFS (P < 0.001), and shorter OS (P < 0.001). At multivariate analysis, the higher tertile of TS mRNA level and TS H-score confirmed their independent prognostic role for DC, PFS, and OS. No significant associations were found among ERCC1 protein expression, TS and ERCC1 polymorphisms, and clinical outcome. Conclusions: In our series of carboplatin-/pemetrexed-treated MPM patients, lowTS protein and mRNA levels were significantly associated to DC, improved PFS, and OS. Prospective trials for the validation of the prognostic/predictive role of TS in MPM patients treated with pemetrexed-based regimens are warranted. © 2011 AACR.
PubMed | University of Florence, Arrhythmologic Center, Ospedale Villa Scassi and Ospedale Generale regionale
Type: | Journal: Heart (British Cardiac Society) | Year: 2016
Most elderly patients affected by reflex vasodepressor syncope take one or more hypotensive drugs. The role of these drugs in causing syncope has not yet been established. We hypothesised that recurrence of syncope and presyncope can be reduced by discontinuing/reducing vasoactive therapy without increasing the risk of cardiovascular and neurological events.This randomised, parallel, prospective, trial was conducted from January 2014 to March 2016 in four general hospitals. Of 328 initially screened participants, 58 patients (mean (SD) age 7411years) affected by vasodepressor reflex syncope, which was reproduced by tilt testing (n=54) or carotid sinus massage (n=4), were randomised to stop/reduce vasoactive therapy or to continue it. Primary end point was recurrence of syncope, presyncope or adverse events (defined as stroke, cerebral transient ischaemic attacks, worsening heart failure, myocardial infarction).Of 58 patients who were randomised, 55 completed the trial. After 1month, systolic blood pressure was significantly higher in the stop/reduce group than in the continue group, in both supine (14113mmHg vs 12814mmHg; p=0.004) and standing (13313mmHg vs 12215mmHg; p=0.02) positions. During a mean follow-up of 137months, the primary combined end point occurred in seven stop/reduce patients (23%): three had syncope, three had presyncope and one had heart failure. Conversely, it occurred in 13 continue patients (54%): 10 had syncope, 2 had presyncope and 1 had cerebral transient ischaemic attack. The log-rank p value was 0.02 and the HR was 0.37 (95% CI 0.15 to 0.91).Recurrence of syncope and presyncope can be reduced by discontinuing/reducing vasoactive therapy in most elderly patients affected by reflex vasodepressor syncope.NCT01509534; EudraCT2013-004364-63; Results.