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Verona, Italy

Ricci R.P.,San Filippo Neri Hospital | Pignalberi C.,San Filippo Neri Hospital | Landolina M.,Fondazione Policlinico S. | Santini M.,San Filippo Neri Hospital | And 10 more authors.
Heart | Year: 2014

Objective: Inappropriate implantable cardioverter defibrillators (ICD) therapies have been associated with multiple adverse effects, including worse quality of life and prognosis. We evaluated the possibility of predicting atrial fibrillation (AF)-related inappropriate ICD shocks through continuous monitoring of device diagnostics. Methods: 1404 ICD patients were prospectively followed in an observational research by 74 Italian cardiology centres. Device diagnostics stored daily information on AF duration and ventricular rate (VR) during AF. Uncontrolled VR was defined as mean VR>80 beats per minute (bpm) and maximum VR>110 bpm. Expert electrophysiologists reviewed the ventricular tachycardia/ventricular fibrillation (VT/VF) episodes electrograms, stored in the device memory, and classified appropriate detections, inappropriate detection mechanisms and ICD therapy outcomes. Results: Over a median follow-up of 31 months, 511 (36%) patients suffered spontaneous VT/VF, which were treated by ICD shocks in a subgroup of 189 (13%) patients. Inappropriate detections occurred in 232 (16%) patients, and inappropriate ICD shocks in 101 (7%) patients. AF was the cause of inappropriate shocks in 60 patients. AF caused 144 inappropriate shocks: 53% of all inappropriate shocks. The likelihood of experiencing AF-related inappropriate shocks was 2.4% at 1 year and 6% at 5 years. Uncontrolled VR during AF proved to be an independent predictor of AF-related inappropriate shocks (OR=3.02, p=0.006); an alarm set at a VR>90 bpm or 100 bpm was associated with prediction of AF-related inappropriate shocks with a sensitivity of 73% or 62%, respectively. Conclusions: AF is the most common cause of inappropriate shocks in ICD patients. Continuous remote monitoring of VR during AF would promptly and efficiently predict AF-related inappropriate shocks. Source

Balbi T.,S. Orsola Malpighi University Hospital | Ghimenton C.,Borgo Trento Hospital | Pasquinelli G.,S. Orsola Malpighi University Hospital | Foroni L.,University of Bologna | And 2 more authors.
American Journal of Forensic Medicine and Pathology | Year: 2011

We have investigated the morphology of the sinus node of the human cardiac conduction system. Until today the sinus node (SN) is described as a heterogeneous system composed of 2 types of cells, namely, P or pale and T or transitional cells which are immersed in the matrix around the sinus nodal artery. T cells are said to share characteristics of P cells and of peripheral working atrial myocardial cells. This study was carried out on autoptic and explanted specimens using histochemical, immunohistochemical, and electron microscopic methods.Our investigations show that SN tissue has a quite different cellular composition, ie, spherical and/or star-shaped cells organized in clusters with long cytoplasmic processes (type P), transitional cells, similar to myocytes but with a reduced number of sarcomeres (type T) and, finally, as yet not described in the literature, fibroblast-like cells with long bi-tripolar extensions contacting cells. Interestingly, SN is squared by connective and elastic fibers geometrically arranged. Immunohistochemistry shows that the 3 cell types of the SN node express mesenchymal markers revelatory of their embryological origin. Innervation appears to be more complex than previously thought; we identified a system of synaptophysin-positive cholinergic vesicles dependent on the sympathetic system and parasympathetic fibers expressing S100 protein.Overall results indicate that the SN has an unexpected, systematic architecture. Copyright © 2011 by Lippincott Williams & Wilkins. Source

Boni L.,Clinical Trials Coordinating Center | Taddei A.,University of Florence | Bencini L.,General Surgery and Surgical Oncology | Bernini M.,General Surgery and Surgical Oncology | And 11 more authors.
Clinical Cancer Research | Year: 2014

Purpose: hERG1 channels are aberrantly expressed in several types of human cancers, where they affect different aspects of cancer cell behavior. A thorough analysis of the functional role and clinical significance of hERG1 channels in gastric cancer is still lacking. Experimental Design: hERG1 expression was tested in a wide (508 samples) Italian cohort of surgically resected patients with gastric cancer, by immunohistochemistry and real-time quantitative PCR. The functional link between hERG1 and the VEGF-A was studied in different gastric cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in vivo in xenograft mouse models. Results: hERG1 was positive in69% of the patients and positivity correlated with Lauren's intestinal type, fundus localization of the tumor, G1-G2 grading, I and II tumor-node-metastasis stage, and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT-dependent regulation of the transcriptional activity of the hypoxia inducible factor. Treatment of immunodeficient mice xenografted with human gastric cancer cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired tumor growth more than single-drug treatments. Conclusion: Our results show that hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages; (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be exploited to identify a gastric cancer patients' group where a combined treatment with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed. © 2014 American Association for Cancer Research. Source

Ridolfi L.,Immunotherapy Unit | Bertetto O.,Le Molinette Hospital | Santo A.,Borgo Trento Hospital | Naglieri E.,Italian National Cancer Institute | And 10 more authors.
International Journal of Oncology | Year: 2011

Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization on the basis of center, ECOG PS, stage of disease and percentage of weight loss. Patients received gemcitabine (1000 mg/m 2) on days 1 and 8 + cisplatin (100 mg/m 2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm]. In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of 12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT arms, respectively. No differences in response were found in any subgroup analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log-rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most common grade ≥3 adverse events were gastrointestinal toxicity (mainly nausea and diarrhea) and myelosuppression. No relevant differences in clinical outcome were observed from the addition of IL-2 to CT. Future studies investigating the role of T-regulators in chemoimmunotherapeutic regimens could be performed. Source

Catalano F.,Emergency Endoscopy Unit | Rodella L.,Emergency Endoscopy Unit | Lombardo F.,Emergency Endoscopy Unit | Silano M.,Human Nutrition and Health | And 5 more authors.
Gastric Cancer | Year: 2013

Background: A submucosal tumor (SMT) of the stomach, which is an occasional finding during routine upper gastrointestinal endoscopy, may pose diagnostic and therapeutic challenges. Methods: To assess whether endoscopic submucosal dissection (ESD) is a feasible approach to definitively cure SMTs, the authors performed a retrospective cohort study with two endoscopic italian centers. Results: The study consisted of 20 patients with SMTs who underwent ESD. The patients underwent ESD and were followed up by endoscopy. We analyzed complete resection rate, frequency of complications, and survival. The overall rate of R0 resection was 90 % (18/20), with two endoscopic failures, one for a submucosal tumor and one for a neoplasm deeply infiltrating the proper muscle layer. The median procedure time was 119.1 min (range 40-240 min). The median size of the resected specimens was 29 mm (range 15-60 mm). Perforation occurred in 3 patients; all were treated conservatively. There were no cases of severe bleeding. Based on histopathological findings, 6 cases of ectopic pancreas, 1 of ectopic spleen, 3 of leiomyoma, and 10 of gastrointestinal stromal tumor (GIST) were diagnosed. Complete resection was obtained in all GIST cases. Among the 10 GIST cases treated by ESD, no death occurred: the 5-year disease-specific survival rate was 100 %. Conclusions: The high success rate of 90 % and the low incidence of complications should indicate ESD is the correct diagnostic and definitive treatment in selected patients. © 2012 The International Gastric Cancer Association and The Japanese Gastric Cancer Association. Source

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