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Genova, Italy

Cenderello G.,Ospedali Galliera | De Maria A.,University of Genoa
Expert Review of Anti-Infective Therapy | Year: 2016

The goal of antiretroviral treatment (ART) in HIV-1 patients is immune reconstitution following control of viral replication. CD4+ cell number/proportions are a crude but essential correlate of immune reconstitution. Despite suppression of HIV replication, a fraction of ART-treated patients still fails to fully reconstitute CD4+ T cell numbers (immunological nonresponders, INRs). New drugs, regimens and treatment strategies led to increased efficacy, lower side effects and higher virological success rates in clinical practice. The multitude of described immune defects and clinical events accompanying INR opposed to the marginal effect of antiretroviral intensification or immunotherapy trials underline the need for continuing efforts at understanding the mechanisms that underlie INR. Here, we reassess INR definition, frequency, and the achievements of active clinical and translational research suggesting a shared definition for insufficient, partial and complete CD4+ cell number recovery thus improving homogeneity in patient selection and mechanism identification. © 2015 Taylor & Francis.

Bertagna F.,University of Brescia | Treglia G.,Catholic University of the Sacred Heart | Piccardo A.,Ospedali Galliera | Giovannini E.,Catholic University of the Sacred Heart | And 5 more authors.
Endocrine | Year: 2013

Thyroid incidental uptake is defined as a thyroid uptake incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for non-thyroid diseases. Aim of the study was to establish the prevalence and pathological nature of focal thyroid incidentalomas detected at F18-FDG-PET/CT in patients studied for oncological purposes and not for thyroid disease. Secondary end point was to establish a possible maximum standardised uptake value cut-off over which a malignant lesion should be suspected. We have retrospectively evaluated 49519 patients who underwent F18-FDG-PET/CT for oncologic purposes in three Nuclear Medicine Centres (N.1 = 11278, N.2 = 31076, N.3 = 7165). A focal incidental thyroid uptake was diagnosed in 729 (1.5 %) patients (287-39.4 % male and 442-60.6 % female; average age: 65.26). Of 729 thyroid incidentalomas 211 (28.9 %) underwent further investigation to determine the nature of the nodule; 124/211 (58.8 %) incidentalomas were benign, 72/211 (34.1 %) malignant, 4/211 (1.9 %) non-diagnostic at cytological examination in the absence of surgery and histological evaluation and 11/211 (5.2 %) were indeterminate at cytological examination. A centre-based receiver operating curve (ROC) analysis of the patients with a definitive diagnosis was performed to identify a SUVmax cut-off useful in differentiating benign from malignant incidentalomas. In the centre N.1 it was 4.8 (sensitivity = 95.7 %, specificity = 46.4 %, area under the curve = 0.758); 5.3 in the centre N.2 (sensitivity = 76.3 %, specificity = 72.5 %, area under the curve = 0.815); 7 in the centre N.3 (sensitivity = 57.1 %, specificity = 79.3 %, area under the curve = 0.627). F18-FDG-PET/CT thyroid incidentalomas are a relevant diagnostic reality which requires further investigations and clinical management especially considering that, despite mainly benign, approximately one third of focal thyroid uptakes are malignant. © 2012 Springer Science+Business Media New York.

Tunn U.W.,Facharztzentrum | Canepa G.,Ospedali Galliera | Kochanowsky A.,Urological Practice | Kienle E.,Medical Consultant
Prostate Cancer and Prostatic Diseases | Year: 2012

Background: Intermittent androgen deprivation (IAD) for prostate cancer was studied with the objective of reducing the side effects of treatment and potentially delaying the development of hormone resistance. There also appears to be a quality of life benefit during off-treatment intervals owing to the recovery of serum testosterone levels. Methods: In this multicentre European prospective randomised phase III trial EC507, testosterone serum concentrations were analysed in prostate cancer patients with PSA progression after radical prostatectomy. Patients were randomised to a continuous androgen deprivation (CAD) and IAD therapy using a 3-month depot with 11.25 mg leuprorelin acetate as microcapsule formulation. A complete IAD cycle comprises both a 6-month androgen deprivation therapy plus the off-treatment time (OTT). Results: Serum testosterone recovery was recorded in 109 patients during OTT in the IAD group. Testosterone recovery to baseline values was achieved in 79.3% during the first and in 64.9% during the second IAD cycle, respectively. Median time to testosterone normalisation was 100 days in the first and 115 days in the second cycle, respectively. No significant difference was observed up to 1000 days between IAD and CAD with regard to time to androgen-independent progression. This is the first prospective study of leuprorelin acetate 11.25 mg demonstrating normalisation of testosterone levels in the off-treatment period in patients undergoing IAD. Conclusions: The prerequisite of an IAD treatment is the testosterone recovery during off-treatment periods. In this study, in patients with PSA relapse after radical prostatectomy, a real achievement of intermittent castration with normalisation of testosterone levels during off-treatment periods could be confirmed. © 2012 Macmillan Publishers Limited All rights reserved.

Spirito P.,Ospedali Galliera | Boni L.,Clinical Trials Coordinating Center
European Heart Journal | Year: 2012

AimsThe recent American College of Cardiology and American Heart Association Guidelines on hypertrophic cardiomyopathy (HCM) have confirmed surgical myectomy as the gold standard for non-pharmacological treatment of obstructive HCM. However, during the last 15 years, an extensive use of alcohol septal ablation has led to the virtual extinction of myectomy programmes in several European countries. Therefore, many HCM candidates for myectomy in Europe cannot be offered the option of this procedure. The purpose of our study is to report the difficulties and results in developing a myectomy programme for HCM in a centre without previous experience with this procedure. Methods and resultsThe clinical course is reported of 124 consecutive patients with obstructive HCM and heart failure symptoms who underwent myectomy at a single European centre between 1996 and 2010. The median follow-up was 20.3 months (inter-quartile range: 3.940.6 months). No patients were lost to follow-up. A cumulative incidence of HCM-related death after myectomy was 0.8, 3.3, and 11.2 at 1, 5, and 10 years, respectively, including one operative death (procedural mortality 0.8). The left ventricular (LV) outflow gradient decreased from 95 ± 36 mmHg before surgery to 12 ± 6 mmHg at most recent evaluation (P < 0.001), with none of the patients having a significant residual LV outflow gradient. Of the 97 patients in New York Heart Association functional class IIIIV before surgery, 93 (96) were in class III at most recent evaluation (P < 0.001). ConclusionOur results show that the development of a myectomy programme at a centre without previous experience with this procedure is feasible and can lead to highly favourable clinical results. © 2012 The Author.

Pelosi G.,Italian National Cancer Institute | Pelosi G.,University of Milan | Rossi G.,Section of Pathologic Anatomy | Bianchi F.,IFOM | And 12 more authors.
Journal of Thoracic Oncology | Year: 2011

Introduction: More detailed typing of non-small cell lung cancer on small biopsy specimens is increasingly required, albeit sometimes demanding with morphology alone. Little, however, is known about the likelihood of immunohistochemistry (IHC)-assessed small biopsies to effectively parallel profiling and, hence, eventual diagnoses of surgical specimens. Methods: Sixty-three preoperative biopsies and the corresponding surgical specimens from 30 consecutive squamous cell carcinomas, 22 adenocarcinomas, 2 adenosquamous carcinomas, eight sarcomatoid carcinomas, and one yolk sac tumor were jointly evaluated semiquantitatively for cytokeratins 5/6 and 7, p63, thyroid transcription factor-1, and vimentin immunoreactivity. Surgical specimens were the gold standard for morphology and IHC. Results: Hierarchic clustering analysis of both surgical specimens and biopsies showed a nonrandom and overlapping distribution of the relevant markers, which closely correlated with each other and the diverse tumor categories, as confirmed by mosaic plot analysis. There were no differences in area under the curve-receiver operating characteristic curves for each marker between any two samples, with the exception of p63 that paralleled more effectively squamous cell carcinoma on biopsies than surgical specimens. Fifty-nine of 63 (94%) lesions were correctly classified by IHC on biopsy compared with 53 of 63 (84%) by revised morphology, with the predictive positive value being 97% for squamous cell carcinoma, 88% for adenocarcinoma, and 100% for sarcomatoid and adenosquamous carcinoma. Yolk sac tumor and three of eight sarcomatoid carcinomas, however, failed any diagnostic recognition. Conclusions: Diverse cell differentiation lineages of non-small cell lung cancer may be consistently detected by IHC in small biopsies, making the eventual typing of tumors effective in most cases. Copyright © 2011 by the International Association for the Study of Lung Cancer.

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