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De Silvestri A.,Foundation IRCCS San Matteo Hospital | Colao G.,Careggi Hospital | Di Biagio A.,University of Genoa | Bruzzone B.,University of Genoa | And 4 more authors.
AIDS | Year: 2010

OBJECTIVE: To compare the emergence of drug-resistant HIV variants at failure of lamivudine (3TC)/tenofovir (TDF)-containing or emtricitabine (FTC)/TDF-containing HAART as a consequence of the different 3TC and FTC intracellular half-lives. DESIGN: Retrospective evaluation of 859 patients selected from an Italian HIV resistance database (Antiretroviral Resistance Cohort Analysis). METHODS: Patients were selected for analysis if treated with a HAART whose nucleoside/nucleotide reverse transcriptase inhibitor backbone was either 3TC/TDF or FTC/TDF; if they experienced a virological failure after at least 6 months of plasma HIV-RNA undetectability; and if HIV genotypes before treatment and at failure were available. Univariate and multivariate logistic regression analyses were done to detect predictors of resistance mutations emerging at failure. RESULTS: Of 714 patients failing with 3TC/TDF and 145 with FTC/TDF, 35.8 and 21.1% were in Centers for Disease Control and Prevention stage C, and 8.8 and 15.2% were on first-line HAART, respectively. At multivariate analysis, the emergence of K70R (P = 0.002), M184V (P = 0.031), T215F (P = 0.020) and Y181C (P = 0.005) was significantly more common in 3TC-treated than in FTC-treated patients, with an odds ratio of 4, 1.56, 1.89 and 3.84, respectively. CONCLUSION: Despite their close structural similarity, 3TC and FTC are associated with a significantly different rate of drug resistance at treatment failure when combined with TDF in HAART regimens independently of the third drug used. Copyright © 2010 Lippincott Williams & Wilkins.


Giaccardi M.,San Giovanni Of Dio Hospital | Del Rosso A.,San Giuseppe Hospital | Guarnaccia V.,San Giuseppe Hospital | Ballo P.,Santa Maria Annunziata Hospital | And 3 more authors.
Heart Rhythm | Year: 2016

Background Radiation exposure related to conventional tachyarrhythmia radiofrequency catheter ablation (RFCA) carries small but not negligible stochastic and deterministic effects on health. These effects are cumulative and potentially more harmful in younger individuals. Nonfluoroscopic mapping systems can significantly reduce the radiological exposure and in some cases it can completely eliminate it. Objective The aim of this study was to assess the safety, feasibility, and efficacy of a complete nonfluoroscopic approach for RFCA compared with ablation procedures performed under fluoroscopic guidance. Methods RFCA was performed in 442 consecutive patients (mean age 58 ± 19 years). The first 145 patients (group 1) were treated only under fluoroscopic guidance, and the following 297 patients (group 2) were treated using a nonfluoroscopic electroanatomic mapping system (EnSite Velocity). RFCA was completely performed without fluoroscopy in 255 of 297 patients in group 2 (86%). Results The acute success rate did not differ between group 1 and group 2 (97% vs 96%; P =.46), and there were no differences in either procedure time (87 ± 57 minutes vs 91 ± 52 minutes; P =.41) or complication rate. Fluoroscopic exposure in group 2 was significantly reduced in comparison with group 1 (14 ± 6 seconds vs 1159 ± 833 seconds; P <.0001). Conclusion Compared with the conventional fluoroscopic technique, the near-zero radiation (RX) approach provides similar outcomes and may significantly reduce or eliminate ionizing radiation exposure in RFCA. These reductions are achieved without altering the duration or compromising the safety and effectiveness of the procedure. © 2016 Heart Rhythm Society.


Bartoletti R.,University of Florence | Cai T.,Santa Chiara Regional Hospital | Nesi G.,University of Florence | Albanese S.,Santa Maria Annunziata Hospital | And 3 more authors.
World Journal of Urology | Year: 2014

Purpose: We aim to evaluate the role of biofilm-producing bacteria in the clinical response to antibiotic therapy among patients affected by chronic bacterial prostatitis (CBP). Methods: All patients attending our centre from January to December 2008 due to prostatitis-like symptoms with a positive Meares-Stamey test were enroled. The clinical symptoms were assessed according to the NIH-CPSI, and the bacterial strains isolated from the patients enroled were identified and tested for antibiotic sensitivity using cards of the Vitek II semi-automated System for Microbiology (BioMerieux). Quantitative bacterial slime production was assessed by the Christensen microwell assay. All patients were treated with fluoroquinolones for 4 weeks and reevaluated clinically and microbiologically after 3 months. Results: One hundred and sixteen patients were enroled, and 150 bacterial strains were isolated from all patients. About 85 % of these strains were strong or moderate biofilm producers. Patients with strong or moderate biofilm-producing bacteria had a higher NIH-CPSI symptom score than those without biofilm-producing bacteria (mean 17.6 ± 5.6 vs. 14.1 ± 3.3; p = 0.0009). At the follow-up, 68 patients (58.6 %) had negative microbiological tests, but only 11 (9.48 %) reported a reduction in NIH-CPSI score. Improvement of symptoms was found statistically significantly less frequent in patients with biofilm-producing bacteria than in those without (p = 0.03). Ultrastructural analysis showed cellular forms in active replication with aberrant morphology of unknown cause and confirmed strong slime production with consistent bacterial stratification. Conclusion: In our CBP population, biofilm-producing bacteria were commonly found and had a significant negative impact on the clinical response to antibiotic therapy. © 2013 Springer-Verlag Berlin Heidelberg.


Cai T.,Santa Chiara Regional Hospital | Wagenlehner F.M.E.,Justus Liebig University | Mondaini N.,University of Florence | D'Elia C.,Santa Chiara Regional Hospital | And 5 more authors.
BJU International | Year: 2014

Objective To investigate the effect of human papillomavirus (HPV) and Chlamydia trachomatis (Ct) co-infection on sperm concentration, motility and morphology, in a large cohort of young heterosexual male patients with chronic prostatitis-related symptoms. Patients and Methods Patients with chronic prostatitis-related symptoms, attending the same centre for sexually transmitted diseases from January 2005 and December 2010, were consecutively enrolled in this cross-sectional study. All patients underwent clinical and instrumental examination, microbiological cultures for common bacteria, DNA extraction, mucosal and serum antibodies evaluation for Ct, specific tests for HPV and semen analysis. The semen variables analysed were: volume; pH; sperm concentration; motility; and morphology. Subjects were subdivided in two groups: group A, patients with Ct infection alone and group B, patients with Ct and HPV co-infection. The main outcome measurement was the effect of Ct and HPV co-infection on the semen variables examined. Results Of 3050 screened patients, 1003 were enrolled (32.9%) in the study. A total of 716 (71.3%) patients were allocated to group A, and 287 (28.7%) to group B. Significant differences between the two groups were reported in terms of percentage of motile sperm (degrees of freedom [df] = 1001; t-test = 11.85; P < 0.001) and percentage of normal morphological forms (df = 1001; t-test = 7.18; P < 0.001), while no differences were reported in terms of semen volume or pH. According to World Health Organization thresholds for normal semen, 364 (50.8%) men in group A and 192 (66.8%) men in group B were subfertile (odds ratio = 1.95; 95% confidence interval 1.46-2.60; P < 0.001). No correlation between HPV genotype, mucosal IgA type and semen variables was found. Conclusion In a population of prostatitis-related symptoms attributable to Ct infection, co-infection with HPV has a significant role in decreasing male fertility, in particular with regard to sperm motility and morphology. © 2013 The Authors. BJU International © 2013 BJU International.


Mazzoli S.,Santa Maria Annunziata Hospital | Cai T.,University of Florence | Addonisio P.,Santa Maria Annunziata Hospital | Bechi A.,Santa Maria Annunziata Hospital | And 2 more authors.
European Urology | Year: 2010

Background: The impact of chronic prostatitis resulting from Chlamydia trachomatis infection on male fertility is controversial. Objective: To investigate the correlation between C. trachomatis infection and semen quality in young male patients affected by chronic prostatitis resulting from C. trachomatis infection and to evaluate the correlation between anti-C. trachomatis immunoglobulin (Ig) A against heat shock protein 60 (HSP60), heat shock protein 70 (HSP70), and semen parameters. Design, setting, and participants: All patients with clinical and instrumental diagnosis of chronic prostatitis underwent microbiological cultures for common bacteria, DNA extraction, mucosal and serum antibody evaluation for C. trachomatis, and semen parameter analysis. Western blot analysis of mucosal anti-C. trachomatis IgA was performed. Interventions: Subjects were split into two groups: Group A consisted of patients with chronic prostatitis resulting from common bacteria (uropathogens), and group B consisted of patients with chronic prostatitis resulting from C. trachomatis infection. Measurements: The relationship between C. trachomatis infection and semen parameters as well as the correlation among IgA levels, IgA characterisation, and semen analysis were determined. Results and limitations: We enrolled 1161 patients (mean age: 36.5 yr). Of these, 707 patients were placed in group A, and 454 were placed in group B. Significant statistical differences were reported between groups in terms of sperm concentration (p < 0.001), percentage of motile sperm (p < 0.001), and normal morphologic forms (p < 0.001). Strong correlations between mucosal anti-C. trachomatis IgA and sperm concentration (p < 0.001) and normal morphologic forms (p < 0.001) were reported. Correlations among positivity to HSP60, HSP70, and sperm concentration (p < 0.003) and normal morphologic forms (p < 0.001) were also reported. Conclusions: This study demonstrated the role of chronic prostatitis resulting from C. trachomatis in male fertility decrease, highlighting probable immunomediated damage to germinal cells because of C. trachomatis infections. © 2009 European Association of Urology.


Prignano F.,University of Florence | Pescitelli L.,University of Florence | Ricceri F.,University of Florence | Ermini A.,Santa Maria Annunziata Hospital | Lotti T.,University of Florence
Journal of the European Academy of Dermatology and Venereology | Year: 2012

Background Monoclonal gammopathies are haematological conditions characterized by the clonal proliferation of plasma cells which produce a monoclonal immunoglobulin that accumulates in the blood. They have already been reported during treatment with a range of drugs but never before during treatment with the anti-TNF-α treatments: adalimumab, etanercept and infliximab currently used in the therapy of moderate-severe psoriasis and psoriatic arthritis. Objective This is a case series describing the development of MGUS in psoriatic patients treated with anti-TNF-α. Methods Three hundred patients receiving an anti-TNF-α treatment for chronic plaque psoriasis or psoriatic arthritis in a clinical setting in Italy, These patients were screened through serum protein electrophoresis to investigate the possible development of MGUS. Results Eight patients were found to have developed monoclonal gammopathy of undetermined significance. The median treatment duration for the eight patients was 1 year with excessive IgG present in five patients, IgM accumulation in one patient and a double monoclonal component in two patients. Conclusion Our data suggest that there may be an association between anti-TNF-α therapy and development of MGUS. © 2011 European Academy of Dermatology and Venereology.


Cai T.,Santa Chiara Hospital | Mazzoli S.,Santa Maria Annunziata Hospital | Meacci F.,Santa Maria Annunziata Hospital | Nesi G.,University of Florence | And 3 more authors.
Oncology Reports | Year: 2011

The relationship between urothelial bladder cancer and high-risk human papillomaviruses (HR-HPV) is still a poorly understood entity, even if some studies have supposed a probably correlation. The aim of the present study was to assess the potential relationship between the presence of HR-HPV and non-muscle invasive urothelial bladder cancers (NMIBC). One hundred and thirty-seven subjects (78 patients affected by NMIBC and 59 controls) were recruited in this prospective study. HR-HPV DNA was evaluated both in urine and tumour tissues. Data from patients were compared with data from controls. The relationship between patients and controls, in terms of HR-HPV presence was performed. The relationship between all pathological data and HR-HPV presence in patient group was carried out. HR-HPV DNA in tissue was found in 27 of 78 (34.6%) tumour samples and in 6 of 59 (10.1%) specimens from TUR-P, with a statistically significant difference (p=0.0009; dF=1; χ2=10.98). HR-HPV DNA in urine was found in 36 of 78 (46.1%) samples obtained from patients, whereas in only 8 of 59 (13.5%) samples from controls (p<0.0001: dF=1; χ2=16.37). A statistical significant difference in terms of HR-HPV frequency between high-grade and low-grade urothelial bladder cancer, was found (p=0.032; RR=0.52 - 95% CI 0.27-0.93; OR=0.34 - 95% CI 0.13-0.90). In conclusion, this study highlights the correlation between urothelial bladder cancer and high-risk type HPV infection, suggesting the potential etiopathogenetic role of HR-HPV in urothelial bladder cancer development.


Calvani M.,University of Florence | Pelon F.,University of Florence | Comito G.,University of Florence | Taddei M.L.,University of Florence | And 9 more authors.
Oncotarget | Year: 2015

Stress has an emerging role in cancer and targeting stress-related β-adrenergic receptors (AR) has been proposed as a potential therapeutic approach in melanoma. Here we report that β3-AR expression correlates with melanoma aggressiveness. In addition, we highlight that β3-AR expression is not only restricted to cancer cells, but it is also expressed in vivo in stromal, inflammatory and vascular cells of the melanoma microenvironment. Particularly, we demonstrated that β3-AR can (i) instruct melanoma cells to respond to environmental stimuli, (ii) enhance melanoma cells response to stromal fibroblasts and macrophages, (iii) increase melanoma cell motility and (iv) induce stem-like traits. Noteworthy, β3-AR activation in melanoma accessory cells drives stromal reactivity by inducing pro-inflammatory cytokines secretion and de novo angiogenesis, sustaining tumor growth and melanoma aggressiveness. β3-ARs also play a mandatory role in the recruitment to tumor sites of circulating stromal cells precursors, in the differentiation of these cells towards different lineages, further favoring tumor inflammation, angiogenesis and ultimately melanoma malignancy. Our findings validate selective β3-AR antagonists as potential promising anti-metastatic agents. These could be used to complement current therapeutic approaches for melanoma patients (e.g. propranolol) by targeting non-neoplastic stromal cells, hence reducing therapy resistance of melanoma.


Gerlini G.,Santa Maria Annunziata Hospital | Sestini S.,Santa Maria Annunziata Hospital | Di Gennaro P.,University of Florence | Urso C.,Santa Maria Annunziata Hospital | And 2 more authors.
Clinical and Experimental Metastasis | Year: 2013

Electrochemotherapy (ECT) is a novel treatment for recurrent or in-transit unresectable melanoma metastases based on the administration of anti-neoplastic drugs followed by cancer cell electroporation. Whether ECT can also induce anti-tumour immunity is unclear. We addressed this issue investigating the presence of dendritic cells (DCs) in the inflammatory infiltrate of ECT-treated lesions. Biopsies from melanoma patients (n = 9) were taken before ECT (T0), at d7 and d14 after treatment and studied by immunofluorescence with DCs-related antibodies. Epidermal Langerin+ Langerhans cells (LCs) were the most represented subset before treatment. ECT induced a significant reduction in epidermal LCs number at d7 (p < 0.001), while they were completely replaced at d14. Similarly, the few LCs observed intermingled with metastatic melanoma cells at T0 decreased after treatment (p < 0.001), suggesting an ECT-induced activation of LCs. Consistently, at d1 after ECT (n = 3 patients), LCs were found to express CCR7, which mediates LCs migration to regional lymph nodes, and CD83, the typical DCs maturation marker. In contrast, plasmacytoid DCs (pDCs) were not present at T0, but significantly increased after ECT both in melanoma metastasis (p < 0.001) and perilesionally (p < 0.05). Similarly, CD1c + dermal DCs (dDCs), observed in low number before ECT, strongly increased at d7 and even more at d14 (p < 0.05 and p < 0.001, respectively). Notably, some dDCs expressed CD83. These data suggest that ECT promotes LCs migration from the tumour to draining lymph nodes and pDCs and dDCs recruitment at the site of the lesion. These findings may help to design new strategies of in situ DCs vaccination in cancer patients. © 2012 Springer Science+Business Media B.V.


Mazzoli S.,Santa Maria Annunziata Hospital
FEMS Immunology and Medical Microbiology | Year: 2010

The prevalence of inflammatory conditions of the prostate gland is increasing. In Italy, there is a high incidence of prostatitis (13.3%), also accompanied by prostatic calcifications. Cat NIH-II chronic bacterial prostatitis (CBPs) are the most frequent. Their aetiology theoretically involves the whole range of bacterial species that are able to form biofilms and infect prostate cells. The aim of our study was to isolate potential biofilm-producing bacteria from CBP patients, to evaluate their ability to produce in vitro biofilms, and to characterize intraprostatic bacteria and prostatic calcifications using scanning electron microscopy. The 150 clinical bacterial strains isolated from chronic prostatitis NIH-II patients were: 50 Enterococcus faecalis; 50 Staphylococcus spp.; 30 Escherichia coli; 20 gram-negative miscellanea. Quantitative assay of biofilm production and adhesion was performed according to the classic Christensen microwell assay. Isolates were classified as nonproducers, weak, moderate or strong producers. The majority of E. coli, gram-negative bacteria, Staphylococci and Enterococci strains were strong or medium producers: 63-30%, 75-15%, 46-36%, and 58-14%, respectively. Prostatic calcifications consisted of bacteria-like forms similar to the species isolated from biological materials and calcifications of patients. Our study proves, for the first time, that bacterial strains able to produce biofilms consistently are present in CBP. Additionally, prostatic calcifications are biofilm-related. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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