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Bellino S.,National Center | Tripiciano A.,National Center | Tripiciano A.,San Gallicano Institute | Picconi O.,National Center | And 30 more authors.
Retrovirology | Year: 2014

Background: Tat is a key HIV-1 virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. After release, extracellular Tat accumulates in tissues and exerts effects on both the virus and the immune system, promoting immune activation and virus spreading while disabling the host immune defense. In particular, Tat binds Env spikes on virus particles forming a virus entry complex, which favors infection of dendritic cells and efficient transmission to T cells via RGD-binding integrins. Tat also shields the CCR5-binding sites of Env rendering ineffective virus neutralization by anti-Env antibodies (Abs). This is reversed by the anti-Tat Abs present in natural infection or induced by vaccination.Findings: Here we present the results of a cohort study, showing that the presence of anti-Tat Abs in asymptomatic and treatment-naïve HIV-infected subjects is associated with containment of CD4+ T-cell loss and viral load and with a delay of disease progression. In fact, no subjects with high anti-Tat Ab titers initiated antiretroviral therapy during the three years of follow-up. In contrast, no significant effects were seen for anti-Env and anti-Gag Abs. The increase of anti-Env Ab titers was associated with a reduced risk of starting therapy only in the presence of anti-Tat Abs, suggesting an effect of combined anti-Tat and anti-Env Abs on the Tat/Env virus entry complex and on virus neutralization.Conclusions: Anti-Tat immunity may help delay HIV disease progression, thus, targeting Tat may offer a novel therapeutic intervention to postpone antiretroviral treatment or to increase its efficacy. © 2014 Bellino et al.; licensee BioMed Central Ltd.

Ensoli F.,San Gallicano Institute | Cafaro A.,National Center | Casabianca A.,Urbino University | Tripiciano A.,San Gallicano Institute | And 32 more authors.
Retrovirology | Year: 2015

Background: The phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks. Results: The vaccine was safe and well tolerated and induced anti-Tat Abs in most patients (79%), with the highest frequency and durability in the Tat 30 μg groups (89%) particularly when given 3 times (92%). Vaccination promoted a durable and significant restoration of T, B, natural killer (NK) cells, and CD4+ and CD8+ central memory subsets. Moreover, a significant reduction of blood proviral DNA was seen after week 72, particularly under PI-based regimens and with Tat 30 μg given 3 times (30 μg, 3x), reaching a predicted 70% decay after 3 years from vaccination with a half-life of 88 weeks. This decay was significantly associated with anti-Tat IgM and IgG Abs and neutralization of Tat-mediated entry of oligomeric Env in dendritic cells, which predicted HIV-1 DNA decay. Finally, the 30 μg, 3x group was the only one showing significant increases of NK cells and CD38+HLA-DR+/CD8+ T cells, a phenotype associated with increased killing activity in elite controllers. Conclusions: Anti-Tat immune responses are needed to restore immune homeostasis and effective anti-viral responses capable of attacking the virus reservoir. Thus, Tat immunization represents a promising pathogenesis-driven intervention to intensify HAART efficacy. © Ensoli et al.; licensee BioMed Central.

Maneschi F.,S. Maria Goretti Hospital | Ceccacci I.,S. Maria Goretti Hospital | Vestri A.,University of Rome La Sapienza | Pane C.,S. Maria Goretti Hospital | And 2 more authors.
Minerva Ginecologica | Year: 2011

Aim. The aim of this paper was to evaluate the feasibility, morbidity, and reproductive performance of fertile women undergoing minilaparotomic myomectomy for large uterine myomas. Methods. Ninety-nine consecutive women with symptomatic myomas underwent myomectomy through a skin incision ≤8 cm. Operative, postoperative and reproductive data were prospectively collected. Results. Median (range) age and Body Mass Index (BMI) were 37 years (23-44) and 23 (18-43), respectively. Median (range) myoma diameter was 7 cm (4-20), and the median number of myomas removed was 1 (range 1-31). Myomas were intramural in 76 (76%) cases. Median incision length was 7 cm (range 4-13) and median duration of surgery was 70 min (range 40-180). Operative time and length of skin incision were not correlated with the progressive number of interventions. An incision larger than 8 cm was necessary in 7 (7%) patients and the length of incision was significantly correlated with the diameter of the largest myoma (P<0.01).The feasibility of minilaparotomy was significantly reduced when the diameter of the largest myoma was >12 cm (P<0.05). Operative time was significantly longer in patients having >1 myoma (P<0.05). Three (3%) patients underwent blood transfusion. Median (range) postoperative stay was 2 days (range 2-12). Fever occurred in 8 (8%) patients, and wound complications in 5 (5%). Conclusion. Myomectomy by minilaparotomy is a feasible procedure in more than 90% of unselected patients with large symptomatic myomas. Feasibility is questionable when the myoma is >12 cm. This technique is a mini-invasive option to treat patients with large and multiple myomas.

Martinelli O.,University of Rome La Sapienza | Malaj A.,University of Rome La Sapienza | Gossetti B.,University of Rome La Sapienza | Bertoletti G.,S. Maria Goretti Hospital | And 2 more authors.
Journal of Vascular Surgery | Year: 2013

Thoracic aorta blunt injury (BAI) is a highly lethal lesion. A large number of victims die before obtaining emergency care. Thoracic endovascular aneurysm repair (TEVAR) is a less invasive method compared with open surgery and may change protocols for BAI treatment. This retrospective study was developed to evaluate the potential issues about thoracic endografting in the management of these patients. Twenty-seven patients with a BAI underwent aortic stent grafting. Intervention was preceded by the treatment of more urgent associated lesions in nine cases. In-hospital mortality was 7.4%. No paraplegia or ischemic complications developed because of the coverage of the left subclavian artery. In one case (3.2%), a type I endoleak was detected, proximal endograft infolding in two cases (7.4%) and endograft distal migration in further two cases were detected during follow-up (6-110 months). Thoracic endovascular aneurysm repair of BAI showed encouraging results in terms of perioperative mortality and morbidity. Concerns still remain about the potential mid- and long-term complications in younger patients. Copyright © 2013 by the Society for Vascular Surgery.

Benedetti Panici P.,University of Rome La Sapienza | Basile S.,Azienda Ospedaliero Universitaria Pisana | Salerno M.G.,Azienda Ospedaliero Universitaria Pisana | Di Donato V.,University of Rome La Sapienza | And 24 more authors.
American Journal of Obstetrics and Gynecology | Year: 2014

Objective The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer. In the attempt to identify the patients with poorer prognosis, the impact of age and body mass index were also thoroughly investigated by cancer-specific survival (CSS) analyses. Study Design Survival outcomes of trial patients were analyzed in relation to age (>65 years and >65 years) in the 2 arms (lymphadenectomy and no lymphadenectomy) and in the whole population of the trial. Results Univariate and multivariable analyses of CSS and overall survival (OS) of patients showed that age >65 years is a strong independent poor prognostic factor (5-y OS 92.1% and 78.4% in >65 years and >65 years patients, respectively, P <.0001; 5-y CSS 93.8% and 83.5% in >65 years and >65 years patients, respectively, P =.003). Among women >65 years, node negative patients had 94.4% 5-y OS and 96.3% 5-y CSS vs 74.3% 5-y OS and 74.3% 5-y CSS for node positive patients (P =.009 and P =.002, respectively), while among women >65 y, node negative patients had 75.7% 5-y OS and 83.6% 5-y CSS vs 74.1% 5-y OS and 83.3% 5-y CSS for node positive patients (P =.55 and P =.58, respectively). Univariate and multivariable survival analyses in the whole trial population showed that older age, and higher tumor grade and stage were significantly associated to a worse prognosis. Conclusion Older women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy, and, unexpectedly, irrespective of the presence of nodal metastasis. Only in older patients was obesity (body mass index >30) significantly associated with scarce prognosis. © 2014 Mosby, Inc. All rights reserved.

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