Policlinico Gemelli

Rome, Italy

Policlinico Gemelli

Rome, Italy
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Giani T.,University of Siena | Antonelli A.,University of Florence | Caltagirone M.,University of Pavia | Mauri C.,A Manzoni Hospital | And 23 more authors.
Eurosurveillance | Year: 2017

Extended-spectrum beta-lactamases (ESBLs), AmpCtype beta-lactamases (ACBLs) and carbapenemases are among the most important resistance mechanisms in Enterobacteriaceae. This study investigated the presence of these resistance mechanisms in consecutive non-replicate isolates of Escherichia coli (n = 2,352), Klebsiella pneumoniae (n = 697), and Proteus mirabilis (n = 275) from an Italian nationwide cross-sectional survey carried out in October 2013. Overall, 15.3% of isolates were non-susceptible to extended-spectrum cephalosporins but susceptible to carbapenems (ESCR-carbaS), while 4.3% were also non-susceptible to carbapenems (ESCR-carbaR). ESCR-carbaS isolates were contributed by all three species, with higher proportions among isolates from inpatients (20.3%) but remarkable proportions also among those from outpatients (11.1%). Most ESCRcarbaS isolates were ESBL-positive (90.5%), and most of them were contributed by E. coli carrying blaCTX-M group 1 genes. Acquired ACBLs were less common and mostly detected in P. mirabilis. ESCR-carbaR isolates were mostly contributed by K. pneumoniae (25.1% and 7.7% among K. pneumoniae isolates from inpatients and outpatients, respectively), with blaKPC as the most common carbapenemase gene. Results showed an increasing trend for both ESBL and carbapenemase producers in comparison with previous Italian surveys, also among outpatients. © 2017, European Centre for Disease Prevention and Control (ECDC). All rights reserved.


Vallasciani S.,Pediatric Urology Unit | Berrettini A.,Pediatric Urology Unit | Nanni L.,Policlinico Gemelli | Manzoni G.,Pediatric Urology Unit | Marrocco G.,Azienda Ospedaliera San Camillo Forlanini
Journal of Pediatric Urology | Year: 2013

Introduction: Acquired megalourethra (AMU) after repair of proximal hypospadias can be a serious complication. An observational retrospective study of its incidence among different types of repair was performed. Materials and methods: Clinical charts of patients operated on for proximal hypospadias were reviewed. Inclusion criteria: all primary hypospadias operated in 1991-2004, with the meatus positioned in proximal penile, scrotal or perineal position. Results: Of 770 hypospadias cases treated, 130 (16%) were proximal. Seventy-two patients (55%) were treated using preputial flaps: 36 with a tubularized preputial island flap (TIF) and 36 an onlay island flap (OIF). Fifty-eight patients (45%) underwent staged repairs: Belt-Fuquà (BF) in 18 and Bracka procedure in 40 cases. After a mean follow up of 16 years (range 6-19) the overall incidence of complications for each technique was: TIF 36%; OIF 33%; BF 25%; two-stage Bracka 7.5%. The most common complication encountered was neo-urethral fistula. AMU occurred in only 5 cases, none with associated distal urethral stenosis, all in the TIF and OIF groups, and all successfully treated by reduction re-do urethroplasty. Conclusion: A very small number of the patients operated using preputial island flaps techniques developed AMU. None of the staged repairs developed AMU, and this is the preferred choice in proximal hypospadias when the urethral plate requires division and/or substitution. All cases of AMU resolved after urethral tapering. © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.


Servidei T.,Catholic University of Rome | Meco D.,Catholic University of Rome | Trivieri N.,Stemgen SPA | Patriarca V.,Catholic University of Rome | And 5 more authors.
International Journal of Cancer | Year: 2012

Some lines of evidence suggest that tumors, including ependymoma, might arise from a subpopulation of cells, termed cancer stem cells (CSCs), with self-renewal and tumor-initiation properties. Given the strict dependence of CSCs on epidermal growth factor (EGF) through EGF receptor (EGFR), we investigated the effects of EGFR inhibitors in ependymoma-stem cells (SCs) in vitro and in orthotopic mouse models. We established two ependymoma-SC lines from two recurrent pediatric ependymoma. Both lines expressed markers of radial glia-the candidate SCs of ependymoma-and showed renewal ability, multipotency, and tumorigenicity after orthotopic implantation, despite markedly different expression of CD133 (94 vs. 6%). High phosphorylated-EGFR/EGFR ratio was detected, which decreased after differentiation. EGFR inhibitors (gefitinib and AEE788) reduced clonogenicity, proliferation and survival of ependymoma-SC lines dose-dependently, and blocked EGF-induced activation of EGFR, Akt and extracellular signal-regulated kinase 1/2. Overall, AEE788 was more effective than gefitinib. EGFR blockade as well as differentiation strongly reduced CD133 expression. However, ex vivo treatment with AEE788 did not impair orthotopic tumor engraftment, whereas ex vivo differentiation did, suggesting that CD133 does not absolutely segregate for tumorigenicity in ependymoma-SCs. Orally administered AEE788 prolonged survival of mice bearing ependymoma-SC-driven orthotopic xenografts from 56 to 63 days, close to statistical significance (log-rank p = 0.06). Our study describes for the first time EGFR signaling in ependymoma-SCs and the effects of EGFR blockade in complementary in vitro and in vivo systems. The experimental models we developed can be used to further investigate the activity of EGFR inhibitors or other antineoplastic agents in this tumor. © 2011 UICC.


PubMed | Ospedale SantAntonio Abate, Ospedale di Bolzano., Ospedale Salesi, Ospedale Garibaldi and 47 more.
Type: Journal Article | Journal: Journal of pediatric surgery | Year: 2015

Our study aims at disclosing epidemiology and most relevant clinical features of esophageal atresia (EA) pointing to a model of multicentre collaboration.A detailed questionnaire was sent to all Italian Units of pediatric surgery in order to collect data of patients born with EA between January and December 2012. The results were crosschecked by matching date and place of birth of the patients with those of diagnosis-related group provided by the Italian Ministry of Health (MOH).A total of 146 questionnaires were returned plus a further 32 patients reported in the MOH database. Basing on a total of 178 patients with EA born in Italy in 2012, the incidence of EA was calculated in 3.33 per 10,000 live births. Antenatal diagnosis was suspected in 29.5% patients. 55.5% showed associated anomalies. The most common type of EA was Gross type C (89%). Postoperative complications occurred in 37% of type C EA and 100% of type A EA. A 9.5% mortality rate was reported.This is the first Italian cross-sectional nationwide survey on EA. We can now develop shared guidelines and provide more reliable prognostic expectations for our patients.


Uccioli L.,University of Rome Tor Vergata | Giurato L.,University of Rome Tor Vergata | Ruotolo V.,University of Rome Tor Vergata | Ciavarella A.,S. Orsola Malpighi University Hospital | And 9 more authors.
International Journal of Lower Extremity Wounds | Year: 2011

This study evaluated the efficacy and tolerability of an autologous tissue-engineered graft-a 2-step HYAFF autograft-in the treatment of diabetic foot ulcers compared with standard care. In all, 180 patients with dorsal or plantar diabetic foot ulcers (unhealed for ≥1 month) were randomized to receive Hyalograft-3D autograft first and then Laserskin autograft after 2 weeks (n = 90; treatment group) or nonadherent paraffin gauze (n = 90; control group). Efficacy and adverse events were assessed weekly for 12 weeks, at 20 weeks, and at 18 months. The primary efficacy outcome was complete ulcer healing at 12 weeks. Wound debridement, adequate pressure relief, and infection control were provided to both groups. At 12 weeks, complete ulcer healing was similar in both groups (24% of treated vs 21% controls). A 50% reduction in ulcer area was achieved significantly faster in the treatment group (mean 40 vs 50 days; P =.018). Weekly percentage ulcer reduction was consistently higher in the treatment group. At 20 weeks, ulcer healing was achieved in 50% of the treated group as compared with 43% of controls. Dorsal ulcers had a 2.17-fold better chance of wound healing per unit time following autograft treatment (P =.047). In a subgroup with hard-to-heal ulcers, there was a 3.65-fold better chance of wound healing following autograft treatment of dorsal ulcers ( P =.035). Adverse events were similar in both groups. The study results demonstrated the potential of this bioengineered substitutes to manage hard-to-heal dorsal foot ulcers. © The Author(s) 2011.


Rubboli A.,Laboratorio Of Cardiologia Interventistica | Sciahbasi A.,Policlinico Casilino | Briguori C.,Clinica Mediterranea | Saia F.,Ospedale Universitario | And 17 more authors.
Journal of Invasive Cardiology | Year: 2013

The in-hospital management of patients on warfarin undergoing coronary stent implantation (PCI-S) is variable, and the in-hospital outcome incompletely defined. To determine the adherence to the current recommendations, and the incidence of adverse events, we carried out the prospective, multicenter, observational WARfarin and coronary STENTing (WAR-STENT) registry (ClinicalTrials.gov identifier NCT00722319). All consecutive patients on warfarin undergoing PCI-S at 37 Italian centers were enrolled and followed for 12 months. Outcome measures were: major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, need for urgent revascularization, stroke, and venous thromboembolism, and major and minor bleeding. In this paper, we report the in-hospital findings. Out of the 411 patients enrolled, 92% were at non-low (ie, moderate or high) thromboembolic risk. The radial approach and bare-metal stents were used in 61% and 60% of cases, respectively. Drug-eluting stents were essentially reserved to patients with diabetes, which in turn, significantly predicted the implantation of drug-eluting stents (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.29-3.17; P≤.002). The in-hospital MACE and major bleeding rates were 2.7% and 2.1%, respectively. At discharge, triple therapy (TT) of warfarin, aspirin, and clopidogrel was prescribed to 76% of patients. Prescription of TT was significantly more frequent in the non-low thromboembolic risk group. Non-low thromboembolic risk, in turn, was a significant predictor of TT prescription (OR, 11.2; 95% CI, 4.83-26.3; P<.0001). In conclusion, real-world warfarin patients undergoing PCI-S are largely managed according to the current recommendations. As a consequence, the risk of in-hospital MACE and major bleedings appears limited and acceptable.


Ferrari G.,Ospedale San Giovanni Bosco | Milan A.,University of Turin | Groff P.,Policlinico S. Orsola Malpighi | Pagnozzi F.,Ospedale San Giovanni Bosco | And 3 more authors.
Journal of Emergency Medicine | Year: 2010

Background: Both non-invasive continuous positive airway pressure (nCPAP) and non-invasive pressure support ventilation (nPSV) have been shown to be effective treatment for acute cardiogenic pulmonary edema (ACPE). In patients with severe ACPE who are treated with standard medical treatment, the baseline intubation rate is approximately 24%. Study Objective: This study was conducted to compare the endotracheal intubation (ETI) rate using two techniques, nCPAP vs. nPSV. In addition, mortality rate, improvement in gas exchange, duration of ventilation, and hospital length of stay were also assessed. Methods: This prospective, multi-center, randomized study enrolled 80 patients with ACPE who were randomized to receive nCPAP or nPSV (40 patients in each group) via an oronasal mask. Inclusion criteria were severe dyspnea, respiratory rate > 30 breaths/min, use of respiratory accessory muscles, or PaO2/FiO 2 < 200. Results: ETI was required in 0 (0%) and in 3 (7.5%) patients in the nCPAP group and in the nPSV group, respectively (p = 0.241). No significant difference was observed in in-hospital mortality: 2 (5%) vs. 7 (17.5%) in nCPAP and nPSV groups, respectively (p = 0.154). No difference in hospital length of stay was observed between the two groups, nor was there a difference observed in duration of ventilation, despite a trend for reduced time with nPSV vs. nCPAP (5.91 ± 4.01 vs. 8.46 ± 7.14 h, respectively, p = 0.052). Both nCPAP and nPSV were effective in improving gas exchange, including in the subgroup of hypercapnic patients. Conclusions: Both methods are effective treatment for patients with ACPE. Non-invasive CPAP should be considered as the first line of treatment because it is easier to use and less expensive than non-invasive PSV. © 2010 Elsevier Inc.


Galeano F.,Laboratorio Of Rna Editing | Rossetti C.,Laboratorio Of Rna Editing | Tomaselli S.,Laboratorio Of Rna Editing | Cifaldi L.,Laboratorio Of Rna Editing | And 8 more authors.
Oncogene | Year: 2013

Grade IV astrocytoma or glioblastoma multiforme (GBM) is one of the most aggressive and lethal tumors affecting humans. ADAR2-mediated A-to-I RNA editing, an essential post-transcriptional modification event in brain, is impaired in GBMs and astrocytoma cell lines. However, the role of ADAR2 editing in astrocytomas remains to be defined. Here, we show that ADAR2 editing rescue in astrocytomas prevents tumor growth in vivo and modulates an important cell cycle pathway involving the Skp2/p21/p27 proteins, often altered in glioblastoma. We demonstrate that ADAR2 deaminase activity is essential to inhibit tumor growth. Indeed, we identify the phosphatase CDC14B, which acts upstream of the Skp2/p21/p27 pathway, as a novel and critical ADAR2 target gene involved in glioblastoma growth. Specifically, ADAR2-mediated editing on CDC14B pre-mRNA increases its expression with a consequent reduction of the Skp2 target protein, as shown both in vitro and in vivo. We found that, compared to normal brain, both CDC14B editing and expression are progressively impaired in astrocytomas from grade I to IV, being very low in GBMs. These findings (1) demonstrate that post-transcriptional A-to-I RNA editing might be crucial for glioblastoma pathogenesis, (2) identify ADAR2-editing enzyme as a novel candidate tumor suppressor gene and (3) provide proof of principle that ADAR2 or its substrates may represent a suitable target(s) for possible novel, more effective and less toxic approaches to the treatment of GBMs. © 2013 Macmillan Publishers Limited All rights reserved.


Manila A.,University of Rome La Sapienza | Mariangela N.,Policlinico Gemelli | Libero L.,Policlinico Gemelli | Francesca G.,University of Rome La Sapienza | And 2 more authors.
Pediatric and Developmental Pathology | Year: 2014

The cone-rod homeobox (CRX) is a gene that belongs to the member of the orthodenticle homeobox (Otx) family, with important function in development and differentiation of retinal and pineal cells. Moreover, CRX appears to be specifically expressed in pineal tumors and retinoblastomas. We performed an immunohistochemical study on 91 pediatric and adult central nervous system tumors, plus 2 normal brain samples. Our results demonstrated that CRX is expressed not only in pineal parenchymal tumors and retinoblastoma, but also in a some medulloblastomas and supratentorial primitive neuroectodermal tumors. None of the glial tumors screened were positive for CRX. In conclusion, CRX could be useful in surgical neuropathology for the differential diagnosis of pineal region tumors, in particular to discriminate pineal tumors from glial tumors. © 2014 Society for Pediatric Pathology.


Meco D.,Catholic University | Servidei T.,Catholic University | Zannoni G.F.,Policlinico Gemelli | Martinelli E.,Catholic University | And 3 more authors.
Translational Oncology | Year: 2010

Medulloblastoma is the most frequent malignant pediatric brain tumor with a dismal prognosis in 30% of cases. We examined the activity of AEE788, a dual inhibitor of human epidermal receptor (HER) 1/2 and vascular endothelial growth factor receptor (VEGFR) 1/2, in medulloblastoma preclinical models. Established lines (Daoy and D283), chemoresistant (DaoyPt), and ectopically HER2-overexpressing (DaoyHER2) cells expressed diverse levels of total and activated AEE788 target receptors. In vitro, AEE788 inhibited cell proliferation (IC50 from 1.7 to 3.8 μM) and prevented epidermal growth factor- and neuregulin-induced HER1, HER2, and HER3 activation. Inhibition of Akt paralleled that of HER receptors. In vivo, AEE788 growth inhibited Daoy, DaoyPt, and DaoyHER2 xenografts by 51%, 45%, and 72%, respectively. Immunohistochemical analysis of mock- and HER2-transfected xenografts revealed that the latter showed, along with high HER2 expression, high VEGFR2 staining in tumor and endothelial cells and increased expression of the endothelial marker CD31. AEE788 reduced the activation of target receptors and angiogenesis. In 21 primary medulloblastoma, HER2 expression significantly correlated (P <. 01) with VEGFR2 r = 0.56) and VEGF (r = 0.61). In conclusion, AEE788 shows similar growth-suppressive activities in chemosensitive and chemoresistant medulloblastoma cells in vitro and in vivo. Ectopic HER2 overexpression sensitizes cells to AEE788 in vivo, but not in vitro, possibly through host-mediated processes. Together with the experimental data, the finding that HER2 positively correlates with VEGFR2 and VEGF in human medulloblastoma specimens indicates HER2-overexpressing medulloblastoma as the subset that most likely might benefit from AEE788 treatment. © 2010 Neoplasia Press, Inc. All rights reserved.

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