EDTA and Taurolidine affect Pseudomonas aeruginosa virulence in vitro: impairment of secretory profile and biofilm production onto peritoneal dialysis catheters

Introduction: peritoneal catheter-associated biofilm infection is reported to be the main cause of refractory peritonitis in peritoneal dialysis patients. The application of antimicrobial lock therapy, based on results on central venous catheters, may be a promising option also for treatment of biofilm-harboring peritoneal catheters. In this study, we investigated the effects of two lock solutions, EDTA and Taurolidine, on an “in-vitro” model of Pseudomonas aeruginosa biofilm-related peritoneal catheter infection. Materials and Methods: silicon peritoneal catheters were incubated for 24 h with a bioluminescent strain of P. aeruginosa. After washing, serial concentrations of Taurolidine (0.5, 0.25 and 0.125 %) and EDTA (2.5, 0.75 and 0.25 %), either alone or in combination, were applied for 24 h, once or twice, onto the contaminated catheters and then P. aeruginosa viability/persistence was evaluated in real time up to 120 h, by a Fluoroskan reader. Moreover, on selected supernatants from biofilm treated or not with EDTA and/or Taurolidine, High-Performance Liquid Chromatography-Mass (HPLC) analysis was performed to measure phenazine and pyocianine production. Results: Taurolidine alone or in combination with EDTA caused a significant decrease of bacterial load and biofilm persistence onto the contaminated catheters. The lock solution treatment did not lead to the sterilization of the devices; yet, it resulted in a substantial destructuration of the peritoneal catheter-associated P. aeruginosa biofilm. Moreover, HPLC analysis showed that the treatment of biofilm-harboring catheters with EDTA and Taurolidine deeply affected the secretion of some key virulence-related molecules by P. aeruginosa, such as phenazines and pyocianines. Discussion and conclusions: EDTA and Taurolidine affect the formation and persistence of P. aeruginosa biofilm onto peritoneal catheters; moreover, also the secretion of P. aeruginosa virulence factors is profoundly compromised. Future studies are needed to establish whether such lock solutions can be used to render peritoneal catheter-related infections more susceptible to antibiotic treatment, thus avoiding/reducing the onset of the antibiotic resistance phenomena

Marche

In Marche region 68% of women (aged 24-64) are screened regularly, meaning every 3 years. The analysis on cross-protective activity exercised by bivalent and quadrivalent vaccines shows that the bivalent vaccine could prevent more pre-cancerous lesions and cases of cervicocarcinoma than quadrivalent, and that the latter could prevent genital warts that are not prevented by bivalent. The major number of cases avoided by the bivalent make it possible to fully offset the cost savings related to warts associated with the quadrivalent vaccine. Furthermore, a cost-effectiveness analysis shows that, considering regional tariffs, the multiple cohort (12-year-old + 25-year-old women) vaccination strategy with a 90% coverage could prevent 18 cases of cervicocarcinoma and 8 related deaths more than the vaccination of only 12-year-old girls, and thus proves to be cost-effective (10,700 €/QALY)

International Benchmark Activity in the Field of Sodium Fast Reactors

Global interest in fast reactors has been growing since their inception in 1960 because they can provide efficient, safe, and sustainable energy. Their closed fuel cycle can support long-term nuclear power development as part of the world’s future energy mix and decrease the burden of nuclear waste. In addition to current fast reactors construction projects, several countries are engaged in intense R&D and innovation programs for the development of innovative, or Generation IV, fast reactor concepts. Within this framework, NINE is very actively participating in various Coordinated Research Projects (CRPs) organized by the IAEA, aimed at improving Member States’ fast reactor analytical simulation capabilities and international qualification through code-to-code comparison, as well as experimental validation on mock-up experiment results of codes currently employed in the field of fast reactors. The first CRP was focused on the benchmark analysis of Experimental Breeder Reactor II (EBR-II) Shutdown Heat Removal Test (SHRT-17), protected loss-of-flow transient, which ended in the 2017 with the publication of the IAEA-TECDOC-1819. In the framework of this project, the NINE Validation Process– developed in the framework of NEMM (NINE Evaluation Model Methodology) – has been proposed and adopted by most of the organizations to support the interpretation of the results calculated by the CRP participants and the understanding of the reasons for differences between the participants’ simulation results and the experimental data. A second project regards the CRP focused on benchmark analysis of one of the unprotected passive safety demonstration tests performed at the Fast Flux Test Facility (FFTF), the Loss of Flow Without Scram (LOFWOS) Test #13, started in 2018. A detailed nodalization has been developed by NINE following its nodalization techniques and the NINE validation procedure has been adopted to validate the Simulation Model (SM) against the experimental data of the selected test. The third activity deals with the neutronics benchmark of China Experimental Fast Reactor (CEFR) Start-Up Tests, a CRP proposed by the China Institute of Atomic Energy (CIAE) launched in 2018 the main objective of which is to improve the understanding of the start-up of a SFR and to validate the fast reactor analysis computer codes against CEFR experimental data. A series of start-up tests have been analyzed in this benchmark and NINE also proposed and organized a further work package focused on the sensitivity and uncertainty analysis of the first criticality test. The present chapter intends to summarize the results achieved using the codes currently employed in the field of fast reactor in the framework of international projects and benchmarks in which NINE was involved and emphasize how the application of developed procedures allows to validate the SM results and validate the computer codes against experimental data

Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial

Aprospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (RHDS) versus conventional chemotherapy with rituximab (CHOP-R) as firstline therapy in 134 high-risk follicular lymphoma patients aged <60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13- year estimates of 77.0% and 36.8% for complete remission versus no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (P<0.001), along with younger age (P=0.002) and female sex (P=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma

Puglia

In Puglia region 58% of women (aged 24-64) are screened regularly, meaning every 3 years. The analysis on cross-protective activity exercised by bivalent and quadrivalent vaccines shows that the bivalent vaccine could prevent more pre-cancerous lesions and cases of cervicocarcinoma than quadrivalent, and that the latter could prevent genital warts that are not prevented by bivalent. The major number of cases avoided by the bivalent make it possible to fully offset the cost savings related to warts associated with the quadrivalent vaccine. Furthermore, a cost-effectiveness analysis shows that, considering regional tariffs, the multiple cohort (12-year-old + 25-year-old women) vaccination strategy with a 90% coverage could prevent 70 cases of cervicocarcinoma and 31 related deaths more than the vaccination of only 12-year-old girls, and thus proves to be cost-effective (9,935 €/QALY)

Calabria

In Calabria region 56% of women (aged 24-64) are screened regularly, meaning every 3 years. The analysis on cross-protective activity exercised by bivalent and quadrivalent vaccines shows that the bivalent vaccine could prevent more pre-cancerous lesions and cases of cervicocarcinoma than quadrivalent, and that the latter could prevent genital warts that are not prevented by bivalent. The major number of cases avoided by the bivalent make it possible to fully offset the cost savings related to warts associated with the quadrivalent vaccine. Furthermore, a cost-effectiveness analysis shows that, considering regional tariffs, the multiple cohort (12-year-old + 25-year-old women) vaccination strategy with a 90% coverage could prevent 37 cases of cervicocarcinoma and 17 related deaths more than the vaccination of only 12-year-old girls, and thus proves to be cost-effective (9,767 €/QALY)

Umbria

In Umbria region 85% of women (aged 24-64) are screened regularly, meaning every 3 years. The analysis on cross-protective activity exercised by bivalent and quadrivalent vaccines shows that the bivalent vaccine could prevent more pre-cancerous lesions and cases of cervicocarcinoma than quadrivalent, and that the latter could prevent genital warts that are not prevented by bivalent. The major number of cases avoided by the bivalent make it possible to fully offset the cost savings related to warts associated with the quadrivalent vaccine. Furthermore, a cost-effectiveness analysis shows that, considering regional tariffs, the multiple cohort (12-year-old + 25-year-old women) vaccination strategy with a 90% coverage could prevent 6 cases of cervicocarcinoma and 3 related deaths more than the vaccination of only 12-year-old girls, and thus proves to be cost-effective (11,615 €/QALY)

Lombardia

In Lombardia region 75% of women (aged 24-64) are screened regularly, meaning every 3 years. The analysis on cross-protective activity exercised by bivalent and quadrivalent vaccines shows that the bivalent vaccine could prevent more pre-cancerous lesions and cases of cervicocarcinoma than quadrivalent, and that the latter could prevent genital warts that are not prevented by bivalent. The major number of cases avoided by the bivalent make it possible to fully offset the cost savings related to warts associated with the quadrivalent vaccine. Furthermore, a cost-effectiveness analysis shows that, considering regional tariffs, the multiple cohort (12-year-old + 25-year-old women) vaccination strategy with a 90% coverage could prevent 92 cases of cervicocarcinoma and 42 related deaths more than the vaccination of only 12-year-old girls, and thus proves to be cost-effective (10,919 €/QALY)

Sardegna

In Sardegna region 75% of women (aged 24-64) are screened regularly, meaning every 3 years. The analysis on cross-protective activity exercised by bivalent and quadrivalent vaccines shows that the bivalent vaccine could prevent more pre-cancerous lesions and cases of cervicocarcinoma than quadrivalent, and that the latter could prevent genital warts that are not prevented by bivalent. The major number of cases avoided by the bivalent make it possible to fully offset the cost savings related to warts associated with the quadrivalent vaccine. Furthermore, a cost-effectiveness analysis shows that, considering regional tariffs, the multiple cohort (12-year-old + 25-year-old women) vaccination strategy with a 90% coverage could prevent 17 cases of cervicocarcinoma and 8 related deaths more than the vaccination of only 12-year-old girls, and thus proves to be cost-effective (10,841 €/QALY)

Bolzano

In the province of Bolzano 86% of women (aged 24-64) are screened regularly, meaning every 3 years. The analysis on cross-protective activity exercised by bivalent and quadrivalent vaccines shows that the bivalent vaccine could prevent more pre-cancerous lesions and cases of cervicocarcinoma than quadrivalent, and that the latter could prevent genital warts that are not prevented by bivalent. The major number of cases avoided by the bivalent make it possible to fully offset the cost savings related to warts associated with the quadrivalent vaccine. Furthermore, a cost-effectiveness analysis shows that, considering regional tariffs, the multiple cohort (12-year-old + 25-year-old women) vaccination strategy with a 90% coverage could prevent 4 cases of cervicocarcinoma and 2 related deaths more than the vaccination of only 12-year-old girls, and thus proves to be cost-effective (11,035 €/QALY)