Fungicidal activity and PK/PD of caspofungin as tools to guide antifungal therapy in a fluconazole-resistant C. parapsilosis candidemia

Candida parapsilosis may be responsible for bloodstream infections (BSI) and it is characterised by an increased incidence of fluconazole resistance. A 75-year old woman with severe comorbidities received the insertion of a peripherally inserted central venous catheter. Fluconazole did not prevent a C. parapsilosis BSI hence caspofungin was started after a nephrotoxic first-line treatment with amphotericin B. The ratio of peak plasma concentration over the minimum inhibitory concentration (Cmax/MIC) was adopted to maximise efficacy of caspofungin. MIC and plasma Cmax values were obtained by broth microdilution and LC-MS, respectively. Interestingly, daily doses of 1 mg/kg (total daily dose, 50 mg) allowed the achievement of Cmax/MIC values > 10. The optimised regimen was safe and effective, leading to negative blood culture at day 8. The patient was discharged home at day 21. Therefore, individualised dosing regimens of caspofungin may be effective and safe even in the case of C. parapsilosis BSI

New perspectives for undoped CaF2 scintillator as a threshold activation neutron detector

In this paper we present the prompt photofission neutron detection performance of undoped CaF2 scintillator using Threshold Activation Detection (TAD). The study is carried out in the frame of C-BORD Horizon 2020 project, during which an efficient toolbox for high volume freight non-intrusive inspection (NII) is under development. Technologies for radiation monitoring are the part of the project. Particularly, detection of various radiological threats on country borders plays an important significant role in Homeland Security applications. Detection of illegal transfer of Special Nuclear Material (SNM) - 235U, 233U and 239Pu - is particular due to the potential use for production of nuclear weapon as well as radiological dispersal device (RDD) V known also as a "dirty bomb". This technique relies on activation of 19F nuclei in the scintillator medium by fast neutrons and registration of high-energy β particles and γ-rays from the decay of reaction products. The radiation from SNM is detected after irradiation in order to avoid detector blinding. Despite the low 19F(n,α)16N or 19F(n,p)19O reaction cross-section, the method could be a good solution for detection of shielded nuclear material. Results obtained with the CaF2 detector were compared with the previous study done for BaF2 and 3He detector. These experimental results were obtained using 252Cf source and 9 MeV Varian Linatron M9 linear accelerator (LINAC). Finally, performance of the prompt neutron detection system based on CaF2 will be validated at Rotterdam Seaport during field trails in 2018

Comparison and combination of a hemodynamics/biomarkers-based model with simplified PESI score for prognostic stratification of acute pulmonary embolism: findings from a real world study

Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI).Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpointsResults: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1.Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry

AimsTo analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients.Methods and resultsPatients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6-12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.ConclusionIn 'real world' clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available

The Future of Cities

This report is an initiative of the Joint Research Centre (JRC), the science and knowledge service of the European Commission (EC), and supported by the Commission's Directorate-General for Regional and Urban Policy (DG REGIO). It highlights drivers shaping the urban future, identifying both the key challenges cities will have to address and the strengths they can capitalise on to proactively build their desired futures. The main aim of this report is to raise open questions and steer discussions on what the future of cities can, and should be, both within the science and policymaker communities. While addressing mainly European cities, examples from other world regions are also given since many challenges and solutions have a global relevance. The report is particularly novel in two ways. First, it was developed in an inclusive manner – close collaboration with the EC’s Community of Practice on Cities (CoP-CITIES) provided insights from the broader research community and city networks, including individual municipalities, as well as Commission services and international organisations. It was also extensively reviewed by an Editorial Board. Secondly, the report is supported by an online ‘living’ platform which will host future updates, including additional analyses, discussions, case studies, comments and interactive maps that go beyond the scope of the current version of the report. Steered by the JRC, the platform will offer a permanent virtual space to the research, practice and policymaking community for sharing and accumulating knowledge on the future of cities. This report is produced in the framework of the EC Knowledge Centre for Territorial Policies and is part of a wider series of flagship Science for Policy reports by the JRC, investigating future perspectives concerning Artificial Intelligence, the Future of Road Transport, Resilience, Cybersecurity and Fairness Interactive online platform : https://urban.jrc.ec.europa.eu/thefutureofcitiesJRC.B.3-Territorial Developmen

Peripherally inserted central catheter as a predominant risk factor for candidemia in critically ill patients in Internal Medicine wards in Italy

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Design of the rapidly relocatable tagged neutron inspection system of the C-BORD project

International audienceWithin the framework of the European H2020 C-BORD project, aiming at improving container inspection technologies, a compact and "Rapidly Relocatable Tagged Neutron Inspection System", called RRTNIS, is being developed taking into account past EURITRACK experience with a portal TNIS, and the latest technologies in terms of associated particle neutron generator and data acquisition electronics. A dedicated shield surrounding the neutron generator has been designed with MCNP6 to limit the size of the restricted area and the count rate on gamma detectors, which are located very close to the generator. This new design with "reflection" detectors only, i.e. in backscattering position, is indeed more efficient to detect suspect items, like explosives or illicit drugs, in bottom regions of the container, compared to EURITRACK detectors which were mainly located above the container. It also allows designing a relocatable system for different inspection sites like seaports, borders, or other checkpoints. Dose and count rate calculations are presented to determine the restricted area and facilitate the design of the data acquisition electronics, respectively

A prediction rule for early recognition of patients with candidemia in Internal Medicine: results from an Italian, multicentric, case-control study

PurposeIncreasing prevalence of candidemia in Internal Medicine wards (IMWs) has been reported in recent years, but risk factors for candida bloodstream infection in patients admitted to IMW may differ from those known in other settings. The aim of this study was to identify risk factors and define a prediction rule for the early recognition of the risk of candidemia in IMW inpatients.MethodsThis was a multicentric, retrospective, observational case-control study on non-neutropenic patients with candidemia admitted to IMWs of four large Italian Hospitals. Each eligible patient with candidemia (case) was matched to a control with bacteremia. Stepwise logistic regression analyses were performed.ResultsOverall, 300 patients (150 cases and 150 controls) were enrolled. The following factors were associated with an increased risk of candidemia and weighted to build a score: total parenteral nutrition (OR 2.45, p=0.008; 1 point); central venous catheter (OR 2.19, p=0.031; 1 point); peripherally inserted central catheter (OR 5.63, p<0.0001; 3 points), antibiotic treatment prior (OR 2.06; p=0.059; 1 point) and during hospitalization (OR2.38, p=0.033; 1 point); neurological disability (OR 2.25, p=0.01; 1 point); and previous hospitalization within 3 months (OR 1.56, p=0.163; 1 point). At ROC curve analysis, a final score4 showed 84% sensitivity, 76% specificity, and 80% accuracy in predicting the risk of candidemia.ConclusionsThe proposed scoring system showed to be a simple and highly performing tool in distinguishing bloodstream infections due to Candida and bacteria in patients admitted to IMW. The proposed rule might help to reduce delay in empirical treatment and improve appropriateness in antifungal prescription in septic patients