SP628BENEFITS OF VITAMIN E-COATED VERSUS CONVENTIONAL MEMBRANES IN CHRONICHAEMODIALYSIS PATIENTS: A SYSTEMATIC REVIEW & META-ANALYSIS

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Effects of Vitamin E-Coated versus Conventional Membranes in Chronic Hemodialysis Patients: A Systematic Review and Meta-Analysis

Introduction: Accruing evidence suggests that vitamin E-coated membranes (ViE-m) might improve the clinical management of chronic hemodialysis (HD) patients. Methods: We conducted a systematic review and meta-analysis of RCTs comparing ViE-m to conventional HD. Endpoints of interest were a series of biomarkers pertaining to anemia status, inflammation, oxidative stress and dialysis efficacy/status. Results: Sixty studies were included. ViE-m significantly improved the Erythropoietin Resistance Index but had no impact on other anemia parameters. As for oxidative stress and inflammation, ViE-m produced a significant decrease in interleukin-6 levels, thiobarbituric acid reactive substances, plasma and red blood cell (RBC) malonylaldehyde and a significant increase in blood and RBC vitamin E. Conversely, ViE-m use had no impact on lipid profile, dialysis adequacy, blood pressure, albumin and uric acid. Conclusions: ViE-m might ameliorate anemia management by reducing oxidative stress and inflammation. Benefits of these bio-membranes on harder clinical outcomes are uncertain and need to be investigated by future, targeted trials

New Directions in Understanding Atopic March Starting from Atopic Dermatitis

Recent evidence showed that the postulated linear progression of the atopic march, from atopic dermatitis to food and respiratory allergies, does not capture the heterogeneity of allergic phenotypes, which are influenced by complex interactions between environmental, genetic, and psychosocial factors. Indeed, multiple atopic trajectories are possible in addition to the classic atopic march. Nevertheless, atopic dermatitis is often the first manifestation of an atopic march. Improved understanding of atopic dermatitis pathogenesis is warranted as this could represent a turning point in the prevention of atopic march. In this review, we outline the recent findings on the pathogenetic mechanisms leading to atopic dermatitis that could be targeted by intervention strategies for the prevention of atopic march

442. LV Expressing MR Reporter Genes Allows In Vivo Monitoring of Stem Cell Gene Therapy

Somatic stem cells (SSC) have raised interest because of their therapeutic potential in both cell-based and gene therapy applications. Towards this goal, tracking the fate of either delivered cells or of genetically modified endogenous cells is of utmost importance. Diverse imaging approaches are available for cell tracking and among these MRI shows a greater resolution and allows direct anatomic correlation and long-term studies of dynamic cell migration on living animals. Superparamagnetic iron oxide (SPIO) has been used to label SSC in vitro and to make them detectable in vivo upon transplantation. However, major limitations of this approach are the progressive dilution of the contrast media among cell progeny and the need for ex vivo SPIO loading. We thus explored an alternative strategy based on the combination of lentiviral vectors (LV), which efficiently transduce SSC both ex vivo and in vivo and allow long-term expression in their progeny, and MR reporter genes, able to increase iron uptake and accumulation into different cell types

[Cost-Utility Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Children and Adolescents in Italy]

BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a chronic, multifactorial, inflammatory condition characterized by a significant impact on patients' quality of life. Dupilumab is reimbursed by the Italian Medicines Agency (AIFA) for the treatment of adolescent and adult patients with severe AD (according to AIFA registry criteria). Recently, dupilumab has been reimbursed in the treatment of children with severe AD. The objective of this analysis was to estimate the incremental cost-utility ratio (ICUR) of dupilumab compared to current supportive care (SC), for the treatment of severe AD in children (6-11 years) and adolescents (12-17 years) in Italy.MATERIALS AND METHODS: Cost-effectiveness analysis was conducted using a 1-year decision tree followed by a Markov model over a lifetime period. The base case analysis was performed on the overall population of the LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914) studies, adopting the National Health Service (NHS) perspective. The following costs were considered: acquisition of treatment, management of disease, adverse events and complications. The robustness of the model was tested through sensitivity analysis. In addition, a scenario analysis adopting the social perspective was performed.RESULTS: In the base case, over a lifetime, dupilumab was more effective than SC in both children and adolescents (+2.44 and +1.62 quality-adjusted life years—QALYs, respectively). The introduction of dupilumab generated an increase in treatment costs (+€ 64,800 and +€ 52,853 € for children and adolescents, respectively), partially offset by a decrease in the costs of disease management and complications. Incremental cost-utility ratios (ICURs) were € 21,189 per QALY gained, for children, and € 26,569 per QALY gained, for adolescents. In both cases, the ICUR was lower than the willingness to pay threshold considered in Italy (€ 50,000 per QALY gained). Both the deterministic and probabilistic sensitivity analysis confirmed the robustness of the base case results. Finally, the scenario analysis, adopting the social perspective, showed coherent results compared to the base case.DISCUSSION: Dupilumab is a cost-effective option for the treatment of children and adolescents with severe AD eligible for systemic treatment in Italy compared to SC, from both the NHS and social perspective, confirming the results obtained in the adult population

Brain tumor stem cell dancing

Background. Issues regarding cancer stem cell (CSC) movement are important in neu-rosphere biology as cell-cell or cell-environment interactions may have significant impacts on CSC differentiation and contribute to the heterogeneity of the neurosphere. Aims. Despite the growing body of literature data on the biology of brain tumor stem  cells, floating CSC-derived neurospheres have been scarcely characterized from a morphological and ultrastructural point of view. Results. Here we report a morphological and ultrastructural characterization performed  by  live  imaging  and  scanning  electron  microscopy.  Glioblastoma  multiforme  (GBM)  CSC-derived neurospheres are heterogeneous and are constituted by cells, morphologically different, capable of forming highly dynamic structures. These dynamic structures  are regulated by not serendipitous cell-cell interactions, and they synchronously pulsate  following a cyclic course made of “fast” and “slow” alternate phases. Autocrine/paracrine  non  canonical  Wnt  signalling  appears  to  be  correlated  with  the  association  status  of  neurospheres. Conclusions. The results obtained suggest that GBM CSCs can behave both as independents cells and as “social” cells, highly interactive with other members of its species,  giving rise to a sort of “multicellular organism”.   

Co-Graft of Allogeneic Immune Regulatory Neural Stem Cells (NPC) and Pancreatic Islets Mediates Tolerance, while Inducing NPC-Derived Tumors in Mice

Data available on the immunomodulatory properties of neural stem/precursor cells (NPC) support their possible use as modulators for immune-mediated process. The aim of this study was to define whether NPC administered in combination with pancreatic islets prevents rejection in a fully mismatched allograft model.Diabetic Balb/c mice were co-transplanted under the kidney capsule with pancreatic islets and GFP(+) NPC from fully mismatched C57BL/6 mice. The following 4 groups of recipients were used: mice receiving islets alone; mice receiving islets alone and treated with standard immunosuppression (IL-2Ralpha chain mAbs + FK506 + Rapamycin); mice receiving a mixed islet/NPC graft under the same kidney capsule (Co-NPC-Tx); mice receiving the islet graft under the left kidney capsule and the NPC graft under the right kidney capsule (NPC-Tx). Our results demonstrate that only the co-transplantation and co-localization of NPC and islets (Co-NPC-Tx) induce stable long-term graft function in the absence of immunosuppression. This condition is associated with an expansion of CD4(+)CD25(+)FoxP3(+) T regulatory cells in the spleen. Unfortunately, stable graft function was accompanied by constant and reproducible development of NPC-derived cancer mainly sustained by insulin secretion.These data demonstrate that the use of NPC in combination with islets prevents graft rejection in a fully mismatched model. However, the development of NPC-derived cancer raises serious doubts about the safety of using adult stem cells in combination with insulin-producing cells outside the original microenvironment

Development and commissioning of the Timing Counter for the MEG Experiment

The Timing Counter of the MEG (Mu to Electron Gamma) experiment is designed to deliver trigger information and to accurately measure the timing of the $e^+$ in searching for the decay $\mu^+ \rightarrow e^+\gamma$. It is part of a magnetic spectrometer with the $\mu^+$ decay target in the center. It consists of two sectors upstream and downstream the target, each one with two layers: the inner one made with scintillating fibers read out by APDs for trigger and track reconstruction, the outer one consisting in scintillating bars read out by PMTs for trigger and time measurement. The design criteria, the obtained performances and the commissioning of the detector are presented herein.Comment: 10 pages, 20 figures. Presented at the IEEE Nuclear Science Symposium 2010, Knoxville, TN, USA. Accepted by IEEE Transaction on Nuclear Scienc

Does lung ultrasound have a role in the clinical management of pregnant women with SARS COV2 infection?

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is a major health threat. Pregnancy can lead to an increased susceptibility to viral infections. Although chest computed tomography (CT) represents the gold standard for the diagnosis of SARS-CoV-2 pneumonia, lung ultrasound (LUS) could be a valid alternative in pregnancy. The objectives of this prospective study were to assess the role of LUS in the diagnosis of lung involvement and in helping the physicians in the management of affected patients. Thirty pregnant women with SARS-CoV-2 infection were admitted at the obstetrical ward of our Hospital. Mean age was 31.2 years, mean gestational age 33.8 weeks. Several LUS were performed during hospitalization. The management of the patients was decided according to the LUS score and the clinical conditions. Mean gestational age at delivery was at 37.7 weeks, preterm birth was induced in 20% of cases for a worsening of the clinical conditions. No neonatal complications occurred. In 9 cases with a high LUS score, a chest CT was performed after delivery. CT confirmed the results of LUS, showing a significant positive correlation between the two techniques. LUS seems a safe alternative to CT in pregnancy and may help in the management of these patient

Atopic dermatitis

Atopic dermatitis (AD) is a common in ammatory skin disease, clinically characterized by recur- rent eczematous lesions and intense itching, leading to excoriations and susceptibility to cutaneous infections. Although it is considered a pediatric disorder, mainly starting in infancy, it is also very common in adults. Etiology of AD is complex and multifactorial: interaction between genetic susceptibility and environment, but also cutaneous barrier impairment, change in microbiome composition and innate and adaptive immune dysregulation are the main factors involved in the pathogenesis of the disease. Originally, the disorder was considered mediated by an imbalance towards a T-helper 2 response and excessive IgE production to aller- gens, but now it is recognized as a lifelong disposition with variable clinical expressivity, where dysfunctions of the epidermal barrier, immune system and microbiome play a central role. AD leads to a substantial psycho- social burden on patients and their relatives and increases the risk of other allergic and non allergic disorders. e real economic impact of AD is di cult to measure due to the broad spectrum of disease severity and the multiple direct and indirect costs, but the overall medical expenses seem to be very high and similar to those of other diseases such as diabetes. Currently, a multiple therapeutic approach is aimed only at improving the skin state, reducing itching and keeping a stable condition. New safety and curative treatments may be devel- oped only after enhancing our understanding on the pathogenesis of AD and the heterogeneity of its clinical manifestations. (www.actabiomedica.it