Daclatasvir-based regimens in HCV cirrhosis: experience from the Italian early access program

We reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n\u2009=\u2009221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n\u2009=\u200954, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustained virological response at week 12 post-treatment (SVR12). Liver function changes between baseline and follow up were assessed in 228 patients. 240 patients achieved SVR12 (87.3%), post transplant and HIV co-infected patients were equally distributed among SVR and no SVR (35% vs 34.3%; p\u2009=\u20090.56 and 24.2% vs 11.4%, p\u2009=\u20090.13, respectively). SVR rate was significantly higher with the combination DCV\u2009+\u2009SOF compared with DCV\u2009+\u2009SIM or ASU (93.2% vs 63.0%, p\u2009<\u20090.0001). Bilirubin value (OR: 0.69, CI95%: 0.54-0.87, p\u2009=\u20090.002) and regimen containing SOF (OR: 9.99, CI95%: 4.09-24.40; p\u2009<\u20090.001) were independently related with SVR. Mean albumin and bilirubin values significantly improved between baseline and follow-up week 12. DCV-based antiviral therapy was well tolerated and resulted in a high SVR when combined with SOF either in pre-transplant and in OLT patients and in "difficult to treat" HCV genotypes. Regimens containing DCV in combination with NS3 protease inhibitors obtained suboptimal results

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project

Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan-Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (≥4.7 mg/dL) and CVM (≥5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12-1.40], p < 0.001) and CVM (1.31 [1.11-1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12-1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02-1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23-1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99-1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels

Serum uric acid and left ventricular mass index independently predict cardiovascular mortality: The uric acid right for heart health (URRAH) project

A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study. Aim: of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death. Methods: Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men. Results: A significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P<0.0001). At multivariate Cox regression analysis in women LVH alone and the combination of higher SUA and LVH but not hyperuricemia alone, were associated with a higher risk of CV death, while in men hyperuricemia without LVH, LVH without hyperuricemia and their combination were all associated with a higher incidence of CV death. Conclusions: Our findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women

Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan-Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (&gt;= 4.7 mg/dL) and CVM (&gt;= 5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12-1.40], p &lt; 0.001) and CVM (1.31 [1.11-1.74], p &lt; 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12-1.43], p &lt; 0.001) and hypertriglyceridemia (1.31 [1.02-1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23-1.73], p &lt; 0.001) and hypertriglyceridemia (HR 1.31 [0.99-1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels

Manifattura additiva di scaffold a base di poli(3-idrossibutirrato-co-3-idrossivalerato) per Ingegneria Tissutale

Il presente lavoro di tesi ha riguardato lo studio di un poliestere alifatico di origine microbica, il poli(3-idrossibutirrato-co-3-idrossivalerato) (PHBV), per applicazioni avanzate in Ingegneria Tissutale (Tissue Engineering TE). TE è campo multidisciplinare che sviluppa dispositivi medici impiantabili biodegradabili per la rigenerazione di organi e tessuti compromessi e il ripristino delle loro funzioni attraverso l’impiego di supporti temporanei (scaffold). Il polimero termoplastico PHBV è stato studiato come materiale per la progettazione, fabbricazione e caratterizzazione di scaffold biodegradabili mediante l’impiego due metodi di estrusione di Manifattura Additiva (Additive Manufacturing AM) 1) da soluzione mediante Computer-Aided Wet-Spinning (CAWS) e 2) da stato fuso mediante Fused Deposition Modelling (FDM). Queste tecniche permettono la realizzazione di scaffold con geometria esterna e porosità interna controllate. La tecnica CAWS permette di ottenere scaffold macroporosi con una micro/nanoporosità della fibra determinata dal processo di precipitazione per inversione di fase. È stato svolto, inoltre, uno studio di fattibilità di fabbricazione mediante CAWS di scaffold a base di i) solo PHBV ii) miscele con poli(lattide-co-glicolide) (PLGA) e iii) nanocompositi preparati con nanoparticelle di idrossiapatite (HAp). Prototipi ottimizzati degli scaffold sviluppati sono stati caratterizzati da un punto di vista chimico-fisico, morfologico, termico, meccanico e biologic

Procedural Feasibility and Long-Term Efficacy of Catheter Ablation of Atypical Atrial Flutters in a Wide Spectrum of Heart Diseases: An Updated Clinical Overview

Atypical atrial flutters (AAFL) are difficult-to-manage atrial arrhythmias, yet potentially amenable to effective radiofrequency catheter ablation (CA). However, data on CA feasibility are only sparingly reported in the literature in different clinical settings, such as AAFL related to surgical correction of congenital heart disease. The aim of this review was to provide an overview of the clinical settings in which AAFL may occur to help the cardiac electrophysiologist in the prediction of the tachycardia circuit location before CA. Moreover, the role and proper implementation of cutting-edge technologies in this setting were investigated as well as which procedural and clinical factors are associated with long-term failure to maintain sinus rhythm (SR) to find out which patients may, or may not, benefit from this procedure. Not only different surgical and non-surgical scenarios are associated with peculiar anatomical location of AAFL, but we also found that CA of AAFL is generally feasible. The success rate may be as low as 50% in surgically corrected congenital heart disease (CHD) patients but up to about 90% on average after pulmonary vein isolation (PVI) or in patients without structural heart disease. Over the years, the progressive implementation of three-dimensional mapping systems and high-density mapping tools has also proved helpful for ablation of these macro-reentrant circuits. However, the long-term maintenance of SR may still be suboptimal due to the progressive electroanatomic atrial remodeling occurring after cardiac surgery or other interventional procedures, thus limiting the likelihood of successful ablation in specific clinical settings

Assessment of land degradation susceptibility by scenario analysis: a case study in Southern Tuscany, Italy

In the Mediterranean area land degradation phenomena are becoming more and more important due to future climate change and increasing climate variability, as highlighted in recent global assessment projects such as the "Millennium Ecosystem Assessment" or "The Dialogue on Water and Climate". Thus, there is consistent evidence that extreme events such as droughts and floods are more frequent than before. On the other hand the Mediterranean area is strongly influenced by human activities such as cultivation over hundreds of years. However, in the last decades the cultivation methods and techniques are subject to profound changes such as mechanization, use of fertilizers and pesticides, remodellation of entire hillslopes etc. This particular situation leads to, and aggravates the existing stress on land resources. As a result, land degradation and soil erosion phenomena are leading to decreasing soil productivity or the loss of fertile top soil and related water quality and quantity issues. The Centre for Soil Erosion Studies (CRES) in Grosseto, Tuscany recently started a study to identify and monitor changes of land-use in southern Tuscany, Italy. The aim of this study is to assess land degradation sensitivity by scenario analysis. As a proxi for land degradation surface wash erosion processes such as rill and interill erosion processes are chosen. These present day processes are identified by aerial photo interpretation and subsequently modelled with a simple RUSLE approach on a monthly basis. In this study boundary conditions such as future precipitation were taken from the A2 future climate scenario published by the International Panel on Climate Change (IPCC)-Special Report on Emission Scenarios (SRES). Moreover, current land-use was identified from aerial photographs and future land-use scenarios were developed considering ecological and socio-economical issues for present day conditions of the test area. Subsequently, the different climate and land-use scenarios were analysed to study soil erosion susceptibility on the landscape scale. The study shows that even with a decline in precipitation volume until 2070, in some months higher erosion rates occur due to higher rainfall erosivity. Furthermore, land-use changes play an important role for soil erosion susceptibility. As shown, the various scenarios can effectively reduce or enhance soil erosion. © 2007 Elsevier B.V. All rights reserved

In vitro gastrointestinal gas monitoring with carbon nanotube sensors

In vitro simulators of the human gastrointestinal (GI) tract are remarkable technological platforms for studying the impact of food on the gut microbiota, enabling continuous and real-time monitoring of key biomarkers. However, comprehensive real-time monitoring of gaseous biomarkers&nbsp;in these systems is required with a cost-effective approach, which has been challenging to perform experimentally to date. In this work, we demonstrate the integration and in-line use of carbon nanotube (CNT)-based chemiresitive gas sensors coated with a thin polydimethylsiloxane (PDMS) membrane for the continuous monitoring of gases within the Simulator of the Human Microbial Ecosystem (SHIME). The findings demonstrate the ability of the gas sensor to continuously monitor the different phases of gas production in this harsh, anaerobic, highly humid, and acidic environment for a long exposure time (16&nbsp;h) without saturation. This establishes our sensor platform as an effective tool for real-time monitoring of gaseous biomarkers in in vitro systems like SHIME