1,441 research outputs found

    Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.

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    Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin\ub1pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3\ub16.5 vs 10.5\ub13.8, P<.0001 and 8.4\ub12.1 vs 5.7\ub11.3, P<.0001, respectively) and FCH (17.3\ub15.9 vs 10.1\ub12.8, P=.001 and 8.2\ub11.6 vs 5.5\ub11, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD 6525 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD 6520 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments

    Timing for treatment of HCV recurrence after liver transplantation: the earlier the better.

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    HCV is the leading cause of death from liver disease and is the most common indication for a liver transplantation. Although HCV is a widespread health problem, disease management is particularly challenging in several key subpopulations, including liver transplant recipients. HCV recurrence after liver transplantation constituted a major challenge for the physicians during the last years. The recommended standard of care before the advent of new regimen was the treatment of confirmed recurrent disease, based either on persistent, unexplained elevated alanine aminotransferase levels or on histologically confirmed fibrosis, once rejection, biliary obstruction, and vascular damage have been ruled out. Moreover, early therapy (including interferon) has been associated with high rates of adverse effects, an increased risk of graft rejection, and higher proportions of patients requiring dose reductions. We are now facing a "new era" of direct antiviral agents that is already changing the approach to HCV burden in the post liver transplantation setting. Available data on treatment of HCV recurrence with the new antiviral drugs showed sustained virological response that ranges between 60 to 100%. In this comment we have focused on both the utility of non invasive test to evaluate the fibrosis progression and on timing of antiviral therapy for HCV recurrence. This article is protected by copyright. All rights reserved

    New Perspectives on Treatment of Hepatitis B Before and After Liver Transplantation

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    open5noThe hepatitis B virus (HBV) infects more than 260 million people globally, with increasing incidence, especially in developing countries. Despite antiviral therapies, HBV-related end-stage liver disease remains one of the most important indications for liver transplantation worldwide. Although new available treatments have improved the outcome of patients with both compensated and decompensated liver disease in some specific clinical settings as acute-on-chronic liver failure mortality is still high. Moreover, the incidence of HBV-related hepatocellular carcinoma (HCC) seems to be increasing and represents a major challenge for the transplant team. In the post-transplant setting, combination of anti-HBV immunoglobulins and oral nucleos(t)ides provided significant improvement on graft and patient survival. Furthermore, recent data suggested the possibility of personalized therapeutic algorithms based on pre and post-transplant viral and host risk factors. Finally, liver grafts from HBV core antibody (anti-HBc) positive or hepatitis B surface antigen (HBsAg) donors can be safely used in order to expand the donor pool, considering adequate allocation and tailored prophylaxis after LT. In this review we have focused on the evolution of antiviral therapy for HBV, highlighting useful information to aid the transplant hepatologist in clinical practice.ReviewopenZanetto, Alberto; Ferrarese, Alberto; Bortoluzzi, Ilaria; Burra, Patrizia; Russo, Francesco PaoloZanetto, Alberto; Ferrarese, Alberto; Bortoluzzi, Ilaria; Burra, Patrizia; Russo, FRANCESCO PAOL

    Deep sea as a source of novel-anticancer drugs

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    The deep-sea habitat is a source of very potent marine-derived agents that may inhibit the growth of human cancer cells “in vitro” and “in vivo”. Salinosporamide-A, Marizomib, by Salinispora species is a proteasome inhibitor with promising anticancer activity (Phase I/II trials). Different deep-sea-derived drugs are under preclinical evaluation. Cancer is a complex disease that may be represented by network medicine. A simple consequence is the change of the concept of target entity from a single protein to a whole molecular pathway and or cellular network. Deep-sea-derived drugs fit well to this new concept

    Aprendizaje y adquisiciĂłn de lenguas extranjeras: el estudiante de lengua italiana en la Escuela Oficial de Idiomas de CastellĂłn

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    Treball Final de Màster en Comunicació Intercultural i d'Ensenyament de Llengües. Codi: SBC042. Curs acadèmic: 2017/201

    Invasive meningococcal disease in the Veneto region of Italy: A capture-recapture analysis for assessing the effectiveness of an integrated surveillance system

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    open8noBACKGROUND: Epidemiology of Neisseria meningitidis has been changing since the introduction of universal vaccination programmes against meningococcal serogroup C (MenC) and meningococcal serogroup B (MenB) has now become dominant. This study aimed to analyse the cases reported in institutional data recording systems to estimate the burden of invasive meningococcal diseases (IMDs) and assess the effectiveness of surveillance in Veneto region (Italy). METHODS: Analysis was performed from 2007 to 2014 on data recorded in different systems: Mandatory Notification System, National Surveillance of Invasive Bacterial Diseases System and Laboratories Surveillance System (LSS), which were pooled into a combined surveillance system (CSS) and hospital discharge records (HDRs). A capture-recapture method was used and completeness of each source estimated. Number of cases with IMD by source of information and year, incidence of IMD by age group, case fatality rate (CFR) and distribution of meningococcal serogroups by year were also analysed. RESULTS: Combining the four data systems enabled the identification of 179 confirmed cases with IMD, achieving an overall sensitivity of 94.7% (95% CI: 90.8% to 98.8%), while it was 76.7% (95% CI: 73.6% to 80.1%) for CSS and 77.2% (95% CI: 74.1% to 80.6%) for HDRs. Typing of isolates was done in 80% of cases, and 95.2% of the typed cases were provided by LSS. Serogroup B was confirmed in 50.3% of cases. The estimated IMD notification rate (cases with IMD diagnosed and reported to the surveillance systems) was 0.48/100 000 population, and incidence peaked at 6.2/100 000 in children aged <1 year old (60.9% due to MenB), and increased slightly in the age group between 15 and 19 years (1.1/100 000). A CFR of 14% was recorded (8.7% in paediatric age). CONCLUSIONS: Quality of surveillance systems relies on case ascertainment based on serological characterisation of the circulating strains by microbiology laboratories. All available sources should be routinely combined to improve the epidemiology of IMD and the information used by public health departments to conduct timely preventive measures.openBaldovin, Tatjana; Lazzari, Roberta; Cocchio, Silvia; Furlan, Patrizia; Bertoncello, Chiara; Saia, Mario; Russo, Francesca; Baldo, VincenzoBaldovin, Tatjana; Lazzari, Roberta; Cocchio, Silvia; Furlan, Patrizia; Bertoncello, Chiara; Saia, Mario; Russo, Francesca; Baldo, Vincenz

    Markers of acute rejection and graft acceptance in liver transplantation.

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    The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct post-transplant management and a major step towards the personalisation of the immunosuppressive therapy. However, current immunological monitoring after liver transplantation relies mainly on clinical judgment and on immunosuppressive drug levels, without a proper assessment of the real suppression of the immunological system. Various markers have been studied in an attempt to identify a specific indicator of graft rejection and graft acceptance after liver transplantation. Considering acute rejection, the most studied markers are pro-inflammatory and immunoregulatory cytokines and other proteins related to inflammation. However there is considerable overlap with other conditions, and only few of them have been validated. Standard liver tests cannot be used as markers of graft rejection due to their low sensitivity and specificity and the weak correlation with the severity of histopathological findings. Several studies have been performed to identify biomarkers of tolerance in liver transplanted patients. Most of them are based on the analysis of peripheral blood samples and on the use of transcriptional profiling techniques. Amongst these, NK cell-related molecules seem to be the most valid marker of graft acceptance, whereas the role CD4+CD25+Foxp3+ T cells has still to be properly defined

    Comparison between soluble ST2 and high-sensitivity troponin I in predicting short-term mortality for patients presenting to the Emergency Department with chest pain

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    Background: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. Methods: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. Results: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P35 ng/mL at ED arrival died during the 30-day follow-up. Conclusions: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value > 35 ng/mL at ED arrival showed the highest predictive power for short-term mortality

    Submagmatic to Solid-State Deformation Microstructures Recorded in Cooling Granitoids during Exhumation of Late-Variscan Crust in North-Eastern Sicily

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    Late-Variscan granitoid rocks of trondhjemitic and granitic composition, intruded in migmatitic paragneisses in the north-eastern Peloritani Mountains (southern Italy) at ~310 Ma and ~300 Ma, respectively, exhibit a range of deformation microstructures developed under a shear regime at decreasing temperatures. Non-coaxial deformation is documented by sigmoidal feldspar porphyroclasts, mica fish, and asymmetric boudins affecting tiny andalusite crystals. Late-Variscan shearing during granitoid cooling is constrained by largely represented chessboard patterns in quartz and, especially, submagmatic fractures in plagioclase, indicating deformation at high-temperature conditions (T > 650 °C), in the presence of melt. Submagmatic deformation was extensively superseded by deformation at lower temperatures. Examples of solid state-high temperature deformation-related microstructures (T > 450 °C) include feldspar bulging, quartz grain boundary migration, and subgrain rotation recrystallization. Finally, low temperature subsolidus microstructures (T < 450 °C) consist of quartz bulging, mica kinks, and feldspar twinning and bending. A complete sequence of deformation, operating from submagmatic to low-temperature subsolidus conditions is recorded in both the older and younger granitoids, suggesting a duration of ~20 Ma for shear zone activity during post-collisional exhumation of the Variscan middle crust in southernmost Italy
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