Novel Molecular Mechanisms in the Development of Non-Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in adults and children worldwide. NAFLD has become a severe health issue and it can progress towards a more severe form of the disease, the non-alcoholic steatohepatitis (NASH). A combination of environmental factors, host genetics, and gut microbiota leads to excessive accumulation of lipids in the liver (steatosis), which may result in lipotoxicity and trigger hepatocyte cell death, liver inflammation, fibrosis, and pathological angiogenesis. NASH can further progress towards liver cirrhosis and cancer. Over the last few years, cell-derived extracellular vesicles (EVs) have been identified as effective cell-to-cell messengers that transfer several bioactive molecules in target cells, modulating the pathogenesis and progression of NASH. In this review, we focused on recently highlighted aspects of molecular pathogenesis of NASH, mediated by EVs via their bioactive components. The studies included in this review summarize the state of art regarding the role of EVs during the progression of NASH and bring novel insight about the potential use of EVs for diagnosis and therapeutic strategies for patients with this disease

Comparison between traditional and goal directed perfusion in cardiopulmonary by-pass. Adaptation of a differential cost analysis

BACKGROUND: A previous patient-level discrete event simulation (DES) model was developed to perform an economic evaluation of GDP strategy with respect to TP in US. Aim of this supplement is provide results of the adaptations of the differential cost analysis to Belgium, Canada, France, Germany, Italy, and UK. METHODS: A Discrete Event Simulation model was developed to compare TP and GDP strategy in patients undergoing CPB. National perspective was adopted to calculate costs associated to each event while GDP strategy was exploited the introduction of Sorin Heartlink (HL) Card/GDP Card and Sorin Connect (electronic data management system). RESULTS: GDP reduces the total cost with respect to traditional perfusion; furthermore the cost of GDP strategy (Sorin GDPTM Monitor and Sorin ConnectTM) is completely offset by the saving in hospital stay. CONCLUSION: GDP seems to improve significantly the main outcomes related to CPB surgery, when compared to TP techniques. Additional costs due to perform GDP strategy have no impact on the total cost since completely offset by the savings in hospital cost

Comparison between traditional and goal directed perfusion in cardiopulmonary by-pass. A differential cost analysis in US

OBJECTIVES: High oxygen delivery (DO2) during cardiopulmonary bypass (CPB) is associated with better renal outcomein cardiac surgery. Traditional perfusion (TP) techniques, targeted on body surface area and CPB temperature, achieveshigh DO2 in about 50% of the cases while a goal directed perfusion (GDP) approach can lead to more than 90% of casesachieving high DO2 with a consequent reduction in Acute Kidney Injury (AKI) rate of about 40%. Aim of this study isto perform an economic evaluation of GDP strategy with respect to TP in US. METHODS: A Discrete Event Simulationmodel was developed to compare TP and GDP strategy in patients undergoing CPB. The patient’s pathways from operationto discharging from hospital was simulated: AKI incidence, in-hospital mortality, hospital length of stay, transfusions werecorrelated to probability to achieve high DO2 target using published correlations. National perspective was adopted to calculate costs associated to each event while GDP strategy was exploited the introduction of Sorin Heartlink (HL) Card/GDPCard and Sorin Connect (electronic data management system). RESULTS: GDP strategy saved more than 3 days in hospitaland 11% of AKI episodes. The cost-saving is $3,137 (95$180, 95% CI: 113-249) is more than offset by savings in hospital stay that result the main driver in cost ($ 3,222, 95% CI:1,235-4,950). Deterministic sensitivity analysis shows that the total savings are mainly influenced by nadir haematocritduring CPB and hospital LOS/cost per day both in ICU and in ward. CONCLUSIONS: GDP seems to improve significantlythe main outcomes related to CPB surgery, when compared to TP techniques. Additional costs due to perform GDP strategyhave no impact on the total cost since completely offset by the savings in hospital cost

PIN20 Budget Impact of Backbone Choice in Italian Treatment- Naïve, HIV-Infected Patients

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Effectiveness of Long-Acting Injectable Antipsychotics in Schizophrenia: A Literature Review and Bayesian Meta-Analysis Informing Economic Considerations

BACKGROUND: Although the use of long-acting injectable antipsychotics (LAIs) is considered an important option in the management of schizophrenia two recent meta-analysis, which aimed to compare LAIs vs oral antipsychotics (OAPs) in terms of relapse rate, showed discordant results.AIM: To investigate factors affecting the efficacy of antipsychotics in terms of relapse prevention in the real-world and to estimate the management cost of an episode of relapse.METHODS: We conducted a literature search using MEDLINE/PubMed with the aim to extract efficacy, effectiveness and adherence data of LAIs and OAPs. The primary outcome was the relative risk (RR) of relapse between two strategies. The extracted RR were included in a series of Bayesian statistical models based on the starting hypotheses. The RR rates obtained from the meta-analysis have been used as input for an economic evaluation of the total costs associated with the management of the patient with schizophrenia from the Italian NHS perspective.RESULTS: The literature search identified 34 studies which met the inclusion criteria and were analyzed. According to the model that best explains the data, in the real-world setting the effectiveness with LAIs is greater than with OAPs, with a more pronounced effect for SGAs than for FGAs. Taking into account generation, route and frequency of administration, the RR decreased with lower administration frequency, with SGA LAI administered once every 90 days which is associated with the greatest reduction in the risk of relapse (-85%). When the results of the meta-analysis are used to feed an economic evaluation the results show that the SGA administered every 90 days is the strategy with the least expected cumulative cost both at 1 (€ 3,509) and 5 years (€ 19,690).CONCLUSION: SGA LAIs administered every 90 days seems to be the best option for the treatment of patient with schizophrenia from both the clinical and economic perspectives.An erratum to this article is available online at: https://doi.org/10.7175/fe.v20i1.140

Composición de la materia orgánica particulada en un sistema periantártico semi-cerrado: el Estrecho de Magallanes

The elemental and biochemical composition of particulate organic matter (POM) was investigated in the Straits of Magellan during February-March 1991. Twenty-two stations were selected in order to identify different areas of the Magellan ecosystem from a trophic point of view. The Strait of Magellan can be divided into three subsystems characterized by different hydrological and geomorphological conditions. Seston concentrations were mostly constrained by physical events, particularly the influence of oceanic and land run-off water inputs and the strong vertical mixing and resuspension events. POM composition displayed quali-quantitative differences between the three areas. In the first subsystem, influenced by Pacific waters, the low seston and POM concentrations and the high POC/Chl-a ratio values indicated the general predominance of the detrital and heterotrophic fractions. In the second subsystem, characterized by superficial stratification, higher seston and organic matter concentrations and lower values of POC/Chl-a ratio were found, indicating that this subsystem was influenced by an active autotrophic component. Shallow waters with intense tidal regime and strong vertical mixing characterized the third subsystem, connected to the Atlantic Ocean, which displayed an increasing importance of the inorganic fraction (values of the POC/TSM ratio lower than in the other systems). Moreover, the third subsystem showed higher values of the RNA/DNA ratio, possibly indicating that resuspension events may enhance the metabolic state of the organic particles mainly dominated by heterotrophic components.Se estudió la composición elemental y bioquímica de la POM (materia orgánica particulada) en el Estrecho de Magallanes durante el periodo febrero-marzo de 1991. Se eligieron 22 estaciones a fin de identificar diferentes áreas del ecosistema magallánico desde un punto de vista trófico. De acuerdo con las características hidrológicas y geomorfológicas dicho Estrecho se puede dividir en 3 subsistemas. Las concentraciones de seston estuvieron condicionadas, principalmente, por los fenómenos físicos y, en particular, por los aportes oceánicos y terrestres, por la mezcla vertical y por los fenómenos de resuspensión. La composición de la materia orgánica particulada (POM) mostró diferencias cualitativas y cuantitativas en las tres áreas. En el primer subsistema, influenciado por las aguas del Océano Pacífico, las bajas concentraciones de seston y POM y los altos valores de la relación POC/clorofila a indicaron una predominancia general de las fracciones detrítica y heterótrofa. En el segundo subsistema, caracterizado por una estratificación superficial, se encontraron altas concentraciones de seston y de materia orgánica y bajos valores de la relación POC/clorofila a, señalando una influencia de la componente autótrofa activa. El tercer subsistema, conectado con el Océano Atlántico y caracterizado por aguas poco profundas y por un régimen mareal intenso y una fuerte mezcla vertical, mostró un importante aumento de la fracción inorgánica (valores de la relación POC/TSM más bajos que en los otros dos subsistemas). Por otra parte, el tercer subsistema mostró altos valores de la relación RNA/DNA, indicando que posiblemente el estado metabólico de las partículas orgánicas (dominadas principalmente por componentes heterótrofas) estaría influenciado por fenómenos de resuspensión

Physiological and genetic control of anthocyanin pigmentation in different species

Koes, R.E. [Promotor]Quattrocchio, F. [Copromotor]Perata, P. [Copromotor