Bacterial or fungal infections in patients with cirrhosis: epidemiology across the world, definition of sepsis and predictors of post discharge outcomes

Background and aims: Bacterial infections are frequently observed in patients with cirrhosis and confers a poor survival. In recent years an increase in mortality rate has been observed in patients with cirrhosis. In addition, an increase in the prevalence of multi drug (MDR) bacterial infections has been described, reducing the efficacy of commonly used antibiotics such as third generation cephalosporins. In this thesis we conducted 3 studies aimed to: a) provide data about epidemiology of infections across countries and continents; b) assess the ability of the new criteria for sepsis (Sepsis-3) in predicting poor outcomes in patients with cirrhosis and bacterial infections; c) to assess predictor of early readmission (within 30 days) and mid-term survival (6 months) after discharge for bacterial infections Methods: For the first study, we conducted a prospective, multicenter, intercontinental, cross sectional study including patients with cirrhosis and bacterial/fungal infections (1,302 patients). For the second study, we conducted a prospective cross sectional study in two cohort of patients (primary cohort [259 patients] and validation cohort [197 patients]). For the third study, patients discharged after a hospitalization for bacterial/fungal infections were followed up for 6 months (199 patients). In all the 3 studies, demographic, clinical, laboratory and microbiological characteristics were collected at inclusion in the study and during the follow up. Results: In the first study we showed several differences among countries in the prevalence and the type of MDR bacterial infections, that were more prevalent in Indian or other Asian centers as well as in Southern American centers. These findings were associated with a significantly lower probability of microbiological susceptibility to antibiotic regimens suggested by the current guidelines. Remarkably, some infections were poorly treated even in countries with a low prevalence of MDR bacteria. The second study showed that Sepsis-3 criteria and quick SOFA have a significantly greater discrimination for in-hospital mortality (AUROC=0.784 and 0.732, respectively) than SIRS (AUROC=0.606;p10 mg/l at discharge had a significantly higher probability of being readmitted within 30 days (44 vs 24%; p=0.007) and a significantly lower probability of 6-month survival (62 vs 88%;p<0.001) than those with a CRP≤10 mg/L Conclusions: The first studies allowed to clarify the different epidemiology of bacterial infections in different centers suggesting different approach for the empirical treatment. The second study suggests that Sepsis-3 criteria and qSOFA are reliable tools to define the severity of infections and thus “sepsis” in patients with cirrhosis. Accordingly, an algorithm has been provided for the application of these criteria in patients with cirrhosis. Finally, the third study suggest that CRP levels may be potentially used to guide the antimicrobial stewardship in patients with cirrhosis and bacterial infections

Mechanical oil extraction of Nicotiana tabacum L. seeds: analysis of main extraction parameters on oil yield

The aim of this study is to find the best conditions of tobacco seed oil (TSO) press extraction, combining multiple extraction factors such as screw rotational speed, seeds preheating and extraction temperature, in order to have a higher oil yield. The extracted oil, having peculiar chemical properties, can be used for several purposes, also as edible oil. TSO was obtained using a mechanical screw press that has been assembled with a head press and with speed and temperature sensors mounted on the machine. Results show that the combination of high extraction temperature, slow rotational screw speed and seeds preheating has a significant effect on the oil yield. Extracting under such conditions, oil yield is 79.47±0.12 as % (w/w), which is 25% (w/w) more than the lowest yield among investigated condition

Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium

Clinical trials; Liver transplant; Quality of lifeEnsayos clínicos; Trasplante de hígado; Calidad de vidaAssaigs clínics; Trasplantament de fetge; Qualitat de vidaManagement of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis

Reply to: "A cut-off serum creatinine value of 1.5mg/dl for AKI – To be or not to be"

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Synergetic Application of Zero-, One-, and Three-Dimensional Computational Fluid Dynamics Approaches for Hydrogen-Fuelled Spark Ignition Engine Simulation

Nowadays hydrogen, especially if derived from biomass or produced by renewable power, is rising as a key energy solution to shift the mobility of the future toward a low-emission scenario. It is well known that hydrogen can be used with both internal combustion engines (ICEs) and fuel cells (FCs); however, hydrogen-fuelled ICE represents a robust and cost-efficient option to be quickly implemented under the current production infrastructure. In this framework, this article focuses on the conversion of a state-of-the-art 3.0L diesel engine in a hydrogen-fuelled Spark Ignition (SI) one. To preliminarily evaluate the potential of the converted ICE, a proper simulation methodology was defined combining zero-, one-, and three-dimensional (0D/1D/3D) Computational Fluid Dynamics (CFD) approaches. First of all, a detailed kinetic scheme was selected for both hydrogen combustion and Nitrogen Oxides (NOx) emission predictions in a 3D-CFD environment. Afterward, to bring the analysis to a system-level approach, a 1D-CFD predictive combustion model was firstly optimized by implementing a specific laminar flame speed correlation and, secondly, calibrated against the 3D-CFD combustion results. The combustion model was then integrated into a complete engine model to assess the potential benefit derived from the wide range of flammability and the high flame speed of hydrogen on a complete engine map, considering NOx formation and knock avoidance as priority parameters to control. Without a specific modification of turbocharger and combustion systems, a power density of 34 kW/L and a maximum brake thermal efficiency (BTE) of about 42% were achieved, thus paving the way for further hardware optimization (e.g., compression ratio reduction, turbocharger optimization, direct injection [DI]) to fully exploit the advantages enabled by hydrogen combustion

Continuous recurrence of type 1 hepatorenal syndrome and long-term treatment with terlipressin and albumin: A new exception to MELD score in the allocation system to liver transplantation?

Background & Aims The recurrence of type 1 hepatorenal syndrome has been described in up to 20% of responders to terlipressin and albumin after the discontinuation of the treatment. Subsequent recurrence of type 1 hepatorenal syndrome may require long-term treatment with terlipressin and albumin. Methods We describe our experience of long-term administration of terlipressin as a bridge to LT in three patients with cirrhosis and recurrent type 1 hepatorenal syndrome. For all three patients we requested an "early transplant" which is an option recognized in our country to reduce waiting times for liver transplantation. Results All three patients were transplanted within 2months of onset of hepatorenal syndrome. All patients are still alive and none of them have developed chronic kidney disease. Conclusions The outcomes of these patients suggest that long-term treatment with terlipressin and albumin is effective and well tolerated in patients with continuous recurrence of type 1 hepatorenal syndrome and, therefore, should be considered an absolute priority criterion in the allocation system for liver transplantation

Performance of non-invasive respiratory function indices in predicting clinical outcomes in patients hospitalized for COVID-19 pneumonia in medical and sub-intensive wards: a retrospective cohort study

Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease which can lead to acute respiratory distress syndrome requiring ventilatory support and intensive care unit admission. The aim of our study is to evaluate the performance of two non-invasive respiratory function&nbsp;indices (the ROX index and the SatO2/FiO2 ratio), as compared to the traditional PaO2/FiO2 ratio, in predicting a clinically relevant composite outcome (death or intubation) in hospitalized patients for COVID-19 pneumonia. Four hospital centers in Northern Italy conducted an observational retrospective cohort study during the first wave of COVID-19 pandemic. Four hundred and fifty-six patients with COVID-19 pneumonia admitted to medical or sub-intensive wards were enrolled. Clinical, laboratory, and respiratory parameters, for the calculation of different indices, were measured at hospital admission. In medical wards (Verona and Padua) the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio were able to predict intubation or death with good accuracy (AUROC for the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio of 75%, 75% and 74%, respectively). Regarding sub-intensive wards (Milan and Mantua), none of the three respiratory function indices was significantly associated with the composite outcome. In patients admitted to medical wards for COVID-19 pneumonia, the ROX index and the SatO2/FiO2 ratio demonstrated not only good performance in predicting intubation or death, but their accuracy was comparable to that of the PaO2/FiO2 ratio. In this setting, where repeated arterial blood gas tests are not always feasible, they could be considered a reliable alternative to the invasive PaO2/FiO2 ratio

Adipocyte fatty-acid binding protein is overexpressed in cirrhosis and correlates with clinical outcomes

Fatty-acid-binding proteins (FABPs) are small intracellular proteins that coordinate lipid-mediated processes by targeting metabolic and immune response pathways. The aim of the study was to investigate plasma FABPs levels and their relationship with clinical outcomes in cirrhosis. Plasma levels of L-FABP1(liver and kidney), I-FABP2(intestine), and A-FABP4(adipocyte and macrophages) were measured in 274 patients with decompensated cirrhosis. Hepatic gene expression of FABPs was assessed in liver biopsies from patients with decompensated cirrhosis and in liver cell types from mice with cirrhosis. Immunohistochemistry of A-FABP4 in human liver biopsy was also performed. Plasma levels of FABPs were increased in patients with decompensated cirrhosis compared to those of healthy subjects (L-FABP1: 25 (17-39) vs 10 (9-17) ng/mL p = 0.001, I-FABP2: 1.1 (0.5-2.1) vs 0.6 (0.4-1) ng/ mL p = 0.04 and A-FABP4: 37 (20-68) vs 16 (11-33) ng/mL p = 0.002), respectively. Increased A-FABP4 levels were associated with complications of cirrhosis, acute-on-chronic liver failure and poor survival. Hepatic A-FABP4 gene expression was upregulated in decompensated cirrhosis. Macrophages were the main liver cell that over-expressed A-FABP4 in experimental cirrhosis and increased A-FABP4 was found in macrophages of human biopsies by immunohistochemistry. A-FABP4 levels are increased in decompensated cirrhosis and correlate with poor outcomes. Liver macrophages appear to be the main source of A-FABP4 in decompensated cirrhosis