Treatment of severe alcoholic hepatitis: A systematic review

Severe alcoholic hepatitis is the most severe form of alcohol-related liver disease. Corticosteroids remain the first choice of treatment. However, they are only effective in a subset of patients and are associated with an increased infection risk. Furthermore, nonresponders to corticosteroids have a poor prognosis with a mortality of 70% over 6 months. As such, there is a high need for a more personalized use of corticosteroids and the development and identification of alternative therapeutic strategies. In this review, we summarize the recent and ongoing randomized controlled trials concerning the treatment of severe alcoholic hepatitis

Acute-on-chronic liver failure in cirrhosis

The definition of acute-on-chronic liver failure (ACLF) remains contested. In Europe and North America, the term is generally applied according to the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium guidelines, which defines this condition as a syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure and high short-term mortality. One-third of patients who are hospitalized for acute decompensation present with ACLF at admission or develop the syndrome during hospitalization. ACLF frequently occurs in a closed temporal relationship to a precipitating event, such as bacterial infection or acute alcoholic, drug-induced or viral hepatitis. However, no precipitating event can be identified in approximately 40% of patients. The mechanisms of ACLF involve systemic inflammation due to infections, acute liver damage and, in cases without precipitating events, probably intestinal translocation of bacteria or bacterial products. ACLF is graded into three stages (ACLF grades 1-3) on the basis of the number of organ failures, with higher grades associated with increased mortality. Liver and renal failures are the most common organ failures, followed by coagulation, brain, circulatory and respiratory failure. The 28-day mortality rate associated with ACLF is 30%. Depending on the grade, ACLF can be reversed using standard therapy in only 16-51% of patients, leaving a considerable proportion of patients with ACLF that remains steady or progresses. Liver transplantation in selected patients with ACLF grade 2 and ACLF grade 3 increases the 6-month survival from 10% to 80%

Ectoplasm with an Edge

The construction of supersymmetric invariant actions on a spacetime manifold with a boundary is carried out using the "ectoplasm" formalism for the construction of closed forms in superspace. Non-trivial actions are obtained from the pull-backs to the bosonic bodies of closed but non-exact forms in superspace; finding supersymmetric invariants thus becomes a cohomology problem. For a spacetime with a boundary, the appropriate mathematical language changes to relative cohomology, which we use to give a general formulation of off-shell supersymmetric invariants in the presence of boundaries. We also relate this construction to the superembedding formalism for the construction of brane actions, and we give examples with bulk spacetimes of dimension 3, 4 and 5. The closed superform in the 5D example needs to be constructed as a Chern-Simons type of invariant, obtained from a closed 6-form displaying Weil triviality.Comment: 25 page

Investigation of Performance and Cavitation Treatment in a Kaplan Hydro Turbine

Cavitation is a phenomenon that occurs in various turbomachinery applications causing drawbacks on the. Some of these downsides are damaging the components of the system, generating noise and vibration, and loss of the turbine efficiency over time. Thus, it is imperative to address issue of cavitation to increase the life span of the equipment in addition to improve the system performance. This thesis introduces a method used to mitigate the cavitation phenomenon in a 3-inch Kaplan hydro turbine via injecting air at the leading edge of the rotor blades. The study is based on modeling the turbine using Computational Fluid Dynamics (CFD) software as well as carrying out experimental tests. The simulations were conducted at different air injection pressures over a spectrum of rotational speeds using Large Eddy Simulation (LES) for turbulence and volume of fluid for multiphase interactions: water, vapor water and air. The cavitation behavior was observed first without aeration, then followed by air injection simulations to investigate the effect of aeration. Each case was simulated for 12 cycles at rotational speeds of 1000, 2000, 3000, 4000, and 5000 rpm. The Vapor Volume Fraction (VVF) and the output mechanical power were monitored throughout the simulations. The data acquired from the simulations were compared to the experimental results for verifications. It was observed that the cavitation was mitigated in both the computer simulations and the experiment testing reaching up to 49.7% as an average reduction, while the output power was reduced by 6.6%

Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study

Abstract In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant

Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1

Background No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients. Objective The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods The prognostic score was developed using uni- & multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort. Results In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60-202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95% CI 0.790-0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25-142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%-24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%-9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%-11.4%); C-statistic 0.744 [95% CI 0.644-0.844]). Conclusions A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated