a b s t r a c t a r t i c l e i n f oAcute liver failure is a rare but potentially devastating disease. Throughout the last few decades, acute liver failure outcomes have been improving in the context of the optimized overall management. This positive trend has been associated with the earlier recognition of this condition, the improvement of the intensive care unit management, and the developments in emergent liver transplantation. Accordingly, we aimed to review the current diagnostic and therapeutic approach to this syndrome, especially in the intensive care unit setting.

The development of human cell models that can efficiently restore hepatic functionality and cope with the reproducibility and scalability required for preclinical development poses a significant effort in tissue engineering and biotechnology. Primary cultures of human hepatocytes (HHs), the preferred model for in vitro toxicity testing, dedifferentiate and have short-term viability in two-dimensional (2D) cultures. In this study, hepatocytes isolated from human liver tissue were co-cultured with human bone marrow mesenchymal stem cells (BM-MSCs) as spheroids in automated, computer-controlled, stirred-tank bioreactors with perfusion operation mode. A dual-step inoculation strategy was used, resulting in an inner core of parenchymal liver tissue with an outer layer of stromal cells. Hepatocyte polarization and morphology as well as the mesenchymal phenotype of BM-MSCs were maintained throughout the culture period and the crosstalk between the two cell types was depicted. The viability, compact morphology and phenotypic stability of hepatocytes were enhanced in co-cultures in comparison to monocultures. Gene expression of phase I and II enzymes was higher and CYP3A4 and CYP1A2 activity was inducible until week 2 of culture, being applicable for repeated-dose toxicity testing. Moreover, the excretory activity was maintained in co-cultures and the biosynthetic hepatocellular functions (albumin and urea secretion) were not affected by the presence of BM-MSCs. This strategy might be extended to other hepatic cell sources and the characterization performed brings knowledge on the interplay between the two cell types, which may be relevant for therapeutic applications. Copyright © 2015 John Wiley & Sons, Ltd.

SOD-enzymosomes were shown to be a new and successful therapeutic approach to oxidative stress-associated inflammatory situations/diseases.

The authors analyzed 704 transthoracic echocardiographic (TTE) examinations, performed routinely to all admitted patients to a general 16-bed Intensive Care Unit (ICU) during an 18-month period. Data acquisition and prevalence of abnormalities of cardiac structures and function were assessed, as well as the new, previously unknown severe diagnoses.A TTE was performed within the first 24 h of admission on 704 consecutive patients, with a mean age of 61.5 ± 17.5 years, ICU stay of 10.6 ± 17.1 days, APACHE II 22.6 ± 8.9, and SAPS II 52.7 ± 20.4. In four patients, TTE could not be performed. Left ventricular (LV) dimensions were quantified in 689 (97.8%) patients, and LV function in 670 (95.2%) patients. Cardiac output (CO) was determined in 610 (86.7%), and mitral E/A in 399 (85.9% of patients in sinus rhythm). Echocardiographic abnormalities were detected in 234 (33%) patients, the most common being left atrial (LA) enlargement (n = 163), and LV dysfunction (n = 132). Patients with these alterations were older (66 ± 16.5 vs 58.1 ± 17.4, p b 0.001), presented a higher APACHE II score (24.4 ± 8.7 vs 21.1 ± 8.9, p b 0.001), and had a higher mortality rate (40.1% vs 25.4%, p b 0.001). Severe, previously unknown echocardiographic diagnoses were detected in 53 (7.5%) patients; the most frequent condition was severe LV dysfunction. Through a multivariate logistic regression analysis, it was determined that mortality was affected by tricuspid regurgitation (p = 0.016, CI 1.007-1.016) and ICU stay (p b 0.001, CI 1-1.019). We conclude that TTE can detect most cardiac structures in a general ICU. One-third of the patients studied presented cardiac structural or functional alterations and 7.5% severe previously unknown diagnoses.

This study sought to evaluate the potential impact of domino liver transplantation (DLT) on initial graft function and early postoperative outcome in patients with cirrhosis in a Portuguese liver transplantation center. A retrospective comparative analysis was performed between 77 domino recipients (from familial amyloidotic polyneuropathy donors) and 91 deceased donor recipients, all submitted to primary elective whole liver transplantation, using the piggyback technique, in a 42-month period. Outcome parameters included graft dysfunction (defined as either primary nonfunction or initial poor function, according to the Ploeg-Maring criteria) and Clavien II-IV complications in the first postoperative week. Domino and deceased donor recipients had similar preoperative severity indices (Child-Pugh classification and Model for End-Stage Liver Disease score) and immediate postoperative severity scores (APACHE II [Acute Physiology and Chronic Health Evaluation II] and SAPS II [Simplified Acute Physiology Score II]). In DLT, donors were younger, cold ischemia time was shorter, and intraoperative transfusion requirements of packed red blood cells and fresh-frozen plasma were significantly lower. Graft dysfunction incidence was 3.4-fold lower in DLT: 5.2% (only 4 cases of initial poor function) versus 18.0% (1 primary nonfunction and 15 cases of initial poor function), P ¼ 0.010. Postoperative bleeding was the most frequent early Clavien II-IV complication (n ¼ 29, 17.3%), with an incidence 2.2-fold lower in domino recipients. A statistically significant difference was not found in the other analyzed Clavien II-IV complications, intensive care unit stay, mechanical ventilation time, intensive care unit mortality, and 1-year survival rate. In conclusion, in this study the younger donors and shorter ischemic time associated with DLT may provide a protective role in regards to graft dysfunction and perioperative bleeding, which are 2 important determinants of early morbidity after liver transplantation. Liver Transpl 17:270-278, 2011. V C 2011 AASLD.Received May 11, 2010; accepted October 2, 2010.The sequential or domino liver transplantation (DLT), using the morphologically normal liver from a familial amyloidotic polyneuropathy (FAP) patient, was first performed in 1995. 1,2 The DLT created a new category of donors and expanded the donor pool, but also raised new technical and ethical issues. 3,4 A technical difficulty arose because domino donors and recipients must share a relatively short segment of the suprahepatic vena cava. Regarding this technical issue, the conventional technique (retrohepatic vena cava excision and venovenous bypass) has been traditionally used in the FAP patient, nonetheless with potential complications. 3,5 A modified piggyback technique, 6 with reconstruction of the suprahepatic venous outflow of the domino graft, allowed FAP hepatectomy to be performed with inferior vena cava preservation and became the standard domino technique in our center. The DLT has also created an ethical dilemma conce...