A simple dummy liver assist device prolongs anhepatic survival in a porcine model of total hepatectomy by slight hypothermia

<p>Abstract</p> <p>Background</p> <p>Advances in intensive care support such as therapeutic hypothermia or new liver assist devices have been the mainstay of treatment attempting to bridge the gap from acute liver failure to liver transplantation, but the efficacy of the available devices in reducing mortality has been questioned. To address this issue, the present animal study was aimed to analyze the pure clinical effects of a simple extracorporeal dummy device in an anhepatic porcine model of acute liver failure.</p> <p>Methods</p> <p>Total hepatectomy was performed in ten female pigs followed by standardized intensive care support until death. Five animals (dummy group, n = 5) underwent additional cyclic connection to an extracorporeal dummy device which consisted of a plasma separation unit. The separated undetoxified plasma was completely returned to the pigs circulation without any plasma substitution or exchange in contrast to animals receiving intensive care support alone (control group, n = 5). All physiological parameters such as vital and ventilation parameters were monitored electronically; laboratory values and endotoxin levels were measured every 8 hours.</p> <p>Results</p> <p>Survival of the dummy device group was 74 ± 6 hours in contrast to 53 ± 5 hours of the control group which was statistically significant (p < 0.05). Body temperature 24 hours after hepatectomy was significantly lower (36.5 ± 0.5°C vs. 38.2 ± 0.7°C) in the dummy device group. Significant lower values were measured for blood lactate (1.9 ± 0.2 vs. 2.5 ± 0.5 mM/L) from 16 hours, creatinine (1.5 ± 0.2 vs. 2.0 ± 0.3 mg/dL) from 40 hours and ammonia (273 ± 122 vs. 1345 ± 700 μg/dL) from 48 hours after hepatectomy until death. A significant rise of endotoxin levels indicated the onset of sepsis at time of death in 60% (3/5) of the dummy device group animals surviving beyond 60 hours from hepatectomy.</p> <p>Conclusions</p> <p>Episodes of slight hypothermia induced by cyclic connection to the extracorporeal dummy device produced a significant survival benefit of more than 20 hours through organ protection and hemodynamic stabilisation. Animal studies which focus on a survival benefit generated by liver assist devices should especially address the aspect of slight transient hypothermia by extracorporeal cooling.</p

Jewish Immigrants in Israel: Disintegration Within Integration?

In her chapter, ‘Disintegration within integration’, Amandine Desille examines more recent transformations of Israel’s Law of Return – the Israeli immigration policy which provides the (imagined) repatriation of Diaspora Jews to Israel – in a context of liberalisation of the Israeli economy and the devolution of power to local authorities. Today, new immigrants follow two paths of ‘integration’: ‘direct absorp-tion’, where immigrants are granted benefits while being free to settle wherever they find fit; and ‘community absorption’, where immigrants are placed in ‘absorption centres’ and see their entitlements conditioned by residence, religious observance and more. Those two paths are ‘ethnicised’ in the sense that they depend on country of origin – Western immigrants, considered as economically useful, benefit from direct absorption and a more pluralist attitude of local governments, while immi-grants from Africa and Asia are the objects of an assimilationist policy. This situa-tion of ‘(dis)integration’ within what is supposed to be an inclusive immigrant policy for all Jews, shows the extent to which new criteria of perceived economic performance limit the integration of specific segments of newcomers. The rescaling of immigration and immigrant policies to subnational governments, although it has introduced a more multicultural approach, antagonist to the assimilationist ideology at work in Israel, has not enabled an alternative policy framework which is more accommodating to all.info:eu-repo/semantics/publishedVersio

Profiling the Impact of Medium Formulation on Morphology and Functionality of Primary Hepatocytes in vitro

The characterization of fully-defined in vitro hepatic culture systems requires testing of functional and morphological variables to obtain the optimal trophic support, particularly for cell therapeutics including bioartificial liver systems (BALs). Using serum-free fully-defined culture medium formulations, we measured synthetic, detoxification and metabolic variables of primary porcine hepatocytes (PPHs) - integrated these datasets using a defined scoring system and correlated this hepatocyte biological activity index (HBAI) with morphological parameters. Hepatic-specific functions exceeded those of both primary human hepatocytes (PHHs) and HepaRG cells, whilst retaining biotransformation potential and in vivo-like ultrastructural morphology, suggesting PPHs as a potential surrogate for PHHs in various biotech applications. The HBAI permits assessment of global functional capacity allowing the rational choice of optimal trophic support for a defined operational task (including BALs, hepatocellular transplantation, and cytochrome P450 (CYP450) drug metabolism studies), mitigates risk associated with sub-optimal culture systems, and reduces time and cost of research and therapeutic applications

Stud Health Technol Inform

Development of biobanks is still hampered by difficulty to collect high quality sample annotations using patient clinical information. The IBCB project evaluated the feasibility of a nationwide clinical data research network for this purpose. METHOD: the infrastructure, based on eHOP and I2B2 technologies, was interfaced with the legacy IT components of 3 hospitals. The evaluation focused on the data management process and tested 5 expert queries in Hepatocarcinoma. RESULTS: the integration of biobank data was comprehensive and easy. Five out of 5 queries were successfully performed and shown consistent results with the data sources excepted one query which required to search in unstructured data. The platform was designed to be scalable and showed that with few effort biobank data and clinical data can be integrated and leveraged between hospitals. Clinical or phenotyping concepts extraction techniques from free text could significantly improve the samples annotation with fine granularity information

P0709 : Survival of patients infected by chronic hepatitis c and f0f1 fibrosis at baseline after a 15 years follow-up

International audienceno abstrac

Chyme reinfusion restores the regulatory bile salt-FGF19 axis in intestinal failure patients

International audienceBackground and aims - Automated chyme reinfusion (CR) in patients with intestinal failure (IF) and a temporary double enterostomy (TDE) restores intestinal function and protects against liver injury, but the mechanisms are incompletely understood. The aim was to investigate whether the beneficial effects of CR relate to functional recovery of enterohepatic signaling through the bile salt-FGF19 axis. Approach and results - Blood samples were collected from 12 patients, 3 days before, at start, and 1, 3, 5, and 7 weeks after CR initiation. Plasma FGF19, total bile salts (TBS), 7-α-hydroxy-4-cholesten-3-one (C4; a marker of bile salt synthesis), citrulline (CIT), bile salt composition, liver tests, and nutritional risk indices were determined. Paired small bowel biopsies prior to CR and after 21 days were taken, and genes related to bile salt homeostasis and enterocyte function were assessed. CR induced an increase in plasma FGF19 and decreased C4 levels, indicating restored regulation of bile salt synthesis through endocrine FGF19 action. TBS remained unaltered during CR. Intestinal farnesoid X receptor was up-regulated after 21 days of CR. Secondary and deconjugated bile salt fractions were increased after CR, reflecting restored microbial metabolism of host bile salts. Furthermore, CIT and albumin levels gradually rose after CR, while abnormal serum liver tests normalized after CR, indicating restored intestinal function, improved nutritional status, and amelioration of liver injury. CR increased gene transcripts related to enterocyte number, carbohydrate handling, and bile salt homeostasis. Finally, the reciprocal FGF19/C4 response after 7 days predicted the plasma CIT time course. Conclusions - CR in patients with IF-TDE restored bile salt-FGF19 signaling and improved gut-liver function. Beneficial effects of CR are partly mediated by recovery of the bile salt-FGF19 axis and subsequent homeostatic regulation of bile salt synthesis

Correction: An Alternative to the Light Touch Digital Health Remote Study: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study.

[This corrects the article DOI: 10.2196/32165.]