Sarcopenia from mechanism to diagnosis and treatment in liver disease

Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and is a frequent complication in cirrhosis that adversely affects clinical outcomes. These include survival, quality of life, development of other complications and post liver transplantation survival. Radiological image analysis is currently utilized to diagnose sarcopenia in cirrhosis. Nutrient supplementation and physical activity are used to counter sarcopenia but have not been consistently effective because the underlying molecular and metabolic abnormalities persist or are not influenced by these treatments. Even though alterations in food intake, hypermetabolism, alterations in amino acid profiles, endotoxemia, accelerated starvation and decreased mobility may all contribute to sarcopenia in cirrhosis, hyperammonemia has recently gained attention as a possible mediator of the liver-muscle axis. Increased muscle ammonia causes: cataplerosis of α-ketoglutarate, increased transport of leucine in exchange for glutamine, impaired signaling by leucine, increased expression of myostatin (a transforming growth factor beta superfamily member) and an increased phosphorylation of eukaryotic initiation factor 2α. In addition, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy mediated proteolysis, also play a role. These molecular and metabolic alterations may contribute to the anabolic resistance and inadequate response to nutrient supplementation in cirrhosis. Central and skeletal muscle fatigue contributes to impaired exercise capacity and responses. Use of proteins with low ammoniagenic potential, leucine enriched amino acid supplementation, long-term ammonia lowering strategies and a combination of resistance and endurance exercise to increase muscle mass and function may target the molecular abnormalities in the muscle. Strategies targeting endotoxemia and the gut microbiome need further evaluatio

A new Definition and Classification of Physical Unclonable Functions

A new definition of "Physical Unclonable Functions" (PUFs), the first one that fully captures its intuitive idea among experts, is presented. A PUF is an information-storage system with a security mechanism that is 1. meant to impede the duplication of a precisely described storage-functionality in another, separate system and 2. remains effective against an attacker with temporary access to the whole original system. A novel classification scheme of the security objectives and mechanisms of PUFs is proposed and its usefulness to aid future research and security evaluation is demonstrated. One class of PUF security mechanisms that prevents an attacker to apply all addresses at which secrets are stored in the information-storage system, is shown to be closely analogous to cryptographic encryption. Its development marks the dawn of a new fundamental primitive of hardware-security engineering: cryptostorage. These results firmly establish PUFs as a fundamental concept of hardware security.Comment: 6 pages, 3 figures; Proceedings "CS2 '15 Proceedings of the Second Workshop on Cryptography and Security in Computing Systems", Amsterdam, 2015, ACM Digital Librar

Bleeding with direct oral anticoagulants vs warfarin: clinical experience.

The risk of bleeding in the setting of anticoagulant therapy continues to be re-evaluated following the introduction of a new generation of direct oral anticoagulants (DOACs). Interruption of DOAC therapy and supportive care may be sufficient for the management of patients who present with mild or moderate bleeding, but in those with life-threatening bleeding, a specific reversal agent is desirable. We review the phase 3 clinical studies of dabigatran, rivaroxaban, apixaban, and edoxaban in patients with nonvalvular atrial fibrillation, in the context of bleeding risk and management

Contagion effects of successive bond rating downgrades

The object of this paper is to study the impact of successive changes in ratings of a leading firm on competitors of the same sector. Two courses of research are being mobilized regarding, on the one hand, the incidence of downgrading of ratings on the value of the firms and on the other hand, the contagion effects associated with the report of bad news. The analysis of the successive downgrading of the ratings of Alcatel, world leader in the telecommunications infrastructure allows us to point out the contagion effects among the main French and European competitors.Ratings, Contagion effects, Event studies, Telecommunications.

Grand Rounds: What\u27s in It for You?

No abstract available

Beta-blokers in patients with cirrhosis and infection: don't blame too soon.

We found that PPI-users had a higher rate and BBs-users a lower rate of infections. The lower infection rate and better prognosis of BB-users can not be attributed, as suggested by Schiavon et al., to a higher proportion of variceal bleeding in this group; in fact, the large majority of patients hospitalized for bleeding were excluded from the study as they came to our ward already on systemic antibiotic treatment (which is usually started in the Emergency room) and this would have represented a confounding factor. Only few patients with variceal bleeding were included: they developed bleeding after enrolment and were equally distributed between those taking and not taking BBs. Following the recent debate about the ‘therapeutic window’ of BBs in cirrhotic patients (2–4), we were also interested in evaluating possible harmful effects of BBs in cirrhotic patients with infections. This was a secondary aim of our study and we certainly recognize that the study was underpowered for this purpose

Albumin infusion in cirrhotic patients with infections other than spontaneous bacterial peritonitis: End of the story?

Non-invasive assessment of liver fibrosis with impulse elastography: Comparison of Supersonic Shear Imaging with ARFI and FibroScan

The use of non-selective beta-blockers in patients with cirrhosis: more doubts than certainties

In conclusion, prospective RCT would be needed on the use of NSBBs in decompensated cirrhotic patients with ascites however these trials are difficult to organize and will need a large sample size. A case control study could be useful if the two groups were patients matched for MELD, MELD Na, creatinine, mean arterial pressure, with the same type of ascites (refractory, recurrent, severe) taking or not taking NSBBs. The better and more relevant end pointshould probably be survival. In the meanwhile, the Baveno recommendations can be utilized in clinical practice to remind that severe hypotension is a well-known contraindication for NSBBs which may suggest dose reduction or even therapy discontinuation. Last but not least, NSBBs may have several beneficial effects in patients with cirrhosis beyond the reduction in portal hypertension. They reduce markers of intestinal permeability, bacterial translocation and systemic inflammation, and also the risk of SBP (15,16). The risk to enlarge the indication to stop NSBBs in cirrhotic patients without a real evidence could be as to “throw the baby out with the bath water

A Behavioural Approach To Financial Puzzles

Many financial puzzles have been solved, at least partially, by the introduction of alternative assumptions on the behaviour of investors. Cumulative prospect theory and mental accounting are two such approaches which are used in this paper to analyze some of the most important financial puzzles. We first focus our attention on anomalies (or considered as such in the standard expected utility model) at the individual level, for example the disposition effect or the low diversification puzzle. We then address two aggregate puzzles, namely the equity premium puzzle and the return predictability puzzle. We show how recent behavioral models allow to explain these anomalies in a very natural way.