Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In ...this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines’ Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.
Preliminary studies on HCV‐cirrhotics listed for transplant suggest that sofosbuvir in combination with ribavirin is very effective in promoting viral clearance and preventing disease recurrence. ...Unfortunately, the high cost of such treatment (€46 500 per 12 weeks of treatment) makes its cost‐effectiveness questionable. A semi‐Markov model was developed to assess the cost‐effectiveness of sofosbuvir/ribavirin treatment in cirrhotic patients without HCC (HCV‐CIRRH) and with HCC (HCV‐HCC) listed for transplant. In the base‐case analysis, the incremental cost‐effectiveness ratio for 24 weeks of sofosbuvir/ribavirin was €44 875 per quality‐adjusted life‐year gained in HCV‐CIRRH and €60 380 in HCV‐HCC patients. Both results were above the willingness to pay threshold of €37 000 per quality‐adjusted life‐year. Our data also show that in order to remain cost‐effective (with a 24‐week treatment), any novel interferon‐free treatment endowed with ideal efficacy should cost less than €67 224 or €95 712 in HCV‐cirrhotics with and without HCC, respectively. The results shows that sofosbuvir/ribavirin therapy, given to patients listed for transplant, is not cost‐effective at current prices despite being very effective, and new, more effective treatments will have little economic margins to remain cost‐effective. New interferon‐free combinations have the potential to revolutionize the treatment and prognosis of HCV‐positive patients listed for transplant; however, without sustainable prices, this revolution is unlikely to happen.
The authors show that DAA‐based interferon‐free treatments in patients listed for transplantation are borderline cost‐effective at the current price, and the cost‐effectiveness estimates are critically influenced by the duration of treatment. See editorial by Brown on page 1741.
Probably as a function of their wide geographical distribution, the different population of Macrobrachium amazonicum shrimp may present distinct physiological, biochemical, reproductive, behavioral, ...and ecological patterns. These differences are so accentuated that the existence of allopatric speciation has been suggested, although initial studies indicate that the genetic variability of populations happen at an intraspecific level. Among the biological responses described for M. amazonicum populations, those regarding osmoregulation and metabolism play a key role for being related to the occupation of diverse habitats. To this effect, we investigated osmoregulation through the role of free amino acids in cell volume control and metabolism, through oxygen consumption in larvae (zoeae I, II, V and IX) and/or post-larvae of a M. amazonicum population from Amazon, kept in aquaculture fish hatcheries in the state of São Paulo. The results add information regarding the existence of distinct physiological responses among M. amazonicum populations and suggest that possible adjustments to metabolism and to the use of free amino acids as osmolytes of the regulation of the larvae and post-larvae cell volume depend on the appearance of structures responsible for hemolymph osmoregulation like, for example, the gills. In this respect, we verified that zoeae I do not alter their metabolism due to the exposition to fresh or brackish water, but they reduce intracellular concentration of free amino acids when exposed to fresh water, what may suggest the inexistence or inefficient performance of the structures responsible for volume regulation and hemolymph composition. On the other hand, in zoeae II and V exposed to fresh and brackish water, metabolism alterations were not followed by changes in free amino acids concentration. Thus it is possible, as the structures responsible for osmoregulation and ionic regulation become functional, that the role of free amino acids gets diminished and oxygen consumption elevated, probably due to greater energy expenditure with the active transportation of salts through epithelial membranes. Osmotic challenges also seem to alter throughout development, given that in zoeae II oxygen consumption is elevated on brackish water of 18, but in zoeae V it happens in fresh water. After M. amazonicum metamorphosis, free amino acids begin to play an important role as intracellular osmolytes, because we verified an increase of up to 40% in post-larvae exposed to brackish water of 18. The main free amino acids involved in cell volume regulation of ontogenetic stages evaluated were the non essential ones: glutamic acid, glycine, alanine, arginine, and proline. Interestingly, larvae from estuarine population studied here survived until the zoeae V stage in fresh water, but in some populations far from the sea, zoeae die right after eclosion in fresh water or they do not reach zoeae III stage. In addition, given that in favorable conditions caridean shrimp larvae shorten their development, we may infer that the cultivation environment, in which larvae developed in the present work, was appropriate, because almost all zoeae VIII kept on brackish water underwent metamorphosis directly to post-larvae and did not go through zoeae IX stage.
Summary
Different strategies of DAAs treatment are currently possible both pre‐ and postliver transplantation (LT). Clinical and economic consequences of these strategies still need to be adequately ...investigated; this study aims at assessing their cost‐effectiveness. A decision analytical model was created to simulate the progression of HCV‐infected patients listed for decompensated cirrhosis (DCC) or for hepatocellular carcinoma (HCC). Three DAAs treatment strategies were compared: (i) a 12‐week course of DAAs prior to transplantation (PRE‐LT), (ii) a 4‐week course of DAAs starting at the time of transplantation (PERI‐LT) and (iii) a 12‐week course of DAAs administered at disease recurrence (POST‐LT). The population was substratified according to HCC presence and, in those without HCC, according to the MELD score at listing. Data on DAAs effectiveness were estimated using a cohort of patients still followed by 11 transplant centres of the European Liver and Intestine Transplant Association and by data available in the literature. In this study, PRE‐LT treatment strategy was dominant for DCC patients with MELD<16 and cost‐effective for those with MELD16‐20, while POST‐LT strategy emerged as cost‐effective for DCC patients with MELD>20 and for those with HCC. Sensitivity analyses confirmed PRE‐LT as the cost‐effective strategy for patients with MELD≤20. In conclusion, PRE‐LT treatment is cost‐effective for patients with MELD≤20 without HCC, while treatments after LT are cost‐effective in cirrhotic patients with MELD>20 and in those with HCC. It is worth reminding, though, that the final choice of a specific regimen at the patient level will have to be personalized based on clinical, social and transplant‐related factors.
Focal splenic lesions: US findings Caremani, M.; Occhini, U.; Caremani, A. ...
Journal of ultrasound,
06/2013, Volume:
16, Issue:
2
Journal Article
Peer reviewed
Open access
Ultrasound (US) imaging of the spleen was considered of little use in the past and was performed only to distinguish between cystic and solid lesions. However, in the last decade due to experience ...acquired and the introduction of second-generation contrast agents, this technique has been re-evaluated as contrast-enhanced US (CEUS) allows detection and characterization of most focal lesions of the spleen with a high sensitivity and a good specificity. Gray-scale US presents a low specificity in splenic infarctions with a high rate of false negative cases, whereas specificity reaches 100 %, if the examination is performed using US contrast agents. Gray-scale US can provide a correct diagnosis in simple cysts, whereas CEUS is useful when cystic lymphangioma is suspected. In the study of splenic lesions, the most important problem is to differentiate between angioma, hamartoma, lymphoma, and metastasis. CEUS reaches a good specificity in the differentiation of benign from malignant splenic lesions, as hypo-enhancement in the parenchymal phase is predictive of malignancy in 87 % of cases. In conclusion, Gray-scale US and particularly CEUS are at present widely indicated in the study of focal splenic lesions.
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