Is de novo hepatocellular carcinoma after transjugular intrahepatic portosystemic shunt increased?

BACKGROUND: Portal hypertension is a major complication of liver cirrhosis. Transjugular intrahepatic portosystemic shunt is effective in treatment of portal hypertension. However, decreased parenchymal portal venous flow after transjugular intrahepatic portosystemic shunt insertion favours ischaemic liver injury which has been discussed to induce hepatocarcinogenesis causing hepatocellular cancer. AIM: This study aimed to explore the association between transjugular intrahepatic portosystemic shunt placement and the development of hepatocellular cancer. METHODS: A total of 1338 consecutive liver cirrhosis patients were included in this retrospective study between January 2004-December 2015. Data were analysed with regard to development of hepatocellular cancer during follow-up. Binary logistic regression and Kaplan-Meier analyses were conducted for the assessment of risk factors for hepatocellular cancer development. In a second step, to rule out confounders of group heterogeneity, case-control matching was performed based on gender, age, model of end-stage liver disease score and underlying cause of cirrhosis (non-alcoholic steatohepatitis, alcoholic liver disease and viral hepatitis). RESULTS: Besides established risk factors such as older age, male gender and underlying viral hepatitis, statistical analysis revealed the absence of transjugular intrahepatic portosystemic shunt insertion as a risk factor for hepatocellular cancer development. Furthermore, matched-pair analysis of 432 patients showed a significant difference (p = 0.003) in the emergence of hepatocellular cancer regarding transjugular intrahepatic portosystemic shunt placement versus the non-transjugular intrahepatic portosystemic shunt cohort. CONCLUSION: In patients with end-stage liver disease, transjugular intrahepatic portosystemic shunt insertion is significantly associated with reduced rates of hepatocellular cancer development.

Interplay of H2A deubiquitinase 2A-DUB/Mysm1 and the p19(ARF)/p53 axis in hematopoiesis, early T-cell development and tissue differentiation.

Monoubiquitination of core histone 2A (H2A-K119u) has a critical role in gene regulation in hematopoietic differentiation and other developmental processes. To explore the interplay of histone H2A deubiquitinase Myb-like SWIRM and MPN domain containing1 (2A-DUB/Mysm1) with the p53 axis in the sequential differentiation of mature lymphocytes from progenitors, we systematically analyzed hematopoiesis and early T-cell development using Mysm1(-/-) and p53(-/-)Mysm1(-/-) mice. Mysm1(-/-) thymi were severely hypoplastic with <10% of wild-type cell numbers as a result of a reduction of early thymocyte progenitors in context with defective hematopoietic stem cells, a partial block at the double-negative (DN)1-DN2 transition and increased apoptosis of double-positive thymocytes. Increased rates of apoptosis were also detected in other tissues affected by Mysm1 deficiency, including the developing brain and the skin. By quantitative PCR and chromatin immunoprecipitation analyses, we identified p19(ARF), an important regulator of p53 tumor suppressor protein levels, as a potential Mysm1 target gene. In newly generated p53(-/-)Mysm1(-/-) double-deficient mice, anomalies of Mysm1(-/-) mice including reduction of lymphoid-primed multipotent progenitors, reduced thymocyte numbers and viability, and interestingly defective B-cell development, growth retardation, neurological defects, skin atrophy, and tail malformation were almost completely restored as well, substantiating the involvement of the p53 pathway in the alterations caused by Mysm1 deficiency. In conclusion, this investigation uncovers a novel link between H2A deubiquitinase 2A-DUB/Mysm1 and suppression of p53-mediated apoptotic programs during early lymphoid development and other developmental processes.

Partial liquid ventilation: effects of closed breathing systems, heat-and-moisture-exchangers and sodalime absorbers on perfluorocarbon evaporation.

BACKGROUND AND OBJECTIVES: During partial liquid ventilation perfluorocarbons are instilled into the airways from where they subsequently evaporate via the bronchial system. This process is influenced by multiple factors, such as the vapour pressure of the perfluorocarbons, the instilled volume, intrapulmonary perfluorocarbon distribution, postural positioning and ventilatory settings. In our study we compared the effects of open and closed breathing systems, a heat-and-moisture-exchanger and a sodalime absorber on perfluorocarbon evaporation during partial liquid ventilation. METHODS: Isolated rat lungs were suspended from a force transducer. After intratracheal perfluorocarbon instillation (10 mL kg(-1)) the lungs were either ventilated with an open breathing system (n = 6), a closed breathing system (n = 6), an open breathing system with an integrated heat-and-moisture-exchanger (n = 6), an open breathing system with an integrated sodalime absorber (n = 6), or a closed breathing system with an integrated heat-and-moisture-exchanger and a sodalime absorber (n = 6). Evaporative perfluorocarbon elimination was determined gravimetrically. RESULTS: When compared to the elimination half-life in an open breathing system (1.2 +/- 0.07 h), elimination half-life was longer with a closed system (6.4 +/- 0.9 h, P 0.05) when compared to a closed system. CONCLUSIONS: Evaporative perfluorocarbon loss can be reduced effectively with closed breathing systems, followed by the use of sodalime absorbers and heat-and-moisture-exchangers.

Exact determination of UV-induced crosslinks in 16S ribosomal RNA in 30S ribosomal subunits.

Escherichia coli 30S ribosomal subunits were UV-irradiated to induce intramolecular crosslinks in the 16S rRNA. Intact 16S rRNA was purified and subjected to gel electrophoresis, under denaturing conditions, to separate molecules on the basis of the crosslinked loop size. Molecules separated this way were enriched for specific crosslinks and could be analyzed by the reverse transcription arrest assay to determine exact crosslinking sites. Thirteen crosslinking sites have been identified at single nucleotide resolution. Of these, eight are within or adjacent to secondary structure elements: one of these (C582 x G760) involves an interaction between nucleotides within an interior loop, one (C1402 x X1501) involves an interaction between nucleosides in adjacent base pairs, and the others involve interactions between nucleotides that are within junction regions (A441 x G494, U562 x U884, C934 x U1345, and U991 x U1212) or are interactions between nucleotides (C54 x A353 and U1052 x C1200) that somehow cross known base pairs. Five other crosslinks connect sites distant in the secondary structure and provide global constraints for the arrangement of RNA regions within RNA domains I and II (U244 x G894, G894 x A1468, C967 x C1400) and within domain III (U1126 x C1281 and A1093 x G1182). These crosslinks, known at single-nucleotide resolution, are useful in the prediction of local RNA regions, as well as the global structure.

[Small-caliber polyurethane arterial prosthesis: clinical and angiomorphological follow-up of 20 patients in a prospective study]. / Prothèses artérielles de petit calibre en polyuréthane: Suivi clinique at angio-morphologique de 20 patients d'une étude prospective.

The five year patency rate for femoropopliteal vein bypass grafts is around 70% according to the literature. Patency rates for synthetic grafts (eg PTFE, Dacron) range between 43 and 57%. If a vein is not available there is a new polyurethane 6 mm artery substitute on the market, that has shown in vitro promising physical characteristics and good long term results after implantation in dogs. In a prospective, randomized trial the results of the new polyurethane graft (PUR) were compared with those of a Dacron graft of the same diameter. Included in the study were 20 patients with lower limb ischemia stage Fontaine II B, III and IV, 10 in each group. Patency rates, handling of the graft and complications were analysed. During the one year follow up 7 PUR grafts had to be changed due to recurrent bypass occlusion within the first 3 months. At the end of the year there were only one PUR-bypass but 8 Dacron grafts open. 5 PUR grafts were examined histologically and no morphological reason for the occlusion, especially no myointimal hyperplasia, was found. A special regard was brought to the arterial run-off in both groups. It was confirmed to be comparable with only slightly better data for the PUR group. The exact reasons for the astonishing bad results of the PUR graft for femoropopliteal above knee bypass cannot be explained in our study. Due to the unexpected high occlusion rate the study was stopped earlier then planned.

The results of posterior chamber lens implantation in a teaching hospital.

In 1984 extracapsular cataract extraction with the implantation of a posterior chamber lens became the procedure of choice in the treatment of cataracts at this institution. A retrospective study was carried out to assess the results of this operation in the hands of registrars. The results suggest that extracapsular cataract extraction with the implantation of a posterior chamber lens can be performed safely and effectively in a residency setting when accompanied by appropriate education and faculty supervision.