by Keyword: TIPS

Blaya, D, Pose, E, Coll, M, Lozano, JJ, Graupera, I, Schierwagen, R, Jansen, C, Castro, P, Fernandez, S, Sidorova, J, Vasa-Nicotera, M, Sola, E, Caballeria, J, Trebicka, J, Gines, P, Sancho-Bru, P, (2021). Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure Jhep Rep 3, 100233

Background & Aims: MicroRNAs (miRNAs) circulate in several body fluids and can be useful biomarkers. The aim of this study was to identify blood-circulating miRNAs associated with cirrhosis progression and acute-on-chronic liver failure (ACLF). Methods: Using high-throughput screening of 754 miRNAs, serum samples from 45 patients with compensated cirrhosis, decompensated cirrhosis, or ACLF were compared with those from healthy individuals (n = 15). miRNA levels were correlated with clinical parameters, organ failure, and disease progression and outcome. Dysregulated miRNAs were evaluated in portal and hepatic vein samples (n = 33), liver tissues (n = 17), and peripheral blood mononuclear cells (PBMCs) (n = 16). Results: miRNA screening analysis revealed that circulating miRNAs are dysregulated in cirrhosis progression, with 51 miRNAs being differentially expressed among all groups of patients. Unsupervised clustering and principal component analysis indicated that the main differences in miRNA expression occurred at decompensation, showing similar levels in patients with decompensated cirrhosis and those with ACLF. Of 43 selected miRNAs examined for differences among groups, 10 were differentially expressed according to disease progression. Moreover, 20 circulating miRNAs were correlated with model for end-stage liver disease and Child-Pugh scores. Notably, 11 dysregulated miRNAs were associated with kidney or liver failure, encephalopathy, bacterial infection, and poor outcomes. The most severely dysregulated miRNAs (i.e. miR-146a5p, miR-26a-5p, and miR-191-5p) were further evaluated in portal and hepatic vein blood and liver tissue, but showed no differences. However, PBMCs from patients with cirrhosis showed significant downregulation of miR-26 and miR-146a, suggesting a extrahepatic origin of some circulating miRNAs. Conclusions: This study is a repository of circulating miRNA data following cirrhosis progression and ACLF. Circulating miRNAs were profoundly dysregulated during the progression of chronic liver disease, were associated with failure of several organs and could have prognostic utility. Lay summary: Circulating miRNAs are small molecules in the blood that can be used to identify or predict a clinical condition. Our study aimed to identify miRNAs for use as biomarkers in patients with cirrhosis or acute-on-chronic liver failure. Several miRNAs were found to be dysregulated during the progression of disease, and some were also related to organ failure and disease-related outcomes. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).

JTD Keywords: aclf, acute-on-chronic liver failure, alt, alanine aminotransferase, ast, aspartate aminotransferase, biomarkers, chronic liver disease, cxcl10, c-x-c motif chemokine ligand 10, ef clif, european foundation for the study of chronic liver failure, foxo, forkhead box o, inr, international normalised ratio, ldh, lactate dehydrogenase, liver decompensation, mapk, mitogen-activated protein kinase, meld, model for end-stage liver disease, nash, non-alcoholic steatohepatitis, non-coding rnas, pbmcs, peripheral blood mononuclear cells, pca, principal component analysis, tgf, transforming growth factor, tips, transjugular intrahepatic portosystemic shunt, Biomarkers, Chronic liver disease, Expression, Liver decompensation, Markers, Mir-146a, Non-coding rnas, Qpcr, quantitative pcr

Praktiknjo, M., Simón-Talero, M., Römer, J., Roccarina, D., Martínez, J., Lampichler, K., Baiges, A., Low, G., Llop, E., Maurer, M. H., Zipprich, A., Triolo, M., Maleux, G., Fialla, A. D., Dam, C., Vidal-González, J., Majumdar, A., Picón, C., Toth, D., Darnell, A., Abraldes, J. G., López, M., Jansen, C., Chang, J., Schierwagen, R., Uschner, F., Kukuk, G., Meyer, C., Thomas, D., Wolter, K., Strassburg, C. P., Laleman, W., La Mura, V., Ripoll, C., Berzigotti, A., Calleja, J. L., Tandon, P., Hernandez-Gea, V., Reiberger, T., Albillos, A., Tsochatzis, E. A., Krag, A., Genescà , J., Trebicka, J., (2020). Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis Journal of Hepatology 72, (6), 1140-1150

Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis. Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint. Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA. Conclusion: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.

JTD Keywords: ACLF, Acute decompensation, Acute-on-chronic liver failure, Ascites, Cirrhosis, Computed tomography, Hepatic encephalopathy, Liver, Portal hypertension, Spontaneous portosystemic shunt, SPSS, TIPS

Fumagalli, L., Edwards, Martin Andrew, Gomila, G., (2014). Quantitative electrostatic force microscopy with sharp silicon tips Nanotechnology 25, (49), 495701 (9)

Electrostatic force microscopy (EFM) probes are typically coated in either metal (radius ~ 30 nm) or highly-doped diamond (radius ~ 100 nm). Highly-doped silicon probes, which offer a sharpened and stable tip apex (radius ~ 1–10 nm) and are usually used only in standard atomic force microscopy, have been recently shown to allow enhanced lateral resolution in quantitative EFM and its application for dielectric constant measurement. Here we present the theoretical modelling required to quantitatively interpret the electrostatic force between these sharpened tips and samples. In contrast to a sphere-capped cone geometry used to describe metal/diamond-coated tips, modelling a sharpened silicon tip requires a geometry comprised of a cone with two different angles. Theoretical results are supported by experimental measurements of metallic substrates and ~10 nm radius dielectric nanoparticles. This work is equally applicable to EFM and other electrical scanned probe techniques, where it allows quantifying electrical properties of nanomaterials and 3D nano-objects with higher resolution.

JTD Keywords: AFM, Dielectric constant, EFM, Dielectrics, Nanoparticles, Sharp tips

Caballero, D., Villanueva, G., Plaza, J. A., Mills, C. A., Samitier, J., Errachid, A., (2010). Sharp high-aspect-ratio AFM tips fabricated by a combination of deep reactive ion etching and focused ion beam techniques Journal of Nanoscience and Nanotechnology , 10, (1), 497-501

The shape and dimensions of an atomic force microscope tip are crucial factors to obtain high resolution images at the nanoscale. When measuring samples with narrow trenches, inclined sidewalls near 90 or nanoscaled structures, standard silicon atomic force microscopy (AFM) tips do not provide satisfactory results. We have combined deep reactive ion etching (DRIE) and focused ion beam (FIB) lithography techniques in order to produce probes with sharp rocket-shaped silicon AFM tips for high resolution imaging. The cantilevers were shaped and the bulk micromachining was performed using the same DRIE equipment. To improve the tip aspect ratio we used FIB nanolithography technique. The tips were tested on narrow silicon trenches and over biological samples showing a better resolution when compared with standard AFM tips, which enables nanocharacterization and nanometrology of high-aspect-ratio structures and nanoscaled biological elements to be completed, and provides an alternative to commercial high aspect ratio AFM tips.

JTD Keywords: Atomic-Force Microscope, Carbon nanotube tips, Probes, Roughness, Cells, Microfabrication, Calibration, Surfaces