Electromechanically active pair dynamics in a Gd-doped ceria single crystal.

Oxygen-defective ceria, e.g. Gd-doped ceria, shows giant electromechanical properties related to a complex local rearrangement of its lattice. Although they are not entirely identified, the electroactive mechanisms arise from cation and oxygen vacancy (VO) pairs (i.e. Ce-VO), and the local structural elastic distortion in their surroundings. Here, we study the geometry and behaviour of Ce-VO pairs in a grain boundary-free bulk Ce0.9Gd0.1O1.95 single crystal under an AC electric field of ca. 11 kV cm-1. The analysis was carried out through X-ray absorption spectroscopy (XAS) techniques at the Ce L-III edge. Using Density Functional Theory (DFT) calculations, we investigated the effects of the strain on density of states and orbitals at the valence band edge. Our research indicates that electrostriction increases at low temperatures. The electromechanical strain has a structural nature and can rise by one order of magnitude, i.e., from 5 × 10-4 at room temperature to 5 × 10-3 at -193 °C, due to an increase in the population of the electrically active pairs. At a constant VO concentration, the material can thus configure heterogeneous pairs and elastic nanodomains that are either mechanically responsive or not.

Short- and long-term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma.

Background: Transarterial chemoembolization (TACE) affects hepatic perfusion, and might have an impact on portal pressure in patients with hepatocellular carcinoma (HCC). Objective: The objective of this article is to report the secondary outcome "hepatic hemodynamics" from the AVATACE trial, a prospective randomized, placebo-controlled trial on the efficacy of conventional TACE in combination with bevacizumab or placebo. Methods: Hepatic venous pressure gradient (HVPG) was measured at baseline (prior to first TACE), within nine days ("acute effects"), two months ("intermediate effects") and six months ("long-term effects") after the first TACE. Results: Of 28 patients with early-intermediate stage HCC, n = 20 (71%) had clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) at baseline (median, 12 (interquartile range (IQR): 9-19) mmHg). TACE had neither "acute effects" nor "intermediate effects" on HVPG. However, in 13 patients with available HVPG measurement at month 6, there was a significant increase in HVPG (median, 16 (IQR: 11-19) mmHg) compared with baseline (median, 10 (IQR: 5-12) mmHg; p = 0.007). Portal hypertension-related complications occurred exclusively in patients with CSPH (8 (40%) vs 0). Conclusions: Repeated TACE was associated with a significant long-term increase in HVPG. This should be considered when deciding whether to continue with TACE or switch to systemic treatment, since CSPH drives the development of complications.

Combining two redox active rare earth elements for oxygen storage - electrical properties and defect chemistry of ceria-praseodymia single crystals.

Solid solutions of ceria and praseodymia are highly relevant for electrochemical applications as the incorporation of praseodymium into the ceria lattice shifts the range of mixed ionic electronic conductivity to higher oxygen partial pressures. To better understand the influence of praseodymium substitution on the transport processes and oxygen storage capacity in ceria, single crystals of ceria substituted with 14 mol% praseodymium have been investigated, obtaining the bulk properties without the influence of grain boundaries. Beside the characterization of structural changes caused by the substitution using XRD and Raman spectroscopy, the electrochemical transport properties of ceria-praseodymia single crystals are reported. Measurements of the total electrical conductivity, the ionic transference number and the non-stoichiometry of Ce0.85Pr0.14Zr0.01O2-δ were performed in an oxygen partial pressure range of -25 < lg[p(O2)/bar] < 0 at 700 °C. With praseodymium being redox active itself, higher values of oxygen deficiency and electrical conductivity than in pure ceria have been observed in the high oxygen partial pressure region, while no significant structural changes occur due to the similar ionic radii of both cations. From measurements of the impedance at different temperatures, the migration enthalpy for the electronic charge carriers has been determined. By analysing the non-stoichiometry at 700 °C using a defect chemical model it was also possible to determine the equilibrium constants of Pr and Ce reduction in Ce0.85Pr0.14Zr0.01O2-δ single crystals.

Hepatocellular Carcinoma: A Phase II Randomized Controlled Double-Blind Trial of Transarterial Chemoembolization in Combination with Biweekly Intravenous Administration of Bevacizumab or a Placebo.

PURPOSE: To investigate the efficacy and safety of conventional transarterial chemoembolization (TACE) (cTACE) in combination with bevacizumab or a placebo in patients with hepatocellular carcinoma (HCC) in a randomized controlled double-blind phase II trial. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained prior to inclusion. A total of 40 patients (20 patients per group, all 18 years or older) with histologically confirmed early- or intermediate-stage HCC and Child-Pugh class A or B cirrhosis were scheduled for inclusion. The primary endpoint was radiologic progression at 12 months according to European Association for the Study of the Liver criteria. Secondary endpoints were safety and overall survival (OS). Patients underwent cTACE with doxorubicin and intravenous administration of a placebo (cTACE-C) or bevacizumab (cTACE-B) (5 mg per kilogram of body weight) every 2 weeks for 52 weeks. After the first TACE procedure, TACE was repeated twice in 4-week intervals if indicated and technically feasible and on demand thereafter. Statistical analyses were performed with statistical software. P < .05 indicated a significant difference. RESULTS: Thirty-two patients were recruited between January 2006 and December 2009 (29 male, three female; mean age, 61 years ± 8 [standard deviation]; Barcelona Clinic Liver Cancer stage A, n = 4; Barcelona Clinic Liver Cancer stage B, n = 28; predominant cause, alcohol [n = 15]; Child-Pugh class A disease, n = 22; Child-Pugh class B disease, n = 10; 16 patients received bevacizumab; 16 patients received a placebo). Patients underwent a median of three TACE cycles and received 13 infusions of bevacizumab versus 11 infusions of the placebo before the trial was stopped prematurely for safety reasons. Severe (grade 3-5) septic (n = 8 vs n = 3) and vascular (n = 9 vs n = 0) side effects were observed almost exclusively in the cTACE-B group. Median survival was worse in the cTACE-B group than in the cTACE-C group (5.3 vs 13.7 months; hazard ratio [HR], 1.7; 95% confidence interval [CI]: 0.8, 3.6; P = .195) and reached significance in patients with Child-Pugh class A cirrhosis (7.3 vs 26.5 months; HR, 2.6; 95% CI: 1.0, 6.6; P = .049). The primary endpoint was not met, since there was no difference in radiologic response between the groups at 3, 6, or 12 months. CONCLUSION: No improvement in radiologic tumor response or OS was observed in patients with HCC who received cTACE and bevacizumab, but severe and even lethal septic and vascular side effects occurred. Thus, bevacizumab cannot be recommended as an adjuvant treatment to cTACE.

The model case of an oxygen storage catalyst - non-stoichiometry, point defects and electrical conductivity of single crystalline CeO2-ZrO2-Y2O3 solid solutions.

The ternary solid solution CeO2-ZrO2 is known for its superior performance as an oxygen storage catalyst in exhaust gas catalysis (e.g. TWC), although the defect chemical background of these outstanding properties is not fully understood quantitatively. Here, a comprehensive experimental study is reported regarding defects and defect-related transport properties of cubic stabilized single crystalline (CexZr1-x)0.8Y0.2O1.9-δ (0 ≤x≤ 1) solid solutions as a model system for CeO2-ZrO2. The constant fraction of yttria was chosen in order to fix a defined concentration of oxygen vacancies and to stabilize the cubic fluorite-type lattice for all Ce/Zr ratios. Measurements of the total electrical conductivity, the partial electronic conductivity, the ionic transference number and the non-stoichiometry (oxygen deficiency, oxygen storage capacity) were performed in the oxygen partial pressure range -25 < lg pO2/bar < 0 and for temperatures between 500 °C and 750 °C. The total conductivity at low pO2 is dominated by electronic transport. A strong deviation from the widely accepted ideal solution based point defect model was observed. An extended point defect model was developed using defect activities rather than concentrations in order to describe the point defect reactions in CeO2-ZrO2-Y2O3 properly. It served to obtain good quantitative agreement with the measured data. By a combination of values for non-stoichiometries and for electronic conductivities, the electron mobility could be calculated as a function of pO2, ranging between 10(-2) cm(2) V(-1) s(-1) and 10(-5) cm(2) V(-1) s(-1). Finally, the origin of the high oxygen storage capacity and superior catalytic promotion performance at a specific ratio of n(Ce)/n(Zr) ≈ 1 was attributed to two main factors: (1) a strongly enhanced electronic conductivity in the high and medium pO2 range qualifies the material to be a good mixed conductor, which is essential for a fast oxygen exchange and (2) the equilibrium constant for the reduction exhibits a maximum, which means that the reduction is thermodynamically most favoured just at this composition.

Austrian consensus on the definition and treatment of portal hypertension and its complications (Billroth II).

In November 2004, the Austrian Society of Gastroenterology and Hepatology (ÖGGH) held for the first time a consensus meeting on the definitions and treatment of portal hypertension and its complications in the Billroth-Haus in Vienna, Austria (Billroth I-Meeting). This meeting was preceded by a meeting of international experts on portal hypertension with some of the proponents of the Baveno consensus conferences (http://www.oeggh.at/videos.asp). The consensus itself is based on the Baveno III consensus with regard to portal hypertensive bleeding and the suggestions of the International Ascites Club regarding the treatment of ascites. Those statements were modified by new knowledge derived from the recent literature and also by the current practice of medicine as agreed upon by the participants of the consensus meeting. In October 2011, the ÖGGH organized the second consensus meeting on portal hypertension and its complications in Vienna (Billroth II-Meeting). The Billroth II-Guidelines on the definitions and treatment of portal hypertension and its complications take into account the developments of the last 7 years, including the Baveno-V update and several key publications.

Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.

OBJECTIVE: Non-selective ß-blockers or endoscopic band ligation (EBL) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Additional α-adrenergic blockade (as by carvedilol) may increase the number of patients with haemodynamic response (reduction in hepatic venous pressure gradient (HVPG) of ≥ 20% or to values <12 mm Hg). DESIGN: Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment (80-160 mg/day) were included. HVPG responders were kept on propranolol (PROP group), while non-responders were placed on carvedilol (6.25-50 mg/day). Carvedilol responders continued treatment (CARV group), while non-responders to carvedilol underwent EBL. The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders. RESULTS: 36% (37/104) of patients showed a HVPG response to propranolol. Among the propranolol non-responders 56% (38/67) eventually achieved a haemodynamic response with carvedilol, while 44% (29/67) patients were finally treated with EBL. The decrease in HVPG was significantly greater with carvedilol (median 12.5 mg/day) than with propranolol (median 100 mg/day): -19 ± 10% versus -12 ± 11% (p<0.001). During a 2 year follow-up bleeding rates for PROP were 11% versus CARV 5% versus EBL 25% (p=0.0429). Fewer episodes of hepatic decompensation (PROP 38%/CARV 26% vs EBL 55%; p=0.0789) and significantly lower mortality (PROP 14%/CARV 11% vs EBL 31%; p=0.0455) were observed in haemodynamic responders compared to the EBL group. CONCLUSIONS: Carvedilol leads to a significantly greater decrease in HVPG than propranolol. Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response, which is associated with improved outcome with regard to prevention of variceal bleeding, hepatic decompensation and death.

von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis.

UNLABELLED: von Willebrand factor antigen (vWF-Ag) is elevated in patients with liver cirrhosis, but the clinical significance is unclear. We hypothesized that vWF-Ag levels may correlate with portal pressure, measured by hepatic venous pressure gradient (HVPG), and predict clinically significant portal hypertension (CSPH; HVPG ≥ 10 mmHg), decompensation and mortality. Portal hemodynamics were assessed by HVPG measurement, whereas vWF-Ag levels were measured by enzyme-linked immunosorbent assay. During follow-up, complications of liver cirrhosis, death or transplantation were recorded. Two hundred and eighty-six patients (205 male and 81 female; mean age, 56 years) with liver cirrhosis were included. vWF-Ag correlated with HVPG (r = 0.69; P < 0.0001) and predicted CSPH independently of Child Pugh score. Higher vWF-Ag levels were associated with varices (odds ratio [OR] = 3.27; P < 0.001), ascites (OR = 3.93; P < 0.001) and mortality (hazard ratio: 4.41; P < 0.001). Using a vWF-Ag cut-off value of ≥ 241%, the AUC for detection of CSPH in compensated patients was 0.85, with a positive predictive value and negative predictive value of 87% and 80%, respectively. Compensated patients had 25% mortality after 53 months if the vWF-Ag was <315% compared to 15 months in patients with vWF-Ag >315% (P < 0.001). Decompensated patients had a mortality of 25% after 37 and 7 months if their vWF-Ag was <315% and >315%, respectively (P = 0.002). In compensated patients with a vWF-Ag >315% median time to decompensation or death was 32 months compared with 59 months in patients with vWF-Ag <315%. vWF-Ag equals Model for End-Stage Liver Disease (MELD) in mortality prediction (area under the curve [AUC] = 0.71 for vWF-Ag versus AUC = 0.65 for MELD; P = 0.2). CONCLUSION: vWF-Ag is a new, simple and noninvasive predictor of CSPH. A vWF-Ag cut-off value at 315% can clearly stratify patients with compensated and decompensated liver cirrhosis in two groups with completely different survival. vWF-Ag may become a valuable marker for the prediction of mortality in patients with liver cirrhosis in clinical practice.

Austrian Joint ÖGGH-ÖGIR-ÖGHO-ASSO position statement on the use of transarterial chemoembolization (TACE) in hepatocellular carcinoma.

Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is one of the most frequently applied standard treatments for this disease. The role for TACE is fairly well defined within the most widely used treatment algorithm for HCC, die Barcelona Clinic Liver Cancer (BCLC) staging system and treatment algorithm. But no general treatment algorithm will go into the technical details of any procedure and several patients will not fit ideally into the patient groups predefined in BCLC or any other treatment algorithm. Furthermore, indications and contraindications sometimes are viewed differently by the various medical specialties involved in taking care of such patients. We present here the joint expert position statement of the Austrian Societies of Gastroenterology and Hepatology (ÖGGH), Interventional Radiology (ÖGIR), Hematology and Oncology (ÖGHO), and Surgical Oncology (ASSO) on the technical aspects, indications, and contraindication for the use of TACE in the management of HCC.

6-thioguanine associated nodular regenerative hyperplasia in patients with inflammatory bowel disease may induce portal hypertension.

BACKGROUND: Recent studies suggest an association between 6-thioguanine (6-TG) therapy and hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD). An influence of 6-TG on portal pressure remains to be determined. The aim of the study was to examine the functional relevance of long-term 6-TG treatment on hepatic hemodynamics in IBD patients and its association with NRH. METHODS: Patients treated with 6-TG for IBD underwent measurement of the hepatic venous pressure gradient (HVPG) and liver biopsy. 6-TG therapy was stopped when NRH was diagnosed. If elevated, HVPG measurement was repeated after 1 yr. RESULTS: Twenty-six patients (15 women, 11 men; median age 41 yr, range 23-76) treated with 6-TG for 38 months (median; range 12-45) were included. Among 24 patients with sufficient liver biopsy, 6 patients (25%) were diagnosed with NRH. In these 6 patients, the HVPG was higher (median HVPG 7 mmHg, range 3-14) than in the 18 patients without NRH (median 3 mmHg, range 2-5; P < 0.001). In the patients with NRH, two had clinically significant portal hypertension (CSPH) (13 and 14 mmHg, respectively); in one patient the HVPG was slightly elevated (7 mmHg). No overt clinical signs of portal hypertension were observed. One year after stopping 6-TG therapy, HVPG decreased in all 3 patients with initially elevated HVPG levels. CONCLUSIONS: We demonstrate that IBD patients under long-term 6-TG therapy are at a substantial risk for developing NRH. NRH results in elevation of HVPG and may cause CSPH. Discontinuation of 6-TG therapy extenuates portal hypertension and may thus reduce the risk of complications.