Fluorinated Linkers Enable High-Voltage Pyrrolidinium-based Dicationic Ionic Liquid Electrolytes.

Novel fluorinated, pyrrolidinium-based dicationic ionic liquids (FDILs) as high-performance electrolytes in energy storage devices have been prepared, displaying unprecedented electrochemical stabilities (up to 7 V); thermal stability (up to 370 °C) and ion transport (up to 1.45 mS cm­1). FDILs were designed with a fluorinated ether linker and paired with TFSI/FSI counterions. To comprehensively asess the impact of the fluorinated spacer on their electrochemical, thermal, and physico-chemical properties, a comparison with their non-fluorinated counterparts was conducted. With a specific focus on their application as electrolytes in next-generation high-voltage lithium-ion batteries, the impact of the Li-salt on the characteristics of dicationic ILs was systematically evaluated. The incorporation of a fluorinated linker demonstrates significantly superior properties compared to their non-fluorinated counterparts, presenting a promising alternative towards next-generation high-voltage energy storage systems.

Atezolizumab/bevacizumab or lenvatinib in hepatocellular carcinoma: Multicenter real-world study with focus on bleeding and thromboembolic events.

Background & Aims: Atezolizumab/bevacizumab (atezo/bev) and lenvatinib have demonstrated efficacy as first-line therapies for hepatocellular carcinoma (HCC). However, vascular endothelial growth factor (VEGF) inhibition with these therapies may be associated with the risk of bleeding and thromboembolic events. In this study, we evaluated the efficacy and safety with focus on the bleeding and thromboembolic events of atezo/bev vs. lenvatinib in a large, multicenter real-world population. Methods: This study is based on HCC cohorts from seven centers in Germany and Austria. Incidences of bleeding or thromboembolic events and efficacy outcomes were assessed and compared. Results: In total, 464 patients treated with atezo/bev (n = 325) or lenvatinib (n = 139) were analyzed. Both groups were balanced with respect to demographics, presence of liver cirrhosis, and variceal status. Duration of therapy did not differ between groups. Within 3 months of therapy, bleeding episodes were described in 57 (18%) patients receiving atezo/bev compared with 15 (11%) patients receiving lenvatinib (p = 0.07). Variceal hemorrhage occurred in 11 (3%) patients treated with atezo/bev compared with 4 (3%) patients treated with lenvatinib (p = 0.99). Thromboembolic events were reported in 19 (6%) of patients in the atezo/bev cohort compared with 5 (4%) patients in the lenvatinib cohort (p = 0.37). In addition, incidence of overall bleeding, variceal hemorrhage, and thromboembolic events did not differ significantly in patients who received either atezo/bev or lenvantinib for 6 months. Conclusions: Safety considerations related to bleeding and thromboembolic events may not be helpful in guiding clinical decision-making when choosing between atezo/bev and lenvatinib. Impact and implications: The inhibition of VEGF by current first-line therapies for HCC, such as atezolizumab/bevacizumab or lenvatinib, may be associated with the risk of bleeding and thromboembolic events. Studies comparing the incidence of these side effects between atezolizumab/bevacizumab and lenvatinib, which are preferred treatments over sorafenib for HCC, are needed. Differences in this side effect profile may influence the choice of first-line therapy by treating physicians. Because no significant differences were observed regarding bleeding or thromboembolic events between both therapies in the present study, we conclude that safety considerations related to these events may not be helpful in guiding clinical decision-making when choosing between atezolizumab/bevacizumab and lenvatinib.

PHES scores have limited impact on the risk of overt HE in patients with minimal HE.

BACKGROUND: Minimal hepatic encephalopathy, defined by the portosystemic hepatic encephalopathy score (PHES), is associated with a higher risk of subsequent OHE. It remains unclear if there is a stepwise increase in OHE risk with worse PHES results. METHODS: In this multicenter study, patients with minimal hepatic encephalopathy, as defined by abnormal PHES, were followed for OHE development. RESULTS: In all, 207 patients were included. There was no stepwise increase in OHE risk with worse PHES results. CONCLUSIONS: Abnormal PHES is associated with a higher OHE risk, but we found no stepwise increase in OHE risk with worse PHES results below the established cutoff.

A High Copper Concentration Copper-Quadrol Complex Electroless Solution for Chip Bonding Applications.

This article presents a novel bonding method for chip packaging applications in the semiconductor industry, with a focus on downsizing high-density and 3D-stacked interconnections to improve efficiency and performance. Microfluidic electroless interconnections have been identified as a potential solution for bonding pillar joints at low temperatures and pressures. However, the complex and time-consuming nature of their production process hinders their suitability for mass production. To overcome these challenges, we propose a tailored plating solution using an enhanced copper concentration and plating rate. By eliminating the need for fluid motion and reducing the process time, this method can be used for mass production. The Taguchi approach is first used to optimize the copper-quadrol complex solution with the plating rate and decomposition time. This solution exhibits a copper concentration that is over five times higher than that of conventional solutions, a plating rate of 22.2 µm/h, and a decomposition time of 8 min on a Cu layer substrate. This technique enables Cu pillars to be successfully bonded within 7 min at 35 °C. Planarizing the pillar surface yields a high bonding percentage of 99%. Mechanical shear testing shows a significant fracture strength of 76 MPa.

Lower uromodulin serum levels are associated with poorer prognosis in patients with cirrhosis and hepatorenal syndrome type 2.

Hepatorenal syndrome (HRS) is associated with a dismal prognosis in patients with cirrhosis, and therapeutic options are limited. Biomarkers to identify patients with poor response to therapy are urgently needed. This study aimed to evaluate the predictive value of serum levels of uromodulin (sUMOD) in patients with cirrhosis and HRS treated with terlipressin and albumin (T/A). In total, 156 patients [81 patients with HRS treated with T/A, 42 patients with cirrhosis without kidney injury, and 33 patients with cirrhosis with prerenal acute kidney injury (AKI)] were included. sUMOD levels were analyzed by ELISA. Patients with HRS were prospectively followed for the composite endpoint of hemodialysis-/liver transplantation-free survival (HD/LTx-free survival). Of the 81 patients with HRS, 40 had HRS type 1 and 41 type 2. In the cohort of patients with HRS treated with T/A, median sUMOD level was 100 ng/mL (IQR 64; 144). sUMOD differed significantly between patients with HRS compared with patients without AKI (P = 0.001) but not between patients with HRS and prerenal AKI (P = 0.9). In multivariable analyses, sUMOD levels in the lowest quartile were independently associated with a lower rate of complete response to T/A (OR 0.042, P = 0.008) and a higher risk for reaching the composite endpoint of HD/LTX-free survival (HR 2.706, P = 0.013) in patients with HRS type 2 treated with T/A. In contrast, sUMOD was not significantly associated with these outcomes in patients with HRS type 1. sUMOD may be a valuable biomarker for identifying patients with HRS type 2 treated with T/A to predict response and prognosis.NEW & NOTEWORTHY Biomarkers identifying patients with hepatorenal syndrome (HRS) and poor response to therapy are urgently needed. In this study, lower serum uromodulin (sUMOD) levels were associated with poorer response to therapy with terlipressin and albumin and consequently with poorer prognosis in patients with HRS type 2. In patients with HRS type 1, there was no association between sUMOD and poorer prognosis.

Minimal hepatic encephalopathy is associated with a higher risk of overt hepatic encephalopathy and poorer survival.

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a frequent complication in patients with liver cirrhosis. Its impact on predicting the development of overt hepatic encephalopathy (OHE) and survival has not been studied in large multicenter studies. METHODS: Data from patients recruited at eight centers across Europe and the United States were analyzed. MHE was detected using the psychometric hepatic encephalopathy score (PHES). A subset was also tested with the simplified animal naming test (S-ANT1). Patients were followed for OHE development and death/liver transplantation (LTx). RESULTS: A total of 1462 patients with a median model of end-stage liver disease of 11 were included (Child-Pugh (CP) stages: A 47%/B 41%/C 12%). Median follow-up time was 19 months, during which 336 (23%) patients developed an OHE episode and 464 (32%) reached the composite end point of death/LTx (369 deaths, 95 LTx). In multivariable analyses, MHE (defined by PHES) was associated with the development of OHE (subdistribution hazard ratio 1.74, p < 0.001) and poorer LTx-free survival (hazard ratio 1.53, p < 0.001) in the total cohort as well as in the subgroup of patients without a history of OHE. In subgroup analyses, MHE (defined by PHES) was associated with OHE development in patients with CP B, whereas there was no association in patients with CP A or C. In the subgroup of patients with available S-ANT1, MHE (defined by S-ANT1) was independently associated with OHE development. Combined testing (PHES+S-ANT1) was superior to single testing for predicting OHE and poorer LTx-free survival. CONCLUSIONS: This large multicenter study demonstrates that screening for MHE is a useful tool for predicting OHE and poorer survival.

Higher scores in the Clinical Frailty Scale are associated with covert and overt hepatic encephalopathy in patients with cirrhosis.

BACKGROUND: Frailty increases the vulnerability to internal and external stressors and may therefore be an indicator of a higher frequency of cirrhosis complications. We aimed to investigate the association of the Clinical Frailty Scale (CFS) with covert (CHE) and overt HE (OHE) development in patients with cirrhosis. METHODS: This study analyzed data of 228 patients with cirrhosis. Frailty was assessed using CFS. Patients were examined for the presence of CHE (using PHES) at study inclusion and followed for OHE. RESULTS: Median CFS was 3 and 26 (11 %) patients were at least pre-frail (CFS>3). In multivariable logistic regression analysis in patients without a history of OHE (n = 195), a higher CFS was associated with the presence of CHE at baseline (OR 1.6, p = 0.039). During follow-up, 42 (18 %) patients developed an episode of OHE. In multivariable competing risk regression analyses, a higher CFS was independently associated with the development of an OHE episode in the total cohort (sHR 1.97, p < 0.001) and in the subcohort of patients without a history of OHE (sHR 1.88, p = 0.008). CONCLUSION: CFS appears to be a reliable tool to identify patients at higher risk of HE in whom intensified monitoring and treatment may be justified.

Comparison of Inflammatory Cytokine Levels in Hepatic and Jugular Veins of Patients with Cirrhosis.

Background: Systemic inflammation with elevated inflammatory cytokines is a hallmark in patients with cirrhosis and the main driver of decompensation. There is insufficient data on whether inflammatory cytokine levels differ between hepatic and jugular veins, which may have implications for further immunological studies. Methods: Blood from the hepatic and jugular veins of 40 patients with cirrhosis was collected during hepatic venous pressure gradient (HVPG) measurements. Serum levels of 13 inflammatory cytokines (IL-1ß, Int-α2, Int-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33) were quantified by cytometric bead array. Results: Cytokine levels of IFN-α2, IFN-γ, TNF-α, IL-6, IL-8, IL-10, IL-17A, IL-18, IL-23, and IL-33 were significantly elevated in patients with decompensated cirrhosis compared to patients with compensated cirrhosis. When comparing patients with clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) to patients without CSPH, there were significantly enhanced serum levels of IL-6 and IL-18 in the former group. There was no significant difference between cytokine serum levels between blood obtained from the jugular versus hepatic veins. Even in subgroup analyses stratified for an early cirrhosis stage (Child-Pugh (CP) A) or more decompensated stages (CP B/C), cytokine levels were similar. Conclusion: Cytokine levels increase with decompensation and increasing portal hypertension in patients with cirrhosis. There is no relevant difference in cytokine levels between hepatic and jugular blood in patients with cirrhosis.

Dislodgement of Hydrogen Bubbles in Microchannels with Embedded Pillars: An Analytical, Experimental, and Numerical Study.

Microchannels with integrated pillars have enhanced the production capabilities and performance of various applications due to their high surface-to-volume ratio. However, emerging gas bubbles can become trapped, potentially limiting the functionality or efficiency of the device when scaled down to the low-micrometer scale. Understanding the conditions required to dislodge these bubbles is thus critical for optimizing microfluidic devices with complex physical behaviors. Here an analytical model is presented that outlines the dislodgment conditions and driving forces for such gas-liquid flows. These terms are derived from the gas-liquid interface properties, geometry, and processing parameters. As the density of the pillar arrangement is scaled down, the resistance to bubble dislodgment typically increases. Nevertheless, the bubble is compelled to dislodge at lower pressure loads when critical volumes are reached. This newly discovered effect is particularly noticeable in densely packed arrays and can be explained by the interplay of increased surface tension, geometrical restrictions, and volume-preserving forces. The analytical terms and effects are validated through novel experimental and numerical methods tailored for microchannels in the low-micrometer scale, showing strong agreement.

Multimethod Approach to the Low-Overpotential Region of Micro- to Macro-Scale Working Electrodes of Sub-10 nm Gold Nanoparticles in the CO2 Reduction Reaction.

The electrochemical carbon dioxide reduction reaction (CO2RR) over carbon-supported gold nanoparticles (AuNP) was investigated using a broad variety of (electro)analytical methods, including linear sweep voltammetry with a rotating disk electrode (LSV-RDE), sample-generation tip-collection mode of scanning electrochemical microscopy (SG/TC-SECM), as well as full cell tests with highly sensitive online gas chromatography (GC). In contrast to most other studies, this work focuses on the low-overpotential region (0 to -0.4 V vs RHE) where initial product formation is already detected and addresses micro- to macro-sized electrodes. The sub-10 nm AuNPs supported on three different carbon supports (CNTs and carbon blacks) were pretreated in H2/Ar to remove the stabilizer used during AuNP synthesis. LSV-RDE points toward different CO2RR mechanisms at the samples, additionally confirmed by the SG/TC-SECM and full cell tests with online GC. Besides H2 and CO, the AuNP supported on carbon nanotubes showed significant evolution of H2CO in contrast to the other two samples, which was additionally confirmed by accumulating the product during chronoamperometric RDE experiments followed by mass spectroscopic analysis. Surface analysis indicated a complete removal of residual thiolate stabilizer molecules exclusively at the AuNPs supported on carbon nanotubes, which may result in a change in the adsorption geometry or reaction mechanism at this sample. The results demonstrate the effectiveness of the combination of these multiple methods to investigate the CO2RR in the low-overpotential region.

Elevated serum levels of glial fibrillary acidic protein are associated with covert hepatic encephalopathy in patients with cirrhosis.

Background & Aims: Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. Astrocyte swelling is a major component of hepatic encephalopathy. Thus, we hypothesised that glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes, might facilitate early diagnosis and management. This study aimed to investigate the utility of serum GFAP (sGFAP) levels as a biomarker of CHE. Methods: In this bicentric study, 135 patients with cirrhosis, 21 patients with ongoing harmful alcohol use and cirrhosis, and 15 healthy controls were recruited. CHE was diagnosed using psychometric hepatic encephalopathy score. sGFAP levels were measured using a highly sensitive single-molecule array (SiMoA) immunoassay. Results: In total, 50 (37%) people presented with CHE at study inclusion. Participants with CHE displayed significantly higher sGFAP levels than those without CHE (median sGFAP, 163 pg/ml [IQR 136; 268] vs. 106 pg/ml [IQR 75; 153]; p <0.001) or healthy controls (p <0.001). sGFAP correlated with results in psychometric hepatic encephalopathy score (Spearman's ρ = -0.326, p <0.001), model for end-stage liver disease score (Spearman's ρ = 0.253, p = 0.003), ammonia (Spearman's ρ = 0.453, p = 0.002), and IL-6 serum levels (Spearman's ρ = 0.323, p = 0.006). Additionally, sGFAP levels were independently associated with the presence of CHE in multivariable logistic regression analysis (odds ratio 1.009; 95% CI 1.004-1.015; p <0.001). sGFAP levels did not differ between patients with alcohol-related cirrhosis vs. patients with non-alcohol-related cirrhosis or between patients with ongoing alcohol use vs. patients with discontinued alcohol use.Conclusions: sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker. Impact and implications: Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. In this study, we were able to demonstrate that sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker.

Prevalence of Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Multicenter Study.

INTRODUCTION: The prevalence of minimal hepatic encephalopathy (MHE), in particular in different subgroups, remains unknown. This study aimed to analyze the prevalence of MHE in different subgroups to identify patients at high risk and to pave the way for personalized screening approaches. METHODS: In this study, data of patients recruited at 10 centers across Europe and the United States were analyzed. Only patients without clinical signs of hepatic encephalopathy were included. MHE was detected using the Psychometric Hepatic Encephalopathy Score (PHES, cut-off < or ≤-4 depending on local norms). Clinical and demographic characteristics of the patients were assessed and analyzed. RESULTS: In total, 1,868 patients with cirrhosis with a median model for end-stage liver disease (MELD) of 11 were analyzed (Child-Pugh [CP] stages: A 46%, B 42%, and C 12%). In the total cohort, MHE was detected by PHES in 650 patients (35%). After excluding patients with a history of overt hepatic encephalopathy, the prevalence of MHE was 29%. In subgroup analyses, the prevalence of MHE in patients with CP A was low (25%), whereas it was high in CP B or C (42% and 52%). In patients with a MELD score <10, the prevalence of MHE was only 25%, but it was 48% in patients with a MELD score ≥20. Standardized ammonia levels (ammonia level/upper limit of normal of each center) correlated significantly, albeit weakly with PHES (Spearman ρ = -0.16, P < 0.001). DISCUSSION: The prevalence of MHE in patients with cirrhosis was high but varied substantially between diseases stages. These data may pave the way for more individualized MHE screening approaches.

Hospitalizations, emergency room visits and causes of death in 198 patients with permanent hypoparathyroidism: a retrospective Austrian study (2005-2022).

Objective: Chronic hypoparathyroidism (HP) is associated with acute and chronic complications, especially those related to hypocalcemia. We aimed to analyze details on hospital admissions and the reported deaths in affected patients. Design and methods: In a retrospective analysis, we reviewed the medical history of 198 patients diagnosed with chronic HP over a continuous period of up to 17 years at the Medical University Graz. Results: The mean age in our mostly female cohort (70.2%) was 62.6 ± 18.7 years. The etiology was predominantly postsurgical (84.8%). About 87.4% of patients received standard medication (oral calcium/vitamin D), 15 patients (7.6%) used rhPTH1-84/Natpar® and 10 patients (4.5%) had no/unknown medication. Two hundred and nineteen emergency room (ER) visits and 627 hospitalizations were documented among 149 patients, and 49 patients (24.7%) did not record any hospital admissions. According to symptoms and decreased serum calcium levels, 12% of ER (n = 26) visits and 7% of hospitalizations (n = 44) were likely attributable to HP. A subgroup of 13 patients (6.5%) received kidney transplants prior to the HP diagnosis. In eight of these patients, parathyroidectomy for tertiary renal hyperparathyroidism was the cause of permanent HP. The mortality was 7.8% (n = 12), and the causes of death appeared to be unrelated to HP. Although the awareness for HP was low, calcium levels were documented in 71% (n = 447) of hospitalizations. Conclusions: Acute symptoms directly related to HP did not represent the primary cause of ER visits. However, comorbidities (e.g. renal/cardiovascular diseases) associated with HP played a key role in hospitalizations and deaths. Significance statement: Hypoparathyroidism (HP) is the most common complication after anterior neck surgery. Yet, it remains underdiagnosed as well as undertreated, and the burden of disease and long-term complications are usually underestimated. There are few detailed data on emergency room (ER) visits hospitalizations and death in patients with chronic HP, although acute symptoms due to hypo-/hypercalcemia are easily detectable. We show that HP is not the primary cause for presentation but that hypocalcemia is a typical laboratory finding (when ordered) and thus may contribute to subjective symptoms. Patients often present with renal/cardiovascular/oncologic illness for which HP is known to be a contributing factor. A small but very special group (n = 13, 6.5%) are patients after kidney transplantations who showed a high ER hospitalization rate. Surprisingly, HP was never the cause for their frequent hospitalizations but rather the result of chronic kidney disease. The most frequent cause for HP in these patients was parathyroidectomy due to tertiary hyperparathyroidism. The causes of death in 12 patients appeared to be unrelated to HP, but we found a high prevalence of chronic organ damages/comorbidities related to it in this group. Less than 25% documented HP correctly in the discharge letters, which indicates a high potential for improvement.

An Optical Approach for Cell Pellet Detection.

Cell-based screening methods are increasingly used in diagnostics and drug development. As a result, various research groups from around the world have been working on this topic to develop methods and algorithms that increase the degree of automation of various measurement techniques. The field of computer vision is becoming increasingly important and has therefore a significant influence on the development of various processes in modern laboratories. In this work we describe an approach for detecting two height information, the phase boundary of a cell pellet and the bottom edge of the tube, and thereby a method for determining the highest point of the topology. The starting point for the development of the method described are cells obtained by various procedures and stabilized by a fixative. Centrifugation of the tube causes the cells to settle to the bottom of the tube, resulting in a cell pellet with a clear phase boundary between the cells and the fixative. For further studies, the supernatant fixative has to be removed without reducing the number of cells. The fixative is to be extracted automatically by a liquid robot, which is only possible by accurately determining the cell pellet height. Due to centrifugation, an uneven topology is formed, which is why the entire phase boundary must be examined to detect the highest point of the cell pellet. For this approach, the tube to be examined, which contains the cells and the fixative, is rotated 360° in defined small steps after centrifugation. During rotation, an image is captured in each step, after which a defined image area is separated from the center of the image and merged into a panoramic image. This produces a panoramic image of the cell topology which represents the complete phase boundary, the boundary located on the outside of the tube. This panoramic image is modified through various image processing steps to extract and detect the phase boundary. Various image processing algorithms from the OpenCV library are used. In the first step, the panoramic image is convolved with a Gaussian blur filter to reduce noise. In the following step, a black and white image is generated by a thresholding process. This black and white image, or binary image, is convolved with a Sobel operator in the x and y directions and the results are superimposed. This overlaid image shows the top edge of the cell pellet and other edges located in the image. A logical exclusion method of the obtained boundaries is used for the detection of the phase boundary. To detect the tube bottom, a multilevel model was trained in advance with an appropriate data set. This model can detect and localize in near real time the tube bottom in an image. By using the two-height information of the different boundaries, phase boundary and tube bottom, the highest point of the cell pellet can be detected. This information is then passed on to a higher-level process so that the liquid robot can approach this point with the pipette tip to remove the excess fixative. By determining the highest point, the probability of being able to remove a larger amount of fixative without reducing the number of cells is highest. This ensures that post-processing studies have the largest possible number of cells available with complete automation.

Bevacizumab in combination with octreotide rescues a patient with liver cirrhosis, GAVE syndrome and refractory hemorrhage - a case report.

Gastric antral vascular ectasia (GAVE) syndrome is a rare but often challenging etiology of upper gastrointestinal bleeding (UGIB).We report on a 60-year-old patient with liver cirrhosis, GAVE syndrome and recurrent and refractory GAVE-related UGIB. During a 5-month hospital stay, the patient required a total of 82 packed red blood cells (pRBCs) and 23 gastroscopies. All endoscopic approaches, including multiple argon plasma coagulation and band ligation sessions, remained unsuccessful. Antrectomy was waived because of the high perioperative mortality risk in Child-Pugh B liver cirrhosis. TIPS insertion also failed to control the bleeding. Only continuous intravenous octreotide infusion slowed the bleeding, but this forced the patient to be hospitalized. After 144 inpatient days, administration of subcutaneous octreotide allowed the patient to be discharged. However, the patient continued to require two pRBCs every 2-3 weeks. Based on recently published data, we treated the patient with bevacizumab (anti-VEGF antibody) off-label at a dose of 7.5 mg/kg body weight every three weeks in nine single doses over six months. Since the first administration, the patient has remained transfusion-free, has not required hospitalization, and leads an active life, working full-time. He remains on octreotide, which has been reduced but not yet discontinued. Additionally, no adverse events were observed.Thus, in patients with liver cirrhosis and refractory GAVE-related hemorrhage, bevacizumab combined with subcutaneous octreotide should be considered as an effective and durable pharmacological treatment option.

Diabetes mellitus - risk factor and potential future target for hepatic encephalopathy in patients with liver cirrhosis?

Hepatic encephalopathy (HE) is one of the major complications of cirrhosis, and its presence is associated with poor survival. Several risk factors for HE are well established, including age, history of HE, portosystemic shunts, or poorer liver function. In recent years, diabetes mellitus (DM) has emerged as another potential risk factor for the development of HE. This may be important for many patients, as the incidence of type 2 DM (T2DM) is increasing worldwide and, consequently, the incidence of NAFLD-related cirrhosis is rising simultaneously. In addition, DM is a critical factor in the progression of other liver diseases, such as alcohol-related liver disease. Thus, the number of patients with cirrhosis and comorbid T2DM will also increase. To date, the prevalence of DM already ranges between 22 - 40% in patients with cirrhosis. DM-associated factors that may influence the risk of HE include systemic inflammation, insulin resistance with increased muscle protein breakdown as well as autonomic dysfunction with prolonged intestinal transit time and small intestinal bacterial overgrowth. Currently, the evidence for an association between DM and both minimal and overt HE is weak and it seems likely that only poor glycemic control has an impact on HE risk. In addition, there are some early signs indicating that DM may impair the response of patients with HE to pharmacological therapies such as rifaximin. Thus, improvements in the management of glycemic control may be a candidate future target to reduce the risk of HE. In this concise review, we summarize the current evidence on the association between DM and HE and its potential future implications.

Quantifying the removal of stabilizing thiolates from gold nanoparticles on different carbon supports and the effect on their electrochemical properties.

Gold nanoparticles <10 nm in size are typically prepared using stabilizing agents, e.g. thiolates. Often standard recipes from literature are used to presumably remove these stabilisers to liberate the surface, e.g. for catalytic or electrocatalytic applications, however the success of these procedures is often not verified. In this work, thiolate-stabilised AuNPs of ca. 2 nm in size were synthesized and supported onto three different carbon supports, resulting in loadings from 15 to 25 wt% Au. These materials were post treated using three different methods in varying gas atmospheres to remove the stabilizing agent and to liberate the surface for electrochemical applications. Using thermogravimetry - mass spectroscopy (TG-MS), the amount of removed stabilizer was determined to be up to 95%. Identical location scanning transmission electron microscopy (il-(S)TEM) measurments revealed moderate particle growth but a stable support during the treatments, the latter was also confirmed by Raman spectroscopy. All treatments significantly improved the electrochemically accessible gold surface. In general, the results presented here point out the importance of quantitatively verifying the success of any catalyst post treatment with the aim of stabilizer removal.

Outcome after Resection for Hepatocellular Carcinoma in Noncirrhotic Liver-A Single Centre Study.

Liver cirrhosis is the most common risk factor for the development of hepatocellular carcinoma (HCC). However, 10 to 15% of all HCC arise in a non-cirrhotic liver. Few reliable data exist on outcome after liver resection in a non-cirrhotic liver. The aim of this single-centre study was to evaluate the outcome of resection for HCC in non-cirrhotic liver (NC-HCC) and to determine prognostic factors for overall (OS) and intrahepatic recurrence-free (RFS) survival. From 2008 to 2020, a total of 249 patients were enrolled in this retrospective study. Primary outcome was OS and RFS. Radiological and pathological findings, such as tumour size, number of nodules, Tumour-, Nodes-, Metastases- (TNM) classification and vascular invasion as well as extent of surgical resection and laboratory liver function were collected. Here, 249 patients underwent liver resection for NC-HCC. In this case, 50% of patients underwent major liver resection, perioperative mortality was 6.4%. Median OS was 35.4 months (range 1-151 months), median RFS was 10.5 months (range 1-128 moths). Tumour diameter greater than three centimetres, multifocal tumour disease, vascular invasion, preoperative low albumin and increased alpha-fetoprotein (AFP) values were associated with significantly worse OS. Our study shows that resection for NC-HCC is an acceptable treatment approach with comparatively good outcome even in extensive tumours.

A higher FIB-4 index is associated with an increased incidence of renal failure in the general population.

The Fibrosis-4 index (FIB-4) is a recommended noninvasive fibrosis test in patients at risk of liver fibrosis. Chronic liver diseases are often associated with kidney diseases. This study aimed to investigate the association between FIB-4 and the development of renal failure among the general population. For this study, we used the Disease Analyzer database, which includes diagnoses and basic medical and demographic data of patients followed in general practices in Germany. Using these data, we extensively matched patients with a FIB-4 index ≥ 1.3 (n = 66,084) to patients with a FIB-4 index < 1.3 (n = 66,084). The primary outcome was the incidence of renal failure or chronic renal failure during a 10-year period. Within 10 years of the index date, 9.2% of patients with a FIB-4 < 1.3 and 10.6% of patients with a FIB-4 ≥ 1.3 were diagnosed with renal failure (p = 0.007). The endpoint chronic renal failure was reached by 7.9% with a FIB-4 < 1.3 and 9.5% with a FIB-4 ≥ 1.3 (p < 0.001). A FIB-4 index ≥ 1.3 was associated with a slight increase in renal failure incidence (hazard ratio [HR]: 1.08, p = 0.009). There was an increasing association between an increase in FIB-4 index and the incidence of renal failure with the strongest association for a FIB-4 index ≥ 2.67 (HR: 1.34, p = 0.001). In sensitivity analyses, a significant association was found for the age group of 51-60 years (HR: 1.38, p < 0.001), patients with arterial hypertension (HR: 1.15, p < 0.001), obese patients (HR: 1.25, p = 0.005), and patients with lipid metabolism disorders (HR:1.22, p < 0.001). Conclusion: A higher FIB-4 index is associated with an increased incidence of renal failure. Therefore, the FIB-4 index may be useful in identifying patients who are at risk not only for liver-related events but also for renal disease.