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•Sorafenib combined with concurrent chemoembolization did not improve overall survival.•Combination therapy significantly improved tumor response and secondary outcomes.•Sorafenib ...alone remains first-line standard of care for advanced hepatocellular carcinoma.
Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC.
In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7–21 days of randomization. The primary endpoint was overall survival (OS).
For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio HR 0.91; 90% CI 0.69–1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53–0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59–0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40–0.82; p = 0.006).
Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC.
For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma.
Clinical Trial Number: NCT01829035.
Mn-Ce/TiO2 and Mn-Ce/TiO2-CNTs were tested for the low-temperature selective catalytic reduction of NO with NH3. The CNTs were in intimate contact with the catalyst surface, and the catalyst ...crystallinity, BET surface area, and porosity barely changed after CNTs addition. Compared to Mn-Ce/TiO2, Mn-Ce/TiO2-CNTs exhibited superior catalytic activity and N2 selectivity at 140–240 °C. High Mn4+ concentration and abundant chemisorbed oxygen species were found on the Mn-Ce/TiO2-CNTs. Monodentate nitrate species were mainly formed on Mn-Ce/TiO2-CNTs, which reacted with NH3, leading to a more reactive intermediate (Mn(n-1)+–O–NO2NH32). Therefore, CNTs addition provided an enhanced favorable NOx adsorption sites resulting in high catalytic efficiency.
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•Mn-Ce/TiO2 and Mn-Ce/TiO2-CNTs are synthesized via sol-gel and impregnation method.•Mn-Ce/TiO2-CNTs exhibit better catalytic performance at 180–240 °C than Mn-Ce/TiO2.•High Mn4+ concentration and chemisorbed oxygen are found on Mn-Ce/TiO2-CNT surface.•CNT addition provides more NO adsorption sites, resulting in more monodentate nitrate composition.
Circulating microbial dysbiosis is associated with chronic liver disease including nonalcoholic steatohepatitis and alcoholic liver disease. In this study, we evaluated whether disease-specific ...alterations of circulating microbiome are present in patients with cirrhosis and hepatocellular carcinoma (HCC), and their potential as diagnostic biomarkers for HCC. We performed cross-sectional metagenomic analyses of serum samples from 79 patients with HCC, 83 with cirrhosis, and 201 matching healthy controls, and validated the results in the same number of subjects. Serum bacterial DNA was analyzed using high-throughput pyrosequencing after amplification of the V3-V4 hypervariable regions of 16S rDNA. Blood microbial diversity was significantly reduced in HCC, compared with cirrhosis and control. There were significant differences in the relative abundances of several bacterial taxa that correlate with the presence of HCC, thus defining a specific blood microbiome-derived metagenomic signature of HCC. We identified 5 microbial gene markers-based model which distinguished HCC from controls with an area under the receiver-operating curve (AUC) of 0.879 and a balanced accuracy of 81.6%. In the validation, this model accurately distinguished HCC with an AUC of 0.875 and an accuracy of 79.8%. In conclusion, circulating microbiome-based signatures may be potential biomarkers for the detection HCC.
Localization of messenger RNA (mRNA) in dendrites is crucial for regulating gene expression during long-term memory formation. mRNA binds to RNA-binding proteins (RBPs) to form messenger ...ribonucleoprotein (mRNP) complexes that are transported by motor proteins along microtubules to their target synapses. However, the dynamics by which mRNPs find their target locations in the dendrite have not been well understood. Here, we investigated the motion of endogenous β-actin and Arc mRNPs in dissociated mouse hippocampal neurons using the MS2 and PP7 stem-loop systems, respectively. By evaluating the statistical properties of mRNP movement, we found that the aging Lévy walk model effectively describes both β-actin and Arc mRNP transport in proximal dendrites. A critical difference between β-actin and Arc mRNPs was the aging time, the time lag between transport initiation and measurement initiation. The longer mean aging time of β-actin mRNP (~100 s) compared with that of Arc mRNP (~30 s) reflects the longer half-life of constitutively expressed β-actin mRNP. Furthermore, our model also permitted us to estimate the ratio of newly generated and pre-existing β-actin mRNPs in the dendrites. This study offers a robust theoretical framework for mRNP transport, which provides insight into how mRNPs locate their targets in neurons.
The present study aimed to compare clinical and radiological differences of ONFH patients who were treated with denosumab, and a control group. A total of 178 patients (272 hips) with symptomatic, ...nontraumatic ONFH were divided into a denosumab group (98 patients, 146 hips) and a control group (80 patients, 126 hips). Patients in the denosumab group received a 60 mg subcutaneous dose of denosumab every 6 months. For the clinical assessments, Harris hip scores (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were evaluated. Plain radiographs and MRI were performed before and a minimum of 1 year after administration of denosumab, which were evaluated for radiological results including femoral head collapse (≥ 2 mm) and volume change of necrotic lesion. Femoral head collapse occurred in 36 hips (24.7%) in the denosumab group, and 48 hips (38.1%) in the control group, which was statistically significant (P = 0.012). Twenty-three hips (15.8%) in the denosumab group and 29 hips (23%) in the control group required THA, which showed no significant difference (P = 0.086). At the final follow-up, 71.9% of hips in the denosumab group had a good or excellent HHS compared with 48.9% in the control group, showing a significant difference (P = 0.012). The denosumab group showed a significantly higher rate of necrotic lesion volume reductions compared with the control group (P < 0.001). Denosumab can significantly reduce the volume of necrotic lesions and prevent femoral head collapse in patients with ARCO stage I or II ONFH.
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•Au NP showed catalytic activity when applied to the ECL device.•Au NP attached to ZnO NR electrode was successfully fabricated by simple methods.•Au NP attached to ZnO NR electrode ...reduced the driving voltage of the ECL device.•The optimized electrodes improved the light-emission of R, G and B ECL devices.
The advantages of ion-gel-based electrochemiluminescence (ECL) displays over organic light emitting diode (OLED) displays are their simple structure, low processing cost, and insensitivity to moisture. Despite these advantages, ion-gel-based ECL displays suffer from low light-emission efficiencies. Therefore, in this study, catalytic Au nanoparticles (NPs) were applied in ECL displays to improve their light-emission efficiency. Furthermore, the catalytic activity of the Au NPs was maximized by applying three dimensional ZnO nanorods (NRs) on the bottom electrode. Whereas the conventional ion-gel-based red (R), green (G), and blue (B) ECL devices with indium tin oxide (ITO) electrodes are driven at 3.0 VPP, the R, G, and B ECL devices with Au NPs can be driven at 2.0, 1.8, and 1.9 VPP, respectively, because the activation properties of the catalysts were maximized by incorporating ZnO NRs in the electrode. Thus, this study demonstrates that Au NPs can be applied as electrochemical catalysts in ECL devices. Furthermore, by employing the ZnO NRs, ECL devices that can be driven by extremely low voltages were successfully fabricated with a simple structure, using a simple process.
Summary
Background
Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis.
Aims
This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic ...patients.
Methods
We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high‐dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low‐dose PPI group) for each outcome.
Results
Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high‐dose PPI group. High‐dose PPI use was independently associated with a higher risk of death (adjusted HR aHR = 1.71, 95% confidence interval CI = 1.38–2.11, p < 0.001). This result was reproducible after propensity score‐matching (PSM) (aHR = 1.90, 95% CI = 1.49–2.44, p < 0.001). High‐dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66–2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70–2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43–2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31–2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02–2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95–2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12–1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28–2.37, p < 0.001).
Conclusions
The use of high‐dose PPI was independently associated with increased risks of mortality and cirrhotic complications.
The use of high‐dose PPI was independently associated with increased risks of mortality and cirrhotic complications in patients with advanced liver cirrhosis who experienced hepatic encephalopathy.
One of the most significant complications after a femoral neck fracture is osteonecrosis of the femoral head (ONFH). The concomitant use of single-photon emission computed tomography (SPECT) with ...computed tomography (CT) increases the sensitivity for detecting the anatomic location and severity of ONFH. In this study, we evaluated the diagnostic value of SPECT/CT for the occurrence of ONFH by quantifying the perfusion status of the femoral head.
A total of 30 patients who had multiple pinnings for femur neck fractures were included in this study. We classified the perfusion status into three groups: normal perfusion, decreased perfusion, and avascular groups, and compared the occurrence of femoral head necrosis between them. For quantitative analysis, we evaluated the uptake ratio of both femur heads (head-to-head uptake ratio). If the patient's contralateral hip was incomparable, we measured the uptake ratio from the superior dome of the ipsilateral acetabulum (head-to-acetabulum uptake ratio).
Twenty-four patients out of 30 achieved bone union, whereas the others developed ONFH. When the population was divided into intact and defective perfusion groups on scintigraphy, the sensitivity, specificity, and accuracy of the test were 83.3, 75.0, and 76.7%, respectively. The mean head-to-head uptake ratio value with a 95% confidence interval (CI) was 1.10 (95% CI: 0.85-1.36). In the osteonecrosis group, the mean value of the head-to-head uptake ratio was 0.33 (95% CI: 0.28-0.38). In contrast, the ratio was 1.30 (95% CI: 1.03-1.57) in the non-osteonecrosis group, demonstrating a significant difference in the uptake ratio (P < 0.001). When the cutoff value of the uptake ratio was set to 0.5, both the sensitivity and specificity were 100%. There was also a significant difference in the head-to-acetabulum uptake ratio between the two groups (P < 0.001).
SPECT/CT was useful in evaluating the perfusion status of the femoral head, showing high accuracy in predicting the occurrence of avascular necrosis. To demonstrate the reliability and validity of SPECT/CT, further prospective studies on a larger scale are warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Severe alcoholic hepatitis (AH) is the most aggressive form of alcohol‐related liver disease with high mortality. The microbiome is an emerging therapeutic target in ...alcohol‐related liver disease.
Aims
To investigate the microbiome composition in patients with severe AH, and to determine microbiome recovery after rifaximin treatment in gut bacteria and bacteria derived‐extracellular vesicles.
Methods
We enrolled 24 patients with severe AH and 24 healthy controls. Additional faecal samples were collected after 4 weeks in 8 patients with severe AH who completed rifaximin treatment. Treatment response was defined based on Lille score model after 7 days of treatment. Metagenomic profiling was performed using 16S ribosomal RNA amplicon sequencing.
Results
Faecal microbiomes of patients with severe AH had lower alpha diversity and higher beta diversity than those of healthy controls in both gut bacteria and extracellular vesicles. Bacilli, Lactobacillales and Veillonella were significantly increased in the gut bacteria of patients with severe AH, and Veillonella, Veillonella parvula group and Lactobacillales were significantly increased in the extracellular vesicles of patients with severe AH. Eubacterium_g23, Oscillibacter and Clostridiales decreased in the gut bacteria of patients with severe AH, and Eubacterium_g23, Oscillibacter and Christensenellaceae decreased in the extracellular vesicles of patients with severe AH. After rifaximin treatment, 17 taxa in the gut bacteria and 23 taxa in extracellular vesicles were significantly restored in patients with severe AH. In common, Veillonella and Veillonella parvula group increased in patients with severe AH and decreased after rifaximin treatment, and Prevotella and Prevotellaceae decreased in patients with severe AH and increased after rifaximin treatment. Treatment non‐responders showed a significantly lower abundance of Prevotella at baseline than did treatment responders.
Conclusion
Dysbiosis was confirmed in severe AH but was alleviated by rifaximin treatment. Taxa associated with severe AH can be candidate biomarkers or therapeutic targets.
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