The Clinical Significance of Myosteatosis in Survival Outcomes in Patients with Hepatocellular Carcinoma Treated with Sorafenib.

The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0-78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258-2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028-1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105-2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112-2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients.

Ultra-Wideband Electromagnetic Composite Absorber Based on Pixelated Metasurface with Optimization Algorithm.

An ultra-wideband electromagnetic (EM) absorber is proposed. The proposed absorber consists of two thin metasurfaces, four dielectric layers, a glass fiber reinforced polymer (GFRP), and a carbon fiber reinforced polymer (CFRP) which works as a conductive reflector. The thin metasurfaces are accomplished with 1-bit pixelated patterns and optimized by a genetic algorithm. Composite materials of GFRP and CFRP are incorporated to improve the durability of the proposed absorber. From the full-wave simulation, more than 90% absorption rate bandwidth is computed from 2.2 to 18 GHz such that the fractional bandwidth is about 156% for the incidence angles from 0° to 30°. Absorptivity is measured using the Naval Research Laboratory (NRL) arch method in an EM anechoic environment. It was shown that the measured results correlated with the simulated results. In addition, the proposed absorber underwent high temperature and humidity tests under military environment test conditions in order to investigate its durability.

Non-Inferior Efficacy of Tenofovir Disoproxil to Tenofovir Disoproxil Fumarate in Virologically Suppressed Chronic Hepatitis B Patients.

Purpose: Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet's size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB). Patients and Methods: CHB patients with HBV-DNA <69 IU/mL after ≥24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA <69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities. Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was -2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; -0.8 ± 9.8 versus -2.4 ± 12.8 mL/min, respectively (P=0.017). Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.

A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF, Viread®) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. METHODS: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. RESULTS: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. CONCLUSION: DA-2802 is considered an effective and safe treatment for patients with CHB. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967939.

Investigation on Beam Alignment of a Microstrip-Line Butler Matrix and an SIW Butler Matrix for 5G Beamforming Antennas through RF-to-RF Wireless Sensing and 64-QAM Tests.

In this paper, an intuitive approach to assessing advantages of beamforming in 5G wireless communication is proposed as a novel try and practical demonstration of importance of alignment between the transmitter's and receiver's beams working in millimeter-wave frequency bands. Since the diffraction loss of millimeter-wave signals matters seriously in propagation, the effects of the misalignment and alignment between beams need to be checked for, which was conducted with a horn antenna and the 4 × 4 Butler matrix which mimic the relationship of the base station and handset antennas. Designing and using the microstrip-line and the substrate integrated waveguide (SIW) Butler matrices, RF-to-RF wireless connectivity between the horn and the microstrip line beamformer as case 1 and the horn and the SIW beamformer as case 2, concerning the changing angle of the beam from either of the two Butler matrices, was tested, showing over 12 dB enhancement in received power. This direct electromagnetic link test was accompanied by examining 64-QAM constellations for beam-angle changing from -30° to +30° for the two cases, where the error vector magnitude in the QAM-diagram becomes less than 10% by beam-alignment for the changing angle.

A Planar Millimeter-Wave Resonator-Array to Sense the Permittivity of COP Film with the 5G Handset Back-Cover.

In this paper, a new sensor is developed to estimate the dielectric constant of Cyclo Olefin Polymer (COP) film utilizable for 5G mobile phones' multi-layered back-cover. It is featured by the electrical characterization of the thin layer of the COP film at 28 GHz as the material under test (MUT) directly contacting the planar probe (which is an array of resonating patches) and a new meta-surface as metal patterned on the COP film inserted between the planar probe and the 5G multi-layered back-cover for enhanced physical interpretation of the data by way of impedance matching. In this approach to delving into the material, a thin and small meta-surface film with an area of 25.65 × 21.06 mm2 and a thickness of 55 µm is examined for applications to 5G mobile 28 GHz-frequency communication on the basis of the below -10 dB-impedance matching for the 1-by-4 array sensor. Along with this, the real and commercial handset back-cover is brought to the test. The proposed method presents the advantages of geometrical adequacy to the realistic 5G handset antenna configuration, the idea of impedance-matching via meta-materials, and the suitability of characterizing the film-type structure as compared to the open-ended coaxial waveguide, waveguide-to-waveguide and TX horn-to-RX horn free-space test methods.

Fibrosis-4 index as a predictor for mortality in hospitalised patients with COVID-19: a retrospective multicentre cohort study.

OBJECTIVE: The reliable risk factors for mortality of COVID-19 has not evaluated in well-characterised cohort. This study aimed to identify risk factors for in-hospital mortality within 56 days in patients with severe infection of COVID-19. DESIGN: Retrospective multicentre cohort study. SETTING: Five tertiary hospitals of Daegu, South Korea. PARTICIPANTS: 1005 participants over 19 years old confirmed COVID-19 using real-time PCR from nasopharyngeal and oropharyngeal swabs. METHODS: The clinical and laboratory features of patients with COVID-19 receiving respiratory support were analysed to ascertain the risk factors for mortality using the Cox proportional hazards regression model. The relationship between overall survival and risk factors was analysed using the Kaplan-Meier method. OUTCOME: In-hospital mortality for any reason within 56 days. RESULTS: Of the 1005 patients, 289 (28.8%) received respiratory support, and of these, 70 patients (24.2%) died. In multivariate analysis, high fibrosis-4 index (FIB-4; HR 2.784), low lymphocyte count (HR 0.480), diabetes (HR 1.917) and systemic inflammatory response syndrome (HR 1.714) were found to be independent risk factors for mortality in patients with COVID-19 receiving respiratory support (all p<0.05). Regardless of respiratory support, survival in the high FIB-4 group was significantly lower than in the low FIB-4 group (28.8 days vs 44.0 days, respectively, p<0.001). A number of risk factors were also significantly related to survival in patients with COVID-19 regardless of respiratory support (0-4 risk factors, 50.2 days; 49.7 days; 44.4 days; 32.0 days; 25.0 days, respectively, p<0.001). CONCLUSION: FIB-4 index is a useful predictive marker for mortality in patients with COVID-19 regardless of its severity.

Clinical outcomes of coronavirus disease 2019 in patients with pre-existing liver diseases: A multicenter study in South Korea.

BACKGROUND/AIMS: Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved.
. METHODS: A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed.
. RESULTS: Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P<0.05). The overall survival rate was significantly lower in patients with liver cirrhosis than in those without liver cirrhosis (log-rank test, P=0.003). Along with old age and diabetes, the presence of liver cirrhosis was found to be an independent predictor of severe disease (odds ratio, 4.52; 95% confidence interval [CI], 1.20-17.02;P=0.026) and death (hazard ratio, 2.86; 95% CI, 1.04-9.30; P=0.042) in COVID-19 patients.
. CONCLUSION: This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.

A Fully-Printed CRLH Dual-Band Dipole Antenna Fed by a Compact CRLH Dual-Band Balun.

In this paper, a new design method is proposed for a planar and compact dual-band dipole antenna. The dipole antenna has arms as a hybrid CRLH (Composite right- and left-handed) transmission-line comprising distributed and lumped elements for the dual-band function. The two arms are fed by the outputs of a compact and printed CRLH dual-band balun which consists of a CRLH hybrid coupler and an additional CRLH phase-shifter. Its operational frequencies are 2.4 and 5.2 GHz as popular mobile applications. Verifying the method, the circuit approach, EM (Electromagnetics) simulation and measurement are conducted and their results turn out to agree well with each other. Additionally, the CRLH property is shown with the dispersion diagram and the effective size-reduction is mentioned.

RF Channel-Selectivity Sensing by a Small Antenna of Metamaterial Channel Filters for 5G Sub-6-GHz Bands.

In this paper, a new small antenna is suggested for 5G Sub-6-GHz band mobile communication. It can change the channel among the three given bands (called the 3.5-GHz area), as a wide-band antenna is connected to a small multiplexer comprising three metamaterial channel filters. The function of channel selection of this antenna system is experimentally demonstrated to prove the validity of the presented scheme. The channel selection for 5G mobile communication is conducted from f1 (channel 1) through f2 (channel 2) to f3 (channel 3), when TX and RX antennas with gains over 0 dBi and S11 less than -10 dB are located far-field apart (RFar ≫ 2.1 cm), and result in the transmission coefficient (S21) being the greatest at the selected channel, which is detected by a vector network analyzer.

Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries.

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial.

Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM-MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy-two patients with baseline biopsy-proven alcoholic cirrhosis who had been alcohol-abstinent for more than 6 months underwent a multicenter, randomized, open-label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM-MSC groups that underwent either one-time or two-time hepatic arterial injections of 5 × 107 BM-MSCs 30 days after BM aspiration. A follow-up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child-Pugh score, and Model for End-stage Liver Disease score. Outcomes were analyzed by per-protocol analysis. In terms of fibrosis quantification (before versus after), the one-time and two-time BM-MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two-time BM-MSC transplantation in comparison with one-time BM-MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child-Pugh scores of both BM-MSC groups (one-time 7.6 ± 1.0 versus 6.3 ± 1.3 and two-time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM-MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups. CONCLUSION: Autologous BM-MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185-2197).

Decreased intrahepatic response to alpha(1)-adrenergic agonists in lipopolysaccharide-treated rats is located in the sinusoidal area and depends on Kupffer cell function.

BACKGROUND AND AIM: Livers from lipopolysaccharide-treated rats have a decreased vascular response to alpha(1)-adrenergic agonists due to an increased production of nitric oxide. Kupffer cells play a central role in the development of intrahepatic microvascular abnormalities during endotoxemia. We investigated the role of Kupffer cells in the intrahepatic vascular tone control in normal and endotoxemic rats. METHOD: Twenty-four hours after pretreatment with gadolinium chloride (to eliminate/inactivate Kupffer cells) or saline, rats were treated with lipopolysaccharide or a second dose of saline. Six hours later, rats (under deep anesthesia) were submitted to liver perfusion with Krebs-Henseleit solution using a system that allowed the measurement of both perfusion and sinusoidal pressures. Dose-response curves to methoxamine (alpha(1)-adrenergic agonist) were obtained in the absence or the presence of the nitric oxide synthase inhibitor N-monomethyl-L-arginine. RESULTS: Pretreatment with gadolinium did not change the intrahepatic vascular response to methoxamine in normal livers. Livers from lipopolysaccharide-treated rats showed a decreased sinusoidal vascular response to methoxamine and a 10-fold increase in nitric oxide production during liver perfusion. Either pretreatment with gadolinium or the presence of N-monomethyl-L-arginine in the perfusate restored the response to methoxamine and decreased the nitric oxide overproduction by more than 50%. CONCLUSIONS: Kupffer cells neither mediate nor modulate the intrahepatic vascular response to alpha(1)-adrenergic agonists in normal livers. Reduction in intrahepatic vascular response to alpha(1)-adrenergic agonists in livers from lipopolysaccharide-treated rats is located in the sinusoidal area and depends on Kupffer cell function.