Atezolizumab plus bevacizumab has been approved as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma (uHCC). This study was designed to assess the clinical ...impact of atezolizumab plus bevacizumab in uHCC patients. A total of 48 uHCC patients receiving atezolizumab plus bevacizumab were identified, including first-line, second-line, third-line, and later-line settings. In these patients, the median progression-free survival (PFS) was 5.0 months, including 5.0 months for the first-line treatment, not reached for the second-line treatment, and 2.5 months for the third line and later line treatment. The objective response rate and disease control rate to atezolizumab plus bevacizumab were 27.1% and 68.8%, respectively. The severity of most adverse events was predominantly grade 1-2, and most patients tolerated the toxicities. The ratios of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) were used to predict PFS in these patients. The optimal cutoff values of NLR and PLR were 3 and 230, and NLR and PLR were independent prognostic factors for superior PFS in the univariate and multivariate analyses. Our study confirms the efficacy and safety of atezolizumab plus bevacizumab in uHCC patients in clinical practice and demonstrates the prognostic role of NLR and PLR for PFS in these patients.
The development of new methodologies that enable chemo- and stereoselective construction of fluorinated substituents, such as the trifluoromethyl (CF
) group, plays an essential role in the synthesis ...of new pharmaceutical agents. The exceptional ability of the CF
moiety to prevent in vivo metabolism as well as improve other pharmacological properties has led to numerous innovative strategies for installing this unique functional group. One potential yet underdeveloped approach to access these trifluoromethylated products is direct substitution of α-trifluoromethyl carbanions. Although the electron-withdrawing nature of the CF
group should facilitate deprotonation of adjacent hydrogens, the propensity of the resulting carbanions to undergo α-elimination of fluoride renders this process highly challenging. Herein, we describe a new strategy for stabilizing and utilizing transient α-trifluoromethyl carbanions that relies on a neighbouring cationic π-allyl palladium complex. These palladium-stabilized zwitterions participate in asymmetric 3 + 2 cycloadditions with a broad range of acceptors, generating valuable di- and trifluoromethylated cyclopentanes, pyrrolidines and tetrahydrofurans.
Data on direct‐acting antiviral agent (DAA) treatment for mixed genotype hepatitis C virus (HCV) infection are scant. This study examined the effectiveness of glecaprevir/pibrentasvir (GLE/PIB) and ...ledipasvir/sofosbuvir (LDV/SOF) for mixed HCV genotype infection in a real‐world setting in Taiwan. We analysed the data from all patients with mixed HCV genotype infections treated with GLE/PIB or LDV/SOF from 2017 to 2019 in three Chang Gung Memorial Hospitals in Taiwan. The primary treatment outcome was sustained virologic response 12 weeks after treatment cessation (SVR12). Adverse events (AEs) were also evaluated. A total of 5190 HCV patients received DAA treatment during this time period. Among them, 116 patients (2.2%) had mixed infections of any 2 or 3 genotypes of 1a, 1b, 2, 3 and 6. Fifty‐four patients received GLE/PIB and 62 received LDV/SOF. SVR12 rates for LDV/SOF vs GLE/PIB therapy were 96.6% (56/58) vs 100% (51/51) by the per‐protocol analysis and 90.3% (56/62) vs 94.4% (51/54) by the evaluable population analysis. Two patients with 1b + 6 and 1b + 2 genotype infections in the LDV/SOF group had relapse. Evaluating the GLE/PIB vs LDV/SOF groups for the most common AEs revealed pruritus (16.7% vs 4.8%), abdominal discomfort (5.6% vs 8%) and fatigue (5.6% vs 4.8%). One patient with AE‐related treatment discontinuation presented with liver decompensation after 4‐week GLE/PIB therapy. DAA‐related significant laboratory abnormalities occurred in two patients with >3× elevated bilirubin level in the GLE/PIB group. GLE/PIB and LDV/SOF are well tolerated and achieve high SVR12 rates for patients with mixed HCV genotype infection.
The mass-luminosity relation for late-type stars has long been a critical tool for estimating stellar masses. However, there is growing need for both a higher-precision relation and a better ...understanding of systematic effects (e.g., metallicity). Here we present an empirical relationship between and M* spanning 0.075 M < M* < 0.70 M . The relation is derived from 62 nearby binaries, whose orbits we determine using a combination of Keck/NIRC2 imaging, archival adaptive optics data, and literature astrometry. From their orbital parameters, we determine the total mass of each system, with a precision better than 1% in the best cases. We use these total masses, in combination with resolved KS magnitudes and system parallaxes, to calibrate the -M* relation. The resulting posteriors can be used to determine masses of single stars with a precision of 2%-3%, which we confirm by testing the relation on stars with individual dynamical masses from the literature. The precision is limited by scatter around the best-fit relation beyond measured M* uncertainties, perhaps driven by intrinsic variation in the -M* relation or underestimated uncertainties in the input parallaxes. We find that the effect of Fe/H on the -M* relation is likely negligible for metallicities in the solar neighborhood (0.0% 2.2% change in mass per dex change in Fe/H). This weak effect is consistent with predictions from the Dartmouth Stellar Evolution Database, but inconsistent with those from MESA Isochrones and Stellar Tracks (at 5 ). A sample of binaries with a wider range of abundances will be required to discern the importance of metallicity in extreme populations (e.g., in the Galactic halo or thick disk).
We compute the hadronic light-by-light scattering contribution to the muon
g
-
2
from the up, down, and strange-quark sector directly using lattice QCD. Our calculation features evaluations of all ...possible Wick-contractions of the relevant hadronic four-point function and incorporates several different pion masses, volumes, and lattice-spacings. We obtain a value of
a
μ
Hlbl
=
106.8
(
15.9
)
×
10
-
11
(adding statistical and systematic errors in quadrature), which is consistent with current phenomenological estimates and a previous lattice determination. It now appears conclusive that the hadronic light-by-light contribution cannot explain the current tension between theory and experiment for the muon
g
-
2
.
Background and Aim
This study investigated whether hepatitis B surface antigen (HBsAg) could predict hepatitis B virus (HBV) relapse after cessation of entecavir or tenofovir disoproxil fumarate ...(TDF) prophylaxis for chronic hepatitis B cancer patients who are undergoing chemotherapy.
Methods
The study enrolled 122 hepatitis B e‐antigen‐negative cancer patients who underwent chemotherapy with entecavir or TDF for antiviral prophylaxis and posttreatment follow‐up for at least 6 months.
Results
Of the 122 patients, 52 and 18 experienced virological and clinical relapse, which had 3‐year cumulative incidences of 46.6% and 18.6%, respectively. Multivariate analysis showed that end‐of‐treatment HBsAg levels and baseline HBV‐DNA ≥ 2000 IU/mL were independent predictors of virological relapse. The best HBsAg cutoff value was 500 IU/mL. An end‐of‐treatment HBsAg of 500 IU/mL was useful for predicting virological relapse in patients with baseline HBV‐DNA < 2000 IU/mL (3‐year rate: 21.3% vs 46.4%, P = 0.038, in patients with HBsAg < 500 and ≥ 500 IU/mL, respectively), but not in patients with baseline HBV‐DNA ≥ 2000 IU/mL. Of the 52 patients who experienced virological relapse, 13 experienced transient virological relapse. Patients with baseline HBV‐DNA level < 2000 IU/mL experienced a higher rate of transient virological relapse (42.1% vs 15.2%, P = 0.031). Three patients experienced hepatic decompensation upon alanine aminotransferase flares, and no patient died after timely retreatment. Ten patients experienced posttreatment HBsAg loss, and the 3‐year HBsAg loss rate was 30.7% in patients with end‐of‐treatment HBsAg < 100 IU/mL.
Conclusions
The baseline HBV‐DNA and end‐of‐treatment HBsAg levels could predict virological relapse after withdrawal of entecavir and TDF prophylaxis for chemotherapy.
Summary
This study was done to elucidate the influence of direct-acting antiviral (DAA) agents on the recurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC ...(HCV-HCC) after curative therapies. HCV-HCC patients who received curative therapies and obtained a complete response were analyzed. From January 2017 to September 2017, 112 HCV-HCC patients received DAA and obtained a sustained virological response (SVR). From January 2006 to December 2014, another 345 HCV-HCC patients received peg-interferon-based treatment and 118 obtained SVR. From January 2012 to December 2016, 248 HCV-HCC patients had complete HCC response and did not receive antiviral treatment. Patients were divided into DAA, IFN, and Untreated groups based on what antiviral treatment they received. There were 82 patients in the DAA group, 80 patients in the IFN group, and 160 patients in the Untreated group. During the follow-up period, the DAA group had 22 (26.8%) recurrent cases, whereas the IFN group had 46 (56.8%) cases after antiviral treatment. Among the 22 recurrent cases in the DAA group, 19 (86.9%) experienced HCC recurrence during 1 year after DAA initiation. Compared with the IFN group, the DAA group had poorer one-year recurrence-free survival (75.4% vs. 95%,
p
< 0.001), even after adjustment with propensity score matching (81.4% vs. 93.9%,
p
= 0.034). However, DAA was an improving factor for HCC recurrence compared with the Untreated group in the multivariate analysis. Among HCV-HCC patients with complete treatment, those with DAA-induced SVR had a higher one-year recurrence rate than those who received IFN-based antiviral therapy, but DAA did not seem to increase HCC recurrence compared to untreated patients.
Without analyzing the status of viremia, hepatitis C virus-related hepatocellular carcinoma (HCV-HCC) patients are proposed to have better prognosis than hepatitis B virus-related HCC (HBV-HCC) ...patients using sorafenib. We aimed to elucidate the efficacy of concurrent sorafenib and anti-viral treatment for HCC patients with HBV or HCV infection in real world. Between January 2018 and January 2021, 256 unresectable HCC patients receiving first-line sorafenib were evaluated. High-potency nucleoside analogs were used for HBV control, whereas direct-acting antivirals were administered for HCV eradication. Well-controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before sorafenib. We recruited 116 (65.2%) HBV-HCC patients and 62 (34.8%) HCV-HCC patients. Using sorafenib, progression-free survival and overall survival (OS) rates between these two groups were not different. Before sorafenib, 56% of HBV-HCC patients and 54.8% of HCV-HCC patients had well-controlled viremia and their OS was superior to those who had uncontrolled viremia (15.5 vs. 11.1 months, p = 0.001). Dividing our patients into four subgroups as well-controlled HCV viremia, well-controlled HBV viremia, uncontrolled HCV viremia, and uncontrolled HBV viremia, their OS rates were distributed with a significantly decreasing trend as 21.9 months, 15.0 months, 14.2 months, and 5.7 months (p = 0.009). Furthermore, well-controlled viremia was associated with mortality in multivariate analysis (Hazard ratio: 0.63, 95% confidence interval: 0.42–0.93, p = 0.022). In real-life, HBV or HCV infection did not contribute to the prognosis of HCC patients receiving sorafenib; however, whether viremia was controlled or not did contribute.
No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis ...for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF).
A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled.
The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment.
In patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment.
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