Summary
Background
With the development of direct‐acting anti‐virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR).
Aim
To ...evaluate the short‐term risk of HCC among patients with SVR by DAAs, including those with cirrhosis or previous HCC.
Methods
This large‐scale, multicentre cohort study included 1,675 consecutive patients who achieved SVR by treatment with interferon‐free sofosbuvir‐based regimens, divided into groups with (n = 152) or without previous HCC (n = 1,523). The Kaplan‐Meier method and Cox proportional hazard analysis were used to calculate the cumulative HCC incidence and related factors of HCC.
Results
During the follow‐up period (median: 17 months), 46 (2.7%) patients developed HCC. The 1‐year cumulative rates of de novo HCC were 0.4% and 4.9% for the noncirrhosis and cirrhosis groups respectively (log‐rank test: P < 0.001). For cirrhotic patients, serum α‐fetoprotein level at the end of treatment (EOT‐AFP) was the strongest predictor of de novo HCC. The 1‐year cumulative de novo HCC rates were 1.4% and 13.1% in the EOT‐AFP < 9.0 ng/mL and ≥ 9.0 ng/mL groups (cut‐off value) respectively (log‐rank test: P < 0.001). The 1‐year cumulative rates of HCC recurrence were 6.5% and 23.1% for the noncirrhosis and cirrhosis groups respectively (log‐rank test: P = 0.023). For cirrhotic patients, previous HCC characteristics were significantly associated with HCC recurrence. In contrast, sex, age and metabolic features did not influence de novo HCC or recurrence.
Conclusions
For cirrhotic patients after elimination of HCV, serum EOT‐AFP level and previous HCC characteristics would be useful markers for predicting de novo HCC or recurrence.
Linked ContentThis article is linked to Tan and Lim paper. To view this article visit https://doi.org/10.1111/apt.14437.
Summary
Background
Direct‐acting antiviral (DAA) regimens have shown high efficacy and tolerability for patients with HCV genotype 1/1b (GT1/1b) in clinical trials. However, robust real‐world ...evidence of interferon (IFN)‐free DAA treatment for HCV GT1‐infected patients in Asia is still lacking.
Aim
To systematically review and meta‐analyse the effectiveness and tolerability of IFN‐free DAA therapy for HCV GT1 infection in Asia.
Methods
We included studies that enrolled adult patients with HCV GT1 infection in routine clinical practice in Asia, using IFN‐free DAA regimens, and reported sustained virological response (SVR) after 12/24 weeks end‐of‐treatment by 31 May 2017. The pooled SVR rates were computed with a random‐effects model. Subgroup analysis and meta‐regression as previously registered in PROSPERO were performed to determine how pre‐planned variables might have affected the pooled estimates.
Results
We included 41 studies from eight countries and regions, comprising of 8574 individuals. The pooled SVR rates for GT1 were 89.9% (95% CI 88.6‐91.1, I2 = 55.1%) with daclatasvir/asunaprevir (DCV/ASV) and 98.1% (95% CI 97.0‐99.0, I2 = 41.0%) with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV). Baseline cirrhosis but not prior treatment history and age, attenuated the effectiveness of both regimens. Baseline resistance associated substitutions (RASs) severely attenuated SVR of DCV/ASV (65.4% vs 94.3%, P < 0.001) and only minimally with LDV/SOF ± RBV (94.5% vs 99.2%, P = 0.003). Patients with renal dysfunction treated with DCV/ASV showed a higher SVR rate (93.9% vs 89.8%, P = 0.046). Patients with hepatocellular carcinoma (HCC) LDV/SOF ± RBV achieved a lower SVR than those without HCC (94.1% vs 98.7%, P = 0.001).
Conclusion
All oral DAA treatment of HCV GT1 resulted in high cure rates in Asian patients in routine clinical practice setting including elderly patients and those with end‐stage renal disease.
SuperKEKB personnel protection system Mimashi, T; Ono, M; Kudo, K ...
Journal of physics. Conference series,
01/2024, Letnik:
2687, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Abstract
The Super-KEKB1 personnel protection system (PPS) takes care of not only Super-KEKB accelerator, but also Photon Factory - Advanced Ring (PF-AR), Positron Damping Ring (PDR)2 and their beam ...transport lines (BT)3. The logic of the PPS has been changed to adapt the new accelerator operation scheme. The Experimental Physics and Industrial Control System (EPICS) was introduced into the PPS. Many tools developed under EPICS environment are used.
Background:The association between gastro-oesophageal reflux disease (GORD) and chronic obstructive pulmonary disease (COPD) exacerbation has so far remained unclear.Objective:To prospectively ...establish the clinical significance of GORD symptoms on exacerbation.Methods:82 patients with COPD and 40 age matched controls were enrolled in this study. Symptoms were evaluated by a questionnaire using the Frequency Scale for the Symptoms of GORD (FSSG). Patients with COPD were prospectively surveyed for 6 months, and episodes of exacerbation were identified using a diary based on modified Anthonisen’s criteria. Exhaled breath condensate (EBC) pH was measured in both groups, and induced sputum was evaluated in patients with COPD.Results:Positive GORD symptoms were reported in 22 (26.8%) patients with COPD and in five (12.5%) controls (p = 0.10). The frequency of exacerbations was significantly associated with the FSSG score (p = 0.03, r = 0.24, 95% CI 0.02 to 0.43). Multiple regression analysis revealed that GORD symptoms were significantly associated with the occurrence of exacerbations (p<0.01; relative risk 6.55, 95% CI 1.86 to 23.11). EBC pH was inversely correlated with FSSG score in both groups (p = 0.01, r = –0.37, 95% CI –0.55 to −0.14 in patients with COPD, and p<0.01, r = –0.45, 95% CI –0.67 to −0.16 in control subjects).Conclusions:GORD symptoms were identified as an important factor associated with COPD exacerbation.
Summary
Background
The Wisteria floribunda agglutinin‐positive human Mac‐2‐binding protein (WFA+‐M2BP) is a new liver fibrosis glycobiomarker with unique fibrosis‐related glyco‐alteration. WFA+‐M2BP ...is also a useful surrogate marker for the risk of developing hepatocellular carcinoma and for the liver functional reserve.
Aim
To evaluate the diagnostic ability of WFA+‐M2BP for liver fibrosis in the clinical setting and the clinical utility of WFA+‐M2BP for predicting the efficacy of direct‐acting anti‐viral (DAA) treatment for chronic hepatitis C patients.
Methods
The study included 159 genotype 1 hepatitis C patients who received DAA‐based treatment (telaprevir or simeprevir) combined with pegylated‐interferon alpha plus ribavirin (108 telaprevir‐ and 51 simeprevir‐based triple treatment). The relation between baseline serum WFA+‐M2BP and treatment efficacy was evaluated.
Results
The serum WFA+‐M2BP level significantly increased with the progress of liver fibrosis. Area under the receiver operating characteristic curve analysis identified 2.17 as the cut‐off index (COI) for WFA+‐M2BP for diagnosing advanced fibrosis. The sustained virological response (SVR) rate was significantly, negatively correlated with the serum WFA+‐M2BP level. Multiple logistic regression analysis found a low serum WFA+‐M2BP level (<2.17 COI) to be independently associated with SVR (odds ratio, 4.35, P = 0.027). Even for prior nonresponders and patients with the interleukin‐28B minor allele or histological advanced fibrosis, treatment outcome was favourable for patients with a low serum WFA+‐M2BP level.
Conclusion
Serum WFA+‐M2BP is a non‐invasive liver fibrosis marker useful for predicting the efficacy of DAA‐based triple therapy for chronic hepatitis C patients.
Developmental and aging changes in testicular factors related to steroidogenesis are unknown in dogs. Using reverse transcription quantitative real-time PCR, this study examined testicular mRNA ...levels of CYP11A1 (P450 cholesterol side-chain cleavage enzyme, P450scc), CYP17A1 (P450 17α-hydroxylase/C17–20 lyase, P450c17), HSD3B2 (3β-hydroxysteroid dehydrogenase, 3β-HSD), CYP19A (P450 aromatase, P450arom), STAR (steroidogenic acute regulatory protein, StAR), cyclooxygenase (COX) -1 and COX-2 in prepubertal (4–6 months of age), postpubertal (1 year of age), and aging (2–18 years of age) dogs. Testicular mRNA levels for P450scc, 3β-HSD, StAR, COX-1, and COX-2 did not change from prepubertal to postpubertal stages, whereas that for P450arom markedly and abruptly increased and that for P450c17 gradually decreased. In postpubertal and aging dogs, a negative correlation was found between aging and testicular P450arom mRNA levels. Based on the rapid testicular growth observed during puberty, these results suggested that total testis gene expression for steroidogenesis-related factors, in particular for P450arom, increases during puberty in dogs. In addition, the decline in P450arom gene expression during aging may affect the ability to synthesize steroids in canine testes.
Summary
Introduction
To provide target values for the manufacturers’ survey of the Japanese Society for Laboratory Hematology (JSLH), accurate standard data from healthy volunteers were needed for ...the five‐part differential leukocyte count. To obtain such data, JSLH required an antibody panel that achieved high specificity (particularly for mononuclear cells) using simple gating procedures. We developed a flow cytometric method for determining the differential leukocyte count (JSLH‐Diff) and validated it by comparison with the flow cytometric differential leukocyte count of the International Council for Standardization in Haematology (ICSH‐Diff) and the manual differential count obtained by microscopy (Manual‐Diff).
Methods
First, the reference laboratory performed an imprecision study of JSLH‐Diff and ICSH‐Diff, as well as performing comparison among JSLH‐Diff, Manual‐Diff, and ICSH‐Diff. Then two reference laboratories and seven participating laboratories performed imprecision and accuracy studies of JSLH‐Diff, Manual‐Diff, and ICSH‐Diff. Simultaneously, six manufacturers’ laboratories provided their own representative values by using automated hematology analyzers.
Results
The precision of both JSLH‐Diff and ICSH‐Diff methods was adequate. Comparison by the reference laboratory showed that all correlation coefficients, slopes and intercepts obtained by the JSLH‐Diff, ICSH‐Diff, and Manual‐Diff methods conformed to the criteria. When the imprecision and accuracy of JSLH‐Diff were assessed at seven laboratories, the CV% for lymphocytes, neutrophils, monocytes, eosinophils, and basophils was 0.5~0.9%, 0.3~0.7%, 1.7~2.6%, 3.0~7.9%, and 3.8~10.4%, respectively. More than 99% of CD45 positive leukocytes were identified as normal leukocytes by JSLH‐Diff.
Conclusions
When JSLH‐Diff method were validated by comparison with Manual‐Diff and ICSH‐Diff, JSLH‐Diff showed good performance as a reference method.
The objective of the study was to investigate whether an infant formula supplemented with galacto-oligosaccharides (GOS; OM55N) was able to stimulate the growth of indigenous bifidobacteria and to ...establish microbiota similar to that of breastfed infants. A randomised, double-blind, placebo-controlled trial was performed using 35 healthy term infants (31-54 days of age; 42±6 days) to determine whether infant formula with 0.3 g/dl GOS (OM55N) stimulated the growth of bifidobacteria in the infants’ guts. At the trial onset and 2 weeks after, the infants’ faecal samples were examined for microbiota composition (bacterial abundance and α-diversity) and faecal characteristics. Among the 35 infants, 5 were withdrawn and 8 were excluded from the final evaluation before breaking the blinding since the indigenous bifidobacteria were not detected at the trial onset. After 2 weeks, the abundance of Bifidobacteriaceae was significantly increased in the GOS feeding group compared to the control (+11.6±24.1% vs -3.9±13.0%; P=0.043). The Shannon index, which accounts for both abundance and evenness of the present species, was significantly decreased with GOS supplementation (-0.1±0.4 vs +0.4±0.4; P=0.014). Faecal characteristics such as pH and organic acids were similar in both groups, with no statistical differences. No adverse side effects related to the formula consumption were reported. Although the concentration of GOS was relatively low, the infant formula with GOS increased the abundance of bifidobacteria and resulted in a reduced α-diversity of the microbiota.
Background:Chronic obstructive pulmonary disease (COPD) is characterised by the presence of airflow limitation caused by loss of lung elasticity and/or airway narrowing. The pathological hallmark of ...loss of lung elasticity is emphysema, and airway wall remodelling contributes to the airway narrowing. Using CT, these lesions can be assessed by measuring low attenuation areas (LAA) and airway wall thickness/luminal area, respectively. As previously reported, COPD can be divided into airway dominant, emphysema dominant and mixed phenotypes using CT. In this study, it is postulated that a patient’s physique may be associated with the relative contribution of these lesions to airflow obstruction.Methods:CT was used to evaluate emphysema and airway dimensions in 201 patients with COPD. Emphysema was evaluated using percentage of LAA voxels (LAA%) and airway lesion was estimated by percentage wall area (WA%). Patients were divided into four phenotypes using LAA% and WA%.Results:Body mass index (BMI) was significantly lower in the higher LAA% phenotype (ie, emphysema dominant and mixed phenotypes). BMI correlated with LAA% (ρ = −0.557, p<0.0001) but not with WA%. BMI was significantly lower in the emphysema dominant phenotype than in the airway dominant phenotype, while there was no difference in forced expiratory volume in 1 s %predicted between the two.Conclusion:A low BMI is associated with the presence of emphysema, but not with airway wall thickening, in male smokers who have COPD. These results support the concept of different COPD phenotypes and suggest that there may be different systemic manifestations of these phenotypes.
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