An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting ...of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.
The usefulness of pharmacokinetic parameters for glioma grading has been reported based on the perfusion data from parts of entire-tumor volumes. However, the perfusion values may not reflect the ...entire-tumor characteristics. Our aim was to investigate the feasibility of glioma grading by using histogram analyses of pharmacokinetic parameters including the volume transfer constant, extravascular extracellular space volume per unit volume of tissue, and blood plasma volume per unit volume of tissue from T1-weighted dynamic contrast-enhanced perfusion MR imaging.
Twenty-eight patients (14 men, 14 women; mean age, 49.75 years; age range, 25-72 years) with histopathologically confirmed gliomas (World Health Organization grade II, n = 7; grade III, n = 8; grade IV, n = 13) were examined before surgery or biopsy with conventional MR imaging and T1-weighted dynamic contrast-enhanced perfusion MR imaging at 3T. Volume transfer constant, extravascular extracellular space volume per unit volume of tissue, and blood plasma volume per unit volume of tissue were calculated from the entire-tumor volume. Histogram analyses from these parameters were correlated with glioma grades. The parameters with the best percentile from cumulative histograms were identified by analysis of the area under the curve of the receiver operating characteristic analysis and were compared by using multivariable stepwise logistic regression analysis for distinguishing high- from low-grade gliomas.
All parametric values increased with increasing glioma grade. There were significant differences among the 3 grades in all parameters (P < .01). For the differentiation of high- and low-grade gliomas, the highest area under the curve values were found at the 98th percentile of the volume transfer constant (area under the curve, 0.912; cutoff value, 0.277), the 90th percentile of extravascular extracellular space volume per unit volume of tissue (area under the curve, 0.939; cutoff value, 19.70), and the 84th percentile of blood plasma volume per unit volume of tissue (area under the curve, 0.769; cutoff value, 11.71). The 98th percentile volume transfer constant value was the only variable that could be used to independently differentiate high- and low-grade gliomas in multivariable stepwise logistic regression analysis.
Histogram analysis of pharmacokinetic parameters from whole-tumor volume data can be a useful method for glioma grading. The 98th percentile value of the volume transfer constant was the most significant measure.
There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have ...failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.
Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10mg/kg by intravenous infusion every 2weeks or physician’s choice of chemotherapy (paclitaxel 80mg/m2 on days 1, 8, and 15 or irinotecan 150mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0months; hazard ratio (HR)=1.1 95% confidence interval (CI) 0.9–1.4; P=0.81} or the secondary end points of PFS median, 1.4 versus 2.7months; HR=1.73 (95% CI 1.4–2.2); P>0.99 or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.
Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.
ClinicalTrials.gov: NCT02625623.
Summary
Background
Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect ...of TRPV1 antagonist via topical application in patients with AD remains unknown.
Objectives
To assess the clinical efficacy and safety of PAC‐14028, a TRPV1 antagonist, via topical application in patients with AD.
Methods
In this 8‐week, phase IIb, randomized, double‐blind, multicentre, vehicle‐controlled study, patients with mild‐to‐moderate AD were randomized to receive PAC‐14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90.
Results
A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC‐14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC‐14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC‐14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two‐grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported.
Conclusions
PAC‐14028 cream may be an effective and safe treatment modality for the treatment of patients with mild‐to‐moderate AD.
What is already known about this topic?
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases characterized by pruritic erythematous skin lesions and barrier dysfunction.
Transient receptor potential vanilloid subfamily, member 1 (TRPV1) antagonists suppress the release of pruritic and proinflammatory mediators.
The preclinical results demonstrate the feasibility of TRPV1 as a potential therapeutic target for the treatment of AD.
What does this study add?
TRPV1 regulates inflammation and pruritus in patients with AD.
PAC‐14028 cream, a novel TRPV1 antagonist, was superior to vehicle in improving clinical symptoms and signs with a favourable safety profile in adults with mild‐to‐moderate AD.
TRPV1 antagonism may play a role as a promising nonsteroidal topical treatment target for AD with a new mechanism of action.
Linked Editorial: Song and Armstrong. Br J Dermatol 2019; 180:971–972.
Plain language summary available online
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Subgingival microorganisms are potentially associated with periodontal diseases. However, changes in the subgingival microbiota during the progress of periodontal diseases are poorly understood. In ...this study, we analyzed bacterial communities in the subgingival paper point samples from 32 Korean individuals with no sign of disease, gingivitis, or periodontitis using 454 FLX Titanium pyrosequencing. A total of 256,113 reads representing 26 phyla, 433 genera, and 1,016 species were detected. Bacteroidetes, Fusobacteria, Synergistetes, and Spirochaetes were the abundant phyla in periodontitis subjects, whereas Firmicutes and Proteobacteria were identified as the dominant phyla in the gingivitis and healthy subjects, respectively. Although high levels of Porphyromonas, Fusobacterium, Fretibacterium, Rothia, Filifactor, and Treponema genera were observed in the periodontitis subjects, Streptococcus, Capnocytophaga, Leptotrichia, and Haemophilus genera were found at high frequency in the gingivitis subjects. Species including Porphyromonas gingivalis, Fusobacterium nucleatum, and Fretibacterium fastidiosum were significantly increased in periodontitis subjects. On the other hand, Streptococcus pseudopneumoniae, Haemophilus parainfluenzae, and Leptotrichia hongkongensis were preferentially observed in the gingivitis subjects. Intriguingly, the halophile Halomonas hamiltonii was revealed as a predominant species in the healthy subjects. Based on Fast UniFrac analysis, distinctive bacterial clusters were classified for the healthy, gingivitis, and periodontitis state. The current findings might be useful for understanding the pathogenesis, diagnosis, and treatment of periodontal diseases.
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the ...potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
Background
Robot‐assisted gastrectomy (RAG) has been developed in the hope of improving surgical quality and overcoming the limitations of conventional laparoscopically assisted gastrectomy (LAG) and ...open gastrectomy (OG) for gastric cancer. The aim of this study was to determine the extent of evidence in support of these ideals.
Methods
A systematic review of the three operation types (RAG, LAG and OG) was carried out to evaluate short‐term outcomes including duration of operation, retrieved lymph nodes, estimated blood loss, resection margin status, technical postoperative complications and hospital stay.
Results
Nine non‐randomized observational clinical studies involving 7200 patients satisfied the eligibility criteria. RAG was associated with longer operating times than LAG and OG (weighted mean difference 61·99 and 65·73 min respectively; P ≤ 0·001). The number of retrieved lymph nodes and the resection margin length in RAG were comparable with those of LAG and OG. Estimated blood loss was significantly less in RAG than in OG (P = 0·002), but not LAG. Mean hospital stay for RAG was similar to that for LAG (P = 0·14). In contrast, hospital stay was significantly shorter, by a mean of 2·18 days, for RAG compared with OG (P < 0·001). Postoperative complications were similar for all three operative approaches.
Conclusion
Short‐term oncological outcomes of RAG were comparable with those of the other approaches. LAG was a shorter procedure and less expensive than RAG. Future studies involving RAG should focus on minimizing duration of operation and reducing cost.
Expensive, but no great advantage for robotics
(
) promoter methylation status in primary and recurrent glioblastoma may change during treatment. The purpose of this study was to correlate
promoter methylation status changes with DWI and DSC PWI ...features in patients with recurrent glioblastoma after standard treatment.
Between January 2008 and November 2016, forty patients with histologically confirmed recurrent glioblastoma were enrolled. Patients were divided into 3 groups according to the
promoter methylation status for the initial and recurrent tumors: 2 groups whose
promoter methylation status remained, group methylated (
= 13) or group unmethylated (
= 18), and 1 group whose
promoter methylation status changed from methylated to unmethylated (
= 9). Normalized ADC and normalized relative CBV values were obtained from both the enhancing and nonenhancing regions, from which histogram parameters were calculated. The ANOVA and the Kruskal-Wallis test followed by post hoc tests were performed to compare histogram parameters among the 3 groups. The
test and Mann-Whitney
test were used to compare parameters between group methylated and group methylated to unmethylated. Receiver operating characteristic curve analysis was used to measure the predictive performance of the normalized relative CBV values between the 2 groups.
Group methylated to unmethylated showed significantly higher means and 90th and 95th percentiles of the cumulative normalized relative CBV values of the nonenhancing region of the initial tumor than group methylated and group unmethylated (all
< .05). The mean normalized relative CBV value of the nonenhancing region of the initial tumor was the best predictor of methylation status change (
< .001), with a sensitivity of 77.78% and specificity of 92.31% at a cutoff value of 2.594.
promoter methylation status might change in recurrent glioblastoma after standard treatment. The normalized relative CBV values of the nonenhancing region at the first preoperative MR imaging were higher in the
promoter methylation change group from methylation to unmethylation in recurrent glioblastoma.
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