Abstract Background Programmed death-ligand 1 (PD-L1) expression has been suggested as a potential predictive biomarker of response to anti-PD-1/PD-L1 therapy. In this study, we investigated whether ...the expression of PD-L1 in tumour cells is affected by neoadjuvant concurrent chemoradiotherapy (CCRT) or chemotherapy in oesophageal squamous cell carcinoma. Patients and methods Between 2004 and 2014, we collected the medical records of locally advanced oesophageal cancer patients consecutively diagnosed and treated with neoadjuvant CCRT or chemotherapy, followed by curative resection. PD-L1 expression in acquired tissue specimens was evaluated by immunohistochemistry using the H-score. The changes in PD-L1 expression between paired samples were evaluated and we also analysed PD-L1 expression in surgical tumour specimens to evaluate its prognostic role. Results Twenty-eight paired tumour tissues that were acquired before and after neoadjuvant therapy were available: 19 patients with CCRT and 9 with chemotherapy before complete oesophagectomy. The PD-L1 H-score increased significantly from baseline tumour tissues to surgical tumour tissues after neoadjuvant CCRT ( P = 0.007, median H-score from 28 to 52), whereas it decreased significantly after neoadjuvant chemotherapy ( P = 0.048, median H-score from 53 to 22). In a total of 73 patients, including 45 additional cases for the prognosis analysis, patients with higher PD-L1 H-scores (≥20) had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores (<20). Conclusions PD-L1 expression in tumour cells increased in oesophageal cancer patients who received neoadjuvant CCRT. Further studies with more cases are necessary to validate these findings.
Background
Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of ...cephalosporin‐induced anaphylaxis and evaluate the clinical efficacy of screening skin tests.
Methods
In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin‐induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side‐chain structures. The incidence of cephalosporin‐induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side‐chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins.
Results
We identified 76 cases of cephalosporin‐induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side‐chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06).
Conclusions
The incidence of cephalosporin‐induced anaphylaxis differed according to individual drugs and side‐chain structure. Screening IDT showed no clinical efficacy at a population level.
Among total 1 140 354 cephalosporin treatment courses from 12 hours hospitals, the incidence of cephalosporin induced anaphylaxis was 6.8 per 100 000 exposures and the related fatality was 1.3%. The incidence of cephalosporin induced anaphylaxis varies with each drug type, and the highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures). Screening intradermal tests with cephalosporin failed to show preventive effect on cephalosporin‐induced anaphylaxis.
Aim
Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely ...insufficient. The aim of this study was to elucidate the microbiota‐driven mechanisms involved in the development of nonalcoholic hepatic steatosis.
Methods and Results
Ob/ob mice and their wild‐type lean control mice were fed an AIN‐93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine‐conjugated BAs compared to their lean controls. The proportions of butyrate‐producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol‐7α‐hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice.
Conclusion
Microbiota‐associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR‐SHP pathway, thereby accelerating fat synthesis.
Significance and Impact of the Study
We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.
Renewable energy sources like wind energy are copiously available without any limitation. Wind turbines are used to tap the potential of wind energy, which is available in millions of MW. Reliability ...of wind turbine is critical to extract this maximum amount of energy from the wind. We reviewed different techniques, methodologies and algorithms developed to monitor the performance of wind turbine as well as for an early fault detection to keep away the wind turbines from catastrophic conditions due to sudden breakdowns. To keep the wind turbine in operation, implementation of condition monitoring system (CMS) and fault detection system (FDS) is paramount and for this purpose ample knowledge of these two types of systems is mandatory. So, an attempt has been made in this direction to review maximum approaches related to CMS and FDS in this piece of writing.
In this study, we undertook a randomized phase III trial of 105 NSCLC patients with oligo (one to four) -brain metastases. Patients were randomly assigned (1:1) to receive either stereotactic ...radiosurgery (SRS) followed by chemotherapy or upfront chemotherapy alone. The results demonstrated that SRS followed by chemotherapy did not improve overall survival compared with upfront chemotherapy only.
It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases.
We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome.
The median age was 58 years (range, 29–85) with ECOG 0–1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months 95% confidence interval (CI), 9.2–20.0 in the SRS group and 15.3 months (95% CI, 7.2–23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy),P = 0.248. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance.
Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients.
NCT01301560.
The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 ... GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.
In this study, we demonstrated that graphene could selectively absorb/desorb NO
x
molecules at room temperature. Chemical doping with NO
2 molecules changed the conductivity of the graphene layers, ...which was quantified by monitoring the current–voltage characteristics at various NO
2 gas concentrations. The adsorption rate was found to be more rapid than the desorption rate, which can be attributed to the reaction occurred on the surface of the graphene layer. The sensitivity was 9% when an ambient of 100
ppm NO
2 was used. Graphene-based gas sensors showed fast response, good reversibility, selectivity and high sensitivity. Optimization of the sensor design and integration with UV-LEDs and Silicon microelectronics will open the door for the development of nano-sized gas sensors that are extremely sensitive.
The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, ...identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (Chinese Society of Clinical Oncology), Korea (Korean Association for Clinical Oncology), Malaysia (Malaysian Oncological Society), Singapore (Singapore Society of Oncology) and Taiwan (Taiwan Oncology Society). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
To identify potential microRNA (miRNA) links between Smad3, a mediator of TGF-β (transforming growth factor-β) signaling, and E-cadherin, we characterized the miRNA profiles of two gastric cancer ...cell lines: SNU484-LPCX, which does not express Smad3, and SNU484-Smad3, in which Smad3 is overexpressed. We found that among differentially expressed miRNAs, miR-200 family members are overexpressed in SNU484-Smad3 cells. Subsequent studies, including analysis of the effects of silencing Smad3 in SNU484-Smad3 cells and a luciferase reporter assay, revealed that Smad3 directly binds to a Smad-binding element located in the promoter region of miR-200b/a, where it functions as a transcriptional activator. TGF-β did not affect the regulatory role of Smad3 in transcription of miR-200 and expression of epithelial-mesenchymal transition markers. We conclude that Smad3 regulates, at the transcriptional level, miR-200 family members, which themselves regulate ZEB1 and ZEB2, known transcriptional repressors of E-cadherin, at the posttranscriptional level in a TGF-β-independent manner. This represents a novel link between Smad3 and posttranscriptional regulation by miRNAs in epithelial-mesenchymal transition in gastric cancer cells.
Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC).
Eligibility criteria included advanced nccRCC except ...for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR).
Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3–19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2–8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7–23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4–42.9 months). Toxicity profiles were commensurate with prior reports.
Sunitinib has promising activity in patients with nccRCC (NCT01219751).
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