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1.
Purpose

Stereotactic radiation therapy (SRT) and immune checkpoint inhibitors (ICI) may act synergistically to improve treatment outcomes but may also increase the risk of symptomatic radiation necrosis (RN). The objective of this study was to compare outcomes for patients undergoing SRT with and without concurrent ICI.

Methods and materials

Patients treated for BMs with single or multi-fraction SRT were retrospectively reviewed. Concurrent ICI with SRT (SRT-ICI) was defined as administration within 3 months of SRT. Local control (LC), radiation necrosis (RN) risk and distant brain failure (DBF) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. Wilcoxon rank sum and Chi-square tests were used to compare covariates. Multivariate cox regression analysis (MVA) was performed.

Results

One hundred seventy-nine patients treated with SRT for 385 brain lesions were included; 36 patients with 99 lesions received SRT-ICI. Median follow up was 10.3 months (SRT alone) and 7.7 months (SRT- ICI) (p = 0.08). Lesions treated with SRT-ICI were more commonly squamous histology (17% vs 8%) melanoma (20% vs 2%) or renal cell carcinoma (8% vs 6%), (p < 0.001). Non-small cell lung cancer (NSCLC) compromised 60% of patients receiving ICI (n = 59). Lesions treated with SRT-ICI had significantly improved 1-year local control compared to SRT alone (98 and 89.5%, respectively (p = 0.0078). On subset analysis of NSCLC patients alone, ICI was also associated with improved 1 year local control (100% vs. 90.1%) (p = 0.018). On MVA, only tumor size ≤2 cm was significantly associated with LC (HR 0.38, p = 0.02), whereas the HR for concurrent ICI with SRS was 0.26 (p = 0.08). One year DBF (41% vs. 53%; p = 0.21), OS (58% vs. 56%; p = 0.79) and RN incidence (7% vs. 4%; p = 0.25) were similar for SRT alone versus SRT-ICI, for the population as a whole and those patients with NSCLC.

Conclusion

These results suggest SRT-ICI may improve local control of brain metastases and is not associated with an increased risk of symptomatic radiation necrosis in a cohort of predominantly NSCLC patients. Larger, prospective studies are necessary to validate these findings and better elucidate the impact of SRT-ICI on other disease outcomes.

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The film thickness plays an important role in the performance of materials applicable to different technologies including chemical sensors, catalysis and/or energy materials. The relationship between the surface and volume of the functional layers is key to high performance evaluations. Here we demonstrate the thermophoretic deposition of different thicknesses of the functional layers designed using flame combustion of tin 2-ethylhexanoate dissolved in xylene, and measurement of thickness by scanning electron microscopy and focused ion beam. The parameters such as spray fluid concentration (differing Sn2+ content), substrate-nozzle distance and time of the spray were considered to investigate the layer growth. The results showed ≈ 23, 124 and 161 μm thickness of the SnO2 layer after flame spray of 0.1, 0.5 M and 1.0 M tin 2-EHA-Xylene solutions for 1200 s. While Sn2+ concentration was 0.5 M for all the flame sprays, the substrates placed at 250, 220 and 200 mm from the flame nozzle had layer thicknesses of 113, 116 and 132 µm, respectively. Spray time dependent thickness growth showed a linear increase from 8.5 to 152.1 µm when the substrates were flame sprayed for 30 s to 1200 s using 0.5 M tin 2-EHA-Xylene solutions. Changing the dispersion oxygen flow (3–7 L/min) had almost no effect on layer thickness. Layers fabricated were compared to a model found in literature, which seems to describe the thickness well in the domain of varied parameters. It turned out that primary particle size deposited on the substrate can be tuned without altering the layer thickness and with little effect on porosity. Applications depending on porosity, such as catalysis or gas sensing, can benefit from tuning the layer thickness and primary particle size.  相似文献   
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Borderline personality (BPD) and complex posttraumatic stress disorders (PTSD) are both powerfully associated with the experience of interpersonal violence during childhood and adolescence. The disorders frequently co-occur and often result in pervasive problems in, e.g., emotion regulation and altered pain perception, where the endocannabinoid system is deeply involved. We hypothesize an endocannabinoid role in both disorders. We investigated serum levels of the endocannabinoids anandamide and 2-arachidonoylglycerol and related fatty acid ethanolamides (FAEs) in BPD, PTSD, and controls. Significant alterations were found for both endocannabinoids in BPD and for the FAE oleoylethanolamide in PTSD suggesting a respective link to both disorders.  相似文献   
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ObjectivesUrothelial carcinoma of the bladder (UCB) is a highly heterogeneous malignancy that causes significant morbidity and mortality. Standard pathologic features (stage, grade, and nodal status) are insufficient to predict accurately a patient's outcome. Biomarkers could help clinicians provide individualized prognostications and allow risk-stratified clinical decision making regarding surgical and medical treatment. This review summarizes the existing tissue- and blood-based biomarkers in UCB.Material and methodsA PubMed/Medline search was conducted to identify original articles regarding molecular biomarkers and UCB. Searches were limited to papers published in English. Keywords included urothelial carcinoma, bladder cancer, transitional cell, biomarker, marker, staining, cystectomy, recurrence or progression, survival, prediction, and prognosis.ResultsThe articles with the highest level of evidence were selected and reviewed, with the consensus of all the authors of this paper.ConclusionsThere is no doubt that a panel of biomarkers would eventually improve our clinical decision making regarding treatment and follow-up. However, to date, no biomarker panel is yet validated for daily clinical practice.  相似文献   
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