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PTV delineations were varied due to protocol differences and extended parametrial tissue inclusion. All centres met EMBRACE II plan aims for PTV V 95 and CTV HR D 90 EQD 2, despite variation in prescription dose, fractionation and treatment technique. CONCLUSIONS Brachytherapy target volume delineations are varied due to differences in contouring guidelines and protocols used. PTV delineations are varied due to the uncertainties surrounding the extent of parametrial involvement. Dosimetric optimisation is sufficient across all centres to satisfy EMBRACE II planning aims despite significant variation in protocols used. ADVANCES IN KNOWLEDGE Previous multi-institutional audits of cervical cancer radiotherapy practices have been performed in Europe and the US. This study is the first of its kind to be performed in the UK.RATIONALE Aspirin-exacerbated respiratory disease is characterized by severe asthma, non-steroidal anti-inflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin-hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner. OBJECTIVES To evaluate omalizumab efficacy against aspirin-hypersensitivity, leukotriene E4 overproduction, and symptoms during oral aspirin challenge in aspirin-exacerbated respiratory disease using a randomized design. METHODS We performed a double-blind, randomized, cross-over, placebo-controlled, single-centre study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients aged 20-79 years with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (11) to 3-month treatment with omalizumab or placebo, followed by >18-week washout period (croistration available at https//www.umin.ac.jp/ctr/index.htm, ID UMIN000018777. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http//creativecommons.org/licenses/by-nc-nd/4.0/).BACKGROUND Uncontrolled blood pressure (BP) is a leading preventable cause of death that remains common in the US population despite the availability of effective medications. New technology and program innovation has high potential to improve BP but may be expensive and burdensome for patients, clinicians, health systems, and payers and may not produce desired results or reduce existing disparities in BP control. METHODS AND RESULTS The PCORnet Blood Pressure Control Laboratory is a platform designed to enable national surveillance and facilitate quality improvement and comparative effectiveness research. The platform uses PCORnet, the National Patient-Centered Clinical Research Network, for engagement of health systems and collection of electronic health record data, and the Eureka Research Platform for eConsent and collection of patient-reported outcomes and mHealth data from wearable devices and smartphones. Three demonstration projects are underway BP track will conduct national surveillance of BP controesigned to be a reusable platform for efficient surveillance and comparative effectiveness research; results from demonstration projects are forthcoming.PURPOSE The purpose of OncoMX1 knowledgebase development was to integrate cancer biomarker and relevant data types into a meta-portal, enabling the research of cancer biomarkers side by side with other pertinent multidimensional data types. METHODS Cancer mutation, cancer differential expression, cancer expression specificity, healthy gene expression from human and mouse, literature mining for cancer mutation and cancer expression, and biomarker data were integrated, unified by relevant biomedical ontologies, and subjected to rule-based automated quality control before ingestion into the database. RESULTS OncoMX provides integrated data encompassing more than 1,000 unique biomarker entries (939 from the Early Detection Research Network [EDRN] and 96 from the US Food and Drug Administration) mapped to 20,576 genes that have either mutation or differential expression in cancer. Sentences reporting mutation or differential expression in cancer were extracted from more than 40,000 publications, and healthy gene expression data with samples mapped to organs are available for both human genes and their mouse orthologs. CONCLUSION OncoMX has prioritized user feedback as a means of guiding development priorities. By mapping to and integrating data from several cancer genomics resources, it is hoped that OncoMX will foster a dynamic engagement between bioinformaticians and cancer biomarker researchers. This engagement should culminate in a community resource that substantially improves the ability and efficiency of exploring cancer biomarker data and related multidimensional data.RATIONALE We previously demonstrated involvement of nicotinamide phosphoribosyl-transferase (NAMPT) in pulmonary arterial hypertension (PAH) and now examine NAMPT regulation and extracellular NAMPT's role in PAH vascular remodeling. METHODS NAMPT transcription and protein expression in human lung endothelial cell (EC) was assessed in response to PAH-relevant stimuli (PDGF, VEGF, TGFβ1 and hypoxia). Endothelial to mesenchymal transition (EndMT) was detected by SANI1 and PECAM1 immunofluorescence. An eNAMPT-neutralizing polyclonal antibody (pAb) was tested in a PAH model of monocrotaline (MCT) challenge in rats. RESULTS Plasma eNAMPT levels, significantly increased in IPAH patients, were highly correlated with indices of PAH severity. Extracelluar NAMPT increased EndMT and each PAH stimulus significantly increased EC NAMPT promoter activity involving transcription factors STAT5, SOX18, and SOX 17, a newly GWAS-defined PAH candidate gene. The hypoxia-induced transcription factor, HIF-2α, also potently regulated NAMPT promoter activity and HIF-2α binding sites were identified between -628bp and -328bp. The prolyl hydroxylase domain-containing protein 2 (PHD2) inhibitor (FG-4592) significantly increased NAMPT promoter activity and protein expression in a HIF-2α-dependent manner. Finally, the eNAMPT-neutralizing pAb significantly reduced MCT-induced vascular remodeling, PAH hemodynamic alterations and NFkB activation. CONCLUSIONS eNAMPT is a novel and attractive therapeutic target essential to PAH vascular remodeling.CONTEXT.— The use of neoadjuvant therapy in the management of early-stage invasive breast cancer is increasing. Residual Cancer Burden and other similar tools use pathologic characteristics of post-neoadjuvant therapy breast tumors to determine long-term outcome. However, there are no standardized guidelines for the pathologic evaluation of these specimens in the routine clinical setting. OBJECTIVE.— To assess current practices among Canadian pathologists and pathology assistants with regard to the processing and reporting of post-neoadjuvant therapy breast specimens. DESIGN.— An electronic survey was distributed to pathologists and pathology assistants across Canada. RESULTS.— Sixty-three responses were obtained. A total of 48% (15 of 31) of surveyed pathologists reported familiarity with the Residual Cancer Burden tool. A total of 40% (25 of 63) of respondents reported a lack of routine use of specimen photography, and 35% (22 of 63) reported a lack of routine use of grossing diagrams. There was significant variation with respect to tumor bed sampling; the most common method was to submit 1 block per centimeter of tumor (20 of 63; 32%). There was also significant variation in the method of measuring residual tumor; the most common method was to measure the largest cross-section of residual tumor (16 of 32; 50%). CONCLUSIONS.— There is a need for standardization of the evaluation of post-neoadjuvant therapy breast specimens in the routine clinical setting in Canada. We recommend the routine use of specimen mapping, submitting the largest cross section of tumor bed in toto, reporting tumor size as per American Joint Committee on Cancer and Residual Cancer Burden guidelines, and routinely including measurements of residual tumor cellularity and in situ disease in the final pathology report as per Residual Cancer Burden guidelines.CONTEXT.— The updated American Society of Clinical Oncology/College of American Pathologists guideline for human epidermal growth factor receptor 2 (HER2) testing in breast cancer requires pathologists to re-evaluate HER2 status. OBJECTIVE.— To define HER2 status of breast cancer using immunohistochemistry and fluorescence in situ hybridization. DESIGN.— Diagnostic reports of invasive breast cancers made between 2014 and 2018 with HER2 immunohistochemistry and fluorescence in situ hybridization results were retrieved. HER2 status was re-defined using the updated recommendations. RESULTS.— Of 2514 tumors, 89.7% (2254 of 2514) suggested for fluorescence in situ hybridization assay were HER2 immunohistochemistry 2+. Approximately 8.9% (225 of 2514) and 1.4% (35 of 2514) of tumors were of immunohistochemistry 0/1+ and 3+, respectively. Based on the average HER2 copy number and HER2CEP17 ratio, tumors were assigned into 5 groups, including 13.1% (330 of 2514) group 1 tumors, 2.1% (52 of 2514) group 2 tumors, 1.1% (27 of 2514) group 3 tumors, 7.0% (175 of 2514) group 4 tumors, and 76.8% (1930 of 2514) group 5 tumors. In combination with immunohistochemistry, all tumors in group 2 and group 4 changed HER2 status, from positive and equivocal into negative, respectively, while group 3 tumors remained positive. Comparative analyses of clinicopathologic features of tumors in different groups revealed that group 2 and 4 tumors displayed worse clinicopathologic features than those of group 5, while group 3 tumors shared similar clinicopathologic features to those of group 1. CONCLUSIONS.— Following the updated guideline, HER2 status is clearly designated. Significant differences regarding clinical features were observed between tumors in different groups but they share the same HER2 status, suggesting further validation of the accuracy of this diagnostic approach is warranted.Purpose The purpose of this article was to determine whether patients who complain of bolus stasis are accurate at localizing bolus stasis as measured by a videofluoroscopic swallowing study with an esophagram. Method This study used a prospective analysis of outcomes data from the University of Wisconsin-Madison Voice and Swallow Outcomes database in patients with complaints of bolus stasis who completed the combined videofluoroscopic swallowing study and esophagram to determine the accuracy of bolus stasis localization. TTNPB Results Dysphagia evaluation was completed in 301 patients with complaints of bolus stasis. Patients with complaints of bolus stasis in the throat (i.e., pharynx and cervical esophagus) were less accurate at localizing bolus stasis than patients with complaints in the thoracic esophagus (p less then .001). Esophageal stasis was the most common finding regardless of complaint location. Conclusion Patients are poor at localizing bolus stasis, and esophageal stasis is common in patients who complain of pharyngeal stasis. This work supports a comprehensive evaluation of both the pharynx and the esophagus for patients with complaints of bolus stasis in the throat. Future research should focus on identifying symptom profiles that could lead to targeted swallowing evaluations based on patient history and complaint.