Citations

BackgroundStudies comparing the ability of staining methods to detect eosinophils in formalin‐fixed canine skin are lacking.Hypothesis/ObjectivesThe aim of this study was to compare the effectiveness of eosinophil peroxidase monoclonal antibody (EPXmAb), Luna and haematoxylin and eosin (H&E) to detect eosinophils in fixed canine skin by assessing the following parameters: (i) specificity of eosinophil staining; (ii) extracellular eosinophil granule staining; (iii) tissue background staining; (iv) contrast between eosinophil and surrounding tissue staining; and (v) differences in the number of eosinophils detected by each stain.MethodsThree serial sections of formalin‐fixed, paraffin‐embedded tissues of predominantly eosinophilic skin diseases (n = 8), noneosinophilic skin diseases (n = 7) and normal canine skin (n = 1) were stained with the three stains. Each parameter was independently assessed and scored by two investigators.ResultsLuna and EPXmAb were specific in detecting eosinophils. The EPXmAb was significantly more effective than Luna (P < 0.001) and H&E (P < 0.001) in its ability to detect extracellular eosinophil granules (i.e. to detect intact and released eosinophil granules). The EPXmAb showed significantly less background staining compared with Luna (P = 0.0005). Moreover, significantly more stain contrast was noted with EPXmAb compared with Luna (P = 0.003) and H&E (P < 0.001). There was no significant difference between the mean eosinophil counts among the three stains.Conclusion and clinical importanceThe three stains were shown to be useful to detect and quantify eosinophils in fixed canine skin. The EPXmAb‐based immunohistochemical stain proved to be a novel tool to detect eosinophils in canine skin.

ABSTRACTThe quantile regression (QR) framework provides a pragmatic approach in understanding the differential impacts of covariates along the distribution of an outcome. However, the QR framework that has pervaded the applied economics literature is based on the conditional quantile regression method. It is used to assess the impact of a covariate on a quantile of the outcome conditional on specific values of other covariates. In most cases, conditional quantile regression may generate results that are often not generalizable or interpretable in a policy or population context. In contrast, the unconditional quantile regression method provides more interpretable results as it marginalizes the effect over the distributions of other covariates in the model. In this paper, the differences between these two regression frameworks are highlighted, both conceptually and econometrically. Additionally, using real‐world claims data from a large US health insurer, alternative QR frameworks are implemented to assess the differential impacts of covariates along the distribution of medication adherence among elderly patients with Alzheimer's disease. Copyright © 2013 John Wiley & Sons, Ltd.

BackgroundWe conducted a retrospective review of patients with unknown primary head and neck cancer who underwent a transoral laser microsurgery (TLM)‐assisted search for an occult tumor.MethodsFifty‐two patients at a single center with unknown primaries of squamous cell carcinoma (SCC) were treated with a surgical algorithm.ResultsThe overall rate of primary tumor identification was 75% (39 of 52 patients). When selecting those cases in which a TLM algorithm with lingual tonsillectomy was utilized, the detection rate was 86% (31 of 36). Tumors were most commonly found in the lingual (65.0%) and palatine tonsils (27.5%). When directed biopsies did not locate a tumor, a higher yield was obtained with the addition of a lingual tonsillectomy in 8 patients.ConclusionA surgical algorithm for the unknown primary that includes TLM‐assisted techniques, including a lingual tonsillectomy, offers the greatest likelihood of successfully detecting the location of occult primary tumors. © 2014 Wiley Periodicals, Inc. Head Neck 36: 942–946, 2014

AbstractIntroduction.DNA variants of uncertain significance (VUS) are common outcomes of clinical genetic testing for susceptibility to cancer. A statistically rigorous model that provides a pathogenicity score for each variant has been developed to aid in the clinical management of patients undergoing genetic testing.Methods.The information in this article is derived from multiple publications on VUS in BRCA genes, distilled for communicating with clinicians who may encounter VUS in their practice.Results.The posterior probability scores for BRCA1 or BRCA2 VUS, calculated from a multifactorial likelihood model, are explained, and links for looking up specific VUS are provided. The International Agency on Cancer Research (IARC) of the World Health Organization has proposed a simple five-tier system for clinical management that is not widely known to clinicians. Classes 1 and 2 in this system are managed as neutral variants, classes 4 and 5 are managed as pathogenic variants, and class 3 variants still have insufficient evidence to move to either end of this scale and, thus, cannot be used in medical management.Conclusions.Development of models that integrate multiple independent lines of evidence has allowed classification of a growing number of VUS in the BRCA1 and BRCA2 genes. The pathogenicity score that is generated by this model maps to the IARC system for clinical management, which will assist clinicians in the medical management of those patients who obtain a VUS result upon testing.

Abstract Aims The proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also leads to structural and functional changes of the heart. Methods and results Female domestic pigs were randomized to a normal diet without (N) or with twice-weekly subcutaneous injections of the proteasome inhibitor MLN-273 (0.08 mg/kg, N + PSI, n = 5 each group). In vivo data on cardiac structure and function as well as myocardial perfusion and microvascular permeability response to adenosine and dobutamine were obtained by electron beam computed tomography after 11 weeks. Subsequent ex vivo myocardial analyses included immunoblotting, immunostaining, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling), Masson trichrome, and Congo red staining. Compared with N, an increase in LV mass was observed in N + PSI (106.5 ± 16.4 g vs. 183.1 ± 24.2 g, P &lt; 0.05). The early to late diastolic filling ratio was increased in N + PSI vs. N (3.5 ± 0.6 vs. 1.8 ± 0.1, P &lt; 0.05). The EF tended to be lower (46 ± 12% and 53 ± 9%, respectively) and cardiac output was significantly lower in N + PSI than in N (2.9 ± 1.1 vs. 4.7 ± 1.1 L/min, P &lt; 0.05). Tissue analyses demonstrated an accumulation of proteasome substrates, apoptosis, and fibrosis in the PSI group. Compared with N, the myocardial perfusion response was reduced and microvascular permeability was increased in N + PSI. Conclusion The current study demonstrates that chronic proeasome inhibition affects the cardiovascular system, leading to functional and structural alteration of the heart consistent with a hypertrophic–restrictive cardiomyopathy phenotype.

Palliative care services are not available in most outpatient oncology practices. A program training 11 mid-level providers from oncology practices on advanced directive discussions and supportive symptom assessment and management performed by palliative care specialists was completed. A follow-up session 9 months later identified barriers to implementation. Of the 11 mid-level providers, 8 participated in the follow-up session, and 9 of the 11 providers implemented advanced directive’s discussions and symptom assessment and management for patients with metastatic cancer. Main barriers included uncertainties about reimbursement, patients’ lack of knowledge about palliative care, and lack of access to supportive services. This program successfully promoted advanced directive discussions and supportive/palliative care symptom assessment and management to community oncology practices, which will hopefully translate into improved quality of life for patients with metastatic cancer.