Mouridsenrichards4550

OBJECTIVES First, to investigate the biological variability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in healthy Labrador retrievers and compare this with current laboratory recommendations for dilated cardiomyopathy screening. Second, to calculate a breed-specific reference interval and validate it in a retrospective cohort. MATERIALS AND METHODS Plasma NT-proBNP was measured in 51 clinically healthy Labrador retrievers at 0, 2, 4, 6 and 8 weeks. Coefficient of variation for individual dogs over time, the coefficient of variation for the group at each time point and the index of individuality were calculated. A reference interval was derived and tested on a clinical dataset available from four UK cardiology referral centres. RESULTS Median NT-proBNP was 865 pmol/L (315 to 2064 pmol/L). Mean individual coefficient of variation was 19% (95% CI 16 to 21%) and group coefficient of variation was 43% (95% CI 41 to 46%), with index of individuality at 0.44. The breed-specific reference interval was 275 to 2100 pmol/L. In the validation group, 93% of NT-proBNP measurements from healthy dogs were within the reference interval. NT-proBNP measurements exceeded the reference interval in 82% of dogs with dilated cardiomyopathy. The upper bound of the reference interval (2100 pmol/L) had a positive predictive value of 90% and a negative predictive value of 87% for identification of dilated cardiomyopathy in this population. CLINICAL SIGNIFICANCE Breed-specific reference intervals might improve the diagnostic accuracy of NT-proBNP measurement. Applying the currently recommended general cut-off value to Labradors is likely to result in frequent false positives and diagnosis would be improved by application of the new breed-specific reference interval calculated here. © 2020 The Authors Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.Immune checkpoint blockers improve the overall survival of a limited number of patients among different cancers. Identifying pathways that influence the immunological and clinical response to treatment is critical to improve the therapeutic efficacy and predict clinical responses. Recently, a key role has been assigned to innate immune mechanisms in checkpoint blockade-driven anti-tumor responses. However, inflammatory pathways can both improve and impair anti-tumor immunity. In this review, we discuss how different inflammatory pathways, particularly inflammasome activation, can influence the clinical outcome of immune checkpoint blockers. Inflammasome activation may reinforce anti-tumor immunity by boosting CD8+ T cell priming as well as by enhancing T helper type 17 (Th17) responses. In particular, we focus on the modulation of the cation channel transmembrane protein 176B (TMEM176B) and the ectonucleotidase CD39 as potential targets to unleash inflammasome activation leading to reinforced anti-tumor immunity and improved efficacy of immune checkpoint blockers. Future studies should be aimed at investigating the mechanisms and cell subsets involved in inflammasome-driven anti-tumor responses. © 2020 British Society for Immunology.in English, Spanish ANTECEDENTES Una adecuada estadificación mediante resonancia magnética nuclear (RMN) de los cánceres de recto en estadios precoces es esencial para la toma de decisiones en una era en la existen diferentes opciones de tratamiento preservadoras del recto. El objetivo de este estudio de base poblacional fue determinar la precisión de la estadificación mediante RMN del cáncer de recto precoz en la práctica diaria, ya sea combinada o no con la ecografía endorectal (endorectal ultrasound, ERUS). MÉTODOS Los pacientes con cáncer de recto en estadio cT1-2 que se sometieron a resección local o resección total del mesorrecto (total mesorectal excision, TME) sin (quimio) radioterapia neoadyuvante fueron seleccionados a partir del registro auditado ColoRectal holandés, entre el 1 de enero de 2011 y el 31 de diciembre de 2018. La precisión de las imágenes se expresó como sensibilidad, especificidad y valores predictivos positivo y negativo (positive- and negative predicting value, PPV / NPV). RESULTADediante RMN, muestra una considerable sobreestadificación, lo que indica las debilidades y oportunidades en las estrategias de preservación del recto.BACKGROUND AND OBJECTIVES Among orbital tumors, metastatic lesions have a prevalence of 1% to 13%; on the other hand, breast cancer is the most common malignancy causing orbital metastases. The aim of this study is to present our experience dealing with orbital metastases caused by breast cancer, to assess characteristics and clinic-pathological data of patients suffering from this rare occurrence and to find indexes related with their prognosis and survival. METHODS Records of 28 patients diagnosed with orbital metastases from breast cancer at the Department of Ophthalmology, Humanitas Clinical and Research Centre of Milano over a 27-year period (1992-2018) were retrieved and analyzed. RESULTS Mean patients' age at breast cancer diagnosis was 56.29 ± 14.63 years. Mean time interval between breast cancer diagnosis and orbital metastasis occurrence was 5 ± 4.17 years. All lesions were estrogen receptor-positive; 79% of patients harbored progesterone receptor-positive lesions. Interestingly, the majority of deceased patients presented orbital lesions with MIB-1 index >50% (P = .0265) and had concomitant lung metastases (P = .0452). CONCLUSIONS The occurrence of orbital metastasis from breast cancer represents a challenging finding. Patients' clinical picture can include exophthalmos, edema, tumefaction, proptosis and/or diplopia. Significant symptomatic improvement can be achieved through surgery and other adjuvant treatments, such as radiation therapy and chemotherapy. © 2020 Wiley Periodicals, Inc.BACKGROUND Merkel cell carcinoma is an uncommon malignancy often requiring multidisciplinary management. The purpose of this study was to determine whether high-volume facilities have improved outcomes in patients with Merkel cell carcinoma relative to lower-volume facilities. METHODS A total of 5304 patients from the National Cancer Database with stage I-III Merkel cell carcinoma undergoing surgery were analyzed. High-volume facilities were the top 1% by case volume. Multivariable Cox regression and propensity score-matching were performed to account for imbalances between groups. selleck inhibitor RESULTS Treatment at high-volume facilities (hazard ratio 0.74; 95% confidence interval 0.65-0.84, P  less then  .001) was independently associated with improved overall survival (OS) in multivariable analyses. In propensity score-matched cohorts, 5-year OS was 62.3% at high-volume facilities vs 56.8% at lower-volume facilities (P  less then  .001). Median OS was 111 months at high-volume facilities vs 79 months at lower-volume facilities.