Variability of blood eosinophil count and prognosis of COPD exacerbations

MPOC; Eosinofília; ExacerbacióEPOC; Eosinofilia; ExacerbaciónCOPD; Eosinophilia; ExacerbationBackground Eosinophils in peripheral blood are one of the emerging biomarkers in chronic obstructive pulmonary disease (COPD) patients. However, when analysing the relationship between peripheral eosinophilia and COPD prognosis, highly variable results are obtained. The aim of our study is to describe the serum eosinophilia levels in COPD patients and to analyse their relationship to prognosis following hospital admission. Methods A prospective observational study was conducted from 1 October 2016 to 1 October 2018 in the following Spanish centres: Salnés County Hospital in Vilagarcía de Arousa, Arquitecto Marcide Hospital in Ferrol and the University Hospital Complex in Santiago de Compostela. The patients were classified using three cut-off points of blood eosinophil count (BEC): 150 cells/µL, 300 cells/µL, and 400 cells/µL; in addition, the peripheral BEC was analysed on admission. Results 615 patients were included in the study, 86.2% male, mean age 73.9 years, and mean FEV1 52.7%. The mean stay was 8.4 days, and 6% of all patients were readmitted early. No significant relationship was observed between the BEC, neither in the stable phase nor in the acute phase, and hospital stay, readmissions, deaths during admission, the need for intensive care, or the condition of frequent exacerbator. Conclusion The results of our study do not seem to support the usefulness of BEC as a COPD biomarker.This paper has not been funded by any project or scholarship

Systematic review of depression in patients with multiple sclerosis and its relationship to interferonβ treatment

BACKGROUND: Multiple sclerosis is a chronic disease considered the major cause of neurological disability in young adults worldwide. While depression is considered a determinant factor of impaired quality of life and poorer prognosis among patients with multiple sclerosis, it is very often dismissed and undertreated by physicians. Depression has been related to treatment with some immunomodulatory drugs, such as IFNβ. Data from patients who committed suicide during the pivotal study of interferon used as a disease modifying treatment in multiple sclerosis support this association. Moreover, there is plenty of evidence of neuropsychiatric toxicity caused by the use of IFNα as a treatment for other medical conditions. Although this link still remains relatively unknown, the presence of warnings regarding the possible relationship between depression and IFNβ led to restriction in medical indications in these patients. The purpose of this paper is to try to understand the reasons for an increased prevalence in depression in multiple sclerosis and to examine the impact that IFNβ treatment has on their mood. METHODS: We performed a literature search on MEDLINE and Google Scholar databases applying PRISMA guidelines for systematic reviews. Studies were included if the participants were diagnosed with MS and prescribed IFNβ as the main treatment. We excluded non-english and full-text non available papers, as well as the articles where mental health was assessed exclusively as a feature of quality of life. The sample includes articles from 1980 to 2014, although filtration by year of publication was not applied and contains data from IFNβ-1a and IFNβ-1b. The Cochrane Collaboration Tool assessing risk of bias was used to determine the quality of the studies. RESULTS: Ten studies met full criteria for inclusion and final data extraction. The articles have heterogeneity regarding the samples, the methodology used and the expression of the results. Only three studies support the evidence of a relationship between depression and interferon, which is statistically significant in some patients at the beginning of the treatment. They suggest that only patients on IFNβ treatment with a past history of depression may develop a major depression episode during the first six months. The remaining articles reviewed (including BENEFIT, BEYOND, and LTF trials) suggest the absence of an association. CONCLUSION: The reviewed studies conclude that there is not a clear relationship between IFNβ and depression. A history of depression is a risk factor for developing depression during the first 6 months of treatment, nevertheless, it is not sufficient to contraindicate it. The development of new strategies is crucial for early detection of depressive symptoms. An adequate treatment can both improve the mood and deal with the neurological disease by increasing treatment adherence and interfering with inflammation. Chronic destructive brain changes and serotonergic depletion due to inflammatory factors have been proposed as the underlying cause of depression in these patients. It is suggested that these patients would have fewer functional reserve remaining to deal with stressful life events, which could precipitate a depressive disorder

Innovación educativa

Resumen basado en el de la publicación. Resumen en gallego y en inglésSe sintetiza la experiencia realizada por un grupo de profesores durante el curso 2000/2001 en un instituto de enseñanza secundaria de la ciudad de Pontevedra. El grupo se reunió durante 17 sesiones de trabajo bajo la modalidad de formación en centros de trabajo que tuvieron por título Educación para la Igualdad, siendo coordinado por una docente del propio centro. En el apartado introductorio se contextualiza la experiencia exponiendose una síntesis de los objetivos previstos, contenidos trabajados y conclusiones generales a las que llegó el grupo. A continuación se presenta una propuesta de trabajo de educación para la igualdad partiendo del visionado de la película Billy Elliot, de Stephen Daldry. El formato se propone para abordar dicha temática desde la transversalidad, así como desde la especificidad de distintas áreas del currículum y unidades temáticas. La téncica que se sugiere se sustenta en el videoforum, aunque se dejan abiertas otras posibilidades.GaliciaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

A randomized trial of deep brain stimulation to the subcallosal cingulate and nucleus accumbens in patients with treatment-refractory, chronic, and severe anorexia nervosa: initial results at 6 months of follow up

Background: The main objective of this study was to assess the safety and efficacy of deep brain stimulation (DBS) in patients with severe anorexia nervosa (AN). Methods: Eight participants received active DBS to the subcallosal cingulate (SCC) or nucleus accumbens (NAcc) depending on comorbidities (affective or anxiety disorders, respectively) and type of AN. The primary outcome measure was body mass index (BMI). Results: Overall, we found no significant difference (p = 0.84) between mean preoperative and postoperative (month 6) BMI. A BMI reference value (BMI-RV) was calculated. In patients that received preoperative inpatient care to raise the BMI, the BMI-RV was defined as the mean BMI value in the 12 months prior to surgery. In patients that did not require inpatient care, the BMI-RV was defined as the mean BMI in the 3-month period before surgery. This value was compared to the postoperative BMI (month 6), revealing a significant increase (p = 0.02). After 6 months of DBS, five participants showed an increase of ≥10% in the BMI-RV. Quality of life was improved (p = 0.03). Three cases presented cutaneous complications. Conclusion: DBS may be effective for some patients with severe AN. Cutaneous complications were observed. Longer term data are needed

Safety and efficacy of self-administered inhaled loxapine (ADASUVE) in agitated patients outside the hospital setting : Protocol for a phase IV, single-arm, open-label trial

There is a need for fast-acting, non-injection antiagitation treatments that are well tolerated and can be used outside of healthcare facilities. In phase II/III trials, an inhaled formulation of loxapine (ADASUVE®), a well-established, first-generation antipsychotic agent, provided rapid control of mild to moderate agitation in the hospital setting. The present study was designed to investigate the safety and efficacy of inhaled loxapine when self-administered outside the hospital setting. This phase IV, multicentre, single-arm, open-label clinical trial is being conducted in five countries in Europe: Spain, Germany, Norway, Romania and Austria. The aim is to include approximately 500 patients with schizophrenia or bipolar disorder who previously received and responded well to inhaled loxapine in the hospital setting. Eligible patients will be followed up for 6 months from baseline. They will be given a 10 mg dose of inhaled loxapine to self-administer outside the hospital setting to treat an agitation episode, should one occur. Patients will also be given a short-acting beta-agonist bronchodilator for treatment of possible severe respiratory side effects. The primary endpoint is incidence of serious adverse events (AEs) and respiratory AEs of special interest related to use of inhaled loxapine outside the hospital setting. Secondary endpoints include incidence of other AEs, Clinical Global Impression-Improvement scores up to 2 hours after self-administration of inhaled loxapine, time to improvement of agitation, patient satisfaction with treatment, treatment outcomes according to agitation severity and concordance between the patient (or a family member/caregiver) and the physician in scoring of agitation severity and the decision to self-administer inhaled loxapine. The protocol received ethics committee approval in the participating countries between January and August 2016. The results of this study will be disseminated through one or more scientific papers. Trial registration number EudraCT2015-003331-36; NCT02525991; Pre-results

Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells.

Most breast cancers exhibit low immune infiltration and are unresponsive to immunotherapy. We hypothesized that inhibition of the receptor activator of nuclear factor-κB (RANK) signaling pathway may enhance immune activation. Here we report that loss of RANK signaling in mouse tumor cells increases leukocytes, lymphocytes, and CD8+ T cells, and reduces macrophage and neutrophil infiltration. CD8+ T cells mediate the attenuated tumor phenotype observed upon RANK loss, whereas neutrophils, supported by RANK-expressing tumor cells, induce immunosuppression. RANKL inhibition increases the anti-tumor effect of immunotherapies in breast cancer through a tumor cell mediated effect. Comparably, pre-operative single-agent denosumab in premenopausal early-stage breast cancer patients from the Phase-II D-BEYOND clinical trial (NCT01864798) is well tolerated, inhibits RANK pathway and increases tumor infiltrating lymphocytes and CD8+ T cells. Higher RANK signaling activation in tumors and serum RANKL levels at baseline predict these immune-modulatory effects. No changes in tumor cell proliferation (primary endpoint) or other secondary endpoints are observed. Overall, our preclinical and clinical findings reveal that tumor cells exploit RANK pathway as a mechanism to evade immune surveillance and support the use of RANK pathway inhibitors to prime luminal breast cancer for immunotherapy.We thank the patients who contributed to this study and acknowledge the clinical staff for their dedication. The D-BEYOND clinical trial was sponsored by Jules Bordet Institute, which was responsible for the management of the study. This work was supported by grants to E. Gonzalez-Suarez by MICINN (SAF2014-55997-R, SAF201786117-R) co-funded by FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 682935), and Fundacio La Marato de TV3. We thank CERCA Programme/Generalitat de Catalunya for institutional support. P.P. and S.B. were and A.B. is recipient of a predoctoral grant from the MICINN. We are grateful to William C. Dougall and AMGEN, Inc. for supporting the design of the D-BEYOND trial and providing RANKL, RANK-Fc reagents, and RANK-/-mice. We thank the IDIBELL Animal Facility for their assistance with mouse colonies, Esther Castano and the scientific services of the University of Barcelona for their assistance with FACS analyses, and P. Gonzalez-Santamaria, G PerezChacon, and M Jimenez for critical reading of the manuscript. C.S. and B.N. are supported by the National Fund for Research (FNRS) and Televie. R.S. is supported by a grant from the Breast Cancer Research Foundation (BCRF), grant number 17-194. This work was also supported in part by the Cancer Center Support Grant of the National Institutes of Health (Grant Number P30CA008748). We thank Samira Majjaj and Delphine Vincent for technical assistance. We extend gratitude to the patients who participated in the D-BEYOND study. This clinical study has been supported by research funding from Amgen.N