Colonización por pneumocystis jirovecii en pacientes en tratamiento con anti-tnf-alfa

BRIEF SUMMARY OF DOCTORAL THESIS Tittle: Pneumocystis jirovecii colonization in patients in treatment with anti-TNF drugs Authors: Conferring a doctor's degree: Isabel Martín Garrido Directors: Enrique Calderón Sandubete MD, PhD. José Manuel Varela Aguilar MD, PhD. Francisco Javier Medrano Ortega MD, PhD. Tutor: Proffesor José Ricardo Villar Ortiz Introduction: Pneumocystis pneumonia (PcP) is an important opportunistic infection, with high mortality rate, not only in patients with acquired immunodeficiency syndrome (AIDS), but also in patients with autoimmune systemic disease, hematological or solid malignancies, transplant recipients or tumors, among others. There exists data that support the idea of which the colonization by P. jirovecii constitutes a risk for development of PCP in subjects submitted to some type of immunosuppression. Tumor necrosis factor alpha (TNF¿) is a pro-inflammatory cytokine that plays a fundamentally role in the control of the Pneumocystis jirovecii infection, for it, It is possible that the effect of the anti-TNF drugs, on having disabled the action of this cytokine, could favor the colonization by P. jirovecii or as PcP's later development in the patients who receive this type of treatments. It could be interesting to know P. jirovecii colonization state in order to know whose patients could receive effective chemoprophylaxis as in tuberculosis infection. Nowadays there is not sufficient information about the frequency of P. jirovecii colonization in patient in treatment with anti-TNF drugs. Objectives: The aims of our study were to obtain information about the colonization by P. jirovecii among patients with systemic diseases treated with different anti TNF drugs and if there were differences rates of colonization by drug or underlying disease. Likewise to know the epidemiological characteristics and the potential risk factors for colonization by P. jirovecii in these patients. Design: we examined oropharingeal washes collected from 195 patients with different autoimmune systemic diseases, rheumatoid arthritis (AR), ankylosing spondylitis (EA), psoriatic arthritis (APS) or psoriasis (PS), using a real-time polymerase chain reaction assay that employs specific primers from a portion of the mitochondrial large-subunit rRNA gene of P. jirovecii. One hundred and thirty two patients were under treatment with anti-TNF¿ drugs, 62 infliximab, 30 adalimumab and 40 etanercept. Sixty three patients without anti-TNF¿ treatment were included as controls. All they fulfilled all the inclusion criteria and they did not have reasons for exclusion. Results: Prevalence of Pneumocystis jirovecii colonization in patients with autoimmune systemic diseases in our study has been high at 21%; and in patients receiving anti-TNF drugs was 20.5% with no statistically significant differences between patients who received these drugs and those who did not. There was a higher rate of colonization among the group of patients under treatment with infliximab (29%) compared to etanercept group (15%) and adalimumab group (10%) although no statistically significant differences. However, we found that colonized individuals increased as the length of treatment with infliximab increased (adjusted OR for every week 1.010, 95% CI 1.004 ¿1.016, p = 0.001). The risk factor associated more strongly to the fact of colonization in the patients studied has been the concomitant use of methotrexate (adjusted OR: 2.386, 95% CI: 1.081-5.266; p = 0.031). We found a relationship, although weaker, with the use of steroids (adjusted OR: 1.894, 95% CI: 0.872-4.111, p = 0.106) and with older patients (adjusted OR: 1.01, 95% CI: 0.983-1.039, p = 0.451). We have not found significant relationship between different studied diseases (AR, APS, PS or EA) smoking or if they had chronic underlying pulmonary disease or previous use of sulfonamides. Conclusions: The overall prevalence of Pneumocystis jirovecii colonization in patients with systemic diseases in our study has been high at 21%; and in particular among patients receiving anti-TNF drugs was 20.5%, with no statistically significant differences between patients who received these drugs and those who do not. There is a higher rate of colonization among the group of patients receiving infliximab compared to other groups, although no statistically significant differences. However, we found that colonized individuals increased as the length of treatment with infliximab increased. Likewise, we have not found significant differences in colonization by studied diseases: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or psoriasis. The risk factor associated more strongly to the fact of colonization in the patients studied has been the concomitant use of methotrexate. We found a relationship, although weaker, with the use of steroids and with older patients. We have not found significant relationship between smoking or if they had chronic underlying pulmonary disease or previous use of sulfonamides.Premio Extraordinario de Doctorado U

Development and validation of the ADAS scale and prediction of attitudes toward affective-sexual diversity among spanish secondary students

Violence against non-heterosexual adolescents in educational contexts remains a worrying reality, but no adequate attitudes towards affective-sexual diversity (AtASD) measure exists for Spanish adolescent students. We developed a 27-item scale including cognitive, affective and behavioral aspects, which was completed by 696 secondary school students from the Madrid area. Factor analyses suggested a unidimensional model, Cronbach’s alpha indicated excellent scale scores reliability, and item calibration under the Item Response Theory framework showed that the scale is especially informative for homophobic attitudes. A hierarchical multiple regression analysis showed that variables traditionally related to AtASD (gender, age, religion, nationality, perceived parental/peer attitudes, direct contact with LGB people) also were so in our sample. Moreover, interest in sexuality topics and perceived center’s efforts to provide AtASD education were related to better AtASD. Our scale was reliable and valid, and it may also prove useful in efforts to detect those students with homophobic attitudes and to guide intervention

Papilopatía diabética: a propósito de dos casos

Unidad Docente de Inmunología, Oftalmología y ORLFac. de Óptica y OptometríaTRUEpu

NT-proBNP as predictor factor of cardiotoxicity during trastuzumab treatment in breast cancer patients

Background Trastuzumab is a drug used in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority. The purpose of this study is to evaluate plasma NT-proBNP level and major cardiovascular risk factors as possible early predictors of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients. Methods We conducted a retrospective observational study involving 66 patients with HER2-positive breast cancer treated with trastuzumab. Left ventricle ejection fraction (LVEF), NT-proBNP values, and the history of cardiovascular risk factors were collected. Cardiotoxicity was diagnosed considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. NT-proBNP cut-off points were considered to establish normal or abnormal values according to patient age. Results 27.3% of the patients suffered cardiotoxicity during trastuzumab treatment. Most cases were diagnosed due to the appearance of cardiac symptomatology (66.7%). Logistic regression analysis showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2–28.5, p = 0.028) and high NT-proBNP levels (OR 22.0, 95% CI 5.7–85.4, p < 0.0001) with the development of trastuzumab-induced cardiotoxicity. Conclusion NT-proBNP levels above the upper limit of the normal range adjusted to age or diabetes mellitus seem to be associated with a higher risk of developing cardiotoxicity. However, some limitations of the present study make necessary further studies aimed to clarify whether NT-proBNP and diabetes-associated markers determinations can be useful in the monitoring of cardiotoxicity risk in breast cancer patients undergoing trastuzumab therapy.Ramon Areces Foundation, Madrid, Spai

EPOC fenotipo no agudizador con enfisema

A 48-year-old male smoker with no other history of interest, who is referred for dyspnea. Following complementary tests, the diagnosis of COPD grade D GOLD, non-aggravating emphysema GesEPOC, was made, he has dyspnea grade 2-3 of MRCm with BODE score of 7 and presence of bullas of predominance in the right lung. After optimization medical treatment, removing inhaled corticosteroids, the clinical situation of the patient improves, but after 3 months there is a sudden worsening with the appearance of pneumothorax requiring drainage tube and bullectomy with posterior clinical and functional improvement.Varón de 48 años fumador excesivo, sin otros antecedentes de interés, derivado para estudio de disnea. Tras la realización de pruebas complementarias, se diagnostica de EPOC grado D de la GOLD y fenotipo enfisema no agudizador según GesEPOC, disnea clase 2-3 de la mMRC con una puntuación BODE de 7 y con presencia de bullas de predominio en pulmón derecho. Tras optimización del tratamiento médico broncodilatador con retirada de corticoides inhalados, inicialmente la situación clínica del paciente mejora, pero 3 meses después presenta empeoramiento paulatino motivado por la aparición de neumotórax leve que precisa tubo de drenaje y posterior bullectomía, con mejoría clínica y funcional

Obstructive uropathy secondary to ureteral inguinoscrotal hernia.

post-print2,18 M

Valores para el liderazgo educativo. Integración de la competencia profesional “Intra e Interpersonal” entre los alumnos de Magisterio

Memoria ID-0193. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2015-2016

Evaluation of Compliance with the Guidelines for the Safe Use of Potassium Chloride

RESUMEN Objetivo: Analizar el grado de cumplimiento del “Protocolo de Utilización de Cloruro potásico” implantado en nuestro hospital, mediante la realización de auditorías periódicas presenciales, durante el periodo 2013-2016. Métodos: Estudio descriptivo de las auditorías realizadas a los 6 meses post-implantación (principios de 2013), y después cada año (2014-2016). Los indicadores de evaluación se establecen siguiendo las recomendaciones recogidas en el Protocolo y se refieren al almacenamiento, prescripción, preparación y administración de soluciones de potasio. Las unidades asistenciales evaluadas son: unidades autorizadas (almacenamiento y doble chequeo en la preparación y antes de la administración) y en todas las unidades de críticos y urgencias clínicas (prescripción y etiquetado correcto para su administración). Resultados: Se audita un total de 55 unidades asistenciales, que han mostrado un 100% de cumplimiento para los indicadores referentes a prescripción y etiquetado correcto. De dichas unidades, 12 (críticos y urgencias) están autorizadas para disponer de ampollas de cloruro potásico 1M. En estas 12, no se obtuvo un cumplimiento correcto de los otros dos indicadores, debido a que una no realizó su almacenamiento de forma adecuada (2014) y, en otras tampoco se cumplimentó el registro de doble chequeo (3 en 2013, 1 en 2014 y 2015). Conclusión: Las auditorías mostraron el correcto seguimiento de dicho Protocolo para la mayoría de los criterios evaluados, si bien, ponen de manifiesto la necesidad de realizar estrategias periódicas de intensificación y recuerdo para garantizar el adecuado cumplimiento de todas las recomendaciones establecidas.ABSTRACT Objective: To analyze the degree of compliance with the “Guidelines for the safe use of potassium chloride” implemented in our hospital, using periodic audits, during the period 2013-2016. Methods: Descriptive study of the audits carried out at 6 months post-implementation (beginning of 2013) and then every year (2014-2016). The evaluation indicators were developed following the recommendations included in the Guidelines and referred to storage, prescription, preparation and administration of potassium solutions. The patient care units evaluated are: critical care authorized units (storage and independent double checks during preparation of solutions and before its administration) and all patient care units (prescription and correct labeling for its correct administration). Results: There were audited 55 patient care units, which showed a compliance of 100% for the prescription and correct labeling indicators. Of those units, 12 (critical and emergency units) are authorized to have concentrated potassium chloride ampoules 1M. These 12 units did not have a correct compliance with the other two indicators, because one unit did not show a correct storage (in 2014) and the double check required was not verified by 3 units in 2013, one in 2014 and 2015. Conclusion: The audits showed the correct follow-up with the Guidelines for most of the evaluated criteria, however demonstrated the need to carry out periodic strategies of intensification and remembrance to guarantee the correct compliance of all the established recommendations

Evaluación del cumplimiento del protocolo de utilización de cloruro potásico

Objective: To analyze the degree of compliance with the “Guidelines for the safe use of potassium chloride” implemented in our hospital, using periodic audits, during the period 2013-2016. Methods: Descriptive study of the audits carried out at 6 months post-implementation (beginning of 2013) and then every year (2014-2016). The evaluation indicators were developed following the recommendations included in the Guidelines and referred to storage, prescription, preparation and administration of potassium solutions. The patient care units evaluated are: critical care authorized units (storage and independent double checks during preparation of solutions and before its administration) and all patient care units (prescription and correct labeling for its correct administration). Results: There were audited 55 patient care units, which showed a compliance of 100% for the prescription and correct labeling indicators. Of those units, 12 (critical and emergency units) are authorized to have concentrated potassium chloride ampoules 1M. These 12 units did not have a correct compliance with the other two indicators, because one unit did not show a correct storage (in 2014) and the double check required was not verified by 3 units in 2013, one in 2014 and 2015. Conclusion: The audits showed the correct follow-up with the Guidelines for most of the evaluated criteria, however demonstrated the need to carry out periodic strategies of intensification and remembrance to guarantee the correct compliance of all the established recommendations.Objetivo: Analizar el grado de cumplimiento del “Protocolo de Utilización de Cloruro potásico” implantado en nuestro hospital, mediante la realización de auditorías periódicas presenciales, durante el periodo 2013-2016. Métodos: Estudio descriptivo de las auditorías realizadas a los 6 meses post-implantación (principios de 2013), y después cada año (2014-2016). Los indicadores de evaluación se establecen siguiendo las recomendaciones recogidas en el Protocolo y se refieren al almacenamiento, prescripción, preparación y administración de soluciones de potasio. Las unidades asistenciales evaluadas son: unidades autorizadas (almacenamiento y doble chequeo en la preparación y antes de la administración) y en todas las unidades de críticos y urgencias clínicas (prescripción y etiquetado correcto para su administración). Resultados: Se audita un total de 55 unidades asistenciales, que han mostrado un 100% de cumplimiento para los indicadores referentes a prescripción y etiquetado correcto. De dichas unidades, 12 (críticos y urgencias) están autorizadas para disponer de ampollas de cloruro potásico 1M. En estas 12, no se obtuvo un cumplimiento correcto de los otros dos indicadores, debido a que una no realizó su almacenamiento de forma adecuada (2014) y, en otras tampoco se cumplimentó el registro de doble chequeo (3 en 2013, 1 en 2014 y 2015). Conclusión: Las auditorías mostraron el correcto seguimiento de dicho Protocolo para la mayoría de los criterios evaluados, si bien, ponen de manifiesto la necesidad de realizar estrategias periódicas de intensificación y recuerdo para garantizar el adecuado cumplimiento de todas las recomendaciones establecidas

Interaction between angiotensin type 1, type 2, and mas receptors to regulate adult neurogenesis in the brain ventricular–subventricular zone

The renin–angiotensin system (RAS), and particularly its angiotensin type-2 receptors (AT2), have been classically involved in processes of cell proliferation and maturation during development. However, the potential role of RAS in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and its aging-related alterations have not been investigated. In the present study, we analyzed the role of major RAS receptors on neurogenesis in the V-SVZ of adult mice and rats. In mice, we showed that the increase in proliferation of cells in this neurogenic niche was induced by activation of AT2 receptors but depended partially on the AT2-dependent antagonism of AT1 receptor expression, which restricted proliferation. Furthermore, we observed a functional dependence of AT2 receptor actions on Mas receptors. In rats, where the levels of the AT1 relative to those of AT2 receptor are much lower, pharmacological inhibition of the AT1 receptor alone was sufficient in increasing AT2 receptor levels and proliferation in the V-SVZ. Our data revealed that interactions between RAS receptors play a major role in the regulation of V-SVZ neurogenesis, particularly in proliferation, generation of neuroblasts, and migration to the olfactory bulb, both in young and aged brains, and suggest potential beneficial effects of RAS modulators on neurogenesis.This research was funded by Spanish grants from Ministerio de Economía y Competitividad (BFU2015-70523 and SAF2017-86690-R), Instituto de Salud Carlos III (Retic TERCEL RD16/0011/0016, RD16/0011/0017, and CIBERNED), Galician Government (XUGA, ED431C2018/10; ED431G/05), FEDER (Regional European Development Fund), Generalitat Valenciana (Prometeo 2017-030), and Fundación Emilio Botín-Banco SantanderS