High frequency of endoluminal thrombus in patients with ischaemic stroke following AARS-CoV-2 infection.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

Electromyographic study of the arms in competitive karting senior category drivers / Estudio electromiográfico de los brazos en pilotos senior de karting de competición

The main goal of this cross-sectional study was to assess the muscular activity of the upper limbs in competitive kart drivers while driving in a closed karting circuit, using surface electromyography (EMGS). The most significant muscles of the upper limbs while driving were evaluated in thirteen drivers. Linear mixed models adjusted to a gamma distribution were used to evaluate differences in muscle activity based on the arm, number of laps, track characteristics, and kart type (with/without gears). Significant differences were found between muscle activity according to the type of kart (p <0.0001). Although changes were observed in the mean EMGS values, there were no significant differences between the laps of the circuit or the dominant arm. However, the results showed that there was a significant interaction between the type of kart and the dominant arm (p = 0.021). Muscle activity increased more significantly in the curves traced towards the dominant arms of the drivers (AU)

El objetivo del estudio transversal fue analizar la actividad muscular de las extremidades superiores en pilotos senior de karting de competición, mediante electromiografía de superficie (EMGS). Se evaluaron los músculos más significativos de las extremidades superiores durante la conducción en trece conductores. Se utilizaron modelos lineales mixtos ajustados a una distribución gamma para evaluar diferencias de actividad muscular en base al brazo, número de vueltas, características del trazado, y tipo de kart (con/sin marchas). Se encontraron diferencias significativas entre la actividad muscular según el tipo de kart (p<0,0001). Aunque se observaron cambios en los valores medios de EMGS, no hubo diferencias significativas entre las vueltas del circuito o el brazo dominante. Sin embargo, los resultados mostraron que hubo una interacción significativa entre el tipo de kart y el brazo dominante (p=0,021). La actividad muscular aumentó de manera más significativa en las curvas trazadas hacia el brazo dominante de los conductores (AU)

Patient preferences in chronic immune-mediated inflammatory diseases potentially treated with biological drugs: discrete choice analysis using real-world data analysis.

OBJECTIVES: Immune-mediated inflammatory diseases (IMIDs) represent a high burden due to their chronicity, high prevalence, and associated comorbidities. Chronic patients' preferences must be considered in IMIDs treatment and follow-up. The objective of this study was to further understand patient's preferences in private settings. METHODS: A literature review was performed to choose the most relevant criteria for patients. A D-efficient discrete choice experiment was designed to elicit preferences of adult patients with IMIDs and potential biological treatment prescription. Participants were collected from private practices (rheumatology, dermatology, and gastroenterology) from February to May 2022. Patients chose between option pairs, characterized by six health-care attributes, as well as monthly out-of-pocket drug price. Responses were analyzed through a conditional logit model. RESULTS: Eighty-seven patients answered the questionnaire. The most frequent pathologies were Rheumatoid Arthritis (31%) and Psoriatic Arthritis (26%). The most relevant criteria were choosing the preferred physician (OR 2.25 [SD0.26]); reducing time until visit with specialist (OR 1.79 [SD0.20]), access through primary care (OR 1.60 [SD0.08]), and an increase in monthly out-of-pocket price from 100€ to 300€ (OR 0.55 [SD0.06]) and to 600€ (OR 0.08 [SD0.02]). CONCLUSIONS: Chronic IMIDs patients showed a preference toward a faster, personalized service, even with a trade-off in terms of out-of-pocket price.

Fluoxetine increased adult neurogenesis is mediated by 5-HT3 receptor.

Adult neurogenesis is an aspect of structural plasticity that remains active during adulthood in some brain regions. One of them is the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. Adult neurogenesis is reduced by different factors and in disorders of the CNS, including major depression. Antidepressant treatments, such as chronic fluoxetine administration, recover the normal level of adult neurogenesis. Fluoxetine treatment increases the free concentration of the neurotransmitter serotonin and this monoamine is implicated in the regulation of the neurogenic process; however, the target of the action of this neurotransmitter has not been fully elucidated. In this study, we have tried to determine the relevance of the serotonin receptor 3 (5-HT3) in the hippocampal neurogenesis of adult rats. We have used fluorescent immunohistochemistry to study the expression of the 5-HT3 receptor in different neurogenesis stages in the SGZ, identifying its expression in stem cells, amplifying neural progenitors and immature neurons. Moreover, we have studied the impact of a 5-HT3 antagonist (ondansetron) in the fluoxetine-induced adult neurogenesis. We observed that fluoxetine alone increases the number of both proliferating cells (ki67 positive) and immature neurons (DCX positive) in the SGZ. By contrast, co-treatment with ondansetron blocked the increase in proliferation and neurogenesis. This study demonstrates that the activation of 5-HT3 receptors is necessary for the increase of adult neurogenesis induced by fluoxetine.

Análisis coste-efectividad del implante percutáneo de válvula aórtica SAPIEN 3 en pacientes con estenosis aórtica grave sintomática / Cost-effectiveness analysis of the SAPIEN 3 transcatheter aortic valve implant in patients with symptomatic severe aortic stenosis

Introducción y objetivos: El implante percutáneo de la válvula aórtica se ha consolidado como tratamiento de la estenosis aórtica grave inoperable o de alto riesgo quirúrgico. Recientemente las indicaciones se han ampliado a riesgo intermedio y bajo. Nuestro objetivo es evaluar la eficiencia de SAPIEN 3 frente al tratamiento médico conservador (TMC) o el reemplazo quirúrgico de válvula aórtica (RVA) en pacientes sintomáticos inoperables con riesgo alto e intermedio.´Métodos: Análisis de coste-efectividad de SAPIEN 3 frente a RVA/TMC mediante un modelo de Markov (ciclos mensuales) adaptado con 8 estados definidos por la New York Hearth Association y resultados a 15 años, incluidos las complicaciones mayores y el tratamiento tras el alta hospitalaria, desde la perspectiva del Sistema Nacional de Salud. Los parámetros de efectividad se basan en los estudios PARTNER. Se incluyeron costes sanitarios (en euros de 2019) derivados del procedimiento, hospitalización, complicaciones clínicas y seguimiento. Se aplicó una tasa de descuento anual del 3% en costes y beneficios. El análisis de sensibilidad fue determinístico y probabilístico (Monte Carlo). Resultados: En comparación con el RVA (riesgo alto e intermedio) y el TMC (inoperables), el SAPIEN 3 implicó mejores resultados en las 3 poblaciones y menor estancia. Las tasas de coste-utilidad incremental fueron 5.471 (riesgo alto), 8.119 (riesgo intermedio) y 9.948 (inoperables) euros/años de vida ajustados por calidad ganados. En el análisis probabilístico, el SAPIEN 3 resultó coste-efectivo por encima del 75% de las simulaciones en los 3 perfiles. Conclusiones: En nuestro medio, el SAPIEN 3 permite un tratamiento eficiente de la estenosis aórtica grave tanto en pacientes inoperables como en riesgo alto e intermedio (AU)

Introduction and objectives: Transcatheter aortic valve implant has become a widely accepted treatment for inoperable patients with aortic stenosis and patients at high surgical risk. Its indications have recently been expanded to include patients at intermediate and low surgical risk. Our aim was to evaluate the efficiency of SAPIEN 3 vs conservative medical treatment (CMT) or surgical aortic valve replacement (SAVR) in symptomatic inoperable patients at high or intermediate risk. Methods: We conducted a cost-effectiveness analysis of SAPIEN 3 vs SAVR/CMT, using a Markov model (monthly cycles) with 8 states defined by the New York Heart Association and a time horizon of 15 years, including major complications and management after hospital discharge, from the perspective of the National Health System. Effectiveness parameters were based on the PARTNER trials. Costs related to the procedure, hospitalization, complications, and follow-up were included (euros in 2019). An annual discount rate of 3% was applied to both costs and benefits. Deterministic and probabilistic sensitivity analyses (Monte Carlo) were performed. Results: Compared with SAVR (high and intermediate risk) and CMT (inoperable), SAPIEN 3 showed better clinical results in the 3 populations and lower hospital stay. Incremental cost-utility ratios (€/quality-adjusted life years gained) were 5471 (high risk), 8119 (intermediate risk) and 9948 (inoperable), respectively. In the probabilistic analysis, SAPIEN 3 was cost-effective in more than 75% of the simulations in the 3 profiles. Conclusions: In our health system, SAPIEN 3 facilitates efficient management of severe aortic stenosis in inoperable and high- and intermediate-risk patients (AU)

High frequency of endoluminal thrombus in patients with ischaemic stroke following SARS-CoV-2 infection. / Alta frecuencia de trombo endoluminal en pacientes con ictus isquémico tras la infección por coronavirus 2019.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with SARS-CoV-2 infection who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

Costilla accesoria cervical como causa de síndrome de apertura torácica superior. Nuestra experiencia de los últimos diez años / Cervical accessory rib, as a cause of thoracic oulet syndrome (tos): our experience of the last ten years

El síndrome de apertura torácica superior por costilla cervical, es una patología no muy frecuente, ocasionada por la persistencia después del nacimiento de la última costilla cervical que debería haberse reabsorbido. La patología que origina, es comprensiva de las estructuras vecinas en especial nerviosas, pero también vasculares. Se manifiesta en pacientes jóvenes después de la adolescencia con una especial incidencia en el sexo femenino. El diagnóstico es sencillo si se piensa en esta causa como la etiológica del síndrome, con la realización de una simple radiografía de base de cuello para evidenciar su presencia, aunque es posible realizar otras complementarias. El tratamiento es la simple extirpación de la costilla que en la mayoría de las ocasiones resuelve el cuadro clínico. Se analiza en la publicación la experiencia de nuestro servicio hospitalario en los últimos diez años, analizando aspectos demográficos, diagnósticos, terapéuticos y los resultados obtenidos

The syndrome of superior thoracic opening due to cervical rib is a not very frequent pathology, caused by the persistence after birth of the last cervical rib that should have been reabsorbed. The pathology that it originates is comprehensive of neighboring structures, especially nervous, but also vascular. It manifests itself in young patients after adolescence with a special incidence in the female sex. The diagnosis is simple if we think of this cause as the etiological cause of the syndrome, with a simple neck base X-ray to show its presence, although it is possible to perform other complementary ones. Treatment is the simple removal of the rib, which in most cases resolves the clinical picture. The experience of our Hospital Vascular Service in the last ten years is analyzed in the publication, analyzing demographic, diagnostic and therapeutic aspects and the results obtained

Aneurismas de la arteria poplítea. experiencia de un centro en un periodo de 10 años / Aneurisms of popliteal artery. experience of a center in a period of 10 years

Los aneurismas de la arteria poplítea son una patología relativamente frecuente al constituir los de mayor incidencia y prevalencia dentro de los periféricos. Este tipo de patología, presenta una serie de peculiaridades de acuerdo a datos demográficos y también con respecto a formas y tipos de presentación. La clínica se centra especialmente en su perfil de bultoma que late y expande y en las complicaciones de frecuente presentación. Su tratamiento quirúrgico está basado en opciones terapéuticas de cirugía abierta y cirugía convencional. Se presenta la experiencia de un solo centro durante diez años en la atención de esta patología

Popliteal artery aneurysms are a relatively frequent pathology as they are those with the highest incidence and prevalence within the peripherals. This type of pathology presents a series of peculiarities according to demographic data and also with respect to forms and types of presentation. The clinic focuses especially on its profile of beating and expanding lump and on complications that frequently appear. His surgical treatment is based on therapeutic options of open surgery and conventional surgery. The experience of a single center for ten years in the care of this pathology is presented

Estudio citogenético de tinción de bandas gtg en angiólogos y cirujanos vasculares expuestos de manera crónica a bajas dosis de radiación ionizante durante procedimientos endovasculares. Iradient study / Cytogenetic gtg-banding analysis in vascular surgeons chronically exposed to low-dose ionizing radiation during endovascular procedures. iradient study

ANTECEDENTES Y OBJETIVO: En las últimas dos décadas, las técnicas endovasculares han supuesto un avance sin precedentes en el tratamiento quirúrgico de las enfermedades vasculares. Sin embargo, dichas técnicas suponen una exposición a radiación ionizante tanto para los pacientes como para el equipo quirúrgico. Algunos estudios sugieren la realización de análisis citogenéticos de manera complementaria a la dosimetría habitual. No obstante, hasta la fecha los datos sobre las alteraciones genéticas producidas por la exposición crónica a dosis bajas de radiación son escasos. El presente estudio es parte del Iradient Study (Ionizing RADiation in ENdovascular Treatments) de inestabilidad genómica en angioIólogos y cirujanos vasculares (PI-18-967). El objetivo principal fue validar el análisis genómico mediante tinción de bandas GTG (G-banding by Trypsin with Giemsa) como marcador de alteraciones genómicas en angiólogos y cirujanos vasculares expuestos de manera crónica a dosis bajas de radiación ionizante. Material y Métodos. Estudio nacional, observacional y transversal de casos y controles de aneuploidias en angiólogos y cirujanos vasculares expuestos de manera crónica a bajas dosis de radiación ionizante versus controles no expuestos a radiación ionizante. Las variables categóricas se analizaron mediante el Test exacto de Fisher siendo que las variables cuantitativas se analizaron prueba de Kruskall-Wallis o U de Mann-Whitney. RESULTADOS: Se incluyeron 24 sujetos como casos, provenientes de 13 centros distintos, y 4 sujetos sanos como controles. El tiempo de exposición medio a radiación ionizante del grupo de casos fue 18.9 ± 3.2 años. No se objetivó correlación entre la edad y el tiempo de exposición a radiación ionizante y la presencia de aneuploidias. En el estudio de tinción de bandas GTG no se observaron diferencias significativas en cuanto al porcentaje de metafases hipodiploides (controles 27.06 ± 16.00% versus casos 18.80 ± 8.59%, p = 0.144), porcentaje de metafases hiperdiploides (controles 3.58 ± 3.55% versus casos 1.48 ± 2.53%, p = 0.082) ni en cuanto al porcentaje de alteraciones estructurales (controles 3.97 ± 3.43% versus casos 10.63 ± 8.89%, p = 0.126). CONCLUSIONES: La edad y el tiempo de exposición a radiación ionizante no se relacionan con un aumento significativo de aneuploidias mediante técnica de tinción de bandas GTG. Ni tipo de actividad endovascular realizada, ni el tipo de quirófano utilizado suponen un aumento de inestabilidad genómica según el análisis de tinción de bandas GTG. Según los resultados del presente estudio no se valida el análisis de tinción de bandas GTG como marcador de inestabilidad genómica en angiólogos y cirujanos vasculares expuestos de manera crónica a radiación ionizante

BACKGROUND AND OBJECTIVES: The past two decades have witnessed the development and growth of the endovascular techniques, however, this new technology is not exempt from risks, since its use requires an ionizing radiation exposure to both patients and surgeons. In this context, the long-term repercussion of this type of chronic exposure to low dose ionizing radiation of the vascular sur-geons is still unknown. Some studies suggest the use of routine cytogenetic analysis to complement the conventional dosimetry, yet he real genomic effects of chronic low dose ionizing radiation exposure is still unclear and an ideal biodosimetry marker hasn't been described. The present study is part of the Iradient Study (Ionizing RADiation in ENdovascular Treatments) of genomic instability in vascular surgeons (PI-18-967). In this setting, the main goal of the present study was to validate the cytogenetic GTG-banding (G-banding by Trypsin with Giemsa) technique as a biomarker of genomic instability associated to the chronic low dose exposure to ionizing radiation of vascular surgeons. MATERIAL AND METHODS: National, observational and transversal case control study of ge-nomic instability among vascular surgeons chronically exposed to low dose ionizing radiation compared to healthy control patients with no previous history of radiation exposure. The statistical analysis of the categorical variables was performed using the Fisher exact test and the quantitative variables were studies using the Kruskall-Wallis or U de Mann-Whitney tests. RESULTS: 24 subjects from 13 different hospitals were included as cases, and 4 healthy non-exposed subjects were included as controls. There were no meaningful differences in terms age and demographical variables between groups. In the case group the mean exposure duration was 18.93±3.2 years. There was no significant correlation between age and duration of exposure and the presence of aneuploidies in the GTG-banding analysis. In the GTG-banding chromosome study there were no significant differences between groups in terms of the rate of hipodiploid metaphases (controls 27.06 ± 16.00% versus cases 18.80 ± 8.59%, p = 0.144), rate of hiperdiploid metapha-ses (controls 3.58 ± 3.55% versus cass 1.48 ± 2.53%, p = 0.082) or rate of structural chromosome aberrations (controls 3.97 ± 3.43% versus cases 10.63 ± 8.89%, p = 0.126). CONCLUSIONS: Nor the age or the duration of exposure to ionizing radiation were associated with a higher rate of chromosomal aberrations with the GTG-banding study. Also, the type of endovascular activity and the type of surgical room weren't associated with an increase in the genomic instability in the GTG-banding study. The present results do not allow the validation of the GTG-banding analysis as a biomarker of long term exposure to low dose radiation during endovascular procedures

Isquemia arterial aguda bilateral de extremidades inferiores y estado protrombótico en infección por SARS-COV-2. A propósito de un caso / Bilateral acute lower limbs ischaemia and prothrombotic status in SARS-COV-2 infection. A case report

La infección por SARS-COV-2 se ha convertido en una emergencia sanitaria internacional. Junto con la infección respiratoria, se pueden presentar complicaciones derivadas de un estado de hipercoagulabilidad, ensombreciendo el pronóstico. Se presenta el caso clínico de un paciente con neumonía vírica por SARS-COV-2, en el que se produce una isquemia arterial bilateral de extremidades inferiores

SARS-COV-2 infection has become an international health emergency. Apart from the respiratory disease, complications arising from an hypercoagulable state may occur, overshadowing the prognostic. The clinical case of a patient with SARS-COV-2 viral pneumonia is presented, in which bilateral arterial ischemia of the lower extremities occurs

Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy

Purpose: Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer. Patients and methods: This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis. Results: The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08-1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR. Conclusion: Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer

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Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy.

PURPOSE: Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer. PATIENTS AND METHODS: This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis. RESULTS: The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08-1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR. CONCLUSION: Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer. TRIAL REGISTRATION: EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). ClinicalTrials.gov Identifier: NCT00129922 (retrospectively registered 10/08/2005). Results of this study were presented in part at the 2016 ESMO conference October 7-11, 2016, Copenhagen, Denmark (oral presentation).

Outcomes of single versus double hormone receptor-positive breast cancer. A GEICAM/9906 sub-study.

BACKGROUND: Retrospective data suggest better outcomes for patients with double hormonal receptor (oestrogen [ER] and progesterone receptor [PgR])-positive (dHR+) early breast cancer, compared with single hormonal receptor-positive, sHR+, (ER+/PgR- or ER-/PgR+) disease. Here, we evaluate the classification according to intrinsic subtypes and clinical outcomes of sHR+ versus dHR+ in HER2-negative breast cancer patients enrolled in GEICAM/9906 study (NCT00129922). METHODS: Archival tumours were retrieved retrospectively for the analysis of ER, PgR and HER2 status and classified into intrinsic subtypes using the PAM50 gene expression assay. Disease-free survival (DFS) and overall survival (OS) were explored using a Cox proportional hazard analysis. RESULTS: Data on intrinsic subtypes were available in 571 (50%) patients with ER+ and/or PR+, and HER2-negative primary tumours. The incidence of luminal A and luminal B subtypes were 52%/36% in dHR+ tumours (ER+/PgR+), and 15%/58% in ER+/PgR-tumours. ER-/PgR+ tumours were mainly luminal A (52%). Compared with ER+/PgR+ patients, DFS was similar in ER-/PgR+ (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.57-2.34, p = 0.70) but worse in ER+/PgR- patients (HR 1.60, 95% CI 1.12-2.28, p < 0.01). Similar results were observed for OS (HR 1.50, p = 0.30 and HR 1.86, p < 0.01, respectively). CONCLUSIONS: The ER+/PgR- group is characterised by higher proliferation and worse outcomes. In spite of the ER-/PgR+ subgroup resembles ER+/PgR+ disease in terms of molecular subtypes and outcomes, the small number of patients in this subgroup prevents from drawing any conclusions. TRIAL REGISTRATION: EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). CLINICALTRIALS. GOV IDENTIFIER: NCT00129922 (retrospectively registered 10/08/2005).

Performance of surface and subsurface flow constructed wetlands treating eutrophic waters.

Three medium size constructed wetlands (CWs) with a total surface of 90ha are working since 2009 in the Albufera de Valencia Natural Park (Spain). Two of them are fed with eutrophic waters from l'Albufera Lake. Their objectives are both reduce the phytoplankton biomass and increase the biodiversity; consequently, improved water quality is returned to the lake. A "science based governance" of these CWs is ongoing inside the LIFE+12 Albufera Project to demonstrate the environmental benefits of these features. In this paper, results and relationships among hydraulic operation, physicochemical variables and plankton in two different CWs typologies, five free water surface CW (FWSCW) and one horizontal subsurface flow CW (HSSFCW), were analysed showing that CWs were capable of improving the water quality and biodiversity but showing clear differences depending on the CW type. The CWs worked under different hydraulic load rates (HLR) from <0.12 to 54.75myr-1. Inflow water quality was typical from eutrophic waters with mean values of chlorophyll a (Chl a) about 22-90µgChlal-1 and mean total phosphorus (TP) between 0.122 and 0.337mgl-1. The main conclusion is that HSSFCW was much more efficient than FWSCW in the removal of organic matter, suspended solids and nutrients. The biological role of several shallow lagoons located at the end of the CWs has also been evaluated, showing that they contribute to increase the zooplankton biomass, a key factor to control the phytoplankton blooms.

[Comparison of the cost-utility of direct oral anticoagulants for the prevention of stroke in patients with atrial fibrillation in Spain]. / Comparacion del coste-utilidad de los anticoagulantes orales de accion directa en la prevencion de ictus en la fibrilacion auricular no valvular en España.

INTRODUCTION: Apixaban, dabigatran and rivaroxaban are three new direct oral anticoagulants (DOACs) used in the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) in Spain. AIM: To assess the relative cost-utility of the three DOACs compared with vitamin K antagonists. PATIENTS AND METHODS: A Markov model with 3-month cycles was used to simulate NVAF patients starting with treatment and followed up for their lifetime from the perspective of the National Health System. The model included 36 health states including treatment combinations, disability and events history and considered a hypothetical cohort of 10,000 NVAF patients. Relative efficacy was calculated from a formal indirect treatment comparison using data from the pivotal trials of each DOAC. RESULTS: Dabigatran was associated with the highest number of quality-adjusted life years (QALY) (8.40 QALY), followed by apixaban (8.33 QALY), rivaroxaban (8.15 QALY) and acenocoumarol (8.03 QALY). Patients taking acenocoumarol had the lowest total costs (€22,230), followed by dabigatran (€24,564), apixaban (€24,655) and rivaroxaban (€25,900). Incremental cost-utility ratios compared to vitamin K antagonists, were €6,397, €8,039 and €29,957/QALY for dabigatran, apixaban and rivaroxaban, respectively. If compared together, dabigatran dominated apixaban and rivaroxaban. Sensitivity analyses confirmed the robustness of the baseline case. CONCLUSIONS: All three direct anticoagulants are cost-effective against acenocoumarol. Dabigatran is economically dominant over rivaroxaban and apixaban in the Spanish setting, as it is more effective and cheaper.

TITLE: Comparacion del coste-utilidad de los anticoagulantes orales de accion directa en la prevencion de ictus en la fibrilacion auricular no valvular en España.Introduccion. El apixaban, el dabigatran y el rivaroxaban son tres anticoagulantes orales de accion directa (ACOD) indicados para la prevencion del ictus y la embolia sistemica en pacientes con fibrilacion auricular no valvular (FANV) en España. Objetivo. Comparar el coste-utilidad de los tres ACOD frente a los antivitamina K. Pacientes y metodos. Se utilizo un modelo Markov con ciclos trimestrales para simular pacientes con FANV desde que inician su tratamiento hasta el resto de su vida desde la perspectiva del Sistema Nacional de Salud. El modelo incorporo 36 estados de salud, incluyendo combinaciones de tratamientos, discapacidad y antecedentes de eventos, y considero una cohorte hipotetica de 10.000 pacientes con FANV. La eficacia relativa se calculo a partir de una comparacion indirecta formal de los tratamientos segun los datos de los ensayos pivotales de cada ACOD. Resultados. El dabigatran se asocio al valor maximo de años de vida ajustados por calidad (AVAC) (8,40 AVAC), seguido del apixaban (8,33 AVAC), el rivaroxaban (8,15 AVAC) y el acenocumarol (8,03 AVAC). Los costes totales fueron menores con el acenocumarol (22.230 €), seguido del dabigatran (24.564 €), el apixaban (24.655 €) y el rivaroxaban (25.900 €). La ratio coste-utilidad incremental frente a los antivitamina K fue de 6.397, 8.039 y 29.957 €/AVAC para el dabigatran, el apixaban y el rivaroxaban, respectivamente. Comparados entre ellos, el dabigatran domino al apixaban y al rivaroxaban. Los analisis de sensibilidad confirmaron la robustez del caso base. Conclusiones. Los tres ACOD son coste-efectivos frente al acenocumarol. El dabigatran es economicamente dominante frente al rivaroxaban y al apixaban en España, al ser mas efectivo y menos costoso.

Biokinetic model for nitrogen removal in free water surface constructed wetlands.

In this article, a mechanistic biokinetic model for nitrogen removal in free water surface constructed wetlands treating eutrophic water was developed, including organic matter performance due to its importance in nitrogen removal by denitrification. Ten components and fourteen processes were introduced in order to simulate the forms of nitrogen and organic matter, the mechanisms of autotrophic and heterotrophic microorganisms in both aerobic and anoxic conditions, as well as macrophytes nitrogen uptake and release. Dissolved oxygen was introduced as an input variable with a time step of 0.5days for mimicking eutrophic environments: aerobic conditions were assigned during daylight hours and anoxic conditions during the night. The sensitivity analysis showed that the most influential parameters were those related to the growth of heterotrophic and autotrophic microorganisms. The model was properly calibrated and validated in two full scale systems working in real conditions for treating eutrophic water from Lake L'Albufera (València). In the studied systems, ammonium was mainly removed by the growth of autotrophic microorganisms (nitrification) whereas nitrate was removed by the anoxic growth of heterotrophic microorganisms (denitrification). Macrophyte uptake removed between 9 and 19% of the ammonium entering to the systems, although degradation of dead standing macrophytes returned a significant part to water column.

Mujer y pintura deportiva: la Colección del Consejo Superior de Deportes (España) / Women and sport painting: collection of Superior Council of Sports (Spain)

El objetivo del presente estudio es analizar cómo es representada la mujer en la pintura deportiva, según la selección avalada por el Consejo Superior de Deportes, que aparece en «Deporte, arte y literatura». El análisis cuantitativo muestra a la mujer en un número muy reducido de obras y caracterizada como joven y delgada. El análisis cualitativo identifica un tratamiento sexista y discriminatorio de la mujer, pintada desde un enfoque androcéntrico: bien como objeto sexual, bien como personaje pasivo, secundario y en función del personaje masculino. En las escasas ocasiones en las que la mujer aparece como personaje activo y central de la obra, aparece con énfasis estético y expresivo del movimiento, lo que caracteriza las actividades físico-deportivas que la ideología de género considera femeninas. En conclusión la pintura sobre el deporte ofrece una imagen sesgada y desigual, reproduciendo los estereotipos respecto a la masculinización del deporte y relega la presencia femenina (AU)

The aim of this study is to analyse how women are represented in the sports paintings, taking as reference a selection of works supported by the Superior Council of Sports, collected in the publication «Sport, art and literature». Quantitative analysis note that the female figure appears in a very small number of works and they are represented young and thin. Qualitative analysis allows to identify a sexist treatment and discriminatory of women, who is painted from an androcentric perspective: a sexual object, passive character, secondary and based on the male character. When the women appears as an active character and central of the work, they are marked by the emphasis in the aesthetic aspects and expressive of the movement, what defines the physical-sports activities that the gender ideology considers to be female. In conclusion, sport painting offers an image skewed and uneven, reproducing stereotypes regarding the masculinization of the sport and the limited nature of female sports (AU)

Carcinoma de células renales con invasión vascular: mortalidad y factores pronósticos / Renal cell carcinoma with vascular invasion: mortality and prognostic factors

Objetivo. Análisis de los resultados obtenidos en el seguimiento de los pacientes intervenidos de carcinoma renal con invasión vascular en nuestro centro, evaluación de los factores pronósticos y de las complicaciones. Material y métodos. Estudio observacional retrospectivo de 37 pacientes diagnosticados de carcinoma renal con invasión vascular intervenidos entre mayo de 1999 y julio de 2013. Se emplean el método de Kaplan-Meier para el análisis de supervivencias y la prueba de Mantel-Haenszel (LogRank) y el modelo de riesgos proporcionales de Cox para el análisis de los factores de riesgo de mortalidad. Resultados. La mediana de edad fue de 60 años. El tiempo de seguimiento medio de 42,1 meses. Las medianas de supervivencia global y supervivencia libre de enfermedad fueron de 53,8 y 36,3 meses respectivamente. Existe asociación estadística entre supervivencia global y el ASA (p=0,047), estadio tumoral (p=0,003), la afectación ganglionar (p=0,024), la presencia de metástasis (p=0,013), el nivel de trombo tumoral (p=0,05) y el tipo histológico (p=0,001). Catorce pacientes presentaron complicaciones grado IIIb o mayor según la clasificación de Clavien-Dindo, siendo la más frecuente el sangrado. Conclusiones. El carcinoma renal con invasión vascular es una enfermedad con alta tasa de mortalidad. La cirugía es una opción terapéutica que puede resultar curativa. El número de complicaciones es importante. La supervivencia está condicionada por el ASA, el estadio tumoral, el nivel de trombo tumoral, la afectación ganglionar, las metástasis y el tipo histológico (AU)

Objective. Analysis of the results of patients who had been operated of renal cell carcinoma with vascular invasion in our institution, evaluation of prognostic factors and complications. Methods. Retrospective observational study of 37 patients diagnosed of renal cell carcinoma with vascular invasion operated between May 1999 and July 2013. We used the method of Kaplan-Meier survival analysis and the Mantel-Haenszel's test (log rank) and the Cox's proportional hazards analysis test to analyse the risk factors of mortality. Results. The median age was 60 years. Mean follow-up period was 42.1 months. The median overall survival and disease-free survival were 53.8and 36.3 months, respectively. There was statistical association between overall survival and ASA (p=0.047), tumor stage (p=0.003), lymph node involvement (p=0.024), presence of metastases (p=0.013), level of tumor thrombus (p=0, 05) and histological type (p=0.001). 14 patients had grade IIIb complications or higher according to the Clavien Dindo classification, the most frequent was bleeding. Conclusions. Renal cell carcinoma with vascular invasion is a disease with high rate of mortality. Surgery is a therapeutic option that can be curative. The number of complications is important. Survival is conditioned by the ASA, tumor stage, the level of tumor thrombus, lymph node involvement, metastasis and histological type (AU)

Renal cell carcinoma with vascular invasion: Mortality and prognostic factors. / Carcinoma de células renales con invasión vascular: mortalidad y factores pronósticos.

OBJECTIVE: Analysis of the results of patients who had been operated of renal cell carcinoma with vascular invasion in our institution, evaluation of prognostic factors and complications. METHODS: Retrospective observational study of 37 patients diagnosed of renal cell carcinoma with vascular invasion operated between May 1999 and July 2013. We used the method of Kaplan-Meier survival analysis and the Mantel-Haenszel's test (log rank) and the Cox's proportional hazards analysis test to analyse the risk factors of mortality. RESULTS: The median age was 60 years. Mean follow-up period was 42.1 months. The median overall survival and disease-free survival were 53.8and 36.3 months, respectively. There was statistical association between overall survival and ASA (p=0.047), tumor stage (p=0.003), lymph node involvement (p=0.024), presence of metastases (p=0.013), level of tumor thrombus (p=0, 05) and histological type (p=0.001). 14 patients had grade IIIb complications or higher according to the Clavien Dindo classification, the most frequent was bleeding. CONCLUSIONS: Renal cell carcinoma with vascular invasion is a disease with high rate of mortality. Surgery is a therapeutic option that can be curative. The number of complications is important. Survival is conditioned by the ASA, tumor stage, the level of tumor thrombus, lymph node involvement, metastasis and histological type.

Panhipopituitarismo secundario a metástasis hipofisaria en una paciente con cáncer de mama / Panhypopituitarism secondary to pituitary metastasis in a patient with breast cancer

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