Asesoramiento genético en cáncer de próstata: ¿cómo implementarlo en la práctica clínica diaria? / Genetic counseling in prostate cancer: How to implement it in daily clinical practice?

El cáncer de próstata tiene un protagonismo socio-sanitario innegable en nuestros días y sistemas de salud. Su impacto epidemiológico cuantitativamente está muy próximo a otros tumores como el cáncer de colon y el cáncer de mama, en los que el asesoramiento genético forma parte de su práctica clínica habitual, tanto en la evaluación inicial como en la selección de estrategias terapéuticas. Los síndromes de cáncer hereditario, mama/ovario y síndrome de Lynch, forman parte del asesoramiento genético en estos tumores y hoy día también sabemos que pueden tener relación con el cáncer de próstata. Ha llegado el momento de implementar el asesoramiento genético en cáncer de próstata desde las etapas más iniciales de su abordaje, desde la sospecha inicial hasta los tumores más avanzados.Presentamos una revisión actualizada de nuestro grupo de trabajo interdisciplinar sobre la literatura científica, guías de práctica clínica y documentos de consenso hasta la creación y redacción de un «Protocolo de asesoramiento genético en cáncer de próstata», centrado en el estudio de línea germinal, de fácil aplicabilidad en los diferentes entornos asistenciales. Dicho protocolo se encuentra actualmente implementado en nuestra práctica habitual y da respuesta a tres preguntas concretas: ¿A quién realizar asesoramiento genético en cáncer de próstata?, ¿qué panel de genes analizar?, y ¿cómo aconsejar de acuerdo con los resultados obtenidos? Otros aspectos acerca de quién debe realizar el asesoramiento genético, consideraciones éticas y normativa también son recogidos

Prostate cancer plays an undeniably prominent role in public health in our days and health systems. Its epidemiological impact is quantitatively very close to that of other tumors such as colon cancer and breast cancer, in which genetic counseling is part of their routine clinical practice, both in the initial evaluation and in the selection of therapeutic strategies. Hereditary cancer syndromes, breast/ovarian and Lynch syndrome are part of genetic counseling in these tumors. Currently, we also know that they can be associated to prostate cancer. The time has come to implement genetic counseling in prostate cancer from the earliest stages of its approach, from initial suspicion to the most advanced tumors. We present an updated review carried out by our interdisciplinary working group on scientific literature, clinical practice guidelines and consensus documents, aimed at the creation and drafting of a'Protocol for genetic counseling in prostate cancer' for the study of germline, with easy application in different healthcare settings. This protocol is currently being implemented in our routine practice and provides answers to 3 specific questions: Who should receive genetic counseling for prostate cancer? Which gene panel should be analyzed? How should counseling be done according to the results obtained? Other aspects about who should perform genetic counseling, ethical considerations and regulations are also collected

Fluticasone in mild to moderate atopic dermatitis relapse: a randomized controlled trial

BACKGROUND: The long-term efficacy of corticosteroids to prevent atopic dermatitis (AD) relapses has partially been addressed in children. This study compared an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% with its vehicle base in reducing the risk of relapse in children with stabilized AD. METHODS: A randomized controlled, multicentric, double-blind trial was conducted. Children (2-10 years) with mild/moderate AD (exclusion criteria: >30% affected body surface area and/or head) were enrolled into an Open-label Stabilization Phase (OSP) of up to 2 weeks on twice daily FP. Those who achieved treatment success entered the Double-blind Maintenance Phase (DMP). They were randomly allocated to receive FP or vehicle twice-weekly on consecutive days for 16 weeks. The primary study endpoint was relapse rate; time to relapse and severity of disease were also studied. Kaplan-Meier estimates were calculated. RESULTS: Fifty-four patients (29 girls) entered the OSP (23 mild AD) and 49 (26 girls) continued into the DMP. Mean age was 5.5 (SD: 2.8) and 5.1 (SD: 2.3) yrs for FP and vehicle groups, respectively. Four patients withdrew from the DMP (two in every group). Patients treated with FP twice weekly had a 2.7 fold lower risk of experiencing a relapse than patients treated with vehicle (relative risk 2.72, SD: 1.28; p = 0.034). FP was also superior to vehicle for delaying time to relapse. Both treatment therapies were well tolerated. CONCLUSION: This long-term study shows that twice weekly FP provides an effective maintenance treatment to control the risk of relapse in children with AD

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Infiltrado parahiliar / Parahilar Injection

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4Kscore Test, Prostate Cancer Prevention Trial-Risk Calculator y European Research Screening Prostate-Risk Calculator en la predicción del cáncer de próstata de alto grado; estudio preliminar / A Preliminary Study of the Ability of the 4Kscore test, the Prostate Cancer Prevention Trial-Risk Calculator and the European Research Screening Prostate-Risk Calculator for Predicting High-Grade Prostate Canc

Introducción: Frente al sobrediagnóstico y al sobretratamiento en cáncer de próstata (CaP) se establecen estrategias terapéuticas como la vigilancia activa o la terapia focal, o métodos para precisar el diagnóstico del CaP de alto grado (CaP-AG), Gleason ≥ 7, como la resonancia magnética multiparamétrica o nuevos marcadores como el 4Kscore Test (4KsT). Es nuestro propósito testar mediante un estudio piloto la capacidad del 4KsT como identificador de CaP-AG (suma de Gleason ≥ 7) en biopsia de próstata (Bx) y compararlo con otros modelos pronósticos multivariantes disponibles, como el Prostate Cancer Prevention Trial-Risk Calculator 2.0 (PCPTRC 2.0) y elEuropean Research Screening Prostate Cancer-Risk Calculator 4 (ERSPC-RC 4). Material y métodos: Cincuenta y un pacientes sometidos a BxP según práctica clínica habitual, con un mínimo de 10 cilindros. Diagnóstico de CaP-AG consensuado por 4 uropatólogos. Comparación de las predicciones ofrecidas por los diferentes modelos mediante prueba U Mann-Whitney, áreas bajo la curva ROC (AUC) (test de DeLong), funciones de densidad de probabilidad, diagramas de caja y curvas de utilidad clínica (CUC). Resultados: Un 43% presentaron CaP y un 23,5% CaP-AG. Las medianas de probabilidad de 4KsT, PCPTRC 2.0 y ERSPC-RC 4 fueron significativamente diferentes entre los pacientes con CaP-AG y no CaP-AG (p ≤ 0,022), siendo más diferenciadas en el caso de 4KsT (mediana en CaP-AG: 51,5% [percentil 25-75: 25-80,5%], frente a 16% [P 25-75: 8-26,5%] en no CaP-AG [p = 0,002]). Todos los modelos mostraron AUC por encima de 0,7 sin diferencias significativas entre ninguno de ellos y 4KsT (p ≥ 0,20). Las funciones de densidad de probabilidad y diagramas de caja muestran una buena capacidad discriminativa, especialmente en los modelos de ERSPC-RC 4 y 4KsT. Las CUC muestran como un punto de corte del 9% de 4KsT identifica a todos los CaP-AG y permite un ahorro del 22% de biopsias, similar a lo que ocurre con los modelos de ERSPC-RC 4 y un punto de corte del 3%. Conclusiones: Los modelos predictivos evaluados ofrecen una buena capacidad de discriminación del CaP-AG en Bx. 4KsT es un buen modelo clasificatorio en su conjunto, seguido de ERSPC-RC 4 y PCPTRC 2.0. Las CUC permiten sugerir puntos de corte de decisión clínica: 9% para 4KsT y 3% en ERSPC-RC 4. Este estudio preliminar debe ser interpretado con cautela por su limitado tamaño muestral

Introduction: To prevent the overdiagnosis and overtreatment of prostate cancer (PC), therapeutic strategies have been established such as active surveillance and focal therapy, as well as methods for clarifying the diagnosis of high-grade prostate cancer (HGPC) (defined as a Gleason score ≥7), such as multiparametric magnetic resonance imaging and new markers such as the 4Kscore test (4 KsT). By means of a pilot study, we aim to test the ability of the 4 KsT to identify HGPC in prostate biopsies (Bx) and compare the test with other multivariate prognostic models such as the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC 2.0) and the European Research Screening Prostate Cancer Risk Calculator 4 (ERSPC-RC 4). Material and methods: Fifty-one patients underwent a prostate Bx according to standard clinical practice, with a minimum of 10 cores. The diagnosis of HGPC was agreed upon by 4 uropathologists. We compared the predictions from the various models by using the Mann-Whitney U test, area under the ROC curve (AUC) (DeLong test), probability density function (PDF), box plots and clinical utility curves. Results: Forty-three percent of the patients had PC, and 23.5% had HGPC. The medians of probability for the 4 KsT, PCPTRC 2.0 and ERSPC-RC 4 were significantly different between the patients with HGPC and those without HGPC (p≤.022) and were more differentiated in the case of 4 KsT (51.5% for HGPC [25-5 percentile: 25-80.5%] vs. 16% [P 25-75: 8-26.5%] for non-HGPC; p=.002). All models presented AUCs above 0.7, with no significant differences between any of them and 4 KsT (p≥.20). The PDF and box plots showed good discriminative ability, especially in the ERSPC-RC 4 and 4 KsT models. The utility curves showed how a cutoff of 9% for 4 KsT identified all cases of HGPC and provided a 22% savings in biopsies, which is similar to what occurs with the ERSPC-RC 4 models and a cutoff of 3%. Conclusions: The assessed predictive models offer good discriminative ability for HGPCs in Bx. The 4 KsT is a good classification model as a whole, followed by ERSPC-RC 4 and PCPTRC 2.0. The clinical utility curves help suggest cutoff points for clinical decisions: 9% for 4 KsT and 3% for ERSPC-RC 4. This preliminary study should be interpreted with caution due to its limited sample size

El ratón deficiente en apolipoproteína E, un modelo traslacional para el estudio de la aterosclerosis / Apolipoprotein E–deficient mouse, a translational model for the study of atherosclerosi

INTRODUCCIÓN: La aterosclerosis es una de las principales causas de morbimortalidad en países desarrollados que presenta varias similitudes histopatológicas con la inflamación crónica. Los ratones deficientes en apolipoproteína E (apoE-/−) son ampliamente utilizados en el estudio de los mecanismos implicados en el inicio y el progreso de las lesiones ateroscleróticas. OBJETIVO: Evaluar el impacto en la formación de la placa de ateroma de una dieta aterogénica en el ratón apoE-/−. MATERIAL Y MÉTODOS: Ratones apoE-/− de 2 meses de edad fueron sometidos o no a una dieta hipercolesterolémica (10,8% de grasa, 0,75% en colesterol) durante 2 meses adicionales. Se determinó el perfil lipídico, la lesión y el contenido en macrófagos, linfocitos, colágeno, células de la musculatura lisa vascular (CMLV) y core necrótico por técnicas histológicas e inmunohistoquímicas. Cuantificación de las interacciones leucocito-endotelio por microscopia intravital en la microcirculación cremastérica. RESULTADOS: Los ratones apoE-/− sometidos a dieta hipercolesterolémica mostraron elevados niveles circulantes de colesterol total y triglicéridos frente aquellos sometidos a dieta control. Estos efectos fueron acompañados de un claro desarrollo de lesión aterosclerótica en la aorta caracterizada por un mayor contenido en macrófagos (Mac3+), linfocitos (CD3+), colágeno, core necrótico y CMLV. Paralelamente hubo una mayor adhesividad de los leucocitos al endotelio arteriolar en aquellos animales sometidos a dieta grasa. CONCLUSIÓN: El modelo de aterosclerosis que se desarrolla en el ratón apoE-/− sometido a dieta aterogénica presenta numerosas similitudes con la lesión humana, y constituye un adecuado modelo para la detección de nuevas dianas terapéuticas y ensayo de nuevos fármacos

INTRODUCTION: Atherosclerosis is one of the leading causes of morbidity and mortality in Western countries and bears several histopathological similarities to chronic inflammation. Mice deficient in apolipoprotein E (apoE-/−) are widely used in the study of the mechanisms involved in the onset and progression of the atherosclerotic lesion. OBJECTIVE: To evaluate the impact of an atherogenic diet in lesion formation in apoE-/− mice. MATERIAL AND METHODS: Two month-old apoE-/− mice were subjected, or not (controls), to a high fat/high cholesterol diet (10.8% fat, .75% cholesterol) for two months. Lipid profile, lesion formation, and macrophage, lymphocyte, collagen, vascular smooth muscle cells (VSMC), and necrotic core content, were determined within the lesion using histological and immunohistochemical techniques. Leukocyte-endothelial cell interactions were quantified by intravital microscopy in the cremaster microcirculation. RESULTS: apoE-/− mice subjected to a hypercholesterolemic diet showed increased circulating levels of total cholesterol and triglycerides compared to those subjected to a control diet. These effects were accompanied by a clear development of atherosclerotic lesion in the aorta, which was characterized by enhanced macrophage (Mac3+), lymphocyte (CD3+) collagen, VSMC and necrotic core content. In parallel, increased adhesiveness of leukocytes to the arteriolar endothelium in those animals subjected to an atherogenic diet was also detected. CONCLUSION: The atherosclerosis model in apoE-/− mice subjected to an atherogenic diet shares common features with the human atherosclerotic lesion, and constitutes an appropriate model to detect new therapeutic targets and evaluate novel developed drugs

Varón de 57 años con episodios recurrentes de rinorrea acuosa desencadenados por cambios bruscos de posición / No disponible

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Utilidad de la determinación de la proteína S-100 beta en el manejo del traumatismo craneoencefálico leve en un servicio de urgencias hospitalario / Usefulness of determining serum S-100 protein expression in screening patients with minor head injury in a hospital emergency department

Objetivos: Validar una técnica de cribaje para la valoración del traumatismo craneoencefálico(TCE) leve con respecto a un patrón-oro de neuroimagen, para confirmar el papel de la proteína (..) (AU)

Objectives: To validate testing for (..) (AU)

Factores pronósticos y evolución a largo plazo de los intentos de suicidio / No disponible

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Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability.

BACKGROUND AND PURPOSE: The present study addressed the effects of the investigational PDE4 inhibitor roflumilast on leukocyte-endothelial cell interactions and endothelial permeability in vivo and in vitro. EXPERIMENTAL APPROACH: In vivo, intravital video-microscopy was used to determine effects of roflumilast p.o. on leukocyte-endothelial cell interactions and microvascular permeability in rat mesenteric venules. In vitro, the effects of roflumilast N-oxide, the active metabolite of roflumilast in humans, and other PDE4 inhibitors on neutrophil adhesion to tumour necrosis factor alpha (TNFalpha)-activated human umbilical vein endothelial cells (HUVEC), E-selectin expression and thrombin-induced endothelial permeability was evaluated. Flow cytometry was used to determine the effect of roflumilast on N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced CD11b upregulation on human neutrophils. KEY RESULTS: In vivo, roflumilast, given 1 h before lipopolysaccharide (LPS), dose-dependently reduced leukocyte-endothelial cell interactions in rat mesenteric postcapillary venules. It also diminished histamine-induced microvascular permeability. Immunohistochemical analyses revealed that roflumilast prevented LPS-induced endothelial P- and E-selectin expression. In vitro, roflumilast N-oxide concentration-dependently suppressed neutrophil adhesion to TNFalpha-activated HUVEC and CD11b expression on fMLP-stimulated neutrophils. It also reduced TNFalpha-induced E-selectin expression on HUVEC, when PDE3 activity was blocked. HUVEC permeability elicited by thrombin was concentration-dependently suppressed by roflumilast N-oxide. While roflumilast N-oxide was as potent as roflumilast at inhibiting stimulated endothelial cell and neutrophil functions, both compounds were significantly more potent than the structurally unrelated PDE4 inhibitors, rolipram or cilomilast. CONCLUSIONS AND IMPLICATIONS: These findings further support earlier observations on the inhibition of inflammatory cell influx and protein extravasation by roflumilast in vivo.

Tratamiento farmacológico del trastorno de estrés postraumático. Especificidades en la población infanto-juvenil / No disponible

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Cáncer de próstata incidental: T1a-T1b. Nuestra experiencia tras observación/intervención radical y revisión de la literatura / Incidental prostatic cancer: T1a- T1b. Our experience after observational/radical surgery and literature review

Objetivos: Analizar el comportamiento del cáncer de próstata T1a y T1b diagnosticados en nuestro centro. Material y métodos: Estudio retrospectivo de 40 pacientes en estadio clínico T1a-T1b diagnosticados de adenocarcinoma de próstata en nuestro centro, entre los años 1986 y 1999. A los 16 pacientes T1a, se les realizó biopsia de reestadificación tras el diagnóstico inicial y control posterior. A los 24 T1b, se les realizó prostatectomía radical. Todos fueron seguidos mediante tacto rectal y PSA semestral. Analizamos progresión biológica y/o clínica, tiempo hasta la progresión, mortalidad por causa tumoral y supervivencia. Resultados: Ninguno de los 16 pacientes con estadio clínico T1a presentó progresión tumoral, con una mediana de seguimiento de 90 meses. El 12,5% de los 24 casos T1b presentaron progresión tumoral, con una mediana de seguimiento de 70 meses. La mortalidad cáncer específica fue de un paciente (4,16 %) que pertenecía al grupo T1b. Conclusiones: La observación y seguimiento mediante PSA y tacto rectal del estadio clínico T1a parece ser una buena opción dado el buen pronóstico. De nuestros resultados podría deducirse que los pacientes con estadio clínico T1a y buenos factores pronósticos podrían considerarse con un riesgo de padecer un nuevo cáncer de próstata clínico similar al de la población normal, si bien, son necesarios estudios prospectivos que validen estos resultados. Los casos T1b precisan un tratamiento activo y seguimiento más estricto

Objectives: To analyse the progress of T1a and T1b prostate cancer diagnosed in our hospital. Material and methods: Retrospective study of 40 patients in T1a-T1b clinical stage diagnosed with prostate adenocarcinoma in our hospital, from 1986 to 1999. A restaging biopsy was performed on the 16 T1a patients after initial diagnosis and control. A radical prostatectomy was performed on the 24 T1b patients. They were all monitored every six months with rectal exam and PSA. We analysed biological and/or clinical progression, time to progression, mortality caused by the tumour and survival. Results: None of the 16 patients with T1a clinical stage presented tumour progression, with a median follow-up of 90 months. 12,5% of the 24 T1b cases presented tumour progression, with a median follow-up of 70 months. Cancer-specific mortality was one patient (4,16 %) in the T1b group. Conclusions: Observation and follow-up with PSA and rectal exam appears to be a good option for T1a clinical stage, given the good prognosis. Our results show that patients with T1a clinical stage and good prognostic factors could be at a similar risk of suffering from a new prostate cancer as the normal population, although prospective studies are required to validate these results. T1b cases require active treatment and closer monitoring

Response of native plants of northeastern United States and southern Spain to ozone exposures; determining exposure/response relationships.

Tropospheric ozone has been identified as the most important regional scale air pollutant across much of eastern United States of America and many areas of Mediterranean climes in southern Europe. Recent field surveys in the northeastern USA and in southeastern Spain have revealed many additional plant species that exhibit symptoms typical of ozone-induced injuries. Objectives of this study were to confirm ozone as the cause of the observed foliar symptoms, determine ozone induced exposure/response relationships, and identify possible bio-indicator species. Thirteen native species of northeastern USA and 27 native species of southeastern Spain were selected for study. Plant species were exposed to ozone within 16 CSTR chambers in a greenhouse during the summer seasons of 2000 and 2001; ozone exposures of 30, 60, 90, and 120 ppb were delivered for 7 h/day, 5 days/week. Results have confirmed that with few exceptions, symptoms observed in the field were induced by exposures to ambient ozone. Species differed significantly in terms of the exposures required for the initiation of visible symptoms and subsequent injury progression.