ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes

The quantity of T-lymphocytes reaching the draining lymph nodes from tumors is likely important to mount effective distant responses and for the establishment of long term systemic memory. Looking into mechanisms behind lymphocyte egress, we directed our attention to leukocyte adhesion mechanisms inside tumors. Here we demonstrate that activated T-cells form intra-tumor aggregates in a LFA-1-ICAM-1-dependent fashion in mouse models of melanoma and breast cancer. We also provide evidence of the presence of T-cell clusters in primary human melanoma. Disruption of LFA-1-ICAM-1 interactions, and thereby T-cell clustering, enhances the arrival of activated CD8+ T-cells to tumor draining lymph nodes in both transplanted and spontaneous cancer models. Interestingly, upon ICAM-1 blockade, the expression of the chemotactic receptor CCR7 augments in tumor infiltrating lymphocytes and in in-vitro de-clustered T cells, as well as their ability to transmigrate across lymphatic endothelial cells. We propose that ICAM-1-mediated homotypic T-lymphocyte aggregation may serve as a tumor-mediated immune retention mechanism entrapping activated CD8+ T cells in the tumor microenvironment. Modulation of T-cell adhesion may be of use to improve the transit of activated lymphocytes toward the lymph nodes and their subsequent recirculation

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry

[Background] Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited.[Objectives] To evaluate the response and tolerance of BV in a cohort of patients with CTCL.[Methods] We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP).[Results] Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2.[Conclusions] These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.The Spanish Primary Cutaneous Lymphoma Registry (RELCP) is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which received an unrestricted grant support from Kyowa Kirin.Peer reviewe

The validity and reliability of the Spanish version of the Severe Cognitive Impairment Profile (SCIP) for the cognitive assessment of persons with advanced stages of Alzheimer’s disease

Existen pocas herramientas validadas al castellano para realizar una evaluación precisa del funcionamiento cognitivo de personas con demencias avanzadas. Esta población supone un reto por el elevado número de personas que alcanzan estos estadios y por la complejidad de cuidados que requieren. Este trabajo presenta la validación al castellano de un instrumento, la escala ‘perfil de deterioro cognitivo grave’ (SCIP), que permite la evaluación del funcionamiento cognitivo de personas con enfermedad de Alzheimer avanzada. Pacientes y métodos. Estudio transversal con 133 sujetos (29 hombres y 104 mujeres; edad media: 81,61 ± 7,41 años) con diagnóstico de enfermedad de Alzheimer en estadios de moderado a muy grave, según la escala de deterioro global (GDS 5-7). Se realizaron análisis de discriminación de los ítems, estudio de la consistencia interna y fiabilidad interjueces y test-retest, y se contrastó la estructura factorial y la validez del instrumento. Resultados. Sólo el 1% de los 160 ítems de la escala resultó no discriminativo. La consistencia interna de la escala es adecuada, así como la fiabilidad interjueces y test-retest. Respecto a la validez de constructo, la correlación con el miniexamen cognitivo es 0,74 (p < 0,01), y se encuentran diferencias significativas entre la escala SCIP y los tres niveles de la GDS analizados. La estructura factorial de la escala muestra la existencia de un solo factor que explica el 66,12% de la varianzaFew validated tools exist in Spanish for conducting a precise assessment of the cognitive functioning of persons with advanced dementia. This population is a challenge due to the large number of persons who reach these states and owing to the complexity of the care that they require. This study presents a validated Spanish version of an instrument, the Severe Cognitive Impairment Profile (SCIP), which allows assessment of the cognitive functioning of persons with advanced Alzheimer’s disease. PATIENTS AND METHODS. We conducted a cross-sectional study with 133 subjects (29 males and 104 females; mean age: 81.61 ± 7.41 years) diagnosed with Alzheimer’s disease in moderate to very severe stages, according to the Global Deterioration Scale (GDS 5-7). The following were performed: discrimination analyses of the items, a study of the internal consistency and interrater reliability and test-retest. Likewise, the factorial structure and the validity of the instrument were also tested. RESULTS. Only 1% of the 160 items on the scale were found to be non-discriminatory. The internal consistency of the scale is adequate, as is the interrater and the test-retest reliability. As regards the validity of the construct, the correlation with the mini-mental state examination is 0.74 (p < 0.01) and significant differences are found between the SCIP and the three levels of the GDS that were analysed. The factorial structure of the scales shows the existence of a single factor that accounts for 66.12% of the variance. CONCLUSIONS. The SCIP scale is a useful, reliable and valid instrument for the exhaustive evaluation in Spanish of the cognitive functions of persons with dementia in moderate to very severe state

Livedo racemosa, reticulated ulcerations, panniculitis and violaceous plaques in a 46-year-old woman

Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) that has conventional cutaneous manifestations of DM, but paradoxically, little or no muscle involvement. In 2005, a novel antibody was described in association with CADM – anti-melanoma differentiation-associated gene 5 (anti-MDA5). Patients with this serologic marker have a characteristic mucocutaneous phenotype consisting of skin ulceration among other signs. We describe the case of a 46-year-old woman with CADM, elevated anti-MDA5 autoantibodies, and unusual clinical features (livedo racemosa, florid acral edema) among the classical phenotype of MDA5 DM (arthralgias, ulcerations, panniculitis) and classical DM lesions (Gottron papules, heliotrope rash). The patients did not develop interstitial lung disease or internal malignancies and experienced a rapid response to prednisolone and intravenous immunoglobulins. After 2 years, she has no relapse of her cutaneous disease and continues 5 mg prednisolone and 2 g/kg kilogram of intravenous immunoglobulin every 3 months for maintenance. Our case highlights the clinical heterogeneity of CADM and underscores the importance of a comprehensive approach to DM patients. It was previously postulated that anti-MDA5 antibody could target vascular cells and compromise vascular function, the presence of livedo racemosa lesions, and MDA5 antibodies in a patient with negative thrombophilia workup, reinforce this idea. This is the first case, to our knowledge, of CADM with acral panniculitis and livedo racemosa

Agminated melanocytic nevus status post dabrafenib therapy for metastatic melanoma

Agminated melanocytic nevus is an uncommon type of mole, characterized by a local group of macular or papular pigmented lesions, well demarcated, without a common pigmented background. This pattern has also been associated with Spitz nevi, dysplastic melanocytic nevi, and non-melanocytic lesions.We describe the onset of an acquired agminated melanocytic nevus after dabrafenib treatment. Our case highlights paradoxical MAPK activation in the setting of single-agent BRAF blockade and underscores the importance of characterizing the diverse side effects of selective BRAF inhibitors. This is the first case, to our knowledge, of agminated melanocytic nevus in association with dabrafenib

Estudio del comportamiento de los IED-EFP

Dentro de los artefactos explosivos improvisados (IEDs) se encuentran aquellos que generan proyectiles formados por explosión (EFPs) que alcanzan velocidades de vuelo superiores a los 1000 m/s y por tanto, poseen una gran capacidad de penetración sobre los blindajes y sistemas acorazados. Estos artefactos, son de uso común entre los grupos terroristas, insurgentes y organizaciones criminales en su lucha contra las fuerzas aliadas desplegadas en zonas de conflicto. El objeto del presente estudio es reproducir y entender el comportamiento de dichos IED-EFP capaces de generar tan desbastadores proyectiles, desde su inicio (formación del artefacto) hasta el momento del impacto en el objetivo pasando por las sucesivas fases de detonación, evolución y formación del frente de onda, incidencia de dicho frente de onda sobre el disco, como este involuciona hasta convertirse en un proyectil, vuelo del proyectil y su impacto final sobre el objetivo. Para ello, este artículo se centra en la descripción de los ensayos realizados, así como en la breve presentación de los modelos numéricos generados a raíz de dichos ensayos, y que describen de manera muy fiable todo el mencionado proceso. Este proyecto supone un importante avance en la lucha frente al terrorismo más "casero". Keywords: IED; EFP; Simulación numérica; Explosivos. 1. Introducció

Pimiento en Navarra: comportamiento de diferentes variedades

El pimiento es una de las principales hortalizas de nuestro país, con aproximadamente 22.900 hectáreas cultivadas en el año 2003 (fuente: MAPA) y una producción estimada de 1.003.500 toneladas, de las cuales solamente el 7% se destina para industria. En el Valle del Ebro, la evolución de la superficie cultivada de pimiento ha sido diferente en función de la comunidad autónoma considerada. Mientras que en La Rioja y Aragón esta superficie está disminuyendo, en Navarra se ha producido un ligero incremento de la misma, pasando de 805 hectáreas cultivadas en 1998 a 1.327 en el año 2003 (Tabla nº 1). En este artículo se van a mostrar los resultados obtenidos durante esta campaña en la experimentación de las variedades de California, Piquillo y Morrón, en acolchado y con riego por goteo. El tipo California es de reciente introducción; la mayoría de sus variedades son híbridas lo que encarece su coste aunque eso mismo hace que reaccionen también mejor a las nuevas técnicas de cultivo. Los pimientos de Piquillo, en los que se incluye la variedad específica "Piquillo de Lodosa", son emblemáticos en Navarra y, por su excelente calidad y delicado sabor, han traspasado nuestras fronteras. El ITGA lleva trabajando desde sus inicios en la selección y mejora de estas variedades El resto de ensayos se comentarán en posteriores artículos y números dentro de esta misma publicación