TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors

Background: Giant cell glioblastoma (gcGBM) is a rare morphological variant of IDH-wildtype (IDHwt) GBM that occurs in young adults and have a slightly better prognosis than "classic" IDHwt GBM. Methods: We studied 36 GBMs, 14 with a histopathological diagnosis of gcGBM and 22 with a giant cell component. We analyzed the genetic profile of the most frequently mutated genes in gliomas and assessed the tumor mutation load (TML) by gene-targeted next-generation sequencing. We validated our findings using The Cancer Genome Atlas (TCGA) data. Results: p53 was altered by gene mutation or protein overexpression in all cases, while driver IDH1, IDH2, BRAF, or H3F3A mutations were infrequent or absent. Compared to IDHwt GBMs, gcGBMs had a significant higher frequency of TP53, ATRX, RB1, and NF1 mutations, while lower frequency of EGFR amplification, CDKN2A deletion, and TERT promoter mutation. Almost all tumors had low TML values. The high TML observed in only 2 tumors was consistent with POLE and MSH2 mutations. In the histopathological review of TCGA IDHwt, TP53-mutant tumors identified giant cells in 37% of the cases. Considering our series and that of the TCGA, patients with TP53-mutant gcGBMs had better overall survival than those with TP53wt GBMs (log-rank test, P < .002). Conclusions: gcGBMs have molecular features that contrast to "classic" IDHwt GBMs: unusually frequent ATRX mutations and few EGFR amplifications and CDKN2A deletions, especially in tumors with a high number of giant cells. TML is frequently low, although exceptional high TML suggests a potential for immune checkpoint therapy in some cases, which may be relevant for personalized medicine

An?lisis de medidas que implementadas por productores ganaderos durante un periodo de verano prolongado en Guanacaste, Costa Rica

Ponencia presentada en: VII Congresso Latinoamericano de Sistemas Agroflorestais para a Producao Pecu?ria Sustent?velEn las ?ltimas d?cadas, los efectos del cambio clim?tico han ocasionado ?pocas secas cada vez m?s extensas y/o periodos de lluvias m?s cortos para la regi?n del Pacifico Norte de Costa Rica. Estudios indican que la mayor?a de eventos extremos secos en esa regi?n se encuentran asociados al fen?meno meteorol?gico de El Ni?o (ENOS). Para el presente estudio, se tom? como referencia el periodo comprendido entre junio del 2009 y abril del 2010 por presentarse un verano seco muy prolongado (8 meses) debido a ENOS, lo que origin? un d?ficit de agua de hasta un 35% seg?n reportes del Instituto Meteorol?gico Nacional de Costa Rica(IMN). Para esto, los sistemas de producci?n se vieron en la necesidad de emplear diferentes medidas de adaptaci?n. Tres sistemas de fincas fueron identificados: 1) fincas de producci?n intensiva; uso de bancos forrajeros, pasturas mejoradas y bebederos, 2) fincas de producci?n semi intensiva; con uso de bancos forrajeros y bebederos 3) fincas con producci?n extensiva; con bajo o nulo uso de bancos forrajeros, pasturas mejoradas y bebederos. Las variables que m?s explicaron la funci?n de descarga o salida de animales por parte de los productores como ajuste en la carga animal en orden de significancia fueron la implementaci?n de bancos forrajeros (P=0.0007), pasturas mejoradas de alta densidad arb?rea (P=0.0016) y la disponibilidad que tienen los animales hacia sus bebederos (P=0.0032)

A comparison of physicians' end-of-life decision making for non-western migrants and Dutch natives in the Netherlands

Background: Non-western migrants have a different cultural background that influences their attitudes towards healthcare. As the first wave of this relatively young group is growing older, we investigated, for the first time, whether end-of-life decision-making practices for non-western migrants differ from Dutch natives. Methods: In 2005, we sent questionnaires to physicians who attended deaths identified from the central death registry of Statistics Netherlands (n = 9651; non-western migrants: n = 627, total response: 78%). We performed multivariate logistic regression analyses adjusted for age, sex and cause of death. Results: Of all deaths of non-western origin, 54% were non-sudden, whereas 67% of all deaths with a Dutch origin were non-sudden (P = 0.00). A relatively large number of non-suddenly deceased persons of non-western origin had died under the age of 65 (53%) as compared to Dutch natives (15%). Euthanasia was performed in 2.4% of all non-suddenly deceased persons in the non-western migrant group as compared to 2.7% in the native Dutch group (adjusted odds ratio = 0.82, P = 0.63). Alleviation of symptoms with a potential life-shortening effect was somewhat lower for non-western migrants (30% vs. 38%; adjusted odds ratio = 0.78, P = 0.07). Physicians decided to forgo potentially life-prolonging treatment in comparable rates (26% vs. 23%; adjusted odds ratio = 1.1, P = 0.73). Yet, the type of treatments forgone and underlying reasons differed. Conclusion: Euthanasia was not less common among non-suddenly deceased non-western migrants as compared to Dutch natives. However, intensive symptom alleviation was used less frequently and forgoing potentially life-prolonging treatment involved different characteristics. These findings suggest that cultural factors may affect end-of-life decision making