Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

Multidisciplinary consensus on screening for, diagnosis and management of fetal growth restriction in the Netherlands

Screening for, diagnosis and management of intrauterine growth restriction (IUGR) is often performed in multidisciplinary collaboration. However, variation in screening methods, diagnosis and management of IUGR may lead to confusion. In the Netherlands two monodisciplinary guidelines on IUGR do not fully align. To facilitate effective collaboration between different professionals in perinatal care, we undertook a Delphi study with uniform recommendations as our primary result, focusing on issues that are not aligned or for which specifications are lacking in the current guidelines. We conducted a Delphi study in three rounds. A purposively sampled selection of 56 panellists participated: 27 representing midwife-led care and 29 obstetrician-led care. Consensus was defined as agreement between the professional groups on the same answer and among at least 70% of the panellists within groups. Per round 51 or 52 (91% - 93%) panellists responded. This has led to consensus on 27 issues, leading to four consensus based recommendations on screening for IUGR in midwife-led care and eight consensus based recommendations on diagnosis and eight on management in obstetrician-led care. The multidisciplinary project group decided on four additional recommendations as no consensus was reached by the panel. No recommendations could be made about induction of labour versus expectant monitoring, nor about the choice for a primary caesarean section. We reached consensus on recommendations for care for IUGR within a multidisciplinary panel. These will be implemented in a study on the effectiveness and cost-effectiveness of routine third trimester ultrasound for monitoring fetal growth. Research is needed to evaluate the effects of implementation of these recommendations on perinatal outcomes. NTR436

Mortalidade perinatal e evitabilidade: revisão da literatura Perinatal mortality and evitability: a review

Neste artigo, realizou-se uma revisão da literatura sobre mortalidade perinatal com maior enfoque na evitabilidade desses óbitos. Foram pesquisadas, sobretudo, publicações da década de 90 nas bases Medline e Lilacs (América Latina e Caribe). Discutiram-se as dificuldades para a realização de estudos nesta área, ainda em número restrito no Brasil, em decorrência do grande subregistro de óbitos fetais e da má qualidade da informação nas declarações de óbitos. Foram apresentadas as principais propostas de classificação dos óbitos perinatais baseadas em enfoque de evitabilidade, com destaque para a classificação de Wigglesworth. Nesta abordagem, os óbitos perinatais foram relacionados a momentos específicos da assistência, sendo evidenciadas as possibilidades de sua prevenção. Recomenda-se o enfoque de evitabilidade para a abordagem da mortalidade perinatal no Brasil, dado que as taxas são ainda elevadas, a maioria dos óbitos é considerada evitável e poderia ser prevenida com a melhoria da assistência pré-natal, ao parto e ao recém-nascido, não apenas quanto à sua resolubilidade clínica, mas também à organização da assistência em sistemas hierarquizados e regionalizados, assegurando o acesso da gestante e do recém-nascido em tempo oportuno a serviços de qualidade.<br>This is a literature review onperinatal mortality focusing its evitability. A Medline and Lilacs (Latin-America and Caribbean) search was conducted for the 90s. There are few research studies on this subject in Brazil due to the great number of underreported fetal deaths and the low quality information provided in death certificates. Different proposals for perinatal death classification are presented. Most are based on grouping the underlying causes of deaths in a functional system in order to facilitate the analysis. In the Wigglesworth classification system, one of the most recommended methods, deaths are related to the different stages of care for pregnant women and children, evidencing the possibilities of their prevention. The evitability approach of perinatal deaths in Brazil is highly recommended, as mortality rates are still very high and most of the deaths are considered avoidable. Premature deaths could be avoided improving the quality of health care. Besides improving the medical assistance, the organization of health care regarding pre-natal, birth and neonatal care must also be better developed to ensure access to qualified assistance