Methotrexate-induced Acute Myelopathy in a Teenager With High-risk Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is one of the most frequent malignancies in childhood whose long-term survival has increased up to 80% thanks to modern therapy enhancements. Nevertheless, methotrexate (MTX) remains a mainstay of ALL therapy, but also represents one of the major causes of neurotoxicity in patients with ALL. MTX-induced toxicity occurs in about 9% of patients treated for ALL. It usually affects deep white matter region leading to leukoencephalopathy, which has varying clinical manifestations ranging from acute neurologic disturbances to seizures or chronic permanent encephalopathy. Here we describe a 13-year-old girl affected with ALL who developed lower limbs hypesthesia and static ataxia due to transverse myelopathy after intrathec administration of MTX therapy. A high-dose corticotherapy combined to vitamin supplementation and rehabilitation was tested. Neurological evolution was characterized by slow and partial recovery.

Re-annotation of 191 developmental and epileptic encephalopathy-associated genes unmasks de novo variants in SCN1A.

The developmental and epileptic encephalopathies (DEE) are a group of rare, severe neurodevelopmental disorders, where even the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. Here, we explore the incompleteness of transcript models used for exome and genome analysis as one potential explanation for a lack of current diagnoses. Therefore, we have updated the GENCODE gene annotation for 191 epilepsy-associated genes, using human brain-derived transcriptomic libraries and other data to build 3,550 putative transcript models. Our annotations increase the transcriptional 'footprint' of these genes by over 674 kb. Using SCN1A as a case study, due to its close phenotype/genotype correlation with Dravet syndrome, we screened 122 people with Dravet syndrome or a similar phenotype with a panel of exon sequences representing eight established genes and identified two de novo SCN1A variants that now - through improved gene annotation - are ascribed to residing among our exons. These two (from 122 screened people, 1.6%) molecular diagnoses carry significant clinical implications. Furthermore, we identified a previously classified SCN1A intronic Dravet syndrome-associated variant that now lies within a deeply conserved exon. Our findings illustrate the potential gains of thorough gene annotation in improving diagnostic yields for genetic disorders.

Contribution to the risk characterization of ciguatoxins: LOAEL estimated from eight ciguatera fish poisoning events in Guadeloupe (French West Indies).

From 2010 to 2012, 35 ciguatera fish poisoning (CFP) events involving 87 individuals who consumed locally-caught fish were reported in Guadeloupe (French West Indies). For 12 of these events, the presence of ciguatoxins (CTXs) was indicated in meal remnants and in uncooked fish by the mouse bioassay (MBA). Caribbean ciguatoxins (C-CTXs) were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Using a cell-based assay (CBA), and the only available standard Pacific ciguatoxin-1 (P-CTX-1), the lowest toxins level detected in fish samples causing CFP was 0.022 µg P-CTX-1 equivalent (eq.)·kg(-1) fish. Epidemiological and consumption data were compiled for most of the individuals afflicted, and complete data for establishing the lowest observable adverse effects level (LOAEL) were obtained from 8 CFP events involving 21 individuals. Based on toxin intakes, the LOAEL was estimated at 4.2 ng P-CTX-1 eq./individual corresponding to 48. 4 pg P-CTX-1 eq.kg(-1) body weight (bw). Although based on limited data, these results are consistent with the conclusions of the European Food Safety Authority (EFSA) opinion which indicates that a level of 0.01 µg P-CTX-1 eq.kg(-1) fish, regardless of source, should not exert effects in sensitive individuals when consuming a single meal. The calculated LOAEL is also consistent with the U.S. Food and Drug Administration guidance levels for CTXs (0.1 µg C-CTX-1 eq.kg(-1) and 0.01 µg P-CTX-1 eq.kg(-1) fish).

First line management of prolonged convulsive seizures in children and adults: good practice points.

Over the past decades, it has become clear that the most efficient way to prevent status epilepticus is to stop the seizure as fast as possible, and early treatment of prolonged convulsive seizures has become an integral part of the overall treatment strategy in epilepsy. Benzodiazepines are the first choice drugs to be used as emergency medication. This treatment in the early phases of a seizure often implies a 'pre-medical' setting before intervention of medically trained persons. In this paper, we propose "good practice points" for first line management of prolonged convulsive seizures in children and adults in a 'pre-medical' setting.

O cuidado em enfermagem no serviço de vigilância sanitária / Nursing care in health surveillance service

O serviço de vigilância sanitária, semelhante à enfermagem, tem sua origem justificada pela preocupação com a saúde dos indivíduos. Apesar da relevância da contribuição do enfermeiro para o serviço de vigilância sanitária, esse permanece pouco conhecido pelos profissionais da enfermagem. Esse estudo busca descrever o contexto do serviço de vigilância sanitária enquanto possibilidade do cuidado em enfermagem, permitindo sua visualização como campo de atuação da enfermagem. Para tanto, optou-se pelo método de estudo de caso com abordagem qualitativa. Os sujeitos são os enfermeiros que atuam no Departamento de Vigilância Sanitária - Goiânia, como Fiscais de Saúde Pública. O estudo foi realizado no período de novembro/2005 a novembro/2006. Os dados coletados foram trabalhados utilizando-se a análise de conteúdo proposta por Bardin, identificando “núcleos temáticos” na comunicação dos sujeitos. Os resultados evidenciam que a compreensão do cuidado em enfermagem, a identificação desse cuidado no serviço de vigilância sanitária e a construção da identidade profissional do enfermeiro que atua nesse serviço guardam relação entre si e estão relacionadas à formação acadêmica e profissional do enfermeiro. Profissionais que referem experiência anterior na área de Saúde Pública identificam mais facilmente o cuidado em enfermagem no serviço de vigilância sanitária, devido ao caráter coletivo desse serviço.

Putting evidence into practice: evidence-based interventions to prevent, manage, and treat chemotherapy-induced nausea and vomiting.

Chemotherapy-induced nausea and vomiting (CINV) continues to have a considerable effect on the physical and psychological well-being of patients with cancer, despite significant advances in antiemetic drugs since the 1990s. This article reviews and summarizes past and current empirical evidence related to interventions for CINV. A resource that summarizes evidence-based interventions for CINV is critical for effective management of this distressing symptom. Pharmacologic and nonpharmacologic interventions are appraised. Finally, gaps in the literature and opportunities for research, education, and practice changes are discussed.