Influence of different asparaginase formulations in the prognosis of children with acute lymphocytic leukaemia in Brazil: a multicentre, retrospective controlled study.

Our group recently showed that the (ASNase) formulation available in Brazil from 2017 to 2018 when used at the same dose and frequency as the formulation provided previously did not reach the activity considered therapeutic. Based on these, our goal was to assess the impact of these facts on the prognosis of children with ALL at different oncology centers. A multicentre retrospective observational study followed by a prospective follow-up. Patients aged >1 and <18 years in first-line treatment followed up at 10 referral centres, between 2014 and 2018 who received the formulation Leuginase® were identified (Group B). For each patient, the centre registered 2 patients who received ASNase in the presentation of Aginasa® exclusively (Group A). Data collection was registered using (Redcap® ). A total of 419 patients were included; 282 in Group A and 137 in B. Group A had a 3-year OS and EFS of 91·8% and 84·8% respectively, while Group B had a 3-year OS of 83·8% (P = 0·003) and EFS of 76·1% (P = 0·008). There was an impact on 3-year OS and EFS of children who received a formulation. This result highlights the importance of evaluating ASNase and monitoring its activity.

Interações iniciais entre pais, mães e bebês de 0 a 3 anos: Revisão de literatura / Early interactions between fathers, mothers and babies from 0 to 3 years old: Review of the literature / Interacciones iniciales entre padres, madres y bebés de 0 a 3 años: Revisión de literatura

Resumo O estudo das interações iniciais dos bebês com seus cuidadores pode ser feito a partir da análise da responsividade parental. Com o objetivo de revisar os aspectos metodológicos e as tendências de análise das interações iniciais em estudos produzidos no Brasil, foram selecionados e analisados 110 artigos em bases eletrônicas de dados (Lilacs, SciELO, IndexPsi-Periódicos e Periódicos Capes). Os resultados apontaram para a predominância de estudos observacionais envolvendo as interações diádicas mãe-bebê. A coleta dos dados mais frequente foi por meio de combinação de instrumentos diretos e indiretos, e a análise se distribuiu de forma equivalente entre métodos qualitativos e quantitativos. Encontraram-se 55% de estudos sobre processos de desenvolvimento típico das interações e 45% de estudos com populações com risco biológico e social, abrindo questões para estudos futuros. Finalmente, sucedeu-se a análise dos fenômenos observados, levantando a discussão sobre os métodos de pesquisa na ciência psicológica.

Abstract The study of early interactions between babies and their caretakers can be performed from the analysis of parental responsiveness. Aiming to review the methodological aspects and trends in the analyses of early interactions from studies performed in Brazil, 110 articles were chosen from electronic databases (Lilacs, SciELO, IndexPsi-Periódicos and Periódicos Capes) and then they were fully analyzed. The results revealed a predominance of observational studies involving dyadic mother-baby interactions. The most frequently form of data collection combined direct and indirect methods; and the analysis was equivalently distributed between qualitative and quantitative methods. Of the studies found, 55% of the studies focused on the developmental processes that are typical of interactions, and 45% of the studies focused on processes among populations at biological and social risk, which brought up relevant questions for future studies. Finally, the analysis of interactions raises discussion of the research methods in the psychological science.

Resumen El estudio de las interacciones iniciales de los bebés con sus cuidadores puede hacerse desde el análisis de la responsividad parental. Para revisar los aspectos metodológicos y tendencias de análisis de las interacciones iniciales en los estudios producidos en Brasil, se seleccionaron y analizaron 110 artículos en bases de datos electrónicas (Lilacs, SciELO, IndexPsi-Periódicos y Periódicos Capes). Los resultados señalaron el predominio de los estudios observacionales que implican interacciones diádicas madre-niño. La recolección de datos más frecuente fue a través de una combinación de instrumentos directos e indirectos, y el análisis se distribuyó de forma equivalente entre métodos cualitativos y cuantitativos. Se han encontrado 55% de estudios sobre los procesos de desarrollo típico de las interacciones y 45% de estudios con poblaciones con riesgo biológico y social, abriendo preguntas para futuros estudios. Por último, se hizo el análisis de los fenómenos observados, levantando la discusión sobre los métodos de investigación en la ciencia psicológica.

Erythrocyte oxidative stress markers in children with sickle cell disease / Marcadores de estresse oxidativo em eritrócitos de crianças com doença falciforme

Abstract Objective To determine eight parameters of oxidative stress markers in erythrocytes from children with sickle cell disease and compare with the same parameters in erythrocytes from healthy children, since oxidative stress plays an important role in the pathophysiology of sickle cell disease and because this disease is a serious public health problem in many countries. Methods Blood samples were obtained from 45 children with sickle cell disease (21 males and 24 females with a mean age of 9 years; range: 3–13 years) and 280 blood samples were obtained from children without hemoglobinopathies (137 males and 143 females with a mean age of 10 years; range: 8–11 years), as a control group. All blood samples were analyzed for methemoglobin, reduced glutathione, thiobarbituric acid reactive substances, percentage of hemolysis, reactive oxygen species, and activity of the enzymes glucose 6-phosphate dehydrogenase, superoxide dismutase, and catalase. Data were analyzed using Student's t-test and were expressed as the mean ± standard deviation. A p-value of <0.05 was considered significant. Results Significant differences were observed between children with sickle cell disease and the control group for the parameters methemoglobin, thiobarbituric acid reactive substances, hemolysis, glucose 6-phosphate dehydrogenase activity, and reactive oxygen species, with higher levels in the patients than in the controls. Conclusions Oxidative stress parameters in children's erythrocytes were determined using simple laboratory methods with small volumes of blood; these biomarkers can be useful to evaluate disease progression and outcomes in patients.

Resumo Objetivo Determinar parâmetros de estresse oxidativo em eritrócitos de crianças com doença falciforme e compará-los com os mesmos parâmetros em eritrócitos de crianças saudáveis, pois o estresse oxidativo desempenha um importante papel na fisiopatologia da doença falciforme, considerada um sério problema de saúde pública em muitos países. Métodos Foram obtidas amostras de sangue de 45 crianças com doença falciforme (21 meninos e 24 meninas com média de 9 anos, variação de 3 a 13) e 280 amostras de sangue de crianças sem hemoglobinopatias (137 meninos e 143 meninas com média de 10 anos, variação de 8 a 11), como grupo controle. Em todas as amostras foram determinados meta-hemoglobina, glutationa reduzida, substâncias reativas ao ácido tiobarbitúrico, porcentagem de hemólise, espécies reativas de oxigênio e atividade das enzimas glucose6-fosfato desidrogenase, superóxido dismutase e catalase. Os dados foram analisados com o teste t de Student e foram expressos como média ± desvio padrão. Um valor de p < 0,05 foi considerado significativo. Resultados Foram observadas diferenças significativas entre as crianças com doença falciforme e o grupo controle para os parâmetros meta-hemoglobina, substâncias reativas ao ácido tiobarbitúrico, porcentagem de hemólise, espécies reativas de oxigênio e atividade da enzima glucose6-fosfato desidrogenase, com níveis aumentados nos pacientes. Conclusões Foi possível determinar parâmetros de estresse oxidativo em eritrócitos de crianças, com técnicas laboratoriais simples e pequenos volumes de sangue. Esses biomarcadores podem ser úteis na avaliação da progressão e dos resultados de tratamentos da doença.

Erythrocyte oxidative stress markers in children with sickle cell disease.

OBJECTIVE: To determine eight parameters of oxidative stress markers in erythrocytes from children with sickle cell disease and compare with the same parameters in erythrocytes from healthy children, since oxidative stress plays an important role in the pathophysiology of sickle cell disease and because this disease is a serious public health problem in many countries. METHODS: Blood samples were obtained from 45 children with sickle cell disease (21 males and 24 females with a mean age of 9 years; range: 3-13 years) and 280 blood samples were obtained from children without hemoglobinopathies (137 males and 143 females with a mean age of 10 years; range: 8-11 years), as a control group. All blood samples were analyzed for methemoglobin, reduced glutathione, thiobarbituric acid reactive substances, percentage of hemolysis, reactive oxygen species, and activity of the enzymes glucose 6-phosphate dehydrogenase, superoxide dismutase, and catalase. Data were analyzed using Student's t-test and were expressed as the mean±standard deviation. A p-value of <0.05 was considered significant. RESULTS: Significant differences were observed between children with sickle cell disease and the control group for the parameters methemoglobin, thiobarbituric acid reactive substances, hemolysis, glucose 6-phosphate dehydrogenase activity, and reactive oxygen species, with higher levels in the patients than in the controls. CONCLUSIONS: Oxidative stress parameters in children's erythrocytes were determined using simple laboratory methods with small volumes of blood; these biomarkers can be useful to evaluate disease progression and outcomes in patients.

Medidas antropométricas para o acompanhamento do estado nutricional de crianças e adolescentes com câncer, o que utilizar na prática clínica? / Anthropometric measures to monitor the nutritional status of children with cancer, which should be used in the practical clinic? / Medidas antropométricas para el acompañamiento del estado nutricional de niños y adolescentes con cáncer, ¿que utilizar en la práctica clínica?

Introdução: A avaliação do estado nutricional de crianças e adolescentes com câncer é fundamental para a elaboração do plano de cuidados nutricionais adequado, entretanto as alterações da própria doença e do tratamento podem dificultar essa avaliação. Objetivo: Descrever quais são os métodos antropométricos mais utilizados na avaliação do estado nutricional de crianças e adolescentes com câncer. Método: Realizou-se revisão sistemática da literatura de publicações referentes à avaliação nutricional de crianças e adolescentes com câncer, dos últimos dez anos nas bases de dados MEDLINE, PubMed, Web of Science e LILACS . Resultados: Foram incluídos nove artigos, nos quais foram destacados a amostra, o objetivo e os métodos de avaliação nutricional utilizados. A avaliação de dados isolados da antropometria como peso e estatura de crianças e adolescentes com câncer não é suficiente, uma vez que essa população apresenta alteração da composição corporal. Conclusão: Na prática clínica, a utilização da circunferência do braço, circunferência muscular do braço e dobra cutânea tricipital é indicada para avaliação e acompanhamento da evolução do estado nutricional.

Introduction: The evaluation of nutritional status of children and adolescents with cancer is fundamental to the elaboration of adequate planning for nutritional monitoring, however alterations caused by the disease and/or the treatment may hamper this evaluation. Objective: Describing anthropometric methods mostly used at the evaluation of nutritional status of children and adolescents with cancer. Method: Systematic review of the literature of publications produced within the last ten years referring to nutritional evaluation of children and teenagers with cancer took place based on data from MEDLINE, PubMed, Web of Science and LILACS . Results: Nine articles were studied from which samples were highlighted, objectives and methods for nutritional evaluation were also used. The evaluation of isolated anthropometric data such as weight and height of children and teenagers with cancer is not sufficient once this specific population presents alteration on body composition. Conclusion: The utilization of arm muscle circumference, arm muscle area and triceps skinfold thickness measurements are proposed in order to evaluate and monitor nutritional status in practical clinics.

Introducción: La evaluación del estado nutricional de niños y adolescentes con cáncer es fundamental para la elaboración de un plan de cuidados nutricionales adecuados, sin embargo las alteraciones de la propia enfermedad y del tratamiento pueden dificultar esta evaluación. Objetivo: Describir cuales son los métodos antropométricos más utilizados en la evaluación del estado nutricional de niños y adolescentes con cáncer. Método: Se realizó revisión sistemática de la literatura y de publicaciones referentes a la evaluación nutricional de niños y adolescentes con cáncer, de los últimos diez años en las bases de datos MEDLINE, PubMed, Web of Science y LILACS . Resultados: Se incluyeron nueve artículos, en los cuales fueron destacados la muestra, objetivo y métodos de evaluación nutricional utilizados. La evaluación de datos aislados de la antropometría como peso y estatura de niños y adolescentes con cáncer no es suficiente, una vez que esta población presenta alteración de la composición corporal. Conclusión: En la práctica clínica, la utilización de la circunferencia del brazo, circunferencia muscular y dobla cutánea tricípite es indicada para evaluación y acompañamiento de la evolución del estado nutricional.

Evolução do estado nutricional na doença de Gaucher tipo I em tratamento com reposição enzimática - relato de dois casos / The evolution of nutritional status in type I Gaucher’s disease treated with enzyme replacement - two case histories

A doença de Gaucher é um erro do metabolismo enzimático que leva ao acúmulo de glicocerebrosídeo nas células, o que caracteriza os sinais e sintomas da doença. No momento do diagnóstico, além de outros sinais e sintomas, é observado retardo no crescimento em crianças e adolescentes. O tratamento é realizado por meio de reposição enzimática, que pode ocasionar ganho de peso no paciente pela diminuição do metabolismo energético. Descrição: dois irmãos com diagnóstico de doença de Gaucher tipo I foram avaliados antes de iniciarem a reposição enzimática e depois a cada 2 meses de tratamento, por um período de 6 meses. A composição corporal foi avaliada por impedância bioelétrica, que avaliou a quantidade de massa livre de gordura e massa de gordura; o consumo energético e a relação de macronutrientes foram avaliados por registro alimentar de 3 dias. Discussão: os dois pacientes apresentavam baixa estatura para idade ao diagnóstico e tiveram aumento de massa de gordura durante o tratamento, sendo que um paciente também apresentou aumento da massa livre de gordura. O consumo energético e a relação de macronutrientes mantiveram-se semelhantes durante todo o período de acompanhamento para ambos os pacientes...

Gaucher’s disease is flaw in enzyme metabolism that leads to the accumulation of glycocerebrosides in cells that characterizes the signs and symptoms of the condition. At the time of diagnosis, retarded growth, among other signs and symptoms, is observed in children and adolescents. The disease is treated by enzyme replacement, which may lead to weight gain in the patient, owing to the reduction in energy metabolism. Description: two brothers diagnosed with type I Gaucher’s disease were evaluated prior to commencing enzyme replacement therapy and subsequently after every two months of treatment, for a period of six months. Body composition was assessed using bioelectrical impedance, which measures the quantity of fat-free and fat mass; energy consumption and macronutrients were evaluated using a three-day food diary. Discussion: the two patients were of low height for age on diagnosis and had experienced an increase in fat mass during treatment, with one patient also presenting with an increase in fat free mass. Energy consumption and macronutrients remained fairly constant during the follow-up period in both patients...

Correlation between FLT3-ITD status and clinical, cellular and molecular profiles in promyelocytic acute leukemias.

Internal tandem duplications (ITD) of FLT3 gene occur in about a third of acute promyelocytic leukemias (APL). We investigated the patterns of blood count, surface antigen, expression, chromosome aberrations, PML-RARa isoform, gene expression profile (GEP) and survival in 34 APL patients according to FLT3-ITD status. 97% had a t(15;17) and all of them carried PML-RARa gene fusion, 8 (23.5%) had a FLT3-ITD mutation. Presence of ITD was associated with higher Hb and WBC levels, bcr3 isoform, CD34 expression, CD2 or CD2/CD34 expression. In a multivariate analysis, Hb>9.6g/dL and WBC≥20 × 10(9)/L were important factors for predicting ITD presence. GEP showed that FLT3-ITD carriers clustered separately, even when as few as 5 genes were considered. This study provides further evidence that FLT3-ITDs carriers constitute a biologically distinct group of APL patients.

Cytomorphometric and cytomorphologic analysis of oral mucosa in children with sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is an autosomal recessive genetic disorder, characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs, consequence of vaso occlusive phenomenon and vasculopathy. Several forms of the chronic anemia, consequence of hemolysis, can be associated with oral epithelial cells changes. Exfoliative cytology can be used to detect real changes in the oral mucosa in SCA. AIMS: To evaluate morphometric and morphological changes in oral epithelial cells by exfoliative cytology in children with SCA. MATERIALS AND METHODS: Oral smears were collected from clinically normal-appearing mucosa by liquid-based exfoliative cytology in 20 SCA children (SCA group) and 20 healthy children (C group), matched for age and gender. The slides were prepared and stained by the Papanicolaou technique. Cell morphology and cellularity were analyzed and compared by Chi-square test (P < 0.05). Images of 50 cells per slide were captured and the nuclear area (NA) and cytoplasmic area (CA) were analyzed using an image analysis system. The nucleus-to-cytoplasmic area ratio (NA/CA) was calculated. To compare the means of groups SCA and C, the Student's t-test (P < 0.05) was applied to NA and CA; test non-parametric Mann Whitney U (P < 0.05) was used to compare NA/CA. RESULTS: MEAN VALUES FOR SCA AND C GROUPS WERE: NA (69.38 and 59.63 µm²; P = 0.01); CA (2321.85 and 2185.60 µm²; P = 0.24); NA/CA (0.03 and 0.02; P = 0.13), respectively. A significant increase in NA for SCA group (P = 0.01) was seen. No morphological differences were found between the groups. There was a predominance of nucleated cells of the superficial layer in the smears of both groups. Class I smears were predominant in both groups. CONCLUSIONS: This study revealed that SCA was able to induce significant changes on nuclear area of the oral epithelial cells.

Placental alkaline phosphatase in pediatric adrenocortical cancer.

The germline R337H mutation in the TP53 gene is considered to be responsible for the increased incidence of adrenocortical tumors (ACTs) in children from Brazil. High level production of hormones in ACTs (>95%) cause virilization alone (60%), Cushing syndrome (<5%), the mixed type (30%), or other rarer manifestations. ACT probably develops owing to events occurring during the final stages of intrauterine life based on the very common early onset of signs and symptoms shortly after birth. In this study, we determined by immunohistochemistry and enzyme assays whether placental alkaline phosphatase (PLAP) is expressed in pediatric ACTs. Immunohistochemical analysis revealed positive p53 expression in 88% of the tested ACTs (29 of 33). PLAP was detected at a slightly lower frequency based on immunohistochemical (17 of 33, 51%) and enzyme activity analyses (9 of 16, 56%). In conclusion, probably at a certain time point during adrenocortical development (end of gestation to early postnatal period), some fetal zone cells survive owing to defective apoptosis and develop into childhood ACT, maintaining some characteristics of the embryonal period, such as PLAP expression. Further studies of PLAP should investigate the functional role, if any, of PLAP in such tumors.

Carcinoma mucoepidermóide de brônquio: uma rara causa de pneumonia recorrente em uma criança / Mucoepidermoid carcinoma of bronchus: a rare cause of recurrent pneumonia in a child

Os autores relatam o caso de um paciente de 13 anos com tosse crônica e pneumonia recorrente, que revelou, na broncoscopia, massa vegetante obstruindo brônquio segmentar superior direito. Foi realizada biópsia, a qual revelou carcinoma mucoepidermóide de baixo grau. O paciente foi submetido posteriormente a bilobectomia. Atualmente encontra-se bem, em seguimento de 14 meses em nosso serviço.

The authors report a case of patient of 13 years of age that presented chronic cough and recurrent pneumonia, whose bronchoscopy showed a polipoid mass obstructing upper right segmental bronchus. Biopsy was performed and revealed low-grade mucoepidermoid carcinoma. Subsequently, the patient was submitted to a bilobectomy. Nowadays, the patient has been met well in follow-up of 14 months in our department.

Aspectos epidemiológicos e expressão de SF-1 dos tumores de cortex adrenal de crianças no Estado do Paraná / Aspects epidemiologists and expression of SF-1 and DAX-1 of the tumors of adrenal cortex of children in the state of the Paraná

Os objetivos deste estudo foram: identificar o coeficiente de mortalidade por TCA na região metropolitana de Curitiba com dados de base populacional , como meio de corroborar a estimativa de maior incidência. Para TCA do período de 1998 a 2003; a partir do conhecimento da amplificação do 9q34e utilizando as técnicas de FISH e western blot, estudar o gene SF-1 e a sua expressão expressão , acreditando-se que estejam amplificados nos TCAs. A amplificação do SF-1 foi avaliada por FISH em 9 tumores fixados em parafina, previamente estudados por hibridização genômica comparativa , e avaliada em 10 tumores, cujas amostras estavam também disponíveis em tecido congelado, por FISH e western blot; estudar a expressão de transcritos e proteínas do gene DAX-1, um dos principais fatores conta reguladores do SF-1, ambos importantes para o desenvolvimento e manutenção do córtex adrenal. Três amostras de tecido adrenocortical normal foram usadas como controle. Os resultados foram: coeficiente de mortalidade padronizado para idade, 1,6 milhão de crianças abaixo de 15 anos. Como a letalidade por TCA nesta região é de 45%, conclui-se que a incidência do TCA seja 3,5 casos/milhão de crianças abaixo de 15 anos, ou seja, confirma a incidência estimada em publicações anteriores; encontrou-se que o gene SF-1 está amplificado em 89% dos 9 tumores e em 60% dos 10 tumores. O número médio de cópias do gene SF-1, 3,26 ± 0,83, encontrado, é compatível com um aumento médio de 6,9 vezes na expressão protéica em relação ao córtex adrenal normal. Estes achados não tiveram correlação com idade e estadiamento, diferiram com o sexo, forma clínica, histologia ou evolução; foi encontrado aumento de concentração de transcritos de DAX-1 E aumento da expressão protéica em 13 tumores analisados. Os adenomas e carcinomas apresentaram valores maiores do que o córtex adrenal normal. Não foi encontrada associação entre os valores de DAX-1, os achados laboratoriais e a forma clínica.