Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology.

PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.

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.

Lowered Cisplatin Dose and No Bleomycin in the Treatment of Pediatric Germ Cell Tumors: Results of the GCT-99 Protocol From the Brazilian Germ Cell Pediatric Oncology Cooperative Group.

PURPOSE: We describe the results of a risk-adapted, response-based therapeutic approach from the Brazilian GCT-99 study on germ cell tumors. PATIENTS AND METHODS: From May 1999 to October 2009, 579 participants were enrolled in the Brazilian GCT-99 study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk-group assignment at diagnosis with consideration for stage and primary tumor site. Patients at low risk received no chemotherapy. Patients at intermediate risk (IR) with a good response (GR) received four cycles of platinum and etoposide (PE), for total doses of platinum 420 mg/m(2) and etoposide 2,040 mg/m(2). Patients at IR with a partial response (PR) received three cycles of PE plus three cycles of ifosfamide, vinblastine, and bleomycin. Patients at high risk (HR) with a GR received four cycles of PE and ifosfamide (PEI) at total doses of platinum 420 mg/m(2), etoposide 1,200 mg/m(2), and ifosfamide 30 g/m(2). Patients at HR with a PR received six cycles of PEI. RESULTS: The risk-group distribution was 213 LR, 138 IR, and 129 HR for 480 evaluable patients. Overall survival (OS) and event-free survival (EFS) rates at 10 years were, respectively, 90% and 88.6% in the IR-GR group (n = 126) and 74.1% and 74.1% in the IR-PR group (n = 12). Ten-year rates for the HR-GR group (n = 86) were an OS of 66.8% and an EFS of 62.5%. The HR-PR group (n = 43) had an OS of 74.8% and an EFS of 73.4%. In univariable and multivariable analysis, increased serum lactate dehydrogenase level and histology for a metastatic immature teratoma were prognostic of a worsened outcome. CONCLUSION: Reduction of therapy to two drugs did not compromise survival outcomes for patients in the IR-GR group, and escalation of therapy with PEI did not significantly improve OS and EFS in patients at HR.

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.

Anemia falciforme: caracterização dos pacientes atendidos em um ambulatório de referência / Sickle cell anemia: characterization of the patients attended in a specialist outpatient center / Anemia falciforme: caracterización de los pacientes atendidos en un ambulatorio de referencia

Pesquisa de abordagem quantitativa que objetivou descrever perfil clínico, social e demográfico de pacientes com anemia falciforme atendidos em ambulatório de referência para Hematologia Pediátrica, em Curitiba/Paraná. Buscaram-se, de 1 a 19 de outubro de 2012, todos os prontuários de hemoglobinopatas do ambulatório e foram identificados 58 que atendiam aos critérios de inclusão. Dados de anamneses e exames clínicos, desde o primeiro atendimento até a data da coleta, foram organizados em categorias. Com predomínio (76%) de crianças (1 a 12 anos), procedentes de 14 regionais de saúde do estado (70,5%), diagnosticadas no primeiro ano de vida (80%), acompanhados há três anos ou mais (86,2%), com sinais clínicos de palidez cutânea (94,8%) e febre (93,1%), e como complicação principal a crise álgica (70,7%). Os resultados podem subsidiar o planejamento e ajustes no cuidado ao paciente com anemia falciforme e seus familiares neste serviço ambulatorial e também em outros semelhantes.

This qualitative research aimed to describe the clinical, social and demographic profile of patients with sickle cell anemia attended in a specialist outpatient center for Pediatric Hematology in Curitiba, Paraná. Between the 1st and 19th of October 2012, all the medical records of persons with hemoglobinopathies in the outpatient center were sought; 58 persons were identified who met the inclusion criteria. Data from case histories and clinical tests, from the first attendance up to the date of collection, were organized in categories. There was a predominance (76%) of children (1 to 12 years old), originating from 14 health regions in the state (70.5%), diagnosed in the first year of life (80%), monitored for three years or more (86.2%), with clinical signs of skin paleness (94.8%) and fever (93.1%), with pain crisis as the main complication (70.7%). The results may support planning and operations in the care of the patient with sickle cell anemia and her family members in this outpatient service and also in other similar services.

Investigación de abordaje cuantitativo cuya finalidad fue describir perfil clínico, social y demográfico de pacientes con anemia falciforme atendidos en ambulatorio de referencia para Hematología Pediátrica, en Curitiba/Paraná. Fueron investigados, de 1 a 19 de octubre de 2012, todos los prontuarios de hemoglobinopatas del ambulatorio e identificados 58 que atendían a los criterios de inclusión. Fueron organizados en categorías los datos de anamnesis y exámenes clínicos desde el primer atendimiento hasta la fecha en que fueron obtenidos. Con predominio (76%) de niños (1 a 12 años), procedentes de 14 regionales de salud del estado (70,5%), diagnosticados en el primer año de vida (80%), acompañados por tres años o más (86,2%), con señales clínicos de palidez cutánea (94,8%) y fiebre (93,1%), y como complicación principal la crisis de dolor intenso (70,7%). Los resultados pueden subsidiar el planeamiento y ajustes en el cuidado al paciente con anemia falciforme y sus familiares en este servicio ambulatorial, así como en otros semejantes.

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.

[Prevalence of hemoglobin S in the State of Paraná, Brazil, based on neonatal screening]. / Prevalência da hemoglobina S no Estado do Paraná, Brasil, obtida pela triagem neonatal.

The Brazilian Ministry of Health created the National Neonatal Screening Program under ruling no. 822/2001, including neonatal screening for hemoglobinopathies. In the State of Paraná, neonatal screening is conducted by the Ecumenical Foundation for the Protection of the Handicapped. The prevalence rates were determined for homozygous and heterozygous hemoglobin S and Sbeta-thalassemia. Blood samples drawn on filter paper were examined by isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). From January 2002 to December 2004, 548,810 newborns were screened, with the detection of 21 with FS, two FSA/FS, and four FSA. After confirmatory tests at six months of age, 12 were defined as sickle-cell anemia, or a prevalence of 2.2:100,000 newborns; Sbeta-thalassemia was confirmed in 15 (2.7:100,000 newborns); and 8,321 newborns were diagnosed as heterozygous HbS (1,500:100,000 newborns). HbS prevalence in Paraná (in southern Brazil) is lower than in the Central-West, North, and Northeast of the country. Ethnic origin of the population, fetal deaths, and non-random procreation may contribute to the relatively low number of homozygous individuals in the State. Sbeta-thalassemia interaction suggests the presence of Euro-Mediterranean peoples in this population's miscegenation.

Prevalência da hemoglobina S no Estado do Paraná, Brasil, obtida pela triagem neonatal / Prevalence of hemoglobin S in the State of Paraná, Brazil, based on neonatal screening

O Ministério da Saúde instituiu o Programa Nacional de Triagem Neonatal através da Portaria nº. 822/GM, incluindo a pesquisa das hemoglobinopatias nos recém-nascidos. No Paraná, é realizada pela Fundação Ecumênica de Proteção ao Excepcional. Determinou-se a prevalência da hemoglobina S em homozigose, heterozigose e Sbeta-talassemia no estado. O sangue coletado em papel filtro foi examinado por focalização isoelétrica e cromatografia líquida de alta precisão (HPLC). De janeiro de 2002 a dezembro de 2004, foram triados 548.810 recém-nascidos e detectados 21 recém-nascidos com os resultados FS, dois FSA e/ou FS e quatro FSA. Após exames confirmatórios aos seis meses de idade, 12 foram definidos como anemia falciforme, com prevalência de 2,2:100 mil recém-nascidos; a interação Sbeta-talassemia foi confirmada em quinze (2,7:100 mil recém-nascidos); e 8.321 recém-nascidos foram diagnosticados como heterozigotos para HbS (1.500:100 mil recém-nascidos). A prevalência da HbS no Paraná é menor do que nas regiões Centro-Oeste, Norte e Nordeste do país. Origem étnica da população, óbitos fetais e casamentos preferenciais podem estar contribuindo para não haver maior número de homozigotos no estado. A interação Sbeta-talassemia sugere presença de povos euro-mediterrâneos na miscigenação dessa população.

The Brazilian Ministry of Health created the National Neonatal Screening Program under ruling no. 822/2001, including neonatal screening for hemoglobinopathies. In the State of Paraná, neonatal screening is conducted by the Ecumenical Foundation for the Protection of the Handicapped. The prevalence rates were determined for homozygous and heterozygous hemoglobin S and Sbeta-thalassemia. Blood samples drawn on filter paper were examined by isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). From January 2002 to December 2004, 548,810 newborns were screened, with the detection of 21 with FS, two FSA/FS, and four FSA. After confirmatory tests at six months of age, 12 were defined as sickle-cell anemia, or a prevalence of 2.2:100,000 newborns; Sbeta-thalassemia was confirmed in 15 (2.7:100,000 newborns); and 8,321 newborns were diagnosed as heterozygous HbS (1,500:100,000 newborns). HbS prevalence in Paraná (in southern Brazil) is lower than in the Central-West, North, and Northeast of the country. Ethnic origin of the population, fetal deaths, and non-random procreation may contribute to the relatively low number of homozygous individuals in the State. Sbeta-thalassemia interaction suggests the presence of Euro-Mediterranean peoples in this population's miscegenation.

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.

Gene expression profiling of childhood adrenocortical tumors.

Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies; little is known regarding their etiology and biology. To provide additional insight into the nature of ACT, we determined the gene expression profiles of 24 pediatric tumors (five adenomas, 18 carcinomas, and one undetermined) and seven normal adrenal glands. Distinct patterns of gene expression, validated by quantitative real-time PCR and Western blot analysis, were identified that distinguish normal adrenal cortex from tumor. Differences in gene expression were also identified between adrenocortical adenomas and carcinomas. In addition, pediatric adrenocortical carcinomas were found to share similar patterns of gene expression when compared with those published for adult ACT. This study represents the first microarray analysis of childhood ACT. Our findings lay the groundwork for establishing gene expression profiles that may aid in the diagnosis and prognosis of pediatric ACT, and in the identification of signaling pathways that contribute to this disease.

Tratamento do tumor do córtex adrenal na infância / Treatment of childhood adrenocortical tumor

O tumor do córtex adrenal (TCA) na infância é raro. Entretanto, no Paraná sua incidência é 15 vezes maior do que a observada em outros países. A mutação germinativa R337H TP53, presente em mais de 95 por cento dos nossos pacientes, provavelmente está relacionada à maior incidência. Cento e vinte e cinco pacientes foram tratados no período de 1966 a 2003. A cirurgia é o único tratamento curativo. Em nossa experiência, tumores no estádio I, ausência de spillage durante a cirurgia e ausência de trombo são parâmetros relacionados à maior sobrevida. Dados preliminares mostram que a associação de etoposídeo, doxorrubicina, cisplatina e mitotano produziu remissão completa do tumor e/ou das metástases em alguns pacientes. Os efeitos colaterais destas drogas são comuns e pode ocorrer insuficiência adrenocortical. As doses de reposição de glicocorticóides e mineralocorticóides devem ser 2 a 3 vezes maiores que as doses fisiológicas.