RESUMO Racional: Mutações KRAS são eventos importantes na carcinogênese colorretal como preditores negativos de resposta ao tratamento. Objetivo: Investigar a associação de características clinicopatológicas com mutações no KRAS em pacientes com câncer colorretal tratados. Métodos: Sessenta e nove pacientes com câncer colorretal metastáticos ao diagnóstico ou posteriormente foram analisados. As técnicas de sequenciamento direto e pirosequenciamento foram relacionadas ao éxon 2 do KRAS e o diagnóstico da mutação e seu tipo foram determinados. Resultados: A mutação KRAS foi identificada em 43,4% dos pacientes, c.35G>T (p.G12V), c.35G>A (p.G12D) e c.38G>A (p.G13D). Não foi encontrada correlação entre a mutação KRAS e a idade (p=0,646) ou o gênero (p=0,815). No entanto, o grupo mutado apresentou níveis mais altos de CEA na admissão (p=0,048). A mutação do códon 13 foi associada ao envolvimento de mais de um local metastático na progressão da doença (p=0,029); não houve associação entre o local primário do tumor e o diagnóstico de mutação (p=0,568); a doença primária do cólon foi associada com pior sobrevida global (p=0,009). Conclusão: A mutação KRAS foi identificada em quase metade dos pacientes. O grupo KRAS mutado apresentou níveis mais altos de CEA na admissão e a mutação no códon 13 foi associada ao envolvimento de mais de um local metastático no curso da doença. A doença do cólon foi associada com pior sobrevida global.

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

ABSTRACT BACKGROUND: There are cases of colorectal tumors that, although small, show more aggressive evolution than large tumors. This motivated us to study whether there are any proteins capable of alerting about these changes. The aim here was to correlate the immunoexpression of the TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers in tumors in patients with colorectal adenocarcinoma, with the degree of cell differentiation, tumor staging and clinical-pathological prognostic factors. DESIGN AND SETTING: Retrospective observational study at a public tertiary-level hospital. METHODS: We analyzed tissue-microarray paraffin blocks of tumor tissues that had been resected from 107 patients. We used Fisher’s exact test to study associations between tumor differentiation/staging and the immunoexpression of biomarkers. We also used Kaplan-Meier estimation, the log-rank test and the adjusted Cox regression model to investigate the patients’ overall survival (in months) according to biomarkers and disease-free interval. RESULTS: The degree of tumor differentiation and tumor staging were not associated with the biomarkers, except in cases of patients in stages III or IV, in which there was a correlation with MLH1 expression (P=0.021). Patient survival and disease-free interval were not associated with the biomarkers. CONCLUSION: There were no associations between the degree of tumor differentiation, staging, length of survival or disease-free interval and the immunoexpression of the TS, p53, COX2, EGFR or MSH6 tumor markers. In advanced cases of colorectal adenocarcinoma (stages III and IV), there was a higher percentage of MLH1-negative results.

RESUMO OBJETIVO: Confrontar o uso de analgesia versus a percepção de neonatologistas quanto ao emprego de analgésicos para procedimentos dolorosos em 2001, 2006 e 2011. MÉTODOS: Coorte prospectiva de todos recém-nascidos internados em quatro unidades universitárias. Avaliou-se a frequência do emprego de analgésicos para procedimentos dolorosos por um mês dos anos de estudo. Dos 202 neonatologistas atuantes nas unidades nos três períodos, 188 assinalaram em escala analógica visual de 10 cm (dor >3 cm) a intensidade da dor sentida pelo recém-nascido na punção lombar, intubação traqueal, ventilação mecânica e no pós-operatório. RESULTADOS: Para punção lombar, 12%, 43% e 36% foram feitas com analgesia em 2001, 2006 e 2011 e 40-50% dos neonatologistas referiam indicar analgésicos na punção lombar nos três períodos. Na intubação, 30% foram feitas sob analgesia nos três períodos e 35% (2001), 55% (2006) e 73% (2011) dos médicos diziam indicar analgésicos. Quanto à ventilação mecânica, 45-64% dos ventilados-dia estavam sob analgesia nos três períodos e 56% (2001), 57% (2006) e 26% (2011) dos neonatologistas diziam usar analgésicos. Dos pacientes-dia nos três primeiros dias de pós-operatório, 37% (2001), 78% (2006) e 89% (2011) receberam alguma dose de analgésico. Mais de 90% dos médicos referiam usar analgesia para essa situação. CONCLUSÕES: Entre 2001 e 2011, ocorreu aumento no uso de analgésicos para procedimentos dolorosos nas unidades neonatais e uma percepção mais acentuada por parte dos médicos de que o recém-nascido sente dor, mas o lapso entre a prática clínica e a percepção médica quanto à presença de dor persistiu.

ABSTRACT OBJECTIVE: To compare the use of analgesia versus neonatologists' perception regarding analgesic use in painful procedures in the years 2001, 2006, and 2011. METHODS: This was a prospective cohort study of all newborns admitted to four university neonatal intensive care units during one month in 2001, 2006, and 2011. The frequency of analgesic prescription for painful procedures was evaluated. Of the 202 neonatologists, 188 answered a questionnaire giving their opinion on the intensity of pain during lumbar puncture, tracheal intubation, mechanical ventilation, and postoperative period using a 10-cm visual analogic scale (VAS; pain >3 cm). RESULTS: For lumbar puncture, 12% (2001), 43% (2006), and 36% (2011) were performed using analgesia. Among the neonatologists, 40-50% reported VAS >3 for lumbar puncture in all study periods. For intubation, 30% received analgesia in the study periods, and 35% (2001), 55% (2006), and 73% (2011) of the neonatologists reported VAS >3 and would prescribe analgesia for this procedure. As for mechanical ventilation, 45% (2001), 64% (2006), and 48% (2011) of patient-days were under analgesia; 56% (2001), 57% (2006), and 26% (2011) of neonatologists reported VAS >3 and said they would use analgesia during mechanical ventilation. For the first three post-operative days, 37% (2001), 78% (2006), and 89% (2011) of the patients received analgesia and more than 90% of neonatologists reported VAS >3 for major surgeries. CONCLUSIONS: Despite an increase in the medical perception of neonatal pain and in analgesic use during painful procedures, the gap between clinical practice and neonatologist perception of analgesia need did not change during the ten-year period.

OBJETIVOS: Foi comparar medidas cefalométricas entre meninos e meninas respiradores bucais com o padrão cefalométrico de pacientes com síndrome da apneia obstrutiva do sono (SAOS). MÉTODOS: Medidas craniofaciais de radiografias cefalométricas laterais de 144 crianças com idade entre 7 e 14 anos foram comparadas entre meninos e meninas, e estas comparadas com o padrão cefalométrico de pacientes com SAOS. RESULTADOS: Meninos e meninas respiradores bucais não apresentaram diferenças em relação à morfologia craniofacial, enquanto meninos e meninas respiradores nasais mostraram as diferenças fisiologicamente esperadas. Meninos respiradores nasais apresentaram mandíbula mais retraída e incisivos superiores inclinados para frente quando comparados com meninas respiradoras nasais, mas os respiradores bucais não apresentaram diferenças. A medida NS.GoGn foi a única variável com interação entre gênero e tipo de respiração. CONCLUSÕES: Não houve diferença cefalométrica entre os respiradores bucais em relação ao crescimento craniofacial, sugerindo que a respiração bucal determina a mesma morfologia, e ambos os gêneros têm morfologia craniofacial semelhante àquela dos pacientes com SAOS.

OBJECTIVES: It was to compare cephalometric measures of mouth-breather boys and girls and with the cephalometric pattern observed in obstructive sleep apnea syndrome (OSAS) patients. METHODS: Craniofacial measurements of lateral cephalometric radiographs obtained from 144 children aged 7-14 years were compared between boys and girls, and both were compared to cephalometric pattern of OSAS patients. RESULTS: Mouth-breather boys and girls had no gender differences regarding to craniofacial morphology while nose-breather boys and girls showed those expected differences. Nose-breather boys presented a more retruded mandible and proinclined upper incisor when compared to nose-breather girls, but mouth-breather boys and girls had no differences. The measure NS.GoGn was the only variable with an interaction with gender and breathing. CONCLUSIONS: There were no cephalometric difference in mouth breather-boys and girls related to normal growth, suggesting that oral breathing make the same craniofacial morphology and both have craniofacial morphology close to that of OSAS patients.

Objetivo Desenvolver e aplicar em um projeto-piloto um questionário de frequência alimentar quantitativo de autopreenchimento destinado a graduandos da área da saúde. Métodos Trata-se de um estudo transversal realizado em 151 universitários de ambos os sexos, usuários do ambulatório de Nutrição do Corpo Discente da Universidade Federal de São Paulo, Brasil. O questionário inicial foi composto a partir dos alimentos e preparações informados no Registro Alimentar de Três Dias. As informações em medidas caseiras foram transformadas em gramas ou mililitros com o auxílio de tabelas, e os alimentos foram ordenados segundo a porcentagem de contribuição para o valor energético total informado. Foram selecionados 198 ali-mentos responsáveis por 95% do consumo energético e agrupados em 77 itens alimentares de acordo com a similaridade nutricional. O tamanho das porções alimentares foi classificado conforme o valor do percentil 50 da distribuição dos pesos correspondentes às medidas caseiras referidas. Definiu-se como porção pequena, aquela cujo valor foi igual ou inferior ao percentil 25; como média, o percentil 50 e grande, o valor igual ou superior ao percentil 75. Resultados Após o pré-teste do questionário inicial, o questionário final resultou em uma lista com 89 alimentos, agrupados em 70 itens alimentares. As instruções para o autopreenchimento foram refeitas, objetivando-se um melhor preenchimento. Conclusão Após as modificações realizadas, o questionário de frequência alimentar quantitativo encontra-se pronto para o estudo de validação e calibração.

Objective The objective of this study was to develop and pretest a self-administered, quantitative food frequency questionnaire for undergraduate students of the health sciences. Methods This is a cross-sectional study with 151 undergraduate students of both genders from the Students' Healthcare Service of the Universidade Federal de São Paulo, Brazil. The first version of the food frequency questionnaire was based on the foods and preparations listed in the 3-day food records. Tables were used to convert cooking units into grams or milliliters and the foods were ranked according to their percentage contribution to the total calorie intake. The 198 foods responsible for 95% of the energy intake were selected and grouped into 77 food items according to nutritional resemblance. Serving size was classified according to the 50th percentile of the weight distribution corresponding to the cooking units. Serving size was defined as small (S) when £25th percentile; average (A) when equal to the 50th percentile and large (L) when ≥75th percentile. Results The pretest of the first version of the questionnaire resulted in a final version with a list of 89 foods, grouped into 70 food groups. The instructions for filling out the questionnaire were rewritten to get better answers from the students. Conclusion After these changes, the quantitative food frequency questionnaire is ready for the validation and calibration study.

INTRODUCTION: It is important to know the reasons for resubmitting research projects to the Research Ethics Committee in order to help researchers to prepare their research projects, informed consent forms and needed research documentation. OBJECTIVES: To verify the reasons for resubmitting projects that were previously rejected by the Ethics Committee. METHOD: This is a cross-sectional study that evaluated research projects involving human beings. Research projects were submitted in 2007 to the Research Ethics Committee of the Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. RESULTS: One thousand two hundred and fifty six research projects were submitted to the ethics committee and the average time for evaluating the research projects and related documents until a final decision was reached was 49.95 days. From the total, 399 projects were reviewed in 2 or more meetings until a final decision was reached. Of these, 392 research projects were included in the study; 35 projects were subsequently excluded for involving animals. Among the research projects included, 42.5% concerned research with new drugs, vaccines and diagnostic tests, 48.5% consisted of undergraduate students' research projects, 68.9% of the research had no sponsorship, and 97.5% were eventually approved. The main reasons for returning the projects to the researchers were the use of inadequate language and/or difficulty of understanding the informed consent form (32.2%), lack of information about the protocol at the informed consent form (25.8%), as well as doubts regarding methodological and statistical issues of the protocol (77.1%). Other reasons for returning the research projects involved lack of, inaccuracy on or incomplete documentation, need of clarification or approval for participation of external entities on the research, lack of information on financial support. CONCLUSION: Among the research projects that were returned to the researchers for additional clarification, the main reasons were inadequacies or doubts about the terms used in the informed consent form as well as lack of information regarding the research at the informed consent form and methodological and statistical issues regarding the protocol.