Novel frameshift variant of the CFTR gene: S511Lfs*2 from phenotype to molecular predictions.

Cystic fibrosis (CF) is a genetic disease caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. There are over 2,000 different pathogenic and non-pathogenic variants described in association with a broad clinical heterogeneity. In this work, we identified a novel variant S511Lfs*2 in CFTR gene that has not been reported in patients with CF. The patient was a female genotyped with c.1000C>T (legacy name: R334W) variant (pathogenic, CF-causing) and the novel variant (S511Lfs*2). We verified the amino acid sequence, the protein structure, and predicted the pathogenicity employing computational analysis. Our findings showed that S511Lfs*2 is a frameshift variant and suggest that it is associated with severe CF phenotype, as it leads to a lack of CFTR protein synthesis, and consequently the loss of its functional activity.

Perfil dos pacientes com tuberculose que foram atendidos em uma unidade de referência do município de Santa Cruz do Sul - RS no período de 2009 a 2013 / Profile of patients with tuberculosis treated in a Reference of the municipality of Santa Cruz do Sul - RS in the period from 2009 to 2013

Introdução: Anualmente, são notificados cerca de seis milhões de novos casos de Tuberculose em todo o mundo. No Brasil, a doença é um problema de saúde pública. Objetivo: Analisar os aspectos clínico-epidemiológicos dos pacientes com tuberculose que foram notificados no município de Santa Cruz do Sul-RS. Métodos: Estudo retrospectivo, descritivo e transversal, por meio da revisão de prontuários de pacientes atendidos com tuberculose na cidade de Santa Cruz do Sul-RS, durante os anos de 2009 a 2013. Os dados foram analisados no SPSS 22.0. Resultados: No ano de 2013, a taxa de incidência da tuberculose em Santa Cruz do Sul foi de 77,7 casos novos/100.000 habitantes. A amostra foi composta de 288 casos de tuberculose notificados na cidade. A análise revelou que apenas 88 (32,83%) pacientes atendidos eram do sexo feminino. A média de idade dos pacientes foi de 41,03 anos. Houve 222 (82,83%) novos casos da doença e apenas 19 casos de recidivas. Os atendimentos a presidiários foram expressivos, totalizando 52 pacientes. O sintoma mais prevalente foi a tosse com expectoração em 195 (67,7%) casos. A forma clínica predominante foi tuberculose pulmonar em todos os anos analisados, totalizando 278 (96,52%) casos. A prevalência da coinfecção tuberculose/HIV variou de 8% a 18,7% dentro dos cinco anos. Conclusões: O município está entre os 15 prioritários no estado do Rio Grande do Sul para o controle da tuberculose, mostrando que os altos índices da doença no município devem alertar para a importância de medidas eficazes no combate da doença. (AU)

Introduction: About six million new cases of Tuberculosis are reported annually worldwide. In Brazil, the disease is a public health problem. Objective: To analyze the clinical and epidemiological aspects of patients with tuberculosis reported in the city of Santa Cruz do Sul, RS. Methods: A retrospective, descriptive and cross-sectional study was carried out through the review of medical records of patients treated with tuberculosis in the city of Santa Cruz do Sul -RS during the years 2009 to 2013. Data were analyzed in SPSS 22.0. Results: In 2013, the incidence rate of tuberculosis in Santa Cruz do Sul was of 77.7 new cases / 100,000 inhabitants. The sample consisted of 288 cases of tuberculosis reported in the city. The analysis revealed that only 88 (32.83%) patients attended were female. The mean age of the patients was 41.03 years. There were 222 (82.83%) new cases of the disease and only 19 cases of relapses. Outpatient visits were significant, totaling 52 patients. The most prevalent symptom was cough with sputum in 195 (67.7%) cases. The predominant clinical form was pulmonary tuberculosis in all analyzed years, totaling 278 (96.52%) cases. The prevalence of tuberculosis / HIV co-infection ranged from 8% to 18.7% within five years. Conclusions: The municipality is among the 15 priorities in the state of Rio Grande do Sul for the control of tuberculosis, showing that the high rates of the disease in the municipality should alert to the importance of effective measures to combat the disease. (AU)

A workshop on asthma management programs and centers in Brazil: reviewing and explaining concepts.

OBJECTIVE: To report the results of a workshop regarding asthma management programs and centers (AMPCs) in Brazil, so that they can be used as a tool for the improvement and advancement of current and future AMPCs. METHODS: The workshop consisted of five presentations and the corresponding group discussions. The working groups discussed the following themes: implementation of asthma management strategies; human resources needed for AMPCs; financial resources needed for AMPCs; and operational maintenance of AMPCs. RESULTS: The workshop involved 39 participants, from all regions of the country, representing associations of asthma patients (n = 3), universities (n = 7), and AMPCs (n = 29). We found a direct relationship between a lack of planning and the failure of AMPCs. Based on the experiences reported during the workshop, the common assumptions about AMPCs in Brazil were the importance of raising awareness of managers; greater community participation; interdependence between primary care and specialized care; awareness of regionalization; and use of medications available in the public health system. CONCLUSIONS: Brazil already has a core of experience in the area of asthma management programs. The implementation of strategies for the management of chronic respiratory disease and their incorporation into health care system protocols would seem to be a natural progression. However, there is minimal experience in this area. Joint efforts by individuals with expertise in AMPCs could promote the implementation of asthma management strategies, thus speeding the creation of treatment networks, which might have a multiplier effect, precluding the need for isolated centers to start from zero.

OBJETIVO: Relatar os resultados de uma oficina de trabalho sobre programas e centros de atenção a asmáticos (PCAAs) no Brasil para que possam servir como instrumento para melhoria e avanço dos PCAAs existentes e criação de novos. MÉTODOS: A oficina de trabalho constituiu-se de cinco apresentações e discussões em grupos. Os grupos de trabalho discutiram os seguintes temas: implementação de uma linha de cuidado em asma; recursos humanos necessários para os PCAA; recursos necessários para financiar os PCAA; e manutenção do funcionamento dos PCAAs. RESULTADOS: A oficina envolveu 39 participantes de todas as regiões do país, representando associações de asmáticos (n = 3), centros universitários (n = 7) e PCAAs (n = 29). Evidenciou-se uma relação direta entre a ausência de planejamento e o insucesso dos PCAAs. Com base nas experiências brasileiras elencadas durante a oficina, as premissas comuns foram a importância da sensibilização do gestor, maior participação da comunidade, interdependência entre a atenção primária e a especializada, observação da regionalização e utilização dos medicamentos disponíveis no sistema público de saúde. CONCLUSÕES: O Brasil já tem um núcleo de experiências na área programática da asma. A implementação de uma linha de cuidado em doenças respiratórias crônicas e sua inclusão nas redes de saúde parecem ser o caminho natural. Porém, a experiência nessa área ainda é pequena. Agregar pessoas com experiência nos PCAAs na elaboração da linha de cuidado em asma encurtaria tempo na criação de redes de atenção com possível efeito multiplicador, evitando que se partisse do zero em cada local isolado.

A workshop on asthma management programs and centers in Brazil: reviewing and explaining concepts / Programas e centros de atenção a asmáticos no Brasil; uma oficina de trabalho: revisitando e explicitando conceitos

Objective: To report the results of a workshop regarding asthma management programs and centers (AMPCs) in Brazil, so that they can be used as a tool for the improvement and advancement of current and future AMPCs. Methods: The workshop consisted of five presentations and the corresponding group discussions. The working groups discussed the following themes: implementation of asthma management strategies; human resources needed for AMPCs; financial resources needed for AMPCs; and operational maintenance of AMPCs. Results: The workshop involved 39 participants, from all regions of the country, representing associations of asthma patients (n = 3), universities (n = 7), and AMPCs (n = 29). We found a direct relationship between a lack of planning and the failure of AMPCs. Based on the experiences reported during the workshop, the common assumptions about AMPCs in Brazil were the importance of raising awareness of managers; greater community participation; interdependence between primary care and specialized care; awareness of regionalization; and use of medications available in the public health system. Conclusions: Brazil already has a core of experience in the area of asthma management programs. The implementation of strategies for the management of chronic respiratory disease and their incorporation into health care system protocols would seem to be a natural progression. However, there is minimal experience in this area. Joint efforts by individuals with expertise in AMPCs could promote the implementation of asthma management strategies, thus speeding the creation of treatment networks, which might have a multiplier effect, precluding the need for isolated centers to start from zero. .

Objetivo: Relatar os resultados de uma oficina de trabalho sobre programas e centros de atenção a asmáticos (PCAAs) no Brasil para que possam servir como instrumento para melhoria e avanço dos PCAAs existentes e criação de novos. Métodos: A oficina de trabalho constituiu-se de cinco apresentações e discussões em grupos. Os grupos de trabalho discutiram os seguintes temas: implementação de uma linha de cuidado em asma; recursos humanos necessários para os PCAA; recursos necessários para financiar os PCAA; e manutenção do funcionamento dos PCAAs. Resultados: A oficina envolveu 39 participantes de todas as regiões do país, representando associações de asmáticos (n = 3), centros universitários (n = 7) e PCAAs (n = 29). Evidenciou-se uma relação direta entre a ausência de planejamento e o insucesso dos PCAAs. Com base nas experiências brasileiras elencadas durante a oficina, as premissas comuns foram a importância da sensibilização do gestor, maior participação da comunidade, interdependência entre a atenção primária e a especializada, observação da regionalização e utilização dos medicamentos disponíveis no sistema público de saúde. Conclusões: O Brasil já tem um núcleo de experiências na área programática da asma. A implementação de uma linha de cuidado em doenças respiratórias crônicas e sua inclusão nas redes de saúde parecem ser o caminho natural. Porém, a experiência nessa área ainda é pequena. Agregar pessoas com experiência nos PCAAs na elaboração da linha de cuidado em asma encurtaria tempo na criação de redes de atenção com possível efeito multiplicador, evitando que se partisse do zero em cada local isolado. .

Profile of eicosanoids in breath condensate in asthma and COPD.

The collection of exhaled breath condensates (EBC) is a noninvasive method for obtaining samples from the lungs. Eicosanoids are lipid mediators implicated in the asthmatic inflammatory response. The objective of our study was to investigate whether the profile of eicosanoid lipid mediators in EBC can characterize the inflammation in asthma and chronic obstructive pulmonary disease (COPD). EBC samples were collected from 22 healthy controls (C), 25 mild intermittent asthmatics (MIA), 20 with moderate to severe asthma (MSA) and 20 with moderate to severe COPD. EBC samples were analyzed by unique tandem mass spectrometry that allows the quantification of up to 25 eicosanoid mediators simultaneously. No differences were found between MIA and C. Subjects with MSA and COPD had higher levels of 6-keto, PGE2, LTB4, 11-12 EET and AA, while lower levels of LXA4, 11DHyTxB2, 11HETE and 8,9EET, when compared to MSA and C (p < 0.05). Our study shows that the analysis of EBC through mass spectrometry is mixed and has a similar response in MSA and COPD when compared to MIA and controls.

Pregnancy after bariatric surgery: 39 pregnancies follow-up in a multidisciplinary team.

BACKGROUND: We investigate the outcomes of pregnancy in women who undergone restrictive-malabsorptive procedure at Centro da Obesidade Mórbida-Hospital São Lucas (COM HSL-PUCRS), Porto Alegre, Brazil. METHODS: All pregnancies started after the bariatric surgery and with estimated due date until June 2008 were eligible for the study. Only the first pregnancy of each patient was included in the data analysis. Data was collected from medical records. RESULTS: Forty seven pregnancies were identified in 41 women. Eight of them were ineligible. There were 30 complete pregnancies and nine miscarriages (23%). Cesarean delivery was performed in 69% of the complete pregnancies. Mature infants occurred in 93.1%. Twelve pregnancies (30.8%) occurred in the first year after surgery. Vitamin B12 was low in 53.4% patients; folic acid in 16.1%, iron in 6.7%, ferritin in 41.7%, calcium in 16.7%, and albumin in 10.3% of the patients. Nineteen women (79.2%) had no complication during the pregnancy and two (8.3%) presented with internal hernia. The average of newborns weight and length on delivery were 3,037 g and 48.07 cm, respectively. Children from pregnancies started in the first year of post operatory had similar outcomes of children from pregnancies started after 1 year of surgery. CONCLUSIONS: Pregnancy after bariatric surgery is safe and has fewer complications than pregnancy in morbidly obese women. However, the recommendation to delay the pregnancy for at least 12-18 months post-operatively should be kept.

The role of the FEF50%/0.5FVC ratio in the diagnosis of obstructive lung diseases.

OBJECTIVE: To evaluate the contribution of a new coefficient, the FEF50%/0.5FVC ratio, obtained from the maximal expiratory flow-volume curve, to the diagnosis of obstructive lung disease (OLD); to test this coefficient in differentiating among patients considered normal, those with OLD and those with restrictive lung disease (RLD); and to determine cut-off points for each functional diagnosis, as well as the probability for each diagnosis based on individual values. METHODS: A prospective, cross-sectional study analyzing the pulmonary function of patients referred to the Porto Alegre Hospital de Clínicas, in Porto Alegre, Brazil, between January and December of 2003. We collected demographic and spirometric data. The patients were divided into three groups: normal; OLD; and RLD. We calculated the FEV1/FVC and FEF50%/0.5FVC ratios, and we compared the mean FEF50%/0.5FVC values among the groups. We used Pearson's correlation test in order to compare FEF50%/0.5FVC with FEV1/FVC. The patients were again divided into two groups: those with OLD and those without OLD. We calculated the likelihood ratio for different cut-off points. RESULTS: The mean age of the patients was 55.8 +/- 14.7 years. There were significant differences among the groups in terms of the mean FEF50%/0.5FVC (2.10 +/- 0.82, 2.55 +/- 1.47 and 0.56 +/- 0.29, respectively, for normal, RLD and OLD; p < 0.001). There was a positive correlation between FEF50%/0.5FVC and FEV1/FVC in the OLD group (r = 0.83). We found that an FEF50%/0.5FVC < 0.79 strongly suggests OLD, whereas an FEF50%/0.5FVC > 1.33 practically excludes this diagnosis. CONCLUSIONS: The FEF50%/0.5FVC ratio is a potentially useful parameter in the differential diagnosis of OLD and correlates positively with the FEV1/FVC ratio.

O papel da razão FEF50 por cento/0.5CVF no diagnóstico dos distúrbios ventilatórios obstrutivos / The role of the FEF50 percent/0.5FVC ratio in the diagnosis of obstructive lung diseases

OBJETIVO: Avaliar a contribuição de um novo coeficiente, a razão FEF50 por cento/0,5CVF, medida através da curva fluxo-volume máximo expiratório, no diagnóstico dos distúrbios ventilatórios obstrutivos (DVOs); testar esse coeficiente na diferenciação entre grupos de pacientes normais, com DVO e com distúrbio ventilatório restritivo (DVR); e estabelecer pontos de corte para cada um dos diagnósticos funcionais e a probabilidade para cada diagnóstico a partir de valores individuais. MÉTODOS: Estudo transversal, prospectivo, com a análise de testes de função pulmonar de 621 pacientes encaminhados ao Hospital de Clínicas de Porto Alegre entre janeiro a dezembro de 2003. Foram coletados dados demográficos e espirométricos. Os pacientes foram divididos conforme o diagnóstico funcional em três grupos: normal; DVO; e DVR. Foram calculadas as razões VEF1/CVF e FEF50 por cento/0,5CVF, e as médias de FEF50 por cento/0,5CVF foram comparadas entre os grupos. Para correlacionar FEF50 por cento/0,5CVF com VEF1/CVF, utilizou-se a correlação de Pearson. Os pacientes foram, então, divididos em dois grupos: com e sem DVO. Foram calculadas as razões de verossimilhança para diferentes pontos de corte. RESULTADOS: A média de idade dos pacientes foi de 55,8 ± 14,7 anos. Houve diferenças significativas nos valores médios de FEF50 por cento/0,5CVF entre os grupos (2,10 ± 0,82, 2,55 ± 1,47 e 0,56 ± 0,29, respectivamente, para normal, DVR e DVO; p < 0,001). Houve uma correlação positiva do FEF50 por cento/0,5CVF com VEF1/CVF no grupo DVO (r = 0,83). Valores de FEF50 por cento/0,5CVF < 0,79 mostraram-se fortes indicadores de DVO e valores > 1,33 praticamente afastam esse diagnóstico. CONCLUSÕES: A razão FEF50 por cento/0,5CVF é um parâmetro potencialmente útil para discriminar DVOs, correlacionando-se positivamente com o VEF1/CVF.

OBJECTIVE: To evaluate the contribution of a new coefficient, the FEF50 percent/0.5FVC ratio, obtained from the maximal expiratory flow-volume curve, to the diagnosis of obstructive lung disease (OLD); to test this coefficient in differentiating among patients considered normal, those with OLD and those with restrictive lung disease (RLD); and to determine cut-off points for each functional diagnosis, as well as the probability for each diagnosis based on individual values. METHODS: A prospective, cross-sectional study analyzing the pulmonary function of patients referred to the Porto Alegre Hospital de Clínicas, in Porto Alegre, Brazil, between January and December of 2003. We collected demographic and spirometric data. The patients were divided into three groups: normal; OLD; and RLD. We calculated the FEV1/FVC and FEF50 percent/0.5FVC ratios, and we compared the mean FEF50 percent/0.5FVC values among the groups. We used Pearson's correlation test in order to compare FEF50 percent/0.5FVC with FEV1/FVC. The patients were again divided into two groups: those with OLD and those without OLD. We calculated the likelihood ratio for different cut-off points. RESULTS: The mean age of the patients was 55.8 ± 14.7 years. There were significant differences among the groups in terms of the mean FEF50 percent/0.5FVC (2.10 ± 0.82, 2.55 ± 1.47 and 0.56 ± 0.29, respectively, for normal, RLD and OLD; p < 0.001). There was a positive correlation between FEF50 percent/0.5FVC and FEV1/FVC in the OLD group (r = 0.83). We found that an FEF50 percent/0.5FVC < 0.79 strongly suggests OLD, whereas an FEF50 percent/0.5FVC > 1.33 practically excludes this diagnosis. CONCLUSIONS: The FEF50 percent/0.5FVC ratio is a potentially useful parameter in the differential diagnosis of OLD and correlates positively with the FEV1/FVC ratio.

Estudo de alguns fatores preditivos de risco para complicaçöes pós-operatórias em cirúrgias de tórax / Study of the predict risk factors for postoperative complications in thoracic surgery

Os autores analisam os resultados de um estudo prospectivo, avaliando diferentes fatores de risco operatório e comparando-os às complicaçöes surgidas no período pós-operatório. Em 35 pacientes acompanhados, embora o fator idade, com limite em 55 anos, demonstre uma tendência a um risco aumentado de complicaçöes, näo foi possivel demonstrar diferença estatística significativa entre estas, assim como tambéem nas demais variáveis de risco avaliadas, quando comparadas à presença de complicaçöes