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.

Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from inpatients at a tertiary care hospital / Cobertura vacinal pneumocócica teórica: análise de sorotipos isolados de pacientes internados em hospital terciário

ABSTRACT Objective: To evaluate Streptococcus pneumoniae serotypes isolated from an inpatient population at a tertiary care hospital, in order to determine the theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). Methods: This was a cross-sectional study involving 118 inpatients at the Hospital São Lucas, in the city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or other sterile body fluid specimens, collected between January 2005 and December 2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied in relation to the serotypes identified in the sample and their relationship with those contained in the pneumococcal vaccines available in Brazil. Results: The majority of the population was male (n = 66; 55.9%), with a median age of 57 years (interquartile range: 33-72 years). The most common manifestation was pneumonia, and the pneumococcus was most commonly isolated from blood cultures. More than one fourth of the study population had some degree of immunosuppression (n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no significant associations between mortality and comorbidity type, ICU admission, or need for mechanical ventilation. The theoretical vaccine coverage of PPV23 alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. Conclusions: If the patients in this sample had been previously vaccinated with PCV13 plus PPV23, theoretically, 50.8% of the cases of invasive pneumococcal disease that required hospital admission could potentially have been prevented. Invasive pneumococcal disease should be prevented by vaccination not only of children and the elderly but also of adults in their economically productive years, so as to reduce the socioeconomic costs, morbidity, and mortality still associated with the disease, especially in underdeveloped countries.

RESUMO Objetivo: Avaliar os sorotipos de Streptococcus pneumoniae isolados de uma população internada em um hospital terciário para verificar a cobertura vacinal teórica das vacinas conjugada pneumocócica 13-valente (VCP13) e pneumocócica polissacarídica 23-valente (VPP23). Métodos: Estudo transversal envolvendo 118 pacientes internados no Hospital São Lucas, na cidade de Porto Alegre (RS), cujas amostras de cultura de sangue, líquor ou outro líquido estéril apresentaram isolados de pneumococos entre janeiro de 2005 e dezembro de 2016. A cobertura vacinal teórica foi estudada em relação aos sorotipos observados na amostra e sua relação com os contidos nas vacinas pneumocócicas disponíveis no Brasil. Resultados: A maioria da população era masculina (n = 66; 55,9%), com mediana de idade de 57 anos (intervalo interquartil: 33-72 anos). O agravo mais frequente foi pneumonia, e o pneumococo foi mais frequentemente isolado em hemocultura. Mais de um quarto da população estudada tinha algum grau de imunossupressão (n = 34; 28,8%). Na amostra geral, 39 pacientes (33,1%) foram a óbito. Não houve associações significativas do número de óbitos com o tipo de comorbidades, internação em UTI ou necessidade de ventilação mecânica. A cobertura vacinal teórica da VPP23 e da combinação VCP13 + VPP23 foi de 31,4% e 50,8%, respectivamente. Conclusões: Nesta amostra, se os pacientes tivessem sido previamente vacinados com a combinação VCP13 seguida de VPP23, teoricamente, 50,8% dos casos de doença pneumocócica invasiva que necessitaram de internação hospitalar poderiam ter sido prevenidos potencialmente. Essa doença deve ser prevenida com a vacinação não só de crianças e idosos, mas também de adultos em idade economicamente ativa, para reduzir o custo socioeconômico, a morbidade e a mortalidade ainda associados à doença, especialmente em países subdesenvolvidos.

Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from inpatients at a tertiary care hospital.

OBJECTIVE: To evaluate Streptococcus pneumoniae serotypes isolated from an inpatient population at a tertiary care hospital, in order to determine the theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). METHODS: This was a cross-sectional study involving 118 inpatients at the Hospital São Lucas, in the city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or other sterile body fluid specimens, collected between January 2005 and December 2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied in relation to the serotypes identified in the sample and their relationship with those contained in the pneumococcal vaccines available in Brazil. RESULTS: The majority of the population was male (n = 66; 55.9%), with a median age of 57 years (interquartile range: 33-72 years). The most common manifestation was pneumonia, and the pneumococcus was most commonly isolated from blood cultures. More than one fourth of the study population had some degree of immunosuppression (n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no significant associations between mortality and comorbidity type, ICU admission, or need for mechanical ventilation. The theoretical vaccine coverage of PPV23 alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. CONCLUSIONS: If the patients in this sample had been previously vaccinated with PCV13 plus PPV23, theoretically, 50.8% of the cases of invasive pneumococcal disease that required hospital admission could potentially have been prevented. Invasive pneumococcal disease should be prevented by vaccination not only of children and the elderly but also of adults in their economically productive years, so as to reduce the socioeconomic costs, morbidity, and mortality still associated with the disease, especially in underdeveloped countries.

The management of asthmatic smokers.

Asthma is still a major public health problem in most countries; new strategies to better control this disease are necessary. Such strategies must include predisposing factors. One of these factors is smoking and a significant fraction of asthmatics are smokers. However, clinical trials studying new drugs or newer therapeutic regimens for asthma generally exclude smokers. Therefore, there is a lack of specific information about the treatment of asthma in smokers. The asthmatic smoker is a special phenotype with important therapeutic and prognostic clinical implications. Any form of tobacco use, especially cigarette smoking, plays an important role in this disease. Asthmatic smokers are prone to several negative outcomes. Smoking cessation results in an improvement of symptoms and pulmonary functioning. Counselling and first-line medications for smoking cessation (nicotine replacement therapy, bupropion and varenicline) significantly increase quitting rates. The role of electronic cigarettes in this group of patients has only begun to be studied. The treatment of asthmatics that smoke has characteristics that need must be well understood by clinicians, especially the poor response to corticosteroids. This condition is not universal and physicians should always consider its inclusion in the treatment of these patients. The association of inhaled corticosteroids (ICS) plus a long-acting beta2 adrenegic (LABA) by smoking asthmatics results in more pronounced improvement in several asthma outcomes compared with the use of corticosteroid alone. Inhaled corticosteroids in extra-fine particles associated with LABA may be a new perspective of treatment. Also the use of leukotriene antagonists may become another therapeutic alternative. The purpose of this narrative review is to discuss the challenges faced by clinicians to control asthma in smokers and to present methods of coping with smoking treatment and avoiding relapses.

Abordagens terapêuticas na cessação do tabagismo / Therapeutic approaches in smoking cessation

Apesar das políticas governamentais investirem na prevenção e em estratégias de combate ao fumo, o tabagismo segue sendo considerada uma pandemia pela Organização Mundial da Saúde. Nesse contexto é importante que todo profissional de saúde conheça abordagens terapêuticas disponíveis, já que os desfechos da doença são desfavoráveis.

Despite government policies invest in the prevention and combat strategies to smoking, it is still considered pandemic by the World Health Organization. In this context it is important that all health care professionals has notions of the therapeutic approaches available, since the outcomes of the disease are extremely unfavorable.

Ventilação mecânica: como iniciar / Mechanical ventilation: how to start

O conhecimento dos conceitos básicos e da utilização prática da ventilação mecânica (VM) é indispensável para médicos que pretendem trabalhar nas áreas de emergência e medicina intensiva. Este artigo de revisão tem como objetivo explicar de forma simplificada os conceitos iniciais, as indicações de VM e o ajuste dos parâmetros iniciais.

The knowledge of the basic concepts and practical use of mechanical ventilation is essential for physicians who intend to work in the areas of emergency and intensive care medicine. The objective of this review article is to explain in simplified form the initial concepts, indications and the general settings of mechanical ventilation.

Prevenção da doença pneumocócica invasiva em adultos / Prevention of invasive pneumococcal disease in adults

A prevenção da doença pneumocócica passa, obrigatoriamente, pela vacinação. As opções para adultos, no momento, são a vacina polissacarídica 23-valente (VPP23) e a vacina conjugada 13-valente (VPC13). As indicações e comparação de eficácia de cada uma delas é o objetivo desta revisão.

Prevention of the invasive pneumococcal disease relies mainly on immunization. The options for the adult population are the pneumococcal polysaccharide vaccine (PPSV23) and the pneumococcal conjugate vaccine (PCV). The indications and efficacy comparison of them are the goals of this review.