Importância da avaliação geriátrica ampla na decisão do tratamento da estenose aórtica grave / Importance of broad geriatric assessment in deciding treatment of severe aortic stenosis

INTRODUÇÃO: A Estenose Aórtica (EAo) é extremamente prevalente em idosos e, quando sintomática, influencia de forma significativa na qualidade e expectativa de vida. Decidir entre o tratamento clínico, percutâneo ou cirúrgico é uma árdua tarefa e deve valorizar, não apenas os aspectos cardiológicos, mas todo o contexto do idoso. O objetivo deste estudo foi utilizar a Avaliação Geriátrica Ampla (AGA) como ferramenta para decisão do tratamento de idosos portadores de EAo Grave Sintomática. MÉTODOS: Selecionados pacientes acima de 75 anos atendidos em ambulatório específico de hospital terciário de São Paulo-SP, de outubro de 2018 a janeiro de 2019, com EAo Grave (área valvar <0,8cm² e gradiente sistólico médio >40mmHg) e sintomas de angina, síncope, dispneia ou sinais de insuficiência cardíaca congestiva. A AGA englobava aspectos da Funcionalidade (Katz e Lawton), Fragilidade (FRAIL), Cognição (Mini-exame do estado mental, teste do relógio, fluência verbal), Depressão (Escala de Depressão Geriátrica) e Estado Nutricional/Sarcopenia (força de preensão palmar, circunferência de panturrilha e velocidade da marcha). Baseados nesta avaliação, integrantes do heart team (clínicos, hemodinamicistas, ecocardiografistas e cirurgiões) se reuniam e chegavam ao consenso de qual tratamento indicar. Estudo observacional, prospectivo, descritivo e aprovado pelo comitê de ética. A estratificação do risco cirúrgico foi feita pelo EuroSCORE II. As variáveis quantitativas foram apresentadas em forma de média e desvio padrão. RESULTADOS: Dos 10 pacientes portadores de EAo Grave Sintomática avaliados, a média de idade foi 83,8 anos (±3,7), sendo 55% homens. Quanto à funcionalidade, 70% eram parcialmente dependentes para atividades diárias; 30% frágeis, 40% tinham humor deprimido, 70% apresentavam boa cognição (de acordo com a escolaridade) e 20% arcopenia e risco de desnutrição. Nos pacientes com EuroSCORE II de alto risco, 20% também apresentavam fragilidade, sendo mantidos em tratamento clínico. Os classificados como risco baixo a intermediário não apresentavam fragilidade associada e foram submetidos à troca valvar aórtica, via aberta ou transcateter (TAVR). CONCLUSÃO: Os achados da AGA, somados aos aspectos clínicos e ecocardiográficos habitualmente utilizados na cardiologia atual, constituem ferramenta importante para a decisão terapêutica em idosos portadores de EAo Grave e Sintomática. (AU)

Growth and metabolism of Oenococcus oeni for malolactic fermentation under pressure.

Malolactic fermentation is a biological deacidification process of wine, characterized by the transformation of l-malic acid to l-lactic acid and CO2 . Oenococcus oeni is able to perform malolactic fermentation and to survive under wine harsh conditions, representing great interest for wine industry. The aim of this work was to evaluate the effect of high pressure on the metabolism of O. oeni growing in culture media, regarding malolactic fermentation, sugars metabolism and bacterial growth. A pressure stress of 50 MPa during 8 h did not result in significant modifications in bacterial metabolism. In contrast, a stress of 100 MPa during 8 h resulted in lower amounts of l-lactic acid, while higher amounts of d-lactic acid were also registered, indicating changes in bacterial metabolism. A pressure stress of 0·5 MPa during 300 h resulted in complete inactivation of O. oeni, but malolactic fermentation was still observed at some extent, showing that malolactic enzyme was not completely inactivated at these conditions. It was concluded that high pressure causes modification of O. oeni metabolism, and possibly in enzyme activities. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that high pressure affects the viability and metabolism of Oenococcus oeni on a culture medium, depending on the pressure intensity and holding time applied. These effects were particularly noteworthy on malolactic fermentation. After high pressure (HP)-stress of 100 MPa for 8 h, modifications in the activity of malolactic enzyme were detected, possibly due to a change in specificity. After a HP-stress of 300 MPa for 0·5 h, malolactic enzyme showed some residual activity, although O. oeni was completely inactivated. This study provides relevant information about the impact of high pressure on malolactic fermentation, opening interesting possibilities to the improvement of biocatalytic processes.

New strategies against prostate cancer--Pt(II)-based chemotherapy.

Prostate cancer is the second most common cancer worldwide and the sixth cause of cancer-related death in men. When hormone therapy fails to control tumour growth, castration-resistant prostate cancer (CRPC) occurs and chemotherapy drugs must be administered. Since 2004, docetaxel administration is the standard of care in metastatic CRPC, although it presents severe limitations such as acquired resistance and poor prognosis. An analogue (cabazitaxel) was approved by the FDA in 2010 as a second-line chemotherapeutic agent. Novel immuno- and hormonal therapy agents, as well as tumour vaccines, have been recently developed, but new strategies are still needed for effectively handling this type of neoplasia. Platinum compounds, in particular, have been the object of a growing interest, despite the former belief that they should have modest activity against prostate cancer. Compounds such as carboplatin, oxaliplatin or satraplatin, either alone or in combination, have lately shown promising results. In order to overcome the deleterious side-effects usually associated to these metal-based agents, several approaches have been followed with a view to optimise drug delivery and targeting, some of which showed considerable success in CRPC. Platinum drugs may therefore have an important role in the chemotherapeutic management of human metastatic castration-resistant prostate cancer, mostly in second-line strategies. The present review addresses the most relevant studies on platinum-based antineoplastic agents towards CRPC in the last decade--from first--and second-generation complexes to newly developed compounds.

Development and validation of a methodology to qualitatively screening veterinary drugs in porcine muscle via an innovative extraction/clean-up procedure and LC-MS/MS analysis.

A qualitative multiresidue method that facilitates rapid monitoring of veterinary drugs in porcine muscle is described. The method comprises the application of an innovative extraction/clean-up procedure, namely liquid-liquid extraction with partition at very low temperature (LLE-FPVLT), and analysis by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Besides the high selectivity, sensitivity and specificity, this high-throughput method proved to be quite general as 34 veterinary drugs (from six distinct classes: tetracyclines, sulfonamides, penicillins, quinolones, macrolides and benzimidazoles) could be successfully detected. The whole screening procedure was validated according to the directives from European Commission Decision 2002/657/EC and guidelines for the validation of screening methods. Acceptable values for the evaluation parameters were achieved for all analytes (except for ampicillin, clindamycin and erythromycin). Finally, these very promising results have strengthened the possibility of inclusion of such a methodology as an integral part of the National Residue Control Plan scope of the Ministry of Agriculture, Livestock and Food Supply of Brazil.

Spontaneous cell proliferation is associated with poor sensitivity to glucocorticoids in patients infected with HTLV.

BACKGROUND: Human T-cell lymphotropic viruses (HTLV)-I/II have a special tropism for infecting T cells and inducing spontaneous lymphocyte proliferation. Leukaemia and neurological manifestations are associated with HTLV-I/II infections, and treatment is usually based on anti-inflammatory drugs including glucocorticoids. Although steroid resistance has been reported, it is unknown whether this condition is related to the infection itself or to the treatment. OBJECTIVE: We investigated whether spontaneous cell proliferation is associated with T-cell sensitivity to glucocorticoids. MATERIALS AND METHODS: Twenty-eight HTLV-I/II patients and 11 healthy age-matched controls took part in this study. Lymphocytes were isolated and cultured in vitro to measure spontaneous and mitogen-induced proliferation as well as cellular sensitivity to dexamethasone. RESULTS: Patients with HTLV-I/II infection showed similar stimulated and unstimulated T-cell proliferation as well as comparable sensitivity to dexamethasone in vitro. There were no group differences in the frequency of glucocorticoid responders versus non-responders. However, T cells of patients with spontaneous proliferation were unresponsive to mitogenic stimulation and were remarkably more resistant to dexamethasone than cells of patients with normal proliferation. CONCLUSION: These data suggest that the poor clinical response to steroids may be associated with spontaneous cell proliferation during HTLV infection.

[Frequency of digestive symptoms in Brazilian patients with Diabetes Mellitus]. / Freqüência de sintomas digestivos em pacientes brasileiros com Diabetes Mellitus.

PURPOSE: To determine the frequencies of digestive symptoms in an unselected sample of Brazilian diabetics, in comparison to those verified in the general population. METHODS: The frequencies of 13 digestive symptoms were determined in 153 type 1 and type 2 diabetics and in 50 apparently healthy controls, utilizing a structured, standardized questionnaire. RESULTS: The percentage of diabetics with at least one symptom was significantly higher than in controls (70% vs 36%, p = 0.01). Higher frequencies of upper digestive symptoms, such as postprandial epigastric fullness (30% vs 35%), heartburn (30% vs 34%), as well as constipation (17% vs 12%) were observed in both groups. Nevertheless, only the prevalence of dysphagia (13% vs 2%) was significantly increased (p = 0.02) in diabetics. CONCLUSION: These findings indicate that gastrointestinal symptoms are common in diabetics, but this seems also to be the case in the general population, with the exception of dysphagia. The frequencies of symptoms observed in Brazil were similar to those reported in studies from the North Hemisphere, a finding that does not support the hypothesis that external factors may influence the prevalence of gastrointestinal symptoms in diabetics.

Freqüência de sintomas digestivos em pacientes brasileiros com Diabetes Mellitus / Digestive symptoms in Brazilian patients with Diabetes Mellitus

Sintomas sugestivos do comprometimento do tubo digestivo säo comuns em pacientes diabéticos, mas estudos comparando as freqüências destes sintomas com as da populaçäo geral säo escassos e näo existem trabalhos dessa natureza com diabéticos brasileiros. OBJETIVO: Determinar as freqüências de diferentes sintomas digestivos em amostra näo selecionada de pacientes diabéticos, em comparaçäo às encontradas em pessoas da comunidade. MÉTODOS: A ocorrência de 13 diferentes sintomas digestivos foi investigada por meio da aplicaçäo de um questionário padronizado, especificamente estruturado, em 153 diabéticos dos tipos 1 e 2 e em 50 pessoas aparentemente sadias, tomadas como controles. RESULTADOS: A freqüência de diabéticos com pelo menos um sintoma digestivo foi significativamente superior à verificada no grupo controle (70 por cento vs 36 por cento, p = 0,01). Freqüências elevadas de plenitude gástrica (30 por cento vs 36 por cento), pirose (30 por cento vs 34 por cento) e de constipaçäo (17 por cento vs 12 por cento), foram observadas tanto entre os diabéticos como nos controles. No entanto, somente a freqüência de um único sintoma, a disfagia, foi significativamente maior entre os diabéticos, em relaçäo ao grupo controle (13 por cento vs 2 por cento, p = 0,02). CONCLUSÄO: Estes resultados indicam que a freqüência de sintomas digestivos em diabéticos, apesar de elevada, näo difere da verificada na populaçäo geral, exceto para a disfagia. As freqüências dos diferentes sintomas estiveram próximas das faixas relatadas em estudos do hemisfério Norte, o que näo apóia a hipótese de que fatores inerentes ao meio afetam a ocorrência de queixas digestivas em diabéticos.