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)

Conservação de inimigos naturais (Insecta) em tomateiro orgânico / Conservation of natural enemies (Insecta) in the organic tomato crop

A adoção de práticas culturais como o consórcio de culturas e o tipo de irrigação podem beneficiar a comunidade de inimigos naturais no agroecossistema ao disponibilizar micro-habitas mais favoráveis e recursos alternativos, principalmente em períodos de baixa precipitação pluviométrica. O objetivo deste trabalho foi avaliar como o consórcio tomate + coentro e o tipo de irrigação (gotejamento e aspersão) podem beneficiar a comunidade de inimigos naturais no agroecossistema do tomateiro. O trabalho foi realizado no campo experimental da Embrapa Hortaliças, Gama, DF, de setembro a novembro de 2008. Os tomateiros foram plantados em monocultura ou consorciados com o coentro e irrigados por gotejamento e por aspersão (três repetições por tratamento), formando dois conjuntos de parcelas experimentais de acordo com o tipo de irrigação. A comunidade de inimigos naturais foi amostrada por observações diretas em 20 plantas de tomate por parcela e nas plantas de coentro sacudindo-se as plantas em cima de uma bandeja onde eram coletados os insetos. A abundância, riqueza e diversidade das espécies de inimigos naturais foram maiores nas parcelas cultivadas com coentro, independente do sistema de irrigação. Nas parcelas plantadas em monocultura foram encontradas mais espécies quando o tomateiro foi irrigado por aspersão. No entanto, a resposta de cada espécie de inimigo natural ou grupo de espécies foi distinta para o consórcio ou o tipo de irrigação. Portanto, em períodos de baixa precipitação, o consórcio tomate + coentro e a irrigação por aspersão podem favorecer a conservação de inimigos naturais no agroecossistema do tomateiro orgânico.

The adoption of cultural practices such as companion plants and the kind of irrigation system can benefit the community of natural enemies in the agroecosystem due to the increase of more favorable microhabitats available and as a source of alternative resources, mainly in periods of low precipitation. This study evaluated how the tomato + coriander intercrop and the kind of irrigation (drip and sprinkler) could benefit the community of natural enemies in the tomato agroecosystem. This work was carried out in the experimental field of Embrapa Hortaliças, Gama, DF, from September to November 2008. The tomatoes were planted in monoculture or with coriander (companion plant) and irrigated by drip and sprinkler irrigation (three replicates per treatment), forming two groups of experimental plots according to the kind of irrigation. The community of natural enemies was sampled by the direct observation of specimens on 20 tomatoes plants per plot and in the treatments. Coriander plants were shaken over a plastic tray for collection of insects. The abundance, richness and diversity of natural enemies were higher in tomato + coriander plots, regardless of the irrigation system. We observed more species of natural enemies in tomato monoculture plots when it was irrigated by sprinkler irrigation. However, the cultural practices adopted had a different effect on each species or group of species. Therefore, in periods of low precipitation, the tomato + coriander consortium associated with sprinkler irrigation can enhance the conservation of natural enemies in the organic tomato agroecosystem.

The missing ApoE allele.

The human apoE gene (APOE, GenBank accession AF261279) shows a common polymorphism, with the three epsilon2, epsilon3 and epsilon4 alleles resulting from the haplotypes of two C-->T SNPs. However, whereas the three common T-T, T-C and C-C haplotypes corresponding to the epsilon2, epsilon3 and epsilon4 alleles are well known, the last C-T haplotype (GenBank accession AY077451), encoding a fourth apoE allele, has rarely been reported. We detected this fourth allele in a Caucasian patient with motor neuron disease (MND). According to the literature we refer to this allele as epsilon3r. Although several explanations may be proposed for its formation, the existence of this fourth allele is consistent with the evolutionary hypothesis generally accepted for the apoE alleles. The rarity and physiological role of epsilon3r remains to be explained, and requires further investigation.

Alzheimer disease risk associated with APOE4 is modified by STH gene polymorphism.

The association of the STH gene polymorphism with Alzheimer disease (AD) is debated. In the analysis of two genetically and diagnostically distinct groups of Alzheimer patients from the USA and Italy, the authors did not find an association with the STH polymorphism. However, the APOE-4-associated risk of AD greatly increased if the STH-G allele was also present. The STH-G allele appears to be a risk modifier for AD.

Sensitive detection of transitional cell carcinoma of the bladder by microsatellite analysis of cells exfoliated in urine.

Transitional cell carcinoma (TCC) is the most common bladder tumor. Urine cytology can identify most high-grade tumors but sensitivity is lower if one includes lesions of all grades. Microsatellite marker alterations have been found in many tumor types including bladder cancer and have been used to detect cancer cells in body fluids including urine. The aim of our study is to further evaluate feasibility and sensitivity of microsatellite analysis to detect bladder cancer cells in urine. We studied 55 individuals: 21 with symptoms suggestive of bladder cancer, 23 patients with previous history of TCC and 11 healthy subjects. Genomic DNA was extracted from blood lymphocytes, urine sediment, bladder washings and tumor or normal bladder mucosa. Twenty highly informative microsatellite markers were analyzed for loss of heterozigosity (LOH) and microsatellite instability (MIN) by polymerase chain reaction. Microsatellite analysis of urine identified 33 of 34 (97%) patients with either primary or tumor recurrence, whereas urine cytology identified 27 of 34 (79%) patients (p = 0.0001). Detection of microsatellite abnormalities improved the sensitivity of detecting low-grade and/or stage bladder tumor: from 75-95% for grades G1-G2 and from 75-100% for pTis-pTa tumors. Bladder washings from 25 patients were also analyzed, and in all cases results were identical to those obtained from voided urine. None of the 16 patients without evidence of TCC showed LOH and/or MIN in urine samples or bladder washings. Interestingly, in a patient with persistent bladder mucosa abnormalities, microsatellite alterations were demonstrated 8 months before the histopathologic diagnosis of tumor recurrence. These results further indicate that microsatellite marker analysis is more sensitive than conventional urine cytology in detecting bladder cancer cells in urine and represents a potential clinical tool for monitoring patients with low-grade/stage TCC.

Ext-mutation analysis in Italian sporadic and hereditary osteochondromas.

Osteochondromas represent the largest group of benign tumors of bone. Multiple osteochondromatosis or hereditary multiple exostoses (EXT) is an autosomal dominant inherited disorder characterized by the presence of multiple benign cartilage-capped exostoses. EXT is genetically heterogeneous with at least 3 chromosomal loci: EXT1 (8q24.1), EXT2 (11p11-p13), and EXT3 (19p). In <5% of EXT patients, the inactivation of both copies of EXT alleles (LOH) is associated with malignant transformation. We have analyzed the EXT1 and EXT2 genes in 9 unrelated EXT families and in a patient with a sporadic osteochondroma, all originating from Italy. Four families show an EXT1 mutation, consisting of a small deletion in 3 of them and a small insertion in the 4th. All these mutations lead to premature termination of translation and thus a truncated EXT1 protein. Three families presented EXT2 mutations consisting of nucleotide substitutions leading to alterations of the third intron splice-site, to an amino acid substitution and to a nonsense mutation. All these mutations cosegregate with the disease phenotype. The sporadic osteochondroma patient carried a novel missense mutation in exon 11 of EXT2 gene, leading to an amino acid substitution. Seven of these mutations have never been described before. EXT2 missense mutations were also confirmed by amino acids conservation between human and mouse and by analysis of a healthy control population. In conclusion, our study provide further evidence that loss of function of the EXT1 or EXT2 gene is the main cause of EXT supporting the putative tumor-suppressor function of these genes.

The Apolipoprotein E genotype in patients affected by syndromes with focal cortical atrophy.

The role of the Apolipoprotein E (APOE) alleles in syndromes associated with focal cerebral atrophy (fronto-temporal dementia, primary progressive aphasia, corticobasal degeneration) is still controversial. We studied the APOE allele distribution in 39 patients with clinically diagnosed syndromes associated with focal cerebral atrophy (FCA), in 50 patients with early-onset probable Alzheimer's disease (EOAD), and in 60 patients with late-onset probable AD (LOAD). The APOE genotype was determined from a blood sample, using polymerase chain reaction and restriction enzyme digestion. The APOE epsilon4 allele frequency was significantly higher in the EOAD (21.0%) and LOAD (33.3%) groups, but not in the FCA group (5.1%), as compared with controls. In our population, the epsilon2 allele frequency was significantly higher in patients with FCA (12.8%) than in controls (4.8%). These results show that the APOE epsilon4 allele is not a risk factor for syndromes associated with FCA. The potential role of the epsilon2 allele in these syndromes needs further investigation.

Apolipoprotein E genotype in sporadic early- and late-onset Alzheimer's disease.

The 84 isoform of apolipoprotein E (ApoE) has been proposed as a risk factor for Alzheimer's disease (AD), while the possible role of the epsilon2 allele in AD is controversial. We have studied the ApoE genotype in 38 patients with early-onset AD (EOAD) and in 43 patients with late-onset AD (LOAD). In the EOAD group we observed a significant increase of epsilon4 allele frequency as compared with normal controls, while there was a more than 3-fold decrease of epsilon2 allele frequency that did not reach statistical significance. In the LOAD group we found a highly significant increase of epsilon4 allele frequency as compared with normal controls, while there was a significant decrease of epsilon2 allele frequency. In both the EOAD and LOAD groups, no significant difference was observed between epsilon4 carriers and epsilon4 noncarriers as for age at disease onset, disease duration, and Mini-Mental State score at observation. However, in both EOAD and LOAD groups a statistical trend towards a longer disease duration was observed in epsilon4 carriers. In both the EOAD and LOAD groups, disease severity was compared in epsilon4 carriers versus epsilon4 noncarriers by means of analyses of covariance, with disease duration as covariate. No significant difference between epsilon4 carriers and epsilon4 noncarriers was observed in both EOAD and LOAD. The results of the present study confirm that epsilon4 allele seems to be associated with an increased risk for sporadic AD, while the significant decrease of epsilon2 allele frequency in the LOAD group supports the hypothesis of a possible protective role of epsilon2 allele in AD.

Prevalence of apolipoprotein E alleles in healthy subjects and survivors of ischemic stroke: an Italian Case-Control Study.

BACKGROUND AND PURPOSE: The epsilon4 allele of the apolipoprotein E (apoE) has been related to the occurrence of myocardial infarction, but its association with ischemic stroke is controversial. We have evaluated the relation between apoE alleles and the occurrence of cerebrovascular ischemia. METHODS: The apoE epsilon genotypes of 100 patients with a documented history of ischemic stroke without clinically apparent dementia (stroke+) and 108 subjects without such history (stroke-) were determined. The relative frequency of the apoE alleles and genotypes was estimated in 398 healthy subjects aged < 40 years from the same ethnic background. RESULTS: The frequency of the apoE epsilon4 allele in stroke+ (0.18 [95% CI, 0.12 to 0.25]) was higher than in stroke- (0.07 [95% CI, 0.03 to 0.12]; P<.001) or in healthy subjects (0.09 [95% CI, 0.07 to 0.12]; P<.001). Carriers of the epsilon4 allele differed between stroke+ (0.30 [95% CI, 0.19 to 0.42]) and stroke- (0.12 [95% CI, 0.5 to 0.22]; P=.004) or healthy subjects (0.16 [95% CI; 0.12 to 0.22]; P=.015). Accordingly, epsilon3/epsilon3 homozygotes were less frequent in stroke+ (0.59 [95% CI, 0.45 to 0.71]) than in stroke- (0.72 [95% CI, 0.59 to 0.82]; P=.063) or in healthy subjects (0.73 [95% CI, 0.67 to 0.78]; P=.01). In a multiple logistic regression analysis, age (P<.03), positive family history (P<.04) and apoE (P<.002) independently contributed to a stroke history, with epsilon4 carriers exhibiting a higher estimated risk (odds ratio, 5.05). CONCLUSIONS: Our data show an association between apoE gene and a personal history of ischemic stroke and support the possibility that the apoE gene is a susceptibility locus for the risk of cerebrovascular ischemic disease.