Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009), whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut-microbiota interactions and in mediating fibrosis. Understanding the effects of several drugs associated with multidrug resistance 1 gene variants may aid in the selection of customized therapeutic regimens

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Mutações no gene TP53 em tumores malignos de mama: associação com fatores de risco e características clínico-patológicas, inclusive risco de óbito, em pacientes residentes no Rio de Janeiro TP53 mutation in malignant breast tumors: association with risk factors and clinical-pathological characteristics, including risk of death, in patients from Rio de Janeiro

No Brasil, o câncer de mama é a primeira causa de óbito por câncer entre mulheres, sendo o Rio de Janeiro o Estado que apresenta o maior coeficiente de mortalidade do país. Estudos que avaliam a sobrevida por câncer de mama têm indicado que vários fatores de ordem genética e molecular podem influenciar a evolução dos casos. O objetivo deste trabalho foi descrever mutações no gene TP53 em 120 pacientes com diagnóstico de carcinoma invasivo de mama, recrutadas no Instituto Nacional de Câncer (INCA), Rio de Janeiro, entre 1995 a 1997, e analisar as possíveis associações entre fatores de risco e presença de mutação e entre características do tumor, incluindo estas mutações e o risco de óbito. A análise molecular detectou 24 mutações no gene TP53 em 22 casos (18,3%), sendo que 2 casos apresentaram 2 mutações cada e, em um caso observamos o polimorfismo no éxon 6. As mutações encontradas eram: 14 com troca de sentido; 2 sem sentido; 2 silenciosas; 2 deleções; 1 inserção e 3 localizadas em íntron. Em relação aos fatores de risco estudados em associação à presença de mutação, observou-se que apenas o consumo de tabaco mostrou associação negativa (OR ajustado= 0,24 (0,06-0,88)). A análise multivariada utilizada para avaliar as características tumorais associadas ao risco de óbito mostrou que apenas a agressividade do tumor apresentou OR indicativo de risco (3,98, IC 95% 1,25-12,72). Estes resultados corroboram outros estudos que mostram que a mutação no gene TP53 pode ser um indicador de tumores de mama biologicamente mais agressivos, apesar de não ser o único parâmetro a ser considerado.<br>Breast cancer is the leading cause of death due to cancer among women in Brazil and, the State of Rio de Janeiro presents the highest mortality coefficient of this disease in the country. Studies have shown that many genetic and molecular factors may be related to the outcome of cases. The aim of this study was to describe the frequency and types of mutations in the tumor suppressor gene TP53 in 120 patients with diagnosis of invasive breast carcinoma recruited from the Instituto Nacional de Câncer (INCA), Rio de Janeiro from1995 to 1997, and to analyze the associations between these mutations and risk factors, and tumor characteristics, including the presence of TP53 mutations, and risk of death. The molecular analysis detected TP53 alterations in 22 cases (18.3%), of which 2 cases presented 2 mutations each; a polymorphism in exon 6 was observed in 1 case. The mutations found were: 14 missense, 2 nonsense, 2 silent, 2 deletions, 1 insertion and 3 located in introns which probably did not change the protein. The analysis of risk factors in relation to TP53 mutations showed that only tobacco consumption had an association (adjusted OR = 0.24 (0.06-0.88)). Multivariate analysis showed that only tumor aggressiveness showed an OR indicative of risk (3.98, IC 95% 1.25-12.72).These results are in agreement with previous studies, which report that the presence of TP53 mutations may indicate more aggressive breast tumors biologically although this is not the only parameter to be considered