Evaluación de la infección por Strongyloides stercoralis en pacientes con HTLV-1

Introduction: Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis (S. stercoralis) infection with low therapeutic response. Objective: To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1, who were seen at a Reference Center for HTLV-1 (CHTLV), in Salvador, Bahia, Brazil. Materials and methods: This was a cross-sectional study conducted with 178 HTLV-1-infected individuals, treated at the HTLV specialized center between January 2014 and December 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed by an in house Enzyme Lynked-Immunosorbent Assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot. Results: The frequency of S. stercoralis infection was 3.4% (6/178). Moreover, individuals infected with S. stercoralis from rural area (50.0%; 3/6), also showed S. stercoralis hyperinfection (> 3,000 larvae/gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178). Conclusions: HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.Introducción. Los individuos infectados por el virus linfotrópico T humano tipo 1 (HTLV-1) pueden presentar formas graves y diseminadas de infección por Strongyloides stercoralis (S. stercoralis) con baja respuesta terapéutica. Objetivo. Investigar la infección por S. stercoralis y la seroprevalencia de IgG anti-S. stercoralis en individuos infectados por HTLV-1, que fueron atendidos en un Centro de Referencia para HTLV-1 (CHTLV), en Salvador, Bahía, Brasil. Materiales y métodos. Estudio transversal realizado con 178 individuos infectados por HTLV-1, atendidos en el centro especializado de HTLV entre enero de 2014 y diciembre de 2018. El diagnóstico parasitológico de S. stercoralis se realizó mediante métodos de Hoffman, Pons y Janer, cultivo en placa de agar y Baermann-Morais. La detección de IgG anti-S. stercoralis se realizó mediante un ensayo de inmunoabsorción enzimática (ELISA) casero. La infección por HTLV-1 se diagnosticó usando un ELISA comercial y se confirmó mediante transferencia Western. Resultados. La frecuencia de infección por S. stercoralis fue del 3,4% (6/178). Además, los individuos infectados por S. stercoralis de la zona rural (50,0%; 3/6) también mostraron hiperinfección por S. stercoralis (> 3.000 larvas / gramo de heces). La frecuencia de anticuerpos IgG anti-S. stercoralis fue del 20,8% (37/178). Conclusiones. las personas infectadas por HTLV-1 que viven en condiciones sanitarias precarias son más propensas a desarrollar formas graves de infección por S. stercoralis. Teniendo en cuenta la alta susceptibilidad y el resultado desfavorable de la infección en estos individuos, se debe considerar el diagnóstico serológico de S. stercoralis para administrar el tratamiento

Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit

ObjectivesTo assess the ABC2-SPH score in predicting COVID-19 in-hospital mortality, during intensive care unit (ICU) admission, and to compare its performance with other scores (SOFA, SAPS-3, NEWS2, 4C Mortality Score, SOARS, CURB-65, modified CHA2DS2-VASc, and a novel severity score).Materials and methodsConsecutive patients (≥ 18 years) with laboratory-confirmed COVID-19 admitted to ICUs of 25 hospitals, located in 17 Brazilian cities, from October 2020 to March 2022, were included. Overall performance of the scores was evaluated using the Brier score. ABC2-SPH was used as the reference score, and comparisons between ABC2-SPH and the other scores were performed by using the Bonferroni method of correction. The primary outcome was in-hospital mortality.ResultsABC2-SPH had an area under the curve of 0.716 (95% CI 0.693–0.738), significantly higher than CURB-65, SOFA, NEWS2, SOARS, and modified CHA2DS2-VASc scores. There was no statistically significant difference between ABC2-SPH and SAPS-3, 4C Mortality Score, and the novel severity score.ConclusionABC2-SPH was superior to other risk scores, but it still did not demonstrate an excellent predictive ability for mortality in critically ill COVID-19 patients. Our results indicate the need to develop a new score, for this subset of patients

MLL2/KMT2D and MLL3/KMT2C expression correlates with disease progression and response to imatinib mesylate in chronic myeloid leukemia

Abstract Background Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm whose pathogenesis is linked to the Philadelphia chromosome presence that generates the BCR–ABL1 fusion oncogene. Tyrosine kinase inhibitors (TKI) such as imatinib mesylate (IM) dramatically improved the treatment efficiency and survival of CML patients by targeting BCR–ABL tyrosine kinase. The disease shows three distinct clinical-laboratory stages: chronic phase, accelerated phase and blast crisis. Although patients in the chronic phase respond well to treatment, patients in the accelerated phase or blast crisis usually show therapy resistance and CML relapse. It is crucial, therefore, to identify biomarkers to predict CML genetic evolution and resistance to TKI therapy, considering not only the effects of genetic aberrations but also the role of epigenetic alterations during the disease. Although dysregulations in epigenetic modulators such as histone methyltrasnferases have already been described for some hematologic malignancies, to date very limited data is available for CML, especially when considering the lysine methyltransferase MLL2/KMT2D and MLL3/KMT2C. Methods Here we investigated the expression profile of both genes in CML patients in different stages of the disease, in patients showing different responses to therapy with IM and in non-neoplastic control samples. Imatinib sensitive and resistant CML cell lines were also used to investigate whether treatment with other tyrosine kinase inhibitors interfered in their expression. Results In patients, both methyltransferases were either upregulated or with basal expression level during the chronic phase compared to controls. Interestingly, MLL3/KMT2C and specially MLL2/KMT2D levels decreased during disease progression correlating with distinct clinical stages. Furthermore, MLL2/KMT2D was decreased in patients resistant to IM treatment. A rescue in the expression of both MLL genes was observed in KCL22S, a CML cell line sensitive to IM, after treatment with dasatinib or nilotinib which was associated with a higher rate of apoptosis, an enhanced expression of p21 (CDKN1A) and a concomitant decrease in the expression of CDK2, CDK4 and Cyclin B1 (CCNB1) in comparison to untreated KCL22S control or IM resistant KCL22R cell line, which suggests involvement of p53 regulated pathway. Conclusion Our results established a new association between MLL2/KMT2D and MLL3/KMT2C genes with CML and suggest that MLL2/KMT2D is associated with disease evolution and may be a potential marker to predict the development of therapy resistance

Prevalence of excessive daytime sleepiness in Brazilian community-dwelling older adults with very low levels of schooling, and its association with sociodemographic characteristics and lifestyle: the Bambuí Health and Ageing Study (BHAS) Prevalência de sonolência diurna excessiva em uma comunidade brasileira de idosos com baixa escolaridade e sua associação com características sociodemográficos e estilos de vida: Projeto Saúde e Envelhecimento Bambuí

OBJECTIVE: Population-based studies on excessive daytime sleepiness (EDS) in older adults living in less developed countries are scarce. The purpose of this paper was to estimate the prevalence of EDS and its association with sociodemographic characteristics and lifestyle factors in Brazilian community-dwelling older adults. METHODS: The study was carried out in Bambuí, a city in the state of Minas Gerais, Brazil. EDS was defined as the presence of sleepiness in the last month occurring three or more times per week, with any interference in usual activities. The exploratory variables were: gender, age, skin color, marital status, schooling level, current employment status, religion, recent migration, smoking, binge drinking and physical activities during leisure time. RESULTS: Of 1,742 residents aged > 60 years, 1,514 (86.9%) participated. The prevalence of EDS was 13%. After adjustment for confounders, female gender and low schooling level remained positively and independently associated with EDS. CONCLUSIONS: The prevalence of EDS in the study population was within the range observed in studies carried out in developed countries. The most impressive finding was the association of EDS with schooling, indicating that even in a population with low levels of schooling, this was an important factor to explain the distribution of EDS.<br>OBJETIVO: Estudos populacionais sobre sonolência diurna excessiva (SDE) em idosos conduzidos em países em desenvolvimento são escassos. A proposta do presente trabalho é estimar a prevalência de SDE e sua associação com características sociodemográficas e estilo de vida em idosos residentes em uma cidade brasileira. MÉTODOS: Este estudo foi conduzido na cidade de Bambuí, localizada no Estado de Minas Gerais. SDE foi definida como presença de sonolência no último mês ocorrendo pelo menos três vezes por semana, com prejuízo das atividades. As variáveis exploratórias foram sexo, idade, cor da pele, estado civil, escolaridade, ocupação, religião, migração recente, tabagismo, uso excessivo de álcool e prática de atividade física. RESULTADOS: Entre os 1.742 residentes com 60 anos ou mais, 1.514 (86,9%) participaram. A prevalência de SDE foi 13%. Após ajustamento por fatores de confusão, sexo feminino e menor escolaridade permaneceram positivamente associadas à SDE. CONCLUSÕES: A prevalência de SDE na população do estudo encontra-se dentro da faixa observada em estudos conduzidos em países desenvolvidos. Um achado relevante foi a associação de SDE com escolaridade, indicando que mesmo em uma população de menor nível de escolaridade, este é um fator importante na distribuição de SDE