Influence of treatment access on survival of metastatic renal cell carcinoma in brazilian cancer center

ABSTRACT Background: Tyrosine kinase inhibitors (TKI) and immunotherapy improved survival in metastatic renal cell carcinoma (mRCC). Disparities in treatment access are present in healthcare systems globally. The aim of this study was to analyze survival outcomes of mRCC patients treated with first-line TKIs in the public (PHS) and private (PrS) health system in a Brazilian Cancer Center. Materials and Methods: Records from all mRCC patients treated with first-line TKIs from 2007-2018 were reviewed retrospectively. Categorial variables were compared by Fisher's exact test. Survival was estimated by Kaplan-Maier method and survival curves were compared using the log-rank test. Prognostic factors were adjusted by Cox regression model. Results: Of the 171 eligible patients, 37 (21.6%) were PHS patients and 134 (78.4%) were PrS patients. There were no difference in age, gender, or sites of metastasis. PHS patients had worse performance status (ECOG ≥2, 35.1% vs. 13.5%, p=0.007), poorer risk score (IMDC poor risk, 32.4% vs. 16.4%, p=0.09), and less nephrectomies (73% vs. 92.5%, p=0.003) than PrS patients. Median lines of therapy was one for PHS versus two for PrS patients (p=0.03). Median overall survival (OS) was 16.5 versus 26.5 months (p=0.002) and progression-free survival (PFS), 8.4 versus 11 months (p=0.01) for PHS and PrS patients, respectively. After adjusting for known prognostic factors on multivariate analysis, PHS patients still had a higher risk of death (HR: 1.61, 95% CI: 1.01-2.56, p=0.047). Conclusion: Patients with mRCC treated via the PHS had worse overall survival, possibly due to poorer prognosis at presentation and less drug access.

Máscaras de tecido em locais públicos: intervenção essencial na prevenção da COVID-19 no Brasil / Cloth masks in public places: an essential intervention to prevent COVID-19 in Brazil

Resumo Acumulam-se evidências de que o uso de máscaras é uma medida indispensável de proteção à COVID-19, devido ao alto poder de transmissão do novo coronavírus por via respiratória, inclusive por indivíduos assintomáticos. Por sua vez, o uso das máscaras de tecido em locais públicos tem se consolidado como medida adicional de proteção às medidas de distanciamento social e higienização das mãos. Objetivou-se sistematizar as evidências científicas que justificam o amplo uso de máscaras de tecido como prevenção à COVID-19 e descrever a evolução dos posicionamentos contrários ou favoráveis ao seu uso em ambientes extradomiciliares, diante do avanço da pandemia do novo coronavírus pelo mundo. A triagem de artigos e documentos oficiais do Brasil e de outros países indica que o uso de máscaras em locais públicos tornou-se uma intervenção essencial graças ao potencial de reduzir a velocidade de propagação do novo coronavírus. Recomenda-se que o poder público adote estratégias para aumentar a oferta deste produto e fomente estudos para avaliação do impacto da medida no controle da pandemia no Brasil. É imperativo assegurar disponibilidade de máscaras a grupos socioeconomicamente desfavorecidos e garantir que determinados grupos raciais não sejam estigmatizados diante do uso de máscaras em ambientes extradomiciliares.

Abstract There is increasing evidence that the use of masks is an indispensable protective measure against COVID-19, given the high transmissibility of the new coronavirus through the respiratory system, including by asymptomatic individuals. The use of cloth masks in public places has been established as a protective measure to be adopted alongside social distancing and hand hygiene. This narrative review aims to systematize the scientific evidence that informs the widespread use of cloth masks as a preventive measure against COVID-19 and to describe the evolution of positions contrary to or in favor of its use outside the home, in view of the advance of the new coronavirus pandemic globally. The scientific articles, technical notes, governmental decrees and other documents analyzed indicate that widespread use of masks has the potential to reduce the spread of the new coronavirus. We recommend that the Brazilian government adopt strategies to increase the supply of reusable cloth masks to the public, especially to vulnerable populations and to support studies on the impact of this measure to control the pandemic in the country. Finally, it is imperative to ensure that use of masks does not exacerbate stigmatization of racial groups that already face prejudice.

Characterisation of alternative expression vectors for recombinant Bacillus Calmette-Guérin as live bacterial delivery systems

BACKGROUND Bacillus Calmette-Guérin (BCG) is considered a promising live bacterial delivery system. However, several proposals for rBCG vaccines have not progressed, mainly due to the limitations of the available expression systems. OBJECTIVES To obtain a set of mycobacterial vectors using a range of promoters with different strengths based on a standard backbone, previously shown to be stable. METHODS Mycobacterial expression vectors based on the pLA71 vector as backbone, were obtained inserting different promoters (PAN, PαAg, PHsp60, PBlaF* and PL5) and the green fluorescence protein (GFP) as reporter gene, to evaluate features such as their relative strengths, and the in vitro (inside macrophages) and in vivo stability. FINDINGS The relative fluorescence observed with the different vectors showed increasing strength of the promoters: PAN was the weakest in both Mycobacterium smegmatis and BCG and PBlaF* was higher than PHsp60 in BCG. The relative fluorescence observed in a macrophage cell line showed that PBlaF* and PHsp60 were comparable. It was not possible to obtain strains transformed with the extrachromosomal expression vector containing the PL5 in either species. MAIN CONCLUSION We have obtained a set of potentially stable mycobacterial vectors with a arrange of expression levels, to be used in the development of rBCG vaccines.

Rheumatic hand's clinical, functional and imagiological correlations following metacarpophalangeal joint silicone arthroplasty / Correlações clínicas, funcionais e imagiológicas após artroplastia da articulação metacarpofalangiana com implante de silicone na mão reumatoide

ABSTRACT Objective: Evaluation of rheumatoid hand-associated metacarpophalangeal joint silicone arthroplasty most often relies on functional scores alone. This study aimed to understand the correlation between perceived and observed function, strength, and alignment. Methods: Cross-sectional study including all 11 women (15 hands) submitted to second to fifth metacarpophalangeal joint arthroplasty due to rheumatoid arthritis involvement for a time period of seven years. Measurements relied on the Michigan Hand Outcomes Questionnaire, Lafayette Purdue Pegboard, pinch and grip strength, and analysis of a lateral "OK-sign" X-ray view. Correlation analysis used Spearman's coefficient, assuming statistical significance for p-values < 0.05. Results: Objective function was strongly correlated with all other variables (p < 0.05), while perceived function failed to correlate with articular alignment in both measurements (p = 0.240 and p = 0.354). Strength and alignment were also strongly correlated (p < 0.05). Conclusions: Most measurements strongly correlate with each other, with emphasis on objective dexterity measurement.

RESUMO Objetivo: Na maioria das vezes, a avaliação da artroplastia da articulação metacarpofalangeana com implante de silicone é feita apenas por meio de escores funcionais. Este estudo teve como objetivo compreender a correlação entre função, força e alinhamento percebidos e observados. Métodos: Este estudo transversal incluiu todas as 11 mulheres (15 mãos) submetidas à artroplastia metacarpofalangeana no segundo ao quinto dedo devido a artrite reumatoide em um período de sete anos. As medições basearam-se no Michigan Hand Outcomes Questionnaire, no Lafayette Purdue Pegboard e nas forças de pinça e preensão, além da análise de radiografia da mão em leque. O coeficiente de Spearman foi usado para avaliar a correlação; valores de p < 0,05 foram considerados estatisticamente significantes. Resultados: A função objetiva foi fortemente correlacionada a todas as outras variáveis (p < 0,05). Por outro lado, a função percebida não foi correlacionada ao alinhamento articular em ambas as medições (p = 0,240 e p = 0,354). A força e o alinhamento também estiveram fortemente correlacionados (p < 0,05). Conclusões: A maioria das medições se correlacionou fortemente entre si, com ênfase na medição objetiva da destreza.

Prevalência de Tracoma em crianças em idade escolar no município de Turmalina, MG / Trachoma prevalence among schoolchildren in the municipality of Turmalina, Minas Gerais state

RESUMO O tracoma, tido equivocadamente como erradicado em nosso meio, encontra-se na lista de doenças negligenciadas. Trata-se da maior causa de cegueira evitável do mundo, sendo encontrado predominantemente nos países subdesenvolvidos. Diversos trabalhos têm demonstrado que esta doença atualmente se faz presente em todas as regiões do Brasil, o que evidencia que tanto o governo (nas esferas federal, estadual e municipal), quanto a academia devem continuar a considerar o tracoma entre as causas de cegueira em nosso meio. Neste trabalho, procurou-se levantar a prevalência de tracoma entre as crianças de sete a quinze anos matriculadas nas escolas da rede pública do município de Turmalina, MG. A pesquisa foi realizada neste município, situado no Vale do Jequitinhonha, considerando que existem nele regiões com populações em situação de alta vulnerabilidade social, portanto com características propícias para o surgimento da doença. Participaram da pesquisa seis médicos e onze enfermeiros com atuação na atenção primária, capacitados e padronizados para tal. Os profissionais de saúde realizaram o exame de 635 estudantes entre 7 a 15 anos nas escolas públicas de Turmalina, MG. Os estudantes com diagnóstico clínico de tracoma foram submetidos à raspagem de conjuntiva com swab e o material enviado para análise laboratorial. Todos os estudantes diagnosticados com tracoma foram tratados no Sistema Único de Saúde (SUS). Os dados coletados foram analisados com auxílio do software Statistical Package for Social Sciences, IBM Inc., USA - SPSS, versão 22.0. Entre os estudantes foi encontrada uma prevalência do tracoma de 4,7%, com predomínio nas áreas rurais.

ABSTRACT Trachoma has been mistakenly assumed as having been eradicated, but is on the list of neglected diseases. It is the leading cause of preventable blindness in the world, being found predominantly in developing countries. Several studies have shown that this disease is currently present in all regions of Brazil, which shows that both the government (at the federal, state and municipal levels) and academia must continue to treat trachoma as one of the causes of blindness. In this study, we sought to identify the prevalence of trachoma among schoolchildren aged between seven and 15 years from public schools in the municipality of Turmalina, Minas Gerais state. The survey was conducted in this municipality, located in the Jequitinhonha Valley, a region that contains populations who live in situations of high social vulnerability, and thus display the characteristics that are conducive to the emergence of the disease. The participants were six doctors and 11 nurses working in primary healthcare, trained and standardized to do so. Health professionals examined 635 students aged 7-15 years in the public schools of Turmalina. Students with a clinical diagnosis of trachoma underwent conjunctiva scraping with a swab and the material was sent for laboratory analysis. All school children diagnosed with trachoma were treated at the Unified Health System (SUS). The collected data were analyzed using the Statistical Package for Social Sciences software, IBM Inc., USA - SPSS, version 22.0. Among the students, a 4.7% prevalence rate of trachoma was found, predominantly in rural areas.

Synaptic vesicle cycling is not impaired in a glutamatergic and a cholinergic synapse that exhibit deficits in acidification and filling

The purpose of the present work was to investigate synaptic vesicle trafficking when vesicles exhibit alterations in filling and acidification in two different synapses: a cholinergic frog neuromuscular junction and a glutamatergic ribbon-type nerve terminal in the retina. These synapses display remarkable structural and functional differences, and the mechanisms regulating synaptic vesicle cycling might also differ between them. The lipophilic styryl dye FM1-43 was used to monitor vesicle trafficking. Both preparations were exposed to pharmacological agents that collapse ΔpH (NH4Cl and methylamine) or the whole ΔµH+ (bafilomycin), a necessary situation to provide the driving force for neurotransmitter accumulation into synaptic vesicles. The results showed that FM1-43 loading and unloading in neuromuscular junctions did not differ statistically between control and experimental conditions (P > 0.05). Also, FM1-43 labeling in bipolar cell terminals proved highly similar under all conditions tested. Despite remarkable differences in both experimental models, the present findings show that acidification and filling are not required for normal vesicle trafficking in either synapse.

O objetivo do presente trabalho foi investigar o tráfego de vesículas sinápticas quando estas apresentam alterações no armazenamento de neurotransmissores e acidificação em duas distintas sinapses: a junção neuromuscular colinérgica de rãs versus o terminal nervoso glutamatérgico do tipo ribbon em céulas bipolares da retina. Essas sinapses exibem notáveis diferenças estruturais e funcionais e os mecanismos de regulação de ciclo das vesículas sinápticas podem ser diferentes entre eles. Para monitorar o tráfego de vesícula, foi utilizado o marcador lipofílico FM1-43. Ambas as preparações foram expostas a agentes farmacológicos que provocam o colapso de ΔpH (NH4Cl e metilamina) ou de todo ΔµH+ (bafilomicina), gradientes necessários para o acúmulo de neurotransmissores em vesículas sinápticas. Nossos resultados demonstram que a marcação e desmarcação de FM1-43 nas junções neuromusculares não foi estatisticamente diferente entre as diversas condições experimentais (P > 0,05). Além disso, a marcação de FM1-43 em terminais sinápticos de células bipolares foram bastante semelhantes em todas as condições testadas. Apesar das diferenças marcantes em ambos os modelos experimentais, nossos achados demonstram que a acidificação e o preenchimento de vesículas sinápticas não são necessários para o tráfico normal da vesícula nas sinapses estudadas.

Tumor desmóide abdominal: dificulades no diagnóstico clínico e radiológico / Abdominal desmoid tumor: difficulties in the clinical and radiological diagnosis

Resumo: Os autores relatam um caso grave de tumor desmóide abdominal com comprometimento pélvico importante e comentam sobre as dificuldades imagenológicas que provém deste diagnóstico. Säo feitos comentários sobre a abrangência clínica dessa doença e discutidos aspectos epidemológicos, diagnósticos e terapêuticos provenientes dos dados clínicos relatados no caso apresentado.

Tumor de células granulares esclerosante de mama simulando fibromatose / Sclerosing granular cell tumor of the breast simulating fibromatosis

Descrevemos um caso de tumor de células granulares esclerosante de mama simulando, histologicamente, fibromatose. Clinicamente, simulava um carcinoma pela consistência fibrosa e fixaçao ao músculo peitoral maior. O exame mamográfico demonstrou uma desinficaçao parenquimatosa e mal definida na uniao dos quadrantes superiores da mama esquerda. O exame ultra-sonográfico demonstrou uma lesao sólida mal definida aderente ao músculo peitoral. Os aspectos clínicos, radiológicos, histopatológicos e terapêuticos do tumor sao discutidos.

Malignant transformation by hydrazine derivatives: a role for carbon-centered radicals?

There are several hydrazine derivatives with pharmacological activity, all of which have carcinogenic properties in experimental animals. Several mono- and disubstituted derivatives have been shown to produce carbon-centered radicals upon oxidation by enzymatic systems such as HbO2' Cytochrome P-450, monoamine oxidases, horseradish peroxidase and myeloperoxidase. Proposed mechanisms of hydrazine metabolism leading to alkylating species are discussed. The in vitro induction of DNA alterations by carbon-centered radicals generated in hydrazine metabolism ascertains the possibility of its occurrence in vivo. Our results, discussed herein, established the induction of cytotoxicity, proliferation and transformation of cultured mouse fibroblasts by systems in which hydrazine-derived alkyl radicals are formed. These studies represent another step towards distinguishing the possible involvement of metabolism-generated carbon-centered radicals in the onset of carcinogenic processes, which reinforces the importance of additional experimental approaches in order to consolidate this hypothesis.