RESUMO
INTRODUCTION: Lung cancer tumors present EGFR mutations associated with an increased response rate to tyrosine kinase inhibitors (TKIs). Afatinib acts as an irreversible pan-ErbB-TKI. Areas covered: This review summarizes the results of clinical trials in NSCLC regarding its safety and efficacy. Expert opinion: Afatinib in 40 mg doses is highly effective in patients with NSCLC and EGFR mutations, improving progression-free survival and disease-related symptoms compared to chemotherapy. Additionally, afatinib has a better response rate and shows a small benefit in progression free survival compared to first-generation TKIs, and patients with exon 19 deletion could represent a subgroup with better prognosis and overall survival. Diarrhea, mucositis and rash are frequent adverse events induced by afatinib, these can impair quality of life and sometimes afatinib discontinuation is necessary. Management of adverse events, including early antidiarrheal treatment and prophylactic or early antibiotic management can reduce the gastrointestinal and cutaneous adverse events, respectively. Different risk factors, including malnourishment, sarcopenia, and low body surface might be associated with a higher toxicity risk, and these groups of patients could begin treatment with a low dose of afatinib followed by a close evaluation on tolerability and toxicity in order to slowly increase the dosage of afatinib.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Afatinib , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Receptores ErbB , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Qualidade de Vida , Quinazolinas/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND: Previous population-based studies have demonstrated an association between metformin use and improved survival among diabetic patients with cancer. We sought to analyze the effects of diabetes and its treatment in terms of the survival of patients with lung cancer. METHODS: Overall, 1106 patients with non-small cell lung cancer (94.3 % with stage IV disease) were included. The outcomes were compared between the patients with (n = 186) and without diabetes (n = 920). The characteristics associated with antidiabetic treatment and proper glycemic control (defined as a mean plasma glucose <130 mg/dL) were examined at diagnosis. The overall survivals (OSs) of the different patient populations were analyzed using Kaplan-Meier curves, and a multivariate Cox proportional hazard model was used to determine the influences of the patient and tumor characteristics on survival. RESULTS: The OS for the entire population was 18.3 months (95 % CI 16.1-20.4). There was no difference in the OSs of the diabetic and non-diabetic patients (18.5 vs 16.4 months, p = 0.62). The diabetic patients taking metformin exhibited a superior OS than did those on other antidiabetic treatments (25.6 vs 13.2 months, p = 0.017). Those with proper glycemic control had a better OS than did those without proper glycemic control and the non-diabetics (40.5 vs 13.2 and 18.5 months, respectively, p < 0.001). Both the use of metformin (HR 0.53, p < 0.0001 and HR 0.57, p = 0.017, respectively) and proper glycemic control (HR 0.49, p < 0.0001 and HR 0.40, p = 0.002, respectively) were significant protective factors in all and only diabetic patients, respectively. CONCLUSIONS: The diabetic patients with proper glycemic control exhibited a better OS than did those without proper glycemic control and even exhibited a better OS than did the patients without diabetes mellitus. Metformin use was independently associated with a better OS.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Neoplasias Pulmonares/mortalidade , Metformina/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaRESUMO
We evaluated the effects of cisplatin and paclitaxel on taste acuity and their associations with nutritional and health-related quality of life (HRQL) in patients with advanced non-small-cell lung cancer (NSCLC). Forty chemotherapy (CT)-naïve patients were assessed at baseline and after two cycles of paclitaxel and cisplatin. The taste evaluation was performed using a rinsing technique to identify detection and recognition thresholds (DT and RT) of bitter, sweet, and umami tastes. At baseline, 37.5% of the patients reported dysgeusia. After CT, the patients showed lower medians DT (p = 0.017) and RT (p = 0.028) for umami taste. These decreases were associated with clinical neuropathy, worse HRQL, and a tendency toward increased appetite loss. Additionally, CT did not significantly reduce the median DT for sweet (p = 0.09), which is associated with lower intake of protein (p = 0.015), animal protein (p = 0.010), fat (p = 0.004), and iron (p = 0.047). CT decreased the median DT for bitter (p = 0.035); however, this decrease was not associated with nutritional parameters or with HRQL. Sensitivity to taste increased with paclitaxel and cisplatin CT, making foods more unpleasant, and it was associated with neuropathy, worse HRQL, and reduced nutrient intake in advanced NSCLC patients. The protocol was registered at clinicaltrials.gov (NCT01540045).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Qualidade de Vida , Paladar/efeitos dos fármacos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Ingestão de Alimentos/efeitos dos fármacos , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paladar/fisiologia , Limiar Gustativo/efeitos dos fármacosRESUMO
BACKGROUND: Nutritional interventions have shown increased energy intake but not improvement in health-related quality of life (HRQL) or prognosis in non small cell lung cancer (NSCLC) patients. Eicosapentaenoic acid has been proposed to have anti-inflammatory, anticachectic and antitumoural effects. OBJECTIVE: To compare the effect of an oral EPA enriched supplement with an isocaloric diet on nutritional, clinical and inflammatory parameters and HRQL in advanced NSCLC patients. DESIGN: Patients with advanced NSCLC were randomized to receive diet plus oral nutritional supplement containing EPA (ONS-EPA) or only isocaloric diet (C). All patients received paclitaxel and cisplatin/carboplatin treatment. Weight, body composition, dietary intake, inflammatory parameters and HRQL were assessed at baseline and after the first and second cycles of chemotherapy. Response to chemotherapy and survival were evaluated. RESULTS: Ninety two patients were analysed (46 ONS-EPA,46 C). ONS-EPA group had significantly greater energy (p < 0.001) and protein (p < 0.001) intake compared with control. Compared with baseline, patients receiving the ONS-EPA gained 1.6 ± 5 kg of lean body mass (LBM) compared with a loss of -2.0 ± 6 kg in the control (p = 0.01). Fatigue, loss of appetite and neuropathy decreased in the ONS-EPA group (p ≤ 0.05). There was no difference in response rate or overall survival between groups. CONCLUSION: Patients with NSCLC receiving ONS-EPA significantly improves energy and protein intake, body composition. and decreased fatigue, loss of appetite and neuropathy. Registered with ClinicalTrials.gov (NCT01048970).
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Suplementos Nutricionais , Ácido Eicosapentaenoico/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apetite/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Qualidade de Vida , Resultado do Tratamento , Adulto JovemRESUMO
En la ciencia moderna,interdisciplinaria e interinstitucional, definir quién es autor y el ordende autoría en artículos científicos se ha convertido en problema anivel ético y legal. No aclarar la autoría antes o durante la realizaciónde la investigación genera problemas entre los que se consideranautores. Este artículo propone un formato cuantitativo y cualitativopara determinar autorías dentro del marco científico, ético y legal.Los principios utilizados para la construcción de este formato sefundamentaron en 2 criterios: a) fases de investigación y métodocientífico; involucrando: 1. planificación y elaboración del proyectode investigación, 2. diseño y obtención de datos, 3. presentaciónde resultados, 4. interpretación de resultados, 5. preparación delmanuscrito para la difusión del nuevo conocimiento, y 6. administracióny gestión; y b) coeficientes de ponderación en cada fase, para tomardecisiones de autoría y titularidad de obra. De la misma manera elformato considera y diferencia que fase y actividad, realizada dentro dela creación de la obra y difusión del conocimiento, es aporte práctico ointelectual; lo cual contrasta y complementa lo que la ley de derechosde autor protege. El formato es aplicable apriori y a posteriori a larealización de un proyecto o manuscrito y adaptable a cualquier tipode investigación y publicación, resolviendo cuantitativamente: 1.Orden de autores (primer autor y orden de coautores), 2. Inclusión yexclusión de colaboradores considerando principios éticos y legales y3. Porcentajes de derecho patrimonial para cada autor...
Determining authorship and the order of authorship inscientific papers, in modern interdisciplinary and interinstitutionalscience, has become complex at a legal and ethical level. Failureto define authorship before or during the research, createssubsequent problems for those considered authors of a publicationor lead authors of a work, particularly so, once the project ormanuscript is completed. This article proposes a quantitativeand qualitative model to determine authorship within a scientific,ethical and legal frame. The principles used for the constructionof this design are based on 2 criteria: a) stages of research andscientific method involving: 1. Planning and development of theresearch project, 2. Design and data collection, 3. Presentationof results, 4. Interpretation of results, 5. Manuscript preparationto disseminate new knowledge to the scientific community, 6.Administration and management, and b) weighting coefficients ineach phase, to decide on authorship and ownership of the work.The model also considers and distinguishes whether the leveland activity performed during the creation of the work and thediffusion of knowledge is an intellectual or practical contribution;this distinction both contrasts and complements the elementsprotected by copyright laws. The format can be applied a prioriand a posteriori to the completion of a project or manuscript andcan conform to any research and publication type. The use ofthis format will quantitatively resolve: 1. The order of authorship(first author and co-author order), 2. Determine the inclusion andexclusion of contributors, taking into account ethical and legalprinciples, and 3. Percentages of economic rights for each authors...
Na ciência moderna, interdisciplinar e inter-institucional,a definição do que é um autor e da ordem de autoría em trabalhoscientíficos tornou-se um problema de ética e legal. A carência de definirautoría, antes ou durante a realização de pesquisas, gera problemasentre os autores considerados. Este artigo propõe um formatoquantitativo e qualitativo para determinar a autoría dentro de umaestrutura científica, ética e legal. Os princípios utilizados na construçãodeste formato basearam-se em dois critérios: a) as fases do método depesquisa científica, envolvendo: 1. planejamento e escrito da pesquisa,2. delineamento e coleta de dados, 3. apresentação dos resultados,4. interpretação dos resultados, 5. preparação do manuscrito para adivulgação de novos conhecimentos, e 6. administração e gestão, e, b)as fases ponderadas, para tomar decisões de autoría e de propriedadeda obra. O formato considera e inclui a diferença entre fase e atividade,realizadas dentro da criação da obra e disseminação do conhecimento,a contribuição intelectual ou prática, que contrasta e complementa oque a lei protege em direitos de autor. O formato se aplica apriori ea posteriori à conclusão de um projeto ou manuscrito e é adaptável aqualquer tipo de pesquisa e publicação, resolvendo quantitativamente:1. a ordem de autores (primeiro autor e co-autores), 2. inclusão eexclusão de contribuintes, considerando os princípios éticos e legais, e3. os percentuais de direitos econômicos para cada autor...
Assuntos
Autoria/normas , Autoria na Publicação Científica , Pesquisa/educação , Pesquisa/legislação & jurisprudência , Ética na Publicação CientíficaRESUMO
Saccharomyces and non-Saccharomyces yeasts release enzymes that are able to transform neutral compounds of grape berries into active aromatic compounds, a process that enhances the sensory attributes of wines. So far, there exists only little information about enzymatic activity in mixed cultures of Saccharomyces and non-Saccharomyces during grape must fermentations. The aim of the present work was to determine the ability of yeasts to produce extracellular enzymes of enological relevance (ß-glucosidases, pectinases, proteases, amylases or xylanases) in pure and mixed Saccharomyces/non-Saccharomyces cultures during fermentation. Pure and mixed cultures of Saccharomyces cerevisiae BSc562, Hanseniaspora vinae BHv438 and Torulaspora delbrueckii BTd259 were assayed: 1% S. cerevisiae/99% H. vinae, 10% S. cerevisiae/90% H. vinae, 1% S. cerevisiae/99% T. delbrueckii and 10% S. cerevisiae/90% T. delbrueckii. Microvinifications were carried out with fresh must without pressing from Vitis vinifera L. c.v. Pedro Jiménez, an autochthonous variety from Argentina. Non-Saccharomyces species survived during 15-18days (BTd259) or until the end of the fermentation (BHv438) and influenced enzymatic profiles of mixed cultures. The results suggest that high concentrations of sugars did not affect enzymatic activity. ß-Glucosidase and pectinase activities seemed to be adversely affected by an increase in ethanol: activity diminished with increasing fermentation time. Throughout the fermentation, Saccharomyces and non-Saccharomyces isolates assayed produced a broad range of enzymes of enological interest that catalyze hydrolysis of polymers present in grape juice. Vinifications carried out by a pure or mixed culture of BTd259 (99% of T. delbrueckii) showed the highest production of all enzymes assayed except for ß-glucosidase. In mixed cultures, S. cerevisiae outgrew H. vinae, and T. delbrueckii was only detected until halfway the fermentation process. Nevertheless, their secreted enzymes could be detected throughout the fermentation process. Our results may contribute to a better understanding of the microbial interactions and the influence of some enzymes on vinification environments.
Assuntos
Enzimas/metabolismo , Fermentação , Saccharomyces/enzimologia , Vinho/microbiologia , Leveduras/enzimologia , Amilose , Argentina , Biomassa , Celulases/metabolismo , Etanol/metabolismo , Concentração de Íons de Hidrogênio , Pectinas/metabolismo , Fatores de Tempo , Vinho/análise , Xilose/metabolismoRESUMO
In Amazonian tropical forests, recent studies have reported increases in aboveground biomass and in primary productivity, as well as shifts in plant species composition favouring fast-growing species over slow-growing ones. This pervasive alteration of mature tropical forests was attributed to global environmental change, such as an increase in atmospheric CO2 concentration, nutrient deposition, temperature, drought frequency, and/or irradiance. We used standardized, repeated measurements of over 2 million trees in ten large (16-52 ha each) forest plots on three continents to evaluate the generality of these findings across tropical forests. Aboveground biomass increased at seven of our ten plots, significantly so at four plots, and showed a large decrease at a single plot. Carbon accumulation pooled across sites was significant (+0.24 MgC ha(-1) y(-1), 95% confidence intervals [0.07, 0.39] MgC ha(-1) y(-1)), but lower than reported previously for Amazonia. At three sites for which we had data for multiple census intervals, we found no concerted increase in biomass gain, in conflict with the increased productivity hypothesis. Over all ten plots, the fastest-growing quartile of species gained biomass (+0.33 [0.09, 0.55] % y(-1)) compared with the tree community as a whole (+0.15 % y(-1)); however, this significant trend was due to a single plot. Biomass of slow-growing species increased significantly when calculated over all plots (+0.21 [0.02, 0.37] % y(-1)), and in half of our plots when calculated individually. Our results do not support the hypothesis that fast-growing species are consistently increasing in dominance in tropical tree communities. Instead, they suggest that our plots may be simultaneously recovering from past disturbances and affected by changes in resource availability. More long-term studies are necessary to clarify the contribution of global change to the functioning of tropical forests.
Assuntos
Árvores/fisiologia , Clima Tropical , Biodiversidade , Evolução Biológica , Biomassa , Ecossistema , Meio Ambiente , Monitoramento Ambiental , Agricultura Florestal , Malásia , Panamá , Porto Rico , Sri Lanka , Tailândia , Fatores de Tempo , Árvores/crescimento & desenvolvimentoRESUMO
The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), the erm(A) gene was also detected in CM-05. The isolate belonged to sequence type 5 and carried staphylococcal chromosomal cassette mec type I. We were unable to detect the cfr gene in any of the human staphylococci screened (either clinical or colonizing isolates). Agar and broth dilution methods detected linezolid resistance in CM-05. However, the Etest and disk diffusion methods failed to detect resistance after 24 h of incubation. Oxazolidinone resistance mediated by the cfr gene is rare, and acquisition by a human isolate appears to be a recent event in Colombia. The detection of cfr-mediated linezolid resistance might be compromised by the use of the disk diffusion or Etest method.
Assuntos
Acetamidas/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Metiltransferases/genética , Oxazolidinonas/farmacologia , RNA Ribossômico 23S/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Proteínas de Bactérias/genética , Cloranfenicol/farmacologia , Colômbia/epidemiologia , Busca de Comunicante , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Características da Família , Evolução Fatal , Feminino , Humanos , Linezolida , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Tianfenicol/análogos & derivados , Tianfenicol/farmacologiaRESUMO
The importance of niche vs. neutral assembly mechanisms in structuring tropical tree communities remains an important unsettled question in community ecology [Bell G (2005) Ecology 86:1757-1770]. There is ample evidence that species distributions are determined by soils and habitat factors at landscape (<10(4) km(2)) and regional scales. At local scales (<1 km(2)), however, habitat factors and species distributions show comparable spatial aggregation, making it difficult to disentangle the importance of niche and dispersal processes. In this article, we test soil resource-based niche assembly at a local scale, using species and soil nutrient distributions obtained at high spatial resolution in three diverse neotropical forest plots in Colombia (La Planada), Ecuador (Yasuni), and Panama (Barro Colorado Island). Using spatial distribution maps of >0.5 million individual trees of 1,400 species and 10 essential plant nutrients, we used Monte Carlo simulations of species distributions to test plant-soil associations against null expectations based on dispersal assembly. We found that the spatial distributions of 36-51% of tree species at these sites show strong associations to soil nutrient distributions. Neutral dispersal assembly cannot account for these plant-soil associations or the observed niche breadths of these species. These results indicate that belowground resource availability plays an important role in the assembly of tropical tree communities at local scales and provide the basis for future investigations on the mechanisms of resource competition among tropical tree species.