Introduction
The best first-line treatment for patients with advanced hepatocellular carcinoma (HCC) and Child–Pugh (CP) class B remains unknown. The aim of the present study was to perform a ...real-world analysis on a large sample of patients with unresectable HCC with CP B treated with atezolizumab plus bevacizumab Vs Lenvatinib.
Methods
The study population included patients affected by advanced (BCLC-C) or intermediate (BCLC-B) HCC patients not suitable for locoregional therapies from both the Western and Eastern world (Italy, Germany, Republic of Korea and Japan), who received atezolizumab plus bevacizumab or Lenvatinib as first-line treatment. All the study population presented a CP class of B. The primary endpoint of the study was the overall survival (OS) of CP B patients treated with Lenvatinib compared to atezolizumab plus bevacizumab. Survival curves were estimated using the product-limit method of Kaplan–Meier. The role of stratification factors was analyzed with log-rank tests. Finally, an interaction test was performed for the main baseline clinical characteristics.
Results
217 CP B HCC patients were enrolled in the study: 65 (30%) received atezolizumab plus bevacizumab, and 152 (70%) received lenvatinib. The mOS for patients receiving Lenvatinib was 13.8 months (95% CI: 11.6–16.0), compared to 8.2 months (95% CI 6.3–10.2) for patients receiving atezolizumab plus bevacizumab as first-line treatment (atezolizumab plus bevacizumab Vs Lenvatinib: HR 1.9, 95% CI 1.2–3.0,
p
= 0.0050). No statistically significant differences were highlighted in terms of mPFS. The multivariate analysis confirmed that patients receiving Lenvatinib as first-line treatment have a significantly longer OS compared to patients receiving atezolizumab plus bevacizumab (HR 2.01; 95% CI 1.29–3.25,
p
= 0.0023). By evaluating the cohort of patients who received atezolizumab plus bevacizumab, we found that Child B patients with ECOG PS 0, or BCLC B stage or ALBI grade 1 were those who had benefited from the treatment thus showing survival outcomes no significantly different compared to those receiving Lenvatinib.
Conclusion
The present study suggests for the first time a major benefit from Lenvatinib compared to atezolizumab plus bevacizumab in a large cohort of patients with CP B class HCC.
Atualmente, é dada uma grande importância ao bem-estar e à hidratação durante todo o dia, em várias circunstâncias, como durante a hora de trabalho como nas horas de lazer. Devido à tentativa de ...redução de gastos, a população acaba por reutilizar garrafas de água comuns inúmeras vezes, sem serem eficazes em todas as situações. Uma garrafa banal apenas serve para transportar uma bebida, não permitindo a conservação da sua temperatura, sendo assim necessária a aquisição de uma garrafa térmica que, passado algum tempo, também altera este estado térmico.É então, através destas práticas, que surge a ideia do desenvolvimento de uma garrafa termoelétrica que, devido à incorporação de uma pastilha de peltier, permite aquecer e arrefecer a bebida que levamos connosco para fora de casa. Este tipo de recipiente necessita de acesso a energia elétrica, possibilitando assim o funcionamento deste artefacto.Este trabalho teve como objetivo a criação de um produto inovador, sustentandose nas necessidades recolhidas junto do público-alvo, e a implementação do sistema termoelétrico.O projeto foi desenvolvido totalmente suportado por ferramentas CAD/CAE e recorreu a uma metodologia projetual estruturada, mais concretamente à utilização do QFD que permitiu diminuir o tempo de desenvolvimento da conceção de uma nova proposta de cadeira de rodas, uma vez que permite combinar as características que o consumidor mais valoriza com os elementos que necessitam de mais atenção. Também a utilização do FMEA permitiu antecipar eventuais problemas da proposta apresentada, tal como, os danos provocados ao utilizador ou ainda no produto.Todo o projeto foi desenvolvido a pensar na simplificação do dia-a-dia dos utilizadores. Só assim foi possível criar um produto diferente dos demais, uma vez que tem a capacidade de responder às necessidades do momento: bebida quente ou fria e um momento de descontração num qualquer lugar e a qualquer hora, com a maior comodidade possível.
Sexually dimorphic traits are common among mammals and are specified during development through the deployment of sex-specific genetic programs. Because little is known about these programs, we ...investigated them using a resource of gene expression profiles in males and females throughout the development of five organs in five mammals (human, mouse, rat, rabbit, and opossum) and a bird (chicken). We found that sex-biased gene expression varied considerably across organs and species and was often cell-type specific. Sex differences increased abruptly around sexual maturity instead of increasing gradually during organ development. Finally, sex-biased gene expression evolved rapidly at the gene level, with differences between organs in the evolutionary mechanisms used, but more slowly at the cellular level, with the same cell types being sexually dimorphic across species.
The development of fast and cheap high-throughput platforms for the detection of environmental contaminants is of particular importance to understand the human-related impact on the environment. The ...application of DNA-directed immobilization (DDI) of IgG molecules is currently limited to the clinical diagnostics scenario, possibly because of the high costs of production of such addressable platforms. We here describe the efficient and specific hybridization of an antibody–oligonucleotide conjugate to a short 12-mer capture probe. The specific antibody used is a monoclonal antibody against caffeine, a stimulant and important anthropogenic marker. With this work, we hope to contribute to broadening the application potential of DDI to environmental markers in order to develop cheaper and more stable high-throughput screening platforms for standard routine analysis of pollutants in a variety of complex matrices.
Chronic rhinosinusitis is currently classified into two types: chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps. In the West, approximately 80% of chronic ...rhinosinusitis with nasal polyps cases are characterized by a predominantly eosinophilic cell infiltrate and a Th2 cytokine pattern.
To evaluate the effect of Interferon-α on cytokine levels of the eosinophilic nasal polyp cell culture supernatant.
Cell cultures were performed based on nasal polypoid tissue samples collected from 13 patients with eosinophilic chronic rhinosinusitis with nasal polyps. Polyps were considered eosinophilic according to the histopathological examination. Cell cultures were stimulated with 3000 IU of interferon-α. Before and after the stimulus, concentrations of Interferon-γ, tumor necrosis factor αand IL 2, 4, 6 and 10, using cytometric bead array, were assessed.
Cell samples from eosinophilic nasal polyps from 13 patients were included in the study. Twenty-four hours after interferon-α stimulation, eosinophilic nasal polyp culture supernatants showed significantly decreased IL-4 concentrations and increase in interferon-γ, IL-10 and IL-6 concentrations compared to controls. There were no significant differences in tumor necrosis factor -α and IL-2 concentrations.
We demonstrated that interferon-α in vitro alters the pattern of cytokines in cell cultures of eosinophilic nasal polyps. Analysis of these alterations suggests that interferon-α promotes a rebalancing of inflammatory profiles in cell cultures, favoring the expression of Th1 and regulatory cytokines over Th2 cytokines.
O desperdício alimentar tem sido alvo de especial atenção nos últimos anos e a sua dimensão tem gerado preocupação a nível dos governos e da sociedade civil em geral. Este estudo foi realizado numa ...Instituição que alberga e apoia os sem-abrigo na cidade do Porto e teve como objetivo quantificar o desperdício alimentar na instituição e identificar as suas causas. A quantificação do desperdício sob a forma de sobras e restos foi realizada durante 21 dias, incluindo as refeições do almoço e jantar servidos a um total de 60 utentes. Para avaliação do desperdício foi utilizado o método de pesagem agregada não seletiva, com pesagem inicial da quantidade total de alimentos confecionados, pesagem dos alimentos confecionados, mas não servidos (sobras) e dos restos após o consumo das refeições. No prato, verificou-se um valor médio de 17,5% para as sobras e 18,9% para os restos. Relativamente à sopa, observou-se um valor médio de 10,5% para as sobras e de 13,1% para os restos. Apesar das diferenças não serem estatisticamente significativas (p>0,05), nos pratos cujo método de confeção foi o estufado e/ou o cozido, verificaram-se percentagens mais elevadas de sobras do que nos pratos cujo método de confeção foi o assado ou frito. A ementa influenciou o desperdício alimentar, verificando-se que para algumas ementas não existiam sobras. A taxa de utentes faltosos influenciou significativamente (p<0,05) a percentagem de sobras do prato. O desperdício alimentar observado implica uma classificação do serviço de alimentação como “mau”. A ementa e o número de utentes faltosos foram causas do desperdício alimentar nesta instituição.
Despite the high morbidity and mortality of metastatic colorectal cancer (mCRC) in older patients, they have been underrepresented in clinical trials and their optimal treatment is yet to be ...determined. This open-label phase II study evaluated the benefits of panitumumab and capecitabine as a first-line chemotherapy regimen in older patients with wild-type WT RAS mCRC.
Patients (≥70 years; ECOG≤2) received 3-week cycles of panitumumab (9 mg/kg on day 1) plus capecitabine (850 mg/m2 twice daily on days 1–14) until disease progression or unacceptable toxicity. Response was evaluated every 9 weeks according to RECIST_1.1. Outcome measures were: objective response rate (ORR), duration of response (DoR), time to response (TTR), progression (TTP) and treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety.
Twenty-seven patients (11 women; median age: 78 years; ECOG: 0 26%, 1 67%, 2 7%) were evaluated. Median follow-up was 17.7 months. Confirmed ORR (95%CI) was 44.4% (25.7–63.2), with 25.9% of patients achieving at least stable disease. Median (95%CI) DoR was 8.7 (5.5–10.4) months, and median TTR was 2.2 (1.9–2.8) months. Median TTP was 9.6 (4.8–11.5) months, with a median TTF of 5.2 (2.8–7.2) months. The median PFS was 7.5 (4.4–10.4) months, and the median OS was 23.7 (7.4–27.5) months. Seventeen (63%) patients reported panitumumab and/or capecitabine-related adverse events grade 3–4, with skin toxicity (18.5%) being the most common. Two (7.4%) deaths were treatment-related.
This study suggests that panitumumab plus capecitabine is a safe and effective regimen in older patients with WT RAS mCRC.
•Panitumumab has a low rate of immunogenicity compared with other antibodies against EGFR because of its fully human nature.•The combination of panitumumab and capecitabine was suggested to be effective in older patients with WT RAS mCRC.•The good tolerability and safety profile of the combination were in line to previous studies in older patients.•Panitumumab with capecitabine may provide an alternative to other anti-EGFR regimens in older patients with WT RAS mCRC.
Perante um mundo de aceleradas mudanças que parecem incontroláveis, a sobrevivência das futuras gerações está a ser desafiada tendo impelido as instituições de ensino superior a atender às ...recomendações recorrentes de organismos internacionais de educação a incluir o Pensamento Crítico (PC) e as soft skills nos curricula. Este artigo contribui para a investigação empírica sobre estratégias ativas de ensino e aprendizagem que promovam o desenvolvimento do PC. Tendo por base uma intervenção pedagógica semestral numa turma de alunos de primeiro ano do curso de licenciatura de engenharia mecânica, procurou-se saber em que medida uma estratégia pedagógica integrada, que articula a Pesquisa Guiada (PG) e o método de Aprendizagem Cooperativa (AC) ‘Jigsaw’, pode promover capacidades e disposições de PC. Os resultados obtidos apontam para o potencial desta metodologia na aquisição de conhecimento, no desenvolvimento das capacidades de questionar, analisar, avaliar e sintetizar informação e das disposições de autoconfiança e de curiosidade intelectual.
Marine kelp forests cover 1/3 of our world's coastlines, are heralded as a nature-based solution to address socio-environmental issues, connect hundreds of millions of people with the ocean, and ...support a rich web of biodiversity throughout our oceans. But they are increasingly threatened with some areas reporting over 90% declines in kelp forest cover in living memory. Despite their importance and the threats they face, kelp forests are entirely absent from the international conservation dialogue. No international laws, policies, or targets focus on kelp forests and very few countries consider them in their national policy. The Kelp Forest Challenge addresses that gap. Together with 252 kelp experts, professionals, and citizens from 25 countries, the Kelp Forest Challenge was developed as a grassroots vision of what the world can achieve for kelp forest conservation. It is a global call to restore 1 million and protect 3 million hectares of kelp forests by 2040. This is a monumental challenge, that will require coordination across multiple levels of society and the mobilization of immense resources. Pledges may therefore include area for protection or restoration, enabling pledges which assist in conservation (funding, equipment, professional expertise, capacity building), or awareness-based pledges which increase awareness or education about kelp forests. Correspondingly, participants may be from government, scientific institutions, private sector, NGOs, community groups, or individuals. This challenge is the beginning of a 17-year mission to save our kelp forests and anyone and any organisation is invited to participate.
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