Fighting childhood cancer and the innovative project of the Princess Maxima Centre for Paediatric Oncology

Cancer is one of the most feared diagnoses for the present generations. Yet, for a parent more than for anyone else, knowing that their child has got cancer can be devastating. Childhood cancer is intense and consuming for all people involved, and its physical and psychological consequences are difficult to evaluate. This dissertation aims to understand the main challenges of paediatric cancer, and explore a possible solution to address some of them with a case study: The Princess Maxima Centre for Paediatric Oncology, the Netherlands. To better contextualize the opening of this Centre, a review of literature was conducted to understand the dimension, costs and most important challenges faced by all stakeholders involved. In fact, the project for the Princess Maxima Centre is the Netherlands’ response to some of these challenges. By concentrating all professionals dedicated to this cause, childhood cancer patients and their families in one single building, the Centre aims to cure all children with cancer in the country, but also to make their lives easier. Children will be receiving the most appropriate care as a result of the Centre’s strategy, with particular attention to their natural development. Great accomplishments are expected by all professionals in virtue of the Centre’s environment and therefore better treatment solutions for their patients.Cancro é um dos diagnósticos mais receados pelas gerações actuais. Para os pais, mais do que ninguém, tomar conhecimento de que um filho tem cancro pode ser devastador. O cancro infantil é intenso e desgastante para todas as pessoas envolvidas, e as suas consequências físicas e psicológicas são difíceis de medir. Esta tese tem como objectivo procurar entender os maiores desafios relativos ao cancro infantil e explorar uma possível solução através de um caso concreto: O Princess Máxima Centre for Paediatric Oncology nos Países Baixos. Para melhor contextualizar a abertura deste Centro, uma recensão da literatura foi conduzida para compreender a dimensão, custos e desafios mais importantes encarados por todas as partes interessadas. De facto, o Princess Máxima Centre é a resposta dos Países Baixos a algumas destas questões. Através da concentração de todos os profissionais envolvidos nesta área, dos pacientes e das suas famílias em um único edifício, o Centro tem como objectivo curar todas as crianças com cancro do país, mas também tornar a sua vida um pouco melhor. Estas crianças vão receber os cuidados mais apropriados graças à estratégia do Centro, com uma atenção especial ao seu desenvolvimento natural. Todos os profissionais envolvidos esperam resultados excepcionais em virtude de toda a envolvente do Centro, e por isso melhores soluções de cura para os seus pacientes

An overlook on the current registries for rare and complex connective tissue diseases and the future scenario of TogethERN ReCONNET

European Reference Networks; Rare and complex connective tissue diseases; RegistriesRedes Europeas de Referencia; Enfermedades raras y complejas del tejido conjuntivo; RegistrosXarxes de referència europees; Malalties rares i complexes del teixit conjuntiu; RegistresBackground: Patient registries play a crucial role in supporting clinical practice, healthcare planning and medical research, offering a real-world picture on rare and complex connective tissue diseases (rCTDs). ERN ReCONNET launched the first European Registry Infrastructure with the aim to plan, upgrade and link registries for rCTDs, with the final goal to promote a harmonized data collection approach all over Europe for rCTDs. Methods: An online survey addressed to healthcare professionals and patients' representatives active in the field of rCTDs was integrated by an extensive database search in order to build a mapping of existing registries for rCTDs. Findings: A total of 140 registries were found, 38 of which include multiple diseases. No disease-specific registry was identified for relapsing polychondritis, mixed connective tissue disease and undifferentiated connective tissue disease. Discussion: This overview on the existing registries for rCTDs provides a useful starting point to identify the gaps and the strengths of registries on the coverage of rCTDs, and to develop a common data set and data collection approach for the establishment of the TogethERN ReCONNET Infrastructure.This work was funded by the European Union's Health Program (2014–2020). ERN ReCONNET is one of the 24 European Reference Networks (ERNs) approved by the ERN Board of Member States. The ERNs are co-funded by the EC (European Commission) (grant no. 947700)

Agrochemicals and their link with health from the perspective of bioethics a literature review

Sofia Gloodtdofsky: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Romina Olivera: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Matilde Pollo: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Agustina Benzo: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Valentina Mermot: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Martina Bejar: Estudiante de Facultad de Medicina, Universidad de la República. Montevideo, Uruguay.-- Elisa Bandeira: Docente supervisor, Departamento de Bioética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.-- Germán Busch: Docente supervisor, Departamento de Bioética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.-- Mariano Montero: Docente supervisor, Departamento de Bioética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.-- Damián Ramirez: Docente supervisor, Departamento de Bioética, Facultad de Medicina, Universidad de la República, Montevideo, UruguayLa presente revisión bibliográfica busca mostrar las distintas perspectivas bioéticas latinoamericanas en relación al uso de agrotóxicos y su repercusión sobre la salud y el medio ambiente. Esta incluye 11 publicaciones académicas, publicadas desde 2011 hasta 2021, en idioma español. De la misma se destaca la necesidad de poner en debate las distintas perspectivas, ya que aún resulta un reto hallar soluciones y alternativas de reducción de daños a todos los involucrados en la problemática. La incorporación de la bioética a la discusión sobre el uso de agrotóxicos abre un capítulo relevante que justifica un debate amplio y esclarecedor que será útil tanto para la concientización de la población sobre los riesgos, como para orientar políticas públicas en este rubro.The intention of this literature review is to show the different ethical perspectives in relation to the use of pesticides, and the repercussions on health and environment. This includes 11 academic publications, published from 2011 to 2021, in Spanish. In conclusion, it is necessary to debate about the different perspectives, based on the fact that it is still a challenge to find solutions and alternatives that reduce damage to all those involved in the problem. The incorporation of bioethics into the discussion on the use of pesticides opens a relevant chapter that justifies a broad and enlightening debate that it will be useful both for raising awareness of the population about the risks and also for guiding public policies in this area

Risk factors for infection, predictors of severe disease, and antibody response to COVID-19 in patients with inflammatory rheumatic diseases in Portugal: a multicenter, nationwide study

Copyright © 2022 Cruz-Machado, Barreira, Bandeira, Veldhoen, Gomes, Serrano, Duarte, Rato, Miguel Fernandes, Garcia, Pinheiro, Bernardes, Madeira, Miguel, Torres, Bento Silva, Pestana, Almeida, Mazeda, Cunha Santos, Pinto, Sousa, Parente, Sequeira, Santos, Fonseca and Romão. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Objective: To identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients. Methods: Nationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register-Reuma.pt-during the first 6 months of the pandemic. We compared patients with COVID-19 with those who did not develop the disease and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. IgG antibodies against SARS-CoV-2 were measured ≥3 months after infection and results were compared with matched controls. Results: 162 cases of COVID-19 were registered in a total of 6,363 appointments. Patients treated with TNF inhibitors (TNFi; OR = 0.160, 95% CI 0.099-0.260, P < 0.001) and tocilizumab (OR 0.147, 95% CI 0.053-0.408, P < 0.001) had reduced odds of infection. Further, TNFi tended to be protective of severe and critical disease. Older age, major comorbidities, and rituximab were associated with an increased risk of infection and worse prognosis. Most patients with inflammatory RMDs (86.2%) developed a robust antibody response. Seroconversion was associated with symptomatic disease (OR 13.46, 95% CI 2.21-81.85, P = 0.005) and tended to be blunted by TNFi (OR 0.17, 95% CI 0.03-1.05; P = 0.057). Conclusions: TNFi and tocilizumab reduced the risk of infection by SARS-CoV-2. Treatment with TNFi also tended to reduce rates of severe disease and seroconversion. Older age, general comorbidities and rituximab were associated with increased risk for infection and worse prognosis, in line with previous reports. Most patients with RMDs developed a proper antibody response after COVID-19, particularly if they had symptomatic disease.We acknowledge the generous sharing of the expression constructs by Dr. Florian Krammer, Icahn School of Medicine at Mount Sinai, New York, USA [Development of SARS-CoV-2 reagents was partially supported by the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C] and the protein production by Drs. Paula Alves and Rute Castro at Instituto de Biologia Experimental e Tecnológica (iBET) Oeiras, Portugal as part of the Serology COVID consortium.info:eu-repo/semantics/publishedVersio

Predictors of cardiac involvement in idiopathic inflammatory myopathies

Copyright © 2023 Bandeira, Dourado, Melo, Martins, Fraga, Ferraro, Saraiva, Sousa, Parente, Soares, Correia, Almeida, Dinis, Pinto, Oliveira Pinheiro, Rato, Beirão, Samões, Santos, Mazeda, Chícharo, Faria, Neto, Lourenço, Brites, Rodrigues, Silva-Dinis, Dias, Araújo, Martins, Couto, Valido, Santos, Barreira, Fonseca and Campanilho-Marques. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Objectives: Idiopathic inflammatory myopathies (IIM) are a group of rare disorders that can affect the heart. This work aimed to find predictors of cardiac involvement in IIM. Methods: Multicenter, open cohort study, including patients registered in the IIM module of the Rheumatic Diseases Portuguese Register (Reuma.pt/Myositis) until January 2022. Patients without cardiac involvement information were excluded. Myo(peri)carditis, dilated cardiomyopathy, conduction abnormalities, and/or premature coronary artery disease were considered. Results: 230 patients were included, 163 (70.9%) of whom were females. Thirteen patients (5.7%) had cardiac involvement. Compared with IIM patients without cardiac involvement, these patients had a lower bilateral manual muscle testing score (MMT) at the peak of muscle weakness [108.0 ± 55.0 vs 147.5 ± 22.0, p=0.008] and more frequently had oesophageal [6/12 (50.0%) vs 33/207 (15.9%), p=0.009] and lung [10/13 (76.9%) vs 68/216 (31.5%), p=0.001] involvements. Anti-SRP antibodies were more commonly identified in patients with cardiac involvement [3/11 (27.3%) vs 9/174 (5.2%), p=0.026]. In the multivariate analysis, positivity for anti-SRP antibodies (OR 104.3, 95% CI: 2.5-4277.8, p=0.014) was a predictor of cardiac involvement, regardless of sex, ethnicity, age at diagnosis, and lung involvement. Sensitivity analysis confirmed these results. Conclusion: Anti-SRP antibodies were predictors of cardiac involvement in our cohort of IIM patients, irrespective of demographical characteristics and lung involvement. We suggest considering frequent screening for heart involvement in anti-SRP-positive IIM patients.info:eu-repo/semantics/publishedVersio

Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.This project was supported by the “Fundação para a Ciência e Tecnologia”, program “Research 4 Covid-19 Apoio especial a projetos de implementação rápida para soluções inovadoras de resposta à pandemia de COVID-19”. It was also partially supported by each institution.info:eu-repo/semantics/publishedVersio

Questão agrária e políticas públicas em Minas Gerais : conflitos sociais e alternativas populares

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Angiotensin-Converting Enzyme Activity May Predict Disease Severity in Psoriasis

Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. ACE activity has been shown to be higher in psoriatic patients and it suggests an oxidative stress state, as seen in many cardiovascular disorders. We aimed to explore the association between ACE activity and polymorphisms and cardiovascular risk amongst psoriatic patients. We included 64 psoriatic patients and 1091 controls and compared ACE I/D polymorphism genotype and serum activity for both groups. ACE genotypes were similar in psoriatic patients and controls. Notably, serum ACE activity was higher in psoriatic patients (19.09 &plusmn; 2.86 U/mL) compared to controls (11.85 &plusmn; 0.40 U/mL), p = 0.015. Non-HDL cholesterol was significantly lower in II polymorphism (p = 0.037). Psoriatic activity (PASI) was associated with a higher cardiovascular risk estimated by lower HDL concentrations (r = &minus;0.496, p = 0.007), and higher triglyceride levels (r = 0.421, p = 0.020) and TC/HDL and LDL/HDL ratios (r = 0.612, p &lt; 0.001 and r = 0.437, p = 0.023, respectively). Patients with psoriasis have higher ACE activity levels, independent of ACE genotype. Moreover, disease activity correlated with cardiovascular risk. This could support the eventual role of ACE as a possible biomarker for disease severity and cardiovascular risk in psoriasis patients

Psoriasis is more than a skin disorder : an ACE study

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2017Introduction: Psoriasis is now known to be a systemic autoimmune disease with an associated increased cardiovascular risk. This seems to rely on systemic inflammation. Angiotensin-converting enzyme (ACE) has been associated with oxidative stress, a state characteristic of cardiovascular disorders and this enzyme’s activity is higher in psoriasis. Our aim is to assess cardiovascular risk in psoriatic patients and its association with ACE polymorphism and activity. Methods: Our population consisted of 1155 individuals (64 psoriatic patients, 1091 controls) whose ACE genotype and activity were determined. The cardiovascular risk was estimated through lipid profiles. PASI score was used as a severity measurement. Results: Psoriatic severity was associated with a higher cardiovascular risk estimated by lower HDL concentrations (r=-0.496, p=0.007) and higher triglyceride levels (r=0.421, p=0.020), as well as TC/HDL and LDL/HDL ratios (r=0.612, p<0.001 and r=0.437, p=0.023, respectively) which have been shown to have stronger predictive value for cardiovascular disorders Conclusions: Psoriatic patients should be treated as a risk group for cardiovascular diseases and new markers for severity and this associated risk may be of worthy pursuit. Further studies are crucial to enhance our knowledge on inflammation and psoriasis.Introdução: A psoríase é atualmente vista como uma doença sistémica autoimune com um risco cardiovascular associado, cuja correlação parece advir de um estado de inflamação sistémica. A enzima conversora de angiotensina (ECA) associa-se a stress oxidativo, característico da patologia cardiovascular e apresenta níveis de atividade superiores na psoríase. O nosso objetivo é avaliar este risco e a sua associação com o polimorfismo e atividade do ECA. Métodos: A amostra consiste em 1155 indivíduos (65 psoriáticos, 1091 saudáveis), dos quais se determinou o genótipo do ECA e a sua atividade. O risco cardiovascular foi estimado a partir do perfil lipídio e a severidade da doença pelo índice PASI. Resultados: A severidade da psoríase associou-se a diminuição do HDL (r=-0.496, p=0.007) e aumento dos triglicerídeos (r=0.421, p=0.020), bem como dos índices CT/HDL e LDL/HDL (r=0.612, p<0.001 e r=0.437, p=0.023, respetivamente), os quais traduzem melhor valor preditivo para doenças cardiovasculares. Conclusões: Os doentes psoriáticos devem ser tratados como um grupo de risco para patologia cardiovascular e deverão ser procurados novos marcadores para a severidade da doença e risco associado. Novos estudos são essenciais para melhorar o conhecimento nesta área