RESUMO
We present the case of a 35-year-old male with a first-degree family history of gastric cancer (his father was diagnosed at the age of 45), who was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis.
Assuntos
Neoplasias Gástricas , Sífilis , Humanos , Masculino , Adulto , Sífilis/diagnóstico , Sífilis/complicações , Diagnóstico Diferencial , Gastropatias/diagnósticoRESUMO
The primary aim of this study was to describe regulations and practices concerning the family approach to discuss donation, specifically after the neurological determination of death, one of the most challenging steps in the donation pathway. A secondary objective was to assess the impact of legislation on consent rates for organ donation. The Council of Europe surveyed 39 member states about national regulations, practices, and consent rates; 34 replied. Opt-out legislation is present in 19, opt-in in 9 and a mixed system in six countries. An opt-out register is kept by 24 countries and an opt-in register by 18 countries, some keeping both. The mean consent rate was 81.2% of all family approaches. Most countries regulate how death using neurological criteria is confirmed (85.3%), while regulation of other aspects of the deceased donation pathway varies: the timing of informing the family about brain death (47.1%) and organ donation (58.8%), the profile of professional who discusses both topics with the family (52.9% and 64.7%, respectively) and the withdrawal of treatment after brain death (47.1%). We also noted a mismatch between what regulations state and what is done in practice in most countries. We suggest possible reasons for this disparity.
Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Morte Encefálica , Doadores de Tecidos , Europa (Continente)RESUMO
Physical examination (PE) of donors is essential to identify potential risks to the safety and efficacy of donated organs and tissues and is mandatory in the EU. However, no detailed guidance is available as to how PE should be performed. Health authorities (HA) and health professionals (HP) in member states of the European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) and observer countries completed surveys relating to the regulatory requirements for PE and the professional practice of PE in their countries for organ and tissue donors. The HA survey addressed regulatory aspects, and the HP survey addressed professional practices, training, and respondents' opinions on the value of PE. These surveys revealed significant inter-country variation in the regulatory approach to PE and the performance of PE by professionals. Most respondents opined that PE was important and yielded valuable information in identifying contraindications to donation. There is no consensus at a regulatory or professional level as to how PE should be performed on organ and tissue donors. There is a requirement for agreed best practice guidelines in this area.
Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Doadores de Tecidos , Europa (Continente) , Exame FísicoRESUMO
Discrepancies in donation and transplantation by sex and gender have previously been reported. However, whether such differences are invariably the inevitable, unintended outcome of a legitimate process has yet to be determined. The European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) is the committee that actively promotes the development of ethical, quality and safety standards in the field of transplantation in Europe. Whilst the ultimate objective is to shed light on the processes underlying potential gender inequities in transplantation, our initial goal was to represent the distribution by sex among organ donors and recipients in the CD-P-TO Member States and observer countries. Our survey confirms previous evidence that, in most countries, men represent the prevalent source of deceased donors (63.3% in 64 countries: 60.7% and 71.9% for donation after brain and circulatory death, respectively). In contrast, women represent the leading source of organs recovered from living kidney and liver donors (61.1% and 51.2% in 55 and 32 countries, respectively). Across countries, most recovered organs are transplanted into men (65% in 57 countries). These observations may be explained, at least in part, by the higher burden of certain diseases in men, childbearing related immune sensitization in women, and donor-recipient size mismatch. Future research should establish whether gender-related socially-constructed roles and socioeconomic status may play a detrimental role reducing the access of women to transplantation.
Assuntos
Transplante de Rim , Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Europa (Continente) , Feminino , Humanos , Masculino , Inquéritos e Questionários , Doadores de TecidosRESUMO
The access of non-resident patients to the deceased donor waiting list (DDWL) poses different challenges. The European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) has studied this phenomenon in the European setting. A questionnaire was circulated among the Council of Europe member states to inquire about the criteria applied for non-residents to access their DDWL. Information was compiled from 28 countries. Less than 1% of recipients of deceased donor organs were non-residents. Two countries never allow non-residents to access the DDWL, four allow access without restrictions and 22 only under specific conditions. Of those, most give access to non-resident patients already in their jurisdictions who are in a situation of vulnerability (urgent life-threatening conditions). In addition, patients may be given access: (i) after assessment by a specific committee (four countries); (ii) within the framework of official cooperation agreements (15 countries); and (iii) after patients have officially lived in the country for a minimum length of time (eight countries). The ethical and legal implications of these policies are discussed. Countries should collect accurate information about residency status of waitlisted patients. Transparent criteria for the access of non-residents to DDWL should be clearly defined at national level.
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Transplante de Rim , Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Europa (Continente) , Humanos , Doadores de Tecidos , Listas de EsperaRESUMO
Donation after circulatory death (DCD) has become an accepted practice in many countries and remains a focus of intense interest in the transplant community. The present study is aimed at providing a description of the current situation of DCD in European countries. Specific questionnaires were developed to compile information on DCD practices, activities and post-transplant outcomes. Thirty-five countries completed the survey. DCD is practiced in 18 countries: eight have both controlled DCD (cDCD) and uncontrolled DCD (uDCD) programs, 4 only cDCD and 6 only uDCD. All these countries have legally binding and/or nonbinding texts to regulate the practice of DCD. The no-touch period ranges from 5 to 30 min. There are variations in ante and post mortem interventions used for the practice of cDCD. During 2008-2016, the highest DCD activity was described in the United Kingdom, Spain, Russia, the Netherlands, Belgium and France. Data on post-transplant outcomes of patients who receive DCD donor kidneys show better results with grafts obtained from cDCD versus uDCD donors. In conclusion, DCD is becoming increasingly accepted and performed in Europe, importantly contributing to the number of organs available and providing acceptable post-transplantation outcomes.
Assuntos
Obtenção de Tecidos e Órgãos/tendências , Transplante/tendências , Bélgica , Morte , Europa (Continente) , França , Sobrevivência de Enxerto , Humanos , Países Baixos , Federação Russa , Espanha , Doadores de Tecidos , Reino UnidoRESUMO
After more than 120 hand-upper extremity and 37 face transplant procedures performed worldwide, vascularized composite allotransplantation (VCA) now falls under the scope of organ transplant legislation in Europe and the United States. While in the USA, VCA has been considered as standard care since 2014, VCA in Europe is still performed through clinical research trials, except in United Kingdom. However, after two decades of favourable experience with upper extremity transplantation (UET), professionals in Europe are proposing hand allotransplantation as "controlled standard" care, as opposed to face transplantation (FT), which is still a challenging activity. The European Committee on Organ Transplantation (CD-P-TO) has elaborated a position paper to provide recommendations concerning regulatory aspects for UET and FT. It is aimed at Health Authorities in charge of the oversight - and coordination - of organ donation and transplantation, and at professional groups to help them manage such complex and costly programs dedicated to properly selected patients.
Assuntos
Alotransplante de Tecidos Compostos Vascularizados/métodos , Transplante de Face , Humanos , Consentimento Livre e Esclarecido , Doadores de Tecidos , Extremidade Superior/cirurgiaRESUMO
RNA interference is an endogenous mechanism present in most eukaryotic cells that enables degradation of specific mRNAs. Pharmacological exploitation of this mechanism for therapeutic purposes attracted a whole amount of attention in its initial years, but was later hampered due to difficulties in delivery of the pharmacological agents to the appropriate organ or tissue. Advances in recent years have to a certain level started to address this specific issue. Genetic diseases are caused by aberrations in gene sequences or structure; these particular abnormalities are in theory easily addressable by RNAi therapeutics. Sequencing of the human genome has largely contributed to the identification of alterations responsible for genetic conditions, thus facilitating the design of compounds that can address these diseases. This review addresses the currently on-going programs with the aim of developing RNAi and other antisense compounds for the treatment of genetic conditions and the pros and cons that these products may encounter along the way. The authors have focused on those programs that have reached clinical trials or are very close to do so.
Assuntos
Elementos Antissenso (Genética)/uso terapêutico , Doenças Genéticas Inatas/terapia , Oligonucleotídeos/uso terapêutico , Interferência de RNA , RNA Interferente Pequeno/uso terapêutico , Humanos , RNA Interferente Pequeno/genéticaRESUMO
Organ, tissue, and cell donation and transplantation legislation and policies vary substantially worldwide, as do performance outcomes in various jurisdictions. Our objective was to create expert, consensus guidance that links evidence and ethical concepts to legislative and policy reform for tissue and cell donation and transplantation systems. Methods: We identified topic areas and recommendations through consensus, using nominal group technique. The proposed framework was informed by narrative literature reviews and vetted by the project's scientific committee. The framework was presented publicly at a hybrid virtual and in-person meeting in October 2021 in Montréal, Canada, where feedback provided by the broader Forum participants was incorporated into the final manuscript. Results: This report has 13 recommendations regarding critical aspects affecting the donation and use of human tissues and cells that need to be addressed internationally to protect donors and recipients. They address measures to foster self-sufficiency, ensure the respect of robust ethical principles, guarantee the quality and safety of tissues and cells for human use, and encourage the development of safe and effective innovative therapeutic options in not-for-profit settings. Conclusions: The implementation of these recommendations, in total or in part, by legislators and governments would benefit tissue transplantation programs by ensuring access to safe, effective, and ethical tissue- and cell-based therapies for all patients in need.
RESUMO
Haematopoietic progenitor cell donation from bone marrow and mobilised peripheral blood obtained from related and unrelated donors is an established procedure. The donation process in general has proven to be safe, but in rare cases severe and even fatal events have been reported. The present study aimed at providing a description of the current situation of donor protection measures in Council of Europe member States. A specific questionnaire was developed to compile information on donation activities, graft sources, legal frameworks, donor protection measures, collection of donor outcome data, and long-term follow-up of paediatric and adult related and unrelated donors. The outcome of this survey served as a basis for elaborating the Recommendation CM/Rec(2020)6 of the Committee of Ministers to member States on establishing harmonised measures for the protection of haematopoietic progenitor cell donors.
Assuntos
Mobilização de Células-Tronco Hematopoéticas , Doadores de Tecidos , Adulto , Humanos , Criança , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas , Doadores não Relacionados , Medula Óssea , Europa (Continente)Assuntos
Pessoal de Saúde/organização & administração , Tráfico de Pessoas/prevenção & controle , Transplante de Rim/efeitos adversos , Tráfico de Órgãos/prevenção & controle , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Aloenxertos/provisão & distribuição , Tráfico de Pessoas/economia , Tráfico de Pessoas/estatística & dados numéricos , Humanos , Incidência , Rim/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/economia , Transplante de Rim/legislação & jurisprudência , Transplante de Rim/métodos , Turismo Médico/economia , Turismo Médico/legislação & jurisprudência , Turismo Médico/tendências , Tráfico de Órgãos/economia , Tráfico de Órgãos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Papel Profissional , Obtenção de Tecidos e Órgãos/economia , Obtenção de Tecidos e Órgãos/organização & administração , Obtenção de Tecidos e Órgãos/estatística & dados numéricosRESUMO
BACKGROUND: Transplant therapy is considered the best and often the only available treatment for thousands of patients with organ failure that results from communicable and noncommunicable diseases. The number of annual organ transplants is insufficient for the worldwide need. METHODS: We elaborate the proceedings of the workshop entitled "The Role of Science in the Development of International Standards of Organ Donation and Transplantation," organized by the Pontifical Academy of Sciences and cosponsored by the World Health Organization in June 2021. RESULTS: We detail the urgency and importance of achieving national self-sufficiency in organ transplantation as a public health priority and an important contributor to reaching relevant targets of the United Nations Agenda for Sustainable Development. It details the elements of a global action framework intended for countries at every level of economic development to facilitate either the establishment or enhancement of transplant activity. It sets forth a proposed plan, by addressing the technical considerations for developing and optimizing organ transplantation from both deceased and living organ donors and the regulatory oversight of practices. CONCLUSIONS: This document can be used in governmental and policy circles as a call to action and as a checklist for actions needed to enable organ transplantation as treatment for organ failure.
Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , Doadores Vivos , Assistência ao PacienteAssuntos
Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Doadores Vivos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/normas , Comitês Consultivos/normas , Europa (Continente) , Feminino , Humanos , Transplante de Rim/normas , Masculino , Melhoria de Qualidade , Fatores de TempoRESUMO
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.Trial registration: NCT04370808.
Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Polimorfismo Genético , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/genética , Idoso , Biomarcadores , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Feminino , Predisposição Genética para Doença , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Portugal/epidemiologia , Prevalência , Índice de Gravidade de Doença , Proteínas de Transporte Vesicular/genética , Proteína de Ligação a Vitamina D/genética , Vitamina D3 24-Hidroxilase/genéticaRESUMO
PURPOSE: Prescription patterns of non-vitamin K antagonist oral anticoagulants (NOACs) are unknown among primary care physicians, where most patients with nonvalvular atrial fibrillation (NVAF) are diagnosed and followed up. The goal of this study was to evaluate overdosing and underdosing of NOACs in patients with NVAF followed up in primary care and determine their clinical predictors. METHODS: This multicenter cross-sectional study included all patients with NVAF followed up in 13 primary care units in the center region of Portugal. Patients receiving antithrombotic regimens other than NOACs and patients with missing data were excluded. FINDINGS: The study included 858 patients with NVAF on an NOAC regimen. Overall, 30.3% were prescribed an off-label dosage (25.4% with infratherapeutic dosing [ITD] and 4.9% with supratherapeutic dosing). Chronic kidney disease (odds ratio, 14.0; 95% CI, 5.4-36.5; P < 0.001) and female sex (odds ratio, 2.6; 95% CI, 1.2-5.7; P < 0.001) were independent predictors of supratherapeutic dosing. We also found a significant effect of chronic kidney disease on ITD (odds ratio, 0.22; 95% CI, 0.258-0.678; P < 0.001). IMPLICATIONS: In primary care, NOACs are frequently prescribed with unadjusted dosages, generally infratherapeutic. Attention should be paid to women and patients with chronic kidney disease.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Erros de Medicação , Padrões de Prática Médica , Atenção Primária à Saúde , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
M cells assist mucosal immune surveillance by transcytosis of particles to underlying lymphoid tissue, but the mechanisms of M cell differentiation are poorly understood. To develop a better defined cell culture model of M cell differentiation, we treated human (Caco-2BBe) and rat (IEC-6) intestinal epithelial cell lines with lymphotoxin beta receptor (LTbetaR) and TNF receptor (TNFR) agonists. Treated cells were studied for regulation of genes associated with M cell and follicle-associated epithelium (FAE). We found that LTbetaR and TNFR agonists induce transcription of FAE-specific genes (Ccl20 and Lamb3) in Caco2-BBe cells and IEC-6 cells as well as rodent M cell specific genes such as Sgne-1/Scg5, Cldn4, and Gp2. The cytokines have distinct but complementary effects; TNFR agonists mainly induced FAE-specific genes, while the LTbetaR agonist induced M cell specific genes. The combination of cytokines showed additive induction of the FAE-associated Ccl20, Lamb3 and a surprising induction of CD137/Tnfrsf9. On the other hand TNF agonists appeared to suppress expression of some LTbetaR-induced genes. Functionally, cytokine treatment led to the reorganization of microvilli and Claudin-4 redistribution. These studies suggest complex interactions between these cytokines in the context of either inflammation or tissue differentiation.
Assuntos
Células Epiteliais/metabolismo , Mucosa Intestinal/citologia , Receptor beta de Linfotoxina/agonistas , Receptores do Fator de Necrose Tumoral/agonistas , Regulação para Cima/efeitos dos fármacos , Animais , Anexina A5/genética , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Células CACO-2 , Moléculas de Adesão Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Quimiocina CCL20/genética , Claudina-4 , Citocinas/genética , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Proteínas Ligadas por GPI , Humanos , Receptor beta de Linfotoxina/imunologia , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Microvilosidades/efeitos dos fármacos , Proteína Secretora Neuroendócrina 7B2/genética , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Transporte Proteico/efeitos dos fármacos , Ratos , Staphylococcus aureus/imunologia , Fator de Transcrição RelB/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa/farmacologia , CalininaRESUMO
The 2018 Edition of the Declaration of Istanbul on Organ Trafficking and Transplant Tourism (DoI) provides an updated set of principles and definitions to guide policymakers and health professionals working in organ donation and transplantation. A draft of the new edition was circulated to the public and transplant professionals through an online consultation process, which also sought feedback on a draft explanatory article that explained the principles and discussed some of their practical implications. Both drafts were revised in response to feedback from participants in the consultation. We present here the discussion article, which is intended to assist stakeholders in applying the principles of the DoI by providing more detailed information about the meaning and potential implications of implementing the DoI in various contexts.