Portuguese recommendations for the use of biological and targeted synthetic diseasemodifying antirheumatic drugs in patients with rheumatoid arthritis – 2020 update

Objective: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). Methods: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. Results: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. Conclusion: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.info:eu-repo/semantics/publishedVersio

Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells

The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals

Tertiary Lymphoid Organs in Rheumatoid Arthritis.

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. RA mainly affects the joints, with inflammation of the synovial membrane, characterized by hyperplasia, neo-angiogenesis, and immune cell infiltration that drives local inflammation and, if untreated, can lead to joint destruction and disability. In parallel to the well-known clinical heterogeneity, the underlying synovitis can also be significantly heterogeneous. In particular, in about 40% of patients with RA, synovitis is characterized by a dense lymphocytic infiltrate that can acquire the features of fully functional tertiary lymphoid organs (TLO). These structures amplify autoimmunity and inflammation locally associated with worse prognosis and potential implications for treatment response. Here, we will review the current knowledge on TLO in RA, with a focus on their pathogenetic and clinical relevance

Hemodiálise: seu significado e impacto para a vida do idoso Hemodiálisis: su significado e impacto para la vida del anciano Hemodialysis: its meaning and impact in the elderly life

O processo de envelhecimento que antes era restrito aos países desenvolvidos está ocorrendo nos países em desenvolvimento e de modo mais rápido. O surgimento de doenças não transmissíveis pode induzir alterações funcionais com maior intensidade, como a doença renal crônica. O objetivo deste trabalho é compreender o significado da hemodiálise para o idoso renal-crônico e o impacto dessa modalidade terapêutica em sua vida. Tratou-se de um estudo exploratório, de abordagem qualitativa, com entrevista com 22 idosos em tratamento dialítico. Foi utilizado como instrumento um roteiro, contendo perguntas abertas. A análise dos dados foi por meio da análise temática de Bardin. Como resultado, obtemos duas categorias: o significado de ser idoso em tratamento hemodialítico; e o impacto da hemodiálise na vida dos idosos. A pesquisa revelou que a hemodiálise afeta o cotidiano dos idosos, pois causa limitações sociais, envolvendo seu trabalho, hábitos alimentares, culturais, além do impacto na saúde mental.<br>El proceso de envejecimiento que anteriormente se limitaba a los países desarrollados se está produciendo en los países en desarrollo y más rápidamente. La aparición de las enfermedades no transmisibles puede inducir cambios funcionales con mayor intensidad, como la enfermedad renal crónica. El objetivo de este estudio es comprender el significado de la hemodiálisis para los ancianos, la insuficiencia renal crónica y el impacto de esta modalidad de tratamiento en su vida. Este fue un estudio exploratorio, cualitativo mediante entrevistas con 22 ancianos en diálisis. Se utilizó como herramienta de escritura, un guía con preguntas abiertas. El análisis de los datos fue por medio del análisis temático de Bardin. Como resultado, se obtienen dos categorías: el significado de los pacientes ancianos en hemodiálisis, el impacto de la hemodiálisis en pacientes ancianos. La pesquisa reveló que la hemodiálisis afecta el cotidiano de las personas mayores, les causa restricciones sociales relacionadas con sus hábitos de trabajo, culturales, además del impacto en la salud mental.<br>The aging process used to be restricted to developed countries, but nowadays it has been occurring faster and in developing countries too. The manifestation of noncommunicable diseases may lead to functional changes with higher complexity such as, Chronic Kidney Disease. The aim of this study was to understand the meaning of hemodialysis for elderly with chronic kidney disease and the impact of this therapy in their lives. This is an exploratory research with a qualitative approach. Twenty-two elderly undergoing hemodialysis were interviewed. A structured interview model containing open questions was used to collect data. The results were analyzed using Bardin's Thematic Analysis. Two categories emerged: the meaning of being an elderly undergoing hemodialysis; and the impact of hemodialysis in the elderly's lives. This research highlighted that hemodialysis affects the daily life of elderly causing social limitations concerning their occupations, eating and cultural habits and also influencing their mental health