Definições para a padronização da pesquisa de auto-anticorpos contra constituintes do núcleo (FAN HEp-2), nucléolo, citoplasma e aparelho mitótico e suas associações clínicas

OBJECTIVE: The Second Brazilian Consensus on Antinuclear Antibodies (ANA) in HEp-2 Cells approved and extended the decision trees developed during the First Brazilian Consensus in order to also offer information about mixed patterns of fluorescence. METHODS: Since this test elicits reactions not only to nuclear autoimmune antigens but also to different cell compartments, new denominations for the test were approved. Results and CONCLUSIONS: These new denominations encompass variations on the autoantibody testing against the nucleus (ANA HEp-2), nucleolus, cytoplasm, and mitotic apparatus issue. Furthermore, major clinical associations were described for each immunofluorescent pattern, facilitating the interpretation of laboratory results in the clinical practice.OBJETIVO: O Segundo Consenso Brasileiro de Fator Antinuclear (FAN) em Células HEp-2 ratificou os algoritmos de decisão para leitura dos padrões do FAN na imunofluorescência indireta vistos na primeira edição do Consenso Brasileiro, adicionando ainda um novo algoritmo relacionado com os padrões mistos. MÉTODOS: Tendo em vista a habilidade do teste em detectar autoantígenos nos distintos compartimentos celulares, e não apenas no núcleo, propõe-se novas denominações para este exame laboratorial. RESULTADOS E CONCLUSÕES: Como novas denominações algumas sugestões foram igualmente aceitas, dentro do tema pesquisa de auto-anticorpos contra constituintes do núcleo (FAN HEp-2), nucléolo, citoplasma e aparelho mitótico. Foram abordadas as principais relevâncias clínicas com os padrões de FAN descritos, facilitando o melhor uso do ensaio pelo médico.FMUSPUNIFESPBio-Rad Laboratório BrasilHospital Geral de GoiâniaBiomédicaUniversidade Federal de UberlândiaUFMG HCPUCRS HCNew Life Produtos HospitalaresUniversidade Católica de GoiásFMUSP HC Laboratório CentralPatologista ClínicaFMUSP HCFrischmann Aisengart Unidad InmunologíaUniversidade Católica de Goiás Laboratório de Auto-ImunidadeExame Medicina LaboratorialFMUFG HC Laboratório de Imuno-Reumatologia e HLALab. Santa LuziaMedivax/BionHSPE/SPUniversidade Católica de Goiás Laboratório da Área de SaúdeFarmacêutica-BioquímicaUniv. Fed. Mato GrossoFMUFG Serviço de ReumatologiaHospital Durand Unidad InmunologíaLaboratório ClínicoUFRGS HCPA Serviço de ReumatologiaUERJ FCMUFMG FMHospital Universitário de Brasília Laboratório de ReumatologiaUNIFESPSciEL

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Immunoglobulins intrathecal synthesis evaluation in bone marrow transplantation

The central nervous system involvement in chronic graft versus host disease (GVHD) has been suggested. Chronic GVHD resembles auto immune connective tissue disorders. In order to investigate the immunoglobulin intra blood brain barrier (BBB) synthesis during chronic GVHD, and contribute to understanding the pathophysiology of the disease, we studied 33 patients who underwent allogeneic bone marrow transplants (BMT) from HLA identical related donors. Immunoglobulin intra BBB synthesis was investigated quantitative and qualitatively. The samples were collected pre BMT, pos BMT and during chronic GVHD. There were no evidence of immunoglobulin intra BBB synthesis, and no oligoclonal bands were found. Only isolated cases suggested IgG and IgA intra BBB synthesis, and in one case IgM during GVHD.UNIV FED PARANA,HOSP CLIN,SERV TMO,BR-80060900 CURITIBA,PARANA,BRAZILUNIV FED PARANA,HOSP CLIN,DISCIPLINA NEUROL,BR-80060900 CURITIBA,PARANA,BRAZILUNIFESP,ESCOLA PAULISTA MED,DISCIPLINA IMUNOL,SAO PAULO,BRAZILUNIV SAO PAULO,FAC MED,CTR INVEST NEUROL,BR-05508 SAO PAULO,BRAZILUNIFESP,ESCOLA PAULISTA MED,DISCIPLINA IMUNOL,SAO PAULO,BRAZILWeb of Scienc

II brazilian consensus on antinuclear antibodies in HEp-2 cells : definitions for standardizartion of autoantibody testing against the nucleus (ANA HEp-2), nucleolus, cytoplasm and mitotic apparatus, as wel as its clinical associations

Objetivo: O Segundo Consenso Brasileiro de Fator Antinuclear (FAN) em Células HEp-2 ratificou os algoritmos de decisão para leitura dos padrões do FAN na imunofluorescência indireta vistos na primeira edição do Consenso Brasileiro, adicionando ainda um novo algoritmo relacionado com os padrões mistos. Métodos: Tendo em vista a habilidade do teste em detectar autoantígenos nos distintos compartimentos celulares, e não apenas no núcleo, propõe-se novas denominações para este exame laboratorial. Resultados e Conclusões: Como novas denominações algumas sugestões foram igualmente aceitas, dentro do tema “pesquisa de auto-anticorpos contra constituintes do núcleo (FAN HEp-2), nucléolo, citoplasma e aparelho mitótico”. Foram abordadas as principais relevâncias clínicas com os padrões de FAN descritos, facilitando o melhor uso do ensaio pelo médico.Objective: The Second Brazilian Consensus on Antinuclear Antibodies (ANA) in HEp-2 Cells approved and extended the decision trees developed during the First Brazilian Consensus in order to also offer information about mixed patterns of fluorescence. Methods: Since this test elicits reactions not only to nuclear autoimmune antigens but also to different cell compartments, new denominations for the test were approved. Results and Conclusions: These new denominations encompass variations on the “autoantibody testing against the nucleus (ANA HEp-2), nucleolus, cytoplasm, and mitotic apparatus” issue. Furthermore, major clinical associations were described for each immunofluorescent pattern, facilitating the interpretation of laboratory results in the clinical practice

Forward-backward correlations and charged-particle azimuthal distributions in pp interactions using the ATLAS detector

"Using inelastic proton-proton interactions at root s = 900 GeV and 7 TeV, recorded by the ATLAS detector at the LHC, measurements have been made of the correlations between forward and backward charged-particle multiplicities and, for the first time, between forward and backward charged-particle summed transverse momentum. In addition, jet-like structure in the events is studied by means of azimuthal distributions of charged particles relative to the charged particle with highest transverse momentum in a, selected kinematic region of the event. The results are compared with predictions from tunes of the PYTHIA and HERWIG++ Monte Carlo generators, which in most cases are found to provide a reasonable description of the data.