Muscle glycome in idiopathic inflammatory myopathies: Impact in IL-6 production and disease prognosis.

Idiopathic inflammatory myopathies (IIM) are a group of chronic autoimmune diseases mainly affecting proximal muscles. Absence of meaningful prognostic factors in IIM has hindered new therapies development. Glycans are essential molecules that regulate immunological tolerance and consequently the onset of autoreactive immune response. We showed that muscle biopsies from patients with IIM revealed a deficiency in the glycosylation pathway resulting in loss of branched N-glycans. At diagnosis, this glycosignature predicted disease relapse and treatment refractoriness. Peripheral CD4+ T cells from active-disease patients shown a deficiency in branched N-glycans, linked to increased IL-6 production. Glycan supplementation, restoring homeostatic glycosylation profile, led to a decrease in IL-6 levels. This study highlights the biological and clinical importance of glycosylation in IIM immunopathogenesis, providing a potential mechanism for IL-6 production. This pinpoints muscle glycome as promising biomarker for personalized follow-up and a potential target for new therapies in a patients' subgroup with an ominous evolution.

Mudança no padrão de vírus respiratórios identificados em uma população pediátrica hospitalizada durante os anos de 2019 e 2020 / Change in the pattern of respiratory viruses identified in a pediatric population hospitalized during the years of 2019 and 2020

Introdução: de destaque como agente etiológico em várias doenças respiratórias, os vírus, tem grande importância dentro da Pneumologia Pediátrica. Objetivo: estudar os vírus identificados de secreções respiratórias de pacientes pediátricos, hospitalizados na enfermaria e UTI pediátrica, durante o período de janeiro de 2019 a dezembro de 2020. Metodologia: levantamento de resultados do RT-PCR (reação da transcriptase reversa seguida pela reação em cadeia da polimerase) de secreções respiratórias de pacientes pediátricos, através do GAL (Gerenciamento de Análises Laboratoriais) aplicando os filtros necessários para selecionar os pacientes da instituição e o período estipulado. Resultados: Foram realizadas 30 coletas em 2019 e 196 em 2020 de secreções respiratórias devido ao quadro de Síndrome Respiratória. As amostras coletadas em 2019 foram positivas para vírus em 56,7% dos casos investigados, sendo 6,7% para Influenza e 50% para Vírus Sincicial Respiratório (VSR), enquanto que em 2020 as amostras foram positivas em 21,4% dos casos, sendo todos eles para SARS-CoV-2. O período do ano com maior número de coletas de secreção foi em maio e junho considerando o ano de 2019 (60% das coletas de 2019), e julho, agosto e dezembro considerando o ano de 2020 (42,8% das coletas de 2020), com uma positividade de 77,7% (2019) e 25% (2020) para os vírus solicitados para pesquisa. Conclusão: Pôde-se perceber uma importante mudança no perfil dos vírus identificados dos quadros respiratórios entre 2019 e 2020, comparáveis ao perfil apresentado pelos Boletins Epidemiológicos do Ministério da Saúde, principalmente no ano de 2020 com o surgimento do novo coronavírus e sua pandemia. A etiologia viral presente na grande maioria dos quadros respiratórios da pediatria, deve sempre ser valorizada e os testes de identificação viral são ferramentas de grande aplicabilidade na clínica.

Introduction: highlighted as an etiological agent in several respiratory diseases, viruses, has great importance in Pediatric Pulmonology. Objective: study the viruses identified from respiratory secretions of pediatric patients hospitalized in the pediatric ward and ICU, during the period from January 2019 to December 2020. Methodology: survey of results of the RT-PCR (reverse transcriptase reaction followed by polymerase chain reaction) of respiratory secretions of pediatric patients, through the LAM (Laboratory Analysis Management) applying the necessary filters to select the patients of the institution and the stipulated period. Results: Thirty collections were performed in 2019 and 196 in 2020 for respiratory secretions due to the Respiratory Syndrome. The samples collected in 2019 were positive for viruses in 56.7% of the investigated cases, with 6.7% for Influenza and 50% for Respiratory Syncytial Virus (RSV), while in 2020 the samples were positive in 21.4% of the cases, all of which were for SARS-Cov-2. The period of the year with the highest number of secretion collections was in May and June considering 2019 (60% of 2019 collections), and July, August and December considering 2020 (42.8% of 2020 collections), with a positivity of 77.7% (2019) and 25% (2020) for viruses requested for research. Conclusion: It was possible to notice an important change in the profile of the viruses identified in respiratory conditions between 2019 and 2020, comparable to the profile presented by the Epidemiological Bulletins of the Ministry of Health, especially in the year 2020 with the emergence of the new coronavirus and its pandemic. The viral etiology present in the vast majority of pediatric respiratory conditions should always be valued and viral identification tests are tools of great applicability in the clinic.

Oral health status of patients with leukemia: a systematic review with meta-analysis.

OBJECTIVE: The aim of this study was to systematically review the literature regarding the prevalence of periodontal diseases and dental caries in patients with leukemia. METHODS: An electronic search for observational studies on oral health outcomes in patients with leukemia was performed on Medline/PUBMED, Embase, Web of Science, and Science Direct databases up to April 2020. Dental caries and periodontal diseases were assessed using the following standardized parameters, respectively: mean number of decayed, missing and filled teeth (DMFT), and presence of marginal inflammation (gingivitis) or clinical attachment loss (periodontitis). Two independent reviewers conducted all phases of review. Included studies reporting similar outcomes were subjected to random-effects meta-analysis. RESULTS: From 1,246 retrieved references, 39 were included. Most studies were cross-sectional investigations involving young patients with acute lymphoblastic leukemia. Nine studies presented high risk of bias and were not included on quantitative analyses. All studies in the meta-analysis (n = 14) were conducted with children/teenagers with acute leukemia. Pooled gingivitis prevalence in patients before and during leukemia treatment was 85% (95%CI 75, 97%; 4 studies) and 82% (95%CI 71, 94%; 6 studies), respectively. Pooled DMFT means were 2.28 (95%CI 1.31, 3.25; 7 studies) and 3.65 (95%CI 1.45, 5.86; 5 studies) respectively for patients during and after leukemia treatment. Studies regarding periodontitis prevalence were too few to run a meta-analysis. CONCLUSIONS: Based on cross-sectional data, young people with acute leukemia have high prevalence of gingivitis and caries experience. These findings indicate that the effect of leukemia on oral health still needs to be better investigated.

Estudo de vida real do perfil epidemiológico e da adesão ao tratamento de pacientes com asma alérgica grave em uso de omalizumabe durante 12 meses / Real-life study of the epidemiological profile and adherence to the treatment of patients with severe allergic asthma using omalizumab for 12 months

Introdução: a asma é uma doença heterogênea, caracterizada por inflamação crônica das vias aéreas inferiores, associada a diferentes fenótipos. O omalizumabe é utilizado em adição ao tratamento quando não se obtém o controle adequado da asma. Este estudo mostra o perfil epidemiológico e a adesão ao tratamento dos pacientes acompanhados no Ambulatório de Especialidades do Hospital Universitário da Universidade Estadual de Londrina (AEHU-UEL) em uso de omalizumabe em um período de 12 meses. Método: realizado um estudo transversal retrospectivo através de dados secundários de prontuário avaliando pacientes com diagnóstico de asma alérgica grave em uso de omalizumabe nos 12 meses prévios ao recrutamento. Resultados: foram selecionados 40 pacientes que preencheram os critérios de inclusão. A média de idade foi de 51,4 anos, com predomínio de mulheres (70%), brancos (48%), não tabagistas (90%), com sobrepeso ou obesidade (75%) e diagnóstico de asma na infância (45%). O tempo médio de tratamento foi de 8,1 anos (DP 0,8). Havia comorbidades em 85% dos pacientes, com predomínio de rinite (62,5%) e DRGE (40%). Houve exacerbação em 29 pacientes levando a 8 internações (27,5%); 93% dos exacerbadores apresentaram faltas. Conclusão: a amostra é comparável a outros estudos de vida real nos achados epidemiológicos (idade, sexo, fenótipo, tempo de diagnóstico, controle da doença e tabagismo). O elevado número de faltas, assim como frequência de DRGE e outras comorbidades e a baixa adesão à terapêutica, podem justificar o elevado número de exacerbações e maior dificuldade de controle.(AU)

Introduction: asthma is a hetereogeneous disease, characterized by chronic inflammation of the lower airways associated with different phenotypes. Omalizumab is used in addition to treatment when adequate asthma control is not achieved. This study shows the epidemiological profile and the adherence to the treatment of patients followed at the Medical Clinic of the State University Hospital of Londrina (AEHU-UEL) using omalizumab in the last 12 months. Methods: severe allergic asthma patients using omalizumab in the last 12 months were evaluated by means of secondary medical records. Results: forty patients were included and had complete medical record. The average age was 51.4 years mostly women (70%), white (48%), non-smoker (90%), overweight or obese (75%) and childhood asthma diagnosis (45%). The average treatment time was 8.1 years (SD0.8). There were co-morbidities in 85% of the patients, mainly rhinitis in 62.5% and GERD in 40%. There were exacerbations in 29 patients, leading to 8 hospitalizations (27.5%), 93% of exacerbators was missed at least one time. Strong association with rhinitis (p=0.07), and no disease control (p=0.22). Conclusion: the sample is comparable to other real-life studies in almost all epidemiological findings (age, sex, phenotype, time of diagnosis, disease control and smoking). The high number of absences and frequency of GERD and other comorbidities, and poor adhesion, may justify the high number of exacerbations and more difficulty to control the disease. (AU)

Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation. Finally, multiple mechanisms, including the inhibition of the production of inflammatory mediators and activation of endogenous opioid pathways, may mediate azadirachtin activities in experimental models of inflammation and pain.