IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

Clinical and molecular correlates of the ASPECTS in the acute phase of stroke / Correlação clínica e molecular com a ASPECTS na fase aguda do acidente vascular cerebral

ABSTRACT Background: The Alberta Stroke Program Early CT Score (ASPECTS) scale was developed for monitoring early ischemic changes on CT, being associated with clinical outcomes. The ASPECTS can also associate with peripheral biomarkers that reflect the pathophysiological response of the brain to the ischemic stroke. Objective: To investigate the association between peripheral biomarkers with the Alberta Stroke Program Early CT Score (ASPECTS) in individuals after ischemic stroke. Methods: Patients over 18 years old with acute ischemic stroke were enrolled in this study. No patient was eligible for thrombolysis. The patients were submitted to non-contrast CT in the first 24 hours of admission, being the Alberta Stroke Program Early CT Score and clinical and molecular evaluations applied on the same day. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale and the Mini-Mental State Examination for clinical evaluation were also applied to all subjects. Plasma levels of BDNF, VCAM-1, VEGF, IL-1β, sTNFRs and adiponectin were determined by ELISA. Results: Worse neurological impairment (NIHSS), cognitive (MEEM) and functional (Rankin) performance was observed in the group with changes in the NCTT. Patients with NCTT changes also exhibited higher levels of IL-1β and adiponectin. In the linear multivariate regression, an adjusted R coefficient of 0.515 was found, indicating adiponectin and NIHSS as independent predictors of ASPECTS. Conclusion: Plasma levels of adiponectin are associated with the ASPECTS scores.

RESUMO Introdução: A Alberta Stroke Early Score (ASPECTS) foi desenvolvida para monitorização de alterações isquêmicas precoces na tomografia computadorizada de crânio, estando associada a desfechos clínicos. A ASPECTS também pode se associar aos biomarcadores periféricos que refletem a resposta fisiopatológica do cérebro ao AVC isquêmico. Objetivo: Investigar à associação entre os parâmetros periféricos com a Alberta Stroke Early Score (ASPECTS) em indivíduos após acidente vascular cerebral isquêmico. Métodos: Pacientes acima de 18 anos com AVC isquêmico agudo foram incluídos neste estudo. Nenhum paciente foi elegível para trombólise. Os pacientes foram submetidos à tomografia computadorizada sem contraste nas primeiras 24 horas da admissão, a ASPECTS e as avaliações clínicas e moleculares aplicadas no mesmo dia. O National Institutes of Health Stroke Scale (NIHSS), a escala de Rankin modificada e o Mini Exame do Estado Mental para avaliação clínica também foram aplicados a todos os indivíduos. Os níveis plasmáticos de BDNF, VCAM-1, VEGF, IL-1β, sTNFRs e adiponectina foram determinados por ELISA. Resultados: Pior desempenho neurológico (NIHSS), cognitivo (MEEM) e funcional (Rankin) foram observados no grupo com alterações na ASPECTS. Pacientes com alterações na ASPECTS também exibiram níveis mais altos de IL-1β e adiponectina. Na regressão multivariada linear, foi encontrado um coeficiente R ajustado de 0,515, indicando adiponectina e NIHSS como preditores independentes para a ASPECTS. Conclusão: Os níveis plasmáticos de adiponectina estão associados aos escores da ASPECTS.

Fatores associados a capacidade funcional de idosos adscritos à Estratégia de Saúde da Família / Factors associated with functional capacity in the elderly enrolled in the Family Health Strategy

Resumo O estudo investigou a prevalência de declínio da capacidade funcional e seus fatores associados em idosos adscritos à Estratégia Saúde da Família (ESF), em um município do sul de Minas Gerais. Estudo observacional, transversal, de base populacional, com 406 idosos. A capacidade funcional foi avaliada pelo Short Physical Performance Battery (SPPB); seus fatores associados foram avaliados por um questionário estruturado incluindo aspectos sociodemográficos, econômicos, clínicos e físicos. Concentrações de mediadores inflamatórios foram dosadas pelo método de Elisa ("Enzyme-Linked Immunosorbent Assay"). Regressão linear múltipla foi usada para as análises (p < 0,05). A prevalência de declínio funcional na amostra foi de 57,6% e os fatores associados à capacidade funcional foram: idade avançada, sexo feminino, número de medicamentos, sintomas depressivos, elevadas concentrações plasmáticas de receptor solúvel 1 do fator de necrose tumoral alfa (sTNFR1) e baixa força de preensão palmar. Os resultados mostraram que a capacidade funcional foi associada a uma rede de fatores multidimensionais. O presente estudo contribui para a prática de profissionais na ESF ao apontar os principais fatores que podem nortear as ações de promoção e prevenção do declínio da capacidade funcional na população idosa.

Abstract The study investigated the prevalence of functional capacity decline and its associated factors in the older people enrolled in the Family Health Strategy (ESF) in a city in the south of Minas Gerais. This is an observational, cross-sectional, population-based study with 406 elderly (70.49 years ± 6.77). The functional capacity was evaluated by the Short Physical Performance Battery (SPPB), and its associated factors were evaluated by a structured questionnaire including sociodemographic, economic, clinical and physical aspects. The analysis of plasma levels of inflammatory mediators was performed by the ELISA method. Multiple linear regression was used for the analyses (p < 0.05). The prevalence of functional decline in the sample was 57.6% and factors associated with functional capacity were advanced age, female gender, number of medications, depressive symptoms, high plasma concentrations of the soluble receptor of tumor necrosis factor alpha 1 (sTNFR1) and low handgrip strength. The results demonstrated that functional capacity was associated with a network of multidimensional factors. This study contributes to the practice of ESF professionals by indicating the main factors that can guide actions to promote and prevent the decline of functional capacity in the elderly population.

Avaliação da interleucina 3 como marcador prognóstico na sepse / Role of interleukin-3 as a prognostic marker in septic patients

RESUMO Objetivo: Avaliar a acurácia dos níveis de interleucina 3 para predizer prognóstico em pacientes sépticos. Métodos: Conduzimos uma coorte prospectiva que incluiu pacientes adultos internados em unidade de terapia intensiva, que apresentassem sepse ou choque séptico iniciados há até 48 horas. Mediram-se os níveis séricos de interleucina 3 quando da inclusão (dia 1) e nos dias 3 e 7. O desfecho primário analisado foi a mortalidade hospitalar por qualquer causa. Resultados: Foram incluídos 120 pacientes. Os níveis séricos de interleucina 3 dosados à inclusão foram significativamente mais elevados em pacientes que faleceram em comparação aos que sobreviveram à internação hospitalar (91,2pg/mL versus 36pg/mL; p = 0,024). Em modelo de sobrevivência de Cox com inclusão de idade e valores sequenciais de SOFA, os níveis de interleucina 3 mensurados na inclusão mantiveram-se independentemente associados à mortalidade hospitalar (HR 1,032; IC95% 1,010 - 1,055; p = 0,005). Em curva Característica de Operação do Receptor construída para investigação adicional da acurácia da interleucina 3 na predição do prognóstico, encontrou-se área sob a curva de 0,62 (IC95% 0,51 - 0,73; p = 0,024) para mortalidade hospitalar. Valores iniciais de interleucina 3 acima de 127,5pg/mL mostraram-se significativamente associados à mortalidade hospitalar (p = 0,019; OR = 2,97; IC95% 1,27 - 6,97; p = 0,019), entretanto com baixo desempenho (especificidade de 82%, sensibilidade de 39%, valor preditivo positivo de 53%, valor preditivo negativo de 72%, razão de verossimilhança negativa de 0,73 e razão de verossimilhança positiva de 2,16). Conclusão: Níveis elevados de interleucina 3 mostraram-se independentemente associados à mortalidade hospitalar em pacientes sépticos, entretanto com baixo desempenho clínico.

ABSTRACT Objective: To evaluate the accuracy of IL-3 to predict the outcome of septic patients. Methods: Prospective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality. Results: One hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio). Conclusion: Higher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

Prevalence of low bone mass and changes in vitamin D levels in human immunodeficiency virus-infected adults unexposed to antiretrovirals

Abstract INTRODUCTION: The prevalence of low bone mass is 3 times higher in people living with human immunodeficiency virus (PLWH) and using antiretrovirals than in the HIV-unaffected population. Changes in vitamin D levels is one of the factors associated with decreased bone mass. The objective of this study is to evaluate the low bone mass and altered vitamin D levels in PLWH who have not been exposed to antiretrovirals. METHODS: A cross-sectional study was carried out with HIV-infected individuals between the ages of 18 and 55 years immediately prior to the start of antiretroviral therapy in a specialized reference center focusing on infectious and parasitic diseases. Results of clinical examination (patient's weight, height, blood pressure, and clinical history), laboratory tests, and X-ray absorptiometry, were collected. RESULTS: Sixty patients were included, with a mean age of 34 years. Nine (16.7%) patients presented with low bone mass and 4 (7.1%) patients showed low total femur BMD. Analysis revealed that 23.3% and 36.7% of the patients had deficient and insufficient levels of 25-hydroxyvitamin D3, respectively. CONCLUSIONS: Our study population presented with compromised bone health and with low bone mineral density and 25-(OH)-vitamin D levels.

Neuroinflamação na esclerose lateral amiotrófica / Neuroinflammation in amyotrophic lateral sclerosis

A esclerose lateral amiotrófica (ELA) esporádica é uma doença neurodegenerativa que acomete o neurônio motor. Sua etiologia ainda não foi totalmente esclarecida e é considerada multifatorial. O objetivo desse trabalho é fazer uma revisão narrativa sobre os mecanismos fisiopatológicos da ELA esporádica, com foco no papel da neuroinflamação, além de descrever estudos envolvendo a pesquisa de biomarcadores de diagnóstico e prognóstico. O processo de neuroinflamação na ELA é considerado secundário às alterações que levam à morte neuronal, podendo influenciar na taxa de progressão da doença. Existem diversos estudos sobre o perfil dos fatores inflamatórios na ELA, por vezes com resultados contraditórios, reforçando a dificuldade de análise desses fatores num organismo dinâmico. Ainda assim, no contexto da ELA, o estudo de possíveis biomarcadores diagnósticos e/ou prognósticos é válido e de grande interesse, pois permitiria um avanço nos ensaios clínicos que buscam novos tratamentos, bem como na condução e planejamento de cada caso.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the motor neuron. Its etiology has not been fully clarified and is considered multifactorial. The aim of this sudy is to perform a narrative review on the pathophysiological mechanisms of sporadic ALS, focusing on the role of neuroinflammation. It will also discuss studies investigating diagnostic and prognostic biomarkers. Neuroinflammation in ALS is considered to be a secondary event, triggered by neuronal death, and it may influence disease progression. There are several studies on inflammatory factors in ALS, some with contradictory findings, reinforcing the difficulty of assessing these factors in a dynamic organism. Even so, in ALS context, the study of possible diagnostic and/or prognostic biomarkers is valid and of great interest. This may allow the advance of clinical trials that investigate new treatments, as well as the management of individual cases.

Evaluation of inflammatory biomarkers, carotid intima-media thickness and cardiovascular risk in HIV-1 treatment-naive patients

Abstract INTRODUCTION Mortality among HIV patients is 3-15 times higher than that among the general population. Currently, most deaths are due to non-infectious diseases. Chronic inflammation and adverse events due to antiretroviral therapy play crucial roles in increasing cardiovascular risk (CVR). METHODS: This cross-sectional study aimed to evaluate carotid intima-media thickness (CIMT) and inflammatory biomarkers (D-dimer, ADAMTS13, GDF-15, sICAM-1, MPO, myoglobin, NGAL, SAA, sVCAM-1, and p-selectin) among naïve patients. RESULTS: Sixty-seven participants were included: median age, 32 years; males, 82.1%; non-white, 61.1%; higher education level, 62.7%; and exposed to HIV through sexual relationship (men who have sex with men), 68.7%. The median viral load and LTCD4+ value were 42,033 copies/mL and 426 cells/mm³. The prevalence of arterial hypertension was 16.4%; those of diabetes mellitus and dyslipidemia were 3% and 70.1%, respectively. The CIMT was 494.08 (± 96.84mm). The mean vascular age was 33.2 ± 18.9 years, one year longer than the chronological age, without statistical significance. CONCLUSIONS The majority of participants had a low CVR (94%). After reclassification, considering the CIMT percentiles, 13 (19.4%) patients had medium/ high CVR, while 54 (80.6%) patients had low CVR. The difference between the proportions of CVR when considering the CIMT and its corresponding percentile was statistically relevant. Body mass index was the only predictor of higher CVR (p = 0.03). No biomarker was found to predict CVR. People living with HIV have a high prevalence of dyslipidemia before ARV therapy.

Toxoplasma gondii infection and chronic schizophrenia: is there any association?

ABSTRACT Background: Toxoplasma gondii (T. gondii) infection has been identified as a risk factor for schizophrenia. Objectives: Herein, we sought to evaluate the association between T. gondii infection and clinical symptoms and quality of life in patients with schizophrenia. Methods: We conducted a cross-sectional study with 48 patients with chronic schizophrenia and 40 controls. Peripheral blood was drawn, and IgM and IgG anti-T. gondii antibodies were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). Depressive, positive and negative symptoms were assessed, respectively, by the Calgary Depression Scale (CDS) and the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed in patients by the Brazilian version of the Schizophrenia Cognition Rating Scale (SCoRS-BR). Quality of life was assessed by the Brazilian version of the Quality of Life in Schizophrenia scale (QLS-BR). Results: The prevalence and titers of T. gondii IgM and IgG antibodies did not differ between patients and controls. The positive serology for T. gondii IgG antibodies was not associated with illness symptoms, cognitive performance, depressive symptoms or quality of life. Discussion: Our findings suggest that toxoplasmosis infection is not associated with severity of symptoms, quality of life, cognitive or depressive symptoms in schizophrenia patients.

Serum levels of neurotrophic factors in active toxoplasmic retinochoroiditis

Abstract Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. Methods: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. Results: BDNF levels were significantly higher in patients before treatment when compared with controls (p = 0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. Conclusion: BDNF may be released in the context of the active TR inflammatory response.