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OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.
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Antimaláricos , Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Inibidores de Janus Quinases , Humanos , Inibidores de Janus Quinases/efeitos adversos , Antimaláricos/efeitos adversos , Estudos de Coortes , Artrite Reumatoide/epidemiologia , Antirreumáticos/efeitos adversos , Produtos Biológicos/uso terapêuticoRESUMO
BACKGROUND: In Brazil, socioeconomic differences in the incidence of rheumatoid arthritis (RA) have been demonstrated, which are important in the formulation of hypotheses regarding the association between environmental factors, lifestyle and the risk of disease development. This study examines how the socioeconomic condition of the patient with RA in Brazil, assessed according to social class, educational level, employment situation and use of caregivers, affects the times between the beginning of symptoms and diagnosis and the beginning of the use of disease-modifying antirheumatic drugs, as well as the presence of erosive disease and functional status. METHODS: This work is part of a multicentric study called REAL - Rheumatoid Arthritis in Real Life in Brazil, which is a prospective observational cohort study. RESULTS: As described in the REAL study, we included a total of 1115 patients. It was noted that patients with an educational classification of up to second grade incomplete presented with erosion percentages above those with a higher grade complete. Patients with caregivers presented a higher percentage of erosion than patients without caregivers. We verified that patients from economic classes above B2 presented fewer occurrences of erosion than those from classes C2, D-E. We also analyzed the average time differences from the beginning of symptoms and diagnosis and the beginning of treatment, according to academic level, erosion and economic classification. Patients with first grade complete showed an HAQ-DI averages higher than those with second grade complete. The patients who had employment showed lower HAQ-DI averages than patients who were not employed. The patients with erosion showed an HAQ-DI value higher than those without erosion. Patients with caregivers showed an HAQ-DI average higher than that of without caregivers. CONCLUSION: This study showed that the therapeutic window of RA is not being reached, and therefore we should have a policy to expand and ensure access to public health for all patients, especially those with lower levels of education and income. TRIAL REGISTRATION: This study was approved by the National Commission of Ethics in Research.
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Artrite Reumatoide/terapia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Brasil , Cuidadores , Estudos de Coortes , Estudos Transversais , Escolaridade , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Classe Social , Fatores SocioeconômicosRESUMO
We report a 44-year-old female patient diagnosed with neuropsychiatric systemic lupus erythematosus and probable ischemia secondary to vasculitis in the speech motor region (Broca's area). After corticosteroid treatment, the patient recovered the speech, presented clinical improvement, and SISCOM showed reperfusion of the ischemic area (luxury perfusion).
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BACKGROUND: Slice cultures have been prepared from several organs. With respect to the brain, advantages of slice cultures over dissociated cell cultures include maintenance of the cytoarchitecture and neuronal connectivity. Slice cultures from adult human brain have been reported and constitute a promising method to study neurological diseases. Despite this potential, few studies have characterized in detail cell survival and function along time in short-term, free-floating cultures. NEW METHOD: We used tissue from adult human brain cortex from patients undergoing temporal lobectomy to prepare 200 µm-thick slices. Along the period in culture, we evaluated neuronal survival, histological modifications, and neurotransmitter release. The toxicity of Alzheimer's-associated Aß oligomers (AßOs) to cultured slices was also analyzed. RESULTS: Neurons in human brain slices remain viable and neurochemically active for at least four days in vitro, which allowed detection of binding of AßOs. We further found that slices exposed to AßOs presented elevated levels of hyperphosphorylated Tau, a hallmark of Alzheimer's disease. COMPARISON WITH EXISTING METHOD(S): Although slice cultures from adult human brain have been previously prepared, this is the first report to analyze cell viability and neuronal activity in short-term free-floating cultures as a function of days in vitro. CONCLUSIONS: Once surgical tissue is available, the current protocol is easy to perform and produces functional slices from adult human brain. These slice cultures may represent a preferred model for translational studies of neurodegenerative disorders when long term culturing in not required, as in investigations on AßO neurotoxicity.
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Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Neurônios/metabolismo , Neurotransmissores/metabolismo , Adulto , Análise de Variância , Epilepsia do Lobo Temporal/patologia , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Fosfopiruvato Hidratase/metabolismo , Cloreto de Potássio/farmacologia , Proteínas tau/metabolismoRESUMO
OBJECTIVES: Neutrophils play a major role in rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate if neutrophil DNA damage in RA patients is associated with the disease activity, autoantibodies status, carriage of the RA shared epitope (SE) and treatment. METHODS: DNA damage was assessed by alkaline comet assay in peripheral blood (77 patients and 55 healthy controls) and in 10 RA synovial fluid neutrophils. Evaluation of the respiratory burst of 30 patients with RA and 30 healthy controls was done. RESULTS: Compared to controls, RA patients exhibited increased neutrophil DNA damage. RA synovial fluid cells DNA damage was increased when compared to OA synovial fluids cells. In addition, our study shows that anti-TNF-α therapy reduces the frequency of DNA damage. Patients with simple or double dose of shared epitope presented a higher frequency of DNA damage compared to patients without the allele. Positive correlation was found between neutrophil DNA damage and DAS-28 and ROS production. CONCLUSIONS: Our results suggest that an increase of respiratory burst of neutrophils reflects the higher levels of DNA damage in neutrophils and a positive correlation between DNA damage and disease activity shows the importance of oxidative stress in the pathogenesis of RA.
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Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Dano ao DNA , Epitopos/imunologia , Antígenos HLA/imunologia , Neutrófilos/imunologia , Neutrófilos/patologia , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Autoanticorpos/sangue , Estudos de Casos e Controles , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Epitopos/sangue , Epitopos/genética , Feminino , Antígenos HLA/sangue , Antígenos HLA/genética , Humanos , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Explosão Respiratória , Índice de Gravidade de Doença , Líquido Sinovial/imunologia , Líquido Sinovial/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Introduction Hydrocephalus is a frequent neurological condition in childhood. The most common approach to this disease is still ventricular shunting. However, shunting problems, including catheter infection or shunting malfunctioning, contribute to several complications, such as extra-axial hematomas, which are a possibly lifethreatening. Case report We report the case of a 6-month-old female infant victim of brain trauma. She was previously shunted because of an obstructive hydrocephalus consequent of an aqueductal stenosis diagnosed early after birth. After brain injury, initial symptoms were only irritability and horizontal nystagmus. A computed tomography scan revealed an extra-axial mass lesion that suggested a giant globular extradural hematoma. The patient was submitted to a small exploratory craniectomy to evacuate the blood clot. Surprisingly, the supposed extradural hematoma was, in fact, a chronic subdural hematoma with an unusual shape. After the surgical drainage, the patient remained asymptomatic. No lesion recurrence has been detected so far. Conclusions The case illustrates a very uncommon and interesting presentation of a common neurosurgical disease. A full characterization of the lesion and its pathophysiology is made, and a particular surgical management is proposed and thoroughly discussed
Introdução A hidrocefalia é uma condição neurológica frequente na infância. A abordagem mais comum continua sendo o shunt ventricular. Contudo, os problemas de shunt, incluindo a infecção do catéter ou o mal funcionamento do shunt, contribuem para diversas complicações, como hematomas extra-axiais, uma complicação com potencial comprometimento de vida. Relato de caso Relatamos o caso de uma recém-nascida de 6 meses de idade vítima de trauma cerebral. Ela recebeu previamente um shunt para hidrocefalia obstrutiva consequente de estenose do aqueduto diagnosticada logo após o nascimento. Após o dano cerebral, os sintomas iniciais foram apenas irritabilidade e nistagmo horizontal. Tomografia computadorizada revelou uma massa extra-axial lesionada que sugeriu um hematoma globular extradural gigante. A paciente foi submetida a uma pequena craniectomia exploratória para extração do coágulo sanguíneo. Surpreendentemente, o suposto hematoma extradural era, na verdade, um hematoma subdural crônico com formato anormal. Após drenagem cirúrgica, a paciente permaneceu assintomática. Nenhuma lesão recorrente foi detectada até a presente publicação. Conclusões O caso exemplifica uma apresentação muito incomum e interessante de um distúrbio neurocirúrgico comum. Uma caracterização completa da lesão e de sua patofisiologia é feita, e um procedimento cirúrgico particular é proposto e exaustivamente discutido.
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Humanos , Feminino , Lactente , Hematoma Subdural Crônico , Hidrocefalia , Derivação Ventriculoperitoneal , Constrição Patológica , Lesões Encefálicas Traumáticas/complicaçõesAssuntos
Aneurisma/terapia , Síndrome de Behçet/terapia , Embolização Terapêutica/métodos , Embucrilato/uso terapêutico , Artéria Pulmonar , Adulto , Aneurisma/diagnóstico por imagem , Angiografia , Síndrome de Behçet/diagnóstico por imagem , Meios de Contraste , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Endothelins (ETs) are involved in several inflammatory events. The present study investigated the efficacy of bosentan, a dual ETA/ETB receptor antagonist, in collagen-induced arthritis (CIA) in mice. TREATMENT: CIA was induced in DBA/1J mice. Arthritic mice were treated with bosentan (100 mg/kg) once a day, starting from the day when arthritis was clinically detectable. METHODS: CIA progression was assessed by measurements of visual clinical score, paw swelling and hypernociception. Histological changes, neutrophil infiltration and pro-inflammatory cytokines were evaluated in the joints. Gene expression in the lymph nodes of arthritic mice was evaluated by microarray technology. PreproET-1 mRNA expression in the lymph nodes of mice and in peripheral blood mononuclear cells (PBMCs) was evaluated by real-time PCR. The differences were evaluated by one-way ANOVA or Student's t test. RESULTS: Oral treatment with bosentan markedly ameliorated the clinical aspects of CIA (visual clinical score, paw swelling and hyperalgesia). Bosentan treatment also reduced joint damage, leukocyte infiltration and pro-inflammatory cytokine levels (IL-1ß, TNFα and IL-17) in the joint tissues. Changes in gene expression in the lymph nodes of arthritic mice returned to the levels of the control mice after bosentan treatment. PreproET mRNA expression increased in PBMCs from rheumatoid arthritis (RA) patients but returned to basal level in PBMCs from patients under anti-TNF therapy. In-vitro treatment of PBMCs with TNFα upregulated ET system genes. CONCLUSION: These findings indicate that ET receptor antagonists, such as bosentan, might be useful in controlling RA. Moreover, it seems that ET mediation of arthritis is triggered by TNFα.
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Artrite Experimental/tratamento farmacológico , Citocinas/metabolismo , Antagonistas dos Receptores de Endotelina , Sulfonamidas/uso terapêutico , Adulto , Animais , Antirreumáticos/uso terapêutico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Bosentana , Células Cultivadas , Endotelina-1/genética , Endotelina-1/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Leucócitos Mononucleares , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Masculino , Metotrexato/uso terapêutico , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Ventricular over-drainage is a common complication of dysfunctional ventriculoperitoneal devices. Subdural haematomas are usually the most common lesions associated with that complication. Such lesions may arise after ventricular collapse and bridging veins disruption that follows over-drainage, thus contributing to distortion of brain parenchyma, increased intracranial hypertension and neurological decline. More rarely, extradural haematomas may also be observed after ventricular shunt hyperfunction and may result in rapid neurological decline unless a surgical procedure can be promptly performed. CASE: This study reports the case of a 38-old-woman who presented supratentorial hydrocephalus and developed bilateral extradural haematomas after the placement of a ventricular shunt device. Both haematomas were surgically approached and the dysfunctional shunt device was replaced. CONCLUSION: Extradural haematomas may develop precociously after ventricular over-drainage. Surgical treatment is mandatory and must include not only the evacuation of haematoma, but also the replacement of dysfunctional shunt to prevent further recurrence. The pathophysiology of extradural haematomas consequent of ventricular over-drainage and the possible use of a programmable valve to prevent these lesions are briefly discussed.