High rate of serious infection in juvenile idiopathic arthritis patients under biologic therapy in a real-life setting.

OBJECTIVES: To assess the rate of serious and/or opportunistic infections in juvenile idiopathic arthritis (JIA) patients from a single tertiary center under biologic therapy and to identify possible risk factors associated to these complications. METHODS: A total of 107 JIA patients followed at the biologic therapy center of our tertiary university hospital using a standardized electronic database protocol including demographic data, clinical and laboratorial findings and treatment at baseline and at the moment of infection. Opportunistic infections included tuberculosis, herpes zoster and systemic mycosis. RESULTS: A total of 398 patient-yrs(py) were included. The median time of biologic exposure was 3.0 years (0.15-11.5). We observed 35 serious/opportunistic infectious events in 27 (25%) patients: 31(88.6%) were serious infections and four (11.4%) opportunistic infections. Serious/opportunistic infections rates were 10.6/100py for ETN, 10.9/100py for ADA, 2.6/100py for ABA and 14.8/100py for TCZ. Comparison of 27 patients with and 80 without infection showed a higher frequency of systemic-onset JIA, lower age at biologic therapy initiation and a history of previous serious infection (p < .05) in the former group. CONCLUSIONS: This study demonstrated a high rate of serious infections in JIA patients under biologic therapy in a real-life setting. Systemic-onset JIA, lower age at biologic therapy start and history of previous serious infections were important risk factors for these complications. Also, higher rates of severe infections comparing to the former studies was possibly due to elevated MTX doses in our patients.

A morphometric and molecular study of the apoptosis observed on tadpoles' tail explants under the exposition of triiodothyronine in different homeopathic dilutions.

BACKGROUND: As a therapeutic system, homeopathy is supported by: i) similitude and experimentation in healthy individuals, ii) potentization. A challenge for researchers consists in looking for signals in water (or vehicle) to explain the storage of information in extremely high dilutions and the transfer of such information to the living systems. Anuran amphibian metamorphosis is controlled by thyroid hormones (TH), including the resorption of the tadpole tail. Apoptosis is a genetically regulated form of cell death that can be triggered by various extracellular and intracellular stimuli resulting in coordinated activation of a family of cysteine proteases called caspases. METHODS: This study was blind and randomized. It performed in three stages: I) the identification of the most effective T3 homeopathic dilution to induce apoptotic reactions in Rana (Lithobates) catesbeianus tadpole tail explants stimulated by T3 in substantial, II) study of different controls and III) detection in explants under the action of the most effective dilution of T3, as established in Stage I. RESULTS: There was no statistically significant difference between tail macroscopic dimensions between the groups. T3 10cH decreased the expression of caspase 3/7 mRNA, in explants treated with T3 20 nM. CONCLUSION: The present experiment is in agreement with the hypothesis that T3, at a 10cH homeopathic dilution, changes the metamorphosis molecular network.

Juvenile dermatomyositis: review and update of the pathogenesis and treatment.

Juvenile dermatomyositis (JDM) is an autoimmune disease characterized by systemic vasculopathy. Its main manifestations include symmetrical proximal muscle weakness, elevated serum muscle enzymes and cutaneous lesions, among which the heliotrope and Gottron's papules are pathognomonic. Early recognition and prompt therapy allow better prognosis and prevent the development of calcinosis. Although the treatment is based on glucocorticoids, the more commonly associated immunosuppressors include methotrexate, azathioprine, cyclosporine, and cyclophosphamide, depending on the severity of disease. The use of immunobiologicals for refractory cases remains under investigation, but the results are controversial or inexpressive. In this review, we highlight recent updates on the pathogenesis and treatment of JDM.

Dermatomiosite juvenil: revisão e atualização em patogênese e tratamento / Juvenile dermatomyositis: review and update of the pathogenesis and treatment

A dermatomiosite juvenil (DMJ) é uma doença autoimune caracterizada por vasculopatia sistêmica. Manifestações principais da DMJ incluem fraqueza muscular proximal simétrica, elevação de enzimas musculares séricas e lesões cutâneas, dentre as quais o heliotropo e as pápulas de Gottron são patognomônicas. Reconhecimento precoce e instituição rápida de terapia adequada permitem melhorar o prognóstico da doença e evitar o aparecimento de calcinose. Embora a base do tratamento seja o glicocorticoide, os imunossupressores mais frequentemente associados são metotrexato, ciclosporina, azatioprina e ciclofosfamida, dependendo da gravidade da DMJ. Atualmente investiga-se a utilidade dos imunobiológicos nos casos refratários, mas os resultados são controversos ou pouco expressivos. Pretende-se neste artigo fazer uma revisão sobre DMJ, com ênfase em recentes atualizações na sua patogênese e tratamento.

Juvenile dermatomyositis (JDM) is an autoimmune disease characterized by systemic vasculopathy. Its main manifestations include symmetrical proximal muscle weakness, elevated serum muscle enzymes and cutaneous lesions, among which the heliotrope and Gottron's papules are pathognomonic. Early recognition and prompt therapy allow better prognosis and prevent the development of calcinosis. Although the treatment is based on glucocorticoids, the more commonly associated immunosuppressors include methotrexate, azathioprine, cyclosporine, and cyclophosphamide, depending on the severity of disease. The use of immunobiologicals for refractory cases remains under investigation, but the results are controversial or inexpressive. In this review, we highlight recent updates on the pathogenesis and treatment of JDM.

Pentoxifylline modifies three-dimensional collagen lattice model contraction and expression of collagen types I and III by human fibroblasts derived from post-burn hypertrophic scars and from normal skin.

Fibroblasts are thought to be partially responsible for the persisting contractile forces that result in burn contractures. Using a monolayer cell culture and fibroblast populated collagen lattice (FPCL) three-dimensional model we subjected hypertrophic scar and non-cicatricial fibroblasts to the antifibrogenic agent pentoxifylline (PTF - 1mg/mL) in order to reduce proliferation, collagen types I and III synthesis and model contraction. Fibroblasts were isolated from post-burn hypertrophic scars (HSHF) and non-scarred skin (NHF). Cells were grown in monolayers or incorporated into FPCL's and exposed to PTF. In monolayer, cell number proliferation was reduced (46.35% in HSHF group and 37.73% in NHF group, p<0.0001). PTF selectively inhibited collagen III synthesis in the HSHF group while inhibition was more evident to type I collagen synthesis in the NHF group. PTF also reduced contraction in both (HSHF and NHF) FPCL.