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Arthritis Rheumatol ; 71(7): 1163-1173, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30848528


OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is a multifactorial autoinflammatory disease with a historically poor prognosis. With current treatment regimens, approximately half of patients still experience active disease after 1 year of therapy. This study was undertaken to evaluate a treat-to-target approach using recombinant interleukin-1 receptor antagonist (rIL-1Ra; anakinra) as first-line monotherapy to achieve early inactive disease and prevent damage. METHODS: In this single-center, prospective study, patients with new-onset systemic JIA with an unsatisfactory response to nonsteroidal antiinflammatory drugs received rIL-1Ra monotherapy according to a treat-to-target strategy. Patients with an incomplete response to 2 mg/kg rIL-1Ra subsequently received 4 mg/kg rIL-1Ra or additional prednisolone, or switched to alternative therapy. For patients in whom inactive disease was achieved, rIL-1Ra was tapered after 3 months and subsequently stopped. RESULTS: Forty-two patients, including 12 who had no arthritis at disease onset, were followed up for a median of 5.8 years. The median time to achieve inactive disease was 33 days. At 1 year, 76% had inactive disease, and 52% had inactive disease while not receiving medication. High neutrophil counts at baseline and a complete response after 1 month of rIL-1Ra were highly associated with inactive disease at 1 year. After 5 years of follow-up, 96% of the patients included had inactive disease, and 75% had inactive disease while not receiving medication. Articular or extraarticular damage was reported in <5%, and only 33% of the patients received glucocorticoids. Treatment with rIL-1Ra was equally effective in systemic JIA patients without arthritis at disease onset. CONCLUSION: Treatment to target, starting with first-line, short-course monotherapy with rIL-1Ra, is a highly efficacious strategy to induce and sustain inactive disease and to prevent disease- and glucocorticoid-related damage in systemic JIA.

Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Criança , Pré-Escolar , Substituição de Medicamentos , Etanercepte/uso terapêutico , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Contagem de Leucócitos , Masculino , Metotrexato/uso terapêutico , Neutrófilos , Prednisolona/uso terapêutico , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
Infect Dis Ther ; 8(1): 33-50, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30607807


The burden of liver-related morbidity remains high among HIV-infected patients, despite advances in the treatment of HIV and viral hepatitis. Especially, the impact of non-alcoholic fatty liver disease (NAFLD) is significant with a prevalence of up to 50%. The pathogenesis of NAFLD and the reasons for progression to non-alcoholic steatohepatitis (NASH) are still not fully elucidated, but insulin resistance, mitochondrial dysfunction and dyslipidemia seem to be the main drivers. Both HIV-infection itself and combination antiretroviral therapy (cART) can contribute to the development of NAFLD/NASH in various ways. As ongoing HIV-related immune activation is associated with insulin resistance, early initiation of cART is needed to limit its duration. In addition, the use of early-generation nucleoside reverse transcriptase inhibitors and protease inhibitors is also associated with the development of NAFLD/NASH. Patients at risk should therefore receive antiretroviral drugs with a more favorable metabolic profile. Only weight reduction is considered to be an effective therapy for all patients with NAFLD/NASH, although certain drugs are available for specific subgroups. Since patients with NASH are at risk of developing liver cirrhosis and hepatocellular carcinoma, several non-antifibrotic and antifibrotic drugs are under investigation in clinical trials to broaden the therapeutic options. The epidemiology and etiology of NAFLD/NASH in HIV-positive patients is likely to change in the near future. Current guidelines recommend early initiation of cART that is less likely to induce insulin resistance, mitochondrial dysfunction and dyslipidemia. In contrast, as a result of increasing life expectancy in good health, this population will adopt the more traditional risk factors for NAFLD/NASH. HIV-treating physicians should be aware of the etiology, pathogenesis and treatment of NAFLD/NASH in order to identify and treat the patients at risk.

Clin Toxicol (Phila) ; 55(3): 167-174, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28074704


CONTEXT: Zinc chloride (ZnCl2)-based smoke bombs and screens are in use since the Second World War (1939-1945). Many case descriptions on ZnCl2 smoke inhalation incidents appeared since 1945. OBJECTIVE: We provide a comprehensive overview of the clinical symptoms and underlying pathophysiology due to exposure to fumes from ZnCl2 smoke producing bombs. In addition, we give a historical overview of treatment regimens and their outcomes. METHODOLOGY: We performed a literature search on Medline, Scopus and Google Scholar databases using combinations of the following search terms "smoke bomb", "smoke screen", "ZnCl2", "intoxication", "poisoning", "case report", "HE smoke", "hexachloroethane smoke", "smoke inhalation" and "white smoke". We retrieved additional reports based on the primary hits. We collected 30 case reports from the last seven decades encompassing 376 patients, 23 of whom died. Of all the patient descriptions, 31 were of sufficient detail for prudent analysis. RESULTS AND CONCLUSIONS: Intoxication with clinical signs mainly took place in war situations and in military and fire emergency training sessions in enclosed spaces. Symptoms follow a biphasic course mainly characterised by dyspnoea, coughing and lacrimation, related to irritation of the airways in the first six hours, followed by reappearance of early signs complemented with inflammation related signs and tachycardia from 24 h onwards. Acute respiratory stress syndrome developed in severely affected individuals. Chest radiographs did not always correspond with clinical symptoms. Common therapy comprises corticosteroids, antibiotics and supplemental oxygen or positive pressure ventilation in 64% of the cases. Of the 31 patients included, eight died, three had permanent lung damage and 15 showed complete recovery, whereas in five patients outcome was not reported. Early signs likely relate to caustic reactions in the airway lining, whereas inhaled ZnCl2 particles may trigger an inflammatory response and associated delayed fibrotic lung damage. Smoke bomb poisoning is a potentially lethal condition that can occur in large cohorts of victims simultaneously.

Cloretos/envenenamento , Lesão por Inalação de Fumaça/fisiopatologia , Fumaça/efeitos adversos , Compostos de Zinco/envenenamento , Animais , Bombas (Dispositivos Explosivos) , Humanos , Exposição por Inalação/efeitos adversos , Lesão por Inalação de Fumaça/terapia , Fatores de Tempo , Guerra