Análise da resposta ao tratamento da psoríase moderada a grave com agentes inibidores do TNF-ALFA no longo prazo

Introdução: A psoríase é uma doença crônica imunomediada. Na sua forma moderada ou grave e na ausência de uma resposta satisfatória ao tratamento convencional, se indica o uso de agentes imunobiológicos. Os agentes antagonistas do fator de necrose tumoral alfa (anti-TNFα) são eficazes e seguros no tratamento a longo prazo. Objetivos: Avaliar a resposta ao tratamento da psoríase com agentes anti-TNFα em longo prazo; descrever o perfil de acometimento da doença em relação a sexo e idade; identificar as comorbidades associadas; identificar se houve falha primária e/ou secundária na utilização de medicamentos biológicos anti-TNFα no tratamento de pacientes psoriáticos e estabelecer a conduta adequada a ser adotada diante da falha; comparar a diferença de resposta entre os medicamentos utilizados; discutir a causa da falha secundária e a sua relação com a forma de apresentação clínica inicial da doença; avaliar a ocorrência de efeitos colaterais e/ou paradoxais durante o período de acompanhamento. Métodos: Seguimento ao longo de 5 anos de todos os pacientes adultos com psoríase moderada a grave que apresentaram falha à terapia convencional e que foram tratados com anti-TNFα no ambulatório de dermatologia do hospital universitário de 2015 a 2019. O Psoriasis Area Severity Index (PASI) foi avaliado pré tratamento, após 12 semanas e a cada dois meses por todo o período de acompanhamento. A falha secundária foi definida como piora do PASI após resposta satisfatória inicial nos primeiros 3 meses de tratamento. Resultados: O estudo englobou 28 pacientes (15 mulheres e 13 homens). A idade média foi de 50±11 anos. Vinte e três pacientes apresentavam a forma em placa, e seis pacientes a forma eritrodérmica. Adalimumabe foi administrado a quatorze pacientes e Etanercepte aos 14 pacientes restantes. Após 12 semanas de tratamento, todos os pacientes apresentaram melhora do PASI, passando de 30 [20 a 40] para 4,7 [2,2 a 10,0], p <0,0001. Houve falha secundária de tratamento em 6 pacientes, com persistência de resposta em 75,6% em 5 anos. A manutenção da resposta foi mais elevada nos pacientes que manifestaram apresentação inicial em placa, e menor nos que inicialmente manifestaram eritrodermia (87,7% vs. 20,0%, P<0,0001). Nenhum paciente apresentou efeito colateral grave. Três pacientes apresentaram efeito paradoxal, sem necessidade de interrupção do tratamento. Conclusão: Os agentes anti-TNFα se mostraram seguros e eficazes no tratamento da psoríase moderada a grave. Somente 6 indivíduos apresentaram falha secundária após 5 anos de seguimento.Introduction: Psoriasis is an immune-mediated chronic disease. That in its moderate or severe form and in the absence of an adequate response to the conventional treatment, may be treated with immunobiological agents. Tumor necrosis factor-alpha (anti-TNFα) antagonists are effective and safe in long-term treatment. Objectives: Assess long-term response to the treatment of psoriasis using anti-TNFα agents; describe the disease occurrence profile in relation to gender and sex; identify any associated comorbidities; identify whether any primary and/or secondary failure occurred in the use of anti-TNFα immunobiological drugs in the treatment of psoriasis patients and establish proper actions according to the failure; compare any differences of response among medicaments; discuss the cause of secondary failure and its relationship to the initial clinical presentation of the disease; assess the occurrence of side and/or paradoxical effects with Etharnecept and Adalimumab during the follow-up period. Methods: Five-year follow-up of all adult patients having moderate-to-severe psoriasis for which the conventional treatment failed and that were treated with anti-TNFα in a dermatological outpatient clinic of a university hospital from 2015 to 2019. PASI was assessed pre-treatment, after 12 weeks, and every 2 months along the follow-up period. Secondary failure was established as worsening of PASI after satisfactory treatment response in 3 mouths. Results: The study was comprised of 28 patients (15 women and 13 men) with average ages of 50±11 years old. 23 patients had plaque psoriasis and 6 erythrodermic psoriasis. Adalimumab was administered to 14 individuals and Etharnecept to the remaining 14 individuals. After 12 weeks of treatment, all patients showed improvement of PASI, increasing from 30 [20 to 40] to 4,7 [2,2 to 10,0], p <0.0001. Secondary failure was observed in 6 patients, with a 75.6% persistence of response in 5 years. Maintenance of response was higher for patients with initial presentation as plaque compared to erythroderma (87.7% vs. 20.0%, P<0.0001). Patients showed no serious side effects. Three patients showed paradoxical effect, with no need to interrupt treatment. Conclusion: Anti-TNFα agents have been proved to be safe and effective to treat moderate-to-severe psoriasis. Just only 6 patients presented secondary failure after 5 years of follow-up.59 f

Heat transfer process simulation by finite differences for online control of ladle furnaces

A numerical method for solving the two-dimensional transient heat conduction equation is presented to determine temperature profiles of ladle furnaces during the casting of special steels. The method is based on an explicit formulation of the heat transfer process in finite differences. In order to improve the efficiency of the method, two auxiliary algorithms are added, one for correcting finite difference results from coarse mesh calculations and the other to perform time extrapolation of the temperature behaviour between furnace batches. The calculated steel temperatures are found to be in good agreement with experimental data, obtained at a Brazilian thin steel casting facility. Currently, about 80% of the ladle batches at this facility come out within their commercial specifications, against 45% previously observed without the use of such a model. With average processing times of the order of 100 s in an AMD K6II 300 MHz computer, the method is suitable for real time thermal tracking of ladles and steel

Injectable silicon oils - complications

There have been reports of the use of silicone oils in injectable form for cosmetic purposes since the 1940s. With the popularization of the use of this technique in the mid-60s, there have been a wide range of adverse effects reported. We report a 32-year-old woman, who had intramuscular injections of an unknown substance, which led to serious complications

Injectable silicon oils - complications

There have been reports of the use of silicone oils in injectable form for cosmetic purposes since the 1940s. With the popularization of the use of this technique in the mid-60s, there have been a wide range of adverse effects reported. We report a 32-year-old woman, who had intramuscular injections of an unknown substance, which led to serious complications

O uso da drotrecogina alfa ativada na prática clínica e as atuais evidências Drotrecogin alfa activated in clinical practice and the current evidences

JUSTIFICATIVA E OBJETIVOS: O debate sobre a segurança e eficácia da drotrecogina alfa (DrotAA) encontra-se na ordem do dia, principalmente, em função dos resultados negativos observados em ensaios clínicos subseqüentes ao PROWESS e do impacto econômico no sistema de saúde relacionado ao custo elevado do fármaco. O objetivo deste estudo foi rever os principais estudos sobre a utilização da DrotAA em pacientes com sepse grave, com ênfase nas questões ligadas a sua eficácia e segurança. CONTEÚDO: Foram selecionados artigos sobre a utilização da DrotAA em pacientes com sepse publicados nos últimos dez anos no MedLine. Os seguintes unitermos foram utilizados: activated protein C; drotrecogin alfa; sepsis; septic shock; Xigris®. Estudos referenciados nos artigos selecionados na busca também foram utilizados. CONCLUSÕES: As taxas de letalidades e as complicações hemorrágicas associadas com o uso do fármaco foram maiores em grandes estudos observacionais do que aquelas descritas previamente nos ensaios clínicos. A luz dos resultados atualmente disponíveis, o uso da DrotAA deve ser reconsiderado até que novos ensaios clínicos possam subsidiar com informações adicionais sobre eficácia, segurança e na identificação dos subgrupos de pacientes com sepse grave que porventura possam ter benefício com o uso deste medicamento. A DrotAA deve servir de exemplo para que haja maior cautela com a rápida transposição de evidências ainda em construção para recomendações e diretrizes de tratamento de pacientes com sepse grave.<br>BACKGROUND AND OBJECTIVES: The debate on efficacy and patient safety related to the use of drotrecogin alfa (DrotAA) is timely, principally due to the negative results observed in clinical studies performed after the PROWESS study, and the economic cost-related impact of the drug on the healthcare system. The aim of this study was to review the main studies on the use of DrotAA in patients with severe sepsis. The focus was on drug efficacy-and patient safety-related issues. CONTENTS: Articles were selected by a MedLine search for studies on the use of DrotAA in patients with sepsis using the following key words: activated protein C; drotrecogin alfa; sepsis; septic shock; Xigris®. Additional references were retrieved from the studies initially selected. CONCLUSIONS: Mortality and bleeding complications associated with the use of DrotAA were more frequent in large observational studies than those reported in randomized trials. In the light of the current knowledge, routine use of DrotAA should be reevaluated until well-designed confirmatory clinical trials can clarify the true efficacy and safety of the drug and help identify the subgroup of patients that can benefit from use of DrotAA. Physicians should be cautious with the rapid transfer of evidences not well-documented, to the guidelines and recommendations practiced in the care and treatment of patients with severe sepsis