ABSTRACT Inflammatory bowel diseases (IBD) currently impose an immense social and economic burden on society in terms of both direct and indirect healthcare costs. Their incurable and progressive nature results in an unavoidable lifetime expense. The introduction of infliximab more than two decades ago had revolutionized IBD treatment. Nowadays, while biologic drugs comprise various vital therapeutic options for patients, they can be associated to significant costs to healthcare systems. The most crucial benefit of biosimilars is that they bring more significant cost reduction and increase access to advanced therapies. They also allow the treatment of newly diagnosed patients and dose optimization for those who need it. There is an inverse relationship between price and demand for treatment with biologics. For a more significant reduction in cost to be possible, greater use of biosimilars is necessary. For this to occur, it is imperative not only to use biosimilars in naïve patients but also to switch to biosimilars in those patients who have started therapy with reference biologics. At present, randomized and observational studies have demonstrated effectiveness and safety results in recommending a single switch between a reference product and a biosimilar, and vice versa. The purpose of this manuscript is to review the literature and discuss whether scientific evidence is enough to support multiple switches of biologics and biosimilars in IBD patients. (IBD expense Nowadays systems therapies possible necessary occur present biosimilar versa

Abstract In the community, malnutrition is manifested by the loss of muscle mass, being associated with a decrease in muscle strength, an increased risk of frailty, functional impairment and impaired healing of chronic wounds, as well as a higher incidence of infections. It is estimated that malnutrition affects one in three elderly people at home and one in three patients in elderly care institutions. Malnutrition is reversible as long as the patient has access to timely nutritional screening that identifies their nutritional risk and as long as an individualized nutritional intervention is instituted. Disease associated malnutrition continues to be perceived as a secondary problem in primary health care, so the implementation of nutritional risk screening, as a routine parameter, is the first step in improving access to nutritional care in the community. In this article, the Malnutrition Universal Screening Tool is proposed for routine nutritional screening in primary care.

Resumo Na comunidade, a malnutrição manifesta-se pela perda de massa muscular, estando associada à diminuição da força muscular, ao aumento do risco de fragilidade, ao comprometimento funcional e da cicatrização de feridas crónicas, assim como a maior incidência de infeções. Estima-se que a malnutrição afete um em cada três idosos no seu domicílio e um em cada três utentes em instituições de cuidados de idosos. A malnutrição é reversível desde que o utente tenha acesso a um atempado rastreio nutricional que identifique o seu risco nutricional e instituída uma intervenção nutricional individualizada. A malnutrição associada à doença continua a ser percecionada como um problema secundário nos cuidados de saúde primários, pelo que a implementação do rastreio do risco nutricional, como um parâmetro de rotina, é o primeiro passo na melhoria do acesso aos cuidados nutricionais na comunidade. Neste artigo, é proposta a ferramenta Malnutrition Universal Screening Tool para rastreio nutricional de rotina nos cuidados de saúde primários.

Abstract Background The Good Practices in Cardiology Program is an initiative created by the Brazilian Society of Cardiology (SBC) to improve the quality of care of cardiovascular disease patients in Brazilian public hospitals. Objectives To characterize patients admitted to a tertiary public hospital with diagnosis of acute coronary syndrome (ACS) or heart failure (HF) and to evaluate performance indicators in both ACS and HF arms, with a pre-established target of 85% adherence to the SBC recommendations. Methods This was a descriptive cross-sectional study through data collection of patients hospitalized between May 2016 and September 2019. Results A total of 1,036 patients were included, 273 in the HF arm and 763 in the ACS arm. Mean age was 59.8 ± 12.0 years in the ACS and 57.0 ± 14.1 years in the HF, with a predominance of male patients in both groups. More than half of patients had some primary education and more than 90% reported a monthly income of less than five minimum wages. In ACS, the diagnosis of ACS with ST segment elevation was predominant (66.3%), and 2.9% of patients died. In HF, the most common etiology was Chagas disease (25.8%), and 17.9% died. Analysis of the performance indicators revealed an adherence rate higher than 85% to nine of the 12 indicators. Conclusion Quality programs are essential for improvement of quality of care. Performance indicators pointed to a good adherence to the SBC guidelines, mainly in the ACS arm. (SBC hospitals (ACS (HF arms preestablished pre established 85 recommendations crosssectional cross sectional 201 2019 1036 1 036 1,03 included 27 76 598 59 8 59. 120 0 12. 570 57 57. 141 14 14. groups 90 wages 66.3%, 663 66.3% , 66 3 (66.3%) 29 2 9 2.9 died 25.8%, 258 25.8% 25 (25.8%) 179 17 17.9 guidelines 20 103 03 1,0 7 5 66.3 6 (66.3% 2. 25.8 (25.8% 17. 10 1, 66. (66.3 25. (25.8 (66. (25. (66 (25 (6 (2 (

Resumo Fundamento O Programa Boas Práticas em Cardiologia é uma iniciativa da Sociedade Brasileira de Cardiologia (SBC) destinada à melhoria do cuidado cardiovascular nos hospitais públicos brasileiros. Objetivos Descrever características dos pacientes internados com Síndrome Coronariana Aguda (SCA) e Insuficiência Cardíaca (IC) e avaliar os indicadores de desempenho alcançados nos braços (SCA e IC) em um hospital público terciário, com uma meta pré-estabelecida de 85% de aderência às recomendações da SBC. Métodos Estudo do tipo transversal descritivo realizado por meio da coleta de dados de pacientes que estiveram internados entre maio de 2016 e setembro de 2019. Resultados Foram incluídos 1036 pacientes, 273 pacientes no braço IC e 763 no braço SCA. A média de idade foi de 59,8 ± 12,0 anos na SCA e 57,0 ± 14,1 anos na IC, com predomínio do sexo masculino em ambos os grupos. Mais da metade dos pacientes não tinham ensino fundamental completo e mais de 90% declararam renda mensal inferior a cinco salários-mínimos. Na SCA, predominou o diagnóstico de SCA com supradesnivelamento do segmento ST (66,3%) e 2,9% dos pacientes foram a óbito. Na IC, a etiologia mais comum foi a Doença de Chagas (25,8%) e 17,9% dos pacientes foram a óbito. Na avaliação dos indicadores de desempenho, nove dos 12 indicadores tiveram taxas de aderência acima de 85%. Conclusão Programas de qualidade são essenciais à melhoria do cuidado e os indicadores de desempenho do hospital apontam para uma boa adesão às diretrizes assistenciais da SBC, particularmente no braço da SCA. SBC (SBC brasileiros (IC terciário préestabelecida pré estabelecida 85 201 2019 103 27 76 598 59 8 59, 120 0 12, 570 57 57, 141 14 1 14, grupos 90 saláriosmínimos. saláriosmínimos salários mínimos. mínimos salários-mínimos 66,3% 663 66 3 (66,3% 29 2 9 2,9 óbito 25,8% 258 25 (25,8% 179 17 17,9 20 10 7 5 66,3 6 (66,3 2, 25,8 (25,8 17, 66, (66, 25, (25, (66 (25 (6 (2 (

Abstract Objective: To descriptively analyze the epidemiological data, clinical stage, and outcomes of oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil, and to estimate the influence of clinical stage and treatment type on overall and disease-free survival. Methods: We retrospectively analyzed epidemiological data from the São Paulo Cancer Center Foundation database relative to patients with oropharyngeal squamous cell carcinoma diagnosed between 2004 and 2014 in the state of São Paulo. Univariate and multivariate Cox regression analyses were performed to assess factors associated with the outcomes. A forward stepwise selection procedure was used. Survival curves were estimated by the Kaplan-Meier method and compared by the Gehan-Breslow-Wilcoxon test. Results: A total of 8075 individuals with oropharyngeal squamous cell carcinoma were identified. Of these, 86.3% were diagnosed at an advanced stage and 13.7% at an early stage. Only 27.2% of patients were treated surgically, whereas 57.5% were treated medically. Patients undergoing surgery had longer overall survival than those receiving medical treatment in both early- and advanced-stage oropharyngeal squamous cell carcinoma. However, there was no significant difference in disease-free survival between surgical and medical treatment. Conclusion: No significant difference in disease-free survival between medical and surgical treatment suggests similar complete remission rates with both approaches. Patients receiving medical treatment had shorter overall survival, which may be due to complications from chemotherapy and radiotherapy. However, we cannot confirm this relationship based on the data provided by the São Paulo Cancer Center Foundation. Prospective studies are warranted to assess whether the lower overall survival rate in patients receiving medical treatment is secondary to complications from chemotherapy and radiotherapy. Level of evidence: 2C. Objective Brazil diseasefree disease free Methods 200 201 used KaplanMeier Kaplan Meier GehanBreslowWilcoxon Gehan Breslow Wilcoxon test Results 807 identified these 863 86 3 86.3 137 13 7 13.7 272 27 2 27.2 surgically 575 57 5 57.5 medically advancedstage However Conclusion approaches radiotherapy evidence 2C C 20 80 8 86. 1 13. 27. 57.

RESUMO A vacinação em massa oferece a melhor estratégia para enfrentamento da pandemia de COVID-19, e as vacinas contra SARS-CoV2 estão sendo aprovadas em vários países para uso emergencial. No Brasil, a aprovação da vacina é esperada em breve, no entanto, existem potenciais preocupações em relação às recomendações de vacinas para populações específicas, como pacientes com doença inflamatória intestinal (DII). Para responder essas questões, o Grupo Brasileiro de Estudos IBD (GEDIIB) fornece conselhos práticos com recomendações importantes sobre as vacinas para COVID-19 na população com DII.

ABSTRACT Mass vaccination offers the best strategy to fight against COVID-19 pandemic, and SARS-CoV2 vaccines are being approved in several countries for emergency use. In Brazil, vaccine approval is expected in the next few days, however potential concerns exist regarding vaccine recommendations for specific populations, such as patients with inflammatory bowel disease (IBD). To address these questions, the Brazilian IBD Study Group (GEDIIB) provides this practical advice with key recommendations about the COVID-19 vaccines in IBD population.

Objetivo: avaliar se a alteração na atividade da alfa amilase salivar está associada à ansiedade e ao estresse dos profissionais de enfermagem hospitalar e, se a ansiedade e o estresse estão associados aos fatores sociodemográficos, epidemiológicos e laborais. Método: estudo transversal, quantitativo, desenvolvido com 210 profissionais de enfermagem de uma instituição hospitalar. Para a coleta de dados, utilizouse um questionário de caracterização dos trabalhadores, o Inventário de Ansiedade de Beck, o Inventário de Sintomas de Stress para Adultos de Lipp e as amostras de saliva coletadas durante os turnos de trabalho. Os dados foram analisados de forma descritiva e inferencial utilizando os softwares Statistical Package for the Social Science e GraphPad Prism. Resultados: a maioria dos profissionais apresentou estresse e ansiedade. As variáveis faixa etária, quantidade de filhos, uso de medicamentos e carga horária de trabalho estavam associadas à ansiedade; faixa etária, tabagismo e uso de medicamentos estavam associadas ao estresse. Observouse um aumento da atividade da alfa amilase salivar no meio do turno de trabalho. Os profissionais que tinham estresse e ansiedade apresentaram alteração significativa da alfa amilase no turno da noite. Conclusão: as alterações na atividade da alfa amilase estavam associadas à ansiedade e ao estresse dos profissionais de enfermagem, demonstrando que essa enzima pode ser um possível biomarcador de ansiedade e estresse em trabalhadores.

Objective: to assess if changes in salivary alpha-amylase activity are associated with anxiety and stress among hospital nursing professionals and whether anxiety and stress are associated with sociodemographic, epidemiological, and occupational factors. Method: cross-sectional, quantitative study, carried out with 210 nursing professionals from a hospital. For data collection, we used a questionnaire to characterize workers, Beck’s Anxiety Inventory, Lipp’s Stress Symptoms Inventory for Adults and samples and saliva samples collected in work shifts. The data were analyzed descriptively and inferentially using the software Statistical Package for the Social Science and GraphPad Prism. Results: most professionals experienced stress and anxiety. The variables age group, number of children, use of medication and workload were associated with anxiety; age group, smoking and medication use were associated with stress. An increase in the salivary alpha-amylase activity was observed in the middle of the work shift. Professionals who had stress and anxiety had significant changes in alpha-amylase in the night shift. Conclusion: changes in salivary alpha-amylase were associated with anxiety and stress among nursing professionals, indicating that this enzyme can be a possible biomarker of anxiety and stress in workers.

Objetivo: evaluar si la alteración en la actividad de la alfa amilasa salival está asociada a la ansiedad y al estrés de los profesionales de enfermería hospitalaria y, si la ansiedad y el estrés están asociados a factores sociodemográficos, epidemiológicos y laborales. Método: estudio transversal, cuantitativo, desarrollado en 210 profesionales de enfermería, en una institución hospitalaria. Para la recogida de datos, se utilizó un cuestionario de caracterización de los trabajadores, el Inventario de Ansiedad de Beck, el Inventario de Síntomas de Stress para Adultos de Lipp y las muestras de saliva recogidas durante los turnos de trabajo. Los datos fueron analizados de forma descriptiva e inferencial utilizando los softwares Statistical Package for the Social Science y GraphPad Prism. Resultados: la mayoría de los profesionales presentó estrés y ansiedad. Las variables intervalo etario, cantidad de hijos, uso de medicamentos y carga horaria de trabajo estaban asociadas a la ansiedad; el intervalo etario, el tabaquismo y el uso de medicamentos estaban asociados al estrés. Se observó un aumento de la actividad de la alfa amilasa salival en los ambientes de los turnos de trabajo. Los profesionales que tenían estrés y ansiedad presentaron alteración significativa de la alfa amilasa en el turno de la noche. Conclusión: las alteraciones en la actividad de la alfa amilasa estaban asociadas a la ansiedad y al estrés de los profesionales de enfermería, demostrando que esa enzima puede ser un posible biomarcador de ansiedad y estrés en trabajadores.

RESUMO A monitorização terapêutica dos níveis séricos (Therapeutic drug monitoring - TDM) de infliximabe (IFX) é uma estratégia reconhecida na tomada de decisão clínica frente a perda de resposta secundária a esta droga no manejo das doenças inflamatórias intestinais (DII). Embora a maioria dos dados sobre a aplicação dessa estratégia para IFX se refira à fase de manutenção do tratamento, muitos estudos associaram concentrações mais altas de IFX, especialmente na fase de indução, com o alcance de importantes alvos de tratamento, como remissão clínica e cicatrização da mucosa. Este artigo visa resumir as evidências da literatura sobre o uso de níveis séricos durante a fase de indução do IFX e propor a aplicação de uma abordagem simplificada que pode ser extremamente útil na prática clínica, visando melhores resultados para os pacientes.

ABSTRACT Therapeutic drug monitoring (TDM) of infliximab (IFX) has been recognized as an important strategy in the management of secondary loss of response to this agent, guiding clinical decision-making in the management of inflammatory bowel diseases (IBD). Although most of the data on the application of TDM for IFX refer to the maintenance phase of treatment, many studies have associated higher drug concentrations, specially in the induction phase, with achievement of important treatment targets, such as clinical remission and mucosal healing. This brief communication aims to summarize the literature on the use of TDM during induction phase of IFX and propose application of a simplified approach which can be useful into clinical practice, aiming better outcomes to IBD patients.

RESUMO CONTEXTO: Os biológicos revolucionaram o tratamento da doença inflamatória intestinal (DII). Ademais, esses medicamentos influenciaram os custos relacionados ao tratamento. Tal aumento significativo nos gastos com o tratamento motivou desenvolvimento dos biossimilares. OBJETIVO: Esta revisão sistemática e metanálise objetivou avaliar a taxa de descontinuação de medicamentos na população com DII que foi submetida à troca do biológico originador para um biossimilar, em estudos observacionais que abordaram possíveis razões para a descontinuação do tratamento. MÉTODOS: Tendo como base de dados Medline (via PubMed), EMBASE, Cochrane Library e resumos de congressos médicos, foram rastreados artigos com relatos de troca de um biológico originador por um biossimilar, com acompanhamento pós-troca de no mínimo 6 meses ou três infusões. Todas as informações disponíveis sobre as taxas de descontinuação foram avaliadas. RESULTADOS: Foram incluídos no total 30 estudos observacionais, envolvendo 3.594 pacientes com DII. Vinte e seis estudos relataram uma mudança do infliximabe para CT-P13, dois estudos envolveram uma mudança para o SB2, e as informações sobre a troca não estavam disponíveis em dois estudos. As taxas de descontinuação foram de 8%, 14% e 21% aos 6, 12 e 24 meses, respectivamente. Os principais motivos para a descontinuação do medicamento e seus respectivos riscos foram: agravamento da doença (2%), remissão (4%), perda de adesão (4%), eventos adversos (5%) e perda de resposta (7%). A qualidade da evidência variou de baixa a muito baixa, dependendo do resultado analisado. Os sintomas subjetivos que levaram à descontinuação do medicamento foram relatados com pouca frequência, e o efeito nocebo foi claramente avaliado em apenas um dos artigos incluídos. CONCLUSÃO: As taxas de descontinuação após a mudança para um biossimilar em pacientes com DII aumentam com o tempo. No entanto, não foi possível confirmar o efeito nocebo como motivo da descontinuação. Portanto, ainda são necessários estudos em longo prazo avaliando o uso de biossimilares para monitorar eventos adversos e potenciais efeitos nocebo na vigilância pós-comercialização.

ABSTRACT BACKGROUND: Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS: Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS: A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION: Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.

ABSTRACT. The objective of this study was to evaluate the activity of invertases and amylases in Brachiaria brizantha cv. Marandu under various shade and nitrogen fertilization conditions. The experiment was carried out in a greenhouse using a 4 x 2 factorial scheme (shading levels of 0, 30, 50, and 80% and fertilization with 0 and 100 kg N ha-1). The activity of the enzymes, cytosol-neutral invertase (Inv-N), vacuole acid (Inv-V) and cell-acidic acid (Inv-CW), reducing sugars (RS), and α and β-amylases were evaluated (α = 0.05). The interaction was significant for Inv-N within the leaf. In the first cycle, the highest activity was in fertilized plants with 30, 50, and 80% shading. For Inv-CW in the 1st cycle, the highest activity occurred with 0, 30, and 50% shading. However, the interaction for Inv-V leaf activity was not significant in the 1st and 2nd cycles. The highest activity observed for Inv-V was in the fertilized plants, suggesting that fertilization increased the enzymatic activity. The activity of the invertases increased both under 30-50% shaded conditions and in full sun. Furthermore, invertase activity was directly linked to the osmoregulatory system. The reduction in RS was related to a low photosynthetic rate, and an increase α and β-amylase was associated with the use of reserve energy sources to meet energetic needs.

RESUMO CONTEXTO: Há escassez de dados sobre a eficácia e segurança do vedolizumabe nas doenças inflamatórias intestinais na América Latina. OBJETIVO: Descrever a primeira experiência observacional de mundo real com vedolizumabe em pacientes latino-americanos com doenças inflamatórias intestinais. MÉTODOS: Estudo retrospectivo multicêntrico observacional de pacientes com doença de Crohn (DC) e retocolite ulcerativa inespecífica (RCUI) que utilizaram vedolizumabe em qualquer fase de seu tratamento. Foram avaliadas a remissão e resposta clínicas (de acordo com o índice de Harvey-Bradshaw para DC e escore de Mayo para RCUI), cicatrização da mucosa, necessidade de cirurgia e eventos adversos. RESULTADOS: Foram incluídos 90 pacientes (52 com DC e 38 com RCUI), a maioria com exposição prévia a agentes anti-TNF (88,46% na DC e 76,31% na RCUI). Na DC (em análise conforme observado), as taxas de remissão nas semanas 12, 26 e 52 foram 42,89% (21/49), 61,9% (26/42) e 46,15% (12/26), respectivamente. Na RCUI, as taxas de remissão nas semanas 12, 26 e 52 foram de 28,94% (11/38), 36,66% (11/30) e 41,17% (7/17). As taxas de cicatrização da mucosa foram 36,11% na DC e 43,4% na RCUI. Durante o período do estudo, 7/52 pacientes com DC foram submetidos a cirurgia abdominal maior e 4/38 pacientes com RCUI necessitaram de colectomia. CONCLUSÃO: O vedolizumabe foi eficaz na indução e manutenção da resposta e remissão clínicas em população refratária na DC e RCUI, com perfil de segurança favorável.

ABSTRACT BACKGROUND: There is scarce data regarding efficacy and safety of vedolizumab in inflammatory bowel diseases in Latin America. OBJECTIVE: To describe the first observational real-world experience with vedolizumab in Latin American inflammatory bowel diseases patients. METHODS: Retrospective observational multicentric study of patients with Crohn’s disease (CD) and ulcerative colitis (UC) who used vedolizumab at any phase of their treatment. Clinical remission and response (according to Harvey-Bradshaw index for CD and Mayo score for UC), mucosal healing, need for surgery and adverse events were evaluated. RESULTS: A total of 90 patients were included (52 with CD and 38 with UC), the majority with previous exposure to anti-TNF agents (88.46% in CD and 76.31% in UC). In CD (as observed analysis) remission rates at weeks 12, 26 and 52 were 42.89% (21/49), 61.9% (26/42) and 46.15% (12/26), respectively. In UC, remission rates at weeks 12, 26 and 52 were 28.94% (11/38), 36.66% (11/30) and 41.17% (7/17). Mucosal healing rates were 36.11% in CD and 43.4% in UC. During the study period, 7/52 CD patients underwent major abdominal surgery and 4/38 UC patients needed colectomy. CONCLUSION: Vedolizumab was effective in induction and maintenance of clinical response and remission in CD and UC, with no new safety signs.

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

RESUMO Os inibidores das Janus kinases (JAK) têm sido incorporados ao tratamento de doenças imunomediadas, como artrite reumatoide e, além disso, têm sido testados no tratamento da psoríase e doenças inflamatórias intestinais, tanto na retocolite ulcerativa quanto na doença de Crohn. Tofacitinibe é uma droga do grupo das pequenas moléculas de uso oral que inibe as Janus kinases 1 e 3 e, em menor grau, a Janus kinases 2. Esta inibição promove o bloqueio de uma série de citocinas pró-inflamatórias que estão envolvidas na patogênese das doenças inflamatórias intestinais e desempenham importante papel nos processos imunes, tais como ativação, função e proliferação linfocitária. Nesta presente comunicação, relatamos um caso de um paciente portador de retocolite ulcerativa refratária a três agentes biológicos (infliximabe, adalimumabe e vedolizumabe), com diferentes mecanismos de ação, que recusou o tratamento cirúrgico, porém, apresentou boa resposta com o uso de tofacitinibe, com remissão clínica e endoscópica. Não foram evidenciados efeitos colaterais com a droga. O presente caso ilustra as dificuldades que podemos enfrentar em relação à identificação da expressão do correto mecanismo de ação envolvido na patogênese dos pacientes com retocolite ulcerativa e a importância de um novo agente terapêutico com diferente mecanismo de ação, como o tofacitinibe.

ABSTRACT Janus kinases inhibitors have already been incorporated into the management of immune-mediated diseases, such as rheumatoid arthritis, and are being investigated for the treatment of psoriasis and inflammatory bowel diseases, both ulcerative colitis and Crohn’s disease. Tofacitinib is an oral small-molecule drug that inhibits Janus kinases 1, Janus kinases 3, and, to a lesser extent, Janus kinases 2. This inhibition ends up blocking signals for several inflammatory cytokines that are involved in the pathogenesis of inflammatory bowel diseases and play a role in many immune signaling routes, including lymphocyte activation, function, and proliferation. We report a patient with active ulcerative colitis with primary non-response to three biologics (infliximab, adalimumab and vedolizumab), with different mechanisms of action, who refused surgical treatment and had a favorable response to tofacitinib with clinical and endoscopic remission. No adverse events were observed with the use of the agent. This case illustrates the difficulties we may face regarding the identification of the expression of proper mechanism of action involved in the pathogenesis of ulcerative colitis patients and the importance of having another treatment option with different mechanism of action, like tofacitinib.

RESUMO CONTEXTO: A monitorização dos níveis séricos do infliximabe (IFX) é uma importante ferramenta para guiar a tomada de decisão nos pacientes com doença inflamatória intestinal. No presente momento existem dois tipos de métodos para quantificar nível sérico de IFX disponíveis no mercado: o ELISA e o teste rápido. O método ELISA é o mais usado em todo o mundo, todavia os resultados demoram de 1 a 2 dias para estar disponíveis para uso clínico. Além disso, o ELISA é um método que requer um técnico especializado para realizá-lo. Ao contrário, os resultados do teste rápido estão disponíveis em 20 a 30 minutos e esse pode ser realizado por um funcionário não especializado. OBJETIVO: O objetivo deste estudo foi comparar o teste rápido (QB-IFX) com o teste ELISA para determinação quantitativa do nível sérico de IFX em uma coorte de pacientes com doença inflamatória intestinal. MÉTODOS: Foi realizado um estudo transversal multicêntrico com inclusão de 49 pacientes em terapia de manutenção com IFX. Amostra sanguínea para dosagem sérica do IFX foi coletada imediatamente antes da infusão. A dosagem sérica do IFX foi classificada em indetectável, baixo (<3,0 μg/mL), adequado (3,1-7,0 μg/mL) ou alto (>7,1 μg/mL). A sensibilidade e a especificidade de cada teste e a comparação entre os testes foram avaliados através de curva ROC. RESULTADOS: Foram avaliados 34 pacientes com doença de Crohn e 15 pacientes com retocolite ulcerativa em remissão clínica da doença. A maioria dos pacientes apresentou níveis baixos ou adequados do IFX sérico de acordo com ambos os métodos de dosagem. Não houve diferença significativa entre os métodos quando avaliados categoricamente (P=0,84). A análise da curva ROC identificou limites de concentrações >2,9 μg/mL com o teste rápido QB-IFX (AUC ROC, 0,82; P<0,0001, sensibilidade: 100%; especificidade: 61.9%), e >3,83 μg/mL usando o método ELISA (AUC ROC, 0,96; P<0,0001, sensibilidade: 100%; especificidade: 92,9%). CONCLUSÃO: Os testes QB-IFX e ELISA foram comparáveis para dosagem do nível sérico de IFX. Ambos os métodos são acurados e apresentaram boa sensibilidade e especificidade para detecção de níveis indetectáveis, níveis baixos e níveis adequados, porém mostraram pouca especificidade para níveis supra terapêuticos da droga.

ABSTRACT BACKGROUND: Infliximab (IFX) therapeutic drug monitoring is an important tool to guide therapeutic decision in inflammatory bowel disease patients. Currently, there are two methods to measure trough levels of IFX, ELISA assays or rapid tests. Despite that the ELISA assay is the most used method in therapeutic drug monitoring, the results take long to be available for clinical use, and it needs to be performed by trained personnel. In contrary, the results of a rapid test take 20 to 30 minutes to be available and can be performed by non-trained lab personnel. OBJECTIVE: The aim of the study was to compare a rapid test (QB-IFX) for quantitative determination of IFX level to one ELISA assay in a cohort of inflammatory bowel disease patients. METHODS: Cross-sectional multicentric study with 49 inflammatory bowel disease patients on maintenance therapy with IFX. Blood samples for IFX serum levels were collected immediately before infusion. IFX serum levels were classified as undetectable, low (<3.0 μg/mL), adequate (3.1-7.0 μg/mL) or high (>7.1 μg/mL). A sensitivity and specificity of each test and a comparison between tests was based on ROC curves. RESULTS: Thirty-four Crohn’s disease patients and 15 ulcerative colitis patients in clinical remission were evaluated. The majority of patients had low or adequate serum levels of IFX. In relation to the serum levels proportions with the two methods, there was no significant difference (P=0.84). The ROC analysis identified a concentration threshold >2.9 μg/mL with the QB-IFX test (area under the ROC, 0.82; P<0.0001, sensitivity, 100%; specificity, 61.9%), and >3.83 μg/mL using the ELISA assay (area under the ROC, 0.96; P<0.0001, sensitivity, 100%; specificity, 92.9%). CONCLUSION: QB-IFX and ELISA assays to measure IFX levels were comparable. Both methods had accurate sensitivity and specificity to detect undetectable, low and adequate levels, but had showed low specificity for supra therapeutic levels of IFX.

ABSTRACT In the search for new anti-schistosomal agents, a series of fifteen ortho-nitrobenzyl derivatives was assayed in vitro against both the schistosomulum (somule) and adult forms of Schistosoma mansoni. Compounds 8 and 12 showed significant activity against somules at low micromolar concentrations, but none was active against adults. The SAR demonstrated that the compounds most active against the parasite were mutagenic to the human cell line RKO-AS45-1 only at concentrations 10- to 40-fold higher than the worm-killing dose. Given their electrophilicity, compounds were also screened as inhibitors of the S. mansoni cysteine protease (cathepsin B1) in vitro. Amides 5 and 15 exhibited a modest inhibition activity with values of 55.7 and 50.6 % at 100 µM, respectively. The nitrobenzyl compounds evaluated in this work can be regarded as hits in the search for more active and safe anti-schistosomal agents.