Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Deficiência de vitamina D entre pacientes com doença inflamatória intestinal na Argentina: um estudo transversal / Vitamin d deficiency among inflammatorybowel disease patients in argentina: a cross-sectional study

ABSTRACT BACKGROUND: An association has been established between low serum values of vitamin D and inflammatory bowel disease. There is a lack of evidence on whether this association is still observed in regions where sun exposure throughout the year is higher. OBJECTIVE: To compare the prevalence of vitamin D deficiency between inflammatory bowel disease patients and healthy controls. METHODS: Inflammatory bowel disease patients were consecutively enrolled as cases. Age and gender-matched healthy subjects who agreed to undertake a determination of serum vitamin D were enrolled as controls. Demographic features, medical treatment, need for hospital admission at diagnosis, steroid treatment, smoking, need for surgical treatment were evaluated as factors associated with vitamin D deficiency. RESULTS: Overall, 59 patients with a diagnosis of either Crohn's disease or ulcerative colitis were enrolled, as well as 56 controls. Median age was 41 years (19-79) and 56% were male. Vitamin D deficiency was observed in 66.1% of inflammatory bowel disease patients versus 21.42% of healthy controls (OR 7.15 (3.1-16.48), P=0.001). Among inflammatory bowel disease patients, male gender, disease duration, moderate-to-severe disease and hospital admission at the moment of diagnosis were found to be associated with vitamin D deficiency. On multivariate analysis, only longer disease duration [(OR 1.01 (1-1.06)] and hospital admission at diagnosis [(OR 5.63 (1.01-31.61)] were found to be significantly associated with the latter. CONCLUSION: Vitamin D deficiency was more frequent among inflammatory bowel disease patients. Longer disease duration and need for hospital admission at diagnosis were associated to vitamin D deficiency among these patients.

RESUMO CONTEXTO: Uma associação foi estabelecida entre os baixos valores séricos de vitamina D e doença inflamatória intestinal. Falta evidência se esta associação ainda é observada em regiões onde a exposição ao sol durante todo o ano é maior. OBJETIVO: Comparar a prevalência de deficiência de vitamina D entre pacientes com doença inflamatória intestinal e indivíduos controles saudáveis. MÉTODOS: Pacientes com doença inflamatória intestinal foram consecutivamente selecionados. Indivíduos saudáveis combinados da mesma idade e gênero que concordaram em fornecer uma determinação da vitamina D do soro foram considerados como controles. Características demográficas, tratamento médico, necessidade de admissão hospitalar no diagnóstico, tratamento de esteroides, tabagismo, necessidade de tratamento cirúrgico foram avaliados como fatores associados à deficiência de vitamina D. RESULTADOS: No geral, 59 pacientes com diagnóstico de doença de Crohn ou colite ulcerosa foram observados, bem como 56 controles. A idade mediana era de 41 anos (19-79) e 56% eram do sexo masculino. A deficiência de vitamina D foi observada em 66,1% dos pacientes com doença inflamatória intestinal versus 21,42% dos controles saudáveis (OR 7,15 (3.1-16.48), P=0,001). Entre os pacientes com doença inflamatória intestinal, sexo masculino, duração da doença, doença de moderada a severa e admissão hospitalar no momento do diagnóstico foram associados com a deficiência de vitamina D. Na análise multivariada, apenas a duração da doença [(OR 1; 1 (1-1,06)] e a admissão hospitalar no diagnóstico [(OR 5,63 (1,01-31,61)] foram encontradas significativamente associadas ao último. CONCLUSÃO: A deficiência de vitamina D foi mais frequente entre os pacientes com doença inflamatória intestinal. Maior duração da doença e necessidade de admissão hospitalar no diagnóstico foram associadas à deficiência de vitamina D entre esses pacientes.

Dosagem do nível sérico do infliximabe em pacientes com doença inflamatória intestinal em remissão: uma análise comparativa de dois diferentes métodos em uma coorte multicêntrica brasileira / Serum infliximab measurement in inflammatory bowel disease patients in remission: a comparative analysis of two different methods in a multicentric brazilian cohort

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.

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.

Importância da medida dos níveis de infliximabe em pacientes com doença inflamatória intestinal: uma coorte Brasileira / Importance of measuring levels of infliximab in patients treating inflammatory bowel disease in a brazilian cohort

ABSTRACT BACKGROUND: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases. In such pathologies, there is an increased production of alpha tumor necrosis factor (TNF-α). Patients, in whom the conventional immunosuppressant treatment fails, require the use of immunobiological therapy, such as anti-TNF-α, a monoclonal antibody. Infliximab is an anti-TNF-α drug, a chimerical immunoglobulin, with a murine component, which is responsible for the generation of immunogenicity against the drug and formation of anti-TNF-α antibodies. The presence of anti-drug antibodies may be responsible for adverse events and reduction of the drug's effectiveness. Patients with inflammatory bowel diseases undergoing therapy with biological medication, such as infliximab, can relapse overtime and this may not be translated into clinical symptoms. Thus, there is a need for a method to evaluate the efficacy of the drug, through the measurement of serum infliximab levels, as well as antibodies research. OBJECTIVE: This study aimed to measure serum infliximab levels and anti-infliximab antibodies in patients with inflammatory bowel diseases post-induction phase and during maintenance therapy, and describe the therapeutic modifications that took place based on the serum levels results. METHODS: It was a retrospective study, that included forty-five patients, with a total of 63 samples of infliximab measurement. RESULTS: Twenty-one patients had an adequate infliximab serum level, 31 had subtherapeutic levels and 11 had supratherapeutic levels. Seven patients had their medication suspended due to therapeutic failure or high levels of antibodies to infliximab. CONCLUSION: In conclusion, only a third of the patients had adequate infliximab levels and 36% presented with subtherapeutic levels at the end of the induction phase. Therapy optimization occurred based in about 46% of the samples results, demonstrating the importance of having this tool to help the clinical handling of patients with inflammatory bowel diseases ongoing biologic therapy.

RESUMO CONTEÚDO: Doença de Crohn e retocolite ulcerativa são doenças inflamatórias intestinais crônicas. Nelas, ocorre aumento da produção de fator de necrose tumoral alfa (TNF-α). Pacientes que falham no tratamento convencional imunossupressor, requerem uso de terapia imunobio­lógica, que são anticorpos monoclonais, principalmente os anti-TNF-α. O infliximabe é uma droga anti-TNF-α, uma imunoglobulina quimérica, com componente murino. Este é responsável pela imunogenicidade da droga e a formação de anticorpos. Presença de anticorpos antidroga pode ser responsável pelos eventos adversos e redução da eficácia da droga. Pacientes com doenças inflamatórias intestinais, em terapia imunossupressora com medicação biológica como o infliximabe, podem ter recaída da doença e muitas vezes isso não se relaciona com a sintomatologia do paciente. Por isso há a necessidade de um método de avaliação do efeito da droga como a dosagem do nivel sérico do infliximabe, bem como da pesquisa de anticorpos. OBJETIVO: O estudo tem como objetivo conhecer os níveis séricos do infliximabe e dos anticorpos anti-infliximabe em pacientes com doença inflamatória intestinal em terapia de manutenção ou pós-indução e descrever as condutas terapêuticas que foram modificadas em função dos níveis séricos de infliximabe e anticorpos para infliximabe. MÉTODOS: Trata-se de estudo restrospectivo, com análise da dosagem dos níveis séricos de infliximabe e anticorpos para Infliximabe. Foram incluídos 45 pacientes, num total de 63 coletas de dosagem de infliximabe. RESULTADOS: Vinte e um paciente estavam com o nível sérico de infliximabe adequado, níveis subterapêuticos em 31 pacientes e níveis supraterapêuticos em 11 pacientes. Sete pacientes tiveram a medicação suspensa por falha terapêutica ou altos níveis de anticorpos para infliximabe. CONCLUSÃO: Apenas um terço dos pacientes apresentavam níveis adequados de infliximabe e 36% dos pacientes apresentavam níveis subterapêuticos ao término da indução. Em cerca de 46% das amostras a conduta adotada se baseou nos níveis de infliximabe e anticorpos para infliximabe demonstrando a importância de se ter esta ferramenta para auxílio no manejo clínico dos pacientes portadores de doenças inflamatórias intestinais em terapia biológica.

Alert for bone alterations and low serum concentrations of vitamin D in patients with intestinal inflammatory disease / Alerta para alterações ósseas e baixas concentrações séricas de vitamina D em pacientes com doença inflamatória intestinal

Summary Background: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the intestine that can reduce the absorption of nutrients such as vitamin D and calcium. Objective: To investigate bone alterations and serum levels of vitamin D in patients with IBD. Method: This was a cross-sectional study based on a review of medical records of patients from a private office in Curitiba, PR, Brazil. Serum levels of vitamin D and bone densitometry were measured at diagnosis of IBD. A total of 105 patients were included; 38 (58.4%) with CD; 27 (41.6%) with UC and 40 with irritable bowel syndrome (IBS) as comparison group. Results: When compared to patients with UC, CD patients showed a higher prevalence of bone alterations, being 15.8% with osteoporosis and 36.8% with osteopenia. In UC, bone alterations occurred in 29.6% of cases, 3.7% with osteoporosis and 25.9% with osteopenia. As for vitamin D levels, among CD patients, 10.5% had vitamin deficiency, 65.8% insufficiency and 23.7% were sufficient. In UC, 7.4% of cases had deficiency, 74.1% insufficiency and 18.5% had sufficient serum levels of vitamin D. In the group with IBS, deficiency was observed in 17.5% of cases, insufficiency in 55% and sufficiency in 27.5% of them. There was no significant difference between groups. Conclusion: IBD patients have a high prevalence of bone changes, especially those with CD. Serum levels of vitamin D are below the recommended in all the evaluated groups.

Resumo Introdução: A doença inflamatória intestinal (DII), como a doença de Crohn (DC) e a retocolite ulcerativa (RU), caracterizam-se pela inflamação crônica no intestino, que pode reduzir a absorção de vitamina D e cálcio. Objetivo: Investigar as alterações ósseas presentes em pacientes com DII e as dosagens séricas de vitamina D. Método: Estudo transversal analítico baseado na revisão de prontuários de pacientes com DII de um consultório privado de Curitiba, PR. Em todos os pacientes, foram dosadas as concentrações séricas de vitamina D e foi feita a densitometria óssea. Cento e cinco pacientes foram incluídos no estudo, dos quais 38 (58,4%) foram diagnosticados com DC, 27 (41.6%) com RU e 40 com síndrome do intestino irritável (SII) como grupo de comparação. Resultados: Quando comparados com pacientes com RU, os pacientes com DC apresentaram maior prevalência de alterações ósseas, sendo 15,8% com osteoporose e 36,8% com osteopenia. Na RU, as alterações ósseas ocorreram em 29,6% dos casos, 3,7% com osteoporose e 25,9% com osteopenia. Em relação às dosagens de vitamina D, dentre os pacientes com DC, 10,5% apresentavam deficiência, 65,8%, insuficiência e 23,7%, suficiência. Na RU, 7,4% dos casos tinham deficiência, 74,1%, insuficiência e 18,5%, suficiência. No grupo com SII, observaram-se deficiência em 17,5%, insuficiência em 55% e suficiência em 27,5%. Não foi observada diferença significativa entre os grupos. Conclusão: Pacientes com DII apresentaram alta prevalência de alterações ósseas, principalmente aqueles com DC. As concentrações séricas de vitamina D estão abaixo do recomendado em todos os grupos avaliados.

LOWER LEVELS OF VITAMIN D CORRELATE WITH CLINICAL DISEASE ACTIVITY AND QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE

Background - Inflammatory bowel disease, comprising Crohn's disease and ulcerative colitis, is a group of debilitating conditions associated with deregulated mucosal immune response. Vitamin D has been implicated in immune response and gastrointestinal function. Objectives - To investigate the correlation between serum vitamin D levels and disease activity and quality of life in patients with inflammatory bowel disease. Methods - This cross-sectional study enrolled ambulatory patients with inflammatory bowel disease and assessed clinical disease activity and quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]). Vitamin D levels were determined via serum 25-hydroxyvitamin D measurement; deficiency was defined as values <20 ng/mL. Statistical analysis was performed with SPSS vs 20.0. Results - A total of 76 patients were enrolled, 19 with ulcerative colitis (25%) and 57 with Crohn's disease (75%). Overall, mean serum 25-hydroxyvitamin D levels were low (26.0±10.0 ng/mL), while those in patients with Crohn's disease were significantly lower than ulcerative colitis (24.6±8.0 vs 30.0±12.5 ng/mL; P=0.032). Vitamin D deficiency was found in 30% of patients. Patients who were in clinical remission were found to have higher levels of vitamin D than those who were not in remission (28.0±10.3 vs 21.6±6.0 ng/mL, P=0.001). Inflammatory bowel disease patients with SIBDQ scores <50 were found to have significantly lower mean vitamin D levels compared with patients who had SIBDQ scores ≥50 (23.4±6.9 vs 27.9±10.8 ng/mL, P=0.041). Conclusions - A high proportion of patients with inflammatory bowel disease were vitamin D deficient, particularly patients with Crohn's disease. Both clinical disease activity and quality of life correlated significantly with lower levels of vitamin D, illustrating a clear need for supplementation in patients with inflammatory bowel disease.

Contexto - A doença inflamatória intestinal, que compreende a doença de Crohn e a colite ulcerosa, é um grupo de entidades incapacitantes associada a uma resposta imunitária desregulada. A vitamina D tem sido associada à resposta imune e funções gastrointestinais. Objetivo - Investigar a correlação entre os níveis séricos de vitamina D, a atividade clínica da doença e a qualidade de vida em doentes com doença inflamatória intestinal. Método - Estudo transversal que incluiu doentes em ambulatório com doença inflamatória intestinal avaliando a atividade clínica da doença e a qualidade de vida (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]). Os níveis séricos de vitamina D foram determinados através dos níveis de 25-hidroxivitamina D; a deficiência de vitamina D foi definida para valores <20 ng/mL. Resultados - Foram incluídos 76 doentes, 19 com colite ulcerosa (25%) e 57 com doença de Crohn (75%). No global, os valores séricos médios de 25-hidroxivitamina D foram baixos (26,0±10,0 ng/mL), os doentes com doença de Crohn apresentaram níveis mais baixos do que os doentes com colite ulcerosa (24,6±8,0 vs 30,0±12,5 ng/mL; P=0,032). O défice de vitamina D foi identificado em 30% dos doentes. Os doentes em remissão clínica apresentaram níveis mais elevados de vitamina D (28,0±10,3 vs 21,6±6,0 ng/mL, P=0,001). Doentes com SIBDQ <50 apresentaram níveis significativamente inferiores de vitamina D em comparação com doentes com SIBDQ ≥50 (23,4±6,9 vs 27,9±10,8 ng/mL, P=0,041). Conclusão - Uma percentagem elevada de doentes apresentou deficiência de vitamina D, em particular doentes com doença de Crohn. A atividade clínica e a qualidade de vida dos doentes com doença inflamatória intestinal correlacionou-se com níveis mais baixos de vitamina D, ilustrando uma clara necessidade de suplementação desta vitamina em doentes com doença inflamatória intestinal.

Acesso ao cuidado à saúde da criança em serviços de atenção primária / Access to child's health care in primary care services / Acceso al cuidado de la salud del niño en servicios de atención primaria

Realizou-se uma pesquisa de abordagem qualitativa com base no referencial metodológico da hermenêutica dialética, com o objetivo de identificar o atributo acesso da atenção primária para a resolução dos problemas de saúde de crianças menores de um ano a partir dos relatos de pais e cuidadores. Envolveram-se 16 cuidadores de crianças atendidas em unidades de pronto atendimento de Cascavel-PR, em 2010. Foram reconhecidas quatro categorias temáticas: Aconselhamento familiar ao buscar atenção à saúde da criança; Ausência de acolhimento ao primeiro contato; Presença de classificação de risco para atenção à saúde da criança; Barreiras que impedem o acesso à atenção à saúde. Concluiu-se que as famílias exibiram dificuldades para alcançar resolutividade aos problemas de saúde dos filhos, mediante a falta de acesso aos serviços de atenção primária.

It was conducted a qualitative study based on the methodological framework of dialectical hermeneutics, aiming to identify the attribute access from primary care to solve the health problems of children under one year old from the reports of parents and caregivers. Sixteen caregivers of children were involved, all of them seen in the emergency units of Cascavel-PR, in 2010. Four thematic categories were recognized: Family counselling in seeking health care for the child; Absence of reception on the first contact; Presence of risk classification to the child´s health attention; Barriers that block the access to health care. It was conclude that, families showed difficulties to reach the solution for their children´s health, because of the lack of access to primary care services.

Llevó-se a cabo un estudio cualitativo basado en el marco metodológico de la hermenéutica dialéctica, con el objetivo de identificar el atributo de acceso a la atención primaria para resolver los problemas de salud de los niños menores de un año, a partir de los informes de los padres y cuidadores. Se involucró 16 cuidadores de niños atendidos en las unidades de emergencia de Cascavel-PR, en 2010. Cuatro categorías temáticas fueron reconocidas: Asesoramiento de la familia en la búsqueda de atención de salud para el niño; Ausencia de acogimiento al primero contacto; Presencia de clasificación de riesgo para el cuidado de la salud del niño; Barreras que impiden el acceso a la atención sanitaria. Se concluyó que las familias tuvieron dificultades para lograr la solución de los problemas de salud de los niños, mediante la falta de acceso a los servicios de atención primaria.

Ulcerative Colitis and Immunoglobulin G4

BACKGROUND/AIMS: Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. METHODS: Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. RESULTS: UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05). CONCLUSIONS: UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.

Nutritional follow-up of patients with ulcerative colitis during periods of intestinal inflammatory activity and remission

CONTEXT: Ulcerative colitis is an inflammatory bowel disease involving superficial inflammation of the mucosa of the colon, rectum, and anus, sometimes including the terminal ileum. When in clinical activity, the disease is characterized by various daily evacuations containing blood, mucus and/or pus alternating periods of remission. OBJECTIVE: To compare nutritional parameters (dietary, biochemical and anthropometric) among patients with ulcerative colitis followed up on an outpatient basis over a period of 1 year and during periods of intestinal inflammatory activity and remission. METHODS: Sixty-five patients were studied over a period of 1 year and divided into two groups: group 1 with inflammatory disease activity (n = 24), and group 2 without disease activity (n = 41). Anthropometric measures, biochemical parameters, quantitative food intake, and qualitative food frequency were analyzed. RESULTS: A significant reduction in body mass index and weight and in the intake of energy, proteins, lipids, calcium, iron and phosphorus was observed in the group with inflammatory activity (group 1) when compared to the period of clinical remission. The most affected food groups were cereals, legumes, oils, and fats. In contrast, in group 2 significant differences in triceps and sub scapular skin fold thickness, total protein, hemoglobin and hematocrit were observed between the first and final visit. Calcium and vitamin B6 intake, as well as the consumption of legumes, meat and eggs, and sugar and sweets, was significantly higher than on the first visit. CONCLUSION: Patients with ulcerative colitis followed up on an outpatient basis tend to be well nourished. However, the nutritional aspects studied tend to worsen during the period of inflammatory disease activity.

CONTEXTO: A retocolite ulcerativa inespecífica compreende uma das doenças inflamatórias intestinais, com características de inflamação superficial da mucosa do cólon, reto, ânus, podendo incluir o íleo terminal. Caracteriza-se por várias exonerações diárias, com a presença de sangue e/ou pus, cursando em períodos de atividade e remissão inflamatória intestinal. OBJETIVO: Comparar os parâmetros nutricionais (alimentares, bioquímicos e antropométricos) em pacientes com retocolite ulcerativa inespecífica acompanhados em ambulatório, durante a atividade e remissão da doença inflamatória, no período de 1 ano. MÉTODOS: Foram estudados 65 pacientes durante 1 ano e divididos em dois grupos: grupo 1 com atividade inflamatória da doença (n = 24) e grupo 2 sem atividade da doença (n = 41), e analisadas as medidas antropométricas, os exames bioquímicos, o consumo alimentar quantitativo e a frequência alimentar qualitativa. RESULTADOS: O grupo com atividade inflamatória (grupo 1) apresentou redução estatisticamente significante no índice de massa corpórea, peso, no consumo de energia, proteínas, lipídios, cálcio, ferro e fósforo, em relação ao período de remissão clínica. Os grupos alimentares com significado prejuízo foram os cereais, as leguminosas, os óleos e as gorduras. Já no grupo 2, foram observadas alterações com significância estatística na dobra cutânea tricipital e subescapular, nos valores de proteínas totais, hemoglobina e hematócrito da consulta inicial para a final. Encontrou-se consumo de cálcio e vitamina B6, assim como na ingestão do grupo das leguminosas, carnes e ovos, açúcares e doces maiores significativamente do que na consulta inicial. CONCLUSÃO: Pacientes com retocolite ulcerativa inespecífica, acompanhados em ambulatório, tendem a ser bem nutridos, mas na fase de atividade inflamatória da doença, há tendência na piora dos aspectos nutricionais estudados.

Niveles de beta2 microglobulina y proteína C reactiva ultrasensible como marcadores de actividad histológica en pacientes con colitis ulcerativa crónica idiopática / Serum levels of beta2 microglobulin and ultrasensitive c-reactive protein as markers of histological activity in ulcerative colitis

Antecedentes: Recientemente hay interés en investigar nuevos marcadores bioquímicos no invasivos con mayor eficacia para evaluar la actividad endoscópica en pacientes con enfermedad inflamatoria intestinal. El objetivo de esta investigación fue evaluar la correlación de los valores séricos de proteína C reactiva ultrasensible (PCR-us) y beta-2 microglobulina (β2M) con la actividad histológica en pacientes con colitis ulcerosa crónica idiopática. Métodos: Se estudiaron 60 pacientes con diagnóstico confirmado de colitis ulcerosa crónica idiopática. Se determinó el Índice de Truelove-Witts, los valores séricos de β2M y PCR-us, así como el grado de actividad histológica. Resultados: 30 pacientes fueron mujeres (50 %) con edad promedio de 41.3 ± 14.5 años. Al evaluar la correlación entre los valores séricos de PCR-us y β2M con la actividad histológica, se documentó un coeficiente de correlación de 0.39 (p = 0.01) y 0.33 (p = 0.02), respectivamente. En un análisis por subgrupos se determinó la utilidad diagnóstica de la PCR-us y β2M. Las curvas ROC mostraron que la mayor área bajo la curva (AUC) para PCR-us y β2M correspondió a los puntos de corte de ≥ 0.36 (AUC = 0.73) y ≥ 1.3 (AUC = 0.69), respectivamente. Conclusiones: Los valores séricos de PCR-us y β2M correlacionaron positivamente con el grado de actividad histológica en pacientes con colitis ulcerosa crónica idiopática.

BACKGROUND: There is currently increasing interest in research focused on new, non-invasive biochemical markers with better efficacy for evaluating endoscopic activity in patients with inflammatory bowel disease (IBD). In the present study, we determined the diagnostic utility of high sensitive C-reactive protein (hs CRP) and beta2 microglobulin (beta2M) levels and analyzed their correlation with the histological activity of ulcerative colitis (UC). METHODS: A total of 60 consecutive patients with UC were studied. Truelove-Witts index, histological activity, and beta2M and CRP levels were determined. Patients were grouped as non-active, mild, moderate, or severe following Riley's classification. Statistical analysis was performed using descriptive statistics. RESULTS: The mean age of the patients was 41.3 +/- 14.5 years. Thirty patients were women (50%). Twenty-one patients had distal UC (35%). The correlations between serum hsCRP and beta2M with histological activity showed coefficients of 0.39 (p = 0.01) and 0.33 (p = 0.02), respectively. The diagnostic utility was determined by ROC curves, which showed that the cutoff with the greatest area under the curve (AUC) for hsCRP and beta2M were > or = 0.36 (AUC = 0.73) and > or = 1.3 (AUC = 0.69), respectively. CONCLUSIONS: In patients with UC, hsCRP and beta2M levels are positively correlated with histological activity.

Effect of Bacillus subtilis PB6, a natural probiotic on colon mucosal inflammation and plasma cytokines levels in inflammatory bowel disease.

The pathophysiology of inflammatory bowel disease (IBD) involves the production of diverse lipid mediators, namely eicosanoid, lysophospholipids, and platelet-activating factor, in which phospholipase A2 (PLA2) is the key enzyme. Thus, it has been postulated that control of lipid mediators production by inhibition of PLA2 would be useful for the treatment of IBD. This hypothesis has been tested in the present study by examining the therapeutic effect of a novel natural probitic Bacillus subtilis PB6 (ATCC- PTA 6737). B. subtilis PB6 is found to secrete surfactins (cyclic lipopeptides) which have anti-bacterial potential. These surfactins inhibit PLA2, a rate-limiting enzyme involved in the arachidonic acid associated inflammatory pathway and could downregulate the inflammatory response by regulating the eicosanoid and cytokine pathways. With this concept, an experimental animal trial has been conducted in a rat model of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. The oral administration of PB6 suppresses the colitis as measured by mortality rate, changes in the weight gain, colon morphology and the levels of plasma cytokines. The animals treated orally with PB6 at 1.5 x 10(8) CFU/kg thrice daily from day 4 to 10 significantly improve gross pathology of the colon and regain the colon weight to normal (p < 0.05), compared to TNBS-induced positive control. The plasma levels of pro-inflammatory cytokines (TNF-alpha, 1L-1beta, IL-6 and IFN-gamma) are also significantly lowered (p < 0.05) and anti-inflammatory cytokine (IL-I0 and TGF-beta) significantly (p < 0.05) increased after the oral administration of PB6 on day 11. The present study supports the concept that PB6 inhibits PLA2 by the secreting surfactins. In a clinical investigation, it is found to be well tolerated by all the healthy volunteers.

Níveis baixos de 25-hidroxivitamina D (25OHD) em pacientes com doença inflamatória intestinal e sua correlação com a densidade mineral óssea / Low levels of 25-hydroxyvitamin D (25OHD) in patients with inflammatory bowel disease and its correlation with bone mineral density

INTRODUÇÃO: Pacientes com doenças inflamatórias intestinais (DII) estão propensos a apresentar níveis baixos de vitamina D (25OHD) e densidade mineral óssea (DMO) diminuída. OBJETIVO: Verificar o nível de 25OHD em jovens com DII submetidos à avaliação clínica, dosagens bioquímicas rotineiras e medida da DMO de coluna lombar e fêmur, comparando-os com controles saudáveis. RESULTADOS: 39 pacientes com doença de Crohn (DC) (p = 0, 003) e 37 com retocolite ulcerativa inespecífica (RCUI) (p < 0,001) apresentaram níveis mais baixos de 25OHD comparados aos controles, 48,5 por cento dos pacientes com RCUI tinham deficiência de 25OHD. A DMO em coluna lombar foi mais baixa nos doentes (DC p = 0,001; RCUI p = 0,008). A 25OHD correlacionou-se significativamente com a DMO do fêmur total (r = 0,391; p = 0,027) e colo do fêmur (r = 0,384; p = 0,03) na DC. CONCLUSÃO: Foram encontrados níveis baixos de 25OHD e DMO em jovens com DII, sugerindo papel importante desta deficiência na patogênese da doença óssea desses pacientes.

Patients with inflammatory bowel disease (IBD) are at risk of having vitamin D deficiency (25-OHD) and low bone mineral density (BMD). OBJECTIVES: To measure 25OHD in a young group of IBD patients submitted to a clinical evaluation, routine biochemistry and BMD measurement (lumbar spine and proximal femur). RESULTS: 39 Crohn disease (CD) and 37 ulcerative colitis (UC) patients had lower serum levels of 25OHD compared to the control group (CD p = 0,003; UC p < 0,001), and 48.5 percent of the UC patients were 25OHD deficient. Lumbar spine BMD was lower in patients than controls (CD p = 0,001; UC p = 0,008). In CD patients, serum levels of 25OHD were significantly correlated with total femur (r = 0,391; p = 0,027) and femoral neck (r = 0,384; p = 0,03) BMD. CONCLUSION: It was found lower levels of 25OHD and BMD in young IBD patients compared to normal controls, suggesting an important role of 25OHD deficiency in the pathogenesis of the IBD bone disease.

Análise descritiva dos perfis social, clínico, laboratorial e antropométrico de pacientes com doenças inflamatórias intestinais, internados no Hospital Universitário Clementino Fraga Filho, Rio de Janeiro / Descriptive analysis of the social, clinical, laboratorial and anthropometric profiles of inflammatory bowel disease inwards patients from the Clementino Fraga Filho University Hospital, Rio de Janeiro, RJ, Brazil

RACIONAL: Estudos epidemiológicos sobre doenças inflamatórias intestinais no Brasil são limitados devido a dificuldades diagnósticas e reduzidas amostras populacionais estudadas. A maioria dos estudos de sua prevalência disponível é composta por amostras de pacientes sob acompanhamento em ambulatório, entretanto a análise do perfil de pacientes com doenças inflamatórias intestinais hospitalizados pode auxiliar na detecção de marcadores preditivos de sua gravidade, o que permitirá intervenções médicas precoces visando a redução da taxa de hospitalização e os gastos do sistema de saúde. OBJETIVOS: Descrever o perfil social, clínico, laboratorial e antropométrico dos pacientes adultos com doenças inflamatórias intestinais internados em hospital universitário terciário. MÉTODOS: Estudo prospectivo com 43 pacientes com doenças inflamatórias intestinais internados nas enfermarias clínicas e cirúrgicas e no setor de emergência do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro, RJ. Foram caracterizados dados demográficos, presença de co-morbidades, localização e comportamento clínico, história cirúrgica, manifestações extra-intestinais utilizando-se definições padronizadas. Os resultados laboratoriais foram verificados nos prontuários e as medidas antropométricas foram realizadas durante a entrevista. RESULTADOS: A maioria dos pacientes apresentou doença de Crohn (72,1 por cento), com localização íleo-colônica (60 por cento) e com comportamento penetrante (77,4 por cento), enquanto no grupo retocolite ulcerativa idiopática predominou a pancolite (50 por cento). No grupo total de retocolite ulcerativa idiopática, a artralgia foi a manifestação extra-intestinal mais freqüente (44,2 por cento) e 97,7 por cento já havia apresentado algum tipo de complicação relacionada à doença de base. Apesar do uso de terapêutica específica para doenças inflamatórias intestinais prévio à hospitalização em 79,1 por cento...

BACKGROUND: The epidemiologic survey in Brazil is limited probably due to a diagnosis deficiency and a small number of population-based studies performed. The majority of the prevalence studies available have evaluated inflammatory bowel diseases outpatients, but the knowledge of the profile of inflammatory bowel diseases inpatients is important in order to detect predictive markers of disease severity that will allow earlier medical intervention decreasing the rate of hospitalization and reducing the Health System costs. AIM: To determine social, clinical, laboratorial and anthropometric profiles of hospitalized adults inflammatory bowel diseases patients of a tertiary university hospital. METHODS: Prospective study was performed with 43 inflammatory bowel diseases inpatients from clinical and surgical wards and emergency section of university hospital. We characterized demographic data, presence of comorbidities, disease location and behavior, surgical past-history, extra intestinal manifestations using standardized definitions. Laboratory results were abstracted from medical records and anthropometric measures were performed during our visit. RESULTS: The vast majority of the inflammatory bowel diseases patients had Crohn's disease (72.1 percent), with ileocolic involvement (60 percent), with a penetrating disease behavior (77.4 percent) while ulcerative colitis group presented mostly pancolitis (50 percent). Articular pain was the most common (44.2 percent) extra intestinal manifestation of inflammatory bowel diseases patients and 97.7 percent of them had at least one type of complication related to disease. Although, the previous use of specific medical therapies to inflammatory bowel diseases before the hospitalization (more frequently corticosteroids) was done (79 percent), the majority of the patients were hospitalized because of inflammatory bowel diseases activity. Disease activity was present in 80.7 percent of Crohn's disease...

Prevalencia de marcadores serológicos ANCA y ASCA en una población con colitis ulcerosa / Presence of antineutrophil cytoplasmic antibodies (ANCA) and anti Saccharomyces cerevisiae antibodies (ASCA) among patients with ulcerative colitis

Background: The diagnosis of inflammatory bowel disease is supported by clinical findings and complementary tests. The presence of specific serological markers could be helpful in the characterization of this condition. Aim: To assess the prevalence of ANCA and ASCA in a group of patients with ulcerative colitis (UC) and its association with clinical features. Material and Methods: Sixty four patients with UC in remission (age range 16-72 years, 33 males) were studied. In a venous blood sample ANCA were measured by indirect immunofluorescence and ASCA by enzyme immune assays for IgG and IgA. Results: Forty four percent of patients were positive for ANCA, 9 percent for ASCA and 6 percent for both markers. There was a significant correlation between the presence of ANCA and duration of the UC (<5 years 50 percent, 5-10 years 42.9 percent, 15 years 30 percent) and the number of crises (one crises 31 percent, 2-5 crises 51.9 percent and >5 crises 87.5). The proportion of colectomized patients with positive ANCA was higher (57.1 percent). Conclusions: The prevalence of ANCA in the studied population is similar to the published data. The presence of ANCA was significantly higher in UC patients with shorter evolution, higher number of crises and in those with a history of colectomy. There was a low prevalence of ASCA positive patients.

Comparative Usefulness of Erythrocyte Sedimentation Rate and C-reactive Protein in Assessing the Severity of Ulcerative Colitis / 대한소화기학회지

BACKGROUND/AIMS: Although erythrocyte sedimentation rate (ESR) is included as a laboratory parameter in Truelove and Witts' classification, C-reactive protein (CRP) is also used for severity assessment in ulcerative colitis (UC). Frequently, the discordance between ESR and CRP is observed in clinical practice. The aim of this study was to determine which parameter is more related with clinical activity in UC patients. METHODS: A total of 155 patients with UC were identified from January 2004 to March 2005. Their medical records were reviewed within these patients, a total of 541 assessments of disease activity were made. Correlation of clinical activity and laboratory tests were evaluated by Pearson's correlation coefficient. RESULTS: Pearson's correlation coefficients of ESR and CRP with clinical symptoms were 0.376 and 0.258, respectively. The correlation coefficient between ESR and CRP was 0.403 (p=0.000). A total of 131 (24.2%) assessments revealed discordance between ESR and CRP. When discordance occurred, the correlation coefficients with clinical symptoms were 0.338 for ESR (p=0.000) and 0.034 for CRP (p>0.01). Dividing discordant patients into high ESR/low CRP group and low ESR/high CRP group, the coefficients were 0.420 for ESR and 0.226 for CRP in high ESR/low CRP group, and 0.333 for ESR and 0.068 for CRP in low ESR/high CRP group. CONCLUSIONS: The correlation analysis indicates that ESR appears to be a more reliable laboratory parameter of disease activity than CRP in assessing the severity of UC. In particular, when the level of ESR and CRP is discordant, ESR is more useful in assessing the disease activity in UC patients.

Significance of tumour markers in colorectal carcinoma associated with Schistosomiasis.

Schistosomiasis as well as Colorectal Carcinoma are equally prevalent in Egypt. However, the role of Schistosomiasis as a risk factor for Colorectal Carcinoma is not well established. Three tumour markers have been assessed in 69 patients with large bowel disease. They were classified into five groups. Group 1 (A) included 21 cases with Schistosomal hepatic fibrosis. Group 2 (B) included 6 cases of ulcerative colitis. Group 3 (C) included 10 cases of adenomatous polypi of which 12 cases had Schistosomiasis. Group 4 (D) consisted of 21 cases of colorectal carcinoma, 12 cases had schistosomiasis in association with colorectal carcinoma constituting group 5 (E). Elevated CEA was observed in benign tumours but showed non significant difference in G4 and G5. Significantly increased AFP levels were evident in G1, G4, and G5. Significant increase of B-HCG was observed only in G4 and G5 indicating its significance as diagnostic index in case of malignancy. It has been observed that Schistosomal hepatic fibrosis induced increased levels of some of the tumour markers. Therefore, the factor of Schistosomal hepatic fibrosis should be considered during the assessment of tumour markers in colorectal carcinoma cases.

Vitamin C status, glutathione and histamine in gastric carcinoma, tuberculous enteritis and non-specific ulcerative colitis.

Studies were conducted to evaluate the blood levels of ascorbic acid, dehydroascorbic acid, glutathione, and histamine in patients with gastric carcinoma, tuberculous enteritis and non-specific ulcerative colitis. Leucocyte ascorbic acid, urinary excretion of total ascorbic acid and ascorbic acid saturation test were also carried out in order to assess the ascorbic acid status of these patients. It was observed that the plasma and leucocyte content of ascorbic acid was significantly lower with markedly decreased urinary excretion in these patients. Further urinary excretion of ascorbic acid after a test dose was also found to be subnormal. Decreased levels of glutathione and significantly higher levels of histamine reflect an overall reducing status of the body is markedly deranged.