Introdução: O envolvimento gastroduodenal pode ocorrer na doença de Crohn (DC). Seu diagnóstico histológico definitivo é habitualmente realizado através da demonstração do granuloma não caseoso. O achado de gastrite focal H. pylori negativa em biopsias gástricas de pacientes com DC ileal e/ou colônica, apesar de não ser específico, também sugere o envolvimento da doença neste segmento. Objetivos: avaliar a frequência da gastrite focal em pacientes com DC comparada à de pacientes com retocolite ulcerativa (RCU) e controles, assim como as frequências da infecção pelo H. pylori nessas populações e correlacioná-las com a presença de gastrite focal; avaliar a capacidade da imunohistoquímica em diferenciar a gastrite focal nos três grupos; avaliar as associações entre dados demográficos, aspectos clínicos, laboratoriais, uso de medicamentos, presença de sintomas do trato gastrintestinal (TGI) superior e achados endoscópicos com presença de gastrite focal em pacientes com doença inflamatória intestinal (DII); e avaliar a associação entre uso de medicamentos nesses pacientes e infecção pelo H. pylori. Métodos: Foram estudados 62 pacientes com DC, 35 pacientes com RCU e 40 pacientes controles. Todos foram submetidos à endoscopia digestiva alta (EDA) com biopsias para o teste da urease, exame histológico e imunohistoquímico. Resultados: Dos 137 pacientes estudados foram excluídos dois pacientes com DC e um com RCU. Não houve diferença estatisticamente significante entre os grupos com relação à idade (p=0,921) e sexo (p=0,192). A maioria dos pacientes com DC estava em remissão clínica (75%). Cerca de 80% dos pacientes com DC faziam uso de azatioprina. H. pylori foi positivo em 18/60 (30%) pacientes com DC, 12/34 (35%) na RCU e 20/40 (50%) no grupo controle sem diferença estatisticamente significante entre os grupos (p=0,131). Não foram observadas associações estatisticamente significantes entre uso de medicamentos e infecção pelo H. pylori nos pacientes com DII. A gastrite focal H. pylori negativa foi diagnosticada em 7/42 (16,7%) na DC, 3/22 (13,6%) na RCU e 2/20 (10%) no grupo controle, sem diferença estatisticamente significante entre eles (p=0,919). A gastrite focal H. pylori positiva foi diagnosticada em 2/18 (11%) na DC, 3/12 (25%) na RCU e 7/20 (35%) no grupo controle, sem diferença estatisticamente significante (p=0,213). Não foram observadas associações estatisticamente significantes entre características clínicas, laboratoriais, uso de medicamentos, sintomas do TGI superior, achados endoscópicos e gastrite focal. No entanto, foi observado que o uso de azatioprina nos pacientes com DC H. pylori negativos apresentou uma tendência a reduzir a gastrite focal. A imunohistoquímica da gastrite focal dos pacientes com DC e RCU H. pylori negativos foi semelhante e diferiu do grupo controle por este apresentar um maior acúmulo de linfócitos B (CD20). Já a imunohistoquímica da gastrite focal dos pacientes com DC, RCU e controles H. pylori positivos foi indistinguível. Conclusões: Pacientes com DII tendem a ser menos infectados pela bactéria H. pylori. A frequência de gastrite focal H. pylori negativa diagnosticada em nosso estudo foi menor do que a descrita na literatura. O uso de imunossupressor (azatioprina) pode estar relacionado com tal achado / Introduction: Gastroduodenal involvement may occur in Crohns disease (CD). Definitive histological diagnosis of CD in the upper gastrointestinal (GI) tract normally relies on the demonstration of epitheloid granuloma which is considered the histological hallmark of gastric CD. If granulomas are absent, the description of focally enhanced gastritis (FEG) or focal active gastritis in gastric biopsies of patients with known ileal and/or colonic CD, although not exclusive to CD, suggests the involvement of the disease at this site. Objectives: To access the prevalence of FEG in CD patients compared with a group of ulcerative colitis (UC) and CD/UC-free controls, as well as the frequencies of H. pylori infection in those population and correlate them to the presence of FEG; evaluate the capacity of immunohistochemistry in differentiating FEG in the three groups; evaluate the correlation with demographic and clinical characteristics, laboratory findings, current medical therapy as well as the presence of forgut symptoms and mucosal lesions at endoscopy with the presence or absence of FEG in patients with inflammatory bowel disease (IBD) and evaluate the association between medical therapy and H. pylori infection in IBD patients. Methods: We studied 62 patients with CD, 35 patients with UC and 40 patients from control group. All underwent upper GI endoscopy. Biopsy specimens taken from angulus, antrum and gastric body were evaluated by urease test, histology and immunohistochemistry. Results: Of the 137 patients studied we excluded 2 patients with CD and 1 with UC. There was no statistically significant difference among the groups in terms of age (p=0.921) and gender (p=0.192). The majority of CD patients were in clinical remission (75%). Around 80% of CD patients were taking azathioprine. H. pylori was positive in 18/60 (30%) CD patients, in 12/34 (35%) UC and in 20/40 (50%) controls with no statistically significance difference among the groups (p=0.131). No association was found between use of medications and H. pylori infection in IBD patients. In H. pylori negative patients, FEG was diagnosed in 16.7% cases (7/42) of CD, compared with 13.6% (3/22) of UC patients and 10% (2/20) of controls, with no statistically significance difference among them (p=0.919). In H.pylori positive patients, FEG was diagnosed in 11% cases (2/18) of DC, 25% (3/12) in UC and 35% (7/20) of controls with no significant difference among them (p=0.213). There was no statistical interrelationship between FEG and demographic and clinical characteristics, laboratory findings, use of medications, upper GI symptoms and endoscopic findings. However, it was observed that use of azathioprine in H. pylori negative CD patients presented a tendency to reduce FEG. In H. pylori negative patients, immunohistochemistry of FEG of CD and UC was similar and differed from controls as it presented a higher accumulation of B lymphocytes (CD20). On the other hand in H. pylori positive IBD patients, immunohistochemistry of FEG was indistinguishable from controls. Conclusions: IBD patients tend to be less infected by H. pylori. The frequency of H. pylori negative FEG diagnosed in our study was lower than described in literature. The use of immunossupressants (azathioprine) may be related to such findings

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-05-06T19:06:26Z No. of bitstreams: 1 glauciosilvadesouza.pdf: 303622 bytes, checksum: 139fcd6cbe1e2b7218e5e48cff0864ba (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-06-08T14:41:58Z (GMT) No. of bitstreams: 1 glauciosilvadesouza.pdf: 303622 bytes, checksum: 139fcd6cbe1e2b7218e5e48cff0864ba (MD5) / Made available in DSpace on 2016-06-08T14:41:58Z (GMT). No. of bitstreams: 1 glauciosilvadesouza.pdf: 303622 bytes, checksum: 139fcd6cbe1e2b7218e5e48cff0864ba (MD5) Previous issue date: 2013-03-27 / As taxas de hospitalização e de cirurgia são consideradas marcadores de agressividade da Doença de Crohn (DC). Os custos do tratamento da DC variam consideravelmente entre os pacientes, mas as hospitalizações, incluindo aquelas em que houve cirurgia, representam um maior impacto nos custos do tratamento da doença. Reduzir a taxa de hospitalização e cirurgia são pontos cruciais na redução dos custos do tratamento da doença. Foram avaliados os efeitos da azatioprina (AZA) comparado com os da mesalazina (MSZ) na incidência de hospitalização por todas as causas ou hospitalização relacionada a cirurgia. Foram analisados 72 pacientes com DC ileocecal sub-oclusiva que responderam ao tratamento clínico inicial. Os pacientes foram então randomizados em 2 grupos de tratamento AZA (2-3 mg/Kg dia) ou MSZ (3,2g/dia) por um período de 3 anos. As a taxa de hospitalização por todas as causas e de hospitalização relacionada a cirurgia foram observadas e comparadas entre os grupos. Também foi analisada a taxa de internação por paciente, o tempo de hospitalização e o intervalo até a primeira hospitalização. As variáveis demográficas foram similares nos grupos AZA e MSZ. A proporção de pacientes hospitalizados em 36 meses por todas as causas foi menor nos pacientes tratados com AZA, comparado àqueles que receberam MSZ (0,39 vs. 0,83, respectivamente; p=0,001). O grupo AZA também teve menor incidência de hospitalizações cirúrgicas (0,25 vs. 0,56, respectivamente; p = 0,011). O número de admissões por pacientes (0,7 vs.1,41, p=0,001) e o tempo de internação (3,8 vs.7,7 dias; p=0,002) também foram menores no grupo AZA. O intervalo até a primeira hospitalização no grupo AZA foi maior que aquele do grupo MSZ (27 vs. 17,9 meses, respectivamente; p=0,001). Pacientes com DC ileocecal sub-oclusiva tratados com AZA tiveram menor taxa de hospitalização por todas as causas e hospitalizações com cirurgia quando comparados a pacientes que receberam tratamento com MSZ num período de 3 anos. O uso prolongado de AZA na DC ileocecal em pacientes sub-ocluidos pode reduzir os custos do tratamento da doença. / Hospitalization and surgery are considered to be hallmarks of more aggressive behavior in Crohn’s disease (CD). Although the cost of CD treatment differs considerably, it is remarkable that hospitalization costs, including surgery, comprise the biggest amount of the total treatment cost. Decreasing hospitalization and surgery rates is of pivotal importance to reduce the health-care costs in this clinical setting. We evaluated the effect of azathioprine (AZA) when compared with mesalazine (MSZ) on incidence of hospitalizations due to all-causes and for CD-related surgical procedures. In this controlled, randomized study 72 subjects with sub-occlusive ileocecal CD were randomized for AZA (2-3 mg/kg per day) or MSZ (3.2 g per day) therapy during a 3-year period. The primary end point was the hospitalization rate due to all-causes as well as for surgical procedures during this period evaluated between the groups. The secondary outcomes were the total inpatient admission number, the length of hospitalization and the time interval until first hospitalization. Patients treated with AZA or MSZ were comparable according to demographics and disease characteristics. On an intention-to-treat basis, the proportion of patients hospitalized on 36 months due to all-causes was lower in patients treated with AZA when compared to those on MSZ (0.39 vs. 0.83, respectively; p=0.035). The AZA group had also significantly lower rates of hospitalization for surgical intervention (0.25 vs. 0.56, respectively; p=0.011). The number of admissions (0.70 vs. 1.41, p=0.001) and the length of hospitalization (3.8 vs. 7.7 days; p=0.002) were both lower in AZA-patients. The time interval until first hospitalization in AZA-group was significantly higher than in those on MSZ (27 vs. 17.9 months, respectively; p=0.001). Patients with sub-occlusive ileocecal CD treated with AZA had lower hospitalization rates due to all-causes and for surgical management of CD when compared to those treated with MSZ in a 3-years period. The long term use of AZA in ileocecal CD patients recovering from a sub-occlusion episode can save health-care cost.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-09-26T14:39:58Z No. of bitstreams: 1 joseeugenioriosriccijunior.pdf: 958378 bytes, checksum: f20499edf79931ac9fe901f9233cd200 (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-09-26T20:34:06Z (GMT) No. of bitstreams: 1 joseeugenioriosriccijunior.pdf: 958378 bytes, checksum: f20499edf79931ac9fe901f9233cd200 (MD5) / Made available in DSpace on 2016-09-26T20:34:06Z (GMT). No. of bitstreams: 1 joseeugenioriosriccijunior.pdf: 958378 bytes, checksum: f20499edf79931ac9fe901f9233cd200 (MD5) Previous issue date: 2016-08-12 / O supercrescimento bacteriano do intestino delgado (SCBID) é definido como um aumento no número e/ou alteração no tipo de bactérias no intestino delgado. Na sua patogênese incluem dano à válvula ileocecal e anormalidades anatômicas, comuns na doença de Crohn (DC). O presente estudo tem como objetivo estudar a prevalência e preditores de SCBID em pacientes com DC, assim como avaliar a relação entre SCBID e inflamação sistêmica e/ou intestinal. Neste estudo transversal, entre Junho de 2013 e Janeiro de 2015, 92 pacientes com DC e 97 controles com queixas gastrointestinais não crônicas foram avaliados quanto à presença de SCBID usando o teste respiratório (TR) com hidrogênio e metano exalados. Regressão logística multivariada foi realizada para investigar a potencial associação entre SCBID com dados demográficos, características da doença, marcadores sistêmicos de inflamação (proteína C reativa - PCR - e velocidade de hemossedimentação de eritrócitos - VHS), e biomarcador fecal de inflamação intestinal (calprotectina fecal - CF). A taxa de SCBID foi significativamente maior em pacientes com DC do que nos controles (32,6% vs. 12,4%, respectivamente; p = 0,0008). Os pacientes com e sem SCBID foram semelhantes de acordo com os dados demográficos, marcadores inflamatórios sistêmicos e características da doença, exceto o fenótipo estenosante, mais comum nos pacientes com DC positivos para SCBID (43,3% vs. 19,3%; p = 0,015). Notavelmente, a concentração de CF foi significativamente mais elevada em pacientes positivos para SCBID (mediana de 485,8 vs.132,7 ug/g; p = 0,004). Os pacientes que apresentaram aumento da CF e doença estenosante tiveram um odds de 9,43 (IC de 95%, 3,04-11,31; p <0,0001) e 3,83 (95% CI, 1,54-6,75; p = 0,025), respectivamente, para o diagnóstico de SCBID. Em pacientes com DC, o SCBID é uma condição altamente prevalente. O fenótipo estenosante e o aumento da concentração de CF foram fortemente e independentemente associados com a presença de SCBID. O diagnóstico de SCBID seguido de tratamento direcionado é recomendado em pacientes com DC, especialmente no cenário de fenótipo estenosante e/ou na presença concomitante de inflamação intestinal. / Introduction: The small intestine bacterial overgrowth (SIBO) is defined as an increase in the number and/or change in the type of bacteria in the small intestine. In its pathogenesis it is important the damage on the ileocecal valve and anatomical abnormalities, both common in Crohn's disease (CD). The aim of this study was to determine the prevalence and predictors of SIBO in CD patients as well as to assess the relationship between SIBO and systemic and/or intestinal inflammation. In this cross-sectional study, between June 2013 and January 2015, 92 CD patients and 97 controls with non-chronic gastrointestinal complaints were assessed for presence of SIBO using the H2/CH4 glucose breath test. Multivariate logistic regression was performed to investigate the potential association between SIBO and demographic, disease-related data, systemic markers of inflammation (C-reactive protein and erythrocyte sedimentation rate), and biomarker of intestinal inflammation (fecal calprotectin concentration - FCC). The SIBO rate was significantly higher in CD patients than in the controls (32.6% vs. 12.4%, respectively, P=0.0008). Patients with and without SIBO were comparable according to demographics, systemic inflammatory biomarkers, and disease characteristics, except to the stricturing phenotype more common in the SIBO-positive CD patients (43.3% vs. 19.3%, P=0.015). Notably, FCC was significantly higher in SIBO-positive patients (median of 485.8 vs.132.7 μg/g; P = 0.004). Patients presenting increased FCC and stricturing disease had an odds of 9.43 (95% CI, 3.04-11.31; P <0.0001) and 3.83 (95% CI, 1.54-6.75; P=0.025) respectively, for SIBO diagnosis. Conclusions: In CD patients, SIBO is a highly prevalent condition. Stricturing phenotype and increased FCC were strongly and independently associated with the presence of SIBO. SIBO diagnostic work-up followed by directed treatment is recommended in CD patients, especially if stricturing disease or concurrent intestinal inflammation is present.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-03-24T15:20:36Z No. of bitstreams: 1 ritadecassiaazevedocoutocornelio.pdf: 3370166 bytes, checksum: e79af08a636d474eca822391703dcc7c (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-03-27T17:36:55Z (GMT) No. of bitstreams: 1 ritadecassiaazevedocoutocornelio.pdf: 3370166 bytes, checksum: e79af08a636d474eca822391703dcc7c (MD5) / Made available in DSpace on 2017-03-27T17:36:55Z (GMT). No. of bitstreams: 1 ritadecassiaazevedocoutocornelio.pdf: 3370166 bytes, checksum: e79af08a636d474eca822391703dcc7c (MD5) Previous issue date: 2008-06-26 / CONTEXTO: A não-adesão ao tratamento medicamentoso, em algum grau, ocorre universalmente. É uma das principais causas de insucesso no tratamento das doenças crônicas, tal como a doença de Crohn. OBJETIVO: Em doentes com doença de Crohn, avaliar a prevalência e os fatores de risco associados à baixa adesão ao tratamento medicamentoso. MÉTODOS: No período entre julho de 2006 e julho de 2007 foram incluídos prospectivamente, para avaliação da não-adesão ao tratamento, 100 doentes com doença de Crohn em seguimento clínico no ambulatório de doenças inflamatórias intestinais. Os pacientes responderam ao Teste de Medida de Adesão a Tratamentos de Morisky e Green, modificado. De acordo com este teste, os pacientes foram classificados em dois grupos, conforme o grau de adesão: adesão e não-adesão. A não-adesão foi subdividida em intencional e não-intencional. Variáveis clínicas, psicológicas e farmacoterapêuticas foram pesquisadas na busca de possíveis fatores associados à não-adesão. RESULTADOS: Entre os pacientes avaliados, 64% apresentaram escore compatível com não-adesão. O perfil mais frequente de não-adesão foi o do tipo não-intencional, e os pacientes mostraram ter conhecimento e motivação para o tratamento. Na comparação entre os dois grupos observou-se somente uma tendência a não-adesão entre os pacientes mais jovens (P = 0,07) e de raça não-branca (P = 0,06). Não houve correlação significativa entre o grau de adesão e as variáveis psicológicas e farmacoterapêuticas. CONCLUSÕES: Em pacientes com doença de Crohn, a prevalência de não-adesão ao tratamento medicamentoso é elevada (64%). Indivíduos jovens e aqueles não-brancos parecem ser os mais predispostos à não-adesão. Portanto, é preciso estar alerta para sua ocorrência e, caso necessário, implementar medidas que busquem aumentar o grau de adesão destes pacientes. / CONTEXT: Non-adherence to therapy, in any degree is a common event and occurs in several circumstances. It is one of most common cause of fail in therapy of chronic diseases and Crohn's disease is not an exception. OBJECTIVE: To evaluate in patients with Crohn's disease the prevalence and the risk factors to non-adherence to therapy. METHODS: From July 2006, for 12 months, were included prospectively, for non-adhesion to therapy 100 patients with Crohn's disease that were assisted in a Center for Inflammatory Bowel Diseases of Universitary Hospital of Federal University of Juiz de Fora, MG, in Brazil. A modified Morisky & Green Test for Measure of Adherence to Therapy was answered by all of them. According to test the patients were classified in two groups defined as adherence and non-adherence, respectively, and the last one was separated in intentional and non-intentional adhesion. Clinical, psychological and pharmacotherapeutics variables were sought to find the factors related to non-adherence. RESULTS: Sixty four percent of total group were noticed to have a score of non-adherence to therapy according to used test and non-intentional was the most common type of behavior in such patients, and they demonstrated to be conscious of therapy. The comparison of adherent and non-adherent patients displayed a significant tendency to occurrence of non-adherence in younger (P = 0,07) and in non-white patients (P = 0,06). No correlation was observed in comparison of psychological and pharmacotherapeutics variables and non-adherence. CONCLUSIONS: In patients with Crohn's disease the prevalence of non-adherence to therapy is high (64%). The younger and non-white patients have higher propensity to non-adherence. In such circumstances efforts should be made to look for strategies to deal with this sort of people suffering from Crohn's disease, trying to increase the degree of adherence in this sort of patients.

B-lymphocytes are lymphoid cells, which are a part of the adaptive/innate immune system and generate antibodies. Recently, many studies have supported hypothesis that different rather minor B-lymphocyte subpopulations may play a direct and indirect role in immunopathogenesis in human pathologies such as Crohn's disease (CD). The aim of current study was therefore to investigate distribution of frequencies of B lymphocyte subpopulations (from transient to mature effector B cell stages) in peripheral blood of healthy subjects (CO), patients with Crohn's disease (CD) and ulcerative colitis (UC). Thus, using 11-colour flow cytometry we have analysed 30 blood samples of individuals, including 14 healthy controls, 11 patients with Crohn's disease and 5 with UC. In 6 patients with CD we have had an opportunity to analyze blood samples collected 2 hours after an administration of anti-TNF therapy. Higher frequencies of memory B-lymphocytes (CD19+ CD27+ , CD19+ CD20+ CD27+ and CD19+ CD20+ CD27+ IgM+) were found in patients with CD as compared to COs. (20.06±13.58%; 17.61±13.48%; 88.60±20.56% vs. 11.75±26.47%; 11.25±26.50%; and 66.82±22.60%), in case of CD19+CD20-CD27-IgM+ B-lymphocytes the difference was statistically significant (57.15±17.21% in CD vs. 19.59±31.79% in CO; p=0.0341), which is in accordance...

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-01-21T13:29:23Z No. of bitstreams: 1 fernandomendoncavidigal.pdf: 1080288 bytes, checksum: 1512d97ed552f3d14c85e421c3f6c0b9 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-01-25T18:45:58Z (GMT) No. of bitstreams: 1 fernandomendoncavidigal.pdf: 1080288 bytes, checksum: 1512d97ed552f3d14c85e421c3f6c0b9 (MD5) / Made available in DSpace on 2016-01-25T18:45:58Z (GMT). No. of bitstreams: 1 fernandomendoncavidigal.pdf: 1080288 bytes, checksum: 1512d97ed552f3d14c85e421c3f6c0b9 (MD5) Previous issue date: 2014-12-12 / Introdução: Pacientes com Doença de Crohn (DC) suboclusiva que receberam tratamento com azatioprina (AZA) tiveram menores taxas de re-hospitalização devido a todas as causas e para tratamento operatório da DC quando comparados àqueles tratados com mesalazina durante um período de três anos. Nós investigamos se a AZA também foi efetiva para a prevenção da obstrução intestinal recorrente. Material e Métodos: Taxas de obstrução intestinal recorrente foram comparadas entre pacientes tratados com AZA e aqueles tratados com mesalazina. Nós avaliamos o intervalo de tempo livre de obstrução intestinal assim como a sobrevida livre de oclusão para ambos os grupos. Resultados: Houve uma taxa cumulativa significativamente mais baixa de pacientes com suboclusão recorrente no grupo da AZA (43,8%) comparado ao grupo da mesalazina (79,4%; OR 3,34, 95% IC 1,67-8,6; p = 0,003) com o número necessário para prevenir um episódio de suboclusão de 3,7 a favor da AZA. O intervalo de tempo livre de oclusão foi maior no grupo da AZA comparado ao grupo da mesalazina (28,8 vs. 18,3 meses, p = 0,000). A sobrevida livre de oclusão aos 12, 24 e 36 meses foi significativamente maior no grupo da AZA (91%, 81%, e 72%, respectivamente) do que no grupo da mesalazina (64,7%, 35,3%, e 23,5%, respectivamente; p < 0.05 para todas as comparações). Conclusão: Em uma análise exploratória de pacientes com DC ileocecal suboclusiva, a terapia de manutenção com AZA é mais efetiva que a mesalazina para evitar ou postergar a obstrução intestinal recorrente durante um período de três anos de tratamento. / Background: Patients with subocclusive Crohn’s disease (CD) who received azathioprine (AZA) therapy had lower re-hospitalization rates due to all causes and for surgical management of CD compared to those treated with mesalazine during a 3-year period. We investigated whether AZA also was effective for prevention of recurrent bowel obstruction. Material and Methods: Rates of recurrent bowel occlusion were compared between patients treated with AZA and those treated with mesalazine. We assessed the time interval-off intestinal obstruction as well as the occlusion-free survival for both groups. Results: There was a significantly lower cumulative rate of patients with recurrent subocclusion in the AZA group (43.8%) compared with the mesalazine group (79.4%; OR 3.34, 95% CI 1.67-8.6; P= 0.003) with a number needed to treat in order to prevent one subocclusion episode of 3.7 favoring AZA. The occlusion-free time interval was longer in AZA compared with the mesalazine group (28.8 vs. 18.3 months; P=0.000).The occlusion-free survival at 12, 24, and 36 months was significantly higher in the AZA group (91%, 81%, and 72%, respectively) than in the mesalazine arm (64.7%, 35.3%, and 23.5%, respectively; P<0.05 for all comparisons). Conclusions: In an exploratory analysis of patients with subocclusive ileocecal CD maintenance therapy with AZA is more effective than mesalazine for eliminating or postponing recurrent intestinal obstruction through 3 years of therapy.

Les neutrophiles infiltrent la muqueuse colique inflammatoire en maladie de Crohn (CD). Cependant, on ignore l’existence d’une corrélation entre la sévérité endoscopique et la fréquence et/ou l’activation des neutrophiles et autres granulocytes. Une cohorte de 73 patients atteints de CD fut recrutée prospectivement. Les participants furent stratifiés selon la Classification de Montréal ou subdivisés selon le phénotype endoscopique (phénotype typique vs apparence endoscopique « UC-Like »). L’index d’Harvey Bradshaw (HBI) et le Simple Endoscopic score (SES-CD) furent calculés au moment de la coloscopie. La fréquence et l’expression de CD66b et de CD64 sur les granulocytes furent évaluées en cytométrie de flux sur des échantillons sanguins et des biopsies coliques. Le SES-CD corrélait avec l’expression du CD66b sur les neutrophiles coliques et du CD64 sur les neutrophiles circulants en présence de maladie active avec comportement inflammatoire (B1). Les fréquences des neutrophiles et des basophiles mais non des eosinophiles étaient augmentées au sein de la muqueuse inflammatoire, mais la fréquence des neutrophiles coliques n’était corrélée avec le SES-CD uniquement en présence d’un phénotype endoscopique « UC-like ». Deux scores d’activation granulocytaire étaient discriminant entre les individus avec maladie légère et sévère dans l’ensemble de la cohorte avec maladie active. L’activation des granulocytes dans le sang et la muqueuse colique corrèle avec le SES-CD dans des sous-groupes de patients avec une maladie B1, alors que les scores d’activation granulocytaire pourraient être pertinent cliniquement pour évaluer la sévérité de la maladie et possiblement avoir une valeur prognostique parmi les individus avec maladie active. / Neutrophils infiltrate the inflamed colon in Crohn’s disease (CD). However, correlation between endoscopic severity, and frequency and/or activation of neutrophils and other granulocytes like basophils and eosinophils remains to be investigated. A cohort of 73 CD patients was prospectively enrolled according to endoscopic severity and treatment history. Patients with active disease were stratified according to Montreal classification or subdivided into typical CD and UC-like endoscopic features. Harvey Bradshaw Index (HBI) and Simple Endoscopic score (SES-CD) were performed at the time of ileocolonoscopy. Frequency and expression of CD66b and CD64 on granulocytes were assessed in paired blood and colonic biopsies using flow cytometry. SES-CD correlated with neutrophil CD66b expression in mucosa but not blood and conversely, with neutrophil CD64 expression in blood but not mucosa in CD patients with inflammatory (B1) active disease. Frequencies of neutrophils and basophils but not eosinophils, increased in inflamed colon, but only in a subgroup of CD patients presenting “UC-like” endoscopic features were the frequencies of colonic neutrophils correlated with SES-CD. Furthermore, a neutrophil activation score (CD66b X CD64 on neutrophils) and a blood granulocyte score (CD66b on eosinophils X CD64 on neutrophils) discriminated between mild and severe disease in the entire cohort of patients with active disease. Activation of granulocytes in blood and/or mucosa correlated with SES-CD in subgroups of patients with B1 inflammatory disease while granulocyte activation scoring systems may be clinically relevant to evaluate disease severity and predict prognosis in the entire cohort of active disease patients.

Bakgrund: Inflammatorisk mag-tarmsjukdom är ett samlingsnamn för Ulcerös kolit och Crohns sjukdom. Gemensamt för sjukdomarna är att de är kroniska och att de går i skov, vilket innebär att sjukdomen är mer aktiv i vissa perioder och mindre aktiv under andra. Inflammatorisk mag-tarmsjukdom påverkar patienterna fysiskt, psykiskt och socialt, vilket påverkar deras livskvalitet. Inflammatoriska mag-tarmsjukdomar kan resultera i psykiska besvär, därför har patienterna ett behov av goda copingstrategier och en god anpassning till livet med sjukdomen. Genom evidensbaserad och personcentrerad vård har sjuksköterskan en stödjande funktion i vården av dessa patienter.  Syfte: Syftet med litteraturstudien var att undersöka patienternas upplevelser av att leva med inflammatorisk mag-tarmsjukdom för att kunna belysa deras behov av stöd. Metod: En litteraturstudie med boolesk sökteknik gjordes i databaserna Cinahl, PubMed och PsycINFO där tio artiklar valdes ut genom granskning med SBU:s granskningsmall.    Resultat: När resultatet av tio artiklar sammanställts framkom fyra teman; patienters upplevelser av att leva med inflammatorisk mag-tarmsjukdom, patienternas behov av stöd, stöd i att acceptera och leva med sjukdomen samt stöd i form av utbildning. Slutsats: Patienter med inflammatorisk mag-tarmsjukdom har behov av stöd både fysiskt, psykiskt och socialt, från både sjukvårdspersonal och anhöriga. Patienterna har ett behov av stöd i form av information, undervisning samt psykiskt och emotionellt stöd. Sjuksköterskans stöd genom personcentrerad och empatisk kommunikation hjälper patienterna att acceptera sjukdomen och deras “nya normala”, vilket främjar deras självständighet, självkännedom och eget ansvar i sjukdomshanteringen. Patientutbildning bidrar till bättre egenvårdsstrategier, ökad följsamhet till behandling och livsstils anpassningar, vilket även bidrar till ökat självförtroende och välmående.

Interleukin(IL)-22, ein Zytokin der IL-10-Interferon-Familie, beeinflusst die Funktion von Gewebezellen, wirkt jedoch nicht auf Immunzellen. In dieser Arbeit konnte ich zeigen, dass IL-22 in Keratinozyten nur eine begrenzte Anzahl von Genen in ihrer Expression reguliert, was eine Hemmung der terminalen Differenzierung und eine Steigerung der antimikrobiellen Abwehr und der zellulären Mobilität bewirkt. Diese IL-22-Effekte konnten in vivo aufgrund ihrer Induzierbarkeit durch eine IL-22-Behandlung in Mäusen bestätigt werden und fanden sich darüber hinaus in der läsionalen Haut von Patienten mit Psoriasis wieder. Eine pathogenetische Rolle von IL-22 bei Psoriasis wurde durch eine gefundene Erhöhung der IL-22-Spiegel im Blut dieser Patienten und eine Korrelation dieser mit dem Schweregrad der Erkrankung untermauert. Eine Untersuchung der Wirkung von IL-22 auf Hepatozyten zeigte, dass IL-22 in diesen Zellen die Produktion des LPS-Bindungsproteins (LBP) steigert, welches in hohen Konzentrationen bakterielle Bestandteile neutralisiert. In vivo zeigte sich, dass eine IL-22-Gabe in der Maus eine verstärkte Expression von LBP in der Leber und erhöhte sytemische LBP-Spiegel bewirkt. Diese Hepatozyten-spezifische IL-22-Wirkung spiegelte sich bei Patienten mit Morbus Crohn in erhöhten systemischen LBP-Spiegeln wieder. Bei der Psoriasis steht vor allem der regenerative Phänotyp der Keratinozyten, gekennzeichnet durch eine verminderte terminale Differenzierung und eine gesteigerte Mobilität, im Vordergrund und bildet die Ursache für die klinisch sichtbaren epidermalen Veränderungen. Demgegenüber könnte bei Morbus Crohn IL 22 durch die Induktion von hepatozytärem LBP zur Neutralisierung von durch die gestörte Darmbarriere ins Blut translozierte bakterielle LPS zur lokalen Begrenzung der Entzündung beitragen. Ausgehend von diesen Beobachtungen wäre eine IL-22-Neutralisierung bzw. IL-22-Applikation ein innovativer Therapieansatz für die Behandlung von Psoriasis und Morbus Crohn. / Interleukin(IL)-22, a cytokine belonging to the IL-10-Interferon-family, regulates the function of tissue cells, but not of immune cells. Here, I could show, that in keratinocytes IL-22 regulates the expression of a limited number of genes leading to an inhibition of the terminal differentiation and an increase of the antimicrobial defense and cellular mobility. These IL-22 effects were also confirmed in vivo as they could be induced in mice by IL-22-treatment and moreover, were also found to be present in the lesional skin of psoriasis patients. A pathogenetic role of IL-22 in psoriasis was substantiated by the finding that IL-22 level are elevated in the blood of these patients and correlated with the disease severity. By investigating the influence of IL-22 on hepatocytes, I found an increase of LPS-binding protein (LBP) production by IL-22, a protein which neutralizes bacterial components at high concentrations. In vivo, IL-22 treatment of mice led to a high hepatic LBP expression and elevated blood LBP level. This hepatocyte-specific IL-22 effect was reflected in patients with crohn´s disease in elevated systemic LBP level. In psoriasis, especially the regenerative phenotype of keratinocytes, characterized by the distorted terminal differentiation and enhanced mobility, is a key feature and the basis for the clinically visible epidermal alterations. In contrast, in crohn´s disease by inducing hepatic LBP production IL-22 likely contributes to the neutralisation of LPS translocated into the blood via the distorted intestinal barrier and thereby to a local limitation of inflammation. Based on these observations a neutralisation or application of IL-22 would be an innovative therapeutic approach for the treatment of psoriasis and crohn´s disease, respectively.

In zahlreichen Studien konnte an Mausmodellen gezeigt werden, dass dendritische Zellen eine wichtige Rolle im Rahmen der mukosalen Immunabwehr spielen. Eine unkontrollierte Aktivierung immunologischer Effektorzellen durch antigenpräsentierende Zellen ist die Folge, welche die Antigene der luminalen Flora folglich falsch erkennen und damit zu einer Schädigung des Gewebes führen. In der Arbeit wurden humane CD1c+CD11c+CD14-CD19- myeloide dendritische Zellen (mDCs) aus dem peripheren Blut und der intestinalen Mukosa von CED Patienten sowie von gesunden Probanden phänotypisch und funktionell näher charakterisiert. mDCs von Patienten reagieren auf LPS im Gegensatz zu DCs von Gesunden mit der Ausbildung eines aktivierten Phänotyps und der Sekretion pro-inflammatorischer Zytokine. Die Daten lassen vermuten, dass ihre tolerogene Rolle gestört ist und die Zellen so möglicherweise aktiv zum Entzündungsgeschehen durch eine Fehlreaktion auf die kommensale Flora beitragen. Es konnte gezeigt werden, dass zirkulierende mDCs von Erkrankten mehr LPS aufnehmen. Des Weiteren ist die Häufigkeit von mukosalen und aktivierten mDCs bei CED Patienten signifikant erhöht. Die vermehrte Häufigkeit von aktivierten mDCs in der entzündeten Mukosa ist ein Hinweis auf intestinales „homing“, also ein Wiedereinwandern der gereiften Lymphozyten in die Darmwand. Es ist bekannt, dass die Hefe Saccharomyces boulardii (Sb) eine Wirksamkeit bei entzündlichen sowie infektiösen Erkrankungen des Gastrointestinaltraktes hat. Kulturexperimente von mDCs mit Zellkulturüberständen von Sb (SbS) und LPS zeigten eine deutliche Reduzierung in der Expression von CD40 und CD80 sowie des Reifemarkers CD197. SbS reduzierte die Sekretion von TNF- und IL-6. Während es die Sekretion von IL-10 bei gesunden Probanden erhöhte, konnte bei CED Patienten eine leichte Abnahme verzeichnet werden. SbS vermindert die Proliferation von naïven T-Zellen in einer gemischten Lymphozytenreaktion mit gesunden mDCs signifikant. / Various animal studies have provided insights that mucosal dendritic cells play a key role in this process. However, the specific function of certain dendritic cells in IBD is still unknown. Primary CD1c+CD11c+CD14-CD19- myeloid blood (mDCs) and mucosal DCs from IBD patients and healthy controls were compared. More mDCs from IBD patients exhibited an activated phenotype shown by expression of co-stimulatory molecules. mDCs from patients secrete higher levels of pro- and anti-inflammatory cytokines. Circulating mDCs from IBD patients take up more LPS and the frequency of mucosal mDCs and the number of activated, i.e. CD40 and CD80 expressing mucosal mDCs, is significantly greater in CED. The increased frequency of activated mDCs in the inflamed mucosa suggests intestinal homing of mDCs in acute stages of IBD. Further, the data suggests an aberrant LPS response of mDCs in patients suffering from IBD which results in an inflammatory phenotype. The most widely accepted hypothesis for the cause of IBD is a disturbed interaction of the host immune system with commensal microflora and other luminal antigens. The well controlled balance of the intestinal immune system is disturbed and luminal antigens like LPS gain access to the underlying mucosal tissue via the leaky barrier. It was investigated whether the yeast preparation Saccharomyces boulardii (Sb) modulates dendritic cell function which has shown efficacy in inflammatory and infectious disorders of the gastrointestinal tract. Culture experiments of mDCs in the presence of Sb culture supernatant (SbS) significantly reduced the expression of CD40 and CD80 as well as the DC maturation marker CD197 (CCR7) induced by the prototypical microbial antigen LPS. SbS reduced secretion of TNF- and IL-6, while the secretion of anti-inflammatory IL-10 increased. IBD patients showed also a reduction in their secretion level of IL-10. SbS inhibited proliferation of naïve T cells in a mixed lymphocyte reaction with healthy mDCs.