Prevalence and Factors Associated With Fatigue in Patients With Inflammatory Bowel Disease: A Multicentre Study.

BACKGROUND AND AIMS: The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. METHODS: This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. RESULTS: A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn's disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37-45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6-3.7], depression [OR = 2.4, 95% CI = 1.4-3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1-2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4-5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3-14.2], anxiety [RC = 25.8, 95% CI = 20.0-31.5], depression [RC = 30.6, 95% CI = 24.3-37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3-20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. CONCLUSIONS: The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Pharmacologic therapy for inflammatory bowel disease refractory to steroids.

Although corticosteroids are an effective treatment for induction of remission in inflammatory bowel disease (IBD), many patients are dependent on or refractory to corticosteroids. This review is based on scrutinizing current literature with emphasis on randomized controlled trials, meta-analyses, and Cochrane reviews on the management of IBD refractory to corticosteroids. Based on this evidence, we propose algorithms and optimization strategies for use of immunomodulator and biologic therapy in IBD refractory to corticosteroids.

Biologic therapies for chronic inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) make up the so-called chronic inflammatory bowel disease (IBD). Advances in the understanding of IBD pathophysiologic mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies, which at least theoretically represent a more specific management of this disease with fewer side effects. Currently, the only effective and widely accepted biologic therapy for the treatment of intraluminal, fistulizing CD, both for remission induction and maintenance, is infliximab. The role of other monoclonal antibodies such as adalimumab is not clearly established. It could be deemed an alternative for patients with allergic reactions to infliximab, and for those with lost response because of anti-infliximab antibody development. However, relevant issues such as dosage and administration regimen remain to be established. Anti-integrin a4 therapies, despite encouraging results in phase-3 studies, are still unavailable, as their marketing authorization was held back in view of a number of reports regarding progressive multifocal leukoencephalopathy cases. Immunostimulating therapy may be highly relevant in the near future, as it represents a novel strategy against disease with the inclusion of granulocyte-monocyte colony-stimulating factors.Regarding ulcerative colitis, results from the ACT-1 and ACT-2 studies showed that infliximab is also useful for the management of serious UC flare-ups not responding to standard treatment, which will lead to a revision of therapeutic algorithms, where this drug should be given preference before intravenous cyclosporine. In the next few years, the role of anti-CD3 drugs (vilisilizumab), T-cell inhibiting therapies, and epithelial repair and healing stimulating factors will be established.

Tratamientos biológicos en la enfermedad inflamatoria crónica intestinal / Biologic therapies for chronic inflammatory bowel disease

La enfermedad de Crohn (EC) y la colitis ulcerosa (CU) constituyenla denominada enfermedad inflamatoria crónica intestinal(EII). Los avances producidos en los últimos años en el conocimientode los mecanismo fisiopatológicos de la EII han permitidoel desarrollo de nuevos tratamientos, como son las terapias biológicas,que suponen, al menos teóricamente un manejo más especificode esta enfermedad y con menos efectos secundarios. En elmomento actual, la única terapia biológica eficaz y aceptada parael tratamiento de la EC intraluminal y fistulizante es el infliximab,tanto para inducir la remisión como para el mantenimiento de lamisma. El papel de otros anticuerpos monoclonales como el adalimumabno esta claramente establecido. Se podría perfilar comouna alternativa en los pacientes con reacciones alérgicas al infliximaby en aquellos que han perdido la respuesta al fármaco por eldesarrollo de anticuerpos al mismo. Sin embargo quedan por determinaraspectos importantes como son las dosis y al pauta deadministración. Las terapias anti-integrina α4, a pesar de los resultadosprometedores de los estudios en fase 3, no se encuentranaún disponibles por estar detenida la comercialización del fármacodebido a la comunicación de varios casos de leucoencefalopatíamultifocal progresiva. En un futuro próximo, quizá tenga gran relevanciala terapia inmunoestimulante que utiliza una nueva estrategiafrente a la enfermedad y que incluye factores estimulantes delas colonias de los granulocitos y monocitos.En la colitis ulcerosa, los resultados de los estudios ACT-1 yACT-2, han demostrado que el infliximab es un fármaco útil en eltratamiento de los brotes graves de CU sin respuesta al tratamientoestándar lo que obligará a revisar los algoritmos de tratamientoy anteponer este fármaco a la ciclosporina intravenosa. En lospróximos años, probablemente quedará definido el papel de losfármacos anti-CD3 (vilisilizumab) y de las terapias inhibidoras delos linfocitos T o del empleo de factores estimulantes de la reparacióny cicatrización epitelial

Crohn's disease (CD) and ulcerative colitis (UC) make up theso-called chronic inflammatory bowel disease (IBD). Advances inthe understanding of IBD pathophysiologic mechanisms in the lastfew years have allowed the development of novel therapies suchas biologic therapies, which at least theoretically represent a morespecific management of this disease with fewer side effects. Currently,the only effective and widely accepted biologic therapy forthe treatment of intraluminal, fistulizing CD, both for remission inductionand maintenance, is infliximab. The role of other monoclonalantibodies such as adalimumab is not clearly established. Itcould be deemed an alternative for patients with allergic reactionsto infliximab, and for those with lost response because of anti-infliximabantibody development. However, relevant issues such asdosage and administration regimen remain to be established. Antiintegrinα4 therapies, despite encouraging results in phase-3 studies,are still unavailable, as their marketing authorization was heldback in view of a number of reports regarding progressive multifocalleukoencephalopathy cases. Immunostimulating therapy maybe highly relevant in the near future, as it represents a novel strategyagainst disease with the inclusion of granulocyte-monocytecolony-stimulating factors.Regarding ulcerative colitis, results from the ACT-1 and ACT-2studies showed that infliximab is also useful for the managementof serious UC flare-ups not responding to standard treatment,which will lead to a revision of therapeutic algorithms, where thisdrug should be given preference before intravenous cyclosporine.In the next few years, the role of anti-CD3 drugs (vilisilizumab),T-cell inhibiting therapies, and epithelial repair and healing stimulatingfactors will be established

Budd-Chiari syndrome associated with nodular regenerative hyperplasia of the liver.

The Budd-Chiari syndrome due to membranous obstruction of the hepatic blood outflow tract is a rare condition in western countries, and its association with nodular regenerative hyperplasia of the liver has never been described. We present the case of a 34-year-old woman with membranous obstruction of hepatic veins and nodular regenerative hyperplasia of the liver. Although webs have been difficult to demonstrate by sonography, we were able to image a structure in the hepatic vein near the junction with the inferior vena cava, suggesting a membranous nature.

[Multiple gastric carcinoids, atrophic gastritis, hypergastrinemia: a confirmed association (a new case)]. / Carcinoides gástricos múltiples, gastritis atrófica, hipergastrinemia: una asociación que se confirma (un nuevo caso).

Although carcinoid tumors only infrequently (2-6%) have a gastric localization, in recent years several cases have been described of this tpe of neoplasm in association with atrophic gastritis (with or without pernicious anemia). A possible carcinogenetic effect of sustained hypergastrinemia on the enterochromaffin-like cells (ECL) of the gastric mucosa has been postulated. A new case of these characteristics in reported, and a review is made of the pathogenic hypotheses in the literature on this peculiar type of tumors and their possible clinical implications.