关键词： Crohn's disease   Inflammatory bowel disease   Leukocytapheresis   Ulcerative colitis  

摘要： Studies about leukocytapheresis have emerged with the need of search for alternatives to conventional treatment in inflammatory bowel diseases (IBD). Leukocytapheresis is a novel non-pharmacologic approach for active ulcerative colitis (UC) and Crohn's disease (CD), in which leukocytes are mechanically removed from the circulatory system. Patients with active IBD treated with leukocytapheresis using a Cellsorba E column between 2012 and 2015, were enrolled in Turkey. In our experience, the results of leukocytapheresis therapy in 6 patients with CD and 20 patients with active UC were overviewed. Leukocytapheresis (10 sessions for remission induction therapy, 6 sessions for maintenance therapy) was applied to the patients with their concomitant medications. Intensive leukocytapheresis (>= 4 leukocytapheresis sessions within the first 2 weeks) was used in 30% patients with active severe UC. The overall clinical remission rate in patients with UC was 80%, and the mucosal healing rate was 65%. Patients were followed for an average of 24 months. It was observed that clinical remission has continued in 65% of patients with UC. Mild relapse was observed in 3 patients with UC during follow up period. In 5 patients with CD significant clinical remission was achieved except only one patient. Surgical needs were disappeared in 3 patients with obstructive type Crohn's disease, Adverse events were seen in only 4.3% of 416 sessions. Any concomitant medications did not increase the incidence of adverse events. Our results indicate that leukocytapheresis is efficacious in improving remission rates with excellent tolerability and safety in patients with IBD. (C) 2017 Elsevier Ltd. All rights reserved.

关键词： Cohort Studies   Gaelic   Psoriasiform skin lesions   Inflammatory Bowel Diseases   Psoriasis   Tumor Necrosis Factor-alpha   Intestinal Diseases  

摘要： Aim: To determine the prevalence of psoriasis in an IBD cohort with reference to clinical characteristics and anti-TNF alpha use. Methods: Patients with psoriasis and IBD were retrospectively identified from the IBD database at Tallaght Hospital from 2000 to 2015. Pertinent clinical data were obtained from patients notes including anti-TNF alpha exposure. Prevalence rates of genuine and reactive psoriasis were calculated and compared using Student's T-test. A P values of <0.05 was considered significant. Results: In total, 1384 IBD patients were identified. The overall prevalence rate of IBD and psoriasis was 2.4% (n = 33), with 1.8% (n = 25) in the Crohn's disease group and 0.6% (n = 8) in the ulcerative colitis group. Within the psoriasis group, 24% (n = 8 of 33) had reactive psoriasis. The prevalence rates of psoriasis in the non-biological and biological cohorts were similar 2.5% (25 of 981) and 2% (8 of 403), respectively. There was no significant association with reactive psoriasis and disease type. There was a trend towards higher rates of reactive psoriasis Adalimumab users, 3.6% (6 of 166) vs. 0.8% (2 of 237), OR = 4.283, P = 0.077, 95% CI 0.854-21.483 in infliximab users. In addition, in our cohort, smoking was not associated with any form of psoriasis in IBD, OR = 1.377, 95% CI 0.061-3.087, P = 0.437. Conclusion: In our large study, the prevalence rate of reactive psoriasis was similar to the background rate of psoriasis in the overall IBD cohort (2.0 vs. 2.4%). A 2% prevalence rate represents a common adverse event that clinicians should be aware of.

关键词： Risk Stratification   Immune-Mediated Liver Disease   Autoimmune Liver Disease   Cholestasis  

摘要： BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594);patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62;P <.001 and HR,

关键词： Classification and regression tree analysis   Crohn's disease   Gastroenterology   Inflammatory bowel disease   Mode of administration   Patient preferences   Ulcerative colitis  

摘要： It is important to compare patient and provider discrepancies on stated openness to and preference for biologics as well as predictors associated with initial discussions on biologic use. Patients (N = 263) and physicians (N = 100) completed a self-administered Web-based survey assessing demographics, health characteristics, and behaviors related to inflammatory bowel disease (IBD) treatment. Bootstrap methods were used to check discrepancies between providers' and patients' stated openness to and preference for biologics. Classification and regression tree (CART) analysis identified patient-specific predictors associated with initial biologics discussions. A total of 170 patients responded consistently to preference questions, and 169 patients responded consistently to openness questions. Physicians significantly overestimated patients' openness to biologics in general (85.46% vs. 74.61%, p < 0.0001), but underestimated patients' openness to the intravenous (IV) mode of administration (MOA;55.97% vs. 63.96%, p < 0.0001). Overall, physicians significantly underestimated patient preference for IV MOA (22.07% vs. 42.35%, p < 0.0001) and, to a lesser extent, subcutaneous MOA (48.84% vs. 54.69%, p < 0.0001). Among Crohn's disease (CD) patients (N = 123), CART threshold analysis identified an inpatient visit in the last 6 months, CD diagnosis for more than 3 years, and non-adherence to prior IBD treatment as most positively predictive of having an initial biologics discussion. Physicians appear to underestimate patient preferences in favor of biologics, especially IV formulations. Since it is unclear if physicians were aware of the patients' preferences beforehand, this study supports the need for validated, shared decision-making tools when initiating IBD treatment. Additional studies are necessary to measure physicians' influences on patient preference/treatment-related decisions and the impact on patient outcomes.

关键词： Clostridium difficile   Crohn   Ulcerative colitis  

摘要： Objectives: Clostridium difficile infection (CDI) is a common complication in inflammatory bowel disease (IBD) and has been associated with poor IBD outcome. The aims of our study were to look for predictive factors of CDI in patients hospitalized for IBD flare and to evaluate a rapid testing strategy in this population. Methods: Consecutive patients hospitalized for IBD flare in Saint-Antoine Hospital (Paris, France) were prospectively tested for CDI with a defined strategy involving rapid testing and reference methods. Risk factors for CDI were investigated and performances of diagnostic tests were evaluated. Results: C. difficile testing was performed at admission in 461 hospitalizations for IBD flare. CDI was diagnosed in 35 cases (7.6%) and non-toxigenic C. difficile was identified in 10 cases (2.2%). In multivariate analysis, UC phenotype was associated with CDI (OR 2.2, 95% CI 1.03-4.6, p = 0.047). Glutamate dehydrogenase (GDH) test had a 97.1% sensitivity and a 100% negative predictive value for CDI diagnosis but a positive predictive value of 79.1%. Enzyme immunoassay (EIA)-based toxin detection (C. Diff Quik Chek complete (R), Alere) had a poor sensitivity and diagnosis was rescued by toxin PCR in 100% of cases. Conclusion: CDI is frequent in patients hospitalized for IBD flare. Clinical parameters do not help for the diagnosis and rapid testing should be performed in all patients. Currently, a negative result of an EIA-based toxin search associated with a positive GDH test cannot rule out a CDI and should not delay initiation of specific treatment in case of severe symptoms or high presumption. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

摘要： BACKGROUND/OBJECTIVES: Delayed treatment failure occurs in a significant proportion of inflammatory bowel disease (IBD) patients treated with tumor necrosis factor-alpha (TNF) antagonists. Identification of predictors of loss of response (LOR) may help to optimize therapy. We sought to determine whether body composition parameters at the commencement of anti-TNF therapy were associated with earlier treatment failure. SUBJECTS/METHODS: A retrospective cohort study was performed on 68 patients who had undergone cross-sectional abdominal imaging coincident with the commencement of anti-TNF drugs. Analysis of the images at the third lumbar vertebra was performed using standard techniques to determine cross-sectional areas of skeletal muscle (SM), visceral adipose tissue, subcutaneous adipose tissue and intermuscular adipose tissue. Treatment failure was defined as: post-induction hospital admission or surgery for IBD, escalation of TNF dose or immunosuppressants for clinical LOR, emergence of a new fistula or Crohn's Disease Activity Index (CDAI) > 150. RESULTS: Two-thirds of patients had myopenia. Patients with less than gender-specific median SM area had a median time to failure of 520 (s.d. 135) days compared to 1100 (s.d. 151) days for those with more than median SM area (P = 0.036). No difference was found in disease duration, inflammatory markers or CDAI between quartiles of SM area. No relation between outcomes and measures of adipose tissue, weight or body mass index was observed. CONCLUSIONS: Identifying low muscle mass at anti-TNF induction as a risk factor for treatment failure may contribute to a more tailored approach to IBD therapy.

关键词： Hemoglobin-subunits   IBD   PRDX2  

摘要： Background: Inflammatory bowel diseases (IBD) are chronic multi-factorial inflammatory disorders. Accumulating investigations have provided compelling evidence that describe the interplay of a complex genetic landscape and inappropriate inflammatory response to intestinal microbes in disease etiopathogenesis but still pose challenges in diagnostic practices. Method: In this study, comparative proteomic analysis was conducted to identify disease specific proteins underlying IBD pathogenetic mechanisms. Total blood proteins of the IBD patients and healthy subjects were analyzed with one-dimensional electrophoresis;differentially expressed bands were excised and subjected to matrix-assisted laser desorption ionization-time of flight mass spectrometry along with nanoflow liquid chromatography electrospray ionization-tandem mass spectrometry analysis. Presence of glycosylation, hydroxylation, and phosphorylation post-translational modifications was further investigated by immunoprecipitation. Results: Peroxiredoxin-2 (PRDX2) and hemoglobin-subunits proteins, which are closely involved in the response to oxidative stress, were identified. PRDX2 was selected for further validation using western blot and reverse transcription-polymerase chain reaction. PRDX2 overexpression was restricted to the protein level within the membrane fraction. Immunoprecipitation identified PRDX2 to be post-translationally glycosylated and phosphorylated. Conclusion: Our findings demonstrate the implication of PRDX2 in IBD. Future studies are required to establish its functional role and to determine the clinical utility.

关键词： PDE4   Inflammatory Bowel Disease   apremilast  

摘要： Background. In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. However, in spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies. For these reasons there is an urgent need to look for new pharmacological targets. The novel Phosphodiesterase 4 (PDE4) inhibitors have been recently introduced as new modulators of intracellular signals and gene transcription for the treatment of IBD. Aim. To discuss and describe the state of the art of this new class of compounds in the IBD field, with particular attention to apremilast. Methods. Published articles selected from PubMed were comprehensively reviewed, with key words including apremilast, inflammatory disease, IBD, psoriasis, psoriatic arthritis, pathogenesis, therapies, and treatment. Results. PDE4 inhibitors generate elevated intracellular levels of cyclic Adenosine Monophosphate (cAMP), that consequently down-regulate the release of pro-inflammatory cytokines in the mucosa of IBD patients. The newly developed apremilast is one of these drugs and has already been approved for the treatment of dermatologic/rheumatologic inflammatory conditions;studies in psoriasis and psoriatic arthritis have in fact demonstrated its clinical activity. However, no clinical trials have yet been published on the use of apremilast in IBD. Conclusion. In light of the similarity of pro-inflammatory signaling pathways across the gut, the skin, and joints, apremilast is likely supposed to show its efficacy also in IBD.

关键词： absolute iron deficiency   functional iron deficiency   inflammatory bowel disease   iron-restricted erythropoiesis   red blood cell distribution width   zinc protoporphyrin  

摘要： Objectives: Iron deficiency (ID) in children with inflammatory bowel disease (IBD) is either an absolute (depleted iron stores) or a functional deficiency (caused by chronic inflammation). Differentiating between these 2 types of ID is important because they require a different therapeutic approach. Zinc protoporphyrin (ZPP) and red blood cell distribution width (RDW) are parameters of functional ID. Studies using these parameters to differentiate are nonexistent. We aimed to evaluate the prevalence of and risk factors for absolute and functional ID in paediatric IBD patients while using ZPP and RDW. Methods: We evaluated the iron status and medical charts of 59 paediatric IBD patients in a secondary hospital in the Netherlands. Absolute ID was defined as serum ferritin <15 mu g/L in the absence of infection and/or acute inflammation (C-reactive protein <10 mu g/L). Iron deficiency anaemia (IDA) was defined as absolute ID in combination with anaemia. Functional ID, in patients without absolute ID, was defined as ZPP >70 mu mol/mol haem and/or an RDW >14%. Anaemia of chronic disease (ACD) was defined as functional ID in combination with anaemia. Results: Absolute and functional ID were found in 19/59 (32.2%) and 32/40 (80%) patients, respectively. The prevalence of IDA and ACD was 27.1% (16/59) and 20%(8/40), respectively. Multivariate analyses showed that absolute ID and IDA were both associated with a more recent IBD-diagnosis (both P<0.05). Conclusions: Absolute and functional ID are common in paediatric IBD patients, and this differentiation is important because of therapeutic consequences. Furthermore, absolute ID and IDA are associated with a more recent IBD-diagnosis.

关键词： Health-related quality of life   Psychological adaptation   Inflammatory bowel disease   Chronic disease   Paediatric   Children  

摘要： Little is known about disease-specific health-related quality-of-life (HRQoL) changes over time in paediatric patients with inflammatory bowel disease (IBD), and about their associations with baseline medical characteristics. In this study, 153 paediatric patients with IBD from the multicentre prospective Swiss IBD cohort study were included at baseline. Of these, 90 patients were analysed at a 1-year follow-up. Medical data were extracted from hospital records, while HRQoL data were measured using the standardized, self-report disease-specific IMPACT-III questionnaire. The IBD diagnosis of the included children was made an average of 2.0 years before their baseline assessment. Over the 1-year follow-up period, a significant increase in overall HRQoL and in the HRQoL domain 'physical functioning' was evident. On multivariate analysis, overall HRQoL changes over time were predicted by baseline HRQoL, baseline disease activity, and disease activity changes over time. HRQoL improvements were significantly associated with decreases in physician-assessed disease activity. Children reporting a low baseline HRQoL and children with inactive or mildly-active disease experienced greater improvements. Children with more severe baseline disease activity had the greatest risk for HRQoL deterioration over the 1-year follow-up period. However, among possible factors that might influence HRQoL changes over time, the child's medical characteristics explained only a small proportion of their variability in our sample. We, therefore, recommend that researchers and clinicians focus on factors that are not incorporated within the multidimensional HRQoL concept if they seek to gain better insights into factors that influence HRQoL changes over time in children with IBD.