Search

Background Pouchitis and other inflammatory disorders of the pouch (IDP), such as Crohn′s-like disease of the pouch (CDP), are frequent in patients operated for a previous diagnosis of ulcerative colitis. Many different therapies have been used, but the effectiveness of immunosupresants (IMM) has been poorly explored in this setting. Our aim was to evaluate the use, efficacy and safety of IMM in patients with pouchitis or another IDP. Methods Retrospective and multicentric study of a Spanish cohort of pouch-carrying patients with previous diagnosis of ulcerative colitis, and subsequent diagnosis of IDP, following ECCO diagnostic criteria. Patients who used IMM to treat these conditions were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission, and non-response as no improvement or worsening symptoms. Endoscopic response was evaluated when possible using modified pouchitis disease activity index (PDAI) endoscopic subscore. Adverse events were collected. We used descriptive statistics. Results In the overall cohort of 338 patients with IDP, 93 (27%) were treated with IMM. Of those, 57% males, median age 40 (20-71) ys, and 72% non-smokers. Colectomy was performed at a median age of 31 (18-63) ys and IPD was diagnosed 25 (1-235) months after ileostomy closure. IMM used were thiopurines (n=86), methotrexate (n=4), cyclosporine (n=2) and tacrolimus (n=1). IMM were used as monotherapy in 66 (71%) cases and were indicated as treatment of pouchitis (n=60, 65%), CDP (n=32, 34.4%) and cuffitis (n=1, 1%). Effectiveness was evaluated only for thiopurine monotherapy (n=62). After a median follow-up of 23 (1-234) months, clinical remission was achieved in 31%, clinical response in 31% and non-response in 38% (Figure 1). There were no differences in effectiveness between pouchitis and CDP (63.9% vs 57.7%, p= 0.62). Endoscopic response was evaluated in 19 (30.6%) cases. After a median of 9 months of follow-up median PDAI endoscopic subscore dropped from 3 (range 2-4) to 1 (range 0-3), (Figure 2). Adverse events related with treatment appeared in 28 patients (45%). Thiopurines were discontinued in 39 cases (63%) due to failure (17), toxicity (16) and long remission (6 cases). Conclusion In our cohort, thiopurines were used in 27% of patients with IDP, with long-term benefit (remission or response) in around two-thirds of them. This therapy could be one more option to manage these disorders.

Background Pouchitis and Crohn′s-like disease of the pouch (CDP) can be refractory to conventional therapy. Evidence of biological therapy has been rarely reported in large patient cohorts. We explored the use and effectiveness of these therapies and compared the success of a second biologic after antiTNF failure. Methods This is a retrospective RESERVO study of the Spanish cohort of GETECCU, that included patients operated for ulcerative colitis, with pouch construction, and subsequent diagnosis of pouchitis, CDP or cuffitis second ECCO diagnostic criteria1. Patients treated with antiTNF, Vedolizumab and/or Ustekinumab were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission and non-response as no change or worsening of these symptoms. We also compared the effectiveness of second biologic (antiTNF vs vedolizumab-ustekinumab) after antiTNF failure, using descriptive and comparative statistics. Results The cohort comprised 145 patients. Demographic and clinical characteristics are represented in Table 1. A total of 232 biologic therapies were indicated. Of the total cohort, 60 (41.3%), 21 (14.4%) and 6 (4.1%) used two, three and four lines, respectively. Biologics used were Infliximab (n=95), Adalimumab (n=69), Vedolizumab (n=35), Ustekinumab (n=26) and Golimumab (n=7). Therapy characteristics, clinical effectiveness, need for intensification, discontinuation, and therapy duration for each biological therapy are represented in Table 2. Global rates of clinical remission, response, non-response and loss of response to a first biologic were 21.8%, 27.5%, 21.1% and 29.6%. Female gender was the only factor associated with effectiveness to a first biologic in univariate analysis (OR 2.16, CI 1.08–4.32, p 0.027). There were no significant differences regarding efectiveness between type of pouch disorder (pouchitis vs CDP, 51.6 vs 47.6%, p 0.48) or biologic agents. Thirty-nine patients received a second biologic after prior antiTNF failure (28 a second antiTNF and 11 non-antiTNF: 6 Vedolizumab, 5 Ustekinumab). Basal characteristics in this subgroup showed no significant differences. Clinical response (21.4 vs 63.6%, p 0.02) and discontinuation therapy rates (82.2 vs 54.5 %, p 0.04) after 11 months showed a more favorable profile for non-antiTNF therapy. Conclusion Biologics represent an effective option in the management of pouchitis and Crohn′s like disease of the pouch. Despite our small sample size, non-antiTNF therapy could be the best option after antiTNF failure. 1Fernando Magro. J Crohns Colitis 2017; 11(6): 649–670.

Background Severe haemorrhage is an uncommon but life-threatening complication of ulcerative colitis (UC). Superselective transcatheter embolization has shown to be an effective and safe therapeutic modality in patients with lower gastrointestinal bleeding of various aetiologies; nevertheless, its role in UC-related acute bleeding is unknown. Cases presentation Efficacy and safety of selective transcatheter arterial embolization in three consecutive UC patients diagnosed with massive haemorrhage admitted in a tertiary institution are reported. In all patients computed tomography scan showed active arterial haemorrhage from ascendant or sigmoid colon; subsequent arteriography demonstrated active arterial bleeding from colic branches of the superior or inferior mesenteric arteries, and selective transcatheter embolization was performed with immediate technical success in all three cases. Nevertheless, rebleeding requiring subtotal colectomy occurred between 5 h and 6 days after the procedure. Conclusions Transcatheter arterial embolization is not an effective therapeutic approach in UC patients with severe, acute colonic haemorrhage. Colectomy should not be delayed in this setting.

Purpose: biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naive, IBD patients in the real life clinical practice. Methods: a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naive patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naive patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. Results: two hundred and thirty-nine IBD biologic-naive patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn’s disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. Conclusions: this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.

Background Liver X receptor (LXR) exerts anti-inflammatory effects in macrophages. The aim of this study was to explore the expression and function of LXR in the colonic epithelium under inflammatory conditions. Methods The expression of LXR was explored by Western blot and immunohistochemistry in colonic biopsies from patients diagnosed with inflammatory bowel disease (IBD) and control patients. In addition, LXR and its target gene expression were analyzed in the colon from interleukin (IL)-10-deficient (IL-10-/-) and wild-type mice. Caco-2 cells were pretreated with the synthetic LXR agonist GW3965 and further challenged with IL-1β, the expression of IL-8 and chemokine (C-C motif) ligand (CCL)-28 chemokines, the activation of mitogen-activated protein (MAP) kinases, and the nuclear translocation of the p65 subunit of nuclear factor kappa B was evaluated. Glibenclamide was used as an ABCA1 antagonist. Results We found that LXR expression was downregulated in colonic samples from patients with IBD and IL-10-/- mice. The nuclear positivity of LXR inversely correlated with ulcerative colitis histologic activity. Colonic IL-1β mRNA levels negatively correlated with both LXRα and LXRβ in the colon of IL-10-/- mice, where a decreased mRNA expression of the LXR target genes ABCA1 and FAS was shown. In addition, IL-1β decreased the expression of the LXR target gene ABCA1 in cultured intestinal epithelial cells. The synthetic LXR agonist GW3965 led to a decreased nuclear positivity of the p65 subunit of nuclear factor kappa B, a phosphorylation ratio of the p44-42 MAP kinase, and the expression of CCL-28 and IL-8 in IL-1β-stimulated Caco-2 cells. The pharmacological inhibition of ABCA1 increased the phosphorylation of p44-42 after GW3965 treatment and IL-1β stimulation. Conclusions The LXR-ABCA1 pathway exerts anti-inflammatory effects in intestinal epithelial cells and is impaired in the colonic mucosa of patients with IBD and IL-10-/- mice.

Background Pouchitis and other inflammatory pouch diseases (IPD) are frequent in pouch-carrying patients operated for a previous diagnosis of ulcerative colitis. We evaluated characteristics and differences in therapeutic requirements between pouchitis, Crohn′s-like disease of the pouch (CDP) and cuffitis. Methods This is a retrospective and multicentric Spanish cohort of GETECCU (RESERVO Study), including pouch-carrying patients (operated 1995 to 2016) with previous ulcerative colitis, ileostomy closure and subsequent diagnosis of IPD (pouchitis, CDP or cuffitis), following ECCO diagnostic criteria1. Follow up extended to June 2020. Pouchitis was categorized attending current classifications. Use of medical and surgical therapies was collected and differences between pouchitis and CDP were analyzed using descriptive and comparative statistics. Results A total of 338 patients were included. Demographic and clinical characteristics are presented in Table 1. The most frequent IPD was pouchitis (n=258, 76%), followed by CDP (n=55, 16%) and cuffitis (n=25, 7.4%). Pouchitis was diagnosed at a median time of 27 (range 1–342) months. Prevalence according to pouchitis classification is presented in Figure 1. CDP was diagnosed at a median time of 77 (range 5–324) months, around 75% with a previous pouchitis diagnosis. Location of CDP (not mutually excludent) was pouch CDP (91%), 87% pre-pouch ileitis, and 41% perianal disease. Regarding behavior: 26 (47%) were inflammatory, 12 (22%) stricturing and 17 (31%) penetrating (8 rectovaginal fistulas). Cuffitis was diagnosed at a median time of 18 (range 1–219) months. Medical and surgical therapies used are shown in Figure 2. Immunosuppressants (58.2 vs 22.4%, p 0.001), biologics (74.5 vs 34.8%, p 0.0001), and surgery (41.8 vs 21.3%, p 0.003) were more used in CDP than in pouchitis. Conclusion Pouchitis and CDP are heterogeneous inflammatory pouch complications with a wide and high therapeutic requirement. CDP presents a later diagnosis and has higher therapeutic needs than pouchitis. 1. Fernando Magro, Paolo Gionchetti, Rami Eliakim et al, for the European Crohn’s and Colitis Organisation [ECCO], Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders, J Crohns Colitis 2017; 11(6): 649–670.

Low phospholipid-associated cholelithiasis (LPAC) syndrome is characterized by early intrahepatic and symptomatic gallstones leading to cholangitis, acute pancreatitis and biliary colic. It has been associated with loss of function variants in the ABCB4 gene. ABCB4 encodes for a phospholipid translocator at the canalicular membrane of the hepatocyte, which "flops" phosphatidylcholine into bile. The autosomal recessive form is the most common, although autosomal dominant forms have also been described. We report the first family with autosomal dominant LPAC syndrome due to heterozygosity of the loss of function mutation c.2932T>C in ABCB4, identified by targeted next generation sequencing.

This chapter reviews the basic anatomy and histology of the gastrointestinal (GI) system as well as the main sources of oxidative stress. The GI tract, represents a major interface between the human body and its environment, harbors a large microbial community, and represents the first line of defense against potentially harmful effects of ingested materials. Although it is recognized as a major source of oxidative stress in the human body, the GI tract, and particularly its mucosa is endorsed with effective antioxidant defense systems that prevent injury. Excessive generation of oxidative stress, decrease of antioxidant defense systems, and microbiota dysregulation, however, may play a major role in various GI diseases.

Background and aim: The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but the real contribution of its typing for screening is still uncertain. We aim to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. Methods: Systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease were selected. MEDLINE and EMBASE were searched from 1st January 2004 until 31st December 2013. Two independent researchers carried out selection and classification of studies, data extraction and analysis. Meta-analysis combining sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease were carried out. Results: 6 studies including 1303 individuals were finally evaluated. Pooled sensitivity was 98% (95% confidence interval: 97-99). Overall specificity was 45% (95% confidence interval: 41-48). Regarding specificity, studies were heterogeneous and a subgroup analysis was done according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09). Conclusions: Due to its great sensitivity and low negative likelihood ratio, human leukocyte antigen-DQ2/DQ8 typing would be an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population.

Weber-Christian disease (WCD) is an inflammatory disease whose main histological feature is lobular panniculitis of adipose tissue. The location of panniculitis determines the clinical presentation, being the subcutaneous adipose tissue the most frequent one, followed by liver, spleen, bone marrow and mesenteric adipose tissue. Systemic corticosteroids are first line treatment, but other options should be considered if systemic symptoms are observed or in case of refractory clinical situation. We report herein a case with WCD showing orbital, mesenteric and ileocolonic involvement, which required surgical treatment and also developed postoperative recurrence. Symptoms were resolved by administration of thalidomide and, afterwards, infliximab. To our knowledge, this is the first report of Weber-Christian disease with luminal ileocolonic involvement, treated with infliximab.

Listeria monocytogenes (LM) is a gram-positive intracellular bacillus that in immunodeficient patients, children, geriatric patients, pregnant women, and even in healthy individuals can cause central nervous system infection, bacteremia, and other clinical manifestations, becoming a relevant pathogen.From the Microbiology Service data of 'Gregorio Marañón' Hospital, we selected all positive biological sample cultures for LM from inflammatory bowel disease (IBD) patients, from January 1986 until January 2011. These cases were included in an SPSS database, analyzing several basal clinical characteristics and factors related to the infection.Three patients diagnosed with IBD had positive cultures for LM during this period. All of them were male, and also all of them had a diagnosis of Crohn's disease. Every patient had a corticosteroid cumulated dose of more than 400 mg (equivalency in methylprednisolone doses), adding anti-tumor necrosis factor-α treatment (certolizumab) in one patient. Prior colonoscopy with biopsy was performed in two patients. Clinical presentation of the infection was bacteremia in two patients, accompanied by central nervous system infection in one patient. One patient had isolated meningoencephalitis. Despite correct empiric treatment, one patient died from a cause related to the infection, that is, rombencephalitis. Increased incidence of LM bacteremia was found in IBD patients, compared with the general population (12.2 bacteremias/100 000 IBD patient-years, compared with 1.6 bacteremias/100 000 person-years), with an odds ratio of 7.4.IBD patients may be at risk for more frequent and serious LM infection compared with the general population.

Previous studies analyzing lipid profile in small cohorts of patients with rheumatic and inflammatory bowel diseases (IBD) treated with TNFα blockers showed conflicting results. We aim to evaluate the effect of anti-TNFα monoclonal antibodies, infliximab and adalimumab, on lipid profile in IBD patients followed up to 3 years. Clinical charts of 128 consecutive IBD patients, who received at least three doses of infliximab or two doses of adalimumab, and with a clinical follow-up of at least 1 year, were retrospectively reviewed. Lipid profiles (total, HDL and LDL cholesterol, and triglycerides) before beginning the treatment and after 1 and 3 years of follow-up were collected. Multiple linear regression analysis was performed considering total cholesterol difference at basal time, 1 and 3 years as a dependent variable. There was not a statistically significant difference between pre- and post-treatment lipid profiles. However, the subgroup with normal-range total cholesterol level before anti-TNFα treatment (n = 82) showed a significant increase in total cholesterol after 1 and 3 years, and a significant increase in LDL cholesterol after 3 years. The subgroup with basal normal-range triglycerides showed a significant increase after 1 and 3 years of follow-up. Atherogenic index resulted significantly increased after 3 years of anti-TNFα treatment. Multivariate analysis showed no influence of age, gender, type of IBD, body mass index, or the presence of two or more cardiovascular risk factors. No significant changes in lipid profile of IBD patients on anti-TNFα therapy were observed after 1 and 3 years of treatment.