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Background Adalimumab is used to treat ulcerative colitis, but additional effectiveness and safety data are needed. Patients and methods This retrospective study considered adults with ulcerative colitis treated with adalimumab at 19 hospitals. Clinical data were collected from the start of treatment, after 2, 6 and 12 months, and at the last visit. Outcome measures of effectiveness were treatment duration, reasons for discontinuation and colectomy. Results We studied 381 patients treated with adalimumab for a median of 12.1 months. Disease activity at the start of treatment was moderate to severe in 262 cases (68.8%) and endoscopic activity was moderate to severe in 339 cases (89.0%). At week 8, clinical responses were observed in 177 cases (46.5%) and clinical remission in 136 cases (35.7%). At 12 months, remission was observed in 128 cases (33.6%). Overall, 44 patients required colectomy, and 170 patients (44.6%) were still taking adalimumab when data were collected. Variables associated with adalimumab discontinuation were concomitant steroid treatment, severe clinical-endoscopic activity at baseline, need for adalimumab intensification and drug-related adverse events. Variables associated with colectomy were concomitant steroid treatment and high baseline C-reactive protein. Conclusion Adalimumab is safe and effective for the treatment of ulcerative colitis.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection., Fondazione Cassa di Risparmio in Bologna; Italian Ministry of Education, University and Research; Fondazione del Monte di Bologna e Ravenna [SC1-BHC-01-2019]; European Grant H2020, DISCOvERIE [SC1-BHC-01-2019]; Italian Ministry of Health [Ricerca Finalizzata GR-2018-12367062], G.B. contribution to this research was permitted in part by funding from Fondazione Cassa di Risparmio in Bologna; the ItalianMinistry of Education, University and Research; and Fondazione del Monte di Bologna e Ravenna and European Grant H2020, DISCOvERIE, SC1-BHC-01-2019. M.R.B. is a recipient of a grant from the Italian Ministry of Health (Ricerca Finalizzata GR-2018-12367062). None of the funding organizations have had any role in the design and conduct of the study; in the collection, management, and analysis of the data; or in the preparation, review, and approval of the article.

Summary Collaboration between gastroenterologists and rheumatologists is recommended for the correct management of patients with associated spondyloarthritis (SpA) and inflammatory bowel disease (IBD). We aimed to establish the appropriateness of several red flags for a prompt specialist referral. A systematic review of the literature was performed using the GRADE method to describe the prevalence of co-existing IBD-SpA and the diagnostic accuracy of red flags proposed by a steering committee. Then, a consensus among expert gastroenterologists and rheumatologists (10 in the steering committee and 13 in the expert panel) was obtained using the RAND method to confirm the appropriateness of each red flag as ‘major’ (one sufficient for patient referral) or ‘minor’ (at least three needed for patient referral) criteria for specialist referral. The review of the literature confirmed the high prevalence of co-existing IBD-SpA. Positive and negative predictive values of red flags were not calculated, given the lack of available data. A consensus among gastroenterology and rheumatology specialists was used to confirm the appropriateness of each red flag. Major criteria to refer patients with SpA to the gastroenterologist included: rectal bleeding, chronic abdominal pain, perianal fistula or abscess, chronic diarrhoea and nocturnal symptoms. Major criteria to refer patients with IBD to the rheumatologist included: chronic low back pain, dactylitis, enthesitis and pain/swelling of peripheral joints. Several major and minor red flags have been identified for the diagnosis of co-existing IBD-SpA. The use of red flags in routine clinical practice may avoid diagnostic delay and reduce clinic overload.

Background and aims The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres. Methods All patients with active disease treated with adalimumab were retrospectively reviewed. Co-primary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy. Results Eighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twenty-two patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36–19.44; OR 2.63, 95% CI 2.32–14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, 95% CI 0.08–0.66) and with a higher rate of colectomy (HR 9.7, 95% CI 1.46–9.07). Conclusion In this large “real-life” experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.

Objective: Folate has heterogeneous functions and is involved in several activities in both animal and human body. It is an important constituent of our organism, and its bioavailability is mainly dependent from the correct function of our gastrointestinal tract. Our aim is to describe what happens to folate homeostasis in gastrointestinal health and disease, analyzing the alterations of folate metabolism in some specific conditions of intestinal and liver impairment. Discussion: Folate absorption and metabolization involve the small intestine and the liver; in conditions of gastrointestinal tract disease (i.e. celiac disease, liver disease) folate function may be compromised with important consequences on the whole organism. Moreover, folate deficiency may produce gastrointestinal alterations too. For this reason, the gastrointestinal tract could be the responsible but also the victim of folate deficiency. Conclusions: The presence of folate deficiency should always be assessed in patients with a gastrointestinal disease. Further studies are needed to assess the role of folates in gastrointestinal tract diseases and in other gynecologic, neurologic, psychiatric, cardiovascular, ophthalmic and neoplastic diseases. Folates supplementation could be considered, in the future, as an effective complimentary therapy in several pathologic conditions.

BACKGROUND: Inflammatory bowel disease (IBD) frequently affects women during their reproductive years. Pregnancy outcome in women with IBD is well described, particularly in retrospective studies. AIM: To evaluate the pregnancy outcome in patients with IBD in a prospective European multicentre case-control study. METHODS: Inflammatory bowel disease pregnant women from 12 European countries were enrolled between January 2003 and December 2006 and matched (1:1) to non-IBD pregnant controls by age at conception and number of previous pregnancies. Data on pregnancy and newborn outcome, disease activity and therapy were prospectively collected every third month using a standard questionnaire. Logistic regression analysis with odds ratio was used for statistical analyses. P value

The introduction of biological therapies, particularly anti-TNFα agents, has revolutionized the management of inflammatory bowel disease in those cases which are refractory to conventional treatment; however these drugs are not risk-free and their use has substantially increased the cost of treatment. As marketing protection expires for original, first-generation biopharmaceuticals, lower-cost “copies” of these drugs produced by competitor companies—referred to as biosimilars—are already entering the market. In September 2013, the European Medicines Agency approved two infliximab biosimilars for treatment of adult and paediatric inflammatory bowel disease patients, a decision based largely on efficacy and safety data generated in studies of patients with ankylosing spondylitis and rheumatoid arthritis. For many clinicians, extrapolation practices and the general question of interchangeability between biosimilars and reference biologics are cause for concern. In the present paper, the Italian Group for inflammatory bowel disease presents its statements on these issues, with emphasis on the peculiar clinical characteristics of inflammatory bowel disease and the importance of providing physicians and patients with adequate information and guarantees on the safety and efficacy of these new drugs in the specific setting of inflammatory bowel disease.

Summary Background The impact of pregnancy on the course of IBD is still controversial. Aim To investigate the impact of pregnancy on IBD and to search for factors with potential impact on remission. Methods Pregnant IBD women from 12 European countries were enrolled between January 2003 and December 2006 and compared at conception (1:1) with nonpregnant IBD women. Data on disease course were prospectively collected at each trimester during pregnancy and in the postpartum (6 months) using a standardised questionnaire. Results A total of 209 pregnant IBD women were included: 92 with Crohn's disease (CD; median age 31 years, range 17–40) and 117 with ulcerative colitis (UC; median age 32 years, range 19–42). No statistically significant difference in disease course during pregnancy and postpartum was observed between pregnant and nonpregnant CD women. Longer disease duration in CD and immunosuppressive therapy were found to be risk factors for activity during pregnancy. Pregnant UC women were more likely than nonpregnant UC women to relapse both during pregnancy (RR 2.19; 95% CI: 1.25–3.97, 0.004) and postpartum (RR 6.22; 95% CI: 2.05–79.3, P = 0.0004). During pregnancy, relapse was mainly observed in the first (RR 8.80; 95% CI 2.05–79.3, P

Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects.To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC.Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters.A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group.BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

BACKGROUND & AIMS: Bacteria might be involved in the development and persistence of inflammation in patients with Crohn's disease (CD), and antibiotics could be used in therapy. We performed a clinical phase 2 trial to determine whether a gastroresistant formulation of rifaximin (extended intestinal release [EIR]) induced remission in patients with moderately active CD. METHODS: We performed a multicenter, randomized, double-blind trial of the efficacy and safety of 400, 800, and 1200 mg rifaximin-EIR, given twice daily to 402 patients with moderately active CD for 12 weeks. Data from patients given rifaximin-EIR were compared with those from individuals given placebo, and collected during a 12-week follow-up period. The primary end point was remission (Crohn's Disease Activity Index < 150) at the end of the treatment period. RESULTS: At the end of the 12-week treatment period, 62% of patients who received the 800-mg dosage of rifaximin-EIR (61 of 98) were in remission, compared with 43% of patients who received placebo (43 of 101) (P = .005). A difference was maintained throughout the 12-week follow-up period (45% [40 of 89] vs 29% [28 of 98]; P = .02). Remission was achieved by 54% (56 of 104) and 47% (47 of 99) of the patients given the 400-mg and 1200-mg dosages of rifaximin-EIR, respectively; these rates did not differ from those of placebo. Patients given the 400-mg and 800-mg dosages of rifaximin-EIR had low rates of withdrawal from the study because of adverse events; rates were significantly higher among patients given the 1200-mg dosage (16% [16 of 99]). CONCLUSIONS: Administration of 800 mg rifaximin-EIR twice daily for 12 weeks induced remission with few adverse events in patients with moderately active CD.

To compare beclomethasone dipropionate 3 mg/60 mL enema (BDP) and prednisolone sodium phosphate 30 mg/60 mL enema (PP) once daily in patients with active distal ulcerative colitis.One hundred and fifty-seven patients were enrolled in a multicentre, 4-week, randomized, double-blind trial. Patients were assessed at baseline, 2 and 4 weeks.Both treatment groups showed statistically significant improvement of clinical activity after 2 and 4 weeks. Endoscopy and biopsy showed a reduction in the activity score at the end of the treatment period in both groups. No statistically significant difference was observed between the two treatment groups. After 4 weeks, 29% of patients in the BDP group and 25% in the PP group were considered to be in clinical remission; an improvement was observed in 40% of patients on BDP and in 47% on PP. Mean morning plasma cortisol levels showed a slight but significant reduction in the PP group, while the ACTH test showed that neither drug interfered with the hypothalamic-pituitary-adrenal (HPA) axis function. No significant changes were observed in the laboratory tests. Finally, there was a low incidence of adverse events in both groups.It is concluded that, in the topical treatment of active distal ulcerative colitis, BDP 3 mg enemas are as efficacious as PP 30 mg enemas, without interference with the HPA axis.

Interleukin-1, a cytokine produced by macrophages and other tissue cells, has a major role in inflammatory and immunological responses. Increased levels of IL-1 activity have been reported in experimental colitis and in patients with active Crohn's disease (CD) and ulcerative colitis (UC). IL-1 beta release from fresh and cultured colonic biopsies and IL-1 beta plasma concentrations was determined in 15 patients with active UC, 16 with UC in remission and 10 normal control subjects. Biopsies, taken at colonoscopy were weighed, washed in 1 ml of 0.9% sodium chloride solution and then cultured for 24 h in 10% fetal calf serum/RPMI. IL-1 beta activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1 beta were detected only in 3 plasma samples, all from active patients. Significantly more IL-1 beta was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p less than 0.01). Furthermore, specimens from active UC released significantly more IL-1 beta than those from patients in remission (p less than 0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC.

The course of Crohn's disease is characterised by the occurrence of intestinal complications such as strictures, intra-abdominal fistulas, or abscesses. Standard diagnostic procedures may fail to show these complications, in particular fistulas.To test the value of transabdominal bowel sonography (T) for the detection of intestinal complications in Crohn's disease.T was prospectively performed in 213 patients with Crohn's disease in a university based inflammatory bowel disease referral centre. Thirty three underwent resective bowel surgery and were included in this study. The accuracy of T to detect strictures, intra-abdominal fistulas, or abscesses was compared with surgical and pathological findings.T was able to identify strictures in 22/22 patients and to exclude it in 10/11 patients (100% sensitivity, 91% specificity). Fistulas were correctly identified in 20/23 patients and excluded in 9/10 patients (87% sensitivity, 90% specificity). Intra-abdominal abscesses were correctly detected in 9/9 patients and excluded in 22/24 patients (100% sensitivity, 92% specificity).In experienced hands T is an accurate method for the detection of intestinal complications in Crohn's disease. T is thus recommended as a primary investigative method for evaluation of severe Crohn's disease.

Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment-resistant disease.To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis.Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture.Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9-17) and 4 (range 0-16), respectively (P0.002). No side-effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance.A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment-resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.

Plasma levels of total 5-aminosalicylic acid (5-ASA) were determined after a single administration of 2 g and 4 g 5-ASA enemas to 6 patients with ulcerative colitis. The mean plasma levels and AUC values confirmed that the active substance is poorly absorbed by rectal route.

The exact role of 111In leukocyte scanning in the assessment of clinical activity of Crohn's disease (CD) is still a matter of controversy. In our center we studied 22 patients with CD (8 with active disease) with standard 111In labelled mixed leukocyte scans. We determined the extent of the lesion measured as lesion-occupied cells on scanned area and the degree of inflammatory activity assessed as count ratio between the involved region and the iliac crest. Particularly in delayed scans, these scintigraphic parameters showed good correlation with clinical and laboratory indices of disease activity. In our series, only 6 patients had completely negative scans. They were in clinical and laboratory remission, and 5 of them had undergone surgery for CD during the previous year, with no radiological and/or endoscopic findings of recurrence. Among the other 8 patients in clinical remission, 5 had positive early scans, while the rest showed persistent delayed images. Moreover both early and delayed leukocyte scans were positive in 8 cases in which disease was undoubtedly active. A 1-year follow-up was available for 14 patients in clinical remission when 111In-scan was performed. During this period, 3 patients, all of whom had had early and delayed positive 111In-scan, suffered from clinical relapse; no clinical relapses were documented in patients with only 4th hour positive scans. In conclusion, in our series, 111In-scan was also frequently positive in patients in clinical remission; in this patient subset persistent images on delayed scans might suggest the risk of clinical relapse.

Objectives: The prognosis of attacks of ulcerative colitis is clearly linked to the extent and activity of the disease. The aim of this study was to investigate the value of high resolution ultrasonography in assessing both the extent and activity of severe ulcerative colitis and its response to medical treatment. Methods: Fifty-seven consecutive patients affected by a severe (32 patients) or moderately severe (25 patients) attack of ulcerative colitis underwent ultrasonographic examination. The ultrasonographic extent of the disease was evaluated in 32 patients by comparing ultrasonography and scintigraphy. Results: Compared with scintigraphy, sensitivity, specificity, and overall accuracy of ultrasonographic extent were 89%, 100%, and 91%, respectively. These results were also confirmed in a subgroup of patients submitted to surgery, comparing ultrasonographic and scintigraphic data versus specimens. Using the ultrasonographic score of activity, it was possible to discriminate severe and moderately severe attacks with a specificity, sensitivity, and diagnostic accuracy of 96%, 90.3%, and 92.9% respectively. A close correlation was also found between ultrasonographic and scintigraphic activity (r = 0.78; p < 0.001). After 10 days of intensive treatment, the ultrasonographic activity significantly decreased in severe and moderate groups (p < 0.001) and in both subgroups of nonoperated patients (p < 0.001) but not in operated patients (p = NS). Conclusions: High resolution ultrasonography can be useful in assessing both extent and activity of severe ulcerative colitis, in monitoring the patient's condition, and in objectively evaluating the response to medical therapy.

It has been suggested that colon cancer risk in ulcerative colitis (UC) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proliferation in patients affected by long-standing UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reduction of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P0.01). On the contrary, no significant proliferative changes were observed in the placebo group. These results suggest that folate supplementation contributes to regulating rectal cell proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in these patients.

Perianal fistulizing Crohn's disease (PFCD) is a common, disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Its successful treatment is still a struggle for both physicians and patients. Significant advances in the management of this condition have occurred in the last two decades holding promise for a better future. This culminated into the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical and endoscopic techniques. Despite this, PFCD management and treatment have not been standardized yet. Thus the gastroenterologist and surgeon have to be familiar with several approaches and/or techniques. The positioning of each therapeutic option will certainly evolve with new data, but for the time being it should be driven by patient's characteristics, physician's preference and/or experience, costs and availability in local practice. Additionally, patient's perception of benefits and risks of treatment may differ from those of physicians and recognition of this difference is a starting point for difficult clinical decision-making. In this paper, a multidisciplinary group of Italian IBD experts explore and discuss current medical and surgical therapeutic options, highlighting areas of unmet needs in PFCD, with particular focus on the optimal patient flow within the Italian clinical reality.

hese recommendations summarise the current evidence on the medical management of adult patients with UC. Gaps were iden-tified during the analysis of the data, which should be addressed by further research. Where evidence is lacking or is very weak and evidence-based recommendations cannot be given, ECCO provides alternative tools, such as Topical Reviews28,95,153–158 or Position Papers.159–161 It is important that clinicians use these guidelines within the framework of local regulations, and seek to understand and address the individual needs and expectations of every patient. We recognise that constraints on health care resources are an im-portant factor in determining whether recommendations can be implemented for patients in many countries. The recommendations outlined here should be used to inform treatment decisions and form part of an overall multidisciplinary treatment plan for patients with UC, which may also encompass psychological, nutritional, and other non-pharmacological interventions.

Background & Aims Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. Methods We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012. All study patients had undergone ileocolonic resection within 45 days before randomization. Patients were randomly assigned (1:1) to groups given infliximab (5 mg/kg) or placebo every 8 weeks for 200 weeks. The primary end point was clinical recurrence, defined as a composite outcome consisting of a CD Activity Index score >200 and a ≥70-point increase from baseline, and endoscopic recurrence (Rutgeerts score ≥i2, determined by a central reader) or development of a new or re-draining fistula or abscess, before or at week 76. Endoscopic recurrence was a major secondary end point. Results A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group, but this difference was not statistically significant (12.9% vs 20.0%; absolute risk reduction [ARR] with infliximab, 7.1%; 95% confidence interval: -1.3% to 15.5%; P =.097). A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group (30.6% vs 60.0%; ARR with infliximab, 29.4%; 95% confidence interval: 18.6% to 40.2%; P

Introduction : The incidence of endoscopic recurrence (ER) in Crohn's disease following curative resection is up to 75% at 1 year. Endoscopy is the most sensitive method to detect the earliest mucosal changes and the severe ER at 1 year seems to predict a clinical relapse. Methods : The aim of this prospective study was to evaluate the incidence of early ER 6 months after curative resection. Secondary outcome was to evaluate the role of 5-aminosalicylic acid (5-ASA) in the prevention of ER at 6 months. A total of 170 patients were included in the study. They were carried-out from the evaluation of the appearance of ER during a trial performed to assess the role of azathioprine vs. 5-ASA as early treatment of severe ER. All the patients started 5-ASA treatment 2 weeks after surgery. Results : Six months after surgery ER was observed in 105 patients (62%). The endoscopic score was reported as severe in 78.1% of them (82 out of 105). At univariable analysis only ileo-colonic disease influenced the final outcome associating to a lower risk of severe ER (p = 0.04; OR 0.52, 95% CI 0.277–0.974). Conclusion: In this prospective Italian multicenter IG-IBD study a great proportion of ER occur within 6 months from ileo-colonic resection, with a significant rate of severe ER. Furthermore this study confirms the marginal role of 5-ASA in the prevention of ER. This suggests that post-surgical endoscopic evaluation should be performed at 6 months instead of 1 year to allow an adequate early treatment.

See related article, Oostlander AE et al, on page 116 in Gastroenterology. BACKGROUND & AIMS: Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with tumor necrosis factor (TNF) inhibitors in these patients. METHODS: We collected data from patients with IBD treated with infliximab (n 2475) and adalimumab (n 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohn’s disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 years old or younger who were treated with both biologics and 190 patients older than 65 years who were treated with other drugs. The primary end points were severe infection, cancer, or death. RESULTS: Among patients more than 65 years old who received infliximab and adalimumab, 11% developed severe infections, 3% developed neoplasms, and 10% died. No variable was associated with severe infection or death. Among control patients more than 65 years old, 0.5% developed severe infections, 2% developed cancer, and 2% died. Among control patients less than 65 years old, 2.6% developed severe infections, none developed tumors, and 1% died. CONCLUSIONS: Patients older than 65 years treated with TNF inhibitors for IBD have a high rate of severe infections and mortality compared with younger patients or patients of the same age that did not receive these therapeutics. The effects of anti-TNF agents in older patients with IBD should be more thoroughly investigated, because these patients have higher mortality related to hospitalization than younger patients.

Background: Crohn's disease represents a heterogeneous entity, but its location tends to be relatively stable overtime. For extensive refractory Crohn's colitis, ileorectal anastomosis after colectomy is an engaging option, since the necessity of a permanent ileostomy is avoided. Aims: In our study, the long-term outcome of two groups of patients with Crohn's colitis who underwent colectomy and ileorectal anastomosis was compared. The first group had isolated colonic Crohn's disease without rectal involvement and perianal disease, while the second group included patients who had rectal and/or ileal involvement, with or without perianal disease. Methods: Between 1996 and 2016, in a single IBD tertiary center, 80 patients with a history of colectomy and ileorectal anastomosis for refractory Crohn's colitis were retrospectively identified. Results: Recurrence of disease was diagnosed in 57/64 of patients with Crohn's colitis with rectal and/or ileal and/or perianal involvement compared with 1/16 of patients with isolated Crohn's colitis without rectal and perianal disease in a median time of recurrence of 2 years (IQR 1–6 years, minimum to maximum, 1–18 years, p < 0.001). Only 6 patients (7,5%) underwent definitive end ileostomy without proctectomy (1 in the noIRP group and 5 in the IRP group). Conclusion: Our data suggest that colectomy with ileorectal anastomosis may represent a curative option in patients with refractory isolated colitis without rectal and perianal involvement.

Background: Inflammatory bowel disease (IBD) is an epithelial barrier disease that is thought to result from a dysregulated interaction with bacteria in the intestine of genetically predisposed individuals. The cystic fibrosis transmembrane conductance regulator (CFTR), which is mutated in the autosomal recessive disease cystic fibrosis, modulates gut permeability, mucus production, and epithelial interactions with bacteria. The cystic fibrosis ΔF508 mutation is commonly found in the general population and has been shown to result in a reduced number of CFTR molecules at the surface of epithelial cells. Given the important biological functions of CFTR in the intestine, we tested whether this mutation is of relevance to IBD. Methods: Using DNA heteroduplex analysis, we investigated the distribution of ΔF508 heterozygosity in 2568 subjects from three independent cohorts of Italian, Swedish, and Scottish IBD patients and controls. Results: In all three cohorts an association between ΔF508 and Crohn's disease (CD) was observed. Specifically, ΔF508 heterozygosity was markedly underrepresented in CD patients from Italy and Sweden (P = 0.021 and 0.027 versus controls, respectively), while stratification for disease location revealed an absence of ΔF508 carriers among Scottish CD patients with right-sided colitis (P = 0.023 versus all other locations). Conclusions: ΔF508 heterozygosity might exert a protective effect in CD. (Inflamm Bowel Dis 2007)

Background - Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. Aims - To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. Patients - Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. Methods - A positive ANCA serology was determined with a standard indirect immunofluroescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-. generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. Results - There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-6. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). Conclusions - p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.

Three major variants of the CARD15 gene confer susceptibility to Crohn's disease (CD). Whether or not these variants correlate with specific clinical features of the disease is under evaluation.We investigated the possible association of CARD15 variants with specific clinical characteristics, including the occurrence of anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA), in a large cohort of inflammatory bowel disease (IBD) patients and their unaffected relatives.Three hundred and sixteen CD patients (156 with positive family history), 408 ulcerative colitis (UC) patients (206 with positive family history), 588 unaffected relatives, and 205 unrelated healthy controls (HC) were studied. Single nucleotide polymorphisms (SNPs) R702W, G908R, and L1007finsC of the CARD15 gene were investigated and correlated to age at diagnosis, gender, family history, localization, extraintestinal manifestations, previous resective surgery, stenosing/fistulizing pattern, ANCA, and ASCA.Compared to HC, the frequencies of all three variants in CD were significantly increased: 8.7% versus 4.1% for R702W (p0.006), 7.3% versus 2.7% for G908R (p0.002), 9.3% versus 0.7% for L1007finsC (p0.00001). At least one risk allele was found in 38.2% (p0.0001, compared to HC), 13.7% (NS), and 15.1% of CD, UC, and HC, respectively. The L1007finsC risk allele was also significantly increased in unaffected relatives of familial (9.5%; p0.00001), and sporadic CD (9%; p0.00001), compared to HC (0.7%). Sixteen healthy relatives, carriers of two risk alleles, were asymptomatic after 5-8 yr of follow-up. CD carriers of at least one variant were younger (p= 0.03), more likely to have ileal localization (p= 0.0001), stenosing pattern (p= 0.01), previous resective surgery (p= 0.0001), and presence of ASCA (p= 0.0001). No difference in SNPs frequency between familial and sporadic cases of CD was found.In our population, both familial and sporadic CD patients carrying at least one major variant of CARD15 had an aggressive clinical course.

Background. Three variants of the NOD 2 /CARD 15 gene are strongly associated with susceptibility to Crohn’s disease; however, striking racial and geographic differences of their frequency have been described. Aims. We have compared the allele frequencies of familial cases of Crohn’s disease recruited in a multicentre study across Italy, in order to disclose possible geographic heterogeneity. Moreover, we also compared the allele frequencies in sporadic cases of Crohn’s disease and healthy controls from Southern Italy with those reported in other two populations from Central and Northern Italy. Subjects and Methods. A total of 731 subjects were genotyped for the polymorphism of three main variants (R702W, G908R and 1007 fs): 152 patients were familial cases of Crohn’s disease, 183 were healthy first-degree relatives, 180 were sporadic cases of Crohn’s disease, and 216 were unrelated healthy subjects. Results. The frequency of the frameshift mutation (1007 fs) was significantly higher in both familial and sporadic cases of Crohn’s disease ( P =0.000001), and healthy first-degree relatives ( P =0.0001) compared to controls. At least one risk allele was found in 44% of familial Crohn’s disease patients, compared to 7% of healthy controls (OR=4; CI=2–6.5). Two risk alleles were found in 14% of familial Crohn’s disease, compared to less than 1% of controls (OR=26: CI=4–129). Conclusions. Our data confirm the strong correlation between the 1007 fs variant and Crohn’s disease, in both familial and sporadic cases. Moreover, no significant difference of allele frequencies was detected in familial cases, sporadic cases and healthy controls among different geographic areas of Italy.

Background: The number of indications for strictureplasty for Crohn’s disease has been greatly reduced since the widespread use of biologics, although the risk of intestinal failure remains. The aim of the study was to analyze the outcomes of strictureplasty and to identify risk factors for site-specific recurrence in the era of biologics. Methods: Consecutive patients treated with strictureplasty for Crohn’s disease between 2002 and 2018 were retrospectively included. Univariate analysis was carried out. Risk factors for recurrence were identified through a multilevel logistic regression analysis. Results: Two hundred sixty-six patients were included in the study (171 males, median age 39.5years, range 18–76years). The majority of the 718 strictures requiring surgery in these patients were located in the ileum (61%), treated with conventional strictureplasty (89.6%) and required an additional resection (73.7%). Median follow-up time and time to recurrence were 96months and 62.5months respectively. The site-specific recurrence rate was 12.2% at 5years and 25.7% at 10years. Smoking was associated with a higher risk of recurrence in patients with milder disease. The 10-year recurrence rate was significantly higher for strictureplasties performed in the terminal ileum (30.9%, p = 0.0019) as compared to the ileum (21.8%) and the jejunum (8.4%). Multilevel logistic regression analysis showed that postoperative exposure to biologics (OR 4.74, p 0.001), nonconventional strictureplasty (OR 3.57, p 0.008) and a strictureplasty performed on a previous anastomosis (OR 13.58, p 0.002) were associated with site-specific recurrence. Conclusions: Strictureplasty is associated with optimal long-term outcomes in the biologic era and should be performed when feasible, to reduce the risk of intestinal failure in Crohn’s disease patients.

The management of moderate to severe ulcerative colitis has undergone significant changes over the past 15 years due to the regulatory approval of several new drugs. In particular, following the approval of the first biological, i.e. infliximab, a number of further biological drugs, such as adalimumab, golimumab, vedolizumab and ustekinumab, and small molecules, such as tofacitinib, have been approved, thus enriching the therapeutic armamentarium for ulcerative colitis. Choice of therapy must take into consideration not only the need to induce and maintain disease remission according to the patient's profile, but also age, co-morbidities, and prior treatments. To guide these decisions, the Italian Group for the Study of Inflammatory Bowel Disease has developed clinical guidelines that supersede its earlier document from 2011. These new guidelines were developed following the GRADE methodology for rating the quality of the evidence and for determining the strength of the recommendations. This article presents the methodology and results, in the form of 20 statements with commentary on the use of the five biologics and tofacitinib for managing the intestinal manifestations of active ulcerative colitis and for maintaining remission. A separate technical review reports the analyses of the evidence upon which the present recommendations are based.

This is the second of a series of two articles reporting the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management, and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimisation, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC.

This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines. ispartof: JOURNAL OF CROHNS & COLITIS vol:14 issue:2 pages:155-168 ispartof: location:England status: published

Introduction: Ulcerative colitis is an idiopathic, chronic inflammatory disease of the colonic mucosa. Its clinical course is unpredictable, marked by alternating periods of exacerbation and remission. Traditional oral corticosteroids are still the mainstay treatment for the induction of ulcerative colitis remission in patients failing or intolerant to aminosalicylates, but the risk of side effects and complications limits their usefulness. Based on these considerations, new steroids with low systemic bioavailability, such as Beclomethasone dipropionate and Budesonide, have been developed. Areas covered: We reviewed the current literature about the efficacy, safety and the role of budesonide MMX in the treatment of ulcerative colitis. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. Expert opinion: Budesonide MMX is a novel formulation that uses a Multi‐Matrix System (MMX) technology to facilitat e the release of high concentrations of active drug into the colon. Budesonide MMX at the dose of 9 mg/day for 8 weeks is effective and safe in inducing clinical and endoscopic remission in patients with mild to moderate UC, who had an inadequate response or were intolerant to either first line conventional therapy with topical and oral 5-aminosalicylic acid.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory condition that causes continuous mucosal inflammation of the colon. New biological drugs have been developed in order to avoid colectomy, but corticosteroids still play a crucial role in management of active UC. Areas covered: We reviewed the current literature about the importance of corticosteroid use in the treatment of ulcerative colitis. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Expert opinion: Corticosteroids represent the mainstay of treatment in patients with severe UC and are very effective in inducing remission in mild to moderate flares not responding to combined oral and topical mesalazine. A valid alternative to systemic corticosteroids is represented by poorly absorbed steroids, such as Beclomethasone dipropionate and Budesonide MMX. In mild-moderate distal disease topical administration of corticosteroids (both systemic and BDP) is an effective alternative to topical mesalazine. However, corticosteroids do not represent a therapeutic option as a maintenance treatment since they are associated with multiple adverse effects.

The study exploited autologous microfragmented fat to treat refractory complex Crohn’s perianal fistula, obtaining 66.7% of combined remission at 6 months in patients already treated without success using combined biosurgical approaches and multiple repair surgeries following the failure of biological therapy., Background Complex perianal fistulas represent one of the most challenging manifestations of Crohn’s disease. Combined surgical and medical therapy with biologic drugs today represent the first-line treatment option, but its efficacy does not exceed 60%. Recently, new therapeutic approaches, such as the use of mesenchymal stromal cells, have shown promising results. The adipose tissue is an abundant and easy to access source. The effectiveness, safety, and feasibility of local injections of microfragmented adipose tissue in patients with refractory complex fistulizing perianal Crohn’s disease (PCD) were evaluated. Methods Fifteen patients with persistent complex fistulizing PCD after biosurgical approach and subsequent surgical “rescue” repair were treated in S. Orsola-Malpighi Hospital with a single-local administration of microfragmented adipose tissue prepared using a minimal manipulation technique (Lipogems) in a closed system. Clinical outcomes were determined at 24-week follow-ups assessing success rate, defined as combined clinical and radiological remission. Results Upon clinical examination at 24 weeks, 10 patients had combined remission (clinical and radiographic), 4 patients showed improvements, and 1 patient failed. The results were confirmed in all patients by pelvic MRI. No relevant postoperative complications nor adverse events were reported. Conclusion These results suggest that the local injection of autologous microfragmented adipose tissue is a safe and promising “rescue therapy” for patients with multiresistant complex fistulizing PCD. This approach might be proposed as routine because it is affordable, is minimally invasive, has no risk of sphincteric damage, and can be carried out in a day-surgery setting.

Background: Among patients with limited ulcerative colitis (UC), 30% ultimately extend to pancolitis and are at increased risk of adverse clinical outcomes. Risk of endoscopic extension has been found to correlate with clinical features such as early age of onset. Aims: We sought to determine whether histologic features correlate with disease extension. Methods: The study population consisted of 40 patients with UC from two large academic centers diagnosed between 2006 and 2017. Eligible cases had a diagnosis of endoscopically limited UC (Montreal E1 or E2) at baseline and ≥ 2 subsequent endoscopic examinations with biopsies. Severity of inflammation was scored using both the Mount Sinai Activity Index and Nancy Histological Index. Results: Patients were divided into two cohorts: those who progressed to pancolitis (Montreal E3) were defined as “Extenders” (n = 21), whereas “Non-extenders” (n = 19) were cases without progression in the follow-up period. The median follow-up time was 58.4months. The histologic scores in the endoscopically involved mucosa of the index biopsies were not associated with subsequent extension of disease, overall. However, among extender cohort, the index histology scores correlated with biopsy scores at extension (r = 0.455, P = 0.044) and index severity was associated with a shorter time to extension (r = − 0.611, P = 0.003). Furthermore, female patients had a shorter time to extension (P = 0.013). Conclusions: Histological severity of limited UC is not an independent predictor of extension in UC. However, among patients who subsequently extend, severe inflammation at baseline correlates with shorter progression time and severe inflammation when extension occurs. Patients with limited UC but severe histologic inflammation may warrant more frequent endoscopic surveillance.

Background: Pouchitis is a condition with large unmet medical needs and no approved therapies. Lack of validated instruments to measure disease activity and treatment response is a major barrier to drug development. Aim: To conduct a modified RAND/University of California Los Angeles appropriateness process to produce a standardised assessment of pouchitis disease activity in clinical trials. Methods: A list of 164 items generated upon a systematic review and expert opinion were rated based on a 9-point scale (appropriate, uncertain and inappropriate), by a panel including 16 gastroenterologists, surgeons and histopathologists. Results: Items rated as appropriate to evaluate in pouchitis clinical trials were: (a) clinical: stool frequency and faecal urgency; (b) endoscopic: primary assessment in the pouch body according to the percentage of affected area (75%), evaluation of the presence of ulcers/erosions according to size (erosions 2cm) and ulcerated area (30%); (c) histologic: two biopsies from each segment, from the ulcer's edge when present, or endoscopically normal areas, assessment of lamina propria chronic inflammation, epithelial and lamina propria neutrophils, epithelial damage, erosions and ulcers; and (d) clinical trial inclusion/outcome criteria: minimum histologic disease activity for inclusion, a primary endpoint based on stool frequency and assessment of clinical, endoscopic and histologic response and remission. The overall majority of items surveyed (100/164) were rated ‘uncertain’. Conclusion: We conducted a RAND/UCLA appropriateness process to help inform measurement of pouchitis disease activity within clinical trials and foster the development of novel therapies.

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.

Current guidelines state that systemic inflammation, together with endothelial dysfunction, calcification, and hypercoagulability, predispose to premature atherosclerosis in patients with inflammatory bowel disease (IBD). We assessed whether IBD can affect aortic stiffness, a well-recognized vascular biomarker and an independent risk factor for cardiovascular (CV) disease (CVD) in several populations. Recent studies reported that aortic stiffness is increased in adults with IBD compared with matched controls. This association is dependent on inflammatory burden and disease duration, and is reduced by antitumor necrosis factor therapy. Considered together, current findings suggest that increased aortic stiffness is an extraintestinal manifestation of IBD. This is clinically relevant since measuring aortic stiffness in patients with IBD could improve risk assessment, especially in those without established CVD. Moreover, effective control of inflammation could lower CV risk in patients with IBD by reducing aortic stiffness. Further longitudinal studies are needed to better clarify (i) the relationship between disease duration and irreversible changes of the arterial wall, (ii) the clinical characteristics of patients with IBD that have an increased arterial stiffness at least in part reversible, and (iii) whether arterial stiffness is useful to evaluate the efficacy of immunosuppressive therapy.

Introduction: Biologic agents have revolutionized the therapeutic management of ulcerative colitis. Anti-tumor necrosis factor agents were the first biologic drugs used to induce and maintain remission in this inflammatory bowel disease. Recently, another biologic option, ustekinumab, has become available for the treatment of moderate-to-severe ulcerative colitis. Areas covered: In this article, the authors review the literature on the efficacy and safety of ustekinumab in the context of current biologic agents used for the management of this disease. The potential role of ustekinumab in the treatment paradigm of the disease is also discussed. Expert opinion: The UNIFI trial has demonstrated the efficacy and safety of ustekinumab in induction and maintenance phases of treatment for ulcerative colitis. Ustekinumab may provide clinical benefit in a range of settings in patients with ulcerative colitis, even for those with multiple treatment failures, which are relatively common in daily clinical practice. Future clinical trials should compare the efficacy of ustekinumab with existing biologic agents in the management of ulcerative colitis.

Background A new capsule endoscopy (CE) system featuring two advanced optics for 344°-viewing and a prolonged operative time has been recently developed for Crohn’s disease (CD) patients. Hence, we evaluated, for the first time, the performance of this novel CE and the add-on value of the 344°-viewing in a multi-center real-life setting. Methods Consecutive patients with suspected or established CD received the PillCam™ Crohn’s System as supplementary diagnostic work-up focused on the small-bowel between June 2017 and June 2018. Technical and clinical data, including the panenteric CE diagnostic yield, the Lewis score and the impact of small-bowel findings on clinical management during a 6-months follow-up (new diagnosis, staging or treatment upgrade) were collected, thereby evaluating the added value of the 344° panoramic-view (lesions detected by camera A and B) over the standard 172°-view (lesions detected by one camera only). Results Among 41 patients (aged 43 ± 20 years), 73% underwent CE for suspected CD and 27% for established CD. The rate of complete enteroscopy was 90%. No technical failure or retention occurred. Compared to the standard 172° view, the panoramic 344°-view revealed a greater number of patients with a relevant lesion (56.1% vs. 39.0%; P = 0.023), resulting in higher Lewis score (222,8 vs. 185.7; P = 0.031), and improved clinical management (48.8% vs. 31.7%, P = 0.023). Conclusions The panoramic 344°-view increases small-bowel CE accuracy, thereby improving the clinical management of CD patients with mild small-bowel active disease. This system should be regarded as a new standard for both small-bowel diagnosis and monitoring in inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are currently considered multifactorial pathologies in which various combined environmental factors act on a genetic background, giving rise to a chronic inflammation of the gastrointestinal tract. Among the various environmental factors, it now seems clear that the diet plays the major role in IBD onset and progression. Several clinical studies have attempted to understand the impact of diet in the development and progression of these diseases in order to establish useful guidelines for their management. However, the modest and sometimes contradictory results did not lead to the definition of shared dietary suggestions. On the other hand, food fads and recommendations based on anecdotal episodes are often followed by IBD patients to improve their diet. This review provides a critical overview of existing data on the role of diet as a risk factor for IBD. The methodology used was that of analyzing the results of clinical studies conducted on diet and IBD over the last 12 years through PubMed, as well as analyzing the most relevant studies on nutrients and their possible roles in IBD through the knowledge of the mechanisms by which they can modulate the microbiota or the intestinal physiology.

Background: Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking. Methods: In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid- free remission at week 52. Results: A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5% ; difference, 8.8 percentage points ; 95% confidence interval [CI], 2.5 to 15.0 ; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7% ; difference, 11.9 percentage points ; 95% CI, 5.3 to 18.5 ; P

The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars.

Background In patients with chronic refractory ulcerative colitis (UC) the precise timing for indication to colectomy is unclear. Aims We performed a systematic review of the literature on the risk factors for colectomy in patients with chronic refractory UC in the biologic era. Methods PubMed Central/Medline and Embase were systemically searched for records published between January 2000 and December 2017. Current evidence was summarized and filtered by expert opinion. Results 70 studies were included in the qualitative synthesis. Several factors were found to be associated with a higher or reduced risk for colectomy, including variables at baseline – such as progression from proctitis/left-sided to extensive colitis, extensive colitis at diagnosis, high baseline C Reactive Protein or erythrocyte sedimentation rate, male gender, and younger age at diagnosis – previous medical history, and factors arising during therapy with biologics, including the absence of clinical response after induction with infliximab or adalimumab, and the lack of mucosal healing during therapy with anti-TNFs. Conclusions Two main points may help physicians to decide when the surgical option may be considered in patients with chronic refractory UC: (1) a first risk stratification can be obtained by analyzing factors at baseline and medical history, including the previous exposure to anti-TNFs; (2) during therapy with biologics, the early assessment (after 12–16 weeks of treatment) of clinical and endoscopic response is a strong predictor of the subsequent risk of colectomy.

Intestinal tumors represent less than 6 % of digestive tumors, and, because of the limitations of intestinal investigations, these tumors are difficult to diagnose. In this context, capsule endoscopy has proven effective, especially in patients with obscure digestive bleeding. In a large series of patients undergoing capsule endoscopy, small bowel tumors are found in 2.4–8.9 % of cases. The aim of this retrospective, single-center study, based on prospective database, is to evaluate the frequency of small bowel tumors detected by capsule endoscopy in patients with occult gastrointestinal bleeding. During 2004–2014, 849 consecutive patients underwent CE at our Department for occult gastrointestinal bleeding. Following capsule endoscopy, the medical records of the study population were reviewed. Results of double-balloon enteroscopy or surgery performed after capsule endoscopy were retrieved. Capsule endoscopy identified 55 small bowel tumors (6.5 %), of which 28 malignancies (51 %) and 27 benign neoplasms (49 %) underwent surgery or endoscopic treatment. Malignancies included adenocarcinoma (18.7 %), gastrointestinal stromal tumors (GIST) (12 %) and lymphoma (6.7 %). Benign neoplasms included dysplastic adenomatous polyps (36 %) and hyperplastic polyps (25.3 %). Non-neoplastic masses included one inflammatory polyp. Capsule retention occurred in four patients (5.3 %) and the retained capsule was retrieved during surgery. In our experience neoplasms of small bowel are found in 6.5 % of patients with occult gastrointestinal bleeding. Of these malignancies, small bowel neoplasms are found in 3.3 % of cases. Capsule endoscopy is an effective and sensitive diagnostic tool, and plays an important role in the algorithm for the diagnostic workup of suspected small bowel tumors.

Objectives: To establish clinical consensus on important and relevant quality-of-care (QoC) attributes in ulcerative colitis (UC) treatment that may improve treatment outcomes and guide best practices. Methods: Thirty-eight QoC attributes were identified in a literature review. Sixteen European-based experts were selected based on their contributions to UC guidelines, publications, and patient care. A 3-round, modified Delphi panel was conducted including an interview round, and 2 web-based rounds to reach consensus and finalize a QoC attribute list. Results: The draft QoC attribute list derived from a literature review and Round 1, expert interviews, comprised 63 attributes. In Rounds 2 and 3, the QoC attributes frequently rated as critically important were diagnosis (n = 15, 93.8%), treatment adherence (n = 15, 93.8%), and access to care/treatment (Round 2: n = 14, 87.5%; Round 3: n = 15, 93.8%). The final QoC attribute list consisted of 61 attributes across 20 domains, with the most attributes reported in the “treatment goals” domain (n = 9). Conclusion: QoC is a complex and evolving concept that can improve outcomes while maximizing healthcare resources. Limited time and resources hamper clinicians’ ability to openly and empathetically communicate with patients; novel technology may help to offer solutions.

This expert-opinion paper reviews available evidence for the use of ustekinumab, a human interleukin 12/23 monoclonal antibody, in the treatment of Crohn's disease and discusses its potential role in the current treatment scenario for the condition. Ustekinumab appears to be associated with rapid and sustained clinical effect, as reported from the clinical research program, with additional support for potential mucosal healing. These characteristics are paralleled by a favorable safety profile, lack of immunogenicity and the presence of systemic anti-inflammatory activity. Importantly, ustekinumab requires only one single intravenous administration, while subsequent dosing is administered subcutaneously, with potential advantages for home-based therapy. Lastly, the dosage of ustekinumab is flexible. On the basis of the evidence, ustekinumab has a role in patients with primary failure or secondary loss of response to anti-tumor necrosis factor agents, as well as in those who have adverse events on front-line biologics or are reinitiating therapy after a treatment holiday. Current evidence suggests that ustekinumab may be particularly suitable in patients who present extra-intestinal manifestations of the disease or are at risk of infections. Ustekinumab may also be considered in the first-line setting, especially in frail patients, in young subjects or in those who have concomitant immune-mediated diseases.

The two main forms of intestinal bowel disease, namely ulcerative colitis and Crohn’s disease, are not curable but can be controlled by various medical therapies. The Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) has prepared clinical practice guidelines to help physicians prescribe corticosteroids and immunosuppressive drugs for these patients. The guidelines consider therapies that induce remission in patients with active disease as well as treatment regimens that maintain remission. These guidelines complement already existing guidelines from IG-IBD on the use of biological drugs in patients with inflammatory bowel diseases.

Summary The aim of the present study is to describe the histological and mutational characteristics of a series of both large and small bowel adenocarcinomas in patients with Crohn’s disease from a tertiary referral centre of inflammatory bowel disease. Bowel adenocarcinoma was diagnosed in 11 (1.7%) of 660 consecutive patients submitted to surgery for histologically proven Crohn’s disease in 5 years. The following data were collected: tumour site, stage and grade, intracellular/extra-cellular mucin, lymphovascular invasion, immunohistochem-istry for keratin 7, keratin 20 and CDX-2, mutation analyses of KRAS, B-RAF, PI3K and microsatellite instability. A strong predominance of male gender was observed (10/11). Four (36.4%) adenocarcinomas arose in the small bowel, five (45.4%) in the anus/rectum, and two (18.2%) in anastomosis. Furthermore, all cases of anorectal adenocarcinoma showed >50% of extracellular mucin, with associated KRAS mutations in three of five. No influence in cancer incidence by infliximab therapy was observed. Our series, one of the largest on the topic with immunomorphological and molecular deepening, showed that bowel adenocarcinomas in Crohn’s disease have an aggressive behaviour and a strong predominance of extracellular mucin. In surgical specimens from Crohn’s disease patients, mucinous-looking anal fistulas and ileal areas of adhesion/retraction should always be extensively sampled.