Lipid signature associated with chronic colon inflammation reveals a dysregulation in colonocyte differentiation process.

Inflammatory Bowel Disease (IBD) comprises a heterogeneous group of chronic inflammatory conditions of the gastrointestinal tract that include ulcerative colitis (UC) and Crohn's disease. Although the etiology is not well understood, IBD is characterized by a loss of the normal epithelium homeostasis that disrupts the intestinal barrier of these patients. Previous work by our group demonstrated that epithelial homeostasis along the colonic crypts involves a tight regulation of lipid profiles. To evaluate whether lipidomic profiles conveyed the functional alterations observed in the colonic epithelium of IBD, we performed matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) analyses of endoscopic biopsies from inflamed and non-inflamed segments obtained from UC patients. Our results indicated that lipid profiling of epithelial cells discriminated between healthy and UC patients. We also demonstrated that epithelial cells of the inflamed mucosa were characterized by a decrease in mono- and di-unsaturated fatty acid-containing phospholipids and higher levels of arachidonic acid-containing species, suggesting an alteration of the lipid gradients occurring concomitantly to the epithelial differentiation. This result was reinforced by the immunofluorescence analysis of EPHB2 and HPGD, markers of epithelial cell differentiation, sustaining that altered lipid profiles were at least partially due to a faulty differentiation process. Overall, our results showed that lipid profiling by MALDI-MSI faithfully conveys molecular and functional alterations associated with the inflamed epithelium, providing the foundation for a novel molecular characterization of UC patients.

Combination of granulocyte-monocyte apheresis and ustekinumab: Multicentre and retrospective study.

OBJECTIVE: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. PATIENTS AND METHODS: A retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. RESULTS: Seventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35-61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5-7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. CONCLUSION: GMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.

Controversies in the management of anti-TNF therapy in patients with Crohn's disease: a Delphi consensus.

BACKGROUND: Despite research, there are still controversial areas in the management of Crohn's disease (CD). OBJECTIVE: To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD. METHODS: Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process. RESULTS: Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator. CONCLUSION: This document sought to pull together the best evidence, experts' opinions, and treating physicians' attitudes when using anti-TNF therapies in patients with CD.

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) survey on the management of patients with inflammatory bowel disease. / Encuesta Sociedad Española de Médicos de Atención Primaria (SEMERGEN) y Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el manejo de pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Collaboration between Primary Care (PC) and Gastroenterology in inflammatory bowel disease (IBD) is crucial to provide high-quality healthcare. The aim of this study is to analyse the relationship between PC and gastroenterologists at a national level in order to identify areas for improvement in the management of patients with inflammatory bowel disease (IBD) and how to address them, with the aim of subsequently developing concrete proposals and projects between SEMERGEN and GETECCU. METHODS: Descriptive, observational, cross-sectional study, was carried out using an anonymous online questionnaire between October 2021 and March 2022. RESULTS: A total of 157 surveys from Gastroenterology and 222 from PC were collected. 43.8% and 34.3% of gastroenterologists and family practitioners, respectively, considered that there was a good relationship between the units. The level of knowledge from family practitioners regarding different aspects of IBD out of 10 was: clinical 6.67±1.48, diagnosis 6.47±1.46, treatment 5.63±1.51, follow-up 5.53±1.68 and complications 6.05±1.54. The perception of support between both units did not exceed 4.5 on a scale from 0 to 10 in either of the surveys. The most highly voted improvement proposals were better coordination between the units, implementation of IBD units, and nursing collaboration. CONCLUSION: There are deficiencies in the relationship between PC and Gastroenterology with special dedication to IBD that require the efforts of the scientific societies that represent them for greater coordination with the development of joint protocols and agile, fast, and effective communication channels.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients.

BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study.

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery.

Granulocyte-monocyte apheresis: an alternative combination therapy after loss of response to anti-TNF agents in ulcerative colitis.

Objective: To evaluate the effectiveness and safety of the combination of granulocyte-monocyte apheresis (GMA) after loss of response (LOR) to anti-tumor necrosis factor (TNF) agents in ulcerative colitis (UC). Materials and methods: A retrospective, multicenter study was performed in 11 inflammatory bowel disease (IBD) Units. Clinical remission was defined as a partial Mayo score ≤2. The effectiveness of the treatment was evaluated by the partial Mayo score and the rate of anti-TNF intensification, switch, swap or colectomy. Results: Forty-seven patients with ulcerative colitis were included (mean age 35 years, mean disease duration 52 months, 66% male and 59% extensive colitis). Twenty-three subjects were receiving infliximab, eighteen adalimumab and six golimumab. GMA was combined after a primary non-response (49%) or secondary loss of response (51%) to anti-TNF therapy. We observed a significant decrease in partial Mayo score and fecal calprotectin after GMA. Fifteen patients (32%) responded to the combination therapy without anti-TNF intensification, switch, swap or colectomy. Eight patients (17%) underwent colectomy. Two patients (4%) presented adverse events related to the technique. Conclusions: Combination of GMA and anti-tumor necrosis factor is a safe and effective treatment after the loss of response to these biologic agents, with a significant decrease of the clinical disease activity and biomarkers, in a population with limited therapeutic alternatives.

Tissue-selective alteration of ethanolamine plasmalogen metabolism in dedifferentiated colon mucosa.

Human colon lipid analysis by imaging mass spectrometry (IMS) demonstrates that the lipid fingerprint is highly sensitive to a cell's pathophysiological state. Along the colon crypt axis, and concomitant to the differentiation process, certain lipid species tightly linked to signaling (phosphatidylinositols and arachidonic acid (AA)-containing diacylglycerophospholipids), change following a rather simple mathematical expression. We extend here our observations to ethanolamine plasmalogens (PlsEtn), a unique type of glycerophospholipid presenting a vinyl ether linkage at sn-1 position. PlsEtn distribution was studied in healthy, adenomatous, and carcinomatous colon mucosa sections by IMS. In epithelium, 75% of PlsEtn changed in a highly regular manner along the crypt axis, in clear contrast with diacyl species (67% of which remained constant). Consistently, AA-containing PlsEtn species were more abundant at the base, where stem cells reside, and decreased while ascending the crypt. In turn, mono-/diunsaturated species experienced the opposite change. These gradients were accompanied by a gradual expression of ether lipid synthesis enzymes. In lamina propria, 90% of stromal PlsEtn remained unchanged despite the high content of AA and the gradient in AA-containing diacylglycerophospholipids. Finally, both lipid and protein gradients were severely affected in polyps and carcinoma. These results link PlsEtn species regulation to cell differentiation for the first time and confirm that diacyl and ether species are differently regulated. Furthermore, they reaffirm the observations on cell lipid fingerprint image sensitivity to predict cell pathophysiological status, reinforcing the translational impact both lipidome and IMS might have in clinical research.

Genetic Diversity and Virulence Determinants of Escherichia coli Strains Isolated from Patients with Crohn's Disease in Spain and Chile.

Adherent-invasive Escherichia coli (AIEC) strains are genetically variable and virulence factors for AIEC are non-specific. FimH is the most studied pathogenicity-related protein, and there have been few studies on other proteins, such as Serine Protease Autotransporters of Enterobacteriacea (SPATEs). The goal of this study is to characterize E. coli strains isolated from patients with Crohn's disease (CD) in Chile and Spain, and identify genetic differences between strains associated with virulence markers and clonality. We characterized virulence factors and genetic variability by pulse field electrophoresis (PFGE) in 50 E. coli strains isolated from Chilean and Spanish patients with CD, and also determined which of these strains presented an AIEC phenotype. Twenty-six E. coli strains from control patients were also included. PFGE patterns were heterogeneous and we also observed a highly diverse profile of virulence genes among all E. coli strains obtained from patients with CD, including those strains defined as AIEC. Two iron transporter genes chuA, and irp2, were detected in various combinations in 68-84% of CD strains. We found that the most significant individual E. coli genetic marker associated with CD E. coli strains was chuA. In addition, patho-adaptative fimH mutations were absent in some of the highly adherent and invasive strains. The fimH adhesin, the iron transporter irp2, and Class-2 SPATEs did not show a significant association with CD strains. The V27A fimH mutation was detected in the most CD strains. This study highlights the genetic variability of E. coli CD strains from two distinct geographic origins, most of them affiliated with the B2 or D E. coli phylogroups and also reveals that nearly 40% of Chilean and Spanish CD patients are colonized with E.coli with a characteristic AIEC phenotype.

Lipid fingerprint image accurately conveys human colon cell pathophysiologic state: A solid candidate as biomarker.

Membrane lipids are gaining increasing attention in the clinical biomarker field, as they are associated with different pathologic processes such as cancer or neurodegenerative diseases. Analyzing human colonoscopic sections by matrix assisted laser/desorption ionization (MALDI) mass spectrometry imaging techniques, we identified a defined number of lipid species changing concomitant to the colonocyte differentiation and according to a quite simple mathematical expression. These species felt into two lipid families tightly associated in signaling: phosphatidylinositols and arachidonic acid-containing lipids. On the other hand, an opposed pattern was observed in lamina propria for AA-containing lipids, coinciding with the physiological distribution of the immunological response cells in this tissue. Importantly, the lipid gradient was accompanied by a gradient in expression of enzymes involved in lipid mobilization. Finally, both lipid and protein gradients were lost in adenomatous polyps. The latter allowed us to assess how different a single lipid species is handled in a pathological context depending on the cell type. The strict patterns of distribution in lipid species and lipid enzymes described here unveil the existence of fine regulatory mechanisms orchestrating the lipidome according to the physiological state of the cell. In addition, these results provide solid evidence that the cell lipid fingerprint image can be used to predict precisely the physiological and pathological status of a cell, reinforcing its translational impact in clinical research.

Ustekinumab for the Treatment of Refractory Crohn's Disease: The Spanish Experience in a Large Multicentre Open-label Cohort.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. METHODS: Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. RESULTS: One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. CONCLUSIONS: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.

Effectiveness of anti-TNFα drugs in patients with Crohn's disease who do not achieve remission with their first anti-TNFα agent.

BACKGROUND: Anti-TNF treatment is effective for Crohn's disease (CD); however, some patients did not achieve remission with these drugs. AIMS: To evaluate the short-term effectiveness of a second anti-TNF in CD patients who did not achieve remission with the first one and to assess its durability. METHODS: Patients who did not achieve remission with their first anti-TNF were included. The short-term response of the second anti-TNF was assessed, the long-term response was evaluated in patients who achieved remission (Kaplan-Meier). Cox-regression was performed to identify predictors of loss of efficacy. RESULTS: In all, 118 CD patients received a second anti-TNF after primary failure of the first. The first anti-TNF was discontinued because of non-response in 54% of patients and partial response in 46%. Fifty-one percent of patients achieved remission in the short-term. The probability of remission was lower in patients for whom the drug indication was perianal disease (OR=0.3, 95% CI=0.1-0.7, P=0.005). The dose was increased in 33% of patients, and 37% achieved/regained remission. The probability of maintaining remission was 76%, 68% and 64% at 12, 18 and 24 months, respectively. CONCLUSIONS: Approximately half of the patients achieved remission with a second anti-TNF after primary failure of the first, this strategy was less effective in patients with perianal disease.

Impact of Smoking Cessation on the Clinical Course of Crohn's Disease Under Current Therapeutic Algorithms: A Multicenter Prospective Study.

OBJECTIVES: Given the importance of tobacco smoking (TS) as the only environmental factor repeatedly linked to the development of the Crohn's disease (CD), it is surprising that very few prospective studies have assessed whether TS is associated with an increased frequency of clinical relapse. Our aim was to evaluate the current impact of TS on disease relapse and the clinical benefit of quitting smoking in the present era of widespread use of anti-TNF drugs and immunosuppressants. METHODS: This was a multicenter prospective cohort study, which included 573 CD patients in clinical remission with various smoking habits. All smokers were advised to quit. Patients not exposed to tobacco before inclusion (non- and former smokers), continuing smokers, and quitters were compared regarding differences in disease outcomes during a follow-up of 4 years. RESULTS: A total of 148 continuing smokers, 190 nonsmokers, 160 former smokers, and 75 quitters were included. In comparison with nonsmokers, continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 (95% confidence interval (CI): 1.10-2.17). Former smokers and quitters had similar relapse incidences compared with nonsmokers. Smoking was an independent predictor for disease relapse in the multivariate analysis (hazard ratio: 1.58 (95% CI 1.20-2.09). In the time-dependent analysis, continuing smokers had earlier relapse, regardless of anti-TNF or immunosuppressant use. CONCLUSIONS: Continuing smokers have more disease relapses, and patients who quit smoking have a similar relapse incidence compared with nonsmokers.

Crohn associated microbial communities associated to colonic mucosal biopsies in patients of the western Mediterranean.

Next generation sequencing approaches allow the retrieval of several orders of magnitude larger numbers of amplified single sequences in 16S rRNA diversity surveys than classical methods. However, the sequences are only partial and thus lack sufficient resolution for a reliable identification. The OPU approach used here, based on a tandem combination of high quality 454 sequences (mean >500 nuc) applying strict OTU thresholds, and phylogenetic inference based on parsimony additions to preexisting trees, seemed to improve the identification yields at the species and genus levels. A total of thirteen biopsies of Crohn-diagnosed patients (CD) and seven healthy controls (HC) were studied. In most of the cases (73%), sequences were affiliated to known species or genera and distinct microbial patterns could be distinguished among the CD subjects, with a common depletion of Clostridia and either an increased presence of Bacteroidetes (CD1) or an anomalous overrepresentation of Proteobacteria (CD2). Faecalibacterium prausnitzii presence was undetectable in CD, whereas Bacteroides vulgatus-B. dorei characterized HC and some CD groups. Altogether, the results showed that a microbial composition with predominance of Clostridia followed by Bacteroidetes, with F. prausnitzii and B. vulgatus-B. dorei as major key bacteria, characterized what could be considered a balanced structure in HC. The depletion of Clostridia seemed to be a common trait in CD.

Does smoking influence Crohn's disease in the biologic era? The TABACROHN study.

BACKGROUND: While most studies have found a negative effect of smoking on Crohn's disease (CD) phenotype, more recent data have failed to reproduce this association, which might be due to a current wider use of thiopurines and biologic therapy. The TABACROHN study aimed at defining the impact of smoking on CD in the largest published series. METHODS: This multicenter cross-sectional study included 1170 CD patients. Patients were classified as nonsmokers, current smokers, or former smokers according to their present smoking status. Clinical data regarding disease characteristics, treatment, and complications were collected. RESULTS: Smokers were more frequently under maintenance treatment when compared to nonsmokers. In addition, current smokers presented higher use of biologic drugs compared to nonsmokers. Tobacco exposure and a higher tobacco load were independent predictors of need for maintenance treatment and stenosing phenotype, respectively. CONCLUSIONS: In the era of early and widespread use of immunosuppressants and biologics, tobacco exposure is an independent predictor of need for maintenance treatment, specifically biologic therapy. The wider use of biologics and immunosuppressants could account for the existence of no major differences in disease behavior and complications between nonsmokers and current smokers.

High smoking cessation rate in Crohn's disease patients after physician advice--the TABACROHN Study.

INTRODUCTION: Tobacco smoking has a significant impact on the development of Crohn's disease (CD) and its clinical course, making smoking cessation one of the main goals in CD therapeutic strategy. AIMS: To evaluate the effectiveness of an advice-based smoking cessation strategy among CD patients. METHODS: We have performed a prospective multicenter study which enrolled 408 CD smokers. At inclusion all patients were instructed about the risks of smoking and subsequently followed every 3 months. Each center used additional smoking cessation strategies based on available resources. Urinary cotinine and exhaled carbon monoxide levels were evaluated in a subgroup of patients. RESULTS: Median study follow up was 18 months. 31% of the patients achieved complete smoking cessation and 23% were smoking-free at the end of their follow up with 8% of smoking relapse. Most patients not achieving smoking cessation did not change their smoking habit with only 5% presenting a decrease in tobacco load. 63% of patients willing to quit smoking received help from another specialist, most frequently the pulmonologist (47%). Surprisingly, most patients (88%) tried to quit smoking with no pharmacological therapy and bupropion, varenicline and nicotine replacement treatment were used in few patients. Urinary cotinine and exhaled CO levels tested in a subgroup of patients proved to have a good correlation with the self-reported smoking habit. No predictors of successful smoking cessation were identified. CONCLUSION: Our results underline that an anti-tobacco strategy mostly based on CD patients's education and counseling is feasible and effective in helping patients reach complete abstinence.

Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).

BACKGROUND: There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis. METHODS: An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support. RESULTS: A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p < 0.0001). The overall mortality rate was 7.7%. CONCLUSIONS: The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.

Infliximab maintenance therapy is associated with decreases in direct resource use in patients with luminal or fistulizing Crohn's disease.

GOALS: To estimate the impact of infliximab (IFX) maintenance therapy on the use of hospital resources in patients with Crohn's disease (CD). STUDY: Medical records of patients treated with IFX maintenance therapy (5 mg/kg body weight; intravenous infusion) for luminal (L) or fistulizing (F) CD at 13 hospitals were retrospectively reviewed. Patients were assessed as their own controls. Use of CD-related healthcare resources was recorded comparing 1-year periods before and after first IFX infusion (pre-IFX and post-IFX). RESULTS: One hundred fifty-three CD patients (n=84 L; 69 F) fulfilled the inclusion criteria. Mean number of IFX infusions was 7/y with an average of 335 mg/infusion dose/patient. During the pre-IFX period, 55% of patients needed hospitalization versus 31% in the post-IFX period (P<0.001). Mean inpatient stay was 11.3 d/y [11.2 (L), 11.5 (F)] for the pre-IFX period, and 6.3 d/y [6.2 (L), 6.3 (F)] in the post-IFX period (P<0.001). Surgery was required in 24% patients in the pre-IFX period and in 11% post-IFX (P<0.001). There were no significant changes in the incidence of outpatient visits although emergency room visits fell significantly. CONCLUSIONS: Maintenance IFX in CD patients is associated with decreases in the use and length of hospitalizations and the need for surgery in clinical practice.