Development and validation of the QUECOMIICAT questionnaire: a tool to assess disease-related knowledge in patients with inflammatory bowel disease.

INTRODUCTION: adequate knowledge of inflammatory bowel disease (IBD) is essential for a successful patient-centered management of IBD. OBJECTIVE: due to the scarcity of up-to-date tools for measuring IBD literacy, this single-center, prospective study aimed to develop and validate a new questionnaire to assess IBD-related knowledge. MATERIAL AND METHODS: the study included patients followed up at the Crohn-Colitis Care Unit (UACC) at the Hospital Vall d'Hebron (Barcelona, Spain). Patients admitted to the UACC for the first time were subsequently enrolled into a standard IBD educational program. A pilot questionnaire was developed and validated in 92 IBD patients by determining the internal consistency reliability (Cronbach's α test), feasibility, construct validity (correlation with the Crohn's and Colitis Knowledge [CCKNOW] questionnaire and a knowledge visual analog scale [VAS]) and sensitivity (score change before and after a standard IBD educational program). The questionnaire, named "Qüestionari Coneixements Malaltia Inflamatòria Intestinal Catalunya" (IBD-knowledge questionnaire Catalonia) (QUECOMIICAT) was written in Spanish and had 25 items addressing six dimensions: general concepts, clinic, treatment, surgery, habits and social context. RESULTS: the median (interquartile range) completion time was 15 (10-20) minutes and the floor and ceiling effects were 1.1% and 2.1%, respectively. The Cronbach's α coefficient was α = 0.75. QUECOMIICAT significantly correlated with the VAS (rho = 0.34, p < 0.01) and CCKNOW questionnaires (rho = 0.74, p < 0.01). Patient knowledge significantly increased 24 hours after attending a standard IBD educational program and remained statistically significant one month later (Pearson's test-retest correlation coefficient r = 0.81, p < 0.001). CONCLUSION: in conclusion, the QUECOMIICAT questionnaire is a new up-to-date tool to assess IBD-related knowledge with good feasibility and validation results for use in the routine clinical practice.

Probiotic supplementation with Lactobacillus plantarum and Pediococcus acidilactici for Helicobacter pylori therapy: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the safety, tolerability and efficacy of a probiotic supplementation for Helicobacter pylori (H. pylori) eradication therapy. DESIGN: Consecutive adult naive patients with a diagnosis of H. pylori infection who were prescribed eradication therapy according to clinical practice (10-day triple or nonbismuth quadruple concomitant therapy) randomly received probiotics (1 × 109 colony-forming units each strain, Lactobacillus plantarum and Pediococcus acidilactici) or matching placebo. Side effects at the end of the treatment, measured through a modified De Boer Scale, were the primary outcome. Secondary outcomes were compliance with therapy and eradication rates. RESULTS: A total of 209 patients (33% triple therapy, 66% non-bismuth quadruple therapy) were included [placebo (n = 106) or probiotic (n = 103)]. No differences were observed regarding side effects at the end of the treatment between groups (ß -0.023, P 0.738). Female gender (P < 0.001) and quadruple therapy (P 0.007) were independent predictors of side effects. No differences in compliance were observed, regardless of the study group or eradication therapy. Eradication rates were similar between groups [placebo 95% (95% confidence interval (CI), 89% to 98%) vs probiotic 97% (95% CI, 92% to 99%), P 0.721]. There were no relevant differences in cure rates (>90% in all cases) between triple and quadruple concomitant therapy. CONCLUSION: Probiotic supplementation containing Lactobacillus Plantarum and Pediococcus acidilactici to H. pylori treatment neither decreased side effects nor improved compliance with therapy or eradication rates.

Costs of ulcerative colitis from a societal perspective in a regional health care area in Spain: A database study.

OBJECTIVES: To estimate the management of UC associated costs from the societal perspective in Spain. METHODS: Observational, longitudinal study with retrospective data collection based on reviews of outpatient health records. Socio-demographic, clinical and sick leave information was gathered. Patients diagnosed of UC between 2002 and 2012, older than 18 years, followed-up by a minimum of 12 months post diagnosis, with at least two clinical and use of resources data recorded, were included. RESULTS: 285 UC patients [51.2% men; 44.5 (SD: 15.6) years old; 88.4% without family history of UC; 39.3% proctitis; 5.6 (2.5) years disease follow-up] participated. More than half (65.6%) were active workers, 75.9% were on sick leave for reasons different from UC [mean 0.66 (0.70) times per year] during (mean) 28.43 (34.45) days. Only 64 patients were on UC-related sick-leaves, lasting (mean) 26.17 (37.43) days. Absenteeism due to medical visits caused loss of 29.55 (21.38) working hours per year. Mean direct and indirect annual cost per UC patient were €1754.10 (95%CI: 1473.37-2034.83) and €399.32 (282.31-422.69), respectively. Absenteeism was estimated at €88.21(32.72-50.06) per patient per year, in which sick-leaves were the main component of indirect costs (88.2%). Age, UC family history, diarrhea at diagnosis, blood and blood-forming organs diseases and psychological disorders were the main predictors of indirect costs. CONCLUSIONS: UC is a costly disease for the society and the Spanish National Healthcare System. Indirect costs imply a major burden by affecting the most productive years of patients. Further research is needed considering all components of productivity loss, including presenteeism-associated costs.

Mucosa-associated Faecalibacterium prausnitzii phylotype richness is reduced in patients with inflammatory bowel disease.

Faecalibacterium prausnitzii depletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associated F. prausnitzii populations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprint F. prausnitzii populations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness of F. prausnitzii subtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specific F. prausnitzii phylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P = 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P = 0.005). This study reveals that even though the main members of the F. prausnitzii population are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability of F. prausnitzii phylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis.

Mucosa-associated Faecalibacterium prausnitzii and Escherichia coli co-abundance can distinguish Irritable Bowel Syndrome and Inflammatory Bowel Disease phenotypes.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) diagnosis requires comprehensive examination of the patient. Faecalibacterium prausnitzii and Escherichia coli have been reported as representatives of Inflammatory Bowel Disease (IBD) dysbiosis. The aim was to determine whether or not quantification of these species can be used as a complementary tool either for diagnostic or prognostic purposes. METHODS: Mucosa-associated F. prausnitzii and E. coli abundance was determined in 28 controls (H), 45 CD, 28 UC patients and 10 irritable bowel syndrome (IBS) subjects by quantitative polymerase chain reaction (qPCR) and the F. prausnitzii-E. coli index (F-E index) was calculated. Species abundances were normalized to total bacteria and human cells. Data was analyzed taking into account patients' phenotype and most relevant clinical characteristics. RESULTS: IBD patients had lower F. prausnitzii abundance than H and IBS (P<0.001). CD patients showed higher E. coli counts than H and UC patients (P<0.001). The F-E index discriminated between H, CD and UC patients, and even between disease phenotypes that are usually difficult to distinguish as ileal-CD (I-CD) from ileocolonic-CD and colonic-CD from extensive colitis. E. coli increased in active CD patients, and remission in I-CD patients was compromised by high abundance of this species. Treatment with anti-tumor necrosis factor (TNF) α diminished E. coli abundance in I-CD whereas none of the treatments counterbalanced F. prausnitzii depletion. CONCLUSION: F. prausnitzii and E. coli are useful indicators to assist in IBD phenotype classification. The abundance of these species could also be used as a supporting prognostic tool in I-CD patients. Our data indicates that current medication does not restore the levels of these two species to those found in a healthy gut.

Impact of bread diet on intestinal dysbiosis and irritable bowel syndrome symptoms in quiescent ulcerative colitis: A pilot study.

Gut microbiota may be involved in the presence of irritable bowel syndrome (IBS)-like symptomatology in ulcerative colitis (UC) patients in remission. Bread is an important source of dietary fiber, and a potential prebiotic. To assess the effect of a bread baked using traditional elaboration, in comparison with using modern elaboration procedures, in changing the gut microbiota and relieving IBS-like symptoms in patients with quiescent ulcerative colitis. Thirty-one UC patients in remission with IBS-like symptoms were randomly assigned to a dietary intervention with 200 g/d of either treatment or control bread for 8 weeks. Clinical symptomatology was tested using questionnaires and inflammatory parameters. Changes in fecal microbiota composition were assessed by high-throughput sequencing of the 16S rRNA gene. A decrease in IBS-like symptomatology was observed after both the treatment and control bread interventions as reductions in IBS-Symptom Severity Score values (p-value < 0.001) and presence of abdominal pain (p-value < 0.001). The treatment bread suggestively reduced the Firmicutes/Bacteroidetes ratio (p-value = 0.058). In addition, the Firmicutes/Bacteroidetes ratio seemed to be associated with improving IBS-like symptoms as suggested by a slight decrease in patient without abdominal pain (p-value = 0.059). No statistically significant differential abundances were found at any taxonomic level. The intake of a bread baked using traditional elaboration decreased the Firmicutes/Bacteroidetes ratio, which seemed to be associated with improving IBS-like symptoms in quiescent ulcerative colitis patients. These findings suggest that the traditional bread elaboration has a potential prebiotic effect improving gut health (ClinicalTrials.gov ID number of study: NCT05656391).

Exploring the Associations of Inflammatory and Oxidative Stress Biomarkers with Pancreatic Diseases: An Observational and Mendelian Randomisation Study.

Identifying biomarkers linked to pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) is crucial for early detection, treatment, and prevention. Methods: Association analyses of 10 serological biomarkers involved in cell signalling (IFN-γ, IL-6, IL-8, IL-10), oxidative stress (superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, total glutathione (GSH), malondialdehyde (MDA) levels), and intestinal permeability proteins (zonulin, I-FABP2) were conducted across PDAC (n = 12), CP (n = 21) and control subjects (n = 23). A Mendelian randomisation (MR) approach was used to assess causality of the identified significant associations in two large genetic cohorts (FinnGen and UK Biobank). Results: Observational results showed a downregulation of SOD and GPx antioxidant enzyme activities in PDAC and CP patients, respectively, and higher MDA levels in CP patients. Logistic regression models revealed significant associations between CP and SOD activity (OR = 0.21, 95% CI [0.05, 0.89], per SD), GPx activity (OR = 0.28, 95% CI [0.10, 0.79], per SD), and MDA levels (OR = 2.05, 95% CI [1.36, 3.08], per SD). MR analyses, however, did not support causality. Conclusions: These findings would not support oxidative stress-related biomarkers as potential targets for pancreatic diseases prevention. Yet, further research is encouraged to assess their viability as non-invasive tools for early diagnosis, particularly in pre-diagnostic CP populations.

Clinical performance study of a fecal bacterial signature test for colorectal cancer screening.

The fecal immunochemical test (FIT) is the most widely used test for colorectal cancer (CRC) screening. RAID-CRC Screen is a new non-invasive test based on fecal bacterial markers, developed to complement FIT by increasing its specificity. The test was previously clinically evaluated in FIT-positive patients (>20 µg of hemoglobin/g of feces, "FIT20"), in which it reduced the proportion of false positive results by 16.3% while maintaining most of FIT20's sensitivity. The aim of this study was to compare the sensitivity and specificity of a CRC screening program using RAID-CRC Screen in addition to FIT20 as a triage test in a European screening population undergoing screening colonoscopy with a CRC screening program with FIT20 alone in the same cohort. A cohort of 2481 subjects aged > 55 years from the German screening colonoscopy program was included. The colonoscopy findings were used as the gold standard in calculating the diagnostic capacity of the tests and included 15 CRC and 257 advanced neoplasia cases. RAID-CRC Screen added to FIT20 provided the same sensitivity as FIT20 alone (66.7%) in detecting CRC and a significantly higher specificity (97.0% vs. 96.1%, p<0.0001). The positive predictive value was 11.9% when using RAID-CRC Screen and 9.5% with FIT20 alone, and the negative predictive value was 99.8% in the two scenarios. For advanced neoplasia detection, the use of RAID-CRC Screen yielded significantly lower sensitivity than with FIT20 alone (17.5% vs. 21.8%, p = 0.0009), and the overall specificity was significantly higher when using RAID-CRC Screen compared with FIT20 alone (98.2% vs. 97.8%, p = 0.0039). Our findings confirm the results obtained in previous clinical studies in a CRC screening setting, showing the potential of RAID-CRC Screen to increase the overall specificity of FIT-based screening.

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU.

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-×¥-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18−20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50−0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66−0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20−22%] vs. 14% [95% CI 13−16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.

A case report of gastrointestinal histoplasmosis in a patient treated with infliximab.

Histoplasmosis is an endemic mycosis in some areas of North and South America. This disease is usually asymptomatic, but it can result in severe and disseminated infection involving gastrointestinal tract, especially in immunocompromised individuals. We report a case of a 33-years-old Ecuadorian male treated with infliximab who developed disseminated histoplasmosis with gastrointestinal affection. Due to the non-specific presentation of gastrointestinal histoplasmosis, the diagnosis is often delayed and it causes poor outcomes. It is important to consider this diagnosis in immunocompromised patients with compatible symptoms, like patients on TNF inhibitors.

A Novel Grape-Derived Prebiotic Selectively Enhances Abundance and Metabolic Activity of Butyrate-Producing Bacteria in Faecal Samples.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) patients have different faecal microbiota profiles compared to healthy controls. Prebiotics intake influences intestinal microbiota composition which in turn influence the growth of short-chain fatty acids (SCFA) producing bacteria. This study aimed to evaluate the capacity of Previpect, a new prebiotic obtained from grapes fibre, to balance the dysbiosis found in patients with intestinal disorders. This was achieved through the analysis of specific bacterial markers and SCFA production using an in vitro fermentation system and comparing the obtained results with those obtained with other commercial prebiotics. Fresh faecal samples from patients with IBD (N = 6), IBS (N = 3), and control subjects (N = 6) were used. Previpect showed high fermentative ability enabling the growth of butyrate producing bacteria and increasing SCFA concentration up to 2.5-fold. Previpect is a promising prebiotic which may be used as a therapeutic strategy towards promotion of intestinal microbiota restoration, microbial healing, and as a preventive supplement for healthy individuals.

RAID Prediction: Pilot Study of Fecal Microbial Signature With Capacity to Predict Response to Anti-TNF Treatment.

BACKGROUND AND AIMS: Crohn's disease and ulcerative colitis evolve with alternate outbreaks and remissions of variable duration in both cases. Despite the advances, about 10-30% of patients do not respond to the treatment after the induction period. Besides, between 20% to 50% further patients need an optimization of the dose to respond the treatment. Recent studies have pointed gut microbiota can play a role in the anti-TNF treatment response. This study aimed to define a bacterial signature that could be used to predict the response of patients to anti-TNF treatment. METHODS: There were obtained 38 stool samples from 38 IBD patients before starting anti-TNF treatments: Adalimumab, Golimumab or Infliximab. Patients were differentiated in 2 groups: responders and non-responders to biological treatment. From each sample, DNA was purified and used in a qPCR for the quantification of the 8 microbial markers. RESULTS: In this proof of concept, the predictive ability to identify anti-TNF treatment responders was analyzed. An algorithm consisting in the combination of 4 bacterial markers showed a high capacity to discriminate between responders and non- responders. The algorithm proved high sensitivity and specificity reporting values of 93.33% and 100% respectively, with a positive predictive value of 100% and a negative predictive value of 75% for predicting response to biologic treatment. CONCLUSIONS: A specific bacterial signature could beneficiate patients with inflammatory bowel disease predicting the therapeutic effectiveness of an anti-TNF treatment, leading to a personalized therapy, improving the patients' quality of life, saving costs and gaining time in patient improvement.

This study aimed to define a microbial signature that could be used to predict the response of patients to anti-TNF treatment in inflammatory bowel disease. An algorithm consisting in the combination of 4 bacterial markers showed a high capacity to discriminate between responders and nonresponders.

In vitro Prebiotic Effect of Bread-Making Process in Inflammatory Bowel Disease Microbiome.

Inflammatory bowel disease (IBD), including its two main categories (Crohn's disease and ulcerative colitis), has been linked both to gut microbiota and to diet. Bread is a daily food that has a potential capacity as a prebiotic. Our aim was to evaluate different bread-making processes and their effect on fecal colonic microbiota in IBD patients. The microbial composition of several sourdoughs and dough samples was analyzed by high-throughput sequencing of 16S and 18S rRNA genes. Three types of bread, which followed different bread-making processes, were in vitro digested and incubated with feces from IBD patients. Changes in gut microbiota were assessed by a quantitative polymerase chain reaction using specific bacterial sequence targets. Short-chain fatty acid production was also analyzed by gas chromatography. Lactobacillus sanfranciscensis was the dominant lactic acid bacteria species found in sourdough and bread doughs prepared using sourdough, whereas Saccharomyces cerevisiae was the most dominant yeast in all groups, especially in bread doughs before baking. Differences in microbial composition in raw bread doughs were more related to the type of dough and elaboration than to fermentation time lengths. The analysis of in vitro fecal incubations with bread conditions revealed an increase in most bacterial groups analyzed and short-chain fatty acid production, both in Crohn's disease and ulcerative colitis samples. Most remarkable increases in short-chain fatty acid production mirrored higher abundances of Roseburia species. The potential prebiotic properties observed were mainly obtained when using a high quantity of bread, regardless of bread type. Overall, this study highlights the bacterial dynamics within the bread-making process and the potential prebiotic effect in IBD patients.

Evaluation of bacterial biomarkers to aid in challenging inflammatory bowel diseases diagnostics and subtype classification.

BACKGROUND: The challenges for inflammatory bowel disease (IBD) diagnostics are to discriminate it from gut conditions with similar symptoms such as irritable bowel syndrome (IBS), to distinguish IBD subtypes, to predict disease progression, and to establish the risk to develop colorectal cancer (CRC). Alterations in gut microbiota have been proposed as a source of information to assist in IBD diagnostics. Faecalibacterium prausnitzii (F. prausnitzii), its phylogroups, and Escherichia coli (E. coli) have been reported as potential biomarkers, but their performance in challenging IBD diagnostic situations remains elusive. We hypothesize that bacterial biomarkers based in these species may help to discriminate these conditions of complex diagnostics. AIM: To evaluate the usefulness of indices calculated from the quantification of these species as biomarkers to aid in IBD diagnostics. METHODS: A retrospective study of 131 subjects (31 controls (H); 45 Crohn's disease (CD), 25 ulcerative colitis (UC), 10 IBS, and 20 CRC patients) was performed to assess the usefulness of bacterial biomarkers in biopsies. Further, the performance of biomarkers in faeces was studied in 29 stool samples (19 CD, 10 UC). Relative abundances of total F. prausnitzii (FP), its phylogroups (PHGI and PHGII), and E. coli (E) quantification were determined by qPCR. Loads were combined to calculate the FP-E index, the PHGI-E index and the PHGII-E index. Biomarkers accuracy to discriminate among conditions was measured by the area under the receiver operating characteristic curve (AUC). RESULTS: In biopsies, FP-E index was good for discriminating IBS from CD (AUC = 0.752) while PHGII-E index was suitable for discriminating IBS from UC (AUC = 0.632). The FP-E index would be the choice to discriminate IBD from CRC, especially from all UC subtypes (AUC ≥ 0.875), regardless of the activity status of the patient. Discrimination between UC patients that had the longest disease duration and those with CRC featured slightly lower AUC values. Concerning differentiation in IBD with shared location, PHGI-E index can establish progression from proctitis and left-sided colitis to ulcerative pancolitis (AUC ≥ 0.800). PHG I-E index analysis in tissue would be the choice to discriminate within IBD subtypes of shared location (AUC ≥ 0.712), while in non-invasive faecal samples FP or PHGI could be good indicators (AUC ≥ 0.833). CONCLUSION: F. prausnitzii phylogroups combined with E. coli offer potential to discriminate between IBD and CRC patients and can assist in IBD subtypes classification, which may help in solving IBD diagnostics challenges.

New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population.

Guidelines recommend routine screening for colorectal cancer (CRC) in asymptomatic adults starting at age 50. The most extensively used noninvasive test for CRC screening is the fecal immunochemical test (FIT), which has an overall sensitivity for CRC of approximately 61.0%-91.0%, which drops to 27.0%-67.0% for advanced adenomas. These figures contain a high false-positive rate and a low positive predictive value. This work aimed to develop a new, noninvasive CRC screening tool based on fecal bacterial markers capable of decreasing FIT false-positive rates in a FIT-positive population. We defined a fecal bacterial signature (RAID-CRC Screen) in a proof-of-concept with 172 FIT-positive individuals and validated the obtained results on an external cohort of 327 FIT-positive subjects. All study participants had joined the national CRC screening program. In the clinical validation of RAID-CRC Screen, a sensitivity of 83.9% and a specificity of 16.3% were obtained for the detection of advanced neoplasm lesions (advanced adenomas and/or CRC). FIT 20 µg/g produced 184 false-positive results. Using RAID-CRC Screen, this value was reduced to 154, thus reducing the false-positive rate by 16.3%. The RAID-CRC Screen test could be implemented in CRC screening programs to allow a significant reduction in the number of colonoscopies performed unnecessarily for FIT-positive participants of CRC screening programs.

Impact of comorbidities on anti-TNFα response and relapse in patients with inflammatory bowel disease: the VERNE study.

Objective: To evaluate the impact of comorbidities and extraintestinal manifestations of inflammatory bowel disease on the response of patients with inflammatory bowel disease to antitumour necrosis factor alpha (anti-TNFα) therapy. Design: Data from 310 patients (194 with Crohn's disease and 116 with ulcerative colitis) treated consecutively with the first anti-TNFα in 24 Spanish hospitals were retrospectively analysed. Univariate and multivariate logistic regression analyses were performed to assess the associations between inflammatory bowel disease comorbidities and extraintestinal manifestations with anti-TNFα treatment outcomes. Key clinical features, such as type of inflammatory bowel disease and concomitant treatments, were included as fixed factors in the model. Results: Multivariate logistic regression analyses (OR, 95% CI) showed that chronic obstructive pulmonary disease (2.67, 1.33 to 5.35) and hepato-pancreato-biliary diseases (1.87, 1.48 to 2.36) were significantly associated with primary non-response to anti-TNFα, as was the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease). It was also found that myocardial infarction (3.30, 1.48 to 7.35) and skin disease (2.73, 1.42 to 5.25) were significantly associated with loss of response, along with the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease). Conclusions: Our results suggest that the presence of some comorbidities in patients with inflammatory bowel disease, such as chronic obstructive pulmonary disease and myocardial infarction, and of certain extraintestinal manifestations of inflammatory bowel disease, such as hepato-pancreato-biliary conditions and skin diseases, appear to be related to failure to anti-TNFα treatment. Therefore, their presence should be considered when choosing a treatment. Trial registration number: NCT02861118.

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry.

BACKGROUND: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. METHODS: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. RESULTS: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. CONCLUSIONS: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Biofilm formation as a novel phenotypic feature of adherent-invasive Escherichia coli (AIEC).

BACKGROUND: Crohn's disease (CD) is a high morbidity chronic inflammatory disorder of unknown aetiology. Adherent-invasive Escherichia coli (AIEC) has been recently implicated in the origin and perpetuation of CD. Because bacterial biofilms in the gut mucosa are suspected to play a role in CD and biofilm formation is a feature of certain pathogenic E. coli strains, we compared the biofilm formation capacity of 27 AIEC and 38 non-AIEC strains isolated from the intestinal mucosa. Biofilm formation capacity was then contrasted with the AIEC phenotype, the serotype, the phylotype, and the presence of virulence genes. RESULTS: Specific biofilm formation (SBF) indices were higher amongst AIEC than non-AIEC strains (P = 0.012). In addition, 65.4% of moderate to strong biofilms producers were AIEC, whereas 74.4% of weak biofilm producers were non-AIEC (P = 0.002). These data indicate that AIEC strains were more efficient biofilm producers than non-AIEC strains. Moreover, adhesion (P = 0.009) and invasion (P = 0.003) indices correlated positively with higher SBF indices. Additionally, motility (100%, P < 0.001), H1 type flagellin (53.8%, P < 0.001), serogroups O83 (19.2%, P = 0.008) and O22 (26.9%, P = 0.001), the presence of virulence genes such as sfa/focDE (38.5%, P = 0.003) and ibeA (26.9%, P = 0.017), and B2 phylotype (80.8%, P < 0.001) were frequent characteristics amongst biofilm producers. CONCLUSION: The principal contribution of the present work is the finding that biofilm formation capacity is a novel, complementary pathogenic feature of the recently described AIEC pathovar. Characterization of AIEC specific genetic determinants, and the regulatory pathways, involved in biofilm formation will likely bring new insights into AIEC pathogenesis.

Reduction of faecal immunochemical test false-positive results using a signature based on faecal bacterial markers.

BACKGROUND: Colorectal cancer is the second commonest cause of cancer mortality. Some countries are implementing colorectal cancer screening to detect lesions at an early stage using non-invasive tools like the faecal immunochemical test. Despite affordability, this test shows a low sensitivity for precancerous lesions and a low positive predictive value for colorectal cancer, resulting in a high false-positive rate. AIM: To develop a new, non-invasive colorectal cancer screening tool based on bacterial faecal biomarkers, which in combination with the faecal immunochemical test, could allow a reduction in the false-positive rate. This tool is called risk assessment of intestinal disease for colorectal cancer (RAID-CRC). METHODS: We performed both the faecal immunochemical test and the bacterial markers analysis (RAID-CRC test) in stool samples from individuals with normal colonoscopy (167), non-advanced adenomas (88), advanced adenomas (30) and colorectal cancer (48). All the participants showed colorectal cancer-associated symptoms. RESULTS: Performance of the faecal immunochemical test for advanced neoplasia (ie advanced adenoma and colorectal cancer) was determined by using the cut-off value established in Catalonia (20 µg haemoglobin/g of faeces) for a population-based screening approach. Sensitivity and specificity values of 83% and 80%, respectively, and positive and negative predictive values of 56% and 94%, respectively, were obtained. When both the immunological and the biological analysis were combined, the corresponding values were 80% and 90% for sensitivity and specificity, respectively, and 70% and 94% for positive and negative predictive values, respectively, resulting in a 50% reduction of the false-positive rate. CONCLUSIONS: RAID-CRC test allows a substantial reduction in the faecal immunochemical test false-positive results (50%) in a symptomatic population. Further validation is indicated in a colorectal cancer-screening scenario.