Comparative efficacy and safety of subcutaneous infliximab and vedolizumab in patients with Crohn's disease and ulcerative colitis included in randomised controlled trials.

BACKGROUND: While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. AIM: Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. METHODS: Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. RESULTS: We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. CONCLUSION: IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.

Food additives impair gut microbiota from healthy individuals and IBD patients in a colonic in vitro fermentation model.

Intestinal fibrosis is a long-term complication of inflammatory bowel diseases (IBD). Changes in microbial populations have been linked with the onset of fibrosis and some food additives are known to promote intestinal inflammation facilitating fibrosis induction. In this study, we investigated how polysorbate 80, sucralose, titanium dioxide, sodium nitrite and maltodextrin affect the gut microbiota and the metabolic activity in healthy and IBD donors (patients in remission and with a flare of IBD). The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) with a static (batch) configuration was used to evaluate the effects of food additives on the human intestinal microbiota. Polysorbate 80 and sucralose decreased butyrate-producing bacteria such as Roseburia and Faecalibacterium prausnitzii. Both compounds, also increased bacterial species positively correlated with intestinal inflammation and fibrosis (i.e.: Enterococcus, Veillonella and Mucispirillum schaedleri), especially in donors in remission of IBD. Additionally, polysorbate 80 induced a lower activity of the aryl hydrocarbon receptor (AhR) in the three groups of donors, which can affect the intestinal homeostasis. Maltodextrin, despite increasing short-chain fatty acids production, promoted the growth of Ruminococcus genus, correlated with higher risk of fibrosis, and decreased Oscillospira which is negatively associated with fibrosis. Our findings unveil crucial insights into the potential deleterious effects of polysorbate 80, sucralose and maltodextrin on human gut microbiota in healthy and, to a greater extent, in IBD patients.

Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn's Disease Regardless of Prior Biologic Exposure.

BACKGROUND & AIMS: Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849], U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease. Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status. METHODS: Patients were randomized to placebo or upadacitinib 45 mg (UPA45) for 12 weeks (induction). UPA45 clinical responders were enrolled in U-ENDURE and rerandomized to placebo, upadacitinib 15 mg, or upadacitinib 30 mg (UPA30) for 52 weeks. Assessments were by prior biologic failure. RESULTS: Of 1021 patients, 733 (71.8%) had prior biologic failure. Across outcomes and subgroups, upadacitinib-treated patients achieved higher rates vs placebo. During induction, upadacitinib had higher rates vs placebo for clinical remission based on stool frequency/abdominal pain score (without failure: 54.0% vs 28.3%; with failure: 42.2% vs 14.1%) and endoscopic response (without failure: 52.0% vs 16.2%; with failure: 35.7% vs 5.3%). In maintenance, the greatest treatment effect (upadacitinib vs placebo) was among patients with prior biologic failure treated with UPA30 (clinical remission without failure: 58.5% vs 32.7%; with failure: 42.5% vs 8.7%; endoscopic response without failure: 43.9% vs 17.9%; with failure: 38.9% vs 4.0%). Patients without vs with prior biologic failure had fewer adverse events. CONCLUSIONS: Upadacitinib led to higher absolutes rates of clinical and endoscopic outcomes in patients without vs with prior biologic failure. Patients treated with upadacitinib achieved greater rates of clinical and endoscopic improvements vs placebo, regardless of prior biologic exposure. CLINICALTRIALS: gov: NCT03345849, NCT03345836, NCT03345823.

Matrix gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in crohn's disease.

BACKGROUND: The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn's disease (CD) patients. METHODS: The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn's Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9 CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and Lémann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected. RESULTS: A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75 CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age (p = 0.0032), disease duration (p = 0.0033), corticosteroids use (p = 0.019) and tended to increase in patients with intestinal strictures (p = 0.086) but not with the Lémann index. CONCLUSION: The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.

Sodium fluoride preserves blood metabolite integrity for biomarker discovery in large-scale, multi-site metabolomics investigations.

Background: Metabolite profiling of blood by nuclear magnetic resonance (NMR) is invaluable to clinical biomarker discovery. To ensure robustness, biomarkers require validation in large cohorts and across multiple centres. However, collection procedures are known to impact on the stability of biofluids that may, in turn, degrade biomarker signals. We trialled three blood collection tubes with the aim of solving technical challenges due to preanalytical variation in blood metabolite levels that are common in cohort studies. Methods: We first investigated global NMR-based metabolite variability between biobanks, including the large-scale UK Biobank and TwinsUK biobank of the general UK population, and more targeted biobanks derived from multicentre clinical trials relating to inflammatory bowel disease. We then compared the blood metabolome of 12 healthy adult volunteers when collected into either sodium fluoride/potassium oxalate, lithium heparin, or serum blood tubes using different pre-processing parameters. Results: Preanalytical variation in the method of blood collection strongly influences metabolite composition within and between biobanks. This variability can largely be attributed to glucose and lactate. In the healthy control cohort, the fluoride oxalate collection tube prevented fluctuation in glucose and lactate levels for 24 hours at either 4 °C or room temperature (20 °C). Conclusions: Blood collection into a fluoride oxalate collection tube appears to preserve the blood metabolome with delayed processing up to 24 hours at 4 °C. This method may be considered as an alternative when rapid processing is not feasible.

In-Depth Assessment of Endoscopic Remission in Inflammatory Bowel Disease Treated by Anti-TNF or Vedolizumab.

BACKGROUND AND AIMS: Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in inflammatory bowel disease. However, most of these studies were performed on patients still having incomplete mucosal healing. Our aim was to disclose persisting endomicroscopic anomalies in patients with full endoscopic remission and to compare them between vedolizumab- and anti-tumor necrosis factor-treated patients. METHODS: We screened patients with Crohn's disease (CD) or ulcerative colitis (UC) treated for more than 6 months with biologic therapy, and being in steroid-free clinical and biological remission. White light endoscopy and probe-based confocal laser endomicroscopy (pCLE) analysis were performed in the ileum, right colon, transverse colon, left colon, and rectum. Full endoscopic remission was defined by a Mayo endoscopic score of 0 in UC and no remaining ulcer or erosion in CD. Patients were prospectively followed up and clinical relapses were recorded. RESULTS: Seventy-two CD and UC patients treated by biologic therapy and in clinical and biological remission were screened. A total of 37 were also in full endoscopic remission and were included in our study; 183 intestinal segments were analyzed. We found residual pCLE anomalies in most of the patients. These anomalies were not significantly associated with any demographic or clinical characteristic including the treatment received, nor were they associated with histological parameters, levels of C-reactive protein or fecal calprotectin. Among the 37 patients, 7 (18.9%) relapsed over a median follow-up of 33.7 months. The risk of relapse was not associated with any clinical, biological, histologic, or pCLE feature at baseline. CONCLUSION: Despite endoscopic, biological, and even histological remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-tumor necrosis factor- and vedolizumab-treated patients. The clinical significance of these anomalies remains to be clarified.

We studied the abnormalities found by confocal endomicroscopy in patients with chronic inflammatory disease in deep endoscopic remission under immunosuppressive treatment. Relapse was not associated with the abnormalities found, which, although numerous, remain of unknown significance.

Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study.

BACKGROUND & AIMS: Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). METHODS: This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. RESULTS: In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P = .001), patients treated with vedolizumab (P = .001), patients with moderate endoscopic disease activity (P = .002), and a body mass index <25 kg/m2 (P = .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P = .006). No new safety signals were observed. CONCLUSIONS: Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.

[Iatrogenic colitis following immunotherapy : monocentric retrospective study at the University Hospital of Liège]. / Colites iatrogènes sur immunothérapie : étude rétrospective au CHU de Liège.

Checkpoint inhibitor colitis is a complication that is often underestimated when it is slow-grade, and results in relatively few hospital admissions compared to its frequency of occurrence. A strict history-taking approach, combined with an endoscopic work-up in cases of severity, is recommended. The use of the fecal calprotectin may also be useful. When used appropriately, the various lines of treatment are generally effective, and second-line therapies (biotherapies) are rarely used. However, recent evidence suggests that patients with severe symptoms should be treated more rapidly with biological therapies, especially if severity is endoscopically confirmed, as corticosteroids carry a greater risk of infection. The objective of this study is to demonstrate the efficacy of non-symptomatic, first and second line therapies for immunotherapy-related colitis in a population of patients at the CHU of Liège.

La colite iatrogène sur immunothérapie est une complication souvent sous-évaluée lorsqu'elle est de bas grade et entraîne relativement peu d'hospitalisations par rapport à sa fréquence d'apparition. Une approche stricte au niveau de l'anamnèse, combinée à un bilan endo-scopique en cas de gravité, est conseillée. La mesure de la calprotectine fécale peut également s'avérer utile. Les différentes lignes de traitement sont, en cas d'utilisation adéquate, le plus souvent efficaces et les deuxièmes lignes (biothérapies) ne sont que rarement utilisées. Cependant, de récentes données conseillent une utilisation plus rapide des traitements biologiques chez les patients ayant un tableau sévère, surtout si celui-ci est confirmé au niveau endoscopique, car les corticoïdes entrainent un risque majoré de surinfection. L'objectif de ce travail est de démontrer l'efficacité des traitements non symptomatiques de 1ère et de 2ème lignes dans le cadre de colites liées aux immunothérapies sur une population de patients du CHU de Liège.

Early heart rate variability changes during acute fetal inflammatory response syndrome: An experimental study in a fetal sheep model.

INTRODUCTION: Fetal infection during labor with fetal inflammatory response syndrome (FIRS) is associated with neurodevelopmental disabilities, cerebral palsy, neonatal sepsis, and mortality. Current methods to diagnose FIRS are inadequate. Thus, the study aim was to explore whether fetal heart rate variability (HRV) analysis can be used to detect FIRS. MATERIAL AND METHODS: In chronically instrumented near-term fetal sheep, lipopolysaccharide (LPS) was injected intravenously to model FIRS. A control group received saline solution injection. Hemodynamic, blood gas analysis, interleukin-6 (IL-6), and 14 HRV indices were recorded for 6 h. In both groups, comparisons were made between the stability phase and the 6 h following injection (H1-H6, respectively) and between LPS and control groups. RESULTS: Fifteen lambs were instrumented. In the LPS group (n = 8), IL-6 increased significantly after LPS injection (p < 0.001), confirming the FIRS model. Fetal heart rate increased significantly after H5 (p < 0.01). In our FIRS model without shock or cardiovascular decompensation, five HRV measures changed significantly after H2 until H4 in comparison to baseline. Moreover, significant differences between LPS and control groups were observed in HRV measures between H2 and H4. These changes appear to be mediated by an increase of global variability and a loss of signal complexity. CONCLUSION: As significant HRV changes were detected before FHR increase, these indices may be valuable for early detection of acute FIRS.

Gut Microbiota Associated with Clostridioides difficile Carriage in Three Clinical Groups (Inflammatory Bowel Disease, C. difficile Infection and Healthcare Workers) in Hospital Field.

Clostridioides difficile is an anaerobic spore-forming Gram-positive bacterium. C. difficile carriage and 16S rDNA profiling were studied in three clinical groups at three different sampling times: inflammatory bowel disease (IBD) patients, C. difficile infection (CDI) patients and healthcare workers (HCWs). Diversity analysis was realized in the three clinical groups, the positive and negative C. difficile carriage groups and the three analysis periods. Concerning the three clinical groups, ß-diversity tests showed significant differences between them, especially between the HCW group and IBD group and between IBD patients and CDI patients. The Simpson index (evenness) showed a significant difference between two clinical groups (HCWs and IBD). Several genera were significantly different in the IBD patient group (Sutterella, Agathobacter) and in the CDI patient group (Enterococcus, Clostridioides). Concerning the positive and negative C. difficile carriage groups, ß-diversity tests showed significant differences. Shannon, Simpson and InvSimpson indexes showed significant differences between the two groups. Several genera had significantly different relative prevalences in the negative group (Agathobacter, Sutterella, Anaerostipes, Oscillospira) and the positive group (Enterococcus, Enterobacteriaceae_ge and Enterobacterales_ge). A microbiota footprint was detected in C. difficile-positive carriers. More experiments are needed to test this microbiota footprint to see its impact on C. difficile infection.

Analysis of Clinical Trial Screen Failures in Inflammatory Bowel Diseases (IBD): Real World Results from the International Organization for the study of IBD.

BACKGROUND: Recruitment for randomized controlled trials (RCTs) in IBD have substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicenter phase IIb-III RCTs. METHODS: All IOIBD members (n=58) were invited to participate. We divided barriers to participation as follow: 1) reasons patients with active IBD were not deemed appropriate for a RCT; 2) reasons qualified patients did not wish to participate; 3) reasons for screen failure (SF) in patients agreeing to participate. We assess those in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF. RESULTS: A total of 106 patients (60 male (56.6%), 63 Crohn's disease [CD] (59.4%)), from 10 centers across the world, were included in the prospective study. A RCT has not been proposed to 65 of them (mainly due to eligibility criteria). Of the 41 patients to whom a RCT was offered, 8 refused (mainly due to reluctance to receive placebo) and 28 agreed to participate. Among these 28 patients, 5 failed their screening and 23 were finally included in a RCT. A total of 107 patients (61 male (57%), 67 CD (62.6%)), from 13 centers worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity. CONCLUSION: This first multicenter study analyzing reasons for non-enrollment in IBD RCTs shown that we lose patients at each step. Eligibility criteria, the risk of placebo assignment and insufficient disease activity were part of the main barriers.

Correlations for untargeted GC × GC-HRTOF-MS metabolomics of colorectal cancer.

INTRODUCTION: Modern comprehensive instrumentations provide an unprecedented coverage of complex matrices in the form of high-dimensional, information rich data sets. OBJECTIVES: In addition to the usual biomarker research that focuses on the detection of the studied condition, we aimed to define a proper strategy to conduct a correlation analysis on an untargeted colorectal cancer case study with a data set of 102 variables corresponding to metabolites obtained from serum samples analyzed with comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC × GC-HRTOF-MS). Indeed, the strength of association existing between the metabolites contains potentially valuable information about the molecular mechanisms involved and the underlying metabolic network associated to a global perturbation, at no additional analytical effort. METHODS: Following Anscombe's quartet, we took particular attention to four main aspects. First, the presence of non-linear relationships through the comparison of parametric and non-parametric correlation coefficients: Pearson's r, Spearman's rho, Kendall's tau and Goodman-Kruskal's gamma. Second, the visual control of the detected associations through scatterplots and their associated regressions and angles. Third, the effect and handling of atypical samples and values. Fourth, the role of the precision of the data on the attribution of the ranks through the presence of ties. RESULTS: Kendall's tau was found the method of choice for the data set at hand. Its application highlighted 17 correlations significantly altered in the active state of colorectal cancer (CRC) in comparison to matched healthy controls (HC), from which 10 were specific to this state in comparison to the remission one (R-CRC) investigated on distinct patients. 15 metabolites involved in the correlations of interest, on the 25 unique ones obtained, were annotated (Metabolomics Standards Initiative level 2). CONCLUSIONS: The metabolites highlighted could be used to better understand the pathology. The systematic investigation of the methodological aspects that we expose allows to implement correlation analysis to various fields and many specific cases.

Impact of Dietary Patterns in Inflammatory Bowel Disease Subtypes Versus Healthy Subjects: a Retrospective Cohort Study.

Objectives:Inflammatory bowel diseases (IBD) have been associated with multiple environmental factors, including diet. A dietary pattern characterized by low fiber content, high fat content and high carbohydrate content has been linked to the development of IBD. The objective of the current investigation is to examine the potential link between dietary patterns and the occurrence of IBD and to investigate whether there are any differences in relation to the type of IBD and specific food groups. Material and methods:We conducted an observational retrospective comparative study using three cohorts: 89 Crohn's disease (CD) patients, 40 ulcerative colitis (UC) patients and 64 healthy subjects. All participants underwent structured interviews and were required to complete a questionnaire regarding their dietary habits either prior to the onset of IBD or within the last year for control subjects. Results:A higher proportion of CD patients reported a higher rate of salt intake (71.9% vs. 53.1%, p-value = 0.043), sweetened beverages (38.2% vs. 17.2%, p-value=0.022), processed meat (66.3% vs. 40.6%, p-value=0.007), fatty meat (50.6% vs. 28.1%, p-value=0.021), fried foods (47.2% vs. 9.4%, p-value<0.001) and mayonnaise (21.3% vs. 6.2%, p-value=0.032) and a lower intake of nuts and seeds (20.2% vs. 43.8%, p-value=0.004) and yogurt (23.6% vs. 43.8%, p-value=0.030) compared to healthy subjects. Compared to controls, in the UC group there was a higher consumption of salt (85% vs. 53.1%, p-value=0.003), sweetened beverages (47.5% vs. 17.2%, p-value=0.005), fatty meat (55% vs. 28.1%, p-value=0.025) and fried foods (55% vs. 9.4%, p-value<0.001) and a lower intake of nuts and seeds (10% vs. 43.8%, p-value=0.001). Conclusion:Diet patterns before the onset of the disease are similar in patients with Crohn's disease and patients with ulcerative colitis: increased consumption of sweetened beverages, processed and fatty meat, fried food, salt, store-bought ice cream, and mayonnaise, and decreased intake of seeds, nuts, and yogurt.

Stemming the tide with ileocecal Crohn's disease: when is pharmacotherapy enough?

INTRODUCTION: Crohn's disease (CD) mostly affects the terminal ileum and ileocecal region and up to 80% of patients end up requiring surgery. Previously reserved for complicated or refractory forms, surgery is now considered as an alternative to medical treatment in localized ileocecal disease. AREAS COVERED: This review examines factors associated with response to medical treatment and those associated with the need for surgery in ileocecal CD to identify the patients' profile for whom pharmacotherapy might be enough. Factors associated with the recurrence and the postoperative complications are also reviewed to help the clinician identify patients for whom medical therapy might be preferred. EXPERT'S OPINION: LIR!C study long-term follow-up data show that 38% of infliximab-treated patients were still treated with infliximab at the end of their follow-up, while 14% had switched to another biologic or had received immunomodulator or corticosteroid and 48% had CD-related surgery. Only the combination with an immunomodulator was associated with a greater likelihood of continuing infliximab. Patients with ileocecal CD for whom pharmacotherapy might be sufficient are probably those with no risk factors for CD-related surgery.In addition, patients with high risk of recurrence or of post-operative complications may benefit more from medical treatment than from surgery.

[Functional colopathy : still relevant ? Let's move to irritable bowel syndrome]. / La colopathie fonctionnelle : toujours d'actualité ? Place au syndrome de l'intestin irritable.

Irritable bowel syndrome is a functional disorder that is frequently encountered in general practice as well as in specialized consultations. Diagnostic criteria have been well established but there is currently no specific diagnostic test. The various gastroenterology societies have recently published recommendations for diagnostic and therapeutic management adapted to the pathophysiology and the availability of treatments in different countries. This article summarizes the main lines of these recommendations and in particular those of the Belgian consensus.

Le syndrome de l'intestin irritable est un trouble fonctionnel fréquemment rencontré en médecine générale comme en consultation spécialisée. Les critères diagnostiques ont bien été établis, mais il n'y a actuellement pas de test diagnostique spécifique. Les différentes sociétés de gastroentérologie ont récemment publié des recommandations pour une prise en charge diagnostique et thérapeutique adaptée à la physiopathologie, mais aussi à la disponibilité des traitements selon les pays. Cet article résume les grandes lignes de ces recommandations et, en particulier, celles du consensus belge.

Comparison of Early Postoperative Outcomes for Vaginal Anterior Sacrospinous Ligament Fixation with or without Transvaginal Mesh Insertion.

Pelvic organ prolapse affects one in three women, and cystocele accounts for 80% of the indications for surgery. Following the withdrawal of transvaginal mesh from the market, the objective of the present before-and-after study was to compare of the previous reference technique (UpholdTM (Boston Scientific, Marlborough, MA, USA) mesh insertion) with anterior sacrospinous ligament fixation with suturing in terms of the outcomes 2 months after surgery. We performed a retrospective, observational, before-and-after study at Lille University Medical Center (Lille, France) by including consecutive patients operated on between 2011 and 2018 for UpholdTM mesh insertion and between 2018 to 2020 for anterior sacrospinous ligament fixation. The primary outcome was the early recurrence of prolapse, and the secondary outcomes were the occurrence of early per-operative or post-operative complications and the development of de novo stress urinary incontinence. Here, 466 patients were included in the study (382 in the UpholdTM group and 84 in the anterior sacrospinous ligament fixation group). The failure rate at 2 months was 6.0% (5 out of 84) for anterior sacrospinous ligament fixation and 1.3% (5 out of 382) for UpholdTM (p < 0.01). The prevalence of acute urinary retention was significantly lower in the anterior sacrospinous ligament fixation group (3.6%) than in the UpholdTM group (14.1%; p < 0.01), as was the de novo stress urinary incontinence rate (11.9% vs. 33.8%, respectively; p < 0.01). Anterior sacrospinous ligament fixation appears to be an effective, safe alternative to mesh insertion in the management of cystocele via the vaginal approach; the early complication rate was slightly lower, but the early failure rate was slightly higher.

Comprehensive Insight into Colorectal Cancer Metabolites and Lipids for Human Serum: A Proof-of-Concept Study.

Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths. The current endoscopic-based or stool-based diagnostic techniques are either highly invasive or lack sufficient sensitivity. Thus, there is a need for less invasive and more sensitive screening approaches. We, therefore, conducted a study on 64 human serum samples representing three different groups (adenocarcinoma, adenoma, and control) using cutting-edge GC×GC-LR/HR-TOFMS (comprehensive two-dimensional gas chromatography coupled with low/high-resolution time-of-flight mass spectrometry). We analyzed samples with two different specifically tailored sample preparation approaches for lipidomics (fatty acids) (25 µL serum) and metabolomics (50 µL serum). In-depth chemometric screening with supervised and unsupervised approaches and metabolic pathway analysis were applied to both datasets. A lipidomics study revealed that specific PUFA (ω-3) molecules are inversely associated with increased odds of CRC, while some PUFA (ω-6) analytes show a positive correlation. The metabolomics approach revealed downregulation of amino acids (alanine, glutamate, methionine, threonine, tyrosine, and valine) and myo-inositol in CRC, while 3-hydroxybutyrate levels were increased. This unique study provides comprehensive insight into molecular-level changes associated with CRC and allows for a comparison of the efficiency of two different analytical approaches for CRC screening using same serum samples and single instrumentation.

Defining Biological Remission in Crohn's Disease: Interest, Challenges and Future Directions.

In Crohn's disease, the treat-to-target strategy has been greatly encouraged and has become a standard of care. In this context, defining the target [remission] constitutes a major stake and is fuelling the literature. Currently, clinical remission [symptom control] is no longer the only objective of treatments since it does not allow to closely control inflammation-induced tissue damage. The introduction of endoscopic remission as a therapeutic target clearly represented progress but this examination remains invasive, costly, not well accepted by patients and does not allow tight control of disease activity. More fundamentally, morphological techniques [e.g. endoscopy, histology, ultrasonography] are limited since they do not evaluate the biological activity of the disease but only its consequences. Besides, emerging evidence suggests that biological signs of disease activity could better guide treatment decisions than clinical parameters. In this context, we stress the necessity to define a novel treatment target: biological remission. Based on our previous work, we propose a conceptual definition of biological remission which goes beyond the classical normalization of inflammatory markers [C-reactive protein and faecal calprotectin]: absence of biological signs associated with the risk of short-term relapse and mid-/long-term relapse. The risk of short-term relapse seems essentially to be characterized by a persistent inflammatory state while the risk of mid-/long-term relapse implies a more heterogeneous biology. We discuss the value of our proposal [guiding treatment maintenance, escalation or de-escalation] but also the fact that its clinical implementation would require overcoming major challenges. Finally, future directions are proposed to better define biological remission.

Precision medicine and drug optimization in adult inflammatory bowel disease patients.

Inflammatory bowel diseases (IBD) encompass two main entities including ulcerative colitis and Crohn's disease. Although having a common global pathophysiological mechanism, IBD patients are characterized by a significant interindividual heterogeneity and may differ by their disease type, disease locations, disease behaviours, disease manifestations, disease course as well as treatment needs. Indeed, although the therapeutic armamentarium for these diseases has expanded rapidly in recent years, a proportion of patients remains with a suboptimal response to medical treatment due to primary non-response, secondary loss of response or intolerance to currently available drugs. Identifying, prior to treatment initiation, which patients are likely to respond to a specific drug would improve the disease management, avoid unnecessary side effects and reduce the healthcare expenses. Precision medicine classifies individuals into subpopulations according to clinical and molecular characteristics with the objective to tailor preventative and therapeutic interventions to the characteristics of each patient. Interventions would thus be performed only on those who will benefit, sparing side effects and expense for those who will not. This review aims to summarize clinical factors, biomarkers (genetic, transcriptomic, proteomic, metabolic, radiomic or from the microbiota) and tools that could predict disease progression to guide towards a step-up or top-down strategy. Predictive factors of response or non-response to treatment will then be reviewed, followed by a discussion about the optimal dose of drug required for patients. The time at which these treatments should be administered (or rather can be stopped in case of a deep remission or in the aftermath of a surgery) will also be addressed. IBD remain biologically complex, with multifactorial etiopathology, clinical heterogeneity as well as temporal and therapeutic variabilities, which makes precision medicine especially challenging in this area. Although applied for many years in oncology, it remains an unmet medical need in IBD.

Obesity in adult patients with inflammatory bowel disease: Clinical features and impact on disability. A cross-sectional survey from the GETAID.

BACKGROUND: In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. However, only a few studies have focused on the impact of overweight and obesity on IBD-related disability. AIMS: To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability. PATIENTS AND METHODS: In this cross-sectional study, we included 1704 consecutive patients with IBD in 42 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif (GETAID) using a 4-page questionnaire. Factors associated with obesity and overweight were assessed using univariate and multivariate analyses (odds ratios (ORs) are provided with 95% confidence intervals). RESULTS: The prevalence rates of overweight and obesity were 24.1% and 12.2%, respectively. Multivariable analyses were stratified by age, sex, type of IBD, clinical remission and age at diagnosis of IBD. Overweight was significantly associated with male sex (OR = 0.52, 95% CI [0.39-0.68], p < 0.001), age (OR = 1.02, 95% CI [1.01-1.03], p < 0.001) and body image subscore (OR = 1.15, 95% CI [1.10-1.20], p < 0.001) (Table 2). Obesity was significantly associated with age (OR = 1.03, 95% CI [1.02-1.04], p < 0.001), joint pain subscore (OR = 1.08, 95% CI [1.02-1.14], p < 0.001) and body image subscore (OR = 1.25, 95% CI [1.19-1.32], p < 0.001) (Table 3). CONCLUSION: The increasing prevalence of overweight and obesity in patients with IBD is associated with age and poorer body image. A holistic approach to IBD patient care should be encouraged to improve IBD-related disability and to prevent rheumatological and cardiovascular complications.