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Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD.

The concept of disease clearance has been proposed as a potential target in ulcerative colitis (UC). We conducted a systematic review to investigate the role of disease clearance, defined as a composite outcome including simultaneous clinical, endoscopic, and histologic remission of disease in the management of patients with UC. Based on the literature data, statements regarding disease clearance were developed and voted on by the members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) according to a Delphi methodology. A definition of disease clearance was proposed to standardize its use in clinical practice and clinical trials and to provide practical recommendations for its implementation as a therapeutic target in UC.

In this review, we will describe the importance of fibrosis in inflammatory bowel disease (IBD) by discussing its distinct impact on Crohn’s disease (CD) and ulcerative colitis (UC) through their translation to histopathology. We will address the existing knowledge on the correlation between inflammation and fibrosis and the still not fully explained inflammation-independent fibrogenesis. Finally, we will compile and discuss the recent advances in the noninvasive assessment of intestinal fibrosis, including imaging and biomarkers. Based on the available data, none of the available cross-sectional imaging (CSI) techniques has proved to be capable of measuring CD fibrosis accurately, with MRE showing the most promising performance along with elastography. Very recent research with radiomics showed encouraging results, but further validation with reliable radiomic biomarkers is warranted. Despite the interesting results with micro-RNAs, further advances on the topic of fibrosis biomarkers depend on the development of robust clinical trials based on solid and validated endpoints. We conclude that it seems very likely that radiomics and AI will participate in the future non-invasive fibrosis assessment by CSI techniques in IBD. However, as of today, surgical pathology remains the gold standard for the diagnosis and quantification of intestinal fibrosis in IBD.

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a multifactorial disorder involving a dynamic interplay between genetic susceptibility, gut microbiota, nutrition, environmental exposures, immune dysregulation, and psychosocial factors [...]

Background The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a widely used instrument to assess Health-related Quality of Life (HRQoL) among inflammatory bowel disease (IBD) patients. Our aim was to translate and adapt the SIBDQ so that it could be adequately used in Portugal. Methods This is a prospective design cohort study undertaken at a tertiary hospital. This study took place simultaneously with the first part of the SexIDI study, a study aiming to assess the impact of IBD on patients’ sexual QoL. The original SIBDQ was translated by two independent translators and adapted by an IBD expert panel following the opinions of a convenient sample of 5 IBD patients. Afterwards, IBD patients from the outpatient clinic were consecutively invited to fill the Portuguese version of the questionnaire (SIBDQ-PT) at three different timepoints (0, 2, 4 weeks). Ninety-two patients completed the SIBDQ-PT at baseline, whereas 33 did so after 2 and 4 weeks (approximately). Statistical analysis was performed using SPSS version 25, and the following aspects were analysed: reliability (through internal consistency, test–retest and intraclass correlation), validity (through exploratory factor analysis [EFA], and Pearson correlation coefficient for linear correlations), score distribution, and responsiveness analysis (through t-student tests). Results Overall, SIBDQ-PT was shown to have a high internal consistency (Cronbach's α = 0.80) and a high test–retest reliability (0.80 [CI 0.74–0.86] and 0.69 [CI 0.50–0.82]). EFA detected four dimensions—bowel, social, emotional and systemic. As expected, an overall SIBDQ-PT score was positively correlated with sexual satisfaction (r = 0.27; p  < 0.05) and negatively correlated with depression (r = − 0.63; p  < 0.01). Moreover, SIBDQ-PT was found to have an adequate score distribution, and to be responsive, as there was a significant subscore change for patients who reported an “overall worsening in general well-being” (0.93 ± 0.13 decrease; p  < 0.01). Conclusions The Portuguese version of the SIBDQ hereby presented is a reliable, valid and responsive instrument that can be used to measure HRQoL among Portuguese IBD patients.

ObjectiveThe Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).DesignPatients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.ResultsIn total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).ConclusionDespite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Background Fecal calprotectin (FC) is a non‐invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard. Aims Our aim was to provide clear position statementsabout the pre‐analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus. Materials & Methods Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed. Results Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results. Discussion FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests. Conclusion FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement. Key Summary Summarise the established knowledge on this subject. ‐ FC is a surrogate non‐invasive marker of gut inflammation. ‐ FC is closely correlated with endoscopic and histological activity of disease. ‐ High variability exists between FC measurements. ‐ There is no globally accepted cut‐off of FC. What are the significant findings of this study? ‐ Stool consistency can influence FC extraction. ‐ Quantitative tests are recommended for FC measurement. ‐ Serial FC measurement in an individual patient should be performed with the same FC test. ‐ Interpretation of FC measurement results should include the evaluation of factors that may influence the test.

Background: Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages. Objective: To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD. Design: Systematic scoping review. Data sources and methods: We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included. Results: From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn’s disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase–associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior. Conclusion: Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker. Registration: https://osf.io/kes9a.

Treatment of Crohn’s disease (CD) is intrinsically reliant on imaging techniques, due to the preponderance of small bowel disease and its transmural pattern of inflammation. Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) are the most widely employed imaging methods and have excellent diagnostic accuracy in most instances. Some limitations persist, perhaps the most clinically relevant being the distinction between inflammatory and fibrotic strictures. In this regard, several methodologies have recently been tested in animal models and human patients, namely US strain elastography, shear wave elastography, contrast-enhanced US, magnetization transfer MRI and contrast dynamics in standard MRI. Technical advances in each of the imaging methods may expand their indications. The addition of oral contrast to abdominal US appears to substantially improve its diagnostic capabilities compared to standard US. Ionizing dose-reduction methods in CT can decrease concern about cumulative radiation exposure in CD patients and diffusion-weighted MRI may reduce the need for gadolinium contrast. Clinical indexes of disease activity and severity are also increasingly relying on imaging scores, such as the recently developed Lémann Index. In this review we summarize some of the recent advances in small bowel CD imaging and how they might affect clinical practice in the near future.

Endoscopic recurrence after surgery for Crohn's disease (CD) is high, and it has important prognostic value. Crohn's disease will recur in the majority of patients after surgery. Fecal calprotectin (FC) and lactoferrin (FL) have attracted interest in the postoperative setting for predicting relapse. We have evaluated the accuracy of FC and FL in diagnosing endoscopic recurrence (ER) using the modified Rutgeerts score (MRS) compared with the Rutgeerts score (RS).MethodsA series of consecutive patients who underwent ileocolonic resection for Crohn's disease were evaluated. Biomarkers, clinical indexes, and fecal markers were recorded on the day of ileocolonoscopy. ER was defined as a MRS ≥ i2b or a RS ≥ i2.ResultsNinety-nine patients were included in this prospective cohort. The median time between surgery and colonoscopy was 87.5 months (IQR, 31–137). FC and FL levels were higher in patients with ER than in those in remission (Median FC, 196.5 μg/g [IQR, 96–634 μg/g] versus 42.1 μg/g [IQR 19–91.60 μg/g; P < 0.001]; Median FL, 23.27 μg/g [IQR 8.9–47.8 μg/g] versus 2 μg/g [IQR 0.9–7.26 μg/g; P < 0.001]). Using the MRS, 34% of patients presented with ER compared with 76% if the RS was used. The RS performed worse than the MRS with a decrease in sensitivity (74% versus 48% for FC and 85% versus 55% for FL) and in NPV (91% versus 33% for FC, and 90% versus 37% for FL). Furthermore, the accuracy of the MRS was higher than that of the RS (75% versus 55%).ConclusionsBoth FC and FL proved to correlate well with endoscopic findings in the evaluation of Crohn's disease after surgery. Both markers predicted recurrence with greater accuracy when the MRS was used. Fecal markers can be used to monitor disease recurrence after intestinal resection, with patients being selected to undergo further endoscopic evaluation.