Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which remission is dependent on corticosteroid (CS) treatment. The diversity of disease pathophysiology necessitates optimal case-specific treatment selection. This study aimed to identify prognostic factors for refractory UC using a machine learning model based on nationwide registry data.

The study included 4003 patients with UC with a Mayo score of ≥3 at the time of registration who had been using CS since their entry out of 79,096 newly registered UC cases in a nationwide registry from April 2003 to March 2012 (before the widespread use of biologic agents in Japan) with 3-year data. A pointwise linear (PWL) model was used for machine learning.

A PWL model, which was developed to predict long-term remission (lasting >3 years), had an area-under-the-curve (AUC), precision rate, recall rate, and F-value of 0.774, 0.55, 0.70, 0.62, respectively, in the test dataset from the time of registration to 2 years later. Furthermore, the presence of pseudopolyps at the time of registration was significantly and negatively correlated with remission, highlighting its importance as a prognostic factor.

In this study, we constructed a highly accurate prognosis prediction model for UC, in which inflammation persists for an extensive period, by training a machine learning model for long-term disease progression. The results showed that machine learning can be used to determine the factors affecting remission during the treatment of refractory UC.

Crohn disease is a chronic granulomatous inflammatory disease of gastrointestinal tract. Previous studies showed Crohn disease strictures overexpress fibroblast activation protein and had active 68 Ga-FAPI-04 uptake. Our study was to compare the diagnostic performance of 68 Ga-FAPI-04 and 18 F-FDG PET/CT in Crohn disease.

This is a prospective cohort study recruiting patients with newly diagnosed or relapsed Crohn disease. All the patients underwent 68 Ga-FAPI-04 and 18 F-FDG PET/CT. The diagnostic performance of the 2 PET/CT modalities and their uptake values were compared. The correlation of PET semiquantitative parameters [metabolic intestinal volume (MIV FDG and MIV FAPI ), total intestinal uptake (TIU FDG and TIU FAPI )] with clinical biomarkers were also analyzed.

Seventeen participants (13 men and 4 women, age 32.3 ± 15.9 y) were recruited. The sensitivity of 68 Ga-FAPI-04 and 18 F-FDG PET/CT in detecting Crohn lesions were 90.0% and 85.0%, and the specificities were 93.0% and 88.4%, respectively. In receiver operating characteristic curve analysis, 68 Ga-FAPI-04 PET/CT [area under the curve = 0.92 (95% CI: 0.83-0.97), P < 0.001] showed better diagnostic performance compared with 18 F-FDG PET/CT [area under the curve = 0.87 (95% CI: 0.78-0.93), P < 0.001; P = 0.043]. The SUVmax of 68 Ga-FAPI and 18 F-FDG in stricture/fistula lesions were significantly higher than those in non-stricture/fistula lesions ( 68 Ga-FAPI, 10.9 ± 6.7 vs 5.0 ± 3.5, P = 0.0002; 18 F-FDG, 9.5 ± 4.9 vs 5.3 ± 1.8, P = 0.0016). TIU FAPI and MIV FAPI of 68 Ga-FAPI-04 PET/CT were significantly correlated with high sensitivity C-reactive protein and simple endoscopic score for Crohn disease ( P < 0.05). TIU FDG and MIV FDG of 18 F-FDG PET/CT were also correlated with simple endoscopic scores for Crohn disease ( P < 0.05).

68 Ga-FAPI-04 PET/CT showed better diagnostic performance than 18 F-FDG PET/CT in Crohn disease.

Ulcerative colitis (UC) is a chronic inflammatory condition requiring lifelong management, with anti-tumor necrosis factor α (anti-TNF-α) agents often used for refractory cases. However, secondary loss of response (LOR) to these agents, due to anti-drug antibodies, poses a significant therapeutic challenge. This report describes a case where granulocyte and monocyte adsorptive apheresis (GMA) maintenance therapy successfully restored the efficacy of an anti-TNF-α agent in a 26-year-old male with active UC experiencing LOR to infliximab. Following GMA induction therapy and continued infliximab administration, clinical symptoms improved, fecal calprotectin levels decreased, and clinical remission was achieved. Long-term maintenance with GMA enabled sustained clinical remission, with mucosal healing observed one year post-therapy. This case suggests that GMA maintenance therapy may serve as a novel therapeutic approach for patients with active UC experiencing LOR to anti-TNF-α agents. However, further studies are warranted to elucidate the underlying mechanisms and validate its efficacy.

Earlier studies, mainly prior to the widespread use of advanced therapy and implementation of guidelines for thromboprophylaxis indicate a doubled risk of venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD).

Using Swedish healthcare registers, we identified a population-based cohort of patients with incident IBD 2007-2021. Patients were matched by age, sex, calendar year of birth and place of residence with up to 10 reference individuals. The primary outcome was VTE, i.e., pulmonary embolism (PE) and deep vein thrombosis (DVT). Incidence rates (IRs) per 1000 person-years, cumulative incidence and hazard ratios (HRs) were calculated for IBD overall and according to clinical characteristics. The temporal trend of the incidence of VTE by calendar year was presented.

We followed 55,252 IBD patients and 536,067 reference individuals, for a median of 6.5 years. The incidence of VTE in IBD was 5.03 vs. 2.35 per 1000 person-years among reference individuals, corresponding to a doubled risk of VTE (HR = 2.12; 95% confidence interval [CI] 2.02-2.23). Particularly high risks were seen in the first year of follow-up, and among patients with extensive ulcerative colitis (UC), primary sclerosing cholangitis (PSC), extraintestinal manifestations, perianal disease and hospitalization at diagnosis. The occurrence of VTE in IBD did not decrease across calendar years.

IBD remains linked to an elevated risk of VTE, particularly with disease characteristics associated with a higher inflammatory burden and higher age. Our findings underscore the importance of continuous vigilance and individual assessment of VTE risk in patients with IBD.

This study aims to assess whether the association between chronic pathologies and depressive and/or anxious disorders is high, resulting in a reduction in the patient's quality of life.

This is a prospective cross-sectional study with a descriptive and analytical design. Sociodemographic data and lifestyle habits were collected. Subsequently, the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Hospital Anxiety and Depression Scale (HADS) were applied.

A total of 141 patients participated in the study, with a mean age of 45.78 (SD 16.01) years, of which 60.3% were female (n=85) and 39.7% were male (n=56). 58.9% had ulcerative colitis (UC) (n=83), and 41.1% had Crohn's disease (CD) (n=58). 16.5% of patients had a previous diagnosis of generalized anxiety disorder (GAD) and/or major depression (MD) (n=23). Regarding IBDQ scores, participants with anxiety had significantly lower mean scores in all IBDQ items (p<0.001), while the depression diagnosis obtained significantly lower mean values for systemic (p=0.015), emotional (p=0.001), and intestinal symptoms (p=0.005).

The results indicate that anxiety and depression negatively impact the quality of life of patients with IBD independently of the disease activity.

Endoscopic balloon dilation (EBD) is recognized as a minimally invasive and effective procedure for managing intestinal stenosis in patients with Crohn's disease (CD). It offers an alternative to surgery and has been shown to improve the quality of life for these patients by reducing the need for more aggressive interventions. This study aimed to evaluate factors associated with endoscopic restenosis after EBD and construct a prognostic model.

We retrospectively collected and analyzed data on patients receiving EBD treatment at the Sixth Affiliated Hospital of Sun Yat-sen University from 2013 to 2024. Seven machine learning (ML) algorithms were used to construct prognostic models. Subsequently, we conducted comparative tests on the performance of the models to ensure accuracy and reliability.

A total of 135 patients were included in the statistical analysis. 53% occurred endoscopic restenosis, with an average restenosis time of 183 days. COX and logistic regression analysis showed that 4 features including ever-use glucocorticoids, stenosis position, technical success, and albumin level were associated with restenosis risk. When comparing different ML models, CoxPH and LASSO models performed better on various evaluation metrics, including C-index which was greater than 0.7 in the train and test set. Based on SHapley Additive exPlanations (SHAP), stenosis position, balloon diameter, and albumin level were identified as the top 3 important features associated with prognosis.

The ML-based prognostic model has good predictive performance and can accurately assess the risk of endoscopic restenosis after EBD treatment.

Perianal Crohn's disease (pCD) is a complex manifestation of Crohn's disease. Classifying this patient cohort for both clinical purposes and for inclusion into research trials is challenging but crucial in order to improve outcomes. This review provides an overview of historical classifications of both fistulising and non-fistulising pCD, including the Park's, Cardiff-Hughes and American Gastroenterological Association (AGA) classifications, as well as recent advances including the Treatment Optimisation and CLASSification of perianal Crohn's disease (TOpClass) classification of fistulising pCD. Secondly, this article provides a scoping review of recent trials in pCD and describes how the cohorts in these trials relate to the TOpClass classification. Of the 19 studies relating to pCD that were identified, four could be confidently classified as class 2a. Seven could be classified as class 2a or 2b, but it was not possible to subdivide further, and seven to class 2a, 2b or 2c, but it was not possible to subdivide further. One study population was classified as class 2a or 2c. In eight studies, it was not specified whether patients with a defunctioning stoma were included or excluded. This review demonstrates the heterogeneous nature of some patient cohorts in previous clinical trials, and how the TOpClass classification may be used to group patients more accurately for clinical use and inclusion in research trials.

Mechanisms causing non-response to biological agents in IBD remain to be fully understood. Thus, we aimed to characterize the lipid profile in treatment refractory non-immunogenic patients with adequate trough-levels.

Patients with IBD refractory to treatment with anti-tumour necrosis factor or vedolizumab were included from a Norwegian translation study. Mucosal lipid profiles were compared to reference groups. The reference groups included treatment naïve IBD patients with moderate to severe disease at debut who later achieved remission or response on antiTNFs, IBD patients treated to remission with biological agents, and healthy normal controls. Lipidomics analyses were performed on mucosal biopsies. Statistical analyses of lipid levels were carried out using generalized least squares. Lipidomics data were log2-transformed and auto-scaled before analysis. P-values were adjusted using Benjamini- Hochberg procedure to control the false discovery rate (FDR).

Proinflammatory lipids including ceramides and sphingomyelins and protective lipids like glycerophosphocholines and glycerophosphoethanolamines were significantly decreased in treatment refractory UC patients compared to treatment naïve UC patients with moderate to severe disease. Compared to controls, major changes in ceramides (Cer), hexosyl ceramides (HexCer), sphingomyelins (SM), glycerophosphocholines (PC), glycerophosphoethanolamines (PE) and glycerophosphoserines (PS) were observed in treatment refractory UC patients. Refractory CD patients showed minor changes compared to the other CD-groups. There were no significant differences in the mucosal lipid levels of IBD patients in remission compared to normal controls.

The mucosal lipid profile of treatment refractory UC shows marked shifts compared to treatment naïve UC at debut with moderate to severe inflammation. These are novel findings which possibly indicate dynamic processes of long-standing mucosal inflammation. The mucosal lipid profile of IBD patients in remission seems to be similar to the normal state.

In inflammatory bowel disease (IBD), a flare can be due to natural history of disease or due to gastrointestinal infection. Infection is conventionally diagnosed by stool microscopy and culture. Stool multiplex polymerase chain reaction (PCR) assay or Biofire® FilmArray® GI Panel is a sensitive and rapid test for detecting infection, but is expensive; its impact on management and cost-effectiveness has not been studied in IBD.

To compare stool PCR assay and conventional tests during IBD flare for detection of infection, impact of detection on treatment and cost-effectiveness of the tests.

Sixty-five patients with IBD flare underwent conventional stool tests (microscopy, culture and Clostridioides difficile toxin assay) and stool PCR assay simultaneously.

We prospectively enrolled 65 consecutive patients presenting with disease flare: ulcerative colitis (58 patients, 28 women, mean age 41.1 years) and Crohn's disease (seven patients; three women; mean age 36.1). Stool PCR detected organisms in 36 (55.4%) patients as compared to six (9.2%) by conventional tests (p < 0.0001). The organisms detected by the PCR assay were enteroaggregative (EAEC) (22 patients), enteropathogenic (EPEC) (12), enterotoxigenic Escherichia coli (ETEC) (5), Plesiomonas shigelloides (4), C. difficile (3), norovirus (3), enteroinvasive E. coli (2), rotavirus (2) and G. lamblia, cryptosporidia, cyclospora, Sapovirus, adenovirus and Entamoeba histolytica (one each). PCR organism detection resulted in management change in 13 (20%) patients as compared to five (7.6%) by conventional tests (p < 0.02). Cost to achieve one positive result on stool PCR that led to management change was INR 60,000 (USD 690, EUR 638) as compared to Indian Rupees (INR) 54,600 (United States Dollar [USD] 627, EUR 580) for conventional tests. The incremental cost-effective ratio (ICER) was INR 63,375 (USD 728, EUR 674).

In an IBD flare, stool PCR or Biofire® FilmArray® GI Panel detected more organisms and led to more frequent management change as compared to conventional tests. The ICER was INR 63,375 (USD 728, EUR 674). This test should be considered first-line investigation in an IBD flare.

Objective Crohn's disease (CD) is a chronic inflammatory bowel disease that is associated with malnutrition. Sarcopenia is a malnutrition condition characterized by skeletal muscle loss that impairs the physical function. We investigated the clinical characteristics of patients with CD with sarcopenia and sarcopenic obesity (sarcopenic-o). Methods The body composition of patients with CD was evaluated using a bioelectrical impedance analysis. The clinical characteristics of patients with sarcopenia and sarcopenic-o were analyzed, and a predictive model for sarcopenia was developed. Patients Patients with CD recruited from 2019 to 2021 were included. Results Among the 104 patients, 35 (33.7%) and 10 (9.6%) had sarcopenia and sarcopenic-o, respectively. In the sarcopenia group, the skeletal muscle index (SMI) and body mass index (BMI) were lower than those in the control group (SMI, 6.3 kg/m2 vs. 7.7 kg/m2, p<0.01; BMI, 18.8 kg/m2 vs. 22.6 kg/m2, p<0.01), whereas the Crohn's disease activity index (CDAI) was higher than in the control group (114.2 vs. 42.0, p<0.01). The predictive models of sarcopenia using the BMI and CDAI revealed high performance with areas under the receiver operating characteristic curve (AUC) of 0.87 and 0.72, respectively, and high specificity (0.94) and sensitivity (0.71), respectively. Sarcopenic-o patients could not be screened using the BMI (25 kg/m2), and the SMI and body fat percentage were negatively correlated in patients with sarcopenia (p<0.01). Conclusion Sarcopenia and sarcopenic-o are relatively common conditions among patients with CD. Sarcopenia can be predicted using the clinical parameters of BMI and CDAI. Sarcopenic-o can be a severe form of sarcopenia.

The study investigated the incidence, risk factors, and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with ulcerative colitis (UC).

This single-center retrospective study included patients with UC who underwent total proctocolectomy with ileal pouch-anal anastomosis at the Asan Medical Center in Korea between January 1987 and December 2022. The primary outcomes were endoscopic remission and pouch failure. The Cox's proportional hazard model was used to identify the risk factors for CARP.

The clinical data of 232 patients were analyzed. The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). Among 74 patients (31.9%) with chronic pouchitis (CP), 31 (13.4%) had CARP, and 43 (18.5%) had chronic antibiotic-dependent pouchitis (CADP). The most frequent endoscopic phenotype was focal inflammation of the pouch (CP, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to use concomitant probiotics than patients with CADP (29.0% vs 72.1%, p<0.01). The endoscopic remission rate of CP, CARP, and CADP was 14.9%, 9.7%, and 18.6%, respectively. The pouch failure rate associated with CP, CARP, and CADP was 13.5%, 16.1%, and 11.6%, respectively. Current smoking status (adjusted hazard ratio [aHR], 2.96; 95% confidence interval [CI], 1.27 to 6.90; p=0.01) and previous use of biologics/small molecules (aHR, 2.40; 95% CI, 1.05 to 5.53; p=0.04) were significantly associated with CARP development.

UC patients who were current smokers and previously used biologics/small molecules had a higher risk of developing CARP. Concomitant use of probiotics was less likely to be associated with CARP development.

Magnetic resonance enterography (MRE) is a first-line investigation to diagnose Crohn's disease (CD), but its role for prognostication is unknown. Accordingly, we assessed the predictive ability of prognostic models including MRE scores (MRE Global Score (MEGS), simplified MR Index of Activity (sMARIA), and Lémann index (LI)) against models using clinical predictors alone for the development of modified Beaugerie disabling CD (MBDD) within 5 years of diagnosis.

This was a multicentre, diagnostic inception cohort of patients with newly diagnosed CD across 9 UK hospitals, followed for 4 years or more. We censored development of MBDD ≤ 90 days from diagnosis, and used time-to-event models using Royston-Parmer flexible parametric models.

We included 194 patients, median age 29, IQR 22-44 years, 52% female. Within 5 years of diagnosis, 42% (81/194) developed MBDD. In univariable analysis, initial steroid requirement was associated with increased risk of developing MBDD (HR 2.11 (95% CI 1.36, 3.26). The baseline clinical model had 49% (39, 60) sensitivity and 66% (57, 74) specificity for predicting the top 40% of patients with the greatest risk of developing MBDD, and 86% (77, 92) sensitivity and 35% (27, 45) specificity for predicting the development of MBDD in patients with an absolute risk of ≥ 10%. There was no significant difference in sensitivity when the MEGS, sMARIA, or LI were added to the baseline clinical model.

Addition of MRE scores at diagnosis to a multivariable model comprising clinical predictors did not improve prediction of MBDD within 5 years of diagnosis.

Question Magnetic resonance enterography (MRE) is important for diagnosing and monitoring Crohn's disease (CD), but primary research evaluating its prognostic role is lacking. Findings Adding MRE findings at diagnosis to a multivariable model comprising clinical predictors did not improve the prediction of disabling CD within 5 years of diagnosis. Clinical relevance When tested in a prospective, multicentre trial, current MRE activity and damage scores at diagnosis did not reliably predict whether patients would subsequently develop disabling CD. Notwithstanding this finding, MRE remains an essential tool for diagnosis and monitoring.

The period prior to the diagnosis of inflammatory bowel disease (IBD), defined as the preclinical phase, has emerged as a potential target for disease modification strategies. Despite the relevance of an early diagnosis to the prognosis of the disease, only a limited number of patients are diagnosed during this window of opportunity.

To determine the risk of developing symptoms after an incidental diagnosis of IBD and to describe the clinical, genetic, and immunological characteristics of IBD during its preclinical phase.

This study protocol describes a prospective, multicenter cohort study in which incidental (i.e., asymptomatic) IBD within the colorectal cancer screening program will be characterized from a clinical and multi-omic perspective and compared with symptomatic patients and healthy non-IBD controls.

Samples from blood, urine, stool, and intestinal endoscopic biopsies will be obtained at baseline. A second sample set will be obtained after 52 weeks from those who remain asymptomatic; samples will also be obtained in those with new-onset symptoms. Medical treatment will be prescribed in all patients following current guidelines. Follow-up visits will be performed every 6 months for 10 years, and all new-onset symptoms, changes in disease behavior, extraintestinal manifestations, IBD-related medical therapies, or surgeries will be recorded. Two control cohorts will be included: one including recently diagnosed symptomatic IBD patients (<3 months), and another with healthy non-IBD controls after a normal ileocolonoscopy, in whom samples will be obtained at baseline. Samples from patients and controls will undergo genetic, proteomic, transcriptomic, single-cell RNA sequencing, metabolomic, and microbiome analyses, and integration of data between the different omic perspectives will also be performed. The study has been approved by the Basque Country Ethics Committee (PI2021116).

EARLY will generate a unique dataset addressing a previously unexplored area of IBD, with the final aim of describing the prognosis of patients from its earlier phases on the disease and integrating clinical and omic data into useful tools for the long-term prediction of disease outcomes.

NCT05698745.

Many ulcerative colitis (UC) patients require the use of second-line agents after the failure of anti-TNF therapy.

We conducted a multicenter, retrospective study including 683 chronically active, moderate-to-severe UC patients who failed first-line anti-TNFs. The rate of treatment persistence and colectomy-free survival was assessed up to 3 years after the initiation of second-line therapy. Predictors for colectomy and persistence were investigated.

After the failure of the first-line anti-TNF, ustekinumab had superior persistence and colectomy-free survival rates compared to tofacitinib (p = 0.05; p = 0.001) and vedolizumab (p = 0.02; p = 0.05), but significant difference was only found in persistence rates in comparison with anti-TNFs (p < 0.001). Regardless of the number of prior anti-TNFs, significantly higher persistence (p = 0.05) and colectomy-free survival rates (p = 0.01) were observed over 2 years with ustekinumab than with vedolizumab or tofacitinib, whereas ustekinumab's superiority over tofacitinib seemed to disappear by the third year. Hypoalbuminaemia (p = 0.002) and shorter disease duration at second-line initiation (p = 0.03) increased, while concomitant immunomodulators (p = 0.05) reduced the risk for colectomy. Shorter disease duration (p = 0.01) and primary non-response to the previously used anti-TNF (p < 0.001) negatively influenced persistence with second-line non-TNF-targeted agents.

After first-line anti-TNF failure, switching to a non-anti-TNF agent is worth considering in moderate-to-severe UC.

This study aimed to investigate the clinical relevance of inflammatory markers in the severity assessment of ulcerative colitis (UC). The inflammatory markers included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and calcium ion (Ca2+) levels. A retrospective analysis was on 110 patients with UC and 52 patients with irritable bowel syndrome (IBS), admitted to Weifang People's Hospital between June 2019 and February 2021. UC severity was classified using the modified Mayo score and the Montreal classification system. The study assessed the predictive accuracy and correlation of these inflammatory markers with UC severity and extent. Levels of NLR, PLR, CRP, ESR, and Ca2+ were significantly elevated in individuals with UC compared to those with IBS. Among patients with UC, significant differences in these markers were observed across varying severity levels as defined by the modified Mayo score. However, aside from ESR, no significant differences were noted in NLR, PLR, CRP, or Ca2+ levels across groups defined by lesion extent. Receiver operating characteristic curve analysis indicated that NLR exhibited the highest predictive accuracy for UC, with a cut-off value of 2.603 yielding a sensitivity of 0.545, specificity of 0.288, and an area under the curve (AUC) of 0.896. The combined use of NLR, PLR, CRP, ESR, and Ca2+ demonstrated superior predictive performance, achieving an AUC of 0.972, sensitivity of 0.927, and specificity of 0.923 at a cut-off value of 0.455. NLR, PLR, CRP, ESR, and Ca2+ exhibit predictive value for UC, with NLR demonstrating the highest individual predictive performance. The combined use of these markers enhances predictive accuracy, highlighting their potential application in clinical practice for the evaluation of severity UC. Due to ethical considerations at our institution, the IBS group was used as a substitute for healthy controls. The IBS group was included solely for the calibration and testing of inflammatory biomarkers, as well as for subsequent analysis of their role in assessing UC severity.

Research in Inflammatory Bowel Disease (IBD) assessing the genetic structure and its association with IBD phenotypes is needed, especially in IBD-underrepresented populations such as the South American IBD population. Aim. We examine the correlation between Amerindian ancestry and IBD phenotypes within a South American cohort and investigate the association between previously identified IBD risk variants and phenotypes. We assessed the ancestral structure (IBD = 291, Controls = 51) to examine the association between Amerindian ancestry (AMR) and IBD variables. Additionally, we analyzed the influence of known IBD genetic risk factors on disease outcomes. We used Chi-square and Fisher's tests to analyze the relationship between phenotypes and ancestry proportions, calculating odds ratios (OR) and confidence intervals (CI). Logistic regression examined genetic variants associations with IBD outcomes, and classification models for predicting prolonged remission were developed using decision tree and random forest techniques. The median distribution of global ancestry was 58% European, 39% Amerindian, and 3% African. There were no significant differences in IBD risk based on ancestry proportion between cases and controls. In Ulcerative colitis (UC), patients with a high Amerindian Ancestry Proportion (HAAP) were significantly linked to increased chances of resective surgery (OR = 4.27, CI = 1.41-12.94, p = 0.01), pouch formation (OR = 7.47, CI = 1.86-30.1, p = 0.003), and IBD reactivation during COVID-19 infection (OR = 5.16, CI = 1.61-6.53, p = 0.005). Whereas, in the Crohn's Disease (CD) group, the median Amerindian ancestry proportion was lower in the group with perianal disease (33.5% versus 39.5%, P value = 0.03). CD patients with High Amerindian Ancestry proportion had lower risk for surgery (OR = 0.17, CI = 0.03-0.83, P value = 0.02). Our study highlights the impact of Amerindian ancestry on IBD phenotypes, suggesting a role for genetic and ancestral factors in disease phenotype. Further investigation is needed to unravel the underlying mechanisms driving these associations.

The psychosocial effects of eating and drinking - summarized as food-related quality of life (FR-QoL) - are underexplored in inflammatory bowel disease (IBD). Currently, there is no German instrument to assess FR-QoL in IBD patients. This study aimed to translate the validated English FR-QoL-29 questionnaire into German and evaluate its validity and reliability.A monocentric, cross-sectional study was conducted at a tertiary referral center with IBD patients and healthy controls. Participants completed questionnaires on sociodemographics, disease history, the Malnutrition Universal Screening Tool (MUST), the German Short Health Scale (SHS), and the FR-QoL-29-German. The FR-QoL-29 was translated into German using a forward-backward method. Its reliability and validity was assessed using Pearson correlation coefficients, intraclass correlation coefficients, and Cronbach's α.N=200 IBD patients (Crohn's disease: 61.8%; women: 50.8%; remission: 56.2%) and n=10 healthy controls completed the questionnaires. Overall, 113 IBD patients repeated the questionnaires after an average of six weeks. Significant differences in FR-QoL-29-German sum scores were found between all levels of IBD disease activity, except for remission - mild disease (p = 0.423) and moderate - severe disease (p = 0.999). FR-QoL-29-German scores significantly correlated with age (p = 0.041), disease activity (p < 0.001), MUST (p = 0.015), fecal Calprotectin (p = 0.011) and SHS (p < 0.001). Overall, the FR-QoL-29-German showed excellent internal consistency (Cronbach's α = 0.965) and good test-retest reliability (ICC = 0.85 [95% CI: 0.78-0.89]).The FR-QoL-29-German is a valid and reliable tool for assessing food-related quality of life in German-speaking individuals with IBD.

Musculoskeletal manifestations occur in half of the patients with inflammatory bowel disease (IBD) and contribute to a reduced quality of life (QoL) and increased work disability. We aimed to evaluate the natural disease course, characteristics, and risk factors of musculoskeletal manifestations in patients with IBD.

We performed a prospective longitudinal cohort study in patients with IBD with and without musculoskeletal manifestations with a 1-year follow-up. Primary outcome was the proportion of patients with resolution of musculoskeletal manifestations. Secondary outcomes included the proportion of patients with IBD that developed new musculoskeletal manifestations during follow-up; the correlation among IBD activity, baseline characteristics, and musculoskeletal disease course; and the difference in QoL between patients with and without musculoskeletal manifestations.

In total, 243 patients with IBD were included (124 with and 119 without musculoskeletal manifestations). In the majority of patients (62.2%), musculoskeletal manifestations were of noninflammatory nature. Overall, peripheral and axial manifestations were persistent in 85.7 and 44.6% at 1 year, respectively. The QoL at baseline and at 1 year was lower in the group with musculoskeletal manifestations compared with patients without these manifestations. Female sex and age above 40 were associated with the presence of musculoskeletal manifestations.

Musculoskeletal manifestations in patients with IBD are mostly noninflammatory disorders, persist at 1 year of follow-up, and occur more frequently in patients of age above 40 and female sex. Overall, patients with musculoskeletal manifestations have lower QoL compared with patients without musculoskeletal manifestations.

When golimumab (GLM) was approved for the treatment of moderate to severe ulcerative colitis (UC) in 2013, a post-authorization safety study was conducted.

Our objective was to examine whether exposure to GLM was associated with an increased incidence of all-cause total colectomy, colorectal cancer, and hepatosplenic T-cell lymphoma in Denmark and Sweden.

We conducted a new-user, active comparator cohort study of patients with UC in 2013-2021. Exposure to GLM, other anti-tumor necrosis factor (TNF) agents (infliximab and adalimumab) and thiopurines was a time-varying variable. Therapies were based on prescription redemptions and hospital-based administration of medications from national prescription and hospital registers. The association between exposure to study therapies and outcomes was evaluated using Poisson regression of incidence rates (IRs), presented as IR ratios (IRRs) and 95% confidence intervals (CIs).

A total of 5177 and 7469 patients were included in Denmark and Sweden, respectively. The IR of all-cause total colectomy per 1000 person-years was higher in Denmark (IR 42.6; 95% CI 38.9-46.2) than in Sweden (IR 16.1; 95% CI 14.2-18.0). No significant difference was observed in all-cause total colectomy between GLM and other anti-TNF agents (Denmark: adjusted IRR [aIRR] 1.28; 95% CI 0.98-1.66; Sweden: aIRR 1.17; 95% CI 0.72-1.90). A significant difference was observed between GLM and thiopurines (Denmark: aIRR 13.62; 95% CI 8.73-21.26; Sweden: aIRR 4.52; 2.75-7.41). Privacy regulations prevented analysis of a few colorectal cancer events. No hepatosplenic T-cell lymphoma events were identified.

The IR of all-cause total colectomy with GLM was similar to that with other anti-TNF agents but was much higher than with thiopurines, probably related to confounding by indication.

Medication adherence is critical in 5-aminosalicylate therapy for patients with ulcerative colitis. Patients with a history of previous medication self-discontinuation may continue to have low adherence due to the influence of inappropriate disease awareness. This study aimed to determine the association between the history of previous medication self-discontinuation and current adherence to 5-aminosalicylates in patients with ulcerative colitis.

This cross-sectional study was conducted in Japan from 2021 to 2024. A self-administered questionnaire was used in 228 patients with ulcerative colitis who were taking 5-aminosalicylates. We defined adherence as consumption of ≥ 80% of the prescribed dose. Patients with a history of previous medication self-discontinuation were defined as having discontinued medication at least once in the past by their own judgment. The current adherence rate to 5-aminosalicylates in this study was 92.9% (212/228). The proportion of patients with a history of previous medication self-discontinuation was 7.8% (18/228). History of previous medication self-discontinuation (p < 0.001), younger age (p < 0.001), and once-daily 5-aminosalicylates regimen (p < 0.001) were inversely associated with current adherence to 5-aminosalicylates.

History of previous medication self-discontinuation was inversely associated with current adherence to 5-aminosalicylates among patients with ulcerative colitis. The results of this study suggest that determining the history of previous medication self-discontinuation may be a valuable tool in assessing current adherence to 5-aminosalicylates, which can be cumbersome.

The gut microbiome contributes to chronic inflammatory responses in ulcerative colitis (UC), but molecular mechanisms and disease-relevant effectors remain unclear. Here we analyze the pro-inflammatory properties of colonic fluid obtained during colonoscopy from UC and control patients. In patients with UC, we find that the pelletable effector fraction is composed mostly of bacterial extracellular vesicles (BEVs) that exhibit high IgA-levels and incite strong pro-inflammatory responses in IgA receptor-positive (CD89+) immune cells. Biopsy analyses reveal higher infiltration of CD89+ immune cells in the colonic mucosa from patients with UC than control individuals. Further studies show that IgA-coated BEVs, but not host-derived vesicles nor soluble IgA, are potent activators of pro-inflammatory responses in CD89+ cells. IgA-coated BEVs also exacerbate intestinal inflammation in a dextran sodium sulfate colitis model using transgenic mice expressing human CD89. Our data thus implicate a link between IgA-coated BEVs and intestinal inflammation via CD89+ immune cells, and also hint a potential new therapeutic target for UC.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in inflammatory bowel disease (IBD) patients due to chronic inflammation and metabolic disturbances. However, reliable non-invasive biomarkers for MASLD prediction in this population are lacking. This study evaluated the predictive value of metabolic scores and lipid ratios for MASLD onset in IBD patients. Methods: An observational retrospective study was conducted on 358 IBD patients at the "Renato Dulbecco" Teaching Hospital in Catanzaro, Italy, in a period between 1 January 2021 and 31 December 2024. Clinical and laboratory data, including metabolic scores and lipid ratios, were analyzed using the chi-square and Kruskal-Wallis tests as appropriate. Post hoc comparisons were conducted using Dunn's test. Receiver operating characteristic analysis assessed their predictive accuracy for MASLD. p < 0.05 was considered significant. Results: IBD-MASLD patients had a significantly higher body mass index (BMI, 27 ± 4 vs. 22 ± 2 kg/m2; p < 0.001), waist circumference (100 ± 11 vs. 85 ± 4 cm; p < 0.001), other anthropometric parameters, metabolic scores, and lipid ratios than IBD-only patients. The metabolic score for insulin resistance [METS-IR, area under curve (AUC = 0.754)] and waist circumference (AUC = 0.754) exhibited the highest predictive accuracy, followed by the lipid accumulation product (LAP, AUC = 0.737), BMI (AUC = 0.709), and triglyceride/high-density lipoprotein (TG/HDL, AUC = 0.701). Insulin resistance scores, including the homeostasis model assessment of insulin resistance (AUC = 0.680) and triglyceride-glucose index (AUC = 0.674), were of moderate predictive use. The visceral adiposity index (AUC = 0.664) and low-density lipoprotein/high-density lipoprotein (AUC = 0.656) showed lower discriminative ability, while the fibrosis-4 index (AUC = 0.562) had the weakest diagnostic performance. Conclusions: Our findings suggest that MASLD in IBD is primarily driven by cardiometabolic dysfunction. The introduction of the METS-IR, LAP, and TG/HDL into clinical assessments of IBD patients could prove useful in preventing liver and cardiovascular complications in this setting.

Crohn's disease is one phenotype of inflammatory bowel disease (IBD). Fatigue is a common and burdensome symptom for persons with Crohn's disease. Despite its detrimental impact on health-related quality of life, the pathophysiology of fatigue in Crohn's disease is not fully understood. Specifically, basic research on the difference in brain functioning associated with fatigue in Crohn's disease is scarce. This study aimed to address this knowledge gap by identifying fatigue-related differences in brain resting state functional connectivity. in Crohn's disease.

Participants included 49 adults with Crohn's Disease (M age 53 yrs, 35 females) and 49 healthy controls (M age 50 yrs, 31 females). The Fatigue Impact Scale (FIS) assessed impact of fatigue across three domains (physical, cognitive, and psychosocial) as well as total impact of fatigue. The Harvey-Bradshaw Inventory (HBI) assessed disease activity. Magnetic Resonance Imaging of brain functional connectivity during resting state (i.e.,: wakeful rest) was assessed in relation to scores on the FIS (total and for each domain). Moderation analyses tested whether brain resting state functional connectivity moderates the relationship between disease activity and fatigue.

The Crohn's disease group reported more severe fatigue than the healthy control group in each domain of the FIS. For the Crohn's disease group, increasing fatigue was associated with decreasing synchronicity of brain function (i.e., functional connectivity) between the superior parietal lobule and the parahippocampal gyrus/hippocampus. Unlike in the healthy control group, an increasing impact of physical fatigue was associated with decreasing functional connectivity between these ROIs for the Crohn's disease group (TFCE = 16.88, p-FDR = 0.03). Moderation analyses revealed a significant interaction between disease activity, total fatigue, and functional connectivity of the right superior parietal lobule and left anterior parahippocampal gyrus (ΔR2 = 0.058, F = 5.445, p = 0.0245). Higher scores on the HBI were only associated with higher total scores on the FIS in persons with Crohn's disease who exhibited negative functional connectivity between these brain regions.

In people with Crohn's disease, fatigue increases as functional connectivity between brain regions involved in sensorimotor integration and memory processing decreases.

Background/Objectives: Patients with inflammatory bowel disease (IBD) face an increased risk of developing intestinal and extraintestinal cancers. This retrospective single-center study aimed to quantify cancer risk and identify potential risk factors associated with cancer in IBD patients. Methods: The epidemiological data, disease characteristics, treatment regimens, and occurrences of cancer following IBD diagnosis were collected between January 2021 and February 2022. Hazard ratios (HRs) and standardized incidence ratios (SIRs) were estimated. Results: 560 IBD patients were included; 37 patients developed cancer, with 5 patients developing two distinct cancers, resulting in 42 cancers overall. This translated into a twofold increased risk of developing any cancer compared to the general population (SIR 1.94, 95% CI 1.4-2.6). Colorectal (CRC, 29%), skin (19%), and breast cancer (17%) were the most common malignancies. Female patients showed an increased risk for all cancers (SIR 3.1, 95% CI 2.06-4.3), melanoma (SIR 5.6, 95% CI 1.14-16.2), and CRC (SIR 7.5, 95% CI 3-15.4). Conversely, male patients exhibited a significantly increased risk of lymphoma (SIR 26.2, 95% CI 3.2-95.7). Young age at IBD diagnosis and the use of immunomodulators, whether as monotherapy or in combination with biologics, were associated with an increased risk of cancer. Conclusions: The risk of CRC and lymphoma in IBD patients may be higher than previously reported, potentially due to the increasing use of combination therapy. Cancer risk in IBD should be regularly assessed and personalized throughout the disease course.

Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.

Crohn's disease consists on a complex condition where, despite most patients initially present with an inflammatory behavior, a significant proportion develop complicated lesions such as strictures, fistulas, abscesses, or even perforations. These lesions progressively increase over time and are associated with a higher risk of surgery and hospitalization. Despite significant advances in their management after the introduction of biological therapies, particularly anti-TNF agents, these complications continue to pose challenges for the multiple professionals involved in their care. Fistulas that do not involve the perianal region (entero-enteric, entero-urinary, or entero-cutaneous) require a multidisciplinary strategy that combines medical, interventional, and surgical approaches. Their treatment ranges from general supportive measures to the use of antibiotics or, frequently, advanced therapies. Nevertheless, in cases of certain septic complications or those refractory to medical treatment, percutaneous drainage or surgical intervention remains essential. Although these lesions have a significant impact, evidence regarding the best strategies in this context, as well as the efficacy and safety of different therapies in these patients, remains limited. This is highlighted by the absence of specific recommendations in current guidelines. The objective of this document is to provide a comprehensive overview of non-perianal fistulizing Crohn's disease, addressing its epidemiological, clinical, and therapeutic aspects from a multidisciplinary perspective.

Patients with inflammatory bowel disease (IBD) tend to be less physical active, while maintaining an active lifestyle has been associated with enhanced disease control, diminished fatigue, and improved quality of life. This study aimed to evaluate the feasibility and potential impact of an exercise program for patients with IBD.

Patients with IBD participated in a 16-week personalized exercise program based on their individual fitness level. Outcome measures included body composition (BMI, muscle mass and fat percentage), physical fitness (based on the Fundamental Motor Skills), quality of life, fatigue, and disease control. For statistical analyses, a paired t test or Wilcoxon signed rank test was used.

In total 32 patients were included, mean age was 50.1 years (SD 12.3), 37.5% were male, and 50% had Crohn's disease. The program was completed by 75% of patients, and average rating of the program was 8.6 out of 10. The program significantly improved fatigue scores (P = 0.013). Quality of life scores improved by an average of 8 points, and disease control showed no significant difference. Additionally, muscle mass (P = 0.020), fat percentage (P = 0.003), lower body strength and coordination (P = 0.006), flexibility (P = 0.002), and speed and endurance (P < 0.001) improved significantly after the program.

This pilot study showed that a personalized exercise program could be feasible for patients with IBD and has the potential to have a positive effect on quality of life and fatigue. These findings underline the importance of physical activity and can be used as a step toward integrating an exercise program in standard IBD care.

The patient perspective is essential for assessing disease severity, but it is not always adequately considered. We describe how a comprehensive clinical disease severity index (DSI) for inflammatory bowel disease (IBD) correlates with patient global self-assessment (PGSA).

In an individually linked parallel online survey, physicians provided the DSI, and patients provided self-assessed severity using a global question and visual analog scale (0-100) (PGSA). Mean DSI values by PGSA were calculated with 95% confidence intervals. Pearson correlation (r) and the intraclass correlation coefficient were calculated for PGSA vs DSI. Positive predictive values for identifying severe disease with PGSA categories as a reference were based on a threshold >22 points.

The primary analysis included 89 pairs (46 Crohn's disease [CD], 43 ulcerative colitis [UC]) with strict criteria and 147 pairs when less stringent. Common reasons for exclusion were missing values for albumin or colonoscopy. Mean DSI values showed no clear trend with increasing PGSA in CD but good discrimination between moderate, severe, and very severe PGSA in UC. For PGSA on the visual analog scale, r was 0.54 for CD and 0.59 for UC (difference in means: CD 27.7, UC 13.8; intraclass correlation coefficient: CD 0.48, UC 0.58). A high DSI predicted severe disease in 76.2% of CD and 65.2% of UC.

The DSI showed good discrimination for patient-reported disease severity in UC but performed unsatisfactorily in CD. Correlations were moderate. Further refinement of the DSI is suggested to better reflect the patient perspective.