Bowel Crohn's Disease Research Articles

Inflammatory bowel disease and risk of ophthalmic inflammation-related diseases: a two-sample Mendelian randomization study

AIM: To investigate the causal effect of inflammatory bowel disease (IBD) on ocular inflammation using Mendelian randomization (MR) analysis. METHODS: Genetic instruments associated with inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD) were derived from the largest genome-wide association studies (GWAS) published to date. The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis, keratitis, iridocyclitis, chorioretinitis, episcleritis, and optic neuritis. All participants were of European ancestry. Three methods which included inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression were performed to estimate the causal association in this study. IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes, to summarize the effect sizes of multiple independent studies, which could provide the most precise estimated results. IVW was used as the primary outcome, while WM and MR-Egger were used to improve the estimation of IVW. RESULTS: A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis, keratitis, iridocyclitis, and optic neuritis, but not on chorioretinitis or episcleritis. After Bonferroni correction, the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis (IVW: OR, 1.17; 95%CI, 1.10-1.24, P=2.54×10-7). CD was significantly associated with conjunctivitis (IVW: OR, 1.05; 95%CI, 1.03-1.08, P=3.20×10-5), keratitis (IVW: OR, 1.06; 95%CI, 1.02-1.09; P=1.13×10-3), and iridocyclitis (IVW: OR, 1.09; 95%CI, 1.04-1.14; P=1.43×10-4). CONCLUSION: IBD causally poses a risk of inflammation of conjunctiva, cornea, Iris-ciliary body complex, and optic neuritis. CD is more closely associated with the eye inflammation than UC. These impliy that the relationship of IBD and different parts of the eye structure are different, and provide novel evidence linking based on the association of the gut-eye axis.

Quantitative assessment of ultrasound microvessel imaging in Crohn's disease: correlation with pathological inflammation.

Ultrasound microvessel imaging (UMI) may offer noninvasive, highly sensitive microvessel imaging for assessing Crohn's disease (CD). However, a quantification metric that demonstrates a strong correlation with pathological inflammation is preferred. The objective was to determine if UMI can enhance IBD imaging interrogations. UMI was performed on bowel wall segments from patients with CD requiring surgery (n = 55 patients). The vessel-length ratio (VLR) measured by UMI was compared with that obtained using color flow imaging (CFI) and with a histopathologic standard evaluated on all bowel layers. Correlations between VLR and pathological inflammation and receiver operating characteristic (ROC) curves between different groups were analyzed to demonstrate the advantages of VLR with UMI. The correlation between VLR from UMI and pathological inflammation (R = 0.80) outperformed that of VLR from CFI (R = 0.59). UMI showed a significant difference (p < 0.01) between mild and non-mild inflammation cases, while CFI could not (p = 0.014). In the ROC analysis, VLR with UMI demonstrated an area under the curve (AUC) of 0.93, compared to the AUC of 0.80 for VLR with CFI, indicating better identification of pathological inflammation between mild and non-mild cases. For a sub-cohort of patients with stricture without penetrating complications (n = 19), VLR using UMI also showed better correlation (R = 0.93) with pathological inflammation scores and a higher AUC (0.96) than those of VLR using CFI (R = 0.66 and 0.88, respectively). UMI enhances vessel detection sensitivity compared to CFI and more accurately reflects transmural inflammation in small bowel Crohn's disease. VLR using UMI strongly correlates with pathological inflammation, distinguishing between mild and non-mild cases, notably including patients with stricture without penetrating complications. Question Bowel wall thickness and Limberg score from ultrasound are insufficient quantitative metrics for reliable diagnosis of inflammation severity for Crohn's disease. Findings Ultrasound microvessel imaging (UMI) with vessel-length ratio (VLR) is strongly correlated with pathological inflammation and had improved distinction between mild and non-mild inflammation cases. Clinical relevance UMI with VLR has the potential to enhance clinicians' ability to assess disease activity and evaluate therapeutic responses, thereby improving Crohn's disease patient outcomes.

Combined [18F]-FDG PET-MR Imaging: A promising tool for diagnostics of small bowel Crohn's disease.

Introduction Diagnostics of small bowel Crohn's disease (CD) can be difficult. Combined positron emission tomography-magnetic resonance enterography (PET-MRE) can be used to evaluate intestinal metabolism, but clinical use has been limited due to accessibility, costs, absence of standardized methods and diagnostic thresholds. Our aim was to show that combined PET-MRE can be used to diagnose active small bowel CD. Methods We performed a fusion PET-MRE-scan with [18F]-FDG-tracer to 30 patients with suspected small bowel CD in colonoscopy. Standardized uptake values (SUV) were measured from small bowel. The diagnosis was confirmed with small bowel capsule endoscopy. Clinicians chose appropriate medication to each patient blinded from SUV-results. Endoscopic, laboratory and MRE-findings were investigated in relation to SUV. Results Fusion PET-MRE outperformed MRE in diagnostic accuracy. Patients diagnosed with CD (N=24) had higher SUV than patients not diagnosed with CD (N=6) (3.34 vs. 1.84, p=0.022). A diagnostic cut-off at SUV at 2.5. could be used (AUROC=0.81). A higher SUV predicts need for immunosuppressive medication (p=0.0026) and biologics (p=0.0005). SUV correlates positively with SES-CD-score (Simple Endoscopic Score for Crohn's Disease), fecal calprotectin and CRP and negatively with Hb and serum albumin. Conclusion In future, [18F]-FDG PET-MRE can be used in diagnostics of small bowel CD as a safe alternative for capsule endoscopy. High SUV can predict a more progressive disease course and need for more advanced therapies.

Recurrence rates after strictureplasty for small bowel Crohn's disease remain high in the era of biologics.

Despite advancements in therapeutic options for Crohn's disease (CD), strictureplasty is a mainstay bowel-preserving technique for small bowel CD. We sought to audit international practice across three high-volume centres since the widespread use of biologic medication. A retrospective audit was performed for all strictureplasties undertaken for small bowel CD, over a 15-year period (2006-2021), in three high-volume centres in the United Kingdom and Italy. Primary endpoints were clinical recurrence and reoperation for recurrence. In all, 123 patients were included; 58% were men, 25% smoked and 60% had previous abdominal surgery for CD. Median age was 40 years (interquartile range 30-52 years), mean body mass index 22 (15-31) and median disease duration 138 months (81-255 months). 42% had been treated with biologics preoperatively. In total 338 strictureplasties were performed in 123 patients, with a median of two per patient (interquartile range 1-3). Complications occurred in 35%, with 8% scoring Clavien-Dindo Grade 3. There were no Grade 4/5 complications. Postoperative biologic treatment was administered to 84/123 patients (68.3%). Median follow-up was 54 months. 41/123 patients (33.3%) developed clinical recurrence. Reoperation for recurrent stricturing was performed in 26/123 patients (21%). Clinical recurrence and reoperation rates were significantly higher in patients who continued to smoke after their index surgery. Strictureplasty remains a safe and effective surgical treatment for small bowel CD. Recurrence and reoperation rates remain high, regardless of postoperative biologic therapy. Smoking significantly increases the risk of recurrence.

International expert guidance for defining and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound: a consensus statement

Diagnostic imaging using CT enterography, magnetic resonance enterography, and intestinal ultrasound are important tools in evaluating stricturing Crohn's disease. Definitions of strictures have been developed for CT enterography and magnetic resonance enterography. However, expert recommendations for definitions and treatment response of strictures on intestinal ultrasound are not available. The aim of this study was to standardise definitions, diagnosis, and treatment response criteria in small bowel stricturing Crohn's disease on intestinal ultrasound. Using modified RAND-University of California Los Angeles Appropriateness Method, a diverse expert panel of 13 gastroenterologists, seven radiologists, and two patient representatives was assembled. A total of 466 statements on definitions and response to therapy of stricturing Crohn's disease on intestinal ultrasound were generated from a systematic review and from expert opinion, with subsequent rating for appropriateness. Two rounds of voting with an interposed survey result discussion were performed. Statements were classified as inappropriate, uncertain, or appropriate based on the median panel rating and degree of disagreement. Appropriateness was rated using a nine-point Likert scale (1 being inappropriate, 9 being highly appropriate). A naive or anastomotic small bowel Crohn's disease stricture on intestinal ultrasound is defined by the combination of bowel wall thickening, luminal narrowing, and pre-stenotic dilation. Bowel wall thickness is defined as being more than 3 mm. Luminal narrowing is defined as either a luminal diameter reduction of more than 50% in the narrowest area and relative to a normal adjacent bowel loop, or a luminal diameter of less than 1 cm. Pre-stenotic dilation is defined as more than 2·5 cm or an increase in bowel diameter relative to a normal adjacent bowel loop. Definitions for grading hyperaemia, inflammatory fat, wall stratification, intestinal ultrasound machine technical parameters, and image acquisition were also devised. Treatment response of strictures was defined as reduction in stricture length, bowel wall thickening, luminal narrowing, pre-stenotic dilation, and motility abnormalities. To our knowledge, this is the first intestinal ultrasound appropriateness rating exercise conducted for defining, diagnosing, and measuring response to therapy in small bowel stricturing Crohn's disease and informs future clinical use and intestinal ultrasound index development for clinical trials. Leona M and Harry B Helmsley Charitable Trust.

Unusual causes of Small bowel obstruction: a review of the literature and revisited cross-sectional imaging checklist.

Intestinal obstruction is a common surgical emergency with high morbidity and mortality. Patients presenting with features of small bowel obstruction need urgent evaluation to avoid complications such as bowel gangrene, perforation, or peritonitis. Imaging is necessary in most cases of suspected bowel obstruction, to take an appropriate decision, for apt patient management. Among the common causes of small bowel obstruction, adhesions, external herniae, malignancies, and Crohn's disease top the chart. Imaging helps in determining the presence of obstruction, the severity of obstruction, transition point, cause of obstruction, and associated complications such as strangulation, bowel gangrene, and peritonitis. This review is based on the cases with unusual causes of bowel obstruction encountered during our routine practice and also on the extensive literature search through the standard textbooks and electronic databases. Through this review we want our readers to have sound knowledge of the imaging characteristics of the uncommon yet important causes of bowel obstruction. We have also revisited and structured a checklist to simplify the approach while reporting a suspected case of small bowel obstruction. Imaging plays a key role in the diagnosis of small bowel obstruction and in determining the cause and associated complications. Apart from the common causes of small bowel obstruction, we should also be aware of the uncommon causes of small bowel obstruction and their imaging characteristics to make an accurate diagnosis and for apt patient management.

Bowel Inflammation and Nutrient Supplementation: Effects of a Fixed Combination of Probiotics, Vitamins, and Herbal Extracts in an In Vitro Model of Intestinal Epithelial Barrier Dysfunction.

The gut microbiota is a very important factor in the state of health of an individual, its alteration implies a situation of "dysbiosis," which can be connected to functional gastrointestinal disorders and pathological conditions, such as Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Ulcerative Colitis (UC) and Crohn's Disease (CD), and Colorectal Cancer (CRC). In this work, we studied the effect of a food supplement called ENTERO-AD containing a mix of probiotics (Lactobacillus acidophilus LA1, L. reuteri LR92, Bifidobacterium breve Bbr8), Matricaria Chamomilla, and B group vitamins (B1, B2, B6) on intestinal inflammation. The in vitro model used for the study is the Caco-2 cell, a culture derived from human intestinal adenocarcinoma; the inflammatory condition was achieved with treatment with Lipopolysaccharide (LPS) and the association between Tumor necrosis factor α/Interferon γ (TNF-α/IFN-γ) [1,2]. The effect of ENTERO-AD was evaluated by cell viability, measures of Transepithelial Electrical Resistance (TEER), paracellular permeability, and immunofluorescence. Results of the study have shown that ENTERO-AD has a favorable effect on Caco-2 cells in inflammatory conditions. It improves the integrity of Occludin and Zonula Occludens-1 (ZO-1) proteins, leading to an improvement in terms of TEER values and a reduction of paracellular permeability. This evidence underlines the protective effect of ENTERO-AD and its components in intestinal inflammation.

Small bowel Crohn's disease: Proximal lesions linked to increased inflammation and biologic treatment needs

ObjectiveCrohn's disease (CD) is heterogeneous, and proximal involvement in the small bowel (SB) is associated with worse outcomes. Nonetheless, studies on the impact of duodenal and jejunal lesions in SB CD are limited. This study aimed to investigate the clinical characteristics and outcomes of individuals diagnosed with SB CD, comparing those with and without proximal inflammation. MethodsA cohort of 53 treatment-naive SB CD patients that underwent Capsule Endoscopy at diagnosis were retrospectively selected. The inflammatory activity was quantified using the Lewis Score for each SB tertile. ResultsThirty-seven (69.8%) patients displayed inflammatory activity in the first and/or second tertile together with third tertile involvement (Proximal+T3 group). Sixteen (30.2%) had inflammation in the third tertile only (T3 group). Individuals in the Proximal+T3 group had a higher risk for moderate-to-severe inflammation (OR 4.93, 95% CI: 1.3–18.3, p=0.013). A subgroup analysis for those with mild inflammatory activity showed that individuals in the Proximal+T3 group initiated biologic drugs more often (OR 11, 95% CI: 1.1–109.7, p=0.036). ConclusionProximal SB lesions are associated with increased inflammatory activity, necessitating more frequent use of biologics in patients with mild disease. Early detection of proximal SB CD with Capsule Endoscopy may contribute to timely treatment.

A Rapid and Reliable Spectrofluorimetric Method to Measure the Urinary Lactulose/Mannitol Ratio for Dysbiosis Assessment.

Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn's disease). Traditional methods used to assess dysbiosis include the dual sugar absorption test and the urinary lactulose/mannitol ratio (LMR) measurement using mass spectrometry. Despite its precision, this approach is costly and requires specialized equipment. Hence, we developed a rapid and reliable spectrofluorimetric method for measuring LMR in urine, offering a more accessible alternative. This spectrofluorimetric assay quantifies the fluorescence of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) produced during the enzymatic oxidation of mannitol and lactulose, respectively. The assay requires 100 µL of urine samples and detects LMR values lower (eubiosis) and higher (dysbiosis) than 0.05, ultimately being amenable to high-throughput screening and automatization, making it practical for clinical and research settings. A validation of the method demonstrated its high precision, accuracy, and robustness. Additionally, this study confirmed analyte stability under various storage conditions, ensuring reliable results even with delayed analysis. Overall, this spectrofluorimetric technique reduces costs, time, and the environmental impact associated with traditional mass spectrometry methods, making it a viable option for widespread use in the assessment of dysbiosis.

Quantitative Magnetic Resonance Imaging (qMRI) of the Small Bowel in Crohn's Disease: State-of-the-Art and Future Directions.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract in which repeated episodes of acute inflammation may lead to long-term bowel damage. Cross-sectional imaging is used in conjunction with endoscopy to diagnose and monitor disease and detect complications. Magnetic resonance imaging (MRI) has demonstrable utility in evaluating inflammatory activity. However, subjective interpretation of conventional MR sequences is limited in its ability to fully phenotype the underlying histopathological processes in chronic disease. In particular, conventional MRI can be confounded by the presence of mural fibrosis and muscle hypertrophy, which can mask or sometimes mimic inflammation. Quantitative MRI (qMRI) methods provide a means to better differentiate mural inflammation from fibrosis and improve quantification of these processes. qMRI may also provide more objective measures of disease activity and enable better tailoring of treatment. Here, we review quantitative MRI methods for imaging the small bowel in CD and consider the path to their clinical translation. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Discrimination of pediatric cryptogenic multifocal ulcerous stenosing enteritis from small bowel Crohn's disease and gastrointestinal tuberculosis: A retrospective study (with videos).

Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare entity that mimics various inflammatory strictures of the small intestine. Pediatric literature is scarce. We analyzed the clinical, radiological, endoscopic and histopathological features of children with CMUSE that differentiate it from small bowel Crohn's disease (SBCD) and gastrointestinal tuberculosis (GITB). CMUSE was diagnosed by the following criteria: (1) unexplained small bowel strictures with superficial ulcers, (2) chronic/relapsing ulcers of small bowel after resection, (3) no signs of systemic inflammation, (4) absence of other known etiologies of small bowel ulcers. SBCD and GITB were diagnosed based on standard criteria. The clinical features, laboratory parameters, radioimaging, endoscopy (including video capsule endoscopy [VCE], intra-operative endoscopy), histopathological features and treatment outcome were noted. Out of 48,CMUSE was diagnosed in 13 (27%) isolated small bowel and ileocecal strictures, while GITB and SBCD accounted for 41% and 21% cases, respectively. Common presentations were sub-acute obstruction (46%), obscure gastrointestinal bleeding (38%) and protein-losing enteropathy (38%). CMUSE patients had significantly longer disease duration compared to SBCD and GITB (p < 0.001). SBCD (90.0%) and GITB (85%) cases had elevated C-reactive protein (CRP), none with CMUSE had elevated CRP (p < 0.001). The disease was localized in jejunum (100%) and proximal ileum (56%) in CMUSE, ileocecal region (85%) in GITB, but evenly distributed in small intestine in SBCD. Endoscopy showed evenly placed, superficial, circumferential ulcers with strictures in CMUSE, deep linear ulcers in SBCD and circumferential ulcers in GITB. Upfront immunosuppression was given in four; three (75%) of them relapsed. Only surgery was done in three with one (25%) having relapse. Upfront surgery followed by immunosuppression was used in six, but all relapsed and two required repeat surgery. CMUSE is important but underdiagnosed in children. Lack of constitutional symptoms, normal inflammatory parameters and characteristic ulcers with strictures helped in differentiating CMUSE from GITB and SBCD.

A global consensus on the definitions, diagnosis and management of fibrostenosing small bowel Crohn's disease in clinical practice.

Fibrostenosis of the small bowel is common in patients with Crohn's disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn's disease. It was conducted by a panel of 28 global experts and one patient representative. Following a systematic literature review, 526 candidate items grouped into 136 questions were generated and subsequently evaluated for appropriateness. Strictures are best defined as wall thickening, luminal narrowing and prestenotic dilation. Cross-sectional imaging is required for accurate diagnosis of fibrostenosing Crohn's disease, and itis recommended before making treatment decisions. It should also assess the degree of inflammation in the bowel wall. Multiple options for medical anti-inflammatory, endoscopic and surgical therapies were suggested, including follow-up strategies following therapy. This Consensus Statement supports clinical practice through providing guidance on definitions, diagnosis and therapeutic management of patients with fibrostenosing small bowel Crohn's disease.

Genotype-based "virtual" metabolomics in a clinical biobank identifies novel metabolite-disease associations.

Introduction: Circulating metabolites act as biomarkers of dysregulated metabolism and may inform disease pathophysiology. A portion of the inter-individual variability in circulating metabolites is influenced by common genetic variation. We evaluated whether a genetics-based "virtual" metabolomics approach can identify novel metabolite-disease associations. Methods: We examined the association between polygenic scores for 724 metabolites with 1,247 clinical phenotypes in the BioVU DNA biobank, comprising 57,735 European ancestry and 15,754 African ancestry participants. We applied Mendelian randomization (MR) to probe significant relationships and validated significant MR associations using independent GWAS of candidate phenotypes. Results and Discussion: We found significant associations between 336 metabolites and 168 phenotypes in European ancestry and 107 metabolites and 56 phenotypes in African ancestry. Of these metabolite-disease pairs, MR analyses confirmed associations between 73 metabolites and 53 phenotypes in European ancestry. Of 22 metabolitephenotype pairs evaluated for replication in independent GWAS, 16 were significant (false discovery rate p < 0.05). These included associations between bilirubin and X-21796 with cholelithiasis, phosphatidylcholine (16:0/22:5n3,18:1/20:4) and arachidonate with inflammatory bowel disease and Crohn's disease, and campesterol with coronary artery disease and myocardial infarction. These associations may represent biomarkers or potentially targetable mediators of disease risk.

Prospective characterization of intestinal MRI intravoxel incoherent motion in pediatric and young adultpatients with newly diagnosed small bowel Crohn's disease.

MRI diffusion-weighted imaging (DWI) is commonly used in MR enterography protocols for assessment of intestinal inflammation in patients with Crohn's disease. The intravoxel incoherent motion (IVIM) approach to DWI has been proposed as a more objective approach, providing quantitative parameters that reflect water diffusivity (D), blood flow (D*), and perfusion fraction (f). We aimed to determine if DWI-IVIM metrics from the terminal ileum in patients with newly diagnosed Crohn's disease differ from healthy participants and change in response to biologic medical therapy. In this prospective case-control study, 20 consecutive pediatric patients (mean age = 14years ± 2 [SD]; eight females) with newly diagnosed ileal Crohn's disease and 15 pediatric healthy participants (mean age = 18years ± 4 [SD]; eight females) underwent research MRI examinations of the small bowel between 12/2018 and 10/2021. Participants with Crohn's disease underwent MR studies at baseline, 6weeks, and 6months following initiation of anti-TNF-alpha therapy, whereas control participants underwent one research MRI examination. The MRI protocol included a DWI-IVIM sequence with nine b-values and the IVIM parameters (D, D*, and f) were extracted. Unpaired t-tests and mixed-effects models were used for analyses. Mean IVIM D (P < 0.001), D* (P = 0.004), and f (P = 0.001) metrics were lower for Crohn's patients at the time of diagnosis compared to healthy participants. Mean IVIM f value increased over time in response to medical therapy (mean f at baseline, 22% ± 6%; 6weeks, 25% ± 7%; 6months, 29% ± 10%; P = 0.016). Mean IVIM D* value increased over time in response to treatment (mean D* at baseline, 10.9 ± 3.0 × 10-3 mm2/s; 6weeks, 11.8 ± 2.8 × 10-3 mm2/s; 6months, 13.3 ± 3.3 × 10-3 mm2/s; P = 0.047), while there was no significant change in mean IVIM D value (P = 0.10). MRI DWI-IVIM metrics in patients with ileal Crohn's disease change over time in response to biological therapy and help discriminate these patients from healthy participants.

Genetic liability to inflammatory bowel disease is causally associated with increased risk of erectile dysfunction: Evidence from a bidirectional Mendelian randomization study.

Background: Several observational cohort studies suggested a close correlation between inflammatory bowel disease and erectile dysfunction. Nevertheless, whether there was a causal effect between them remained debatable. In this study, we aimed to detect the underlying causal links between genetically predicted inflammatory bowel disease and the risk of erectile dysfunction. Methods: A bidirectional Mendelian randomization (MR) study was performed to assess the causal link between inflammatory bowel disease and erectile dysfunction. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode were utilized to estimate the causality. The top single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease cases (n = 25,800) and erectile dysfunction cases (n = 1,154) were extracted from the summary genome-wide association study (GWAS) data obtained from a publicly attainable database. MR-PRESSO global outlier test and MR-Egger regression were utilized to explore the horizontal pleiotropy and outlier instrumental variables. Cochran's Q statistic was utilized to detect the heterogeneity. Results: In the forward MR study, the IVW approach demonstrated that genetically determined inflammatory bowel disease exhibited a suggestively causal association with an increased risk of erectile dysfunction (OR: 1.11, 95% CI: 1.02-1.21, p = 0.019), and also the genetically determined Crohn's disease was found to be causally associated with an increased risk of erectile dysfunction (OR: 1.09, 95% CI: 1.02-1.17, p = 0.014). However, the MR analysis results showed no significant evidence supporting a causal effect of ulcerative colitis with erectile dysfunction (OR: 1.02, 95% CI: 0.92-1.14, p = 0.679). Furthermore, the reverse MR analysis showed no causal effects of genetically determined erectile dysfunction on inflammatory bowel disease. Additionally, sensitivity analysis demonstrated no pleiotropy and heterogeneity. Conclusion: Our MR analysis substantiated causal links of inflammatory bowel disease and Crohn's disease on erectile dysfunction, which may further elucidate how inflammatory bowel disease impacted the initiation and development of erectile dysfunction, and facilitated the prevention and clinical management of inflammatory bowel disease in individuals with erectile dysfunction.

Risk factors for surgery in stricturing small bowel Crohn's disease: A retrospective cohort study from the GETAID pédiatrique.

Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received before stricture diagnosis includedMODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection wereantibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.

Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Micellar Matrices for Spectrophotometric Determination of 5-Aminosalicylic Acid in Medicinal Preparations Using Response Surface Methodology and Box-Benken Plans

Determination of the content of insoluble pharmaceutical substances in dosage forms is an urgent task, since their dosage is very important for the optimal ratio between the therapeutic effect and ensuring the necessary bioavailability. The use of micellar media as a matrix allows increasing solubility. This report presents the results of the influence of the micellar system consist from cetyltrimethylammonium bromide, CTAB, dimethyl sulfoxide, DMSO and water on the determination of the content of 5-aminosalicylic acid (5-ASA) in pharmaceutical substances and in dosage forms. 5-ASA is widely used for the treatment of inflammatory bowel diseases, ulcerative colitis and Crohn's disease. To obtain the optimal matrix, the methodology of the response surface (MRS) and three-level Box-Benken plans (BBP) were used. The intensity of the absorption band of 5-ASA (A330), which reflects the acid content, was used as the target function. The independent factors were: the concentration of CTAB (pC(CTAB), mol/l); the acidity of medium (pH); the proportion of DMSO in the binary solvent (αDMSO). The BBP consisting of fifteen compositions were compiled and response surfaces constructed. Optimal conditions for the determination of 5-ASA by the absorption band A330 are: pC(CTAB) = 1.1, pH = 7.6, α(DMSO) = 0.3. In this matrix, the content of 5-ASA in the pharmaceutical substance was established and good metrological performance was achieved. The use of MRS and BBP contributes to the development of effective methods for quality control of 5-ASA dosage forms from different manufacturers.

Validation of rapid fecal calprotectin assay using particle enhanced turbidimetric immunoassay for inflammatory bowel disease.

Fecal calprotectin (FC) is a promising biomarker for diagnosis and treatment of inflammatory bowel disease, ulcerative colitis (UC), and Crohn's disease. An enzyme immunoassay (EIA) is widely used for FC detection, though the considerable lag time, up to several days, causes clinical management delay. This study was performed to examine the new rapid kit fCAL-turbo, which is based on a particle-enhanced turbidimetric immunoassay (15 min), by comparing FC values with other EIAs (EliA, PhiCal, Bühlmann) and endoscopic scores. Using 94 samples, fCAL-turbo showed strong significant positive correlations with the other kits (Spearman's r = 0.9178-0.9886). Of 74 UC patients, 69 underwent an endoscopy and fCAL-turbo reflected endoscopic activity with a moderate correlation with Mayo endoscopic subscore (MES) (r = 0.6945, others r = 0.6682-0.7013). Receiver operating characteristic analyses based on MES 0 versus 1-3 showed a similar efficacy as compared to the other kits (cut-off and area under the curve: 89.70 µg/g and 0.8592, respectively, others 62.35-138.4 µg/g and 0.8280-0.8611, respectively). Furthermore, multiple regression analysis confirmed that fCAL-turbo results significantly contributed to prediction of MES 0 with a higher t-value as compared to the other biomarkers. fCAL-turbo showed strong correlations with the other kits and also demonstrated excellent performance for predicting endoscopic remission of UC.

Assessing quality of magnetic resonance enterography and its impact on disease assessment of ileal Crohn's disease.

Assessment of quality of magnetic resonance enterography (MRE) in small bowel Crohn's disease (CD) activity evaluation has received little attention. We assessed the impact of bowel distention and motion artifact on MRE activity indices in ileal CD. A cohort of patients who underwent contemporaneous MRE and colonoscopy for ileal CD assessment between 2014 and 2021 at 2 centers were audited. An abdominal radiologist blinded to clinical data reviewed each MRE, graded bowel distention and motion artifact upon a pre-specified 3-point scale and calculated the original magnetic resonance index of activity (MaRIA) and simplified MaRIA (sMaRIA), London index and CD MRE index (CDMI). Ileal endoscopic activity was graded via the Simplified Endoscopy Score for CD (SES-CD). The performance of MRE indices in discriminating active disease (SES-CD ≥3) stratified by MRE quality was measured by receiver operator characteristic analyses. One hundred and thirty-seven patients had MRE and colonoscopy within a median of 16 days (range, 0-30 days) with 63 (46%) exhibiting active disease (SES-CD ≥3). Forty-four MREs (32%) were deemed low quality due to motion artifact and/or moderate to poor distention. Low-quality MREs demonstrated reduced discriminative performance between ileal SES-CD ≥3 and MRE indices (MaRIA 0.838 vs. 0.634, sMaRIA 0.834 vs. 0.527, CDMI 0.850 vs. 0.595, London 0.748 vs. 0.511, P<0.05 for all). Individually the presence of any motion artifact markedly impacted the discriminative performance (e.g., sMaRIA area under the curve 0.544 vs. 0.814, P<0.05). Image quality parameters can significantly impact MRE disease activity interpretation. Quality metrics should be reported, enabling cautious interpretation in lower-quality studies.