Inflammation In 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.

Association between nutritional status assessed by body mass index and Crohn's disease phenotype: A Nation-wide analysis

Background & aimsIncidence of obesity and Crohn's disease (CD) is increasing globally. Therefore, understanding any associations between adiposity and disease phenotype is crucial. We aimed explore the relationship between nutritional status measured by body mass index (BMI) and phenotypes of CD using a large national recallable data set. MethodsUsing National Institute for Health and Care Research-IBD Bioresource data base, we retrospectively assessed the relationship between BMI and stenosing CD by logistic regression. BMI was the primary variable of interest; CD behaviour was the dependent variable; stenosing CD was the primary outcome. Confounders were adjusted for in a multivariate model. Results8797 patients diagnosed between 1942 and 2020 were included. Mean overall BMI was 26.3 kg/m2 (SD5.5). 52.7 % had a BMI ≥25 kg/m2 (mean 30.2 kg/m2, SD 4.5). Majority had inflammatory CD (62.9 %) followed by stenosing (25.1 %) and penetrating CD (12 %). Stenosing and penetrating phenotypes were more common in the <25 kg/m2 BMI group (50.7 %, 50.3 % respectively) p < 0.001. Colonic disease location was more common (27.8 % vs 24.3 %, p = 0.001) in patients with high BMI. On univariate analysis, stenosing disease was positively associated with ileal disease location, disease duration, previous surgery, use of infliximab, ustekinumab, vedolizumab, adalimumab and azathioprine but negatively associated with BMI (OR 0.98, 95%CI [0.968–0.99]). On multivariate analyses, BMI remained negatively associated with stenosing CD (OR 0.98, 95%CI [0.97–0.99]); ileal disease location (OR 3.69, 95%CI [3.22–4.24]), adalimumab (OR 1.47, 95%CI [1.30–1.66]), ustekinumab usage (OR 1.51, 95%CI [1.14–2.01] and azathioprine (OR 1.35, 95%CI [1.19–1.53]). ConclusionsAfter multivariate analyses, BMI, ileal disease location and biologic use was negatively associated with a stenosing disease phenotype. This might reflect a change in eating behaviour due to persistent postprandial symptoms related to stenosing disease. Large longitudinal studies are needed to investigate any possible temporal relationship between the obesogenic state and intestinal fibrosis.

MR enterography radiologic ulcers in newly diagnosed ileal Crohn disease in children: frequency, inter-radiologist agreement, and clinical correlation

BackgroundRadiologic ulcers are increasingly recognized as an imaging finding of bowel wall active inflammation in Crohn disease (CD).ObjectiveTo determine the frequency of ulcers at MR enterography (MRE) in children with newly diagnosed ileal CD, assess agreement between radiologists, and evaluate if their presence correlates with other imaging and clinical features of intestinal active inflammation.Materials and methodsThis retrospective study included 108 consecutive pediatric patients (ages 6–18 years) with newly diagnosed ileal CD that underwent clinical MRE prior to treatment initiation between January 2021 and December 2022. MRE examinations were independently reviewed by three pediatric radiologists who indicated the presence vs. absence of ulcers, ulcer severity (categorical depth), and ulcer extent (categorical number of ulcers). Maximum bowel wall thickness and length of disease were measured and averaged across readers. Patient demographics and clinical inflammatory markers were documented from electronic health records. Inter-radiologist agreement was assessed using Fleiss’ kappa (k) statistics. Student’s t-test was used to compare continuous variables.ResultsMean patient age was 13.9 years (67 [62%] boys). Radiologic ulcers were recorded in 64/108 (59.3%) cases by reader 1, 70/108 (64.8%) cases by reader 2, and 49/108 (45.4%) cases by reader 3 (k = 0.36). Based on majority consensus, radiologic ulcers were present in 60/108 (55.6%) participants. Inter-radiologist agreement for ulcer severity was k = 0.23, while ulcer extent was k = 0.66. There were significant differences in C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, albumin, maximum bowel wall thickness, and length of disease between patients without and with radiologic ulcers (P < 0.05). The sensitivity and specificity of MRE for detecting endoscopic ulcers were 66.7% (95% CI, 52.1–79.2%) and 69.2% (95% CI, 48.2–85.7%), respectively.ConclusionRadiologic ulcers are visible in children with newly diagnosed ileal CD, although inter-radiologist agreement is only fair. The presence of ulcers is associated with clinical laboratory inflammatory markers as well as other MRE findings of disease activity and is an additional imaging finding that can be used to evaluate intestinal inflammation.

Quantitative Evaluation of Noncontrast Magnetic Resonance Enterography for Active Inflammation in Crohn Disease Using Native T1 and T2 Mapping.

The aim of this study was to investigate the utility of native T1 and T2 mapping in the bowel to evaluate disease activity in Crohn disease (CD) using endoscopy as the reference standard. This was a prospective study. Magnetic resonance imaging was performed by using a 1.5-T Philips scanner. We used a modified look-locker inversion recovery and a multiecho gradient-spin-echo sequences for single breath-hold native T1 and T2 maps, respectively, for the short-axis image of the intestine, and the measurement at the most severe site was compared with partial Simple Endoscopic Score for Crohn's Disease (pSES-CD, assessed by an expert endoscopist). A pSES-CD ≥ 4 indicated active disease. Statistical analyses were performed using the Student t test, Spearman correlation, and receiver operating characteristic curve analysis. A total of 27 patients (mean age ± standard deviation, 37 ± 18 years; 20 men, 7 women) were included in this study. The native T1 value of active disease was significantly higher than that of inactive disease (1170.8 ± 100.5 milliseconds vs 924.5 ± 95.3 milliseconds; P = 0.018), but the T2 value was not significantly different between active and inactive disease (76.1 ± 7.8 milliseconds vs 69.3 ± 10.9 milliseconds; P = 0.424). A good correlation was found between native T1 value and pSES-CD (ρ = 0.71; P < 0.001) but not between T2 value and pSES-CD (ρ = 0.06; P = 0.790). The area under the receiver operating characteristic curve for differentiating the disease activity was 0.96 (95% confidence interval [CI]: 0.90-1.00) for T1 values and 0.68 (95% confidence interval: 0.41-0.96) for T2 values. Native T1 mapping could be potentially used as a noninvasive method to differentiate disease activity in patients with CD and may be superior to T2 mapping for this purpose.

De-escalating therapy in inflammatory bowel disease: Results from an observational study in clinical practice

Background and objectivesCombination therapy with an immunomodulator (IMM) and an anti-TNF is commonly recommended in Crohn's disease (CD) and ulcerative colitis (UC) patients. However, little is known about relapse rates after therapeutic de-escalation. This study aimed to evaluate the risk of relapse in a cohort of UC and CD patients with long-standing clinical remission after discontinuation of IMM or anti-TNF and to identify predictive factors for relapse. MethodsThis retrospective study included patients with UC or CD on combination therapy and clinical remission for at least 6 months. IMM or anti-TNF was stopped upon physician decision. Primary objective was to evaluate the relapse rates after discontinuation of IMM or anti-TNF and to analyze predictors of relapse. ResultsThe study included 88 patients, 48 patients (54.5%) discontinued IMM and 40 (45.5%) anti-TNF. During follow-up, relapse rates were 16.7% and 52.5% in the IMM discontinuation group and anti-TNF discontinuation group, respectively (p<0.001). Multivariate analysis showed that anti-TNF discontinuation (HR=3.01; 95% CI=1.22–7.43) and ileal CD location (HR=2.36; 95% CI=1.02–5.47) were predictive factors for relapse while inflammatory CD phenotype was a protective factor (HR=0.32; 95% CI=0.11–0.90). Reintroduction of anti-TNF upon relapse was effective and safe. ConclusionAnti-TNF discontinuation led to significantly higher relapse rates compared to IMM discontinuation in UC and CD patients on combination therapy. Anti-TNF discontinuation and ileal CD location were identified as predictive factors for relapse while inflammatory CD phenotype was a protective factor. Retreatment after anti-TNF discontinuation was effective and safe.

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.

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.

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.

Mesalazine Induced Pancytopenia in Crohn's Disease

Mesalazine, or 5-aminosalicylic acid, is an anti-inflammatory drug frequently used in patients suffering from chronic inflammatory bowel disease, and is generally well tolerated. Its most common side effects are mainly limited to gastrointestinal disorders, headaches, joint pain and skin rashes, and are generally modest and transient. Serious hematological toxicity is very rare (&lt;1/10000), but cases of thrombocytopenia, aplastic anemia, pancytopenia and leukopenia/agranulocytosis have been reported. We report here the case of a patient with inflammatory phenotype colonic Crohn's disease on mesalazine 3g/day who presented with initial leukopenia aggravated by the development of pancytopenia

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.

Antibiotics for inflammatory bowel disease: Current status.

There is abundant literature reporting about the use of antibiotics in inflammatory bowel disease (IBD), but their role in the management of IBD is not entirely clear. Diverse infectious organisms have been implicated in the pathogenesis of Crohn's disease. Also, infections are believed to be a trigger for flares of ulcerative colitis. The benefit of the routine use of antibiotics in IBD is equivocal. However, there are certain situations, where antibiotics have a clear role and evidence of benefit: perianal fistula, intra-abdominalabscesses in Crohn's disease, acute pouchitis and infection-related flares. However, there is a lack of supportive evidence for the routine use of antibiotics in all disease-related flares. Evidence indicates a lack of benefit of intravenous antibiotics in acute severe ulcerative colitis and only limited benefit in active ulcerative colitis. Limited evidence suggests the role of a combination of oral antibiotics in pediatric ulcerative colitis. Certain targeted antibiotic regimens have been used in IBD. In ulcerative colitis, limited evidence suggests the benefit of the use of an antibiotic cocktail directed against Fusobacterium varium. Therapy directed against Escherichia coli does not seem to have a benefit in inflammatory Crohn's disease. In Crohn's disease, antimycobacterial therapy may result in symptomatic improvement but no durable benefit. Antitubercular therapy (ATT), on the contrary, may result in fibrotic transformation, suggesting a need to avoid misdiagnosis and limit the duration of ATT in Crohn's disease. This review assesses the published literature with respect to antibiotic use and provides guidance to clinicians in appropriate antibiotic use in various situations in the setting of IBD.

P273 Defining the prognosis of children with Crohn Disease with the support of magnetic resonance enterography: a multi-center multi-reader study

Abstract Background Ileocolonoscopic assessment is the most accurate method for detecting intestinal inflammation in Crohn disease (CD), but it allows the assessment only of a limited tract of the small intestine and does not provide data on inflammation beyond the mucosa. The auxiliary use of magnetic resonance enterography (MRE) can overcome these limitations and allow to predict the course of CD. Paediatric Inflammatory Crohn's MRE Index (PICMI) is a multi-point index of intestinal inflammation (mucosal and transmural) in children with CD created on the basis of MRI. The aim of the present study is to assess whether this completely non-invasive index at diagnosis could predict the course of CD in children and to test the inter-reader agreement as surrogate of index reproducibility. Methods All children diagnosed with CD in two tertiary referral centres with a 1-year minimum follow-up were enrolled in the study. MRE at diagnosis was blindly evaluated by 3 expert radiologists and PICMI was calculated for all patients. Children’s disease was stratified according to PICMI at diagnosis into remission (&amp;lt;10), mild (11-55), moderate (56-120) and severe (&amp;gt;120). Inter-observer agreement among radiologist was calculated. Data at follow-up were collected at 6-8 weeks, 1 year, 3 years and 5 years after CD diagnosis. Association between PICMI at diagnosis and CD prognosis was evaluated. Results A total of 71 children (52 males) with proven CD were enrolled in the study and PICMI was calculated for 68. PICMI at diagnosis was stratified into remission 6 (8.8%), mild 29 (42.6%), moderate 24 (35.3%), severe 9 (13.2%). Inter-observer agreement was calculated with an intraclass correlation coefficient of 0.65 which indicates moderate reliability between the 3 raters. PICMI score at diagnosis significantly correlated with PCDAI (Paediatric Crohn's Disease Activity Index) at diagnosis (p: 0.036). Steroid-free remission at 1, 3 and 5 years was comparable between PICMI groups: remission + mild vs moderate + severe (p: 0.606). CRP and calprotectin negative steroid free remission at 1,3,5 was also comparable (p: 0.578). PICMI at diagnosis was associated with the probability of biologic introduction at 1 year: incidence rate ratio IRR: 2.17 (1.09-4.42); p=0.019, 3-year IRR: 2.12 (1.15-3.96); p=0.011, and 5 years: 2.21 (1.20-4.08); p=0.007 (figure 1). Conclusion PICMI score is a reliable and reproducible index to determine activity in children with Crohn’s disease. Children with more active disease at diagnosis according to PICMI have shown an increased need to progression to biologic treatment in order to gain a comparable rate of steroid free remission and inflammatory marker negativity if compared with children with lower PICMI scores.

P387 Short and long-term outcomes of surgery for inflammatory (uncomplicated) ileocecal Crohn’s disease: multicentric retrospective analysis of 211 patients

Abstract Background Surgical management for patients with inflammatory ileocecal Crohn’s disease (CD) could be a reasonable alternative to second-line medical treatment. Methods A retrospective analysis of patients intervened for primary ileocecal CD with uncomplicated (inflammatory) phenotype at four referral hospitals during 2012-2021 was performed. The objective was to assess short and long-term outcomes of patients operated on for inflammatory, ileocecal CD. Patients operated on due to inflammatory ileocecal CD (last 50 cm of the terminal ileum and cecum), were considered eligible to participate in this study. Operations performed during a 9-year period (2012-2021) were considered for the study. Patients who were operated for CD for advanced structural bowel damage (fibrotic strictures or penetrating phenotype), those who had had previous abdominal CD-related procedures, and patients who had disease activity in other anatomical regions at the time of surgery, were excluded from the study. Results 211 patients were included. 43% of patients underwent surgery more than 5 years after diagnosis, and 49% had been exposed to at least one biologic agent preoperatively. 89% were operated by laparoscopy, with 1.6% conversion rate. The mean length of stay for patients was 5 days, with only 24 patients (11%) requiring a prolonged hospitalization. The complication rate was 23.7% (50 patients), but most complications were minor (Clavien-Dindo &amp;lt; IIIa), with only 11 patients (5%) presenting with major complications. Leak rate for patients who received a primary anastomosis was 2.9%. The median length of the resected bowel was 25 cm (7-92) and three patients (1.43%) received a stoma. Median follow-up was 36 (17-70) months. The endoscopic recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 56%, 52%, 45%, 38%, and 33%, respectively. The clinical recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 83%, 79%, 76%, 74%, and 74%, respectively. In multivariate analysis, previous biological treatment (HR=2.01; p=0.001) was associated with a higher risk of overall recurrence. Conclusion In this study, surgery in patients with primary inflammatory ileocecal CD is associated with good postoperative outcomes, low postoperative morbidity with reasonable recurrence rates. Further studies need to validate the present results.

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.

Short and long-term outcomes of surgery for inflammatory (uncomplicated) ileocecal Crohn's disease: Multicentric retrospective analysis of 211 patients

BackgroundSurgical management for patients with inflammatory ileocecal Crohn's disease (CD) could be a reasonable alternative to second-line medical treatment. AimTo assess short and long-term outcomes of patients operated on for inflammatory, ileocecal Crohn's disease. MethodsA retrospective analysis of patients intervened at four referral hospitals during 2012–2021 was performed. Results211 patients were included. 43% of patients underwent surgery more than 5 years after diagnosis, and 49% had been exposed to at least one biologic agent preoperatively. 89% were operated by laparoscopy, with 1.6% conversion rate. The median length of the resected bowel was 25 cm (7–92) and three patients (1.43%) received a stoma. Median follow-up was 36 (17–70) months. The endoscopic recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 56%, 52%, 45%, 38%, and 33%, respectively. The clinical recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 83%, 79%, 76%, 74%, and 74%, respectively. In multivariate analysis, previous biological treatment (HR=2.01; p = 0.001) was associated with a higher risk of overall recurrence. ConclusionSurgery in patients with primary inflammatory ileocecal CD is associated with good postoperative outcomes, low postoperative morbidity with reasonable recurrence rates.

A bidirectional Mendelian randomization study of sarcopenia-related traits and inflammatory bowel diseases.

There is increasing evidence pointing to a close relationship between sarcopenia and inflammatory bowel disease. However, it remains unclear whether or in which direction causal relationships exist, because these associations could be confounded. We conducted a two-sample bidirectional mendelian randomization analysis using data from European genome-wide association studies of the appendicular lean mass(n = 450,243), walking pace(n = 459,915), grip strength (left hand, n = 461,026; right hand, n = 461,089), inflammatory bowel disease (25,042 patients and 34,915 controls), ulcerative colitis (12,366 patients and 33,609 controls), and Crohn's disease (12,194 patients and 28,072 controls) to investigate the causal relationship between sarcopenia-related traits and inflammatory bowel disease and its subtypes on each other. The inverse-variance weighted method was used as the primary analysis method to assess the causality, and a comprehensive sensitivity test was conducted. Genetically predicted appendicular lean mass was significantly associated with inflammatory bowel disease (OR = 0.916, 95%CI: 0.853-0.984, P = 0.017), ulcerative colitis (OR =0.888, 95%CI: 0.813-0.971, P = 0.009), and Crohn's disease (OR = 0.905, 95%CI: 0.820-0.999, P = 0.049). Similar results also revealed that the usual walking pace was causally associated with Crohn's disease (OR = 0.467, 95%CI: 0.239-0.914, P = 0.026). Reverse mendelian randomization analysis results found that genetic susceptibility to inflammatory bowel disease, and Crohn's disease were associated with lower appendicular lean mass. A series of sensitivity analyses ensured the reliability of the present research results. The mendelian randomization study supports a bidirectional causality between inflammatory bowel disease, Crohn's disease and appendicular lean mass, but no such bidirectional causal relationship was found in ulcerative colitis. In addition, genetically predicted usual walking pace may reduce the risk of Crohn's disease. These findings have clinical implications for sarcopenia and inflammatory bowel disease management.

Natural History of Pediatric Patients With Crohn's Disease Treated With Mesalamine Therapy.

5-aminosalicylates (5-ASA) are used to treat mild to moderate ulcerative colitis. Despite their lack of efficacy in Crohn disease (CD), they are still used in real-world practice. Additionally, when patients have progressive disease, they may escalate to biologic therapy, at which time 5-ASA may or may not be discontinued. The aim of this study is to assess the clinical outcomes of patients started on 5-ASA for the treatment of pediatric CD. The secondary aims were to evaluate the outcomes of those who continue 5-ASA to those who discontinue 5-ASA upon biologic escalation. We performed a single-center retrospective chart review of pediatric CD patients from 2010 to 2019 who were initially treated with 5-ASA. Demographics, medication and laboratory data, and clinical disease activity were collected. Sixty-one patients were included in the study; the majority had inflammatory CD with ileocolonic involvement. Twenty-four patients were on a concomitant immunomodulator. The majority of patients (85.2%) required escalation to biologics. Thirty-two patients (61.5%) who escalated to biologic therapy continued on 5-ASA. Eighty percent of patients achieved clinical remission at 1 year, and there was no difference between those who continued 5-ASA at time of biologic initiation compared to those who did not continue the medication. Patients who discontinued 5-ASA had an average annual cost savings of $6741. 5-ASA is not a durable monotherapy for the treatment of pediatric CD. Patients who require escalation from 5-ASA to biologic therapy do not benefit from concomitant 5-ASA therapy. Further prospective studies are needed to confirm these findings.

Crohn's disease inflammation severity assessment with iodine density from photon counting CT enterography: comparison with endoscopic histopathology.

To determine optimal iodine density thresholds for active inflammation in CD patients with PCCT enterography and determine if iodine density can be used to stratify CD activity severity. A retrospective PACS search identified patients with CD imaged with PCCT enterography from 4/11/2022 to 10/30/2022 and with clinical notes, endoscopic/surgical pathology and available source PCCT data for iodine density analysis. Two abdominal radiologists with expertise in CD each drew two region of interest measurements within the visibly most affected region of terminal or neoterminal ileum wall on commercially available system (SyngoVia). Radiologists were blinded to clinical information and pathologic findings. Disease activity and severity were recorded from the pathology report. Harvey-Bradshaw Index, medications, and laboratory values were recorded. Receiver operating characteristic (ROC) curves were utilized to determine the optimum iodine density threshold for active inflammation and mild versus moderate-to-severe inflammation. Intra- and inter-reader agreement was assessed by intra-class correlation coefficient (ICC). 23 CD patients (15 females; mean [SD] age: 52 [17] years) imaged with PCCT enterography were included. 15/23 had active inflammation: 9/15 mild, 4/15 moderate, and 2/15 severe active inflammation. The optimal iodine density threshold for active inflammation was 2.7 mg/mL, with 97% sensitivity, 100% specificity, and 98% accuracy (AUC = 1.00). The optimal iodine density threshold for distinguishing mild from moderate-to-severe inflammation was 3.4 mg/mL, with 83% sensitivity, 89% specificity, and 87% accuracy (AUC = 0.85). Intra-reader reliability (R1/R2) ICC was 0.81/0.86. Inter-reader reliability ICC was 0.94. Iodine density from PCCT enterography can distinguish mild from moderate-to-severe active inflammation.

Disease Severity Impairs Generation of Intestinal Organoid Cultures From Inflammatory Bowel Disease Patients

IntroductionChronic inflammation of the intestinal epithelium is an underlying cause of the two main types of inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD). Ex vivo organoids derived from the intestinal epithelium are a useful model to study IBD. Whether such cultures can be established from surgically resected diseased IBD intestinal tissues has not been fully explored. In this study, we tested our ability to establish organoids from nondiseased and diseased IBD intestinal tissues. Materials and methodsFrom 12 UC patients (n = 54 tissues) and 20 CD patients (n = 49 tissues), tissues were collected from multiple colonic regions, and for CD, the terminal ileum was also surveyed. Organoids were cultured in Matrigel domes using defined media. In primary tissues, we conducted immunohistochemical analysis for mucin 2 (MUC2) and Alcian blue staining for goblet cells. Organoids were stained for Ki67, E-cadherin, and MUC2. ResultsFor UC, we were highly successful establishing organoids from nondiseased tissue (n = 12 of 13, 92%). This success rates dropped from tissues with mild (n = 6 of 9, 67%), moderate (n = 2 of 9, 22%), or severe disease (n = 1 of 23, 4%). The rates from nondiseased CD tissues were reduced (n = 11 of 23, 48%) in comparison to such tissues from UC patients. In UC, goblet cells and MUC2 were reduced in diseased tissues and these phenotypes were retained in organoids. ConclusionsOrganoids can be readily derived from nondiseased surgically resected IBD tissues. While more work is needed to improve their derivation from diseased tissue, our study supports the use of organoids to study IBD pathophysiology.

De-escalating therapy in inflammatory bowel disease: Results from an observational study in clinical practice

Background and objectivesCombination therapy with an immunomodulator (IMM) and an anti-TNF is commonly recommended in Crohn's disease (CD) and ulcerative colitis (UC) patients. However, little is known about relapse rates after therapeutic de-escalation. This study aimed to evaluate the risk of relapse in a cohort of UC and CD patients with long-standing clinical remission after discontinuation of IMM or anti-TNF and to identify predictive factors for relapse. MethodsThis retrospective study included patients with UC or CD on combination therapy and clinical remission for at least 6 months. IMM or anti-TNF was stopped upon physician decision. Primary objective was to evaluate the relapse rates after discontinuation of IMM or anti-TNF and to analyze predictors of relapse. ResultsThe study included 88 patients, 48 patients (54.5%) discontinued IMM and 40 (45.5%) anti-TNF. During follow-up, relapse rates were 16.7% and 52.5% in the IMM discontinuation group and anti-TNF discontinuation group, respectively (p<0.001). Multivariate analysis showed that anti-TNF discontinuation (HR=3.01; 95% CI=1.22–7.43) and ileal CD location (HR=2.36; 95% CI=1.02–5.47) were predictive factors for relapse while inflammatory CD phenotype was a protective factor (HR=0.32; 95% CI=0.11–0.90). Reintroduction of anti-TNF upon relapse was effective and safe. ConclusionAnti-TNF discontinuation led to significantly higher relapse rates compared to IMM discontinuation in UC and CD patients on combination therapy. Anti-TNF discontinuation and ileal CD location were identified as predictive factors for relapse while inflammatory CD phenotype was a protective factor. Retreatment after anti-TNF discontinuation was effective and safe.